Stony Brook Young Investigators Review Spring 2022 Issue 18

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THE CROSSROADS OF SCIENCE AND ART

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Music Interventions for Alzheimer’s Disease

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Ancient Writing Analysis: How to Unlock Historical Secrets

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Art Therapy: A Novel Neurological Approach to Cancer Treatment

Spring 2022 Volume 18


EDITORIAL Editor-in-Chief: Shrey Thaker `22

Associate Editors: Nicole Gladstein `23 Farah Hasan `23 Colin St. Aubin `23 Andrew Wang `23 Erin Fix `24 Rachel Wong `25 Yun Meng Zhang `25

Managing Editors: Riya Gandhi `22 Gabriela Zanko `23

LAYOUT Layout Chief: Komal Grewal `23 Assistant Layout Chief: Fanny Zhao `22

Isra Ahmed `23 Robin Bath `24 Emma Cherian `24 Ujala Dar `24 Graphic Editors: Annie Li `22 Katie Zeng `24

Layout Editors: Judy Liu `22

Copy Editors: Francesca Serraino `22 Panayiota Siskos `23 Sarah Cheung `24 Megha Gopal `24 Giancarlo Mainardi `24 Shubh Thaker `24 Katherine Wu `24 Ishmam Khan `25

Alexander Ye `25 Peer Reviewers: Gaurav Sharma `22 Roma Kidambi `23 Tharun Alamuri `23 Shreya Addepalli `24 Mrinaleni Das `24 Siya Majmundar `24

CABINET Heads of Cabinet: Matt Ramirez `22 Ruchira Samant `23 Webmaster: Jessica Yeung `25

Event Coordinators: Ashani Escoffery `22 Jasmine Kumar `22 Stephanie Shum `22 Toby Li `23 Hannah Philipose `23 Courtney Bentham `25 Rebecca Ramkaran `24 Julianna Giacoio `25

WRITERS Zhifei Zeng `23

Yukta Kulkarni `22

Aryan Patel `25

Peter Gillespie `25

Joyce Chen `23

Joshua Talabucon `25

Vignesh Subramanian `24

Fiona Murphy `23 Jessica George `24 Daphne Siozios `23

Alex Moir `23

Thumyat Noe `23 Sooraj Shah `24

Travis Cutter `22 Juzer Vasi `24

A SPECIAL THANK YOU TO OUR

FACULTY ADVISORS Dr. John Peter Gergen, Mr. Joshua Rice (MFA), and Dr. Nicole Leavey


A NOTE FROM OUR

EDITOR-IN-CHIEF Completing its 13th year, the Stony Brook Young Investigators Review (SBYIR) has continuously fulfilled and expanded its role of bringing scientific communication, literacy, and awareness to the Stony Brook campus. Having laid the foundation for more student involvement over the past two years, SBYIR has been able to successfully grow to over 60 active staff and writer positions. Over the course of the Spring 2022 semester, our teams have written, edited, designed, and compiled the most recent research on Stony Brook's Campus and around the world. With pieces from 15 undergraduate writers, we proudly present the 18th volume of the biannual SBYIR Journal: The Crossroads of Science and Art. From its tiniest particles to its jaw-dropping nebulas, our universe beholds scientific marvels at each turn woven through the creativity of our minds. To this end, this journal issue undertakes how a distinction that befalls and fuels a division between the humanities and science may not be as clear as most people think. We explore how these two powerful forms of expression and understanding are enmeshed and unravel the beauty underlying scientific understanding. In addition to the journal, SBYIR’s mission of infusing scientific literacy and communication into the undergraduate community was exercised through an array of workshops and events. Our pursual of an official budget allowed us to expand our events on campus, drawing in undergraduates with different backgrounds but similar interests to Scavenger Hunts, Paint Nights, and many more. Our Editorial Workshop series disseminated skills – like Checking for Scientific Accuracy – vital to the future scientists and communicators of our society. Each semester, SBYIR holds a flagship event involving keynote speakers from around the country who deliver informative talks in accordance with the semester’s journal theme. This semester, we held a colloquium where we were grateful to have had Dr. Margaret Schedel, an associate professor of music at Stony Brook University, as our keynote speaker. The expansion of SBYIR is truly inspirational for me since I had joined 4 years ago. Along this way, I would like to thank our hard-working writers and staff in the Editorial, Layout, and Cabinet branches. The executive board of SBYIR is a phenomenal team of talented individuals to have been a part of. I also extend this gratitude to our faculty advisors, Dr. J. Peter Gergen, Dr. Nicole Leavey, and Dr. Joshua Rice, and the Alan Alda Center for Communicating Science for their ceaseless support of our endeavors. I am incredibly proud of our current work, members, and where SBYIR will lead in the future. As I hand over the Editor-in-Chief position to my successors, I foresee a campus where the foundations we laid over the last few years flourish and bloom into the reference point for learning scientific communication. Each one of us are simply trying to tell our story, and the best stories are those that can connect to others. So, as we go forth trying to understand and unpack the universe, our microscopic and mechanistic perspective can only become more elegant when cherishing our connection to each other and the world’s beauty.

SHREY THAKER


CONTENTS

I: SBU-Related Research 1

Highlights Zhifei Zeng `23 Peter Gillespie `25 Vignesh Subramanian `24 Thumyat Noe `23 Sooraj Shah `24 Yukta Kulkarni `22 Joyce Chen `23

II: Music 5 8 13 17

Highlights Peter Gillespie `25 Yukta Kulkarni `22 Sooraj Shah `24 Zhifei Zeng `23 Joyce Chen `23

Artistic Anomalies: The Science Behind Musical Prodigies Fiona Murphy `23

Music Interventions for Alzheimer’s Disease Jessica George `24

Brain Mapping & Music Therapy Linked to Postoperative Success Daphne Siozios `23


III: Art 21 23 27 32 36 41

Highlights Thumyat Noe `23 Joyce Chen `23 Vignesh Subramanian `24 Peter Gillespie `25

A Review of Nitinol’s Application in Vascular Stents Aryan Patel `25

Virtual Reality: A Digital Playground for Artists and Patients Alike Joshua Talabucon `25

Microbial Pigments: A Molecular Palette For Art and Medicine Alex Moir `23

Ancient Writing Analysis: How to Unlock Historical Secrets Travis Cutter `22

Art Therapy: A Novel Neurological Approach to Cancer Treatment Juzer Vasi `24


AN ENZYME-ACTIVATING PROTEIN MAY BE A SWITCH FOR INVASIVE CANCER ZHIFEI ZENG `23

ui d.

Fi

Many breast cancer (BC) patients suffer from complications of metficiently than control cells, which facilitated the movement of cancer cells astatic disease. In order to form metastasis, cancer cells must switch from in vivo. To determine how srGAP1 restricts the growth of primary tumors a proliferative to an invasive state and overcome several physical barriers and promotes metastasis, they labeled a cell division related protein - Cdk2 to reach another site. Interestingly, increased invasiveness of the tumor is - which can be detected in the cytoplasm of dividing cells, or accumulates accompanied by a decrease in its cell proliferation capacity. For breast canin the nucleus of cells that do not divide. Sensors show prolonged accucer, some proteins may help this proliferative-to-invasive switch mulation of Cdk2 in the nucleus of cells with low srGAP1, which by facilitating tumor extravasation from blood vessels while demonstrated that cells with low srGAP1 levels have restricted attenuating tumor growth. A group led by Dr. Benjamin proliferation. They also found that srGAP1low cells secrete L. Martin at Stony Brook University found that srGAP1, more TGFβ2 protein than control cells. Treating cells with an enzyme-activating protein, may mediate the switch TGFβ2 demonstrated increased matrix degradation, from proliferative to invasive in breast cancer cells. which increases the invasion of cancer cells. Researchers injected labeled breast cancer cells Overall, the researchers found that srGAP1low into the bloodstream of transparent zebrafish embryos, cells displayed a highly motile phenotype and restricted including cancer cells with normal amounts of srGAP1 proliferation state. These cells also secreted more TGFβ2 and low srGAP1. After 24 hours, they observed the moveproteins to promote their invasion. This study cautioned g l ment of cancer cells in blood vessels under the microscope. ure l F that current treatments that target only dividing cells may a 1M ur Ple not stop cancer metastasis. Future research could focus on etas Most of the breast cancer cells still circulated in the blood, but t at i c B r in reast Cance few cancer cells close to the blood vessels formed dynamic actin-rich blocking the metastatic pathway of non-dividing invasive cells to infinger-like protrusions, followed by extravasating out of the blood vessels. crease the long-term survival of cancer patients. Also, srGAP1low cells were more likely to form protrusions, thus more likely to extravasate from the blood vessels and enter other tissues. Next, the re1. C. Mondal, et al., A proliferative to invasive switch is mediated by srGAP1 downregulation searchers cultured breast cancer cells and labeled the extracellular matrix. through the activation of TGFβ2 signaling. SSRN, (2021). 2. Image retrieved from: https://commons.wikimedia.org/wiki/File:Metastatic_Breast_Cancer_ They found that srGAP1low cells degraded the extracellular matrix more efin_Pleural_Fluid_(2293305625).jpg

FROM SUGARS TO MEDICINE: ADVANCEMENTS IN SELECTIVE CARBOHYDRATE MODIFICATION PETER GILLESPIE `25 What if simple sugars could be turned into vital medicines? Dr. MingYu Ngai and his team at Stony Brook University are making this dream a reality. Due to their relevance in cell-cell recognition, protein folding, inflammation, and infection, carbohydrate modification poses an intriguing avenue through which scientists can treat issues from viral infection to malfunctions in protein folding. Changing the character of the second carbon in a carbohydrate (C2) holds great promise, as many medicines, imaging techniques, and chemical processes rely upon unique functional groups attached to this carbon. As such, Dr. Ngai and his research team focus on developing an efficient process for a 1,2-spin-center shift (1,2-SCS), in which the reactive radical (one electron species) shifts from the first to the second carbon in the molecule. The novel mechanism relies upon the unique properties of palladium metal complexes. Exposure to blue LED light excites the palladium complexes, which abstract the halogen atom (X) at the C1-position. This process homolytically breaks the C-X bond, meaning one of two electrons in the C-X bond moves to the halogen atom to form a bond with the palladium complex while another electron moves to carbon. The singly occupied orbital of the radical carbon enters a state of hyper-conjugation, in which it interacts with the high-energy orbital of the neighboring acyloxy group. This interaction weakens the C-O bond at the C2-carbon and promotes the switching of the position of the C1-radical and the C2-acyloxy group, forming C2-radical species that can be captured for further C2-functionalization. In initial tests using α-glucosyl bromide, the reaction produced the desired product in 94% yield. Unlike catalysts that lack inner-sphere coordination, the palladium complex reversibly binds to C1-carbon, which

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maintains the integrity of the radical. Both α-bromosugars (sugars with a bromine atom) and α-iodosugars (sugars with an iodine atom) reacted efficiently under the standard conditions. The reaction also proved to be viable for carbohydrates with a diverse array of C6 attachments and for carbohydrates with fused ring structures. It was also applicable in functionalizing C2-carbon with iodine and deuterium, an isotope of hydrogen. Functionalizing carbons with deuterium is promising for modifying pharmaceuticals and utilizing new biomarkers, as deuterium-labeled sugars are frequently used to study biological processes. Additionally, given the influence of C2-iodosugars in directing glycosidic bond formation, this reaction could be helpful in discovering novel bioactive compounds, making this mechanism an important development in carbohydrate editing.

Figure 1 Research by Dr. Ngai provides a method through which carbohydrates could be modified to form important biological molecules.

1. M. Ngai, et al., Excited-state palladium-catalyzed 1,2-spin-center shift enables selective C-2 reduction, deuteration, and iodination of carbohydrates. Journal of the American Chemical Society 143, 1728-1734 (2021). doi: 10.1021/jacs.0c11209. 2. Image retrieved from: https://unsplash.com/photos/u_Mwofs_zu0


CONDITIONED TASTE AVERSION DEPENDS ON LONG-TERM DEPRESSION OF NEURONAL SIGNALING VIGNESH SUBRAMANIAN `24 Conditioned taste aversion (CTA) is a learned association, made by humans as well as other animals, between the taste of food consumed and a subsequent period of illness assumed to be caused by said consumption. This period of illness is paired with an aversive stimulus, such as gastrointestinal malaise, and produces visceral distress that encourages the animal to avoid the food in question. CTA is considered an adaptive, evolutionarily developed trait, with the survival response activated by signaling in the gustatory portion of the insular cortex (GC) as well as the basolateral nucleus of the amygdala (BLA) of the animal’s brain. However, the underlying synaptic connections and expression of contributing genes are poorly understood. A study led by Dr. Arianna Maffei of Stony Brook University aimed to better characterize the relationship between amygdalocortical synaptic efficacy and hedonic, or sensation-based, learning as they collectively establish CTA in animals. The researchers first trained male and female Long Evans rats in a CTA paradigm involving sucrose solution diets paired with gastric malaise-inducing intraperitoneal injections of lithium chloride. These subjects were then submitted to conditioning sessions and 2-bottle tests to assess their learning and consolidation of the aversive memory based on rates of solution consumption. Finally, a combination of whole-cell patch clamp recordings, selective optogenetic activations of terminal fields, and immediate early gene immunohistochemistry was utilized to assess stimulus patterns and circuit plasticity, or the ability to modify the strength of a synapse, among the involved signaling neurons. It was found that the establishment of CTA learning is largely dependent on synaptic long-term depression (LTD), a process in which neuronal signaling responses are decreased in amplitude, or reduced, for extended periods. While CTA directly reduced activity in the GC, LTD was also detected at BLA synapses onto pyramidal neurons in the GC, confirming the crucial role of the BLAto-GC signaling pathway in establishing CTA. Additionally, it was found that low stimulation of BLA terminal fields is sufficient to change the hedonic value of a taste stimulus. Collectively, these findings provide the first known evidence that such plasticity at amygdalocortical synapses can alter the degree of ‘unpleasantness’ expressed by the sensory stimulus in the two regions, and reveal that CTA learning-induced circuit changes rely on decreases in synaptic input rather than the strengthening of remodeled connections.

Figure 1 The amygdala, a

collection of nuclei deep within the temporal lobe of the human brain, integrating and processing emotional, behavioral, and memory-based inputs.

Figure 2 The insular cortex of the brain.

1. A. Maffei, et al., LTD at amygdalocortical synapses as a novel mechanism for hedonic learning. eLife 9, 1–21 (2020). doi: 10.7554/eLife.55175.

Graphics illustrated by Ujala Dar `24

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MAKING MAGIC IN MEDICAL SETTINGS: HOW MAGIC MAY IMPROVE THE PATIENT-STUDENT CONNECTION THUMYAT NOE `23 Many medical students often find themselves feeling emotionally detached from the illness experiences of patients. To combat this sentiment, medical education curricula recommend that students gain clinical immersion experience early to enhance students’ awareness of the patient experience. Past clinical findings suggest that performing magic acts as part of clinical immersion experience can further improve relations between medical staff and child patients. Magic acts consist of performances that elicit enjoyment through demonstration of events appearing to be impossible. Viewing such performances may improve clinical immersion experiences as well as the relationship between health care professionals and patients. Based on these findings, researchers from Renaissance School of Medicine created MagicAids, a voluntary service learning program which facilitates engagement with pediatric patients through magic performance. Researchers also assessed MagicAids’ effectiveness in enabling proper communication between patients and caregivers. Researchers hypothesized that the MagicAid program will be effective in helping medical students develop empathy, compassion, and communication skills. During the first week of classes, researchers introduced the MagicAid program to the medical students. Students interested in the program could then attend training classes where they learned how to perform basic magic tricks. Afterwards, students conducted magic rounds on specified hospital units for patients and their families. At the end of the academic year, students reflected on their experiences and evaluated the effectiveness of the MagicAid program in a survey. Some of the questions asked students how useful they found the program to be in improving communication with the patient, reducing burnout, and helping them acclimate to the clinical immersion experience.

Most students expressed enjoyment of the MagicAid program, emphasizing that it helped develop their communication skills, empathic qualities, leadership skills, and hospital familiarity, and improved overall psychological health. For instance, out of 47 participants, 34 of them rated their experience with the MagicAids program as “Extremely satisfied.” Students considered their experiences in the program as valuable and helpful towards their future careers as physicians. Lastly, students noted that they learned how to provide proper care to pediatric patients, read body language, and effectively communicate with patients. The results of the study suggest that joyful volunteer experiences are important in improving patient care within clinical settings. Introducing similar programs to medical schools would help students develop empathy and appropriately respond to the emotional states of patients.

Figure 1 Magic acts consist of performances that elicit enjoyment through demonstration of events appearing to be impossible.

