Issue 16 by greymattersjournal_issue16

Featuring Code of Conduct: Bayesian Predictive Coding Mind and Matter Mind Your Language

WINTER 2019

CONNECT WITH US! www.greymattersjournal.com

TABLE OF CONTENTS COVER ARTICLE

WITH A GRAIN OF SALT THE MSG MENACE

EXPRESS BEFORE YOU TEST by Elise Stefanou | art by Nina Chen

by Xuan Nhi Nguyen / art by Fiona Seung MSG is often misunderstood, receiving an undeserved bad reputation. Learn more about how this chemical is processed in the body and the brain to

TREATING PEDIATRIC CHRONIC PAIN

EYE OPENING EPILEPSY

help dispel the common myths.

GREY MATTERS | issue 16

by Meena Meyyappan | art by George Song

by Sharda Raina | art by Allegra Johnson

Table of Contents

Production Staff

STAND UP FOR YOUR BRAIN by Neha Krishmam | art by Angelique Guina

FEATURED ARTICLES

CHANGING FOCUS: ADHD IN WOMEN by Sophia Anderson | art by Sarah Wells

Elise Stefanou

Shannon Gu

Teri Guo

Karlee Orvik

Sharda Raina

Editor-in-Chief English | 2019

Senior Editor Physiology | 2019

Editing Coordinator Biochemistry | 2020

Production Manager Neuroscience | 2019

Production Manager Biochemistry & Neuroscience | 2020

CODE OF CONDUCT BAYESIAN PREDICTIVE CODING by Kathryn Stangret / art by Kat Ramus When it comes to perception, everything is not as it seems. Bayesian predictive coding gives us important insights into the mechanisms underlying human cognition.

MIND AND MATTER

Grace Wang

Rohnin Randles

Ariel Chan

Tian Qiu

Haoyi Lei

Art Director Biochemistry & Bioethics | 2020

Fundraising Coordinator Political Science | 2020

Design Director Visual Communication Design | 2020

Events Coordinator Physiology | 2020

Social Media Manager Neuroscience | 2020

by Jan Jimenez /art by Karsten Eckert Meditation has a well-established calming effect on the mind. Discover how the anatomical brain changes associated with this phenomena may supoption for depression.

Sophia Anderson Carina Kill Neha Krishnam Meena Meyyappan Francisco Miralles

MIND YOUR LANGUAGE

CORE EDITORS

art and writing by Carina Kill

Pooja Devanaboyina Lila Faulhaber Gabby Knox

port the use of meditation as a novel treatment

Although language has been an integral part of society for thousands of years, there has been an explosion of language research within the past few decades. Find out what we now know about how the brain processes speech and nonverbal communication.

39 2

AUTHORS

REFERENCES

GREY MATTERS | issue 16

ARTISTS Xuan Nhi Nguyen Sharda Raina Kathryn Stangret Elise Stefanou

Kat Ramus Fiona Seung George Song Sarah Wells

DESIGNERS Janet Lee Emily Yang

EDITORS Mahathi Allepally Evan Anderson Isabelle Bauman Marika Bierma Angela Bleeker Zhong Chan Ian Chandramouli Daniel Chen Charlie Fisher

Noor Al Huda Al Ghezi Nina Chen Angelique Guina Allegra Johnson Carina Kill

Shawn Fisher Christine Hau Layla Jamil Ifrah Javed Stanley Kogin Haoyi Lei Hannah Nguyen Natalia Owen Ishira Parikh

Andrew Nguyen Kacey Ton Jared Lai Michael Owyang

Annie Xu Adam Ahmed Claudia Nguyen

GRADUATE STUDENT REVIEW BOARD Carlos Campos, PhD Laïla-Aïcha Hanafi, PhD Akina Hoshino, PhD Marjorie Levenstein, MS

Maria Mittag, PhD Raymond Sanchez Alison Weber

ADDITIONAL GRADUATE STUDENT REVIEWERS Chris Johnson

GREY MATTERS | issue 16

Issue Notes

Editor’s Note

ON THE COVER

EDITOR’S NOTE

Art by Fiona Seung One of the wonderful things about working with a neuroscience journal is the abundance and variety of article topics. Students sometimes worry that they

HAVE YOUR SAY

will not be able to come up with a unique idea, but our sixteen issues (and

If you have questions or comments regarding this

counting!) prove that is certainly not the case. Neuroscience creates a perfect

issue, please write a letter to the editor at thalamus@

space for conversation between all kinds of disciplines, from computer science

uw.edu

to history to religious studies. This particular issue of Grey Matters illustrates the interdisciplinary work of our student members particularly well.

