YNCA Journal September 2016

The Journal of the

YNCA

Youth Neuroscience Clubs of America

MEMORY AND LEARNING

VOL. 1

ISSUE 4

SEPTEMBER 2016

FEATURED ARTICLES

‘A Teacher’s ‘Our Brain Just Got a ‘Basics of Standardized Testing Whole Lot More Neuroscience IV: LTP Guide: How to Ruin Complicated’ – by and Learning’ – by Curiosity in 3 Easy Sohan Shah Alexander Skvortsov, Steps’ Jacob Umans, – by the YNCA William Ellsworth, Satire Team and Maggie Xia

‘Stigmas and Stereotypes: The Societal Pressures of Memory Loss and Learning Disorders’ – by Neelu Paleti

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Contents

INTRODUCTION Letter from the Editor William Ellsworth

pages 3 - 4

Update from the Chairmen Jacob Umans et al.

page 5

GENERAL NEUROSCIENCE Basics of Neuroscience IV: Learning and Alexander Skvortsov, Memory Jacob Umans, William Ellsworth, Maggie Xia

pages 6 - 8

SATIRE A Teacher’s Standardized Testing Guide: The YNCA Satire Team How to Ruin Curiosity in 3 Easy Steps

Pages 9 - 10

NEW TECHNOLOGY Do Cognitive Enhancement Websites such Sohan Shah as Lumosity really work?

pages 11 - 13

INTERVIEW Studying Memory: A PhD Interview Ethan Solomon interviewed by Alexander Skvortsov

pages 19 - 21

NEUROSCIENCE AND SOCIETY

Memory and Society Jack Ross-Pilkington Stigmas and Stereotypes: The Societal Neelu Paleti Pressures of Memory Loss and Learning Disorders

pages 17 - 18 pages 19 - 21

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____________________________________________________________________________ DISEASE Our Brain Just Got a Whole Lot More Sohan Shah Complicated A Forgotten Past: Retrograde Amnesia Christian Gonzalez Developmental Dyslexia Priya Vijayakumar

Psychogenic Amnesia Alexander Skvortsov

pages 22 - 23 pages 24 - 27 pages 28 - 30 pages 31 - 34

RESEARCH The Power of Play: The E ects of Portal 2 and Jacob Umans and Meenu Lumosity on Cognitive and Noncognitive Johnkutty Skills

pages 35 - 36

Research Summary: Preventing the Return of Eva Kitlen and Shreyas Fear in Humans Using Reconsolidation Parab Update Mechanisms

pages 37 - 39

Aplysia Californica: Little Sea Slug - Big Jacob Umans and Meenu Breakthroughs in Learning and Memory Johnkutty

pages 40 - 41

CONTRIBUTORS’ PAGE

page 42

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____________________________________________________________________________ ・INTRODUCTION・

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LETTER FROM THE EDITOR William Ellsworth Readers,

I hope you enjoy the fourth issue of the YNCA Journal! We greatly appreciate your continued (or new) readership.

Learning and memory is one the most important constructs of the mind. From your 13th birthday party, to that anxiety-inducing roller coaster ride, to the baseball tryout that went awry, memories make us who we are.

Impairment of memory fundamentally alters an individual’s identity. We need only to look at Alzheimer’s patients (covered in our second issue), sleep-deprived individuals (covered in our third issue), or amnesiacs (covered in our rst and fourth issues) to understand the devastating e ects of memory loss. In the disease section, we discuss a plethora of processes that harm learning and memory. Christian Gonzalez covers retrograde amnesia, Alexander Skvortsov covers psychogenic amnesia, and Priya Vijayakumar discusses developmental dyslexia. The damage of such conditions is not limited to the pathology itself; in neuroscience and society, Neelu Paleti writes about the social implications of learning and memory de cits.

Naturally, research on learning and memory can help develop therapy and prophylactics for disease; however, research can also be applied to healthy individuals. The research section covers both: Meenu Johnkutty and Jacob Umans discusses a study comparing the cognitive e ects of Lumosity and Portal 2 (I won’t spoil the results!), Eva Kitlen and Shreyas Parab write about using memory reconsolidation to “rewrite” fear memories, and Jacob Umans and Meenu Johnkutty describe Aplysia Californica as a model organism. Sohan Shah, writing for the new technology section, gives a more general summary of the debate around Lumosity.

In this edition, we were also fortunate enough to interview a memory researcher rst hand: Alexander Skvortsov pro les Ethan Solomon, a PhD student at the University of Pennsylvania’s Computational Memory Lab.

As always, it is critical that we recognize all of our dedicated sta for helping us make this issue the success that it is. You can nd all of their names and positions on our Contributors page. If you have any questions, comments, or suggestions for us, please feel free to contact us at YNCA.info@gmail.com. We hope you enjoy our fourth issue as much as we enjoyed writing it!

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NOTE: It has been brought to my attention that in the “Update from the Directors” in our 2nd issue, we stated that “We have already received an endorsement from Neuroscience News, a prominent group of over one hundred thousand people fascinated with the brain.” This statement may have been construed as saying that Neuroscience News has over one hundred thousand members; rather, we are not referencing membership, but the sum total of likes/followers across social media platforms.

Best Regards,

William Ellsworth Editor-in-Chief, YNCA Journal

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____________________________________________________________________________ ・INTRODUCTION・

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Update from the Directors Board of Directors

Hello readers,

We hope you enjoy this edition of the YNCA Journal. Aside from the journal, we are undertaking several large projects. Here are just a few:

Chapter Clubs: As the school year starts for many of us, one of our most important goals is the formation of YNCA chapter clubs in high schools throughout the country. As the “C” in YNCA states, our organization hopes to establish a strong, national network of local clubs dedicated to neuroscience. Several of us have already established clubs, and others have committed to doing so once the school year starts. These can, ideally, be clubs speci cally dedicated to neuroscience.

Alternatively, they can be any clubs related to biology or psychology that, to some extent, cover neuroscience. If you are interested in starting a chapter club, email info@youthneuro.org for advice.

Membership: As of this month, the YNCA has over 60 members. With the growth of our chapter club system, we have been able to recruit many more members to join our organization.

We would like to invite you, our readers, to take the next step and join us in our mission of inspiring the next generation of neuroscientists. If you are interested in becoming a member, please contact us at info@youthneuro.org.

Best Regards,

Jacob Umans and Nicholas Chrapliwy Presidents

Alexander Skvortsov and Janvie Naik Executive Vice Presidents

Kyle Ryan Outreach Director

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____________________________________________________________________________ ・GENERAL NEUROSCIENCE・

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Basics of Neuroscience IV: Learning and Memory Alexander Skvortsov, Jacob Umans, William Ellsworth, Maggie Xia

Hello YNCA readers, and welcome to our fourth Basics of Neuroscience lesson. Today, we will explain how neuronal bonds grow and decrease in strength to form memories and allow us to learn. Last month, we explained the molecular and chemical basis for neural communication, and provided a basic overview of the most common neurotransmitters and neuroreceptors.

Now that we have nished our introduction into the anatomy and communication of neurons, we can continue to work our way into how the human nervous system creates our consciousness.

Types of Memory

Memory is an extremely complex function of the human brain which neuroscientists are far from understanding. However, over the past several decades we have established a rudimentary idea of what memory is and how it works. There are two general types of memory, those being Short Term Memory and Long Term Memory. Short term memory describes your working memory, and generally lasts for several seconds. For example, while reading, you will vividly remember the last sentence or so, but not much beyond that. Short term memory is what you can hold in your thoughts easily.

Long Term Memory is a bit more complex as it has several di erent categories. It can be divided into two broad categories, those being implicit memory, or procedural memory, and explicit memory, or declarative memory.

Procedural memory, also known as muscle memory, is the ability to do tasks. When you repeat the performance of a task many times over, a procedure on how to do it is established in your cerebellum, allowing you to repeat the procedure faster and more easily in the future.

Declarative memory is what most people think of when they hear the word memory. It includes all forms of memory that can be recalled, such as autobiographical memory, or memory about oneself, episodic memory, or memory of events, and semantic memory, or memory of facts and data. Declarative memory is stored in synapses of neurons in the cerebral cortex.

The Cellular Basis of Memory Formation

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____________________________________________________________________________ Memory is expressed as the strength of synapses between neurons. Consequently, memories are formed by strengthening synapses between neurons. This occurs through a process known as LTP, or Long Term Potentiation, which is a complex chain of molecular reactions going all the way from the dendrite to the nucleus, and back. One important thing to note is that LTP must occur thousands of times for a memory to solidify. The process of LTP starts when a neuron res, and ionotropic neurotransmitters, namely Glutamate, Aspartate, GABA, and Glycine, react with neuroreceptors across the synaptic cleft.

As mentioned in the previous issue, the AMPA and NMDA glutamate receptors (named for molecules that can activate them) are highly linked to the process of memory formation. Both receptors are ionotropic, with the excitatory AMPA receptor opening immediately after contact with glutamate. The NMDA receptor, however, is initially unable to shuttle ions through because of a Mg2+ block. In other words, a Magnesium ion prevents ions from moving through. If enough AMPA stimulation is present to depolarize the cell, the positively-charged cell will expel the Magnesium ion from the receptor. After this, Ca2+ ions are free to enter the cell, triggering a downstream signaling cascade.

Once these ions enter the cell, they rst activate Adenylyl Cyclase. This enzyme converts Adenosine Monophosphate (AMP) into Cyclic Adenosine Monophosphate (cAMP). Not only is cAMP involved in LTP, but it is a very common second messenger within the body, responsible for functions as diverse as immunoregulation . The presence of cAMP triggers a short-term increase in synaptic strength on its own, but to induce long-term memory formation the process does not stop here.