1. H.D. Pravder, et al., An innovative program using magic to provide early clinical experiences for preclinical medical students: goals, experiences, and results of the MagicAid program. Medical Science Educator 32, 111-120 (2022). doi:10.1007/s40670-021-01456-y. 2. Image retrieved from: https://unsplash.com/photos/dttmeqFUDSU

INVESTIGATING INTERLEUKIN-17 ACTIVITY: ONE STEP CLOSER TO TREATING CROHN’S DISEASE? SOORAJ SHAH `24 About 3 million Americans have been diagnosed with Crohn’s disease, a type of inflammatory bowel disease (IBD), with foreboding statistics indicating a rise in the disease’s prevalence. Crohn’s disease debilitates a patient through inflammation of the digestive tract, leading to severe pain and cramping in the abdominal area. The inflammation associated with the IBD is a response to invading pathogens by a group of proteins called cytokines. The function of cytokine interleukin-17A (IL-17A) has become the primary focus of combating this disease. A study led by Dr. Pawan Kumar, an Assistant Professor in the Department of Microbiology and Immunology at Stony Brook University, focused on identifying a beneficial function of IL-17A previously not recognized in standard treatments. Previous research has shown that the body releases IL-17A when it detects microbial pathogens, signaling through other molecules such as the IL-17RA/IL-17RC receptor complex. Neutrophils and peptides, or associated white blood cells and defense molecules, respectively, then work to mitigate the pathogen. While monoclonal antibody treatment has been used to treat other inflammatory response related diseases like psoriasis, this treatment resulted in increased disease for patients with Crohn’s disease, hinting that IL-17A plays a larger role in the proper functioning of intestinal tissue. To investigate the mechanisms behind this finding, Dr. Kumar and

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his team injected IL-17A into a variety of mice models and human organoids and observed the molecule’s role in specific functions of the intestinal tract. The results of the study showed that IL-17A assists in the differentiation of stem cells into epithelial cells that play a crucial role as a barrier between bacteria and body tissue in the gut. When this divisional barrier is disrupted, it results in inflammation. Therefore, impairing IL-17A results in a decrease in epithelial cell production and an increase in observed inflammation in Crohn’s disease. Dr. Kumar believes that a relationship between immune cells and stem cells exists, such that the integrity of the intestinal mucosa (moist tissue) is maintained in order to hinder inflammation. Crohn’s disease is currently incurable; however, the study of IL-17A uncovered a crosslink between its potential functions in inducing or preventing inflammation in the intestinal tract. Finding a balance of treatment so that certain functions of IL-17A are preserved while others are impaired is the next important step for future research, bringing a reliable and efficient cure to Crohn’s one step closer. Figure 1 IL-17A releases peptides and neutrophils in order to fight bacteria in the intestinal tract. 1. P. Kumar, et al., IL-17RA-signaling in Lgr5+ intestinal stem cells induces expression of transcription factor ATOH1 to promote secretory cell lineage commitment. Immunity 55, 237-253 (2021). doi: https://doi.org/10.1016/j.immuni.2021.12.016. 2. Image retrieved from: https://images.unsplash.com/photo-1596051827487-7b3d6f6df842?ixlib=rb-1.2.1&ixid=MnwxMjA3fDB8MHxwaG90by1wYWdlfHx8fGVufDB8fHx8&auto=format&fit=crop&w=1170&q=80


THE COVID-19 PANDEMIC IS ASSOCIATED WITH INCREASED RATES OF OCD IN PREGNANT WOMEN YUKTA KULKARNI `22

Figure 1 More pregnant women during the COVID-19 pandemic are experiencing clinically significant obsessive-compulsive symptoms as compared to before the pandemic.

Obsessive-compulsive disorder (OCD) is a mental health disorder indicated by intrusive thoughts, which lead to repetitive behaviors. While it is common in the U.S., OCD rates have increased in the overall population due to the COVID-19 pandemic. It is thought that higher OCD occurrences are due to fears of how contagious the new virus is. As obsessive compulsive (OC) symptoms surged, researchers investigated how groups susceptible to OCD, such as pregnant women, were faring. Under normal circumstances, 2-3% of women express novel OC symptoms during pregnancy due to their need to keep their child safe. It is possible that these OC symptoms have been exacerbated during the pandemic. Brittain Mahaffey and their team of researchers hypothesized that stress related to the COVID-19 pandemic would be a better indicator of OC symptoms than pregnancy-related stress. To test their hypothesis, the researchers gathered 4,451 pregnant women during the first wave of the COVID-19 pandemic. All participants were initially asked questions from the Structured Clinical Interview for DSM-5 (SCID-5) that screened for OC symptoms. The participants who re-

sponded affirmatively continued to take the Obsessive-Compulsive Inventory-Revised (OCI-R) to determine if their symptoms were clinically significant, or if they presented both obsessions and compulsions. All participants then took the Revised Prenatal Distress Questionnaire (NuPDQ), which measures stress related to pregnancy, and the Pandemic-Related Pregnancy Stress Scale (PREPS), which measures stress related to the COVID-19 pandemic. After statistical analyses were performed, 7.12% of the participants had clinically significant OC symptoms, higher than the previously noted average of 2-3%. It was also seen that the PREP scale more accurately predicted OC symptoms in the 7.12% of pregnant women who were categorized as having OCD than the NuPDQ. The results suggest that OC symptoms are more prevalent in times of crisis since a higher number of pregnant women tested positive for symptoms that were clinically significant. Additionally, the PREP scale predicted OC symptoms more accurately than the NuPDQ, suggesting that the stress endured by pregnant women during a pandemic may have a perceptible influence on developing OC symptoms. Based on these results, it is important for healthcare professionals to take into account the effect of the pandemic on pregnant women’s mental health. This recommendation should also stay in effect for future crises in caring for the mental health of parents and children. However, future studies should collect a larger, and more varied sample size to get a more accurate result based on ethnic, socioeconomic, and racial factors. 1. B. Mahaffey, et al., Elevated risk for obsessive-compulsive symptoms in women pregnant during the COVID-19 pandemic. Archives of Women’s Mental Health 25, 1-10 (2021). doi: https://doi. org/10.1007/s00737-021-01157-w. 2. Image retrieved from: https://www.rawpixel.com/image/3305337/free-photo-image-pregnancybaby-mom-and

COVID-19 PANDEMIC-RELATED STRESS FACTORS CAN INFLUENCE PERINATAL OUTCOMES IN PREGNANT WOMEN JOYCE CHEN `23 The COVID-19 pandemic has caused severe physical and psychological burdens in individuals around the world. Aside from the disease itself, extended quarantine periods and inability to socialize with others have had a tremendous impact on mental wellbeing. Among the many who were negatively affected by COVID-19, pregnant women tend to feel higher levels of anxiety and stress, thereby leading to decreased wellbeing in their infants. Stony Brook University researchers Dr. Heidi Preis and Dr. Marci Lobel investigated how stress levels of pregnant women affect their perinatal outcomes. A total of 1,367 women above the age of 18 with an average age of 31.4 years were recruited and studied for the entirety of the experiment, all of whom had given birth before July 2020. The team assessed the participants’ medical history and sociodemographic factors such as age, race, and financial status. The participants’ engagement in healthy behaviors was measured based on their personal rankings of certain actions, such as exercising or taking vitamins. Stress levels related to the pandemic or any personal issues during pregnancy, such as discrimination, interpersonal violence, or major life events, were assessed by self-ranking. It was discovered that 7.1% of participants had a preterm delivery and that African American women were the most likely out of all races to have a preterm-delivered infant. Furthermore, 8.6% of these women delivered a small gestational age (SGA) infant, meaning that their baby weighed less than the 10th percentile

for gestational age based on the number of weeks of pregnancy. 91% of the participants who had a preterm delivery reported higher levels of prenatal maternal stress and a greater likelihood of experiencing a major life event while pregnant. Those who suffered from interpersonal violence were twice as likely to deliver an SGA infant. Additionally, women who were diagnosed with COVID-19 during pregnancy were five times more at risk for SGA. Dr. Preis and Dr. Lobel’s study of pregnant women and their underlying anxiety shows how certain women are at risk for unhealthy perinatal outcomes that may affect maternal and infant health. In the future, it may be ideal for pregnant women to receive additional care and support in order to feel less overwhelmed and burdened by stress.

Figure 1 Pregnant women experiencing stress from the COVID-19 pandemic are at risk. 1. H. Preis, et al., Adverse perinatal outcomes predicted by prenatal maternal stress among US women at the COVID-19 pandemic onset. Society of Behavioral Medicine 55, 179-191(2021). doi: 10.1093/abm/kaab005. 2. Image retrieved from: https://images.pexels.com/photos/5425108/pexels-photo-5425108. jpeg?auto=compress&cs=tinysrgb&dpr=2&h=750&w=1260

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DANCING: THE SECRET TO REDUCING CHILDBIRTH PAIN PETER GILLESPIE `25

The success of the labor dance is attributed to both the physical and mental care it provides. The dancing provides freedom of movement to the mother, and the sacral massage provided by the midwife alleviates pain. The calming music and emotional connection established through dancing are just as vital, providing critical support to the entire birthing team. Additionally, dancing with the midwife is thought to foster deeper connections with vital healthcare personnel, building rapport and decreasing trauma within the experience. Indeed, labor dancing shines as a potential method to increase comfort and prevent traumatic experiences for mothers. After all, when has dancing not put someone in a good mood? 1. A. Bihter, et al., The effect of labor dance on traumatic childbirth perception and comfort: a randomized controlled study. Clinical Nursing Research 1, 1-9 (2021). doi: /10.1177/10547738211030745.

Graphics illustrated by Ujala Dar `24

Figure 1 It is vital to incorporate emotional support into pain relief for mothers.

Birth is a psychologically traumatic experience for more than 40% of women. In fact, pain during labor has been linked to depression in the weeks after birth. Current methods to reduce pain predominantly focus on pharmacological and physical support, neglecting the psychologically taxing aspect of childbirth. To maximize comfort, it is vital to incorporate emotional support into pain relief for mothers as well. Some studies have shown that dancing the pain away may be a viable option for pregnant women going into labor. During the active phase of labor, from the time when cervical dilation begins right up until the point of labor, the mother slowly dances with the midwife while she massages her sacral area. Based on this calming phenomenon, researchers from Urla State Hospital in Turkey hypothesized that labor dancing can increase comfort during and after birth and, consequently, decrease traumatic perception. To test this, pregnant women who have given birth just once before were randomly divided between two groups: those who participated in a labor dance and those who followed standard birthing procedures. After the labor dance, a researching midwife administered the Childbirth Comfort Questionnaire near the end of dilation. Later, the Postpartum Comfort Scale and the Traumatic Childbirth Perception Scale were administered in both groups, and survey data was analyzed. Women who participated in the labor dance reported childbirth comfort scores five times higher than those who did not, with the higher comfort level extending after birth as well. The women who danced also experienced significantly lower traumatic perceptions around the birth.

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Figure 2 The labor dance has been shown to increase comfort for mothers and decrease traumatic birth perceptions.


MUSIC-BASED COGNITIVE BEHAVIORAL THERAPY CAN IMPROVE TEST ANXIETY YUKTA KULKARNI `22 From the ages of five to eighteen, school is a major part of a child’s life. A great deal of growing, making memories, and nurturing relationships are experienced during the hours a child is in school. However, education, with a focus on test performance, is considered the most important aspect of attending school. Unfortunately, many children suffer from test anxiety, something that is a discomfort before, during, and after a test. Test anxiety can cause grades to decline and mental health issues to develop, in addition to creating a divide between students. One way students have overcome this block is through Cognitive Behavioral Therapy (CBT), a form of therapy that focuses on changing one's way of thinking, and has shown to improve regulation of emotions and encourage coping strategies. Although CBT is offered in various forms, results haven’t been exhibited with online CBT as there are low completion rates. However, previous studies have discovered that music-based CBT demonstrates increased completion rates, leading to its evaluation. Thus, Christian S. Ugwuanyi and their team of researchers hypothesized that music-based CBT will improve the management of test-related anxiety among students taking Basic Science. The researchers accomplished this by finding 58 students in Enugu State Nigeria who both regularly attended school and scored high on a pretest consisting of a test anxiety questionnaire (TAQ), determining their

level of anxiety. All students were randomly split into an experimental (music-based CBT) or control group (conventional counseling) in accordance with the randomized controlled trial. After weekly therapy sessions for 12 weeks, the TAQ posttest was administered. Students in the experimental group had a significantly lower mean test anxiety rating compared to students in the control group, whose level of test anxiety remained relatively constant. It is suggested that the music elicited greater attention while taking the test, leading to a decline in anxiety. These results demonstrate a potential solution for alleviating test anxiety in students. With diminished anxiety, students can focus on learning and absorbing the material, as well as learn to have confidence in themselves and their ability to perform well. Since this method is not as common in schools, the researchers recommended that teachers, community leaders, and guidance counselors should apply for music-based CBT programs for their students. However, additional research will need to be conducted to determine if certain types of music lead to preferable results, and if all students can experience these results with the same type of music. 1. C. Ugwuanyi, C. Okeke, M. Agboeze, Management of test anxiety among pupils in basic science using music-based cognitive behavior therapy intervention: implication for community development. Journal of Rational-Emotive & Cognitive-Behavior Therapy 39, 285-305 (2021). doi: https://doi.org/10.1007/s10942-020-00371-2

MUSICAL CUES: HOW TUNES MAY YIELD GREATER POSITIVE MEMORIES THAN WORDS OR SOUNDS SOORAJ SHAH `24 When hearing a favorite piece of music or seeing an old photograph, one is reminded of the setting where it was first heard or experienced. This recognition allows an individual to relive the moment. While the extent to which a song or photograph evokes a memory is not yet understood, a novel study led by Dr. Kelly Jakubowski, a professor in the Department of Music at Durham University in the United Kingdom, investigated the extent to which music evoked autobiographical memories in comparison to other methods, such as photographs or environmental ambience. To test the effect of unfamiliar music on autobiographical memory accounts, participants over 18 years old with fluency in English were tested across four different conditions. In the first two experiments, composed of 114 and 100 individuals respectively, the effect of music on autobiographical memory recall was tested alongside the effect of sound. Music was selected from either a film or various genres, respectively. After hearing the music or environmental sound, participants pressed a button when they

recalled a memory which was then explained in a questionnaire. To further establish a comparison between music, sound, and word cues, scientists recruited additional individuals for experiments three and four. Music was tested alongside either concrete or abstract words, and participants again described their memory. Results showed that about 50% of the variables evoked memories in participants. From experiment one, researchers found that sound cues evoked more vivid and social memories than music cues, and negatively associated music showed more positive memories than negative sound. Experiment two showed both music and sound evoking similar responses. In experiment three, music evoked more descriptive and important memories; however, word cues received quicker response times. Lastly, data from experiment four found that word cues elicited more vivid responses than music. Thus, the researchers concluded that music evoked less responses than sound and word cues, but these memories from music were more vivid and detailed. Additionally, negatively associated music evoked more positive memories than exposure to negative words or sounds. The use of music for therapeutic use is heavily supported by this study, as even music that is perceived to be negative elicits positive memories. In a therapy setting, the use of music may be a beneficial tool to help ease the patient into confronting their experiences. Future research should focus on fine-tuning the use of music to help people see past memories as positive. 1. K. Jakubowski, T. Eerola, Music evokes fewer but more positive autobiographical memories than emotionally matched sound and word cues. Journal of Applied Research in Memory and Cognition, 1-18 (2021). doi: https://doi.org/10.1016/j.jarmac.2021.09.002 2. Image retrieved from: https://unsplash.com/photos/pTeZKi29EYE

Figure 1 Regardless of positive or negative associations made, music evoked greater positive memories from participants.

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USING COMPUTATIONAL FLUID DYNAMICS TO MITIGATE AIRBORNE DISEASE TRANSMISSION IN ORCHESTRAS ZHIFEI ZENG `23

Figure 1 Computational fluid dynamics can be used to develop mitigation strategies to reduce COVID-19 transmission in orchestras.

Since the start of the COVID-19 pandemic, many performing arts groups such as choirs, orchestras, opera, and dance companies have suffered a heavy loss. This is mainly because COVID-19 can be spread through infectious aerosols produced by singing or playing wind instruments, which led to show cancellations throughout the industry. To assess mitigation strategies to reduce the risk of infection to performers, researchers from the University of Utah Salt Lake City used computational fluid dynamics to simulate aerosol flow and dispersion in a variety of wind instruments at concert venues. Researchers first developed a computerized fluid dynamics code to simulate the airflow circulation structure of the venue. Next, they simulated the flow pattern of the stage with mitigation strategies such as rearranging the locations of instruments, opening doors, and using a plenum space, a

high-pressure space that promotes air circulation in air conditioning systems. Wind instruments with higher emission rates were placed near the vents, while the piano and percussion instruments were placed in the center of the stage. The researchers measured the average aerosol concentrations in the breathing zone where players’ heads were located to investigate the effectiveness of those strategies. The aerosol concentration showed that for stages with good ventilation, such as a large number of vents in the ceiling, a large vortex structure can be formed to quickly remove emissions. Rearranging the position of instruments and opening the doors is enough to reduce the accumulation of emissions. However, for the stage with older air conditioning systems or poor ventilation, aerosol particles spread and accumulated throughout the stage area even after applying the previous strategies. Adding a plenum space is a better strategy, as it significantly changed the flow geometry and reduced the spread of emissions. The researchers concluded that using computational fluid dynamics can help in designing mitigation strategies to alter the airflow patterns, thus effectively reducing the risk of mutual transmission of performers in the orchestra during the pandemic. Computational fluid dynamics not only help the stage performance industry perform normally during a pandemic, but also allow more audiences to enjoy safe performances during this difficult time. 1. H. Hedworth, et al., Mitigation strategies for airborne disease transmission in orchestras using computational fluid dynamics. Sci. Adv 7, 1-9 (2021). doi: 10.1126/sciadv.abg4511. 2. Image retrieved from: https://pxhere.com/zh/photo/708558

SING AND YOU SHALL LEARN: HOW SINGING ENABLES EASIER LANGUAGE ACQUISITION THUMYAT NOE `23 Learning a new language is challenging, but several studies claim that music may improve the learning process. For instance, primary school children with prior musical experience tend to have greater developed auditory working and verbal memories, allowing for easier language acquisition. Furthermore, according to a previous study, singing increased phonological awareness in Spanish-speaking students, yielding an improvement in English vocabulary recall and pronunciation. Musical activities are enjoyable and can enhance positive emotions which in turn may support language acquisition. To explore the effects of singing on language learning and psychological well-being, Dr. Vera Busse and her team of researchers from the University of Münster designed an experiment with a specific focus on the impact of singing on vocabulary development, grammar learning, and whether positive emotions induced by singing play a role in language acquisition. Researchers expected participants in the singing group to make greater progress in acquisition of the English language. Busse et al. recruited 57 primary school students to participate in the study. Researchers randomly assigned participants to either the singing group or the speaking group. Before their assigned interventions, participants completed preliminary language and intelligence tests. Participants in the singing group then learned English via a singing puppet lesson while participants in the speaking group learned English via a speaking puppet lesson. After three weeks of English lessons, participants completed an English language test. A second test was administered six weeks later to measure retention of language acquisition.

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Figure 1 The same brain regions carry out both singing and language processing, suggesting that singing may expedite language acquisition.