LEARN MORE Check out our website to read our blog, find out how to get involved, and more at greymattersjournal.com

Neuroscience not only lends itself to conversations that bridge the gaps between areas of studies that seem opposed, but it also provides different perspectives on issues that are often represented as fixed, unchanging. Nothing is static when studying the brain, meaning even established pieces of research can be challenged and revised with technological advances and better research practices. Our cover article for this issue, “With a Grain of Salt: The MSG

SPECIAL THANKS Grey Matters Journal is funded, in part, by the generous support of the departments of Pharmacology, Psychology, Physiology & Biophysics, the Neurobiology major, and the College of Arts & Sciences at the University of Washington.

We are especially grateful to those mentors and advisors whose encouragement and support make this publication a reality: Dr. Ric Robinson | Biological Structure Dr. William Moody | Neurobiology Dr. Stanley Froehner | Physiology & Biophysics

‘Menace’” by Xuan Nhi Nguyen, shows how negative social opinions affected MSG research that was later disproved. Sophia Anderson’s article, “Changing Focus: ADHD in Women” reviews primary sources that reveal how ADHD affects female populations who often do not receive proper diagnoses because of the gender stereotypes surrounding the disorder. The other articles in this issue also exemplify the impact of interdisciplinary science literature and the potential it has to change minds. Our goal at Grey Matters is to provide all readers with the tools they need to engage with scientific information that often appears inaccessible. We hope you enjoy engaging in these nuanced social conversations through the lens of neuroscience. Sincerely,

Dr. Sheri Mizumori | Psychology Dr. William Catterall | Pharmacology

A special thank you to our Graduate Student Review Coordinator, Chris Johnson, whose expertise and dedication ensures that our work is thorough and

Elise Stefanou Editor-in-Chief

accurate.

GREY MATTERS | issue 16

Express Before You Test

EXPRESS BEFORE YOU TEST

feelings, this written approach often elicits intense emotional re-

the short-term benefits of expressive writing might not manifest

sponses [2]. Certain studies have also showed some physical

immediately, an inhibition model does not provide the fullest ex-

responses to the expression of emotional topics in writing, includ-

planation as to why expressive writing right before an exam might

ing immune system benefits and short-term reductions in heart

be helpful for students. However, the hypothesized benefit of ex-

rate. Psychological and behavioral effects can be difficult to consis-

pressing and articulating one’s thoughts instead of repressing them

tently measure due to the subjective nature of written expression,

is still a foundation for the research.

but reductions in stress and improvements in mood have been reported. Of course, these beneficial effects are dependent on a

Expressive writing has also been shown to improve students’ avail-

number of factors, including what participants write about, how

able working memory when they wrote about intense personal

often and for how long they write, and participants’ socioeconom-

feelings [5]. One particular study divided college freshmen into

ic backgrounds [2]. It should be noted that the benefits of

two groups, the first of which wrote on their feelings about at-

expressive writing are not absolute and can be highly variable be-

tending college while the second group wrote about time

tween individuals.

management. Students were given a working memory test and a College Adjustment Test (CAT) at the beginning of the semester,

by Elise Stefanou

MECHANISMS OF EXPRESSIVE WRITING

then participated in three 20-minute writing sessions over the

art by Nina Chen

To understand why expressive writing might be a useful approach

course of two weeks, took two more working memory tests, and

for students with test anxiety, it is necessary to look at its psycho-

completed a final CAT and questionnaire in the weeks following

logical and neural mechanisms. Early hypotheses included the idea

the writing sessions. Results indicated that the expressive writing

that expressing traumatic or stressful events in writing was an im-

students showed an improvement in working memory compared

portant way to reduce the effects of not talking about the thoughts

to the control group. There was even a correlation between the

INTRODUCTION

and feelings associated with those events [3, 1]. Suppressing trau-

improvement in working memory and higher GPA both during

Anyone who has written an essay for a class knows that writing is

ma through inhibitory behaviors could put people at risk for

the trial semester and the next semester [5].

a difficult yet necessary task. From grocery lists to PhD disserta-

stress-related health problems; thus, expressive writing could pro-

tions, writing is a vital method of manifesting thought, helping us

free writing emerged during this period, providing a space for the

vide an outlet to articulate those events and associated feelings

The researchers conducted a second experiment in which students

remember important information, express ourselves, process the

spontaneous and authentic reactions of students in the classroom

rather than repress them [3]. Based on these assumptions, it was

wrote about negative or positive events in their lives [5].