The next step in the LTP sequence is the activation of an intriguing enzyme called PKA, or Protein Kinase-A. When activated by a cAMP molecule, the PKA catalytic subunits dissociate from the regulatory subunits to phosphorylate various enzymes within the cell. These proteins include Potassium channels and proteins linked to exocytosis, creating a short-term enhancement of synaptic signaling. If repeated stimulation at the synapse occurs, the PKA catalytic subunit recruits another kinase (p42 MAPK) to the nucleus to regulate transcription factors. Such kinases phosphorylate CREB1 (cAMP-Responsive Element Binding Protein), which functions as a transcriptional regulator. This molecule is selectively responsible for long-term memory storage, and inhibition of CREB1 can selectively prevent long-term memory storage. [1]

Memory Brain Regions

There are two regions of the brain heavily linked to the consolidation of memory: the amygdala, which works with emotional memories, and the hippocampus, which works with declarative memory. While we don’t know exactly how these two structures function, we do know several of the tasks they perform.

The hippocampus is most implicated in the conversion of short term memories to long term memory, through the consolidation process. It is located in the medial temporal lobe, right underneath the cortical surface and is a part of the limbic system. The hippocampus is also divided into two halves, left and right. The hippocampus deals with the formation of long term memories and spatial navigation. It also organizes, forms, and stores memories. Emotional response, navigation, and spatial orientation are controlled by the hippocampus. Memories formed by the ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––7

____________________________________________________________________________ hippocampus are declarative and conscious: they can be speci cally stated and recalled. The memories are formed by the linkage of senses and emotions. The hippocampus does not deal with short term memory, but is connected to it through the consolidation process. We know that the hippocampus is extremely important to long term memory, as individuals with their hippocampi removed (Such as H.M., see our article on anterograde amnesia), are unable to create new long term memories. When the hippocampus is damaged, new memories also can’t form, such is the case in amnesia and Alzheimer’s. However, when only one hippocampi is damaged, new memories typically can be formed. The damage to the hippocampus does not a ect the ability to learn a new skill.

The amygdala is a small and round section of nervous tissue located in the temporal lobe of the brain. Each person typically has two amygdalae, one on each side of the brain. While highly controversial, scientists believe the amygdala is part of the limbic system, playing a role in emotions, survival instincts, and memory. Emotions such as anger and fear are perceived by the amygdala.

The amygdala also plays a role in memory, storing memories associated with emotions for future reference. Memories of emotional events are generally more vivid due to the amygdala’s in uence on the hippocampal encoding and storage. Also, emotion is a factor that both captures attention and processes stimuli with greater ease. Damage to the amygdala impairs the processing of emotional stimuli. The amygdala is an unconscious processor, unlike the hippocampus: a conscious processor. The amygdala learns and stores information on its own, controlling emotional responses.

While the amygdala does not tell what to do, it releases stress hormones among other reactions and tells us how to respond and what the stimuli should respond to. When triggered or activated, the amygdala feeds back into other parts of the brain, such as the hippocampus and allows the other parts of the brain to store memories as well. Accuracy of memories changes over time based on personal perception of the situation. Aggression is controlled by the amygdala, and an increase in size of the amygdala leads to an increase of aggression and physical behavior. Surprisingly, the amygdala also deals with libido, also known as the sex drive. Changes in the amygdala can occur based on age, hormones, and gender.

While the hippocampus and the amygdala are mainly associated with long term memory, the prefrontal cortex and the cerebellum are typically associated with short term memory, as that is where long term memory is stored.

All in all, memory and learning are fascinating processes that involve a mass of intracellular, molecular, and large neural processes working together. Understanding how exactly memory works could be a tremendous advance for neuroscience, helping to treat amnesias, help dementia patients, or perhaps even boost human memory.

References

Hawkins, R. D., Kandel, E. R., & Bailey, C. H. (2006). Molecular Mechanisms of Memory Storage in Aplysia. The Biological Bulletin, 210(3), 174–191. doi:210/3/174 [pii]

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Vitreous Humor: The Official Satire Column of the YNCA ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

A Teacher’s Standardized Testing Guide: How to Ruin Curiosity in 3 Easy Steps YNCA Satire Team As eager students return to their classrooms this September, it seems apt to provide a refresher course in e ective, scienti cally proven methods how to inspire students to ace needless exams and quell any and all curiosity they may possess. In a realm of what radical educators consider “modern education”, the eld has seen many transgressions from the customary path our education forefathers laid for us. For example, there have been several reports of teachers attempting to encourage students to take up “independent study projects.” These perpetrators of educational ignominy have clearly violated the essential component of the education system: controlled, supervised mindless rote memorization. Although these individuals haven’t been charged with the corruption of youth, it is important more than ever, to reinforce the fundamentals of educating the youth.

1. There’s No Such Thing As “Too Many Tests.” a. Instead of instigating deep level critical thinking or nurturing analytical thinking in students, teach them how to su er through hours upon hours of cramming information in hopes that they may be able to recall minute and irrelevant details during a high pressure exam period. It is the teacher’s job to prepare them for the real world; in truth, how many times will students be required to think for themselves in the modern workplace?

2. Focus Only on the Subject Matter that Will Be on The Test a. Teachers can’t hear the question, “Will this be on the test?” enough as this is really the only question that students should focus on. Every now and then, an educational dissident will challenge the teacher by asking a related question to the subject matter, such as, “Why does this occur?” or “But, what if…” Although these are the precursory statements of insurrection, students’ radical questions can only be topped by an attempt for a student who attempts to connect the topic to a related topic found in the real world. Teachers, disregard this student’s curiosity and thirst to connect topics in order to create a cohesive understanding of the world, instead refocus the class back on what matters, the things that are going to be on the test 3. Curiosity is a bane to innovation a. Mainstream media may portray curiosity as the fuel for innovation, but rather it is the antithesis. Curiosity serves merely as a distraction for students; curiosity leads to ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––9

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interest and interest leads to passion, and passion as we all know leads to a life of dull paperwork and not living the same life full of adventure that sticking to conventional educational paths provide. Innovation means maintaining the same mindset, technology, and perspective and curiosity would only ruin that.

In summation, the time is upon educators to strongly reassert the tenets of educating the future. As is common knowledge, “Curiosity is what killed the cat,” and in the modern world, teachers bear the onus of ensuring that curiosity NOT kill our cats or our students. The best, sure-shot way to guarantee the students safety, thus, is standardized testing.

Happy Testing!

***DISCLAIMER***: This article is intended purely as satire. As such, any resemblance to existing persons living or dead, events, or locations, is purely coincidental. Any references to well-known celebrities, locations, events, or corporate entities is intended purely as ction, and all statements made in this article are intended to be interpreted as such; no statement made should be interpreted as fact. The YNCA Journal holds high standards of quality and respect. Thus, should any entity want us to change the names used in our article, the YNCA editing sta will promptly rectify this problem. The YNCA extends a sincere and heartfelt apology to anyone who may nd this article o ensive. The YNCA does not intend to give any medical advice, and no statement in this article should be interpreted as such.

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____________________________________________________________________________ ・NEW TECHNOLOGY・

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Do Cognitive Enhancement Websites such as Lumosity really work?

Sohan Shah

Introduction Whether to ward o neurodegenerative disease or to earn an A on a test, many people wish to improve their cognitive abilities. With this rise in consumer interest, many websites have been established that promise to “improve cognition”. Lumosity, for example, with 70 million active users in 182 countries [V], is the largest of these sites and claims that its users “improved more than [the control group] on an aggregate assessment of cognition” [I]. However, the credibility of these claims are widely debated.

Lumosity’s methodology revolves around the idea that regular use of memory, problem solving, and attention exercises will improve people’s mental abilities. According to “The Guardian”, Lumosity claims to work using the concept of neuroplasticity, the concept that, as people repeat the same tasks over and over, the connections in their brain strengthen [3]. Although neuroplasticity was previously believed to occur mainly in children, new research has shown that it can also occur in adults [10]. The key to unlocking the purported e ects of brain training is, according to MDhealth, regular use: around once a day [4].

A cognitive panacea?

Lumosity claims there are e ectively endless bene ts of brain trainings. Almost every day on the television, people hear convincing advertisements stating that users’ decisions come quicker, and they are more productive. “It’s serious brain training, it just feels like games…” (Jhaveri, 2016).

However, companies such as Lumosity often use false advertising. According to Time Magazine, in January 2016, Lumos Labs, Lumosity’s parent company paid a two million dollar ne “ to settle charges that they deceived consumers with unfounded claims, which include protecting against Alzheimer’s disease and helping users perform better at schools” [11].

Research at the University of Michigan and Brown University has shown that people do display a higher memory and attention span and also perform better on tests after a regimen of brain training games. However, the conditions at which the test subjects practiced their “brain games” are not representative of real life. They played the games for hours a day for many days, while most people already have busy lives and not enough time to dedicate to websites such as Lumosity [4].

Sites such as Lumosity could have great potential for aiding struggling students in school. In a study by Andrea Paula Goldin published in the Proceedings of the National Academy of Sciences, she ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––11

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found that struggling rst graders were able to catch up to their peers in most major subjects after a three month course of online cognitive enhancing games [6].

However, D. Zachary Hambrick, professor of psychology at Michigan State University, contends that “It has to be replicated. I don’t nd the results to be compelling.” His concern with the results stems from methodological weaknesses and statistical oddities; furthermore, he believes the results may not apply to many people [7]. While all of the students in the aforementioned study received cognitive enhancing games, only the students who were struggling in class showed any signs of improvement.

For many, the price of $11.95 per month, seems rather excessive when coupled with the fact that results are not guaranteed [1]. People can achieve the same results through exercises conducted at home, while concentrating deeply on a few tasks. Also, while some scientists have provided evidence Lumosity’s claims, other scientists were not able to replicate results. Dr. Susanne M. Jaeggi performed a study in 2008 which concluded that the “extent of gain in intelligence critically depends on the amount of training: the more training, the more improvement in” uid intelligence [8].