Prior to the English lesson interventions, participants in the speaking group showed higher scores on the language tests than those in the singing group. However, after the intervention, participants in the singing group received higher scores on the tests than the speaking group. Overall, the singing group showed the greatest improvement in learning and correctly spelling new vocabulary. While the singing group did show a greater learning retention after six weeks, it should be noted that participants in the speaking group showed greater retention of grammar rules. Lastly, participants in the singing group showed statistically insignificant higher positive affect. Overall, this study suggests that singing can be beneficial for language acquisition especially in young children with shorter attention spans. Future studies should assess mastery of abstract nouns and grammar development between singing and speaking groups and explore how combining singing with discussions of content and idiomatic expressions may lead to improved understanding of lyrics. 1. V. Busse, et al., Learning grammar through singing? An intervention with EFL primary school learners. Learning and Instruction 71, 1-11 (2021). doi: 10.1016/j.learninstruc.2020.101372 2. Image retrieved from: https://unsplash.com/photos/IkEpl3JkVqU


Artistic

Anomalies:

The Science Behind

Musical Prodigies FIONA MURPHY `23 Introduction It seems impossible that a child musician could be as skilled as an adult expert; however, throughout history, child prodigies like Mozart or Chopin have proved this incredible feat to be possible. While audiences marvel at the rare talent of these musicians, scientists search for explanations behind the phenomena of musical prodigies. To gain a better understanding of their exceptional abilities – and the greater implications of this extraordinary talent on humankind’s collective potential for profound intellectual and creative achievement – scientists study various aspects of the lives and talents of musical prodigies. Quantitative differences in musical ability, motivation, and proclivity support the potential for humans to achieve significant standards of excellence within an intellectual domain. Moreover, a distinction in the genetics and lifespan of musical prodigies suggests possible biological differences that predispose some prodigies towards unusually high achievement, extending beyond the realm of music. Musical prodigies can thus provide new insight into how people acquire the skills and talents that enable the continuous intellectual advancement of humankind. Quantitative Identifiers for Musical Prodigies To validate the definition of a musical prodigy as a child able to perform at the level of an adult musician, Dr. Gilles Comeau and his team in the Piano Pedagogy Research Laboratory at University of Ottawa recruited 26 musicians and 25 non-musicians and asked participants to auditorily differentiate a child prodigy from an adult classical pianist (1). The participants listened to 108 audio clips – one

Figure 1 A depiction of one of the world’s most famous musical prodigies, renowned composer Wolfgang Amadeus Mozart.

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half of which were child prodigy performances and the other half adult musician performances – and attempted to identify whether each piece had been performed by a prodigy after each clip. Musicians were, on average, able to correctly identify 62.6% of the prodigy audio clips, while the non-musicians could only identify 52.8% of the prodigy audio clips. The participants failed to correctly identify around one-third of the prodigy audio clips in the study (1). The results of this study suggested that musicians and non-musicians both performed only slightly above random chance in their ability to correctly identify the musical prodigy, indicating a degree of difficulty present in distinguishing child prodigies from adult musicians. From these results, Dr. Comeau and his colleagues developed a working definition for musical prodigies: children under the age of 14 who possess a high degree of musical ability that allows listeners to judge their musicianship by the same criteria as the abilities of adult musicians (1). This classification of prodigies as children with significant musical ability on par with that of adult musicians suggests the bounding capabilities of the human mind. For some, like musical prodigies, this extraordinary ability entails an unusually rapid acquisition of a complex skill, but other facets of exceptionalism include creativity, innovativeness, and even mastery of a field as an adult. To refine the common understanding of musical prodigies as children possessing exceptional musical ability, researchers aimed to discern whether there are empirical differences in the musical abilities and motivations of prodigies and typical musicians. In one study, University of Montreal PhD candidate Chanel Marion-St-Onge and her colleagues recruited 19 musical prodigies who, before age 14, had either won a top prize at a national or international music competition, or had their talent acknowledged in another significant way (such as through a television appearance) (2). The research team assessed the participants via questionnaires which measured aspects of prodigiousness and personality, such as practice time and moti-

... concept of a “rage to master,” or an inherent desire to master a skill that provides prodigies with deep internal motivation necessary to undergo intense practice.

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vation for musical playing, and standardized intellectual quotient (IQ) tests to evaluate problem-solving and reasoning abilities. Marion-St-Onge and her colleagues determined that the prodigies of their study had achieved musical prominence at an average age of approximately ten years old after a mean of about five years of musical play, confirming that mastery was achieved at a very early age. Interestingly, the prodigies on average did not have significantly higher IQs, a greater cumulative amount of practice hours throughout their lifetime, nor a greater sense of fulfillment from their musical play than non-prodigy musicians. However, prodigies spent twice the amount of time practicing during childhood than other musicians who began training at a similar age, had a greater propensity towards experiencing flow (a state of extreme concentration and control) during practice, and exhibited a greater external motivation for playing music, such as parental influence (2). These greater tendencies toward early musical practice suggest a potential proclivity towards excellence in a specific domain, which may be a driving factor in the advancements that humans make across various intellectual and artistic fields. Dr. Comeau et al. also investigated what traits set prodigies apart from traditional musicians through a case study of an 11 year-old piano prodigy, henceforth referred to as LN. Dr. Comeau’s team provided LN with various cognitive tests to assess his musical abilities, and compared his performance to three university students who possessed perfect pitch. LN demonstrated superior skill in some sub-areas within music such as exemplary musical memory and pitch accuracy of a higher standard than the university students. However, LN performed at an average level in other areas such as rhythm, suggesting that prodigies may excel in some areas of their domain, but do not necessarily outperform non-prodigies in every musical aspect. LN also demonstrated a working memory (short-term memory that humans use to perform tasks) that fell between the 95th and 99th percentile, which the researchers posit may contribute to his superior performance in some sub-skills such as pitch memory (the ability to accurately recall a pitch after listening to a piece of music) (3). Dr. Comeau’s study suggests variabil-


Figure 2 Many musical prodigies possess an intense devotion to

musical practice during their childhood years, which some research suggests may have genetic explanations.

ity in which ways prodigies demonstrate extraordinary skill. Thus, exceptionalism is not restricted to certain fields, but rather can spur advancement in intellect across diverse domains, and even subdomains. Innate Influences Another foundational concept that researchers have assessed is whether genes play a role in the formation of a musical prodigy. Dr. Laura W. Wesseldijk’s research team at Karolinska Institutet in Sweden investigated a potential genetic factor in the age at which a child begins their musical training. The researchers hypothesized that an early start to training would increase the likelihood of an individual developing into a musical prodigy, so a genetic influence on age of onset of training would also influence the development of a prodigy. For the study, Dr. Wesseldijk’s team recruited professional musicians who began their musical training between the ages of two and 18 years old. Additionally, they analyzed a survey of 11,543 twin individuals from the Swedish Study of Twin Adults: Gene and Environment cohort to assess the potential genetic role in an individual’s development into a musical expert. Both the musician and twin samples answered questions pertaining to when they started their musical training, cumulative hours of musical practice, musical proficiency (measured through melody, rhythm, and pitch), and musical achievement (categorized by metrics such as a history of professional performances). Researchers determined that an earlier start to one’s musical training correlated positively with higher musical proficiency and greater achievement. However, in the twin sample – which controls for differences in family environments – the association between early training and musical aptitude is reduced, suggesting that there is a genetic factor which inclines children towards music and starting their training earlier (4). An inherent predisposition to music, and as a result early musical practice,

...an earlier start to one’s musical training correlated positively with higher musical proficiency and greater achievement...

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supports the notion of an innate propensity towards intellect or skill that may contribute to remarkable accomplishment across different domains. Professors of psychology Dr. Ellen Winner of Boston College and Dr. Jennifer Drake of Brooklyn College further explored the idea of a genetic predisposition to musical ability impacting a child’s tendency towards intense musical practice at a young age and their future expertise. Through their examination of child prodigies across various domains – including reading, math, drawing, and music – Drs. Winner and Drake developed the concept of a “rage to master,” or an inherent desire to master a skill that provides prodigies with deep internal motivation necessary to undergo intense practice (5). The researchers evaluated testimonies from parents of prodigies over many years, learning that child prodigies often exhibited exceptionalism at their skill before beginning formal practice and a rapid progression upon beginning formal practice of their skill. Parents even reported this “rage to master” conflicting with normal childhood routines, such as attending school or sleeping, as the children were so invested in dedicating time to their field (5). From their observations and parental testimonials, Drs. Winner and Drake propose an underlying genetic influence on prodigy talents that emerges through a child’s “rage to master.” In fact, this propensity to practice appears 40 to 70 percent heritable. Furthermore, the same genes that control musical aptitude also influence this “rage to master,” a case of genetic pleiotropy. This genetic factor points to an inherent difference present in prodigies that contributes to an intense drive to

master a skill, which in turn aids in exceptional development of that skill. A combination of genetic and environmental factors thus play a role in an individual’s ability to make significant intellectual or creative achievements. Intersection of Life and Music Scientists also assessed whether non-music related aspects of a prodigy’s life are connected to their prodigal status. Maurits Hafkamp, a PhD candidate at the Netherland’s Leyden Academy on Vitality and Aging, worked with her colleagues to investigate the impact of a person’s age at the beginning of intellectual maturity – which this study defines as the first public performance of a person’s musical composition – on their lifespan. Hafkamp et al. conducted archival research on various composers from 1400 through 1915 and found that those who became composers later in life, an indication of a later development of intellectual maturity, lived longer on average. In fact, for each additional year before publishing their first work, the musicians’ age at death was on average roughly two months later. The researchers thus concluded that child prodigies, who have the earliest published pieces among composers, are more likely to have shorter lifespans than their non-prodigy counterparts (6). Hafkamp and her colleagues suggest a potential reason for this decrease in lifespan may be that the genes which cause a more rapid development in intellectual maturity have a co-occurring effect where bodily maintenance and cell repair is diminFigure 3 Researchers have constructed a working definition for prodigies as children who are able to musically perform at a level that is indistinguishable from adult musicians.

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ished. This difference between the lifespan of prodigies and non-prodigies points to differences at the biological level, which in addition to inclining an individual towards immense talent, also impacts other aspects of their life. Conclusion Musical prodigies are anomalies defying the norms of progression in acquiring complex skills such as musical ability. As much as musical prodigies influence the musical community, their very existence influences the scientific community too. Researchers seek to learn more about the psychological phenomenon of prodigious talent and investigate other aspects of prodigy status, such as whether exceptionalism in one area may result in diminished ability in another. Musical prodigies also generate interesting biological questions, as genetic explanations for giftedness spur examinations into whether genes play even more of a role in human lives than is currently known. Ultimately, prodigies offer more than their extraordinary talent: research into their abilities provides a more complete understanding of the human mind and its bounding potential. With an intense devotion to any goal, ample practice, and perhaps some genetic influence, humans have the ability to perform incredible accomplishments that push the limits of human potential – progressing humankind both intellectually and artistically.

References 1. G. Comeau, et al., Can you tell a prodigy from a professional musician? Music Perception 35, 200-210 (2017). doi:10.1525/MP.2017.35.2.200. 2. C. Marion-St-Onge, et al., What makes musical prodigies? Frontiers in Psychology 11, 1-13 (2020). doi:10.3389/fpsyg.2020.566373. 3. G. Comeau, et al., Measuring the musical skills of a prodigy: a case study. Intelligence 66, 84-97 (2018). doi:10.1016/j.intell.2017.11.008. 4. L. Wesseldijk, et al., Why is an early start of training related to musical skills in adulthood? A genetically informative study. Psychological Science 32, 3-13 (2020). doi:10.1177/0956797620959014. 5. E. Winner and J. Drake, Giftedness and expertise: the case for genetic potential. Journal of Expertise 1, 114-120 (2018). ISSN:2573-2773. 6. M. Hafkamp, et al., Intellectual maturity and longevity: late-blooming composers and writers live longer than child prodigies. Aging 9, 1433-1439 (2017). doi:10.18632/aging.101245. Images retrieved from: 1. https://commons.wikimedia.org/wiki/File:%D0%A3%D1%98%D1%85% D0%B8%D1%95%D0%B3%D1%95%D0%B3%D1%82%D1%83.jpg 2. https://pixnio.com/miscellaneous/piano-indoors-music-hand-finger 3. https://pixabay.com/photos/violins-musicians-orchestra-1838390/ 4. https://picryl.com/media/5be97a2d-abe0-4ece-a113-f384f68836ef 5. https://picryl.com/media/mirror-83dcab 6. https://picryl.com/media/mirror-221ef8

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Introduction According to the CDC, 5.8 million Americans suffered from Alzheimer’s disease (AD) in 2020, a number projected to triple to 14 million people by 2060 (1). AD is characterized by the progressive decline of cognitive function and behavioral issues, most common in geriatric populations. Given the absence of medications that demonstrate long-term effectiveness, music intervention is a promising treatment for AD, as musical memories remain in contrast to other types of memories which decline with AD (2). Current research has advocated for the increased integration of music in clinical settings as it ameliorates many of the cognitive and behavioral symptoms of AD, such as anxiety and hallucinations. Due to the rehabilitative effects on AD patients and positive reception from caregivers, individualized music therapy should be implemented in conjunction with pharmacological intervention for AD with a focus on active music intervention. Benefits of Individualized Music Intervention Individualized music intervention, which utilizes music that is familiar to the patient, is especially effective in improving the cognitive and behavioral symptoms of AD. A study conducted by M. Gómez Gallego from Universidad Católica San Antonio de Murcia and J. Gómez García from Universidad de Mur-

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cia treated 42 patients with mild to moderate AD with individualized music therapy for six weeks. Music was chosen after the patients completed a questionnaire on musical preference, and songs that most patients enjoyed were used. Researchers measured the effectiveness of treatment by assessing patients before and after intervention with the Hospital Anxiety and Depression Scale (HADS), the Neuropsychiatric Inventory (NPI), and the Mini-Mental State Examination (MMSE). A score of 0-7 on the HADS indicates normal psychiatry, 8-10 borderline depression or anxiety, and 11-21 depression or anxiety. In both mild and moderate AD groups, there was a significant improvement in depression (9.00 to 5.66 and 9.62 to 5.75, respectively) and anxiety (12.66 to 11.33 and 13.37 to 11.50, respectively) (6). The NPI is a questionnaire designed to assess the neuropsychiatric symptoms of the participant over the previous month, including delusions, agitation, and irritability. For each item, a score of 1, 2, or 3 indicates a severity of mild, moderate, and severe, respectively. In the mild AD group, NPI scores suggested a significant improvement in anxiety (2.67 to 0.63) (6). In the moderate AD group, NPI scores suggested a significant improvement in the symptoms of delirium (3.88 to 1.75), hallucinations (3.75 to 2.00), agitation (2.50 to 1.25), irritability (3.25 to 0.88), and disinhibition, or a pattern of norm-violating antisocial behaviors (0.75 to 0.38) (6). The MMSE evaluates behavioral symptoms such as orientation, attention, verbal memory, and motor skills on a scale from 0 to 30, where higher scores indicate better cognition. Music therapy significantly increased MMSE scores in the domains of orientation (3.44 to 6.16) and memory (3.30 to 4.33) for the mild dementia group and the domains of orientation (3.87 to 5.62), language (5.86 to 7.75), and memory (3.37 to 5.03) for the moderate dementia group (6). From Gómez Gallego and Gómez García’s research, it is evident music

therapy has positive effects on a broad range of AD symptoms, whereas current pharmaceutical treatments target certain symptoms while potentially exacerbating others. Thus, the long-term use of music interventions may lead to a decrease in dependence on psychotropic drugs, presenting alternative options for patients who do not benefit from these drugs. In addition, individualized music treatment’s potential to improve symptoms regardless of AD severity supports its use across stages of the disease. Further, music therapy is fast-acting—improvements were observable after four sessions in the above study. Therefore, music intervention may reduce symptoms of AD and improve AD patients’ quality of life (6). Active vs Receptive Music Interventions Within individualized music interventions, active music interventions (AMI) may be more effective than receptive music interventions (RMI). RMI does not involve direct participation. In contrast, AMI involves active participation from patients individually or between each other. A study led by Maria Gomez-Gallego from the Catholic University of Saint Anthony administered twelve 45-minute sessions of AMI, RMI, or hospital care without music intervention to ninety AD patients. Both AMI and RMI were individualized through questionnaires about patient preferences for musical genres, singers, instruments, and songs. In this study, AMI differentiated from RMI in the form of a welcome song, rhythmic exercises, dance exercises, a music quiz, and a goodbye song. Researchers assessed intervention effectiveness by measuring patient symptoms before and after treatment with the MMSE, NPI, and Barthel Index (BI). MMSE results indicated a greater percentage of AMI patients (92.9%) exhibited improvements in behavioral symptoms compared to

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RMI patients (42.9%) and the control group (12.2%). The BI is a 10-item questionnaire that assesses functional state, where a higher score on the BI indicates increased independence in carrying out basic daily living activities. 46.4% of the AMI group exhibited an improvement in functional state as assessed through the BI, compared to 14.3% of the RMI group and 17.1% of the control group (3). The NPI measured changes in cognitive deficits. 85.7% of the AMI group exhibited improvements in cognition compared to 11.9% of the RMI group and 6.3% of the control group (3). Gomez-Gallego’s study suggests AMI is a more effective treatment option than RMI as improvements in mean BI, MMSE, and NPI symptom scores were significantly higher in the AMI group than in the RMI and control groups (3). AMI promotes self-expression, engagement, and socialization (for example, the form of foot-tapping, dancing, and recall), which requires the involvement of task-related brain regions, which may explain AMI’s effectiveness (3). Comparing to what extent active or receptive music intervention improves AD symptoms is key in designing the most effective therapies that work for a greater percentage of AD patients. Benefits of Music Interventions to Caregivers In addition to relieving many AD symptoms for patients, individualized music interventions also relieve the burden from caregivers who often struggle to manage the behavioral challenges of AD patients. A study led by Emmali Buller of Saint Francis Ministries surveyed the caregivers of AD patients enrolled in “The Roth Project,” a program implemented by the Alzheimer’s Association of Central and Western Kansas that provided music-based approaches to address symptoms of AD. Researchers measured the effectiveness of treatment through a survey designed to measure caregiver satisfaction and caregiver perception

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of the impact of individualized music on the mood and behavior of AD patients. 78 of the 79 caregivers who participated in the survey indicated they were either “satisfied” or “very satisfied” with individualized music intervention (5). 94% also indicated they perceived their AD patients to either “like” or “very much like” listening to the individualized music (5). The ability of music intervention to foster a meaningful care environment where both patients and caregivers are satisfied is especially important. If caregivers are satisfied and happy, the quality of care will improve as well. Additionally, the satisfaction of both caregivers and patients would allow for the facilitation of social engagement between each other, which is often not present or strained due to the debilitating behavioral symptoms of AD. Often overlooked, caregiver satisfaction is equally important as patient satisfaction and should be investigated further. As 95% of the patients reported requiring assistance in working the iPod device to listen to music, caregivers must learn how to navigate these music-playing devices for their patients (5). Learning how to operate music devices is a relatively simple procedure that requires a short amount of time to learn compared to procedures caregivers may learn for other interventions. This decrease in time and money spent on training allows music interventions to be easily implemented. As a simple, non-invasive, and cost-effective management strategy of AD, it is quite a breakthrough that music therapy benefits both patients and caregivers.