world around us, and share our ideas with others in a tangible way.

to stimulate further thinking [1].

important to determine how inhibition-related stress might

Compared to students who wrote about positive life events or dai-

There are many theories explaining how people write and what

change in the short- and long-term through the application of ex-

ly routines, the negative expressive writing group experienced

kind of writing is most useful in particular contexts. One specific

Studying expressive writing in a research setting typically involves

pressive writing. A group of undergraduate students was divided

more benefits to their working memory capacity. The negative

body of scientific literature focuses on the therapeutic benefits of

assigning study participants to two groups, both of which are

into an expressive writing group and a group that wrote about

writing group’s working memory scores actually improved by

expressive writing, which includes writing about emotional or

asked to write for three to five days in a row, with each daily writ-

non-traumatic, superficial topics. Both groups were assigned to

the end of the eight-week experiment and were higher than the

traumatic experiences. A subset of these studies explores how ex-

ing session lasting between 15 to 30 minutes. The control group is

write for 15 minutes each night for four consecutive days [3].

positive writing and control groups. Additionally, the negative

pressive writing might help students cope with stress and anxiety

asked to write about routine occurrences, while the expressive

Interestingly, results showed that writing about traumatic events

in academic settings.

writing group reflects on much more significant, emotional as-

generally increased blood pressure and participants’ reports of neg-

pects of their lives—relationships with family and loved ones or

ative moods after the first writing session. However, six months

WHAT IS EXPRESSIVE WRITING?

reflections on the self and identity. Writings are not evaluated for

after the study, participants who wrote about traumatic events re-

The expressive view in the teaching of writing emerged in the

any kind of correctness or value; the only specific requirement is

ported fewer visits to health and counseling centers [3]. Recent

mid-1960s [1]. Characterized by a more personal approach, ex-

that participants write consistently for the allotted time per day

research suggests that using expressive writing exercises to write

pressivist scholars emphasized that writing could be sincere, reflect

[2]. Researchers focus on different elements of the expressive

about past stressful events can actually be helpful in mitigating the

creative processes, and unlock the potential of the writer’s uncon-

writing process depending on the context of the study; sometimes

effects of a current stressful event [4]. One study showed that lev-

scious mind [1]. In other words, expressive writing might allow

they analyze writing samples for linguistic features, like positive or

els of cortisol, a biological correlate of stress, decreased when

the writer to self-actualize through the composition process, creat-

negative emotion words, or they measure physiological responses,

participants wrote about past failures before completing a public

ing a reciprocal relationship between personal development and

such as heart rate, during the act of writing [2].

speaking activity [4].

writing that focused on logical, correct language and set composi-

Research also suggests that expressive writing, when used as a

It should be noted that inhibition studies tend to show varied re-

tion structures, researchers began to develop writing techniques

therapeutic tool, has both mental and physical health benefits [2].

sults and are not always the most conclusive explanation of the

that we still see in classrooms today. For instance, the concept of

Similar to the spoken disclosure and discussion of personal

mechanism behind expressive writing [2]. Additionally, because

writing [1]. Departing from the traditional, highly rigid views of

GREY MATTERS | issue 16

Express Before You Test

writing students reported a decrease in unwanted and intrusive

nothing for 10 minutes before taking the test, and an expressive

expressive writing group was instructed to reflect and write for 20

palliative caregivers to process the emotional nature of their work

thinking, which was not apparent in the students who wrote about

writing group, in which students wrote about their feelings related

minutes per day on their positive emotions for that day; the con-

[9, 10, 11]. While the studies involving the breast cancer survivors

positive events or daily routines. Researchers explained that ex-

to the test for 10 minutes. While the first test did not show any

trol group simply wrote for 20 minutes about their daily activities.

and the palliative care workers suggested positive effects for the

pressive writing could allow students to better store and process

significant difference between student scores, the second test re-

Test Anxiety Scale (TAS) scores were compared between both

participants, the study on postpartum women reported there was

information by reflecting on intense thoughts and feelings, espe-

vealed an improvement in the scores of the expressive writing

groups before and after the experimental period and showed a sig-

no significant change in the psychological health, physical health,

cially those associated with negative events. While the results of

group and a drop in the scores of the control group. In order to

nificant reduction in the expressive writing groupâ&#x20AC;&#x2122;s anxiety scores

or the quality of life between the women who participated in ex-

this study are more long-term, the suggested working memory

confirm that these results were not due to the difference between

[8]. These students were not reflecting on deep thoughts or feel-

pressive writing exercises and the women assigned to control

benefits of expressive writing are likely important for students in a

writing and doing nothing before the test, researchers used the

ings, nor were they asked to reflect on stressful academic

writing exercises and normal care procedures [10, 11, 9]. Thus, the

test-taking environment [5].