However, according to The Guardian, psychologists at Georgia Tech attempted to replicate her experiment with tougher controls and could not nd any noticeable change in intelligence [3].

The improvements cited in previous studies, while possibly due to faulty research methods, may also be due to the placebo e ect. A recent study published in the Proceedings of the National Academy of Sciences by Cyrus K. Foroughi found that when people opt into a cognitive enhancement course which was really a placebo, their IQ rose by 5-10 points [5]. This study provides another alternative to why people “get smarter” due to Lumosity.

While the science community has not reached a complete and full consensus about the credibility of brain training, evidence still points to exercise as a highly e ective method [2]. So the next time you think about brain training, maybe hit the gym instead.

––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– References:

[1]. Brain Games & Brain Training - Lumosity. (n.d.). Retrieved August 24, 2016, from https://www.lumosity.com/

[7]. Hurley, D. (2014, April 7). New Studies Show Promise for Brain Training in Improving Fluid Intelligence. Retrieved August 24, 2016, from http://www.theatlantic.com/health/archive/2014/04/new-studies-s how-promise-for-brain-training-in-improving- uid-intelligence/360 290/

[2]. Brooks, J. (2016, January 15). Government Slams Lumosity ‘Brain Training,’ But What Does Research Say? Retrieved August 24, 2016, from https://ww2.kqed.org/futureofyou/2016/01/15/lumosity-cant-proveclaims-say-scientists-but-brain-training-worth-researching/

[8]. Jaeggi, S. M., Buschkuehl, M., Jonides, J., & Perrig, W. J. (2008, March 18). Improving uid intelligence with training on working memory [Abstract]. Proceedings of the National Academy of Sciences, 105(19), 6829-6833. doi:10.1073/pnas.0801268105

[3]. Day, E. (2013, April 20). Online brain-training: Does it really work? Retrieved August 24, 2016, from

[9]. Jhaveri, A. (2016, January 5). Consumer Information. Retrieved August 24, 2016, from

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https://www.theguardian.com/science/2013/apr/21/brain-training-o nline-neuroscience-elizabeth-day

https://www.consumer.ftc.gov/blog/brain-training-lumosity-does-it -really-work

[4]. Does Lumosity Work? | MD-Health.com. (n.d.). Retrieved August 24, 2016, from http://www.md-health.com/Does-Lumosity-Work.html

[10]. Ewing, G. (2012). From Neuroplasticity to Sca olding.

International Journal of User-Driven Healthcare, 2(2), 24-43. doi:10.4018/ijudh.2012040104

[5]. Gholipour, B. (2016, June 21). Positive Results From Brain Games May Be Just A Placebo E ect. Retrieved August 23, 2016, from http://www.hu ngtonpost.com/entry/brain-games-placebo-e ect_ us_57693035e4b015db1bca8519

[11]. John, T. (2016, January 6). Brain Game App Lumosity To Pay $2 Million Fine For 'Deceptive Advertising' Retrieved August 30, 2016, from http://time.com/4169123/lumosity-2-million- ne/

[6]. Goldin, A. P., Hermida, M. J., Shalom, D. E., Costa, M. E., Lopez-Rosenfeld, M., Segretin, M. S., . . . Sigman, M. (2014, March 12). Far transfer to language and math of a short software-based gaming intervention [Abstract]. Proceedings of the National Academy of Sciences, 111(17), 6443-6448. doi:10.1073/pnas.1320217111

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____________________________________________________________________________ ・INTERVIEW・

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Studying Memory: A PhD Interview Ethan Solomon interviewed by Alexander Skvortsov

I interviewed Ethan Solomon, a PhD student at the University of Pennsylvania’s Computational Memory Lab, where he conducts research on the electrophysiology of memory.

Alexander- What made you interested in neuroscience?

Ethan- I don't understand how anybody could not be interested in neuroscience! Understanding the brain is really about understanding ourselves and what makes us behave the way we do. Every facet of our lives is, in some way, related to the brain, and I think it's fascinating to try to uncover the real core of our everyday experience.

Alexander- Why did you choose computational memory as your research eld?

Ethan- What really drew me to this lab, and consequently memory, was one of the big projects we're working on: Can electrical stimulation delivered directly to the brain enhance memory? I've always been fascinated with the idea that arti cial devices can be used to repair damaged brain function, and this seemed like the perfect possibility to explore that realm. But before we can hope to implement these kinds of devices in patients with memory problems, we need to learn a lot more about how the brain naturally forms memories. That's where all of the basic science comes into play -- teasing apart the electrical and neuronal brain mechanisms associated with memory.

Alexander- What is your role in the UPenn Computational Memory Lab?

Ethan- Like for any lab, my role as a PhD student is ultimately to make a novel contribution to our understanding of the natural world (and in the process, earn a degree). That's a very tall order, which is why PhDs usually take four or more years to complete. For me in particular, I'm very interested in the idea of connectivity and how it relates to memory function. What I mean by that is: How do di erent parts of the brain communicate with each other during the formation of a memory? Where ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––14

____________________________________________________________________________ do electrical signals carry information between, and what kind of information is it? We use electrocorticographic data, which is basically EEG but under the skull, to try to answer these questions. Ultimately, I hope to be able to integrate what I learn about brain connectivity with our e orts to enhance memory formation using electrical stimulation.

Alexander- What do you enjoy most about being a PhD Student?

Ethan- De nitely the exibility to pursue exactly the things I'm interested in. In other phases of my education, I've had some choice in what I learn about, but a lot of it was chosen for me (in high school, this was especially true). Now, I can pick my research topic, and go down avenues that I nd most interesting. On the other hand, I should point out that it's often very important for someone to force you to learn about things outside your comfort zone. It's an important part of becoming a well-rounded scientist.

Alexander- What do you plan to do after completing your PhD program?

Ethan- I should probably have mentioned earlier -- I am an MD/PhD student, so after I complete my PhD I will go on to nish the last 2 years of my MD (which I began before starting the PhD). From there, I will need to decide on my clinical speciality, if I choose to pursue medicine in addition to research. Either way, my long-term goal is essentially to continue doing what I'm doing right now: Learning more about the brain such that I can help develop therapeutic devices for people with neural dysfunction. I may continue down the road in memory, or I may switch to study sensation, perception, or other forms of cognition -- who knows? What is de nite is that I will keep studying neuroscience, no matter what.

Alexander- What would you recommend to someone interested in pursuing a PhD in neuroscience?

Ethan- I should also have probably mentioned earlier -- my PhD is actually in bioengineering, even though I'm working in a neuroscience-focused lab. But the name of the degree program is de nitely not what's important. The biggest piece of advice I can give to someone interested in getting a PhD in neuroscience (or related elds) is something speci c: A lot of cutting-edge science nowadays relies on good computational skills, so don't be afraid to take math, engineering, and programming classes.

Neuroscience is very interdisciplinary, so learning biology is very important too, especially if you're more interested in cellular or molecular neuroscience. But even then, the large amounts of data that ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––15

____________________________________________________________________________ are generated in modern neuroscience increasingly demand students who know how to handle it.

Fortunately, it's almost never too late to start learning!

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____________________________________________________________________________ ・NEUROSCIENCE AND SOCIETY・

Memory and Society

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Jack Ross-Pilkington

“Memory, my dear Cecily, is the diary that we all carry about with us.”

-Oscar Wilde

Memory is one of the most important aspects of the human experience. It is universal - almost everybody is capable of basic memory and recollection. It shapes our lives in countless ways - from learning to recite the ABC’s to forgetting someone's name. It is the source of both comedy and tragedy. As a result, it is no surprise that memory is a common theme in many works of literature and lm.

While basic memory is almost always present in works of literature, it is sometimes manipulated in incredible ways, as in Marcel Proust's In Search of Lost Time. In Search of Lost Time is regarded by some as one of the greatest works of French literature. Edmund White called it “the most respected novel of the twentieth century” [3]. The famous author Virginia Woolf said of it, "Oh if I could write like that!" [2]. It is an enormous work, consisting of seven volumes and over 4000 pages [4]. However, the most important theme in the book is memory. At the beginning of the book, the protaganist dips a madeleine (a type of cookie) into a cup of tea [4]. This provokes a ood of recollection, causing him to involuntarily relive memories from his childhood, and this inspires the entire story (Encyclopaedia Britannica, 1).

This kind of involuntary memory is controversial in the scienti c community. The classic psychology textbook Psychology: The Science of Mental Life says that those wishing to study it “can only sit and wait, hoping for the improbable” [3]. This is because, according to psychologist Endel Tulving, “Few things that we perceive make us think of previous happenings in our own lives … many stimuli that could potentially serve as reminders or cues, even if prominently displayed to person, will have no such e ect”. In other words, it is di cult to study truly spontaneous involuntary memory because it is rare and hard to trigger.

Memories make us who we are. It’s not surprising, therefore, that the complete loss of memory, known as amnesia, is a common trope in popular culture. One type of amnesia is anteretrograde amnesia. Anteretrograde amnesia is de ned as “Impaired ability to learn new information following the onset of amnesia” [2]. In other words, a person who su ers from anteretrograde amnesia is unable to remember things after they develop the disease. This concept is playfully explored in the lm 50 First Dates. Starring Adam Sandler and Drew Barrymore, 50 First Dates tells the story of a woman (played by Drew Barrymore) su ering from anteretrograde amnesia.

[6]. Her short term memory lasts for exactly one day, so she is unable to remember events after that [6]. As a result, her boyfriend (played by Adam Sandler) has to woo her again every single day [6].