Drawbacks to Music Interventions Like every therapeutic intervention, music therapy has its drawbacks. Mahsa Soufineyestani from the University of Minnesota Duluth led a systematic review of studies investigating the effects of music intervention which revealed that while some studies concluded that most AD patients improved by listening to individualized music, some became increasingly agitated (7). A hallmark of music therapy is that it evokes memories, which are linked to emotion which is further linked to behavior such as agitation. However, it is difficult to predict whether these memories and emotions will be positive or negative. Some patients may have music triggers that foster negative memories, and ultimately increase agitation. Sensitivity to a specific song can result in emotional flooding, which overstimulates and agitates the patient. The review also cited a study that observed more behavioral disturbance was observed between experimental groups who were administered Baroque music for 4 hours over a 4-week period than the control group (7). These disturbances could be explained by the fact that not all patients enjoy Baroque music, suggesting the importance of a treatment plan that is specifically catered towards the interests of the patient. Another study that was reviewed showed that AD patients with high levels of depression demonstrated increased levels of sadness after administration of music intervention compared to AD patients with low levels of depression (7). Although music interventions have been successful for some, comorbidities (such as the presence of depression and AD together) may hinder the effectiveness of treatment. This calls for the investigation into the effects of comorbidities of AD and for music treatment approaches to be designed for AD patients with a variety of different illnesses. Lastly, two reviewed studies observed that agitation that was reduced during music therapy returned after the therapy (7). This calls into question the harm of relying on music therapy approaches as the only treatment for AD. Since effects are not sustained, music therapy should be incorporated alongside pharmacological treatments. Conclusion Music interventions are effective in managing the symptoms of AD. Therefore, it is important to promote music therapy as an alternative or co-treatment to the therapeutic management of AD symptoms. Though studies suggest interactive and familiar music is most effective in improving cognitive and behavioral symptoms, the impact of other factors, like music genre (for example, rock music versus classical music), may be of interest for further study. Researchers may also study the effectiveness of combining music interventions with pre-existing medications. Lastly, comparing and combining music therapy with other non-pharmacological therapies, such as art therapy and dance therapy, may yield results of clinical interest and allow a greater variety of people to utilize therapies catered to individual interests.

Figure 1 Even as other types of memories decline as an Alzheimer’s brain (top) deteriorates, memory of music is left intact even in late stages of the disease.

References 1. Alzheimer’s disease and related dementias, CDC, (2020). 2. M. Leggieri, et al., Music intervention approaches for Alzheimer’s disease: A review of the literature. Frontiers in Neuroscience 13 (2019). doi: 10.3389/fnins.2019.00132. 3. M. Gómez Gallego, et al., Comparative efficacy of active group music intervention versus group music listening in Alzheimer’s disease. International Journal of Environmental Research and Public Health 18, 8067 (2021). doi: 10.3390/ijerph18158067. 4. J. Enrique de la Rubia Orti, et al., Does music therapy improve anxiety and depression in Alzheimer’s patients?. The Journal of Alternative and Complementary Medicine 24, 33-36 (2018). doi: 10.1089/acm.2016.0346. 5. E. Buller, et al., The Roth Project — music and memory: a community agency initiated individualized music intervention for people with dementia. Kansas Journal of Medicine, 12, 136-140 (2019). 6. M. Gómez Gallego & J. Gómez García, Music therapy and Alzheimer ‘s disease: cognitive, psychological, and behavioural effects. Neurologia (Barcelona, Spain) 32, 300-308 (2017). doi: 10.1016/j. nrl.2015.12.003. 7. M. Soufineyestani, et al., Impacts of music intervention on dementia: a review using meta-narrative method and agenda for future research. Neurology International 13 (2021). doi: 10.3390/ neurolint13010001. Images retrieved from: 1. https://commons.wikimedia.org/wiki/File:AD_versus_CO.jpg 2. https://www.vecteezy.com/free-vector/treble-clef”>Treble Clef Vectors by Vecteezy 3. https://www.vecteezy.com/free-vector/film-grain”>Film Grain Vectors by Vecteezy

Graphics Illustrated by Ujala Dar`24

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Brain Mapping & MusicTherapy

Linked to Postoperative Success DAPHNE SIOZIOS `23 17

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Introduction Though the fields of science and art may seem disconnected, certain art forms such as music can be applied to traditionally scientific operations, and particular scientific phenomena may be influenced by distinct art forms. Music therapy (MT) is an emerging discipline that allows surgeons to address lingering postoperative (after surgery) psychological effects patients face while improving palliative benefits through the implementation of specially-designed music monitoring techniques (1). Noise-canceling headphones placed on conscious but sedated patients allow for the introduction of intraoperative (during surgical procedures) music, which is thought to diminish the likelihood of negative outcomes, such as nerve damage and chronic pain, brought on by surgical complications. These negative outcomes may further be avoided via brain mapping wherein biological data from the human brain is interpreted as spatial representations resembling maps to further study the anatomy of the central nervous system (CNS). As such, combining MT and brain mapping may have positive implications for postoperative outcomes in the neurological context. According to recent studies, the use of MT and mapping of specific cortical sites in the brain during awake surgical procedures in particular have shown postoperative benefits. By creating cortical maps to distinguish different regions in the cerebral cortex, there is an increased ability to pinpoint which part(s) of the cortex experience disturbances to large neural networks (2). Such disruptions may alter the functionality responsible for carrying out high-level cognitive tasks relating to playing music, thus demonstrating the need to further examine the relationship between music and cognitive behaviors. The effects of MT in conjunction with motor control monitoring, examination of cognitive conformability, and analysis of psychological symptoms have the potential to significantly decrease depressive symptoms and pain episodes while providing a lasting increase in postoperative cognitive capabilities for both musicians and nonmusicians.

like tension and anxiety lead to adverse outcomes, such as abnormal circadian sleep patterns, hypertension, and irregular heart rhythms, which significantly subside with the use of MT. As established by an evaluation of anxiety levels across liver cancer cases, traditional care only provides adjuvant treatment for such maladies; it does not have the same effect on patient outcomes as MT interventions would. In this study, scientists measured anxiety levels in t w o differing groups of patients via the Self-Rating Anxiety Scale (SAS). It was found that anxiety levels of non-MT patients (with a mean of 45.2 points +/- a 9.52 standard margin of error) was much higher than that of patients in the MT group (with a mean of 37.65 points +/- a 8.54 standard error) (1). Even though these statistical findings suggest the effectiveness of MT in diminishing postoperative anxiety, there is still uncertainty surrounding the direct implications of this alternative therapy in further facilitating and maintaining a positive resolution throughout surgery. Craniotomies are a specific type of surgical procedure that allow immediate access to the exposed brain through temporary removal of a bone flap from the skull. Specifically, awake craniotomies provide the opportunity for cortical and subcortical brain mapping, which minimizes surgical morbidity (temporary or permanent disability observed during or after surgery) and optimizes the potential for larger amounts of tissue to be successfully resected, or removed during surgery (2). Similarly, intraoperative musical performance during brain lesion resection may prevent potential subsequent neurological disturbances. Because playing musical instruments requires a substantial amount of skill and simultaneous activation of higher level cognitive tasks, performing music during active surgery may very well help uncover the linkage between music and cognitive function in relation to marked regions of the encephalon (3).

Music Therapy & Brain Mapping MT has largely been regarded as a novel application in clinical practice over the past few years, as it has been shown to improve the emotional states of patients experiencing preoperative (before surgery) stress or long postoperative treatment cycles. New approaches in intraoperative MT also continue to gain recognition as they assist in the restoration of mental health in patients post-surgery and increase clinical efficacy (2). The benefits of MT are derived from resonance (the manner in which music affects individuals psychologically and physically), stimulation of dopamine within the limbic system, and brainstem network theory. Brainstem network theory states that music is passed along the brainstem network structure in a series of impulses, ultimately regulating the activity of the CNS and one’s physiological and psychological states. Previous research studies have found that negative preoperative emotions

Monitoring Motor Control During Awake Craniotomies Recently, researchers have proposed that musicians may benefit from playing their instruments during awake craniotomies, as it enables surgeons to monitor both motor control and preservation of one’s cognitive state after surgery. While traditional MT methods have indicated vast improvements in the emotional states and cognitive abilities of patients throughout recovery, a more focused study of individuals with instrumental experience can help further evaluate the distinct brain region responsible for dissociative motor behavior. A 2019 case study done by Dr. Vitoria Piai and her colleagues at the Donders Institute for Brain Cognition and Behavior in Nijmegen, Netherlands evaluated the resection of a tumor in the left supplementary motor area (SMA) in the brain of a violinist between the ages of 35-40 with more than sixteen years of musical education (4). The SMA is crucial for fine motor skills involved in music performance. In order

...combining MT and brain mapping may have positive implications for postoperative outcomes in the neurological context.

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to carefully monitor changes to the patient’s music performance that would be detected via electrodes placed on the surface of the brain, preoperative and intraoperative monitoring plans with labeled brain regions were composed. In the preoperative preparations, functional magnetic resonance imaging (fMRI) data from finger-tapping, word-reading, and verbal generation tasks were obtained as a baseline reference for comparison with data from the resection period. Preoperative cognitive, language, and motor testing demonstrated that no impairments relative to age were seen within the patient, as he/she exhibited a T-score (how much results vary from the mean) less than the 30th percentile. These low scores indicate low levels of anxiety, as well as depressive states, experienced by the patient prior to the craniotomy. Prior to the procedure, the patient was also asked to familiarize himself/herself with a straightforward piece that could guarantee a near perfect performance during the surgery, so that any changes in music performance would be attributable to intraoperative issues and not the patient’s violin-playing experience. Although the patient experienced an epileptic seizure during cortical stimulation, monitoring his/her complex motor and musical functions as he/she played the violin throughout resection allowed for better analysis of his/her condition. As such, a near complete resection was achieved, showing no postoperative deficits that would lead to future exacerbation of functional impairment. Specifically, 95% of the total tumor was successfully resected, which allowed the patient to resume normal activities as well as professional musical duties after just two weeks (4). While the postoperative results seem promising, it is important to note that they were self-reported by the patient and were not determined via neuropsychological testing, thus affecting the scope of their validity. Another study conducted by a group of clinicians in the Department of Neurosurgery at the Medical University of Warsaw aimed to observe another individual’s ability to perform music. In this evaluation, Dr. Tomasz A. Dziedic and his team examined the performance of a 42-year-old female amateur pianist with transient speech disturbance. An MRI indicated that the presence of a supratentorial cavernoma (a cluster of abnormal blood vessels) was causing symptomatic epilepsy (6). To attempt resection, an awake protocol with anesthesia was initiated, shortly followed by a left-sided temporo-occipital craniotomy. The researchers used a 4 mA current to stimulate the cortex and observe language responses. During the awake craniotomy, the patient was asked to play music that she had memorized solely with her right hand, followed by playing solely with her left hand. The patient appeared to experience extreme difficulty as she could not cognitively process how to continue the movements while playing. Next, the patient was asked to play music from a score, following the same tasks of playing with her right hand, then her left hand. It was found that she was unable to

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read the music or interpret the scores. This study indicates success in optimizing a technique for intraoperative monitoring of music performance using hand movements. The cortical stimulation revealed that the basal ganglia and cerebellar areas are related to music performance, and that to successfully perform music, feedback from the auditory cortex must not be compromised. In these studies, the use of musicians was crucial as their musical ability served as a complex, cognitively-demanding skill that could be monitored via intraoperative music performance. These studies suggest that musicians acquire extensive benefits from awake craniotomies, as these surgeries can pinpoint the exact areas of the cortex that need to maintain viability for an individual to preserve musical functionality. Moreover, by focusing on these specific areas of the brain as opposed to the brain as a whole, awake craniotomies allow for more focused treatment of one’s condition and a more specific approach to applying MT interventions in areas directly associated with music. Maintenance of Cognition While it is important to ensure that the motor control needed for musical performance is preserved during these awake craniotomies, another aspect to maintain in individuals undergoing these procedures is their cognitive states. Electrical stimulation during awake surgery through brain mapping of the right non-dominant hemisphere has revealed the function of visuospatial and social cognition in this area. While visuospatial cognition refers to one’s perception and cognitive representation of space, social cognition encompassess all the cognitive processes involved in nonverbal social interaction (facial emotion recognition or theory of mind) (6). Historically, brain mapping in relation to cognitive function has been fairly limited due to an underestimation of the cognitive implication in the right hemisphere, as well as its anatomical and structural complexities. However, taking a closer look at the right hemisphere can provide surgeons and researchers alike with a better understanding of the maintenance of cognition during awake craniotomies.

Figure 1 Music therapy has been as a successful non invasive surgical technique in improving overall patient statisfaction as seen through inreased post surgery cognitive function and decreased neurological deficits.


During awake craniotomies, attempts have been made to map the right hemispheric cortical areas involved in recognizing facial emotion to understand its relation to preservation of cognition. A study consisting of 18 patients with right hemispheric lesions examined 386 cortical sites using Ekman’s faces (which feature distinctive facial expressions) as a preoperative baseline test. Ekman’s faces involve showing photographs of faces exhibiting one of the 6 facial emotions – anger, happiness, fear, surprise, disgust, and sadness – to patients (6). Of the 386 sites studied during the procedure, researchers identified 5 sites (approximately 1.30%) as responsible for facial emotion recognition in 5 patients (7). These sites consisted of one site in the medial segment of the superior temporal gyrus (STG), one site in the posterior segment of the STG, one site in the posterior segment of the medial temporal gyrus (MTG), and two sites in the supramarginal gyrus. Not only do these findings suggest that the cognitive functions of the right hemisphere are essential for everyday facial emotion recognition, but also that this area of the brain should be a greater focus of study as cortical and subcortical structures involved in visuospatial and social cognition demonstrates marked variability amongst patients. Thus, it can be inferred that cortical and subcortical mapping of the nondominant hemisphere can be used as a gold standard during awake craniotomies to track the development of neuropsychological tasks. Further study is needed to determine the potential of these sorts of mapping to decrease depressive symptoms an individual may experience, measured through levels of emotion and perception. Psychological and Emotional Outcomes A study conducted in 2017 by researcher Dr. Pao-Yuan Wu and colleagues at a medical institution in Taiwan investigated the outcomes of MT interventions on the levels of anxiety and other psychological factors experienced by patients before and after an awake craniotomy. The study consisted of 38 patients divided into two groups of 19, where the experimental group selected and listened to music of their preference in the waiting room and the control group received the usual preoperative care (8). Patients were also included based on having brain tumor diagnoses, being at least 20 years of age, having no visual or auditory impairment, and the ability to communicate in either Mandarin, Chinese, or Taiwanese. The MT intervention group was allowed to choose their music from six types of soothing music, including nature, piano, harp, orchestra, jazz, or synthesis music. During the procedure, these individuals were allowed to listen to their preferred music once again as they laid on the operating table. The results indicated that the patients who had exposure to MT intervention experienced a significant decrease in their level of anxiety and that the music intervention significantly reduced average heartbeat rate to 84.5 bpm with a systolic pressure of 42 mmHg and diastolic pressure of 38 mmHg gradually over time as compared to average preoperative readings of 168 bpm heart rate and 166 mmHg systolic and 164 mmHg diastolic pressures. Such decreases in physiology suggests that MT is associated with decreased levels of anxiety and distress after patients have undergone an awake craniotomy. Moreover, these results can revolutionize the way perioperative (around the time of surgery) care is given to patients in high stress situations before undergoing surgery. Providing opportunities to listen to soothing music in the waiting room and during surgery to reduce anxiety can be a viable goal in improving human care and ensuring lasting positive outcomes from invasive procedures.

Conclusion Brain mapping in combination with MT can lead to extensive postoperative outcomes such as decreased stress and anxiety, motor control management via implementation of intraoperative music techniques, and maintenance of cognitive conformability by examination of specific brain regions. While MT promotes neuronal repair and decreases pain episodes even after patients have stopped listening, brain mapping can pinpoint critical regions and tumor areas to assist in minimizing cognitive impairment postoperatively. Therefore, both of these disciplines can be used in conjunction to further improve upon the recovery process of patients undergoing complex, high stress procedures. However, while the previous studies demonstrate the promise of MT during neurosurgical procedures, there are still many areas to address in order to confirm high postoperative efficacy. For example, disruption of musical ability should always be compared with a baseline speech or motor task to understand the qualitative origin of the deficit brought on by illness. In other words, patients should always be asked to complete certain tasks preoperatively so that intraoperative and postoperative findings may later be compared to account for any changes in the patient’s state. Musical ability should also be assessed with a standardized objective scoring method from before and after surgery to allow for comparison of the effectiveness of this alternative therapy. Possible future avenues may include using successful brain mapping techniques to further assess and prevent the onset of neurodegenerative diseases or disorders that may not be treatable at the current time.