same methods to compare the difference in scores between an ex-

situations. Their reflection on positive emotions suggests that ex-

use of expressive writing can be useful for some individuals, but

pressive writing group that wrote specifically about the test and an

pressive writing does not always have to deal with difficult

the difference between these studies shows that it may be a more

The effects of expressive writing can be observed neurologically,

unrelated writing group that wrote about an unemotional event.

emotions to be an effective resource for students. Writing about

specific intervention tactic rather than a general one with consis-

and the areas of the brain that respond to expressive writing can

The results showed that the expressive writing groupâ&#x20AC;&#x2122;s scores in-

positive emotions could help students focus on what makes them

tent results [9].

help predict changes in physical health, depression, anxiety, and

creased between tests while the scores of the unrelated writing

feel good, even in the face of academic pressures. However, this

life satisfaction [6]. Specifically, the amygdala and the right ventro-

group and control group decreased, supporting the positive bene-

study only measured test anxiety rather than actual test scores, so it

While expressive writing might not be a universally applicable de-

lateral prefrontal cortex (RVLPFC) are involved in the neural

fits of expressive writing [7].

cannot be determined whether writing about positive emotions

stressor, and effectiveness can vary based on its short- or

before a test will improve performance.

long-term use, it may be helpful in certain contexts, such as

processes that occur during an affect labeling activity, like expressive writing, in which a person expresses thoughts and feelings in

Using a procedure similar to the one employed in the lab, this ex-

words. In one study on affect labeling, researchers used fMRI to

periment was repeated in a group of ninth grade biology students

It should be noted that many of the studies explored here vary in

high-pressure testing environments. The articulation of thoughts that might interrupt academic performance can be achieved

observe that increased activity in the RVLPFC was associated with

preparing for their first final exam [7]. The studentsâ&#x20AC;&#x2122; general test

terms of trial period. Some studies show that expressive writing is

through expressive writing, thus reducing intrusive thoughts

a decrease in activity in the amygdala, an area that facilitates emo-

anxiety about the exam was measured six weeks before test day

effective when done consistently over a number of weeks or

caused by test anxiety and improving working memory capacity.

tional responses. This particular effect of the increase in RVLPFC

through a survey administered to them in class. On the day of the

months; others show a more immediate change. When thinking

Making time for reflection in the classroom enables students to

activity and the decrease in amygdala activity predicted a more ef-

final exam, students were randomly split into control and expres-

about how to implement expressive writing in the classroom to

process and express their concerns, allowing them to literally see

fective outcome for participants using an expressive writing

sive writing groups. For 10 minutes before the exam, the

help alleviate test anxiety, it is important to consider these varia-

their worries laid out on the page.

intervention in the study [6]. These results suggest that expressive

expressive writing students were instructed to write about their

tions in timing, especially since not all students

writing could help mitigate intense emotional responses that lead

thoughts and feelings about the test while the control group was

will respond in the same way to this practice.

to intrusive thoughts, which is especially relevant for people trying

instructed to think about a topic that would not appear in their

to focus in stressful situations.

biology exam. In the control group, if the students had higher

pressive writing should be an option

ratings of test anxiety, their scores on the exam were lower;

provided to students, but implemen-

EFFECTS OF EXPRESSIVE WRITING ON STUDENT STRESS AND ANXIETY

however, this was not the case in the expressive writing group.

tation

Results showed that the higher test anxiety

consistent so students feel that there

Expressive writing has been shown to be a low-cost and potential-

students performed better on the exam if

ly beneficial intervention in a targeted context. More specifically, it

they completed the expressive writing

ties. Allowing some time for reflection in

has been used as a tool in studies exploring how to help students

exercise beforehand. Students with

an academic setting can help students

manage stressful academic situations. Because students in stressful

low test anxiety did not display a sig-

make sense of how they relate to the

exam settings tend to worry about the test at hand, which can im-

nificant change in grades in either

classroom and could be a powerful re-

pede their focus and reduce scores, completing an expressive writing

group. This study suggests that students

source for those with test anxiety.

exercise before the exam might help improve performance [7].

who worry significantly about tests and are affected by high-pressure exam situations

must

deliberate

and

is a purpose to expressive writing activi-

CONCLUSION

To test this hypothesis, researchers performed an experiment in

could benefit from pretest expres-

which college students were given two different math exams [7].