While the movie is not exactly dense scienti c material, it does shed some light on what it’s like to su er from anteretrograde amnesia.

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____________________________________________________________________________ Another type of amnesia that is depicted in lm is retrograde amnesia. Put simply, retrograde amnesia is the opposite of anteretrograde amnesia. Those su ering from retrograde amnesia are unable to remember events that occurred before the onset of amnesia [2]. While retrograde amnesia is common in both lm and literature, one of the most famous examples is the action-packed Bourne series. The whole series consists of ve movies, and the most recent one (Jason Bourne) is currently in theaters [5]. The series tells the story of a CIA agent (Matt Damon) who wakes up unable to recall his name or any memories before then [5]. While most people who su er from retrograde amnesia do not spend their time ghting secret CIA plots, the lm does capture the basic essence of retrograde amnesia. However, it is important to note that most of the time, su erers of retrograde amnesia do not forget their entire self [2].

There is no lm or work of literature that can fully capture the complex science of human memory. However, both the act of remembering and the act of forgetting are interesting topics that are covered frequently in works of art. While they are no substitute for a detailed, scienti c understanding of memory, they can provide an interesting glance into how we remember, and what happens when we cannot.

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References

[1] Woolf, V., Nicolson, N., & Banks, J. T. (1975). The letters of Virginia Woolf. New York: Harcourt Brace Jovanovich.

[4] Tulving, E. (2007). Elements of episodic memory. New York: Oxford University Press.

[2] Amnesia. (n.d.). Retrieved August 21, 2016, from http://www.mayoclinic.org/diseases-conditions/amnesia/basics/ de nition/con-20033182

[5] Jason Bourne (2016). (n.d.). Retrieved August 21, 2016, from http://www.imdb.com/title/tt4196776/

[3] White, E. (n.d.). Marcel Proust.

Miller, G. A. (1962). Psychology, the science of mental life. New York: Harper & Row.

[6] 50 First Dates (2004) (n.d.). Retrieved August 21, 2016, from http://www.imdb.com/title/tt0343660/

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____________________________________________________________________________ ・NEUROSCIENCE AND SOCIETY・

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Stigmas and Stereotypes: The Societal Pressures of Memory Loss and Learning Disorders

Neelu Paleti

Introduction After over two months of relaxing summer break, kids from all around the country start to stumble into school hallways, energized and anxious for the new year. But some are di erent. Among the crowds of smiling faces are the gloomy ones portraying sheer misery. This particular group of students may love to learn, but nonetheless, they continue to dread the thought of school. Students with learning disorders are often the victims of such circumstances in schools across the nation. Regardless of their desire to improve and succeed, they may fall short, only leading to more frustration.

While teachers battle to encourage such students to proceed at a pace of their own, many students eventually lose their con dence at the sight of peers striding forward. Soon enough, the friends, who were once patient enough to wait, could skip away. Sometime down the road, a countless number of these students could easily buckle under the societal constraints bestowed to people with learning disorders.

While kids are struggling to make new friends, adults on the opposite end of the spectrum may be dealing with situations of the same sort. As an elderly woman shu es her way out of the house to drive over to the nearest grocery store, she realizes that her keys are not in her bag.

Following fteen minutes of searching around the house, she nds her lanyard of keys lying near her bedstand, where she had last left them. Once she nally made it to the store, there was yet more confusion as she struggled to remember the items on her shopping list. This was not an unusual day for this woman, as old age started to take a toll on her once sharp memory. As her son started to intervene, he noticed the prevalence of her memory loss in every small activity, which prompted him to take action. Out of pure concern, the son prevented his elderly mother from driving, leaving her feeling powerless. With a continuous degradation of memory, even her small home was forced to change, as she was moved to a nursing facility. With such traumatic denial by her own community, the victim of dementia could be brought down more by the society and family than the disease itself.

Learning disorders and memory loss are prevalent conditions that can in uence the lives of its patients in quite profound ways. ADHD, dyslexia, amnesia, and Alzheimer’s are amongst the ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––19

____________________________________________________________________________ most commonly seen disorders with societal e ects extending beyond the physical manifestations.

A child with dyslexia is bound to learn at signi cantly slower rates when compared to peers, and with the heavy competition of today’s world, the initial frustration could double and soon triple.

With lost friendships, anxious parents, and impatient educators, the pressure on a student could lead to irreparable mental damage. This does not even include the painful remarks and unnecessary questions asked by the general public. Likewise, an amnesia patient who has lived a normal life for decades could be losing their precious autonomy for the very rst time. The revocation of a license and the move from home to a care facility could be shocking revelations in the life of an elderly patient who has become accustomed to his/her independence. The lack of trust and overly cautious looks from their friends, family, and public could be distressing, as they nd no one to welcome them anymore.

Over the decades, society has been responsible for developing and perpetuating certain stigmas associated with memory loss and learning disorders. For example, the belief that intellectually challenged students cannot learn has been a perspective quite common in the public (Gibson, 2008). However, success is di erent for every student, and recognizing that the rate of acquiring new knowledge may be di erent for each could be the key to change. Social comparisons can be detrimental to the crucial development of children, and the movement to stop perpetuating such behavior stands to be quite essential. Likewise, the negative perceptions towards people with psychological or memory disorders can be the factor that fuels stigmas against patients with amnesia or Alzheimer’s disease (Batsch, 2012). Global communities and cultures are known to shun memory loss patients and put dementia patients under house arrest to escape public shame. Even in developed countries, the traditions of moving Alzheimer’s disease patients to nursing homes could deprive them of the needed love needed to foster good health. However, due to the bustling lives of the workforce today, such situations cannot be easily averted. Lastly, many stereotypes unrightfully paint victims of dementia in a disrespectful manner. Many people fail to take the words of a dementia patient seriously, whether that is while they o er their opinions at the dinner table or while they give advice to their children. Blatantly rejecting every word of a memory loss patient by citing their words as “foolish nonsense” is not the way society can end the perpetuation of stigmas.

Instead, boosting the self-esteem of people with both memory loss and learning disorders can be the path to heal individuals.

As society begins to ght stigmas associated with these conditions and more, it becomes imperative to review the systems in place for better quality care and reception of those in need.

Whether it is the education systems in place or the nursing facilities around town, each place can change small aspects to diminish stigmas. Educators can develop new ways to integrate students with and without learning disabilities in order to raise awareness of the di erent ways of learning.

Seeing that classmates having trouble in the classroom can be just as good friends as those with straight A’s can certainly boost the perspective of an ordinary elementary student. This would in turn eliminate isolation and allow for ideal emotional development.

In a similar manner, introducing more people to the e ects of dementia can educate and inspire caretakers to treat such patients normally. Being aware that the global treatment of dementia patients is not necessarily the same as conditions in wealthier countries is in fact a large step towards change. Noticing that dementia patients are not receiving the respect they deserve can lower the prevalence of stigmas, as well.

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____________________________________________________________________________ As such societal norms are rethought, a new pathway for change can be carved, leading to a society that reduces, instead of sustains, the arisal of stereotypes and stigmas of these various conditions.

––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– References {1} Gibson, C. P. (2008). Overcoming the Stigma of the Learning Disability Label: A Story of Survival and Recovery. Retrieved August 23, 2016, from http://www.acadcom.com/acanews1/anmviewer.asp?a=53

{2} Batsch, N. L. (2012). Edinburgh Research Archive. Retrieved August 24, 2016, from https://www.era.lib.ed.ac.uk/handle/1842/2630

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____________________________________________________________________________ ・DISEASE・

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Our Brain Just Got a Whole Lot More Complicated Sohan Shah

While the brain looks like a messy gray mass of folded clay, it is actually partitioned into numerous specialized regions. Some regions are excited by a familiar face, others by touching a hot stove, and others by feeling the brisk wind on a winter day. These functional zones were originally codi ed by the German anatomist Dr. Korbinian Brodmann in 1909 based on histologic slide observations and have been gradually re ned ever since.

On July 20, 2016, a research team led by Dr. Matthew Glasser published a new map of our brain in Nature Magazine, titled “A multi-modal parcellation of human cerebral cortex”, which reveals almost one-hundred previously uncharacterized regions of the brain [4]. Although the new zones have been identi ed, scientists have not yet discovered the functions of the new regions.

According to Dr. Glasser, “This map you should think of as version 1.0. There may be a version 2.0 as the data get better and more eyes look at the data. We hope the map can evolve as the science progresses.” [3].

In 2013, Dr. Glasser and his colleagues began using the Human Connectome Project’s (HCP) database of 1,200 volunteers to compare their functional MRI brain scans while the participants were performing a variety of functions: memory, attention, and language [2]. The HCP’s goal is to determine the speci c neural pathways that underlie brain function and behavior by analyzing many di erent aspects of the brain simultaneously (e.g the architecture, function, connectivity or topography). The simultaneous analysis of neuronal data is what di erentiates Dr. Glasser’s work from previous attempts to map the brain. In the past, scientists could only compare one aspect of the brain, such as the architecture, function, connectivity or topography [1]. The combination of di erent types of data allowed for more regions to be determined.

For instance, the scientists looked deeper into the brain’s anatomy and discovered that in some regions the density of neurons was vastly di erent than in others. They also looked at myelin, the protective insulating substance that surrounds cells and speed up neuronal impulses. The amounts of myelin varied vastly from one region to another. The scientists trained a computer to analyze the data from the human subject’s brains and nd the key markers that di erentiated each region. Surprisingly, the number of necessary markers were surprisingly few. This meant that a computer could map an individual's brain in around seventy minutes. The nal di erence between ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––22

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the research of Dr. Glasser’s team and research of years past is that Dr. Glasser’s team analyzed the brain's entire breadth, unlike neuroscientists of past generations who looked at only aspect of the cerebral cortex [1].