References 1. J. Liang, X. Tian, and W. Yang, Application of music therapy in general surgical treatment. Biomed Research International 2021, 1-4 (2021). doi: 10.1155/2021/6169183 2. T. Dziedzic, et al., Awake intraoperative mapping to identify cortical regions related to music performance: technical note. Journal of Clinical Neuroscience 83, 64-67 (2021). doi: 10.1016/j. jocn.2020.11.027. 3. A. Scerrati, et al., Artists playing music while undergoing brain surgery: a look into the scientific evidence and the social media perspective. Clinical Neurology and Neurosurgery 196, 105-111 (2020). doi: 10.1016/j.clineuro.2020.105911. 4. V. Piai, et al., Awake surgery for a violin player: monitoring motor and music performance, a case report. Archives of Clinical Neuropsychology 34, 132-137 (2019). doi: 10.1093/arclin/acy009. 5. F. Bernard, et al., Right hemisphere cognitive functions: from clinical and anatomic bases to brain mapping during awake craniotomy part I: clinical and functional anatomy. World Neurosurgery 118, 348-359 (2018). doi: 10.1016/j.wneu.2018.05.024. 6. F. Bernard, et al., Right hemisphere cognitive functions: from clinical and anatomic bases to brain mapping during awake craniotomy part II: neuropsychological tasks and Brain mapping. World Neurosurgery 118, 360-368 (2018). doi: 10.1016/j.wneu.2018.05.024. 7. P. Wu, et al., Effects of music listening on anxiety and physiological responses in patients undergoing awake craniotomy. Complementary Therapies in Medicine 32, 56-60 (2017). doi: 10.1016/j. ctim.2017.03.007. Image retrieved from : 1. https://pixabay.com/photos/surgeons-operation-operating-room-6841376/

Graphics Illustrated by Annie Li `22

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ART AND MEDICINE: THE EFFECTS OF TECHNICAL DRAWING EXERCISES ON SPATIAL VISUALIZATION OF HUMAN ANATOMY THUMYAT NOE `23 Spatial visualization, the ability to visualize shapes and the orientations of objects in space, can help medical students learn human anatomy, which many consider a challenging area of study. Past studies suggest that high spatial visualization positively correlates with increased success in scientific disciplines, leading researchers from Kansas City University to believe that enhancing spatial visualization through technical drawing exercises may help medical students successfully learn anatomy. In a recent experiment, researchers from Kansas City University tested the effects of technical drawing exercises on spatial visualization of medical students enrolled in neuroanatomy courses. Researchers hypothesized that technical drawing exercises may improve spatial visualization and thus help medical students perform better in anatomy courses. In order to test their hypothesis, researchers recruited 84 medical students enrolled in a neuroscience course to participate in this experiment. For baseline measurements, participants filled out a pre-questionnaire and took the Mental Rotations Test (MRT), a standard spatial skills test. Afterwards, researchers randomly assigned some participants to attend four art sessions. During each art session, participants worked on technical drawing exercises. Upon completion of these sessions, participants completed a post-questionnaire and took the MRT again. Researchers compared initial and final performances on the test to determine if technical drawing exercises improved spatial visualization skills. Although most participants showed improvement on the final assessment, participants who attended art sessions showed greater improvement

Figure 1 Research suggests that studying anatomy requires high spatial visualization skills.

than those in the control group. Researchers also found that participants with prior artistic experience showed greater improvement on the post-assessments, and participants who noticed an improvement in their spatial visualization skills after attending art sessions showed greater improvement compared to those who did not notice a change in their artistic abilities. Overall, the results imply that technical drawing exercises may enhance spatial visualization and help medical students in their anatomy studies. Those who wish to pursue a career in medical care should consider engaging in technical drawing exercises to improve spatial visualization. A possible direction for future studies is to control for a sample of participants who engage in technical drawing exercises during their free time. 1. Y. Na, et al., Spatial visualization of human anatomy through art using technical drawing exercises. Anatomical Science Education 0, 1-12 (2021). doi: 10.1002/ase.2080. 2. Image retrieved from: https://unsplash.com/photos/drkk_Tqbqq4

CAN A VIRTUAL REALITY SIMULATION WITH A CRIMINAL’S FUTURE SELF DECREASE SELF-DESTRUCTIVE BEHAVIOR? JOYCE CHEN `23 Many of us have done things that we regret over the course of our lifetime. Some of us develop from our setbacks, while others are imprisoned and ostracized by society. These criminals’ actions were likely impulsive, completely disregarding the consequences that the future may bring. However, poor decisions can be resolved by introspection. Dr. Jean-Louis van Gelder of the Max Planck Institute for the Study of Crime, Security and Law sought to understand how convicted offenders would react if they engaged with an older version of themselves through virtual reality (VR). He and his research team hypothesized that the offenders would reflect on their actions and grow from them instead of engaging in self-destructive behavior. The team studied 24 young male offenders over the course of three months. Prior to this experience, participants had pictures of their faces taken by the researchers. These images were processed to create aged 3D avatars. The participants were asked to answer several survey questions

Figure 1 The unique usage of virtual reality as a form of treatment for prisoners in Dr. Jean-Louis van Gelder’s study paves the way for possible new intervention methods in the future.

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based on their ability to connect with and imagine their future selves, how much they engaged in self-destructive behavior, and their expectations for their future lives. Afterwards, they were immersed in the VR simulation, where they met their older selves in a futuristic environment. The participants reported their emotions and experiences during the simulation immediately after. The researchers noticed that the offenders reported decreased levels of self-defeating behavior after the VR simulation. Behaviors such as “spending more money on something than intended” had decreased from 71.4% to 52.4% and “drinking alcohol” decreased from 52.4% to 28.6%. Based on a linear regression analysis, a significant positive correlation between the offenders’ poor vision of their future and their self-defeating behavior was represented by p = 0.04 with an adjusted of 0.03. Therefore, an increase in an offender’s vividness of the future is linked to the decrease in their self-destructive behavior. However, future studies with larger sample sizes would be necessary to draw more accurate conclusions. Dr. Gelder and his colleagues’ study showed how art, specifically digital media and virtual reality, can be used for psychological research and possibly therapeutic interventions. Although additional research is needed, the researchers believe that this experiment highlights the potential of the arts and technology in decreasing crime rates by changing behaviors in offenders. 1. J. Van Gelder, et al., Interaction with the future self in virtual reality reduces self-defeating behavior in a sample of convicted offenders. Sci Rep 12, 2254 (2022). doi: 10.1038/s41598-02206305-5. 2. Image retrieved from: https://cdn.pixabay.com/photo/2016/08/18/10/02/smartphone-1602486_1280.jpg


POST-STROKE NEUROPLASTICITY MAY ALTER ARTISTIC SKILLS COMPENSATION VIGNESH SUBRAMANIAN `24 A stroke, or cerebrovascular accident, is a medical emergency in which blood flow to the brain is interrupted or reduced. Strokes are the result of either an ischemic (arterial obstruction) or hemorrhagic (arterial rupture) event and are associated with the arrest of neuronal activity in the brain. However, various regions of the central nervous system (CNS) have demonstrated a capacity for recovering from post-stroke cerebral necrosis by regenerating and reorganizing synaptic connections, an ability known as neuroplasticity. CNS regions that exercise this ability are also among those associated with critical motor skills, visual acuity, and spatial awareness that define an individual’s sensory perception and artistic abilities. A study led by Griffith University researchers aimed to better characterize the relationship between post-stroke neuroplasticity and artistic skills compensation. Researchers conducted a systematic review of fifteen famous artists who each survived a left or right cerebral stroke to assess differences between premorbid and ‘post-stroke’ artistic styles as well as compare clinical outcomes between the two hemispheres. In the ten patients who had right cerebral strokes, particular attention was paid towards evaluating use of elementary bold colors, simplification of images, inability to reproduce chiaroscuro (treatment of light and shade), and left-side neglect. In the five patients who had left cerebral strokes, a loss of tri-dimensionality, perspective, rigidity, and repetitiveness were watched for, as these were previously thought to be perceptual attributes of each hemisphere. Researchers found that in nearly all examined cases, the artists demonstrated statistically significant recovery of artistic skills. Ten artists

Figure 1 Neuroplasticity is the capacity of the brain to develop and reorganize synaptic connections with new experiences or following injury.

adopted new, more expressive designs, while the rest either demonstrated restitutio ad integrum (restoration of premorbid styles) or could not have an attributable style clearly established. Patients with right hemispheric stroke primarily suffered left-side hemineglect, paresis (muscular weakness), visual field omissions, and apraxia (difficulty with skilled movement). Patients with left hemispheric stroke were found to have suffered right-side hemiparesis and aphasia (inability to understand or express speech) as well as having to learn to work with a non-dominant hand. The majority of patients were also found to have developed ischemia (reduced blood flow) in the frontal, temporal-parietal, or occipital cerebral areas associated with the processing and integration of motor functions. These results suggest that in the context of the damage done by stroke-induced lesioning, poststroke neuroplasticity in these artists’ brains was responsible not only for neurological recuperation, but also the development, in some cases, of entirely new artistic sensibilities and styles. 1. E. Petcu, et al., Artistic skills recovery and compensation in visual artists after stroke. Frontiers in Neurology 7, 1–12 (2016). doi: 10.3389/fneur.2016.00076 2. Image retrieved from: https://commons.wikimedia.org/wiki/File:Neuroplasticity.jpg

FEELING THE RAINBOW: ADVANCES IN MULTISENSORY ARTISTIC EXPERIENCES FOR THE VISUALLY IMPAIRED PETER GILLESPIE `25

Figure 1 A color’s hue, warmth, and intensity can now be expressed by sound and temperature.

Is art seen, or is it experienced? Thanks to the work of researchers Jorge Bartolome, Gilsang Cho, and Jun-Dong Cho at Sungkyunkwan University, people with visual impairments can now appreciate artwork through senses other than vision. Previous research in allowing people with visual impairments to experience art has appealed to just one other sense, such as sound or touch. However, Bartolome and his team believe that appealing to multiple senses at once can improve the user’s ability to memorize and integrate artwork. How does one determine the sound of a color or its temperature? To answer this question, Bartolome gave pairs of adjectives to 18 college students with normal vision. They then categorized each pair in relation to brightness or darkness, warmth or coldness, or both of these designations. Later, they rated how strongly related the adjective pair was to these designations. For example, given the adjective pair noisy and quiet, participants may report that the pair relates strongly or weakly to brightness or

darkness, but not feelings of warmth or coldness. Participants then rated the adjective pair to a sensory stimulus. For example, when listening to a musical piece, a participant may say the piece relates strongly to the adjective “noisy.” The researchers also weighted the frequency of responses. By creating a link between adjectives and color character and another between adjectives and sensory stimuli, the researchers essentially created a connection between color character and sensory stimuli and used their unifying adjective list to bridge the gap. The researchers found that a higher temperature was best for representing warm colors like red, and colder temperatures for representing colder colors like blue, suggesting the applicability of temperature in communicating hue. Furthermore, because musical pieces were more easily distinguishable than temperature, they were deemed best for communicating aspects like brightness or darkness. When a different group of participants were asked to guess the color related to each stimulus, hue was determined with 71.6% accuracy and color character with 92.5% accuracy. Given the limited practice with this multimodal model and the supposed heightened sensory ability of visually impaired individuals, this methodology suggests a promising lens through which visually impaired individuals may experience fine art. 1. J. Iranzo Bartolome, G. Cho, and J. Cho, Multi-sensory color expression with sound and temperature in visual arts appreciation for people with visual impairment. Electronics 10, 1336-1336 (2021). doi: 10.3390/electronics10111336. 2. Image retrieved from: https://unsplash.com/photos/dvUyPX0O3-0

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A A REVIEW REVIEW OF OF NITINOL’S NITINOL’S APPLICATION APPLICATION IN IN VASCULAR VASCULAR STENTS STENTS ARYAN ARYAN PATEL PATEL `25 `25 Introduction Vascular stents are surgical implants used in operations to help dilate a narrowed, or stenosed, artery. They are often used to treat the symptoms of severe peripheral arterial disease (PAD), a form of heart disease that affects the limbs as a result of plaque buildup on the arterial walls (1). Stents are commonly fashioned from stainless steel, but the high restenosis and low patency rates of stainless steel stents have led to investigations to find a better material for this device. Restenosis is a phenomenon that occurs after the stent is implanted, where inflammation and growth factors cause the artery to narrow again, causing patency, or the state in which the ar-

Figure 1 Above is a stenosed artery prior

to intervention. The yellow is the plaque buildup that reduces blood flow and often causes claudication and symptoms of PAD.

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tery is fully dilated, to fall. Nitinol, an alloy of nickel and titanium, has become a prime candidate for vascular stent material because it demonstrates high biocompatibility, making the stent more effective than traditionally used materials at lowering restenosis and thus maintaining higher patency rates. Biocompatibility Nitinol is an alloy of nickel and titanium, and the specific ratio in which these two elements are combined determines the properties of the alloy. This unique material demonstrates a high degree of biocompatibility, as the combination of nickel and titanium makes it highly resistant to corrosive compounds in human blood. Corrosion resistance is of special concern as corrosion of the implant may cause toxic amounts of nickel from the stent to be released into the bloodstream. However, nitinol exemplifies properties of a self-passivating material, a type of material which can independently create a protective surface layer to shield the material underneath the surface. This surface layer relies on the build up of titanium oxide to reduce the corrosion of the surface of the stent. A comparative study from 2016 conducted by R.E. Lee in association with the National Aeronautics and Space Administration (NASA) tested stainless steel and nitinol for corrosion resistance by placing them in brine solutions


Figure 2 The stent conforms to the natural bends of an artery, dilating the vessel for uninhibited blood flow.

for six and twelve months. After removal from the brine solution, each alloy was thoroughly rinsed and subject to visual and microscopic evaluation to detect corrosion damage. It was found that the general corrosion resistance of nitinol was between 0.49% and 0.50%, while the general corrosion resistance of stainless steel was 1.60%. This study concluded that nitinol exhibited insignificant general corrosion rates and very pronounced surface repassivation (2). By industry standards, this means that nitinol is more corrosion-resistant than stainless steel, which makes nitinol more biocompatible and less likely to release toxic elements like

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nickel into the bloodstream. This reduces the chance of inflammation in the artery, which is a key cause of restenosis. A 2015 study conducted by Stacey J. Sullivan of the Oak Ridge Institute further analyzed the anticorrosive properties of nitinol by submerging nitinol stents into a nitric acid solution that mimics the environment of the human body. The stents used in the study also received surface treatments prior to corrosion testing. The study found that a measurable release of nickel ions was detected, but the cumulative nickel release was below 1100 nanograms after the stent was immersed in the solution for 60 days, which is well below the recommended daily intake value of 170 micrograms (3). These studies show that nitinol stents (especially when surface polished) do not release high amounts of toxic material into the bloodstream because of self-passivation and resistance to corrosion. This makes nitinol stents a safe implant option for patients. Since nickel release is associated with arterial inflammation, nitinol’s corrosion resistance and biocompatibility makes nitinol stents more effective at preventing restenosis and maintaining patency.

were monitored for symptoms of PAD. Successful dilation of the artery was defined as the restoration of blood flow through the artery without significant restenosis. Primary patency rate was defined as the number of patients who were free of restenosis without repeat intervention or surgical procedures, and secondary patency rate was defined as the number of patients free of restenosis after two rounds of surgery/intervention. The results of the study reveal that the primary and secondary patency rates of nitinol stents 6 to 12 months after implantation (89% and 80.9%, respectively) are significantly higher than the primary and secondary patency rates of stainless steel stents (78.8% and 38.4%, respectively) (4). This suggests that nitinol stents are much more effective at dilating the artery and restoring blood flow to the extremities, especially in severe cases where surgeons had to operate on patients more than once. This is likely a result of nitinol’s corrosion resistance, as arterial inflammation is less likely to occur in patients with nitinol implants, which leads to lower restenosis and higher patency rates. A 2017 study conducted by Mahmoud F. Elmahdy of Cairo University tested the efficacy of nitinol stents on a much larger patient population to verify the outcomes of previous studies. A total of 213 patients were selected based on a history of PAD and claudication, a symptom of PAD that causes pain in the extremities. The patients were monitored 12, 24, and 36 months after the implantation procedure. To demonstrate the efficacy of nitinol stents, researchers calculated primary patency. This study found that nitinol stents provided safe and effective treatment in symptomatic patients with PAD, as patency rates reached 81.4%, 77.7%, and 74.4% at 12, 24, and 36 months, respectively (5). The results of this study confirm

...Patency rates of nitinol stents are higher than those of stainless steel...[and] are much more effective at dilating the artery and restoring blood flow...

Clinical Advantages of Nitinol Stents To test the efficacy of nitinol stents, several patient-centered studies have been conducted in the past decade to measure restenosis and patency rates. In a 2019 study conducted by Dr. Sourav Gur of the University of Arizona, 32 patients were implanted with stents, 22 of which received nitinol stents while the remaining 10 received stainless steel implants. The patients

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Figure 3 Nitinol wire is used in the production of nitinol stents, a self-passivating material that facilitates blood flow without releasing a high amount of toxic material into the bloodstream.

the predictions of the researchers that nitinol stents would be effective at dilating the artery and preventing re-narrowing up to three years after the implantation procedure. This study demonstrates that nitinol stents are effective at dilating the artery and preventing restenosis since a majority of patients implanted with nitinol stents recovered from symptoms of PAD and experienced returning functionality to their extremities. This is likely a result of several factors, one of them being nitinol’s biocompatibility. In this case corrosion resistance of nitinol would prevent nickel release and therefore limit arterial inflammation and restenosis while the stent is in the patient’s body. Further evidence on the longer-term efficacy of nitinol stents was gathered in a 2019 study conducted by Dr. Masato Nakamura of Toho University’s Division of Cardiovascular Medicine, which monitored 77 patients implanted with nitinol stents. Patients that were selected were at least 20 years of age and showed symptoms of lifestyle-limiting claudication. Patients were also selected based on arterial health. Only those with stenosed arteries or arterial lesions with lengths less than 150 mm were selected. Researchers determined the endpoints of the study to be the number of patients free from target-limb failure 12 months after implantation. Target limb failure was defined as procedure-related death, limb amputation, or restenosis. To record the results of the study, ultrasonic and X-ray imaging were used to take images of the arteries. Researchers also conducted routine medical visits on each patient at 1, 6, 12, 24, and 26 months after implantation, which included physical examinations and laboratory blood tests. This study revealed that nitinol stents provided patency in 71% of implanted patients one year after surgery, and 67.8% patency in patients after three years (6). These findings confirm that nitinol stents are effective in dilating the artery up to three years after implantation, demonstrating the potential of nitinol stents for longer-term stenting. Not only were patency rates higher, but patients also reported dramatic changes to quality of life as they recovered from claudication and other complications of PAD. The outcomes of these studies reveal that nitinol is well suited to applications in stenting as seen by high patency rates and positive outcomes. The main reason for nitinol stents being so effective at maintaining patency lies in their inherent biocompatibility. As the stent remains in the patient’s body, it is exposed to corrosive compounds in the patient’s blood. Since nitinol is highly resistive to corrosion, nickel release is limited which reduces the chance of arterial inflammation: a key source of restenosis. Therefore, if the chances of the artery narrowing after intervention are mitigated, patency rates will increase as dilation is restored and blood flow is unhindered.