sive writing exercises [7].

find a voice and express their thoughts and feelings in an

form as well as they could. In the second test, the students were

In general, more recent

for some targeted populations, such as students with high

placed into high pressure scenarios in which the results of their

studies

tests would determine if they would receive a monetary award and

these results. In one study, Chinese high school seniors

positive social evaluations from peers and instructors. The re-

with high levels of test anxiety engaged in expressive writing exer-

writing affects postpartum health, quality of life for

searchers divided the students into a control group, which did

cises or control writing exercises every day for 30 days [8]. The

breast cancer survivors, and how it might be used by

During the first test, the students were simply instructed to per-

References on page 39.

Based on the results of these studies, ex-

Expressive writing is all about helping individuals open, flexible way. As a therapeutic tool, it proves useful

have

GREY MATTERS | issue 16

corroborated

levels of test anxiety. Recently, variations of the expressive writing methodology have been used to study how expressive

GREY MATTERS | issue 16

Code of Conduct: Bayesian Predictive Coding

CODE OF CONDUCT:

BAYESIAN PREDICTIVE CODING

BAYESIAN INFERENCE

of Bayesian inference. When a detective arrives at a crime scene, they

In many situations, it is impossible to know the external cause for

form an initial set of probabilities for, say, a spouse, close friends,

certain sensory stimuli. In order to eliminate some of this

relatives, and strangers based on similar crimes they have investigated.

uncertainty, the brain must have some method of making inferences

This probability distribution represents the prior, and each person

about its environment. The optimal strategy for doing so is using

represents a candidate for the latent variable (the unknown cause of the

probabilities through Bayesian inference [4]. Although Bayesian

crime). As the investigation continues and evidence is collected

inference is more generally used in data analysis, there is considerable

(representing the incoming sensory data), the probability of each

evidence that human and animal behavior use Bayesian inference to

person having committed the crime is revised, creating the posterior

achieve near-optimal performance in a variety of situations, from

probability. This posterior probability will be considered the prior for

decision-making to learning to motor control [4]. Bayesian inference

the next piece of evidence. The probabilities are continuously updated

is the probability of a certain hypothesis, given a set of data [2, 3, 4,

throughout the investigation until no more evidence can be found, and

6]. It uses both known information, called “priors,” and current

one person has a high, relative probability of having committed the

incoming stimuli to form a prediction about the cause of the

crime. The resulting suspect may have been considered improbable if

incoming stimuli, known as the latent (unknown) variable. The

they were one of the least likely candidates at the beginning of the

resulting prediction is known as the posterior probability, which

investigation. However, once all evidence has been considered, the

gives the probability of each conceived latent variable being the cause

resulting probability distribution is the most accurate it can be for that

of the observed sensory data. In summary, the priors are used to give

situation. This cycle of predicting and updating beliefs is used by the

baseline probabilities to the latent variables, while the incoming

brain continuously, with every movement and new sensation as

stimuli are used to update these probabilities to better represent the

evidence of the individual’s surroundings [6].

current situation [2, 3, 4, 6]. The computed posterior probability can

PREDICTIVE CODING

then be used as a prior in the future [3].

Predictive coding is a prominent model describing how the brain can perform Bayesian inference [3]. Predictive coding uses prediction errors to minimize the amount of actual sensory information transmitted to the brain to optimize the integration of sensory information [4]. A prediction error is the difference between the

“When you have eliminated the impossible, whatever remains, however improbable, must be the truth”

by Kathryn Stangret art by Kat Ramus

actual and expected incoming sensory information [3, 4]. The prediction errors can be transmitted to the brain instead of the original sensory signals to improve the efficiency of signal transmission and the acquisition of sensory data [1, 4]. Because prediction errors have a smaller range of possible values, they can be transmitted with greater

Bayesian inference also enables each prior to be weighted according to

accuracy using the same transmission rate [1, 4].

how reliable it is [2, 3]. An unreliable prior will produce a posterior

probability that is based mostly on the incoming sensory data.