The Connectome map created by Dr. Glasser’s team contains 180 regions. Of these, 83 were familiar zones and 97 were previously uncharacterized [2]. The new regions were formed either by reforming the boundaries of older zones or by partitioning larger regions into multiple smaller ones.

For instance, the dorsolateral prefrontal cortex, once thought to be one region, it is now known to contain twelve smaller ones.

There are many important implications of this research, especially in healthcare. According to CNN, as reported in Advisory Board, an organization dedicated to helping healthcare organizations improve performance, the research could be used for teaching neurosurgery students, or for helping to plan more detailed operations. Scientists could also use the more detailed map to gure out how Alzheimer’s and other dementias a ect the brain {3] [1].

The next step in this research is to determine if the identi ed regions are actually separate areas. This would mean analyzing gene expression of neurons in di erent regions. “You can imagine going to these 180 regions, taking a punch of tissue, and seeing if you can really genetically di erentiate them,” said Dr. David Kleinfeld, a neuroscientist at the University of California, San Diego. According to the New York Times, experts believe that scientists will discover the the newly identi ed areas contain multiple smaller regions functioning together. According to Dr. David C. Van Essen, a principal investigator with the Human Connectome Project at Washington University Medical School, “We shouldn’t expect miracles and easy answers, but we’re positioned to accelerate progress.”

––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– References

[1]. Scientists discover almost 100 new brain regions, with possible

[3]. Scutti, S. (2016, July 20). Updated brain map identi es 97 new

implications for Alzheimer's and more. (2016, July 22). Retrieved

areas. Retrieved August 24, 2016, from

August 24, 2016, from

http://www.cnn.com/2016/07/20/health/new-brain-map/

https://www.advisory.com/daily-brie ng/2016/07/22/100-new-brain -regions [2]. Zimmer, C. (2016, July 20). Updated Brain Map Identi es Nearly

[4]. Glasser, M. F., Coalson, T. S., Robinson, E. C., Hacker, C. D.,

100 New Regions. Retrieved August 24, 2016, from

Harwell, J., Yacoub, E., . . . Essen, D. C. (2016, July 20). A

http://www.nytimes.com/2016/07/21/science/human-connectome-b

multi-modal parcellation of human cerebral cortex [Abstract].

rain-map.html?_r=0

Nature,536(7615), 171-178. doi:10.1038/nature18933

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____________________________________________________________________________ ・DISEASE・

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A Forgotten Past: Retrograde Amnesia Christian Gonzalez

Introduction In 1926, an American man was born in Connecticut who would eventually captivate the international medical community for more than half a century and have a legacy that has left a signi cant mark on today’s understanding of modern neuroscience and human memory. Referred to inconspicuously as simply “H.M.,” Henry Molaison lived a normal life for most of his childhood.

However, at age 10 he was involved in a bike accident and the resulting head trauma led to the development of epilepsy. In the years after the incident H.M. was plagued by daily seizures and severe pain, and as a result he was unable to lead a normal life. Desperate to nd relief he visited neurosurgeon Dr. William Scoville. Dr. Scoville performed a radical brain surgery involving the bilateral removal of H.M.’s amygdala and hippocampus. After his surgery, H.M. developed anterograde amnesia, and his inability to form new memories was often cited by those who argued that he was no better o now than before the surgery. While most of the research conducted in regards to H.M. dealt with his pronounced anteretrograde amnesia, his episodes of retrograde amnesia also helped to expand the scienti c community’s knowledge and understanding of the hippocampus and amygdala’s role in memory formation and recall (Godwin, n.d.).

Overview and Symptoms

Retrograde amnesia is a memory disorder characterized by the inability to recall memories of events dating prior to the onset of the disability. Unlike most neurological conditions, retrograde amnesia does not have a typical line of treatment, such as medications or therapies, that can change outcomes. There are four main types of retrograde amnesia that each express their symptoms in slightly di erent ways: pure retrograde amnesia, focal retrograde amnesia, isolated retrograde amnesia, and temporally graded retrograde amnesia. Pure retrograde amnesia is the only type of retrograde amnesia that is not accompanied by anteretrograde amnesia. In all other varieties of the disorder, patients are not only unable to recall memories prior to an accident, but also lose the ability to form new memories. (Winocur, Mcdonald, & Moscovitch, 2000). Focal retrograde amnesia is the only type without a noticeable physical disability along with memory problems. Isolated retrograde amnesia is similar to the other forms, but di ers in that it is primarily the result of a lesion in the thalamus, and recalling memories is often even more di cult than in the other types of the disorder (Miller et al., 2001). In the case of temporally graded retrograde amnesia, patients are typically ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––24

____________________________________________________________________________ fortunate enough to recover most of the memories they lost after the incident which resulted in their condition (Acharya, n.d.). While all four of these types of retrograde amnesia a ect patients di erently, every type of retrograde amnesia can be simply de ned as a type of amnesia that a ects autobiographical memory primarily and semantic memory, (to a lesser degree), and leaves an individual unable to recall memories prior to the onset of amnesia. The primary symptom of retrograde amnesia is usually only memory loss, but physical issues that vary from patient to patient are quite common as well. Confusion and inability to recognize familiar faces are indicative symptoms of an amnesiac having memory loss.

Causes

In most cases, retrograde amnesia is brought about by damage to the hippocampus in the temporal lobe. There are, however, much wider reasons for the initiation of such damage in retrograde amnesia. The most common occurrence that results in hippocampal damage is head trauma. Some frequent events that result in head trauma include sports injuries, car accidents, and falling. As a result of head trauma, individuals may often (afterwards) have (what is known as) a coup countrecoup injury. In this type of injury, both sides of the brain are damaged- the side that absorbed the initial impact (coup), and the side opposite of the impact (countrecoup) (“Types of Neurologic Damage.,” n.d.). Another cause is anoxia and ischemic strokes. Epilepsy can also cause retrograde amnesia in addition to Korsako ’s syndrome. Psychologically disturbing events, infectious conditions, surgery, psychiatric treatment, traumatic injuries, and damage to the temporal lobes and diencephalon can contribute to the onset of retrograde amnesia as well. While the hippocampus is not the primary area that is usually damaged in retrograde amnesia, damage may still occur here that can result in the disorder. Therapeutic measures such as electroconvulsive therapy (ECT) that may be used to treat conditions such as major depression can lead to short term memory loss, and in some cases clinically induce retrograde amnesia due to the e ects of the treatment on the brain.

Diagnosis

The most common method used to diagnose patients with retrograde amnesia, and any form of amnesia, is evaluating a patient’s factual knowledge abilities. Speci cally, autobiographical memory is more important in testing whether or not a patient may be su ering from retrograde amnesia. To evaluate this, a physician or doctor may interview an individual to gain some insight into the capacity of their memory and their abilities. In an interview, a doctor will assess three areas of a patient’s life- childhood, early adulthood, and recent facts. Additionally, the neuroimaging techniques CT and MRI may be employed to assist in the diagnostic process, and abrupt decreases in brain activity in an EEG can indicate structural damage, a key sign of retrograde amnesia (Acharya, n.d.).

Pathophysiology

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____________________________________________________________________________ Typically, amnesia is the result of primary damage to a part in the brain, usually the hippocampus, which results in memory loss. In the case of retrograde amnesia, however, the hippocampus remains in tact for the most part, and other areas of the brain are a ected that play important roles in declarative memory. In the case of retrograde amnesia, the main areas a ected that result in severe memory loss experienced are the diencephalon and temporal lobes, speci cally the thalamus, especially in isolated retrograde amnesia.

Treatment

The course of treatment for a patient with retrograde amnesia depends considerably on which variety they have as well as the cause which initiated the disorder. A common path of treatment involves the use of a learning technique called classical conditioning, also known as Pavlovian learning, in which a stimulus can be used to evoke a response from a patient that can be used to gain back parts of lost autobiographical memory. As retrograde amnesia is closely associated with Korsako ’s syndrome, injection of thiamine supplements into veins can also lessen the recovery time. Drugs may also be taken to mitigate tissue damage of brain structures. Some of the most common classes involved in pharmaceutical treatment include antiepileptic drugs and diuretics. If a doctor believes that a viral infection might have been involved in the induction of the disorder, then anticonvulsants, antibiotics, and steroids may be taken as well. If the amnesia was thought to be caused by psychological trauma, then hypnotherapy might be employed (Acharya, n.d.).

Key Terms Henry Molaison- American memory patient who su ered from severe anteretrograde amnesia with episodes of retrograde amnesia simultaneously; more commonly referred to as “H.M.” Amygdala- Almond shaped brain part in limbic system involved in fear and emotional memory Hippocampus- Seahorse shaped brain part in limbic system involved in control of memory and emotion Anteretrograde amnesia- Inability of the brain to form new memories after the onset of amnesia Thalamus- Egg shaped brain part that relays sensory information to the cerebral cortex Head trauma- Injury that causes brain trauma Coup countrecoup injury- Injury that causes damage to both sides of the brain Anoxia- Absence of oxygen Korsako ’s Syndrome- Disease associated with alcohol misuse that results in an individual fabricating false memories to cover up forgotten ones of past experiences Electroconvulsive Therapy (ECT)- Method of reducing seizures by passing small electrical currents through the brain Autobiographical Memory- Memories of personal experiences from an individual’s life CT- Imaging technique that uses X-rays to take photos of organs and other body parts MRI- Imaging technique that uses magnetic elds to take photos of organs and other body parts EEG- Method used in electrophysiology to detect abnormal electrical activity in the brain Declarative Memory- Memories of facts and events that can be consciously recalled; also known as explicit memory ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––26

____________________________________________________________________________ Diencephalon- The posterior portion of the forebrain (prosencephalon) comprised of the thalamus, hypothalamus, pineal gland, and third ventricle Classical Conditioning- Type of learning in which in which neutral and potent stimuli are paired together to generate a response Diuretics- Drug class that promotes urine production Hypnotherapy- Technique used in psychotherapy to elicit subconscious change by hypnosis ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– References

[1] Acharya, M. (n.d.). Retrograde amnesia. Retrieved August 04, 2016, from

http://www.hxbene t.com/retrograde-amnesia.html

[7] Types of Neurologic Damage. (n.d.). Retrieved August 04, 2016, from http://www.northeastern.edu/nutraumaticbraininjury/what-is-t bi/types-of-damage/

[2] Godwin, D. (n.d.). Patient Zero: What We Learned from H.M. Retrieved August 04, 2016, from http://blog.brainfacts.org/2013/05/patient-zero-what-we-learnedfrom-h-m/#.V6D309IrKUk

[8] Winocur, G., Mcdonald, R., & Moscovitch, M. (2000, August 1). Anterograde and retrograde amnesia in rats with large hippocampal lesions. Hippocampus, 11(1), 18-26. doi:10.1002/1098-1063(2001)11:13.0.co;2-5

[3] Kopelman, M., & Kapur, N. (2001). The loss of episodic memories in retrograde amnesia: Single-case and group studies.