Conclusion With the advent of new biomaterials such as nitinol, stent technology has progressed greatly due to the unique biochemical properties of such materials. The findings of these studies confirm that nitinol is a material better suited to stent applications than stainless steel because nitinol’s composition allows it to slow the rate of corrosion in the body to minimal levels, which minimizes negative immune response and corrosion, two primary factors that cause restenosis. Nitinol stents are already being manufactured and tested on human patients, and trials have been largely successful, improving the quality of life for many patients suffering from PAD. In 2015, nitinol stents manufactured by Abbot were found to meet the safety and efficacy criteria of the Food and Drug Administration (FDA) (7). As stent technology and vascular intervention become more advanced, the number of patients recovering from PAD will likely increase, and nitinol’s place as a prime material for stents may make it possible to improve hundreds or even thousands of lives in the future. This review aims to explain the unique properties that make nitinol biocompatible and how nitinol stents are improving outcomes for patients with PAD, but further research should be conducted on ideal stent design and manufacturing. Stent design is the most impactful factor in the functionality of the implant, so an experimental study testing novel designs and its long-term patency and restenosis rates should be conducted to help researchers determine the best design for the implant.

References 1. Peripheral artery disease (PAD). Mayo Clinic, (2021). 2. R.E. Lee, Electrochemical, polarization, and crevice corrosion testing of nitinol 60, a supplement to the ECLSS sustaining materials compatibility study. NASA Technical Reports Server, (2016). 3. S. Sullivan et al., Effects of oxide layer composition and radial compression on nickel release in nitinol stents. Shape Memory and Superelasticity 1, 319-327 (2015). doi: https://doi.org/10.1007/ s40830-015-0028-x. 4. S. Gür et al., Central venous occlusion in hemodialysis access: comparison between percutaneous transluminal angioplasty alone and nitinol or stainless-steel stent placement. Diagnostic and Interventional Imaging 100, 485–492 (2019). doi: 10.1016/j.diii.2019.03.011 5. M. Elmahdy, Long-term primary patency rate after nitinol self-expandable stents implantation in long totally occluded femoropopliteal lesions. Heart Lung Circ. 26, 6 (2017). doi: 10.1016/j. hlc.2016.09.011 6. M. Nakamura, Nitinol self-expanding stents for the treatment of obstructive superficial femoral artery disease: three-year results of the reliable Japanese multicenter study. Annals of Vascular Diseases 11, 324–334 (2018). doi: 10.3400/avd.oa.18-00067 7. L. Garcia et al., Wire-interwoven nitinol stent outcome in the superficial femoral and proximal popliteal arteries. Circulation: Cardiovascular Interventions 8, 5 (2015). doi: 0.1161/CIRCINTERVENTIONS.113.000937

Graphics Illustrated by Isra Ahmed `23

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Introduction Art has the power to captivate, heal, and change the human perspective. For example, Picasso’s Guernica is a harrowing depiction of the horrors of war, while Spielberg’s Jurassic Park enchants its audience by bringing dinosaurs to life. While these works may seem different, they both utilized technology to share a message with the audience. Without paint, Picasso could not depict war in such a unique and abstract way. Similarly, without the development of film, cameras, audio equipment, and CGI, Spielberg would not have been able to bring extinct dinosaurs to life. Today, virtual reality (VR), or any technology that enables a user to experience and interact with a fully digital environment, is at the forefront of development (1). VR technology enables artists and audiences to engage and create works that can generate interest, heal, and change the human perspective. Currently, there is an immense interest in its applications in the art and healthcare industries. With this tool, artists can create works that spark interest, create safe spaces for patients to explore who they are, and even push the physical limits of patients in physical therapy. How VR Changes the Art Scene VR’s fully digital environment enables artists to create immersive experiences. VR’s immersiveness comes from its ability to exploit the senses. The headset mimics human vision by creating a sense of depth, tracking head movement, and controlling the field of view. Headphones help block outside noise and relay sounds from the virtual world. Users can also use controllers to interact with the digital environment. By engaging the senses, the audience is immersed in the digital environment. As a result, the audience can explore and interact with artwork intimately, forging a closer connection between the audience and the work. To better understand how this connection may be forged, a team of researchers led by Dr. Raya from the Technical University of Madrid and the University of Technology, Arts, and Design in Madrid investigated tools that foster an interest in art in young people (2). The team created immersive, navigable, 3D replicas of Salvador Dali’s The Persistence of Memory and Hieronymus Bosch’s Garden of Earthly Delights (2). Both pieces utilized immersive sound design, which entails a 3D soundscape that interacts with the user based on the user’s position in the virtual environment. The Persistence of Memory utilized the sound of the sea and a ticking clock to transport its audience to the coast, while the Garden of Earthly Delights featured sounds of fire, crows, and cows to immerse the audience in the otherworldly environment (2). The Persistence of Memory also used a special controller that allowed users to “feel” certain surfaces, such as the curvature of a clock and the coarseness of the sand (2). Next, the team recruited 66 university students with varying majors and asked them to view a painting using one of three mediums: an illustrated book, an audio-visual presentation, or the VR environment. After viewing the painting, participants filled out an anonymous questionnaire rating their satisfaction, desire to repeat the experience with the same piece of art, and desire to repeat the experience with another piece of art on a scale of 1 to 5 (2). Analysis of the questionnaire revealed that participants enjoyed the virtual environment the most, with average ratings of 4.25 for the virtual environment, 3.96 for the audio-visual piece, and 3.25 for the illustrated book (2). When asked about their desire to repeat the experience with the same piece, participants gave VR an average of 4.40 against a 3.82 and 3.29 for the audio-visual piece and illustrated book, respectively (2). Finally, when rating their desire to repeat the experience with a different piece, participants gave VR a rating of 4.95 against a 4.36 and 4.12 for the audio-visual piece and illustrated book, respectively (2). Additionally, the results suggested that 90% of the participants who used VR favored using it on another piece of art (2).

WITH THIS TOOL, ARTISTS CAN CREATE WORKS THAT SPARK INTEREST, CREATE SAFE SPACES FOR PATIENTS TO EXPLORE WHO THEY ARE, AND EVEN PUSH THE PHYSICAL LIMITS OF PATIENTS IN PHYSICAL THERAPY. ART

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The study showed that VR’s immersiveness generated a closer connection between the audience and the piece, as reflected by the desire to repeat the experience. Another factor that aided in VR’s success was its interactiveness. Unlike the audio-visual piece or the illustrated book, the virtual environment allowed users to “walk around” the piece at their own pace. Moreover, because the piece was 3D, users could see various elements from different angles. When this is combined with the sound and feel of the elements, users begin to physically experience the piece. Therefore, by using VR as a platform to broadcast art, artists can bridge the gap between the physical and mental experience of art; the audience not only sees a painting, but can also experience the work. VR and Art Therapy While VR art can create stronger connections between artists and the audience, it can also be used as a potential form of mental therapy. Researchers led by graduate student Irit Hacmun from the University of Haifa

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and Bar-Ilan University conducted a study to determine the effectiveness of VR as a potential tool in art therapy. The researchers recruited seven art therapists with at least 17 years of experience in treating a variety of patients within Israel for the study (3). Each therapist was given a ten-minute overview of the VR apparatus, followed by 50-minute and 30-minute sessions to create a piece and observe another piece, respectively (3). Researchers interviewed each therapist for 90 minutes at the conclusion of the study. Qualitative data was collected regarding the participants’ thoughts on the experience and VR’s potential as a tool for art therapy (3). After the interviews, the team found unanimous agreement amongst the therapists that art therapy via VR was a viable treatment method that could be scaled up for patients without detracting from the therapist-patient relationship. When asked about the impact of VR on the patient experience, the therapists agreed that VR’s immersiveness and first-person perspective could be used to detach patients from reality and allow them to focus inward. As a result, they concluded that patients could create works

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WHILE VIRTUAL REALITY ART CAN CREATE STRONGER CONNECTIONS BETWEEN ARTISTS AND THE AUDIENCE, IT CAN ALSO BE USED AS A POTENTIAL FORM OF MENTAL THERAPY.

of their own volition without fear or reprimand (3). Likewise, immersion also gave the therapists a sense of empowerment, promoting confidence and openness, which could be a transferable sentiment experienced by patients as well. The therapists also found that VR was flexible; participants could undo mistakes, erase, change, and cancel actions. The flexibility and freedom in VR could give patients unmatched control and a sense of independence. However, they agreed that VR art therapy should be used in conjunction with a wide range of other treatments, especially as VR’s freedom and immersiveness can lead to a potentially overwhelming overflow of emotions (3). According to most therapists in the study, VR art therapy could be applicable for a wide audience with a particular focus on patients with high anxiety, children, and adolescents, especially as children and adolescents have a greater ability to adapt to technology (3). Overall, the study highlighted VR’s immersiveness, first person perspective, and interactivity as factors that suggest its success as a tool for art therapy. By using this fully digital environment, participants have greater freedom to express themselves, and thus can experience reductions in stress or anxiety. VR and Physical Therapy Researchers also explored the applications of VR to physical therapy. Physical therapy aims to ease pain and improve function of an affected area through movement. Because VR art therapy uses a 3D interface, artists must physically exert multiple parts of the body to create 3D works of art. For some patient populations, such as those suffering from stroke, VR’s physical nature can be manipulated to improve movement and function. In particular, a team of researchers under Dr. Marylyn Alex from the University of Auckland conducted a study to compare the effects of VR art therapy with that of traditional art therapy in stroke patients. The team conducted a field study and a technological study using the same group of patients. The field study, which ran for a total of three weeks, consisted of a weekly in-person class that lasted two hours and 30 minutes. In this class, researchers split participants among tables in groups of three to four. Such an environment simulated a casual setting in which participants could paint and socialize (4). While the participants engaged in the activities, researchers took photos and notes of the participants’ work with a focus on inspiration, accomplishment, physical aspect, and social aspect. The technological study, on the other hand, consisted of a single session in which patients were placed in a room with two controllers and a headset (4). Researchers explained the workings of the system, and gave participants 35 minutes to create an image, providing assistance with controllers when necessary (4). At the end of the session, researchers asked participants about their intentions, the characteristics of the VR paint, the impact of immersiveness, the physical aspect, and the degree of control (4). In both instances, patients felt a deeper sense of accomplishment due to the ability to create meaningful pieces via art therapy. However, the researchers noted that painting in VR necessitated a broader range of movements, such as swiveling or twisting one’s body to access more blank spaces. With these results in mind, researchers concluded that physical therapy via VR was an effective treatment option for patients with stroke with some limitations. While the physical aspects of a 3D environment helped participants with their work, the participants’ ability to express themselves was limited to their physical abilities. Those who could not use their full upper body felt constrained and frustrated, while those with full upper body mobility enjoyed the experience. The group proposed changes to make it easier for therapy such as making controllers that feel and act like actual brushes. Regardless, the interactive interface and 3D environment of VR still encourage physical exertion. Furthermore, improvements to the technology can help refine the treatment for additional patient populations in need of physical therapy.

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VR’S IMMERSIVE AND INTERACTIVE ENVIRONMENT ENGAGES ITS AUDIENCE AND HELPS THEM EXPERIENCE ARTWORK FROM A NEW PERSPECTIVE.

The Future of VR Art Both VR and VR art are still in their infancy. However, new program development is already underway to broaden the scope of VR in art and healthcare. One example is the art program Tilt Brush. Tilt Brush is a 3D virtual art program developed by Google that enables users to create works within a room-sized 3D space (5). Unlike other programs, Tilt Brush offers an unmatched degree of freedom. Additionally, Tilt Brush is widely accessible through Steam, Vive, Oculus, Humble Store, and PlayStation Store. To investigate the potential applications for Tilt Brush, Ying-Chung, Lui, and Chang Chwen-Liang from Shih Hsin University interviewed 8 art therapists, two of whom were professional counselors and another two who were art therapy researchers (6). The therapists noted that Tilt Brush is highly immersive and reliant on first-person perspectives, creating a safe space for patients. Additionally, because it is fully digital, the environment can be altered to the patient's needs. In the study, these elements aided in calming the patient and helping them focus on creating a work. One therapist also noted that Tilt Brush’s 3D environment created a highly interactive space, allowing patients to express themselves physically and artistically. Finally, therapists mentioned that adolescents had the most success because of their technological proficiency. By being in a safe space with familiar tools, adolescent patients were able to express themselves and build self confidence. Because this program is accessible across multiple platforms, it may be possible for an even wider population to access and experience these benefits. Conclusion VR is a new technology with an expanding horizon. The interactive nature of VR creates new experiences and changes the way humans experience the world. VR’s immersive and interactive environment engages its audience and helps them experience artwork from a new perspective. The immersive aspect of VR art can also create a safe space for artists to express themselves, which can be used in art therapy treatment. Additionally, the fully digital environment can help stimulate a physical response in patients in physical therapy. As a result, programs such as Google’s Tilt Brush are giving artists and therapists new tools to enhance their work. However, there is still room for improvement. With further research and development, it may be possible to create more personalized spaces for patients that are suitable for each of their needs. Similarly, incorporating more bodily features may allow VR to act as a physical therapeutic agent for patients with different ailments. By expanding this technology globally, artists and patients alike may find that this digital playground offers more than meets the eye.

References 1. Virtual reality vs. augmented reality vs. mixed reality: what you need to know. Intel, (2020). 2. L. Raya, et al., Virtual reality application for fostering interest in art. IEEE Computer Graphics and Applications 41, 106-113 (2021). doi: 10.1109/MCG.2021.3055685. 3. I. Hacmun, D. Regev, and R. Salomon, Artistic creation in virtual reality for art therapy: a qualitative study with expert art therapists. The Arts in Psychotherapy 72, 101745 (2021). doi: 10.1016/j.aip.2020.101745. 4. M. Alex, B. Wünsche, and D. Lottridge, Virtual reality art-making for stroke rehabilitation: field study and technology probe. International Journal of Human-Computer Studies 145, 102481 (2021). doi: 10.1016/j.ijhcs.2020.102481. 5. Tilt Brush by Google. Tilt Brush, (2016). 6. L. Ying-Chun and C. Chwen-Liang, The application of virtual reality technology in art therapy: a case of Tilt Brush. 2018 1st IEEE International Conference on Knowledge Innovation and Invention (ICKII), 47-50 (2018). doi: 10.1109/ ICKII.2018.8569081 Images retrieved from: 1. https://upload.wikimedia.org/wikipedia/commons/thumb/6/6d/The_Garden_of_Earthly_Delights_by_Bosch_High_Resolution.jpg/1599px-The_Garden_of_Earthly_Delights_by_Bosch_High_Resolution.jpg?20121109122020

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MICROBIAL PIGMENTS A Molecular Palette For Art And Medicine

ALEX MOIR `23 ART

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lo ge ran n e ng ni ts ha e b o c te and ve als nic rm carcinoge exp osure.

duction and use; however, an estimated 15 percent of the dyes used in the coloring process are discharged as wastewater, making textiles a significant contributor to water pollution (4). Recent research efforts have focused specifically on finding alternatives to violet dyes such as crystal violet. While known for its genotoxic and carcinogenic effects, crystal violet can also absorb sunlight and inhibit plant photosynthesis when dissolved in water. Consequently, the amount of dissolved oxygen available in aquatic ecosystems decreases, resulting in the death of aquatic life (4). Due to its complex chemistry, crystal violet dye is also difficult to remove once present in ecosystems, making its prohibition an environmental safety priority (4). To address this issue, Dr. Maria Kanelli and a team of researchers from the National Technical University of Athens investigated the efficacy of violacein, a deep violet colored microbial pigment produced by Janthinobacterial lividum, in dyeing polyamide fabrics (5). Researchers first optimized microbial cultivation and extraction of the pigment using bioreactors, or eco-friendly instruments used to grow bacteria due to their convenience in waste containment (6). Over the course of the next six days, three different dyeing methods of polyamide fabric were tested: direct incubation of fabrics with the bacterium in the bioreactor (SFD), exposure of fabric to bacterium-containing medium extracted from the bioreactor (DAFS), and exposure of fabric to a medium that had been sonicated to destroy and remove cells from violacein pigment (DD) (5). At the end of the exposure period, each conditioned fabric was assessed for important commercial dye standards, such as color fastness (the degree to which a dye can leach color and stain surrounding cloths during washing) and color change (the degree to which dyed fabrics have changed in color from their undyed counterparts). Color fastness was measured on a scale of one to five, where five indicated no contrast between the color of a material before and after treatment, and one indicated complete contrast and high color leaching. When measuring color change, a score of one was considered a perceivable change in color of 50% to the naked eye, while a score of two indicated a 100% perceivable change in color. Researchers also assessed abrasion resistance via washes of varying pressures that simulated washing and drying clothes, and also exposed the violacein-stained fabrics to various pH, temperature, pressure, and light conditions to separately assess for their effects on color fastness. For all dyeing methods, color fastness reached a value of five for every condition except intense light exposure, suggesting that there was no leaching of the violacein dye. Assessment of color strength showed that the SFD dyeing method was most effective out of the three tested. Furthermore, SFD scored a ~1.5 (74.81%) in color change, while undyed control fabric scored a zero (5). The results of the experiment are significant as they suggest that violacein can strongly stain fabric and give a noticeable change in color. A high color change score indicates that it takes less dye to achieve the target color change perceivable by an observer. Furthermore, the results of the color fastness tests also show violacein-stained fabric retains the color

o c c ta i t Many synthe mu lo found to have ith w s t effec Introduction The production of colorants, including pigments and dyes used to color materials, dates back to prehistoric times with evidence of natural pigments present on early human tools approximately 400,000 years ago (1). Most modern colorants are now produced synthetically, and are widely used in commercial products such as clothing and food dyes. However, synthetic colorant production releases both greenhouse gasses and water-polluting chemical discharge, contributing to climate change and ecological destruction, respectively (2). Many synthetic colorants have also been found to have mutagenic and carcinogenic effects with long term exposure (2-3). Due to the synthetic colorants’ negative effects on the environment and human health, there has been recent interest in shifting back to natural methods of colorant production. Current research suggests that microbes are a promising source of natural colorants; these pigments present as a safe and sustainable alternative to synthetic colorants, and also show diverse biotherapeutic properties. Violet Dyes in the Textile Industry The textile industry is responsible for 60 to 70 percent of dye pro-