Predictive coding assumes a

o correctly interpret sensory data, the brain is faced with

conflict with other methods in computational neuroscience but rather

Alternatively, a very reliable prior will resist change and produce a

hierarchical

solving an inverse problem: one where the causes need to be

as a novel, complementary perspective that is often very useful [3].

posterior probability that is very similar to the prior even if the

brain structure

inferred from the perceived outcomes [1]. There are many

Inference on its own only provides a method for computing

stimulus contradicts it [2, 3]. This is what creates illusions [3]. For

[2, 3, 5]. Higher

different computational models and explanations for how the brain

predictions and does not specify the neural representations those

example, a mask has both a concave and a convex side; however, when

levels are considered

codes information and understands its environment. Bayesian

predictions have [4]. This is why Bayesian inference and predictive

watching a video of a rotating mask, both sides will appear to be

to be the parts of the brain

predictive coding, the combination of Bayesian inference and

coding go well together. Predictive coding uses the inferences to

convex. This is because faces are always convex, and the brain considers

that create complex cognition,

predictive coding, is one such model [2, 3, 4, 5]. Although probabilistic

create prediction errors, which the brain can then use to encode values

this fact an extremely reliable prior, so despite the incoming stimuli

and the lower levels are the neurons

representations are not new, Bayesian predictive coding has become

of the unknown variables that better represent the sensory input [4].

indicating a concave face, a convex face is perceived instead [3].

that directly receive external sensory

increasingly popular in the field of cognitive neuroscience over the last

While Bayesian inference and predictive coding are separate concepts,

few decades [2]. This model has made important contributions to our

they work in tandem to create a holistic representation of human

If you have heard of Sherlock Holmes, you have probably heard the

higher levels convey expected incoming

understanding of nearly all areas of cognition, including perception,

cognition. Bayesian predictive coding can be understood by first

saying: “When you have eliminated the impossible, whatever remains,

sensory data to the lower levels while lower

reasoning, and learning [2]. Bayesian predictive coding is not used in

examining how these constituent models work.

however improbable, must be the truth” [7]. This logic is one example

levels send prediction errors back to the higher

GREY MATTERS | issue 16

stimuli [3]. Predictive signals originating at

GREY MATTERS | issue 16

Code of Conduct: Bayesian Predictive Coding

on its own does not determine how the predictions are made or

and other symptoms that directly relate to Bayesian predictive coding

CONCLUSION

how the prediction errors are used [4]. This is where Bayesian

[5]. Most current models for psychosis focus on one specific

Bayesian predictive coding is one of many models used to explain

inference comes in.

symptom; however, it is very common to see a co-occurrence of

neural coding and dynamics. While it does not contradict other

many symptoms at varying degrees. Bayesian predictive coding may

models, its unique method of calculations allows it to explain a

provide a framework that combines the neurobiology and the

comparatively wide variety of behavior. Modeling human cognition

Bayesian inference uses the prediction errors given by predictive

experience of psychosis through computational processes [5].

has many applications not only in understanding how the brain

coding to accurately represent sensory input while predictive

Bayesian predictive coding is unique from other models because it

works, but also in constructing artificial intelligence that mimics

coding uses Bayesian predictions to calculate the prediction

captures many different types of behavior, including what seems like

human computation and behavior. Bayesian-based probability

errors [4]. Together, these models create Bayesian predictive

suboptimal behavior [3]. This is because there is always a set of priors

programming could be revolutionary for machine intelligence for

coding [3, 4, 5]. The lower structures in Bayesian predictive

that produce what Bayesian predictive coding would denote as

multiple reasons [8]. It allows for rapid prototyping and testing of

coding models use a combination of direct coding neurons,

optimal, meaning even pathological behavior can be modeled as the

different models of data, and it cuts out difficult, time-consuming

neurons that transmit the actual sensory information that is

result of Bayesian predictive coding [3]. As mentioned earlier, priors

parts of the programming process. Probability approaches have only

used to create accurate predictions, and predictive coding

are weighted based on their relative reliability, and a failure to

recently become popular and will continue to play a central role in the

neurons, neurons that only code the prediction error to

properly balance priors with sensory evidence may be a common

development of artificial intelligence systems [8]. Assuming Bayesian

increase transmission efficiency [4]. Functional magnetic

theme in many neuropsychiatric disorders [2, 3, 5]. When either

predictive coding uses both direct coding neurons and predictive

resonance imaging (fMRI) has shown that there is feedback,

priors or sensory data are given more weight than they should, the

coding neurons, research needs to be done to reveal the location of

individual no longer has an accurate view of reality [3, 5].