The Royal Society, (356), 1409-1421. doi:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1088524/pdf /TB011409.pdf

[4] Miller, L., Caine, D., Harding, A., Thompson, E., Large, M., & Watson, J. (2001). Right medial thalamic lesion causes isolated retrograde amnesia. Neuropsychologia, 39(10), 1037-1046. doi:10.1016/s0028-3932(01)00041-0

[5] Reed, J., & Squire, L. (1998, May 15). Retrograde Amnesia for Facts and Events: Findings from Four New Cases. The Journal of Neuroscience, 18(10), 3943-3954

[6] Squire, L. R. (2009, January 15). The Legacy of Patient H.M. for Neuroscience. Neuron, 61(1), 6-9. doi:10.1016/j.neuron.2008.12.023

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Developmental Dyslexia Priya Vijayakumar

Introduction Learning disorders are more common than generally conceived: 15-20% of children and adults su er from language-based learning disorders.

Of those people, 5-10% have dyslexia [4][5]. Characterized by de cits in reading and interpreting words, dyslexia is a learning disability that a ects 70-80% of all individuals with reading di culties; the disorder is the result of phonological processing gone awry [3].

Neurological Underpinnings

The past three decades have been signi cant in understanding the neurological mechanisms behind dyslexia. Imaging, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), taken while human subjects engaged in cognitive activity has led to the development of a few theories for the neurological underpinnings behind dyslexia [3].

The phonological theory is the most popular explanation for dyslexia; this theory states that while humans are neurologically hardwired to recognize speech, reading itself is an acquired ability [3]. The process of reading requires the recognition of symbols, the order of which the symbols are in, and the pronunciation of phonemes. Phonemes are the fundamental auditory components of speech; in the English language, there are 44 phonemes. Dyslexics lack uency in this phonological system and thus struggle to read or perform other language-based tasks such as math with accuracy and uency [2].

Brain-imaging studies have identi ed three regions in the left hemisphere of the brain that are implicated in dyslexia. Aligning with the notion that the left hemisphere is dominant in processing language, dyslexics have decreased neural activity in the left parieto-temporal and occipito-temporal regions of their brains. The Broca’s area also exhibits decreased neural activity however, as dyslexia persists into adulthood, activity may normalize due to maturation [3][4].

A cell-level hypothesis for dyslexia asserts that the learning disability is due to a visuomotor coordination impairment. In other words, the eyes’ movement does not coordinate with the letters or words being read. As a result of this discoordination between eye movement and what is being read, dyslexics confuse the order of letters. Research evidences a de cit in the visual magnocellular system in dyslexics. The visual magnocellular system comprises of large neurons found in the retina that are responsible for coordinating movement with visual stimuli. For example, when reading, the eyes focus on the order of which the letters and words should be read in. If the eyes lose focus on their visual target, this information is fed to the magnocellular system which in turn, acts through the cerebellum and motor neurons in the eyes to return focus on reading. Dyslexics face impairment ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––28

____________________________________________________________________________ with this visuomotor system and thus, have less steady control of eye movement which results in the hallmark symptoms of dyslexia [2].

Courtesy of Gary Waters via Getty Images

Symptoms and Diagnosis

Hallmark symptoms of dyslexia include morphological confusions between letters (such as confusing “b” and “d”), slow reading, mispronunciation of words, and even poor handwriting [2][7].

Poor reading skills can easily be confused with dyslexia so thorough screening for diagnosis is preferable.

Dyslexia is easily diagnosable from reading tests. Because of this, dyslexia is often identi ed in young children if de cits in normal reading abilities are observed. However, in order to accurately di erentiate dyslexia from other reading disabilities, professional screening is typically conducted.

Professional screening consists of a comprehensive evaluation of general intelligence, word recognition, word decoding, spelling, verbal uency, reading comprehension, and vocabulary. Such screening for dyslexia is not always accurate; those with less-severe dyslexia often slip through without detection. Regardless, tests such as Predictive Assessment of Reading or Dynamic Indicators of Basic Early Literacy Skills serve as good starting points for diagnosing dyslexia in younger children [1][7]. Dyslexia is notorious for its inheritability thus, analyzing family histories of the disability can be helpful for con rming diagnoses [4].

Therapy

Systematic and goal-oriented intervention serves as the best therapy for dyslexics.

Consistent reading practice as well as understanding how phonemes correlate to their symbol counterparts are e ective forms of intervention [4]. Thankfully, dyslexia is adequately compensated for when interventions take place during early childhood; 70% of at-risk dyslexics who received therapy prior to second grade are pro cient readers [6].

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References

[1] Getting an Assessment for Dyslexia. (n.d.). Retrieved August 23, 2016, from http://www.bdadyslexia.org.uk/dyslexic/getting-an-assessmentfor-dyslexia

[5] Statistics on Dyslexia. (2010). Retrieved August 23, 2016, from http://www.dyslexiacenterofutah.org/dyslexia/statistics/

[2] Morris, R. G., Fillenz, M., & Dickenson, A. H. (1995).

Neuroscience: Science of the Brain. Brain Research Association.

[6] Tackling Dyslexia at an Early Age. (2014). On the Brain: The Harvard Mahoney Neuroscience Institute Letter, 20.

[3] Shaywitz, S. E., Mody, M., & Shaywitz, B. A. (2006). Neural Mechanisms in Dyslexia. Current Directions in Psychological Science, 15(6), 278-281. doi:10.1111/j.1467-8721.2006.00452.x

[7] Testing and Evaluation. (n.d.). Retrieved August 23, 2016, from https://dyslexiaida.org/testing-and-evaluation/

[4] Society for Neuroscience. (2012). Brain Facts: A Primer on the Brain and Nervous System. Washington, D.C.

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Psychogenic Amnesia Introduction

Alexander Skvortsov

Amnesia, or “a condition in which a person is unable to remember things because of brain injury, shock, or illness”{1} is among the most common cause of memory loss, worldwide. This condition includes several distinct types of memory loss, including anterograde amnesia, or inability t0 form long term memories , retrograde amnesia, or loss of memories before a certain occurrence, post-traumatic amnesia, or generally transient amnesia occurring after a physical traumatic injury to the head, and psychogenic amnesia, which, unlike the other three major types of amnesia, which are generally caused by physical trauma, drugs, is caused by psychological reasons. Psychogenic Amnesia is a condition in which a patient is unable to recall autobiographical information, which is usually traumatic [2].

Dissociative amnesia occurs in two versions: global and situation-speci c, and can include several phenomena such as repressed memories and dissociative fugue.

Cause

The primary di erence between Psychogenic Amnesia and organic amnesias lies within the cause. Organic amnesia is triggered by physical damage to the brain, particularly the medial temporal lobe. This damage can stem from a impact, a chemical reaction, a disease, a botched surgery, or any other physical cause. Psychogenic Amnesia, on the other hand is a result of a non physical factor, usually severe stress. Stress can stem from many sources, including abuse, trauma, war, disasters, failed relationships, or other traumatic events. Psychogenic Amnesia is often accompanied by psychological trauma , often appearing alongside trauma-based diseases such as PTSD [2].

Overview

Also known as Dissociative Amnesia or Functional Amnesia, Psychogenic Amnesia is a memory disorder characterized by a combination of retrograde and anterograde loss of memory [3].

In all types of Psychogenic Amnesia, the primary type of memory a ected is episodic memory-

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____________________________________________________________________________ memory about one’s identity. There are two general categories of Psychogenic Amnesia: Global Psychogenic Amnesia and Situation-Speci c Amnesia.

Situation-Speci c Amnesia is a collective term used to describe Psychogenic Amnesias related to, caused by, or centered around speci c event or timeframes. It is often linked to stressful events, and can be a part of Post-Traumatic Stress Disorder. This subtype of Psychogenic Amnesia is the most common category of this amnesia and includes several distinct patterns of memory loss.

Localized Amnesia is a situation-speci c amnesia which entails a total loss of recall for a contained period of time, ranging from several hours to several months to several years. This forgotten period generally follows a traumatic event. Localized amnesia is the most common form of psychogenic amnesia[2], which is why situation-speci c amnesia is also the most common. Localized Amnesia goes hand in hand with an extremely similar amnesial pattern known as Selective Amnesia. Like Localized Amnesia, Selective Amnesia generally follows a traumatic or stressful event, and lasts for a circumscribed period of time, which generally lasts from several hours to several years. However, unlike Localized Amnesia, individuals experiencing selective amnesia will have some limited memories remaining from the given time period. Note that Selective Amnesia di ers from natural forgetting, as the memory loss will be brought on by severe stress, trauma, or some other psychological cause. Selective Amnesia and Localized amnesia can occur side by side, one after the other, or intertwined.