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change when exposed to washes and harsh conditions. These findings point toward the use of violacein as a safe replacement for synthetic violet dyes, such as crystal violet, in clothing because it does not dissolve easily in water. Additionally, all staining methods were done in the absence of organic solvents, which would otherwise contribute significantly to the discussed textile discharge at the end of the dyeing process, meaning violacein could be eco-friendly to produce and use. Red Food Coloring from Fungi In addition to reducing environmental impacts, microbial pigments may also have applications as safer food colorants. Synthetic colorants act as preservatives in some cases and help make consumables more appealing to consumers by artificially changing their color; however, long-term exposure can have detrimental effects on the human body, such as an increased risk of developing tumors (2-3). The failure of producers to regulate these dyes under safe concentrations designated by federal agencies like the Food and Drug Administration (FDA) has yielded great concern in consumers. In contrast, microbial pigments have no known adverse effects with consumption at high concentrations, resulting in rapid FDA approval of several microbial pigments with synthetic counterparts (3). Red pigments from Monascus fungi have been of particular interest. To determine its use as a natural food colorant, Dr. Osama M. Darwesh and his team of researchers from the Egypt Department of Agricultural Microbiology cultured Monascus ruber fungi and isolated a red pigment called OMNRC45. The team first evaluated the biosafety of the pigment via acute toxicity tests with young adult male mice (7). The mice were administered OMNRC45, carmoisine E122 (a synthetic red pigment), or water, with varying dosages ranging from 10 to 5000 mg/kg body weight. The team tested each colorant for its LD50, or the dosage at which it was lethal to 50 percent of the sample population of mice. The mice were also monitored for any signs of toxicity, such as abnormal changes in motor activity, throughout the week-long period of the study. At the end of the week, the mice were dissected, and their organs were examined for damage (7). Analysis of the results indicated that OMNRC45 had no observable detrimental effects on the mice. The LD50 for the positive control synthetic colorant was 4166 mg/kg body weight. 5000 mg/ kg body weight carmoisine E122-fed groups

showed increased male aggression and male and female diarrhea. In contrast, OMNRC45 pigment showed no increased mortality in any of the experimental groups and no observable negative effects compared to the water-fed control group, even at high doses. Additionally, organ dissection analysis found that carmoisine E122-fed mice at higher doses had enlarged and discolored livers, hepatotoxicity, and significant accumulation of carmoisine E122 in all organs. OMNRC45-fed mice showed low accumulation with no abnormalities in extracted organs (7). A sensory assessment wherein lollipops and jellybeans were colored using OMNRC45 pigment was also conducted. A panel judged the appearance and acceptability of the final products and approved OMNRC45 as a suitable pigment for coloring foods and increasing consumer appeal (7). Although carmoisine E122 had been previously approved for use by the FDA in certain foods, OMNRC45 shows promise as a natural alternative based on the results of this study (7). Of most significance is the comparative lack of toxicity in all metrics for OMNRC45 in contrast to carmoisine E122, suggesting OMNRC45 is a safer alternative to synthetic colorants currently in use. Biotherapeutic Applications of Microbial Pigments In addition to microbial pigments being sustainable sources of natural colorants and improving human and environmental health, they may also hold value as novel biotherapeutics. Recent studies have found that microbial pigments possess a plethora of biotherapeutic and medicinal properties. There are over 25 diseases that microbial pigments demonstrate possible efficacy for treating, as well as many possible biomedical applications (1). Of most interest are the antimicrobial and anticancer activities of many well characterized microbial pigments. In a recent study, a team of researchers under Dr. Claira Aruldass demonstrated the antimicrobial activity of the violet microbial pigment violacein against Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA). The researchers first cultured SA and MRSA in growth plate wells (8). Liquid growth medium containing a compound which turns from clear to pink in the presence of bacterial growth was added on top of the plates into the wells. Each well then received a specific concentration of violacein or vancomycin, a known inhibitor of bacterial growth acting as a positive c o n trol.

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Figure 1 Beyond upscale production, the barriers for microbial pigment implementation are low, as many experiments have demonstrated microbial pigments' capability to hold viability as substitute colorants for synthetics currently in use.

Two values were determined based off of the experiment: minimum inhibitory concentration (MIC) of violacein (minimum concentration at which a degree of microbial growth inhibition occurs compared to negative controls), and minimum bactericidal concentration (MBC) of violacein (minimum concentration at which complete inhibition or killing of microbes is achieved). MIC for violacein and vancomycin were 3.9 μg/mL and 1.56 μg/mL, respectively. Similarly, MBC values for violacein and vancomycin were 15.6 μg/mL and 6.25 μg/mL, respectively. However, it was determined no killing activity was present for either, but rather, only complete growth inhibition. Although values for MIC and MBC were approximately 2.5 times higher in violacein than vancomycin, the results still show significant antibacterial activity of violacein. Currently, there is a desperate need for the discovery of safe and effective treatments to methicillin- and vancomycin-resistant strains of SA; as such, violacein may provide a solution to this problem (8). Microbial pigments have also been identified as possessing anticancer properties. Since the 1990s, prodigiosin, a red pigment derived from marine Vibrio sp, has been shown to possess antiproliferative properties, inhibiting the growth of cancer cell lines in vitro. Recent in vivo studies have also demonstrated its efficacy against a variety of cancers; however, the mechanisms behind its anticancer activity are unclear (9). In a recent study, researchers tested the efficacy of prodigiosin against glioblastoma, the most common and deadliest brain cancer, and sought to determine its mechanism of action. Glioblastoma cell lines were cultivated and then treated with prodigiosin at varying concentrations. Caspase 3 levels were then measured as a marker for cell death. To detect target proteins and measure the amount of target RNAs present in the sample, researchers conducted a western blot and polymerase chain reaction, respectively (9). Analysis found that caspase 3 levels were high in treated cultures, indicating activation of cell death pathways. Results from the western blot suggest that multiple proteins related to endoplasmic reticulum stress were also present. The endoplasmic reticulum is responsible for protein production and transport, and when it becomes overloaded, stress pathways are activated, which can lead to cell death. The PCR conducted on the prodigiosin-treated samples found the expression of RNA that encodes for these ER stress proteins was significantly higher than in untreated control samples. These results suggest prodigiosin kills glioblastoma cancer cells by increasing ER stress, sensitizing the cancer cells to pathways associated

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with protein overproduction induced death, as cancer cells already produce excessive amounts of protein (9). Conclusion Currently, microbial pigments are still in their infancy. Upscale production of microbial pigments for industry application relies heavily on the optimization of culturing methods and the maturation of bioreactor technology. However, progress continues in these areas, as seen by the advent of AI-based technologies that help determine optimal culture conditions and manage the precarious balancing act that giant bioreactors present. Beyond upscale production, the barriers for microbial pigment implementation are low, as many experiments have demonstrated microbial pigments' capability to be viable as substitute colorants for synthetics currently in use. Many parts of the world have also started shifting towards safer and more eco-friendly colorants, with Europe leading at 85% use of natural pigments (6). As it stands, future research into microbial pigments should aim to explore how production of pigments can be increased through the use of microbiological and genetic engineering techniques, as well as to elucidate the specific mechanisms that give microbial pigments their biotherapeutic properties. References 1. M. Narsing Rao, M. Xiao, and W. Li, Fungal and bacterial pigments: secondary metabolites with wide applications. Frontiers in Microbiology 8, 1-8 (2017). doi: 10.3389/fmicb.2017.01113. 2. L. Ardila-Leal, et al., Brief history of colour, the environmental impact of synthetic dyes and removal by using laccases. Molecules 26, 1-40 (2021). doi: 10.3390/molecules26133813. 3. Aman Mohammadi, et al., Microbial pigments as an alternative to synthetic dyes and food additives: a brief review of recent studies. Bioprocess and Biosystems Engineering 45, 1-12 (2021). doi: 10.1007/s00449-021-02621-8. 4. S. Mani and R. Bharagava, Exposure to crystal violet, its toxic, genotoxic and carcinogenic effects on environment and its degradation and detoxification for environmental safety. Reviews of Environmental Contamination and Toxicology 237, 71-104 (2016). doi: 10.1007/978-3-31923573-8_4. 5. M. Kanelli, et al., Microbial production of violacein and process optimization for dyeing polyamide fabrics with acquired antimicrobial properties. Frontiers in Microbiology 9, 1-53 (2018). doi: 10.3389/fmicb.2018.01495. 6. C. Venil, L. Dufossé, and P. Devi, Bacterial pigments: sustainable compounds with market potential for pharma and food industry. Frontiers in Sustainable Food Systems 4, 1-17 (2020). doi: 10.3389/fsufs.2020.00100. 7. O. Darwesh, et al., Isolation and optimization of Monascus ruber OMNRC45 for red pigment production and evaluation of the pigment as a food colorant. Applied Sciences 10, 1-15 (2020). doi:10.3390/app10248867. 8. C. Aruldass, et al., Antibacterial mode of action of violacein from Chromobacterium violaceum UTM5 against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). Environmental Science and Pollution Research 25, 5164-5180 (2018). doi: 10.1007/s11356-0178855-2. 9. S. Cheng, et al., Prodigiosin stimulates endoplasmic reticulum stress and induces autophagic cell death in glioblastoma cells. Apoptosis 23, 314-328 (2018). doi: 10.1007/s10495-018-1456-9.

Graphics Illustrated by Katie Zeng `24


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Introduction Writing is a practice so ingrained in modern human life that it can easily be taken for granted. Yet, there was a time when writing was a novel creation, and the idea of creating physical messages, records, or important cultural narratives was unknown. Early writing systems were largely lost to time, and only recently has it become possible to understand the role that writing played in ancient societies. While a human analysis of ancient archeological finds suffices for a discernment of the identity and significance of ancient scripts, anything more technical, such as an identification of authorship, requires more sophisticated techniques. A variety of algorithmic methods, including the creation of heatmaps and pixel patches, can allow for an analysis of ancient text on the level of individual letters or individual parts of letters. By utilizing a variety of algorithmic approaches that examine text with varying levels of detail, from the overall shape of the letters down to handfuls of pixels, it is possible to identify authorship with a degree of accuracy that human analysis alone could never achieve.

While a human analysis of ancient archeological finds suffices for a discernment of the identity and significance of ancient scripts...an identification of authorship, requires more sophisticated techniques. 37

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Human Analysis When faced with a newly discovered ancient text, meaning is the most logical place to begin an analysis, and an understanding of meaning can be achieved with standard human knowledge of language. One newly discovered text of great importance was found on a piece of ceramic smaller than a four centimeter by four centimeter square. In the Shephelah region of modern-day Israel lies the Bronze/Iron Age site of Tel Lachish, where archeologists have unearthed a variety of ancient artifacts, including this piece of ceramic. On the fragment, there are six letters in two lines, which were derived from Egyptian hieroglyphics and appear to be primitive iterations of letters used in the various Semitic languages, such as Hebrew.


This finding marks the earliest example of alphabetic script found in the southern Levant, with all earlier fragments being located in Egypt. Thus, this artifact represents a bridge between the earliest known alphabets from Egypt, and the more well-known alphabets of the Levant of later centuries, filling in a gap in the historical record. A simple examination of the writing was all that was necessary to understand the nature of the text. By comparing the primitive letters to extant Hebrew, they could be identified, and with the known age of the site, the writing’s place in history was established (1). While this not insignificant examination was achieved without the use of computers, it constitutes a relatively simple, surface-level analysis. An exploration of meaning does not involve an exploration of the details of how any given letter was written, only an identification of each letter present in a given text. Thus, for any analysis more sophisticated than an analysis of meaning, computer assistance is needed for a truly accurate understanding of ancient texts.

Figure 2 Fragment of

ceramic discovered in the Shephelah region (other side to the left).

Figure 3 Fragments of

pottery such as this are known as ostraca, and are what comprise the Arad Corpus.

Heatmaps Outside of meaning, authorship is perhaps the most important aspect of any text, and yet for many of the most ancient, culturally significant texts, authorship remains a great mystery. The Dead Sea Scrolls are one of the oldest collections of biblical manuscripts, and a careful analysis of their authorship could provide insights into the scribal culture prior to the creation of the proper Hebrew Bible. Human analysis of the scrolls has long struggled to parse out how many scribes composed the scrolls and which scrolls they may have worked on. The obstacle for researchers lies in the difficulties in determining which variations in the script are due to different authorship. In addition, since any given letter can appear on a scroll thousands of times, the idea of a human identifying the authorship of any one document becomes a Sisyphean task. Researchers from the University of Groningen attempted to circumvent the limits of human analysis in a 2020 study, wherein they applied a novel algorithmic approach to one of the most famous Dead Sea Scrolls, the Great Isaiah Scroll, in order to determine its authorship. To do this, the researchers took digital images of the scroll, rendered the text on them as simple black and white images, and removed artifacts such as stray ink marks so that the text could be read more clearly. From these cleaned up images, particular features of the text, such as varying degrees of bending when writing curved letters, were analyzed with an algorithmic feature extraction method known as Hinge. Hinge features indicate whenever an author subconsciously slowed down or sped up while writing, such as a particular bend in a character. By inputting Hinge features, the researchers provided their algorithm with hundreds of variables to compare to one another. In addition to algorithmic feature analysis, the researchers sought to synthesize the algorithmic analysis with traditional analysis through the creation of heatmaps. No letter is written the same way twice, with variations in line thickness, angle of pen strokes and length of strokes differing between each instance of a letter. Heatmaps are aggregated visualizations of every instance of each letter, showing the frequency of different variations across the whole of a given text. Researchers posit that these heatmaps could supersede traditional charts which do not aggregate each instance of a letter, as the heatmaps can demonstrate that what might otherwise be viewed as an insignificant deviation in writing style is actually indicative of a specific hand. The Great Isaiah Scroll notably has two distinct halves which were sewn together, with the second half’s Hebrew appearing distinct from the first’s. This distinction led to some scholars suggesting throughout history that two different scribes with similar writing styles composed the manuscript, but the belief that the scroll was composed by a single scribe was still deeply held. Thus, heatmaps were created for the entirety of the scroll as well as for each half, so that the frequency and types of variation might be compared between the different sections of the manuscript. The

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heatmaps allow for a comparison of larger features of the script at a glance, while the focus on Hinge features allows for a more careful analysis of subtler details. Differences in these subtle details can be quantified and translated into feature vectors, which can then be plotted on a three-dimensional graph. The plot of Hinge vectors that the researchers derived from the Great Isaiah Scroll showed a complete break in style between the first half and the second half of the manuscript, with a statistical analysis of each half supporting this visual separation. The differences in style within and between each half of the scroll consist entirely of very minute distances, as they constitute slight variations in hand movement. What might not be viewed as a significant variation by a human being is made much clearer thanks to the computer program, allowing researchers to draw more definitive conclusions than have been made previously (2). Combining the findings from both the algorithmic and Hinge analysis methods allowed the researchers to conclude that two separate scribes composed the Great Isaiah Scroll. The researchers posit that theirs is the most comprehensive study on writer identification of the Dead Sea Scrolls using modern computing techniques, and so the fact that such a definitive conclusion can be reached is unprecedented. While a human could conceivably discern significant differences between writing styles, when multiple writers possess exceedingly similar styles, the ability to analyze the minute

details is something that can only be achieved with algorithmic analysis, especially for a text containing as many characters as one of the Dead Sea Scrolls (2). Thus, the utility of algorithmic approaches for any future research in the field is assured, as ever-advancing technology allows for ever-closer examinations of text. As such analysis gets closer to the level of comparing individual pixels to one another, the accuracy of authorial identification will continue to increase. Binary Pixel Patterns While the heatmap method proved useful in identifying the authorship of the Great Isaiah Scroll, it served only to distinguish two authors of a single text, thus leaving room for algorithmic analysis to expand its scope in terms of both the number of authors and the number of texts. Arad is an archeological site from the ancient kingdom of Judah, dating back to around 600 BCE, which has long been known to have hosted an assortment of writers. The site has yielded to archeologists a large corpus of tablets which were written over a short amount of time, and previous analyses determined that around four to seven writers composed these texts. However, algorithmic technology has advanced significantly since the previous examination of the corpus, and thus a team of researchers led by Arie Shaus of Tel Aviv University decided to reexamine the texts. Utilizing a novel algorithmic approach

Figure 4 The

Great Isaiah Scroll is one of the longest Dead Sea Scrolls.