these neural coding pathways anatomically and physiologically in

BAYESIAN PREDICTIVE CODING

assumed to be prediction errors, based on predictions from higher to lower level sensory cortices [5]. These same

levels. These prediction errors can be used to determine the accuracy of the predictions. A condition known as phantom limb, in which an amputee experiences sensations in their missing limb, can be explained through predictive coding and its hierarchical structure. In this case, there are no longer nerves to make up the lower levels of the structure, so there are no prediction errors to contradict the predicted sensations that are coming from the higher levels of the brain [3]. Another prominent example of predictive coding is in the retina [1, 4]. During visual perception, the retina receives information about

existing neural cell types [4]. Further research can also be done to

images show that neural responses are dampened when

LIMITATIONS

determine a more precise role of Bayesian predictive coding in both

predictions are confirmed by sensory input and are

While Bayesian inference and predictive coding work well in

cognition in general and specific neurological disorders.

enhanced when there is a violation of the predictions. This

concert, that is not the only possible model for neural coding and

limits unnecessary attention to predictable stimuli [5]. An

dynamics. Bayesian inference can be performed by many other

example of this is sensory adaptation or desensitization. When

neural algorithms and representations, and predictive coding

a person encounters a persistent stimulus such as a buzzing

performs a useful function that can achieve a variety of

sound, the sound may be distracting at first. As the stimulus

computational goals [4]. It is possible to explain some of the above

continues, the person will no longer perceive the sound because it

examples of Bayesian predictive coding with other models; however,

can be accurately predicted by the brain. However, they will notice

each one requires a different method [4]. Bayesian models

when the buzzing stops because the prediction of the sound is

sometimes require complex calculations, and it is possible that

violated, increasing their attention.

humans are not capable of these calculations [2]. In that case, people may use an approximate inference, which would

Previously, both Bayesian inference and predictive coding have been

not be fully Bayesian, though it would utilize the

used in predicting something that already occurred; however,

same concepts. Approximate inferences could

Bayesian predictive coding can also be used as a forward model,

also be used to explain suboptimal behavior

which predicts the sensory consequences of self-produced actions [2,

[2]. Because Bayesian predictive coding can

3, 4, 5]. Bayesian predictive coding does this by modeling ourselves

include both direct coding neurons and

as agents who change the world around us [2, 3, 4, 5]. A simple

predictive coding neurons, the model is

example of the forward model is why individuals cannot tickle

not necessarily fully based on predictive

themselves [2, 4]. The brain is able to predict the sensory effects of

coding [4]. It is noted earlier that

the movement and therefore dulls the stimuli so an individual does

predictive coding, including Bayesian

not react the same way as when someone else tickles them [2, 4].

predictive coding, assumes a hierarchical brain structure [2, 3, 5]. The case might be

the spatial distribution of the intensity and wavelength of light [1].

APPLICATION IN PSYCHOSIS

The information accurately predicted by the brain is removed from

that only certain levels exhibit this model

The forward model explained above is termed corollary discharge

the transmitted signal to reduce the amplitude, allowing for more

[2]. For instance, Bayesian predictive coding

and plays a role in many forms of psychosis [3, 5]. Psychosis has been

efficient transmission [1]. As stated before, a prediction error is

could explain the neural level of cognition while

associated with a greater resistance to illusions, an impaired corollary

sent to the higher levels of the brain; however, predictive coding

the system as a whole could exhibit non-Bayesian

discharge, improved tracking of unpredictable changes in motion,

behavior or vice versa [2].

References on page 39.

GREY MATTERS | issue 16

“N

With a Grain of Salt: The MSG Menace

o MSG”—two simple words plastered across food

Additionally, packaged and processed foods such as chips, canned

packaging and restaurant windows have consumers

soups, and frozen foods contain added MSG [8]. MSG can be

feeling relieved. MSG has long been criticized by

masked under other names as well—for example, hydrolyzed vege-

consumers; some charge it as guilty for causing a plethora of ad-

table protein, autolyzed yeast extract, and sodium caseinate are all

verse reactions, while others have the preconceived notion that

indicators that MSG is present [7].

MSG is bad but have no idea why. Despite being frowned upon for decades, MSG was not always cuffed to its bad reputation.