Systematized Amnesia is another subtype of situation-speci c amnesia that di ers from the Selective and Localized variants in that it is not limited to a time period. Systematized Amnesia refers to the loss of all memory in a speci c category. This can concern an entity, such as a person or a location, a smell or taste, or a type of object. However, since most dissociative amnesias stem from trauma or stress, the category of information that will be lost will most often relate to the situation that originally caused the stress or trauma.

Continuous Amnesia is the nal pattern of situation-speci c memory loss, and di ers substantially from the rest. Unlike all other psychogenic amnesial patterns, which are mainly characterized by loss of memory before, around, or shortly after the traumatic event, Continuous Amnesia works in an anterograde pattern, meaning that there is a loss of ability to create memory after the triggering event.

In addition to those broad subtypes, situation-speci c amnesia includes several special cases.

In many cases of assault, the o ender will claim, during legal proceedings, to be forgetful of the incident. Most of these claims tend to be dubious, although some may have truth in them. Studies nd that true amnesia for an o ense can occur either through substance use, notably that of alcohol, or when the o ender is feeling passionate about his actions[5]. Another major phenomena associated with situation-speci c amnesia is the idea of memory repression. Memory Repression is a process in which a memory is forgotten for a long period of time, generally several years, and then resurfaces. Most examples of alleged memory repression concern incidents in one’s childhood. The validity of repressed memories is highly contested and controversial, especially where legal matters are concerned. For example, Harrison G Pope of the Royal College of Psychiatrists published an article in 1998 strongly advising against the use of psychotherapy to discover repressed memories, as the process can result in the creation of false memories, which can then lead to false allegations, creating legal trouble. In his article, Dr. Pope states that validity of repressed memories can not be proved [7]. In addition to that, in a Harvard Magazine article concerning Dr. Pope’s work, it is stated ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––32

____________________________________________________________________________ that he was unable to nd any cultural examples of memory repression before 1786, suggesting that the idea of memory repression may be much more cultural than it is scienti c [8].

In addition to being an amnesia, Psychogenic Amnesia is also classi ed as a dissociative disorder by the DSM-V (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) [2]. dissociative disorders are a category of disorders in which the patient loses some contact with their identity, consciousness, or sense of self, which ties in with the primary symptom of Psychogenic Amnesia, namely losing memory about oneself. This aspect of Psychogenic Amnesia is prominent in the global amnesia classi cation. Global amnesia, or generalized amnesia, is the second category of Psychogenic Amnesia, is much less common than situation-speci c amnesias, and is a more complete amnesia. Memory loss during global amnesia can span an individual’s whole life, and can

be semantic or procedural alongside the usual episodic memory loss. This memory loss is primarily of a retrograde nature, and can include loss of personal identity, ability to do tasks, or general information [2]. A more extreme case of global amnesia is generally categorized as a Psychogenic Fugue, or a total loss of personal identity. Individuals su ering through a psychogenic fugue often establish a new identity, wander, or otherwise function separate from their forgotten identity [5]

Psychogenic Amnesias are, in general, very interesting to neuroscientists as they serve as an example of how psychological trauma can a ect the process of memory. While there is currently no cure, a therapist can treat psychogenic amnesia to attempt to make it less severe.

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____________________________________________________________________________ References

[1] Amnesia. 2016. In Merriam-Webster.com .

Retrieved August 8, 2016, from http://www.merriam-webster.com/dictionary/amnesia.

[5] McKay, G. C. M., & Kopelman, M. D. (2009). Psychogenic amnesia: When memory complaints are medically unexplained.

Advances in Psychiatric Treatment, 15(2), 152–158. doi:10.1192/apt.bp.105.001586

[2] American Psychiatric Association. (2013). Dissociative Dissorders. In Diagnostic and statistical manual of mental disorders (5th ed.). doi:10.1176/appi.books.9781585624836.

[7] Pope, H. G. (1998). Recovered memories of childhood sexual abuse. BMJ : British Medical Journal, 316(7130), 488–489.l.

[3] Mastin, L. (2010). Psychogenic Amnesia - memory disorders - the human memory. Retrieved August 8, 2016, from Human Memory, http://www.human-memory.net/disorders_psychogenic.html.

[8] Pettus, A. (2008, January 1). Repressed memory. Harvard Magazine. Retrieved from http://harvardmagazine.com/2008/01/repressed-memory.html.

[4] Dissociative Amnesia. (1995). Retrieved August 8, 2016, from Cleveland Clinic, http://my.clevelandclinic.org/services/neurological_institute/ce nter-for-behavioral-health/disease-conditions/hic-dissociative-a mnesia.

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The Power of Play: The E ects of Portal 2 and Lumosity on Cognitive and Noncognitive Skills

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Jacob Umans and Meenu Johnkutty

Introduction A recent study, conducted at Florida State University, investigated the e cacy of Portal 2 (a video game) and Lumosity (a brain-training program).

This study analyzed problem solving, spatial skills, and persistence in participants of the study who spent eight hours either playing Portal 2 or Lumosity. The researchers found that Portal 2 provides certain cognitive bene ts, whereas Lumosity provided no such bene ts.

Even the occasional video game player has heard the trite, overused comment that video games “rot your brains.” But, video gamers can now take pride in their hobby because a new study has shown that one video game, Portal 2, has outperformed Lumosity, a popular brain training website, in a study in their e ects on cognition. In their study of students from Florida State University, the team of researchers found a statistically signi cant di erence between the e ects of Portal 2 and Lumosity on multiple measures.

Seventy-seven undergraduate students were given one of two games to play: Portal 2, a 3D puzzle-based game, or a collection of training exercises from Lumosity. All of the participants were between the ages of 18 and 22, and consented to the study before participating. The students were prescreened before playing as well. If the student had played Portal 2 before, was susceptible to motion sickness, or self-reported as a frequent video game player, he or she was not approved for the study. This allowed researchers to avoid confounding variables (variables that they are not testing for) a ect the overall results. The population group was made up of 43% male gamers and 57% female gamers. Once approved for the study, all the subjects were randomly assigned to play either Portal 2 or Lumosity.

In order to identify the e ects of Portal and Lumosity on the brain, the researchers gave the test subjects a battery of tests both before and after the study. In these tests, researchers analyzed both problem solving and spatial skills. Within these larger constructs, researchers used a variety of tests to measure subject performance. In addition, they looked at persistence, using a self-report in the pretest and a distinct test in the posttest. This experimental setup allowed them to analyze ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––35

____________________________________________________________________________ improvement of the test subjects after play. Between taking the pretest and posttest, the test subjects spent eight hours playing one of the two games over three di erent sessions.

The results indicate a statistically signi cant di erence between the e ects of Portal 2 and Lumosity on problem solving construct (all of the tests analyzed together), with Portal 2 players showing higher results. There was also a sizeable di erences found with spatial skills construct. In the posttest, persistence was tested by comparing the times students spent attempting to solve impossible problems, prior to the students realizing that the problems truly were impossible. This metric also proved to be a win for Portal 2. Additionally, an enjoyment survey was also conducted, which showed a signi cant di erence between the Lumosity and Portal 2 groups. Those who played Portal 2 reported being happier than those who played Lumosity.

When comparing pretest and posttest results, the researchers found no signi cant improvements in problem solving skills in participants playing either game. The results showed that Portal 2 players showed some improvement in spatial skills, but this improvement was not observed in all tests for spatial skills. In contrast, no signi cant di erences were observed in any spatial test for players of Lumosity.

The results for the study suggest that playing Portal 2 can have a sizeable impact on a limited number of cognitive skills. As included in all experiments, the control group for this study was actually the Lumosity group. Using Lumosity as a control condition would counter any placebo e ects, because all participants would come into the study thinking that their cognitive skills would be improved signi cantly. Lumosity, with its pervasive advertisement as a brain-training tool, would be a better control than Tetris, which is commonly used as a control in video game studies.

These results reveal that learning is more complex than many may imagine, and indicate that brain training apps may not be as applicable to certain skills as the programs claim to be.

Nonetheless, this is only one study focusing on very speci c parameters; this study does not categorically say that all video games are bene cial. Furthermore, this paper suggests that the cognitive bene ts of Portal 2 are limited, and bene ts provided by many other games have not been proven to exist. Taking all of this into consideration, playing video games for eight hours before a big exam may not be the best idea.

Shute, V. J., Ventura, M., & Ke, F. (2015). The power of play: The e ects of Portal 2 and Lumosity on cognitive and noncognitive skills. Computers and Education, 80, 58–67. doi:10.1016/j.compedu.2014.08.013

The YNCA would like to thank the authors of this study for generously providing us with permission to use this article, and for providing valuable feedback.

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Research Summary: Preventing the Return of Fear in Humans Using Reconsolidation Update Mechanisms Eva Kitlen and Shreyas Parab

Abstract In a study led by Daniela Schiller, a team of scientists set out to understand a newly discovered phenomenon in memory retrieval: reconsolidation. For many years, neuroscientists and psychologists believed that during memory retrieval the original memory was left unchanged from its stored state. However, recently, a new understanding of memory retrieval has arisen: that memories are vulnerable to change or adjust. This new line of thinking has created debate in the scienti c community, but shows incredible promise in addressing many mental issues and progressing the human understanding of learning and memory.