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Figure 5

developed by Shaus, they were able to identify at least a dozen unique authors who were either stationed at, or wrote to, the site. When examining the Arad Corpus, Shaus and his team used two algorithms to examine similar details of script as were explored in the Great Isaiah Scroll study, such as legibility, size, spacing, and punctuation. The first of the algorithms restored the strokes a given writer used to write a given character, and then compared these to instances of said character across the whole corpus. The end result of the character reconstruction is a binary, or black and white, digital recreation of the original letter. After the binary image is created, the algorithm analyzes the distance between the character and the characters surrounding it. Finally, the algorithm is set to determine the probability that two texts were written by the same writer. Different letters were analyzed independently of each other, and only two texts were compared to one another at the same time (3). This method is fairly similar to the heatmap method in the level of detail that it can analyze. While it does not aggregate all instances of a given letter across the corpus, it does equalize each instance of the letter by creating the binary images. While a byhand analysis of these images is possible, the computer programs are able to compare details in a way that would otherwise be impossible. To further this point, the second algorithm utilized by Shaus and his team examines a level of detail that is completely impossible for a human to ever discern. A few years prior to the reexamination of the Arad corpus, Shaus developed a novel algorithmic approach that uses the same statistical approach as the previously discussed algorithm, but differs in that it analyzes letters with a level of detail far beyond that algorithm, or the heatmap and Hinge analyses of the Great Isaiah Scroll study. Rather than simply analyze the strokes used to write each letter, and then the spatial relationship between the letters, this second algorithm involves the creation of binary pixel patterns: three pixel by three pixel patterns derived from the letters. All possible patterns that could be formed from each letter were used to form normalizing histograms, after which the individual patterns are compared statistically. This allows for an analysis of the individual features of letters, allowing for a much greater degree of accuracy when identifying authorship (4). The pair of algorithms were found to agree on authorial identity in every case. A forensic, non-algorithmic, analysis also performed by the researchers aligned with these same results and the combined results allowed the researchers to identify as many as twelve authors among the Arad corpus, which consists of only eighteen texts. Based on the meanings of certain texts, which appear to be written by presumably Judahite commanding officers of various mercenary groups employed by the Kingdom of Judah, at least three of the writers can reasonably be assumed to have been stationed at Arad. Since the site was only large enough to house twenty to thirty soldiers, this suggests that at least ten percent of the garrison was literate (3). As such, the researchers posited that this remarkably high literacy rate is indicative of an advanced education system that existed in the kingdom, which would have educated members of the military and other elites. This era of high literacy also aligns with the time period of the dissemination and composition of various biblical texts, such as the Books of Deuteron-

omy, Joshua, Judges and Samuel. Furthermore, an education system akin to what the researchers posit existed in the Kingdom of Judah would allow for more of the populace to appreciate such important cultural touchstones in their written form without having to rely on oral tradition for transmission (3). Such a clear and revelatory understanding of the cultural life of an ancient society would not have been possible without the advancement of algorithmic technology that allowed for the half-dozen new authors to be discovered. Conclusion Ever-advancing technology allows for a wide variety of approaches for analyzing ancient handwriting, and to an exponentially greater degree of accuracy than anything a human could hope to do by hand. Whether it’s through wholly computerized methods, or through syntheses of traditional techniques and modern technology, previously obscure information regarding the authorship and transmission of ancient, culturally significant works can be revealed for the first time. Although human analysis remains adequate when interpreting the meaning of ancient texts, it is completely outclassed in the field of author identification. Algorithmic analysis allows for cultural and historical secrets to be illuminated in a way that they might otherwise never have been, and thus their use in the field will only increase as technology continues to advance. References 1. F. Höflmayer, et al., Early alphabetic writing in the ancient near east: the ‘missing link’ from Tel Lachish. Antiquity 95, 705-719 (2021). doi: 10.15184/aqy.2020.157. 2. M. Popović, M. Dhali, and L. Schomaker, Artificial intelligence based writer identification generates new evidence for the unknown scribes of the Dead Sea Scrolls exemplified by the Great Isaiah Scroll (1qisaa). PLoS ONE 16, 1-28 (2021). doi: 10.1371/journal.pone.0249769. 3. A. Shaus, et al., Forensic document examination and algorithmic handwriting analysis of Judahite biblical period inscriptions reveal significant literacy level. PLoS ONE 15, 1-15 (2020). doi: 10.1371/journal.pone.0237962. 4. A. Shaus and E. Turkel, Writer identification in modern and historical documents via binary pixel patterns, kolmogorov–smirnov test and fisher’s method. Journal of Imaging Science and Technology 61, 0104041-0104049 (2017). Images retrieved from: 1. https://collectionapi.metmuseum.org/api/collection/v1/iiif/473396/1536172/main-image 2. https://www.cambridge.org/core/journals/antiquity/article/early-alphabetic-writing-in-the-ancient-near-east-the-missing-link-from-tel-lachish/C73F769B7CF3A7E4E2607958A096B7D8 3. https://collectionapi.metmuseum.org/api/collection/v1/iiif/473396/1536173/main-image 4. https://commons.wikimedia.org/wiki/File:The_Great_Isaiah_Scroll_MS_A_(1QIsa)_-_Google_Art_Project-x4-y0.jpg 5. https://collectionapi.metmuseum.org/api/collection/v1/iiif/473396/1536171/main-image

Graphics Illustrated by Komal Grewal `23

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JUZER VASI `24 Introduction One of the most pressing issues facing health institutions around the world today is cancer. It is estimated that by 2040, new cases of cancer will rise to 26 million – posing grave physiological ramifications on patients (1). Fortunately, art therapy has the potential to greatly improve both the physical symptoms associated with chemotherapy and the psychological issues of cancer diagnoses. Due to the synergy of the techniques in its unique protocol in reducing pain and increasing quality of life, research suggests that mindfulness-based art therapy (MBAT) is more effective than its traditional counterparts, and understanding the biological mechanism behind art therapy allows medical professionals to personally tailor MBAT to maximize efficacy. What is Art Therapy? Through active art-making such as drawing and creative thinking, combined with applied psychotherapy, art therapy is used to improve cognitive and sensory-motor functions, foster self-esteem, cultivate emotional resilience, reduce conflicts and distress, and promote insight into core issues faced by the patient (2). A subset of art therapy that has recently arisen is mindfulness-based art therapy (MBAT). According to Dr. Caroline Peterson from the Joan Karnell Cancer Center, MBAT integrates general art therapy exercises with mindfulness skills-training and programs that are wellness – rather than illness – focused, such as gentle yoga practice, body scan meditation, and breathing exercises. As a result of the psychological distress of cancer diagnoses, chronic hyperarousal (a symptom of PTSD) can occur, which leads to negatively biased memory and emotions, disruptive thinking, and adverse behavioral inhibition. Additionally, the physical symptoms of treatment can include extreme fatigue, nausea, anemia, and infection. Peterson reveals that MBAT succeeds by activating the body’s rest and repair system, improving psycho-physiological self-regulation, attention, decision-making skills, positive emotion states, and immune functioning, leading to an increase in overall quality of life (3).

and sexual functions, working ability, and lifelong pleasure (5). MBAT may have positive implications for breast cancer patients. A 2019 study conducted by Dr. Zeinab Jalambadani from the Department of Public Health at Neyshabur University of Medical Sciences and Dr. Abasalt Borji from the Department of Basic Medical Sciences set out to determine the effectiveness of MBAT in increasing quality of life (QoL) in women with breast cancer. The researchers divided 100 female participants with breast cancer into a control group that did not receive MBAT intervention and an experimental group that was exposed to an MBAT art therapy course. QoL was measured both before and after treatment using the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire. Each group met for 90 minutes per week for 12 weeks. Activities during therapy sessions included self-picture assessment tasks, exploration of different art materials, yoga, body scan meditation, breathing exercises, freestyle art-making, and group discussions. As measured by the WHOQOL‑BREF stress management subscales, patients under MBAT treatment reported significant increases in physical health, psychological health, and social relationships. Specifically, there was a 20% increase in the level of physical and psychological health, and a 12.7% increase in social relationships between participants. Ultimately, the study displays encouraging data that MBAT is an effective means for reducing symptoms of distress and improving key aspects of the lifestyle of women with breast cancer. Furthermore, the results indicate a possible advantage over standard art therapy approaches when comparing WHOQOL-BREF results of recent studies (5). To determine if MBAT is a possibly more effective approach to alleviating cancer symptoms than traditional art therapies, it is necessary to study cancer patients engaging in strictly traditional art forms without the component of mindfulness. In a 2017 study conducted by Dr. Hakan Bozcuk and Dr. Hulya Oczan at the Medical Park Hospital in Turkey, QoL was measured in 48 patients after undergoing a painting art therapy program (PATP), which was facilitated by a professional watercolor painting artist during patients’ chemotherapy sessions. According to QoL domains of the European Organization for Research and Treatment of Cancer (EORTC) questionnaire and changes in Hospital Anxiety and Depression Scores (HADS), patients who underwent the PATP program experienced a 30% increase in global QoL and a 50% increase in depression scores, which are statistically significant. Additionally, according to the EORTC questionnaire values, among patients who had never been exposed to PATP therapy before, there was a 6.8 and 9.9 increase in emotional and cognitive functioning, respectively, and significant decreases in symptoms such as fatigue, insomnia, dyspnea, and overall pain. Not only did the act of painting enable the catharsis of negative feelings, but patients who participated in PATP were also more likely to engage in open dialogue to discuss problems due to the social and interactive environment that was regularly provided by the program. Interestingly, patients with the poorest

Mindfulness-based art therapy integrates general art therapy exercises with mindfulness skills training...leading to an increase in overall quality of life.

MBAT Increases Quality of Life Receiving an initial diagnosis of cancer evokes sentiments of anger, anxiety, and trauma in patients, often leading to the development of mental health disorders. According to Dr. J.T. Bosman and Dr. Zoe Bood at the Department of Medical Oncology at Amsterdam University, anxiety and depressive disorders are particularly common among cancer patients. In fact, anxiety disorders are estimated to exist in 10% of cancer patients and depression to exist in 20% of cancer patients. Additionally, non-Diagnostic and Statistical Manual of Mental Disorders (DSM)-certified disorders such as insomnia and distractibility are even more common. Thus, quality of life (QoL) is adversely affected (4). QoL, as defined by the World Health Organization, consists of physical, mental, and social health, as well as cognitive

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well-being at the start of the experiment (lowest QoL, highest depression) understanding the physiological effect of art therapy is crucial for the greatexperienced the greatest improvements, indicating that in clinical practice er fine-tuning of treatments to determine where MBAT is most advantaPATP may benefit patients who are relatively in more need of help. Howgeous to use. ever, according to the limitations of the study, the effect of PATP on global Art therapy relies on a series of core tenets, including the corollary quality of life and depression in cancer patients undergoing chemotherapy that different art media activate various brain regions. For instance, the may be compounded by a number of factors such as gender, motivation staamygdala, an area of the brain involved with experiencing emotions, is actitus, and disease factors. Additionally, the results indicate an overall physvated by less resistive media such as water-colors and clay. On the contrary, ical functioning decrease, implying that patients subject to PATP mostly more resistive media (ie., pencils and rulers) affect the more cognitive areas benefited psychologically (6). Bozcuk and Oczan cede that because art is a of the brain including the frontal lobe. Neuroimaging can be used to prove subjective experience, it is possible that different forms of art therapy may the localized stimulation of the brain by different art media (8). affect different patients in different ways. In a 2017 study, Dr. Juliet King, professor of art therapy at Another study, conducted in 2021 at the Sant Pau ReGeorge Washington University, worked with collaborators to search Institute by Dr. Nadia Collete, set out to evaluate the measure cortical (cerebrum) activation patterns in subjects imbenefits of art therapy intervention in adult cancer patients in a mediately following art making and rote motor tasks using elecpalliative care unit, a type of care that focuses on the reduction troencephalography (EEG) recordings. Ten consenting subjects of symptoms rather than curative treatment. By evaluating the underwent EEG recordings to establish a baseline value that was intensity of pain, anxiety, depression, and well-being before compared against EEG recordings taken after participation in and after three trials consisting of 83 patients, it was art making and rote motor movement (coin tossing and revealed that the intermodal expressive art therapy pencil rotation). Ultimately, after performing a series intervention, consisting of both fine arts, as well of t-tests, the study displayed that in the left hemias aspects of MBAT such as breath-based body sphere, the increase in EEG power (a measure of awareness, was beneficial in reducing symptom the activity in a signal) was statistically signifiintensity. In fact, compared to starting levels cant from 4-32 Hz, and exceeded the threshold determined by Edmonton Symptom Assess(0.045) for random variance from 6-16 Hz. ment Scale (ESAS), pain intensity decreased by Similarly, in the right hemisphere, the increase 54%, depression by 38%, anxiety by 48%, and in power was statistically significant from 2-32 overall distress by 35%. According to Collete et al., Hz exceeding the threshold from 6-16 Hz – the area the perceived benefits of art therapy mostly conof greatest difference between the baseline EEG sisted of the positive experience when making and post-art-making value. While EEG power art, leading to relaxation, self-satisfaction, increased as a result of rote motor tasks and the sentiment of being capable and as well, the increase in power seen active. Through mindfulness activities after art making was greater quanand the aesthetic interpretation of cretitatively with increased mean difated art, participants described a deeper ferences. Furthermore, cortical activaself-knowledge, a strengthening of identity, and tion changes in different frequencies (namely, Figure 1 Meditation is heavily incorporated into MBAT exercise, a spiritual connection with their own creations, alpha, theta, and beta ranges) may provide inunlike traditional art therapy sessions. especially important for patients in hospice care. sight into neurophysiological mechanisms and Since the patients in this study were under palliative care, they had a higher processing specific to those frequencies. For instance, a significant mean rate of improvement involving greater motor skills, social function, and audifference in the alpha region (8-12 Hz) displays the activation of the occiptonomy due to the absence of chemotherapy-driven bodily stress (8). ital region of the brain associated with relaxation. Theta frequency (4–7Hz) Out of the three studies discussed, Colette et al. displayed the most is associated with drowsiness, meditative states, and light stages of sleep. significant decreases in psychological and physical issues, supporting that Beta frequency (12.5-30Hz) is associated with active thinking and concenthe inclusion of MBAT activities is beneficial to cancer patients, even those tration. Thus, the study displays an exploration of the relationship between not undergoing chemotherapy. Although traditional art therapy, such as frequency changes and neuro-physiological brain function, which is necesPATP, has its merits in reducing psychological symptoms, the inclusion of sary in understanding how specific areas of the brain are activated during MBAT compared to strictly using PATP in cancer patients represents an art-making and art therapy. This study contributes empirical evidence necopportunity for patients to ameliorate pyschogically and physically more essary for the scientific validation of art therapy, and strongly suggests that effectively. However, understanding the biological mechanism is necessary art therapy is not a placebo, but involves complex cognitive processes which to determine the best therapy course for each patient. lead to the apparent psychological and physical results (9). In another 2017 study, Dr. Girija Kaimal and her colleagues at Drexel Art Therapy and the Brain University explored how coloring, doodling, and drawing affect brain activWhile research suggests that incorporating mindfulity using functional near-infrared spectroscopy (fNIRS) given the principle ness-based components into art therapy sessions is benethat visual self-expression helps with attention, health, and well-being. The ficial and increases the efficacy of reducing psychological study found that the three visual art tasks resulted in significant activation and physical ailments, numerous studies indicate that (measured by mean oxygenated hemoglobin of the medial prefrontal cor-

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tex) with a mean increase of 0.388 for coloring, 0.473 for free drawing, and 0.521 for doodling, all with statistically significant p-values after repeated ANOVA tests. In fact, Kaimal found that compared to a mean baseline value of 0.047, a doodling value of 0.521 corresponded to an approximately 1066% increase in brain activation, measured by blood oxygen in the brain using fNIRS. An important implication of this study is that art-therapy evokes reward pathways; even short spans of artistic activity greatly improve self-perceptions, offering a way to regulate mood and enhance pleasure. This finding corroborates the efficacy of art therapy on the perceived psychological and physical side effects of cancer diagnosis and chemotherapy (10). While Dr. King and Dr. Kaimal’s studies displayed that areas composing the cerebrum are heavily activated by art, a recent 2020 study conducted by Frances J. Griffith at Bowling Green State University utilized an activation likelihood estimation (ALE) meta-analysis to test, when drawing, whether specific brain regions were associated with expression at different levels of the expressive therapies continuum (ETC) – a model of creative functioning used by art therapists to describe and assess an individual’s level of creative functioning. Using neuroimaging and fNIRS, Griffith et al. analyzed two different drawing types: cognitive drawing (internally cued stimulus or objective content) and perceptual drawing (externally cued stimuli and non-objective content). The major findings illustrate that cognitive drawing is associated with prefrontal and cingulate cortex activation, perceptual drawing was associated with cerebellum, frontal, and parietal activation, with the dorsal visual stream being activated for both drawing types. Ultimately, the study suggests that rather than art therapy influencing specific and localized brain regions, larger brain networks are involved with tasks in art therapy and influence health outcomes in patients (11). All three studies analyzing the biological explanation for the high efficacy of art therapy conclude that increased understanding of brain processes and networks activated during art tasks enable art therapists to better understand why specific exercises are successful, and be better equipped to select effective art media. While clinical studies display that MBAT has improved betterment in both psychological and physical symptoms, the biological data demonstrates that certain art media are responsible for the activation of different brain networks, resulting in different sensations of pain reduction. While future research directly measuring brain activity during MBAT is necessary, current research conveys that to achieve maximal efficacy in treatment, the symptoms unique to each cancer patient must be first identified to determine specific areas of the brain to activate, which would determine the specific MBAT course needed.

Conclusion Cancer is undoubtedly one of the most pressing medical challenges of the time, and while art therapies such as MBAT do not pose as a cure, the implementation of simple exercises involving a myriad of media activate areas of the brain, alleviating the effects of cancer diagnoses and chemotherapy. Today, art therapy continues to be heavily researched, as its implementation has the potential to be revolutionary in cancer treatment, representing an efficient, non-invasive, and inexpensive outlet to struggling patients. However, before clinical implementation, increased research on the connection between MBAT and the brain is necessary to corroborate its reviewed efficacy and to determine any possible harmful implications it may have. Nonetheless, art therapy epitomizes the interconnectedness of science and art and is tethered to the future of cancer treatment, remedying patients one brush stroke and breath at a time.

Today, art therapy...has the potential to be revolutionary in cancer treatment, representing an efficient, noninvasive, and inexpensive outlet to struggling patients.

Figure 2 Painting is commonly included in art therapy to treat the psychological and physical

References 1. C. Jarach, More than 50 percent rise in chemotherapy demand by 2040. Cancerworld, (2019). 2. About Art Therapy, The American Art Therapy Association, (2017). 3. C. Peterson, Mindfulness-based art therapy: applications for healing with cancer. Mindfulness and the Arts Therapies, (2014). 4. H. Bozcuk, et al., A comparative study of art therapy in cancer patients receiving chemotherapy and improvement in quality of life by watercolor painting. Complementary Therapies in Medicine 30, 67-72 (2017). doi: /10.1016/j.ctim.2016.11.006. 5. Z. Jalambadani and A. Borji, Effectiveness of mindfulness-based art therapy on healthy quality of life in women with breast cancer. Asia-Pacific Journal of Oncology Nursing 6, 193-197 (2019). doi: /10.4103/apjon.apjon_36_18. 6. N. Collete, et al., Art therapy in a palliative care unit: symptom relief and perceived helpfulness in patients and their relatives. Journal of Pain and Symptom Management 61, 103-111 (2021). doi: /10.1016/j.jpainsymman.2020.07.027. 7. C. Beans, Science and culture: searching for the science behind art therapy. Proceedings of the National Academy of Sciences of the United States of America 116, 707-710 (2019). doi: /10.1073/ pnas.1821297116. 8. J. King, et al., Cortical activity changes after art making and rote motor movement as measured by eeg: a preliminary study. Biomedical Journal of Scientific & Technical Research 1, 1-21 (2017). doi: 10.26717/BJSTR.2017.01.000366. 9. G. Kaimal, et al., Functional near-infrared spectroscopy assessment of reward perception based on visual self-expression: coloring, doodling, and free drawing. The Arts in Psychotherapy 55, 85-92 (2017). doi: /10.1016/j.aip.2017.05.004. 10. F. Griffith and V. Bingman, Drawing on the brain: an ale meta-analysis of functional brain activation during drawing. The Arts in Psychotherapy 71, 1 (2020). doi: /10.1016/j.aip.2020.101690. Image retrieved from: 1. https://pixabay.com/vectors/meditation-meditate-crossed-legs-303260/

Graphics Illustrated by Isra Ahmed `23

side effects of cancer diagnoses and chemotherapy.

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Stony Brook Young Investigators Review would like to give a special thank you to all of our benefactors. Without your support, this issue would not have been possible.

Cover image retrieved from: https://unsplash.com/photos/c7xBEFBJhkg Edited by Komal Grewal `23


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