Background Information on Reconsolidation

Until the early 21st century, researchers believed that memory formation, storage, and retrieval was a linear process. It was believed that a newly formed memory existed in a fragile, changeable state for a limited time, then was stabilized and stored in the process of memory consolidation. However, research has suggested that this is not the case. Instead, a process known as reconsolidation is occurring. Simply put, reconsolidation is the alteration of long-term memories during each instance of retrieval. Instead of being permanently stored, memories revert to a labile state (a state where a memory can be altered or disrupted) each time they are retrieved. In this time window when memories revert to the malleable state, memories of fear and appetite are particularly susceptible to manipulation [1]. Evidence for this rst emerged during research in the eld of electroconvulsive shock therapy (ECT) as scientists realized that an amnesic agent such as ECT was capable of inhibiting fear memories. However, studying memory reconsolidation with ECT poses challenges because ECT does not target a speci c cognitive process.Therefore, research has begun investigating inhibiting reconsolidation pharmacologically. With this method, researchers can target processes more accurately, and therefore establish a stronger cause-and-e ect relationship between reconsolidation and the formation of fearful memories.

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____________________________________________________________________________ Past research on fear and reconsolidation has focused on using Pavlovian fear conditioning (also known as classical conditioning) in animals and using pharmacological agents to inhibit the reconsolidation process. This research has found that inhibiting reconsolidation impairs the formation and storage of emotional memories. The pharmacological agents studied generally inhibit protein synthesis and other essential biological processes, so are not appropriate for use in humans [2]. However, Schiller et al. were able to apply the idea of inhibiting reconsolidation in order to rewrite fearful memories in a recent study.

Schiller et al.’s study used a combination of methods known as classical conditioning and extinction training. Participants were split into three groups. All three groups underwent the same conditioning process. Participants were shown colored squares. When they saw a square of the rst color, they were given a shock. They were not shocked when the square of the other color was presented. The squares were the conditioned stimuli and the shock was the unconditioned stimulus.

An unconditioned stimulus is one that automatically triggers a response without conditioning.

Conditioned stimuli are initially neutral but come to be associated with a response once they are paired with an unconditioned stimulus. After 24 hours, the participants underwent extinction training. Both conditioned stimuli were shown during this period, but a shock (unconditioned stimulus) was not delivered. In two out of the three groups, the fearful memory of the shock was reactivated before the extinction training described in the previous sentence. The memory was reactivated using a single presentation of the colored square with the shock. For one group, this occurred ten minutes before extinction training, so the extinction training occurred in the window during which the fearful memory was being reconsolidated. Another group experienced reactivation six hours before extinction training, outside of the reconsolidation window. The third group never experienced reactivation. During extinction training, the fear levels of each of the groups were measured through their skin conductivity responses to determine the extent to which the fearful memory was rewritten. The study found that the participants who underwent extinction training during the reconsolidation window (reactivation ten minutes before) showed less spontaneous fear recovery, indicating that the extinction training during reconsolidation allowed them to rewrite the fearful memory. This was supported by Schiller et al.’s follow up study conducted one year later, in which the same group showed less fearful memories of the conditioning. This means that inhibiting reconsolidation can be used to prevent the formation of fearful memories and therefore has clinical applications.

Applications

The application of this cutting-edge research extends in a wide spectrum from treating PTSD to innovative psychotherapy techniques for individuals with phobias. Having the ability to update fear memories with non-fearful information, as done in the study, can signi cantly change mental health treatment. Scientists have recently started using a chemical compound called ᵯ-adrenergic receptor blockers [3], which has been approved to test on humans by the FDA, that can inhibit the fear memories in trauma patients. The idea of inhibiting reconsolidation can also be applied to make psychotherapy more e ective. If therapy is delivered during reconsolidation, the memory is in a labile state and therefore more susceptible to changes so the therapy should be more e ective. Research on memory reconsolidation has revealed new ways for doctors and therapists to ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––38

____________________________________________________________________________ use the labile state of recently retrieved memories in order to reduce fear, which has the potential to improve the lives of millions su ering from phobias or PTSD.

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References

[1] Alberini, C. M., & LeDoux, J. E. (2013). Memory reconsolidation. Current Biology, 23(17), R746-R750.

[3] Dębiec, J., & Ledoux, J. E. (2004). Disruption of reconsolidation but not consolidation of auditory fear conditioning by noradrenergic blockade in the amygdala.

Neuroscience, 129(2), 267-272.

[2] Schiller, D., Mon ls, M. H., Raio, C. M., Johnson, D. C., LeDoux, J. E., & Phelps, E. A. (2010). Preventing the return of fear in humans using reconsolidation update mechanisms. Nature, 463(7277), 49-53.

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Aplysia Californica: Little Sea Slug - Big Breakthroughs in Learning and Memory

Jacob Umans and Meenu Johnkutty

Introduction Aplysia Californica, a sea slug, has played a major role in the advancement of neuroscienti c knowledge over the past several decades. Due to its unique biological properties, this model organism has been incredibly valuable to researchers investigating the molecular basis of learning and memory.

Though small and unassuming at rst sight, Aplysia Californica is a giant in the scienti c world. Our rst insights into long-term potentiation came from this seemingly insigni cant organism. Boasting a capacity for classical and operant conditioning, the Aplysia Californica has paved new ground in understanding the mechanisms underlying memory and psychotherapy. The presence of these forms of learning, which exist in other mammals and even humans, provides researchers with valuable insights into their evolutionary history and the molecular basis of learning.

In addition to its exhibition of simple forms of learning, the characteristics of the Aplysia nervous system also make it conducive to research. First, Aplysia has incredibly large neurons, compared to those of humans or other animals.

In fact, the only cell type in the entire animal kingdom larger than their neurons are egg cells. With neurons this large, observation and manipulation of individual cells or even organelles is feasible with modern scienti c tools.

Furthermore, since the Aplysia nervous system has far fewer neurons than the human nervous system, researchers have the ability to easily map circuits responsible for behaviors [2]

One particular characteristic of the Aplysia is its siphon-withdrawal re ex, which involves the structure located on the underside of the slug.

Through this re ex, researchers can observe both sensitization and habituation, two simple forms of learning. Since these behavioral changes must have had a molecular basis, researchers became interested in the biology behind these behavioral phenomena.

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40

____________________________________________________________________________ In the 1960s, Eric Kandel and James Schwartz began their research into the cellular mechanisms of memory formation. Realizing that Aplysia Californica would be conducive to their research needs, they began to look into the cellular mechanisms of learning in Aplysia.

To understand what Kandel and Schwartz did, however, we must rst understand classical conditioning. Classical conditioning is de ned as a learning process where two paired stimuli are repeated until the response usually evoked by the second stimuli becomes the response evoked by the rst stimuli. In classical conditioning, two stimuli are used- the conditioned stimuli and the unconditioned stimuli. In the case of Pavlovian response with dogs, the conditioned stimuli would have been the bell which signaled that the food was ready, and the food itself would have been the unconditioned stimuli. If the dog salivated to the sound of the bell, then it would be evident that learning took place. The siphon-withdrawal re ex deals with similar components. When the siphon of the slug was touched “weakly”, a sharp blow to the tail or head was in icted, thus evoking a gill withdrawal response. However, after a series of trials, the gill withdrawal response was substantially enhanced, indicating that the Aplysia “learned” that the weak touch was followed by a sharp blow [4].

In addition to illuminating the behavioral changes behind sensitization and habituation, Aplysia researchers have elucidated the cellular mechanisms of memory formation. Research in this organism identi ed Cyclic Adenosine Monophosphate (cAMP) as an early signal to induce memory formation on the molecular level. Furthermore, researchers identi ed cAMP-dependent signaling pathway, which activates CREB (cAMP Response Element Binding Protein), a transcription factor.

This then translocates to the nucleus, altering gene expression and inducing the substantial changes responsible for Long Term Potentiation [3].

If it hadn’t done enough in terms of allowing us to understand learning a little bit better, the Aplysia has supported research from subject matters such as aging to neural plasticity to gonadotropin releasing hormone receptors [1] The avenues of research the Aplysia has opened up have left us all the more grateful to this little sea slug, and has shown the scienti c community throughout the decades that big breakthroughs can come from the seemingly insigni cant sea slug.

––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– References

[1] Aplysia. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/?term=aplysia

[3] Hawkins, R. D., Kandel, E. R., & Bailey, C. H. (2006).

Molecular Mechanisms of Memory Storage in Aplysia. The Biological Bulletin, 210(3), 174–191. doi:210/3/174 [pii]

[2] Aplysia Genome Project. (n.d.). Retrieved from: https://www.broadinstitute.org/science/projects/mammals-mod els/vertebrates-invertebrates/aplysia/aplysia-genome-sequencing -project Images

[4] Lodish H, Berk A, Zipursky SL, Mastidaira, P., Baltimore D., & Darnell, J. (2000). Molecular Cell Biology. 4th edition. Retrieved from: http://www.ncbi.nlm.nih.gov/books/NBK21648/

http://www.seaslugforum.net/images/196009lab.jpg (upper picture)

https://en.wikipedia.org/wiki/California_sea_hare#/media/File:A plysia_californica.jpg (lower picture)

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Contributors Page We could not have made this issue of the YNCA possible without the following contributors

YNCA BOARD OF DIRECTORS

Editor in Chief: William Ellsworth Presidents: Jacob Umans and Nicholas Chrapliwy Executive Vice-Presidents: Janvie Naik and Alexander Skvortsov Outreach Director: Kyle Ryan

CONTRIBUTING AUTHORS

Disease Head Writer: Christian Gonzalez Disease Assistant Writer: Priya Vijaykumar Research Head Writer: Jacob Umans Research Assistant Writer: Meenu Johnkutty Neuroethics: Karina Bao and Nicholas Chrapliwy New Technology Head Writer: Dhanya Mahesh New Technology Assistant Writer: Sohan Shah Featured Writers: Alexander Skvortsov, Brendan Mitchell, Kyle Ryan, Karina Bao, Shreyas Parab, Neelu Paleti

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