KEEPING IT LOW There was an especially great interest in studying the effects of

JOURNEY TO THE WEST – MSG’S SUCCESSES AND FALLS

MSG on the brain since glutamate is a neurotransmitter involved

Many people believe that MSG was introduced to the American

(CNS), the neural connection network comprised of the brain and

palate via Chinese food, which can often contain added MSG [1].

spinal cord [9]. The major concern with MSG consumption lies in

However, the true debut of MSG into the lives of Americans oc-

the hypothesis that consuming too much MSG will elevate the free

curred in the processed food industry after World War II. Most

glutamate concentration level in the blood, leading to high concen-

notable was the Campbell’s Soup Company’s recognition of MSG

trations of glutamate in the extracellular fluid (ECF) surrounding

as a potential flavor enhancer. MSG’s popularity went uncontested

brain cells. An increase in glutamate in the ECF will also increase

for many years until the 1960s, when the safety of food additives

the exposure of CNS neurons to glutamate [9]. Low glutamate

was questioned [1]. In the same period, a letter written by Dr. Robert

concentration in the ECF is vital for proper neuronal functioning,

in excitatory neuronal signaling in the central nervous system

Ho Man Kwok to the New England Journal of Medicine also placed MSG on trial [2]. In his letter, Dr. Kwok informed the editors of the journal that he experienced a specific set of symptoms whenever he ate Chinese food. He described it as “numbness at the back of the neck, gradually radiating down to both arms, general weakness and palpitation.” These symptoms were then dubbed “Chinese Restaurant Syndrome,” or more commonly referred to as the MSG

Glutamate is a powerful excitatory neurotransmitter that is released by nerve cells in the brain. It is responsible for sending signals between nerve cells, and under normal conditions it plays an important role in learning and memory.

Symptom Complex, a collective term used to describe the symptoms associated with MSG consumption [2, 3]. With an influx of similar reports by other medical professionals, researchers began to investigate the health effects of MSG [4]. To better understand how MSG

as it prevents the build-up of glutamate in neuronal synapses [10].

might affect the body and what the studies on MSG conclude, we must

Previous research shows that exposure to high concentrations of

take a step back to discuss what MSG is and where it came from.

glutamate overexcites neurons of the CNS by opening channels that allow calcium to enter the cell [9]. The result is intracellular

THE BIRTH OF MSG & UMAMI MSG is an abbreviation for monosodium glutamate, a compound that was first discovered in 1908 by Kikunae Ikeda [5]. When dissolved in water, the molecule dissociates into a sodium ion and

WITH A GRAIN OF SALT THE MSG MENACE

by Xuan Nhi Nguyen

glutamate, an amino acid produced by the body that acts as an es-

art by Fiona Seung

sential neurotransmitter [3]. The glutamate component of MSG is responsible for activating the fifth taste of umami, which was uncovered along with the discovery of MSG [5]. MSG was originally made by extracting and crystallizing glutamate from a seaweed broth, but today, fermentation is the commercially preferred method of production [5, 6]. Although the flavor enhancer is most popularly linked with Asian, specifically Chinese, cuisine, it is found in a variety of foods. Garlic, onions, carrots, eggs, cow’s milk, and protein-rich foods all contain naturally occurring glutamates [7].

GREY MATTERS | issue 16

calcium overload and the activation of pathways that lead to neuronal death via a process known as excitotoxicity [9]. Although excitotoxicity is a concern, the likelihood of this occurring as a result of MSG consumption is minute. After ingestion of MSG, the free glutamates are broken down in the small intestine to be used as an energy source [10]. Even with relatively high MSG ingestion in food, only small changes in blood glutamate concentration have been observed. A significant amount of glutamate reaching the brain is therefore unlikely. Even if glutamate reaches the brain, the body has complex mechanisms involving the blood brain barrier (BBB) that prevent the build-up of glutamate in the ECF. The BBB protects the brain from many harmful substances circulating in the blood. This highly selective, semipermeable

GREY MATTERS | issue 16

With a Grain of Salt: The MSG Menace

Taking the research on MSG one step further, Raif S. Geha conducted

method of MSG delivery into the body has been found to have an

a carefully controlled study in 2000 on the reported reactions to

impact on blood glutamate levels [3]. Of importance are the find-

MSG consumption [14]. The study began by recruiting volunteers

ings that indicate MSG in water causes a greater rise in blood

who had self-reported experiencing the MSG Symptom Complex

glutamate levels than MSG seasoning in food. Furthermore, par-

after eating Asian meals that they believed contained added MSG.

ticipants who fasted are more likely to report symptoms than those

The volunteers were then screened and became participants in the

who did not fast [3]. The need to control for confounds in these

study if they reported experiencing two out of the ten MSG-

experiments is one of the limiting factors in MSG research.

associated symptoms within four hours of eating a meal that contained MSG. Central to this research was the consistency of the partici-

The misconceptions about MSG have taken strong roots in American

pants’ reports [14]. If MSG was truly a culprit in causing these

culture. The phrase “MSG is bad for you” has been presented to the

symptoms, it was expected that the participants would report symp-

public by media and by word-of-mouth for so long that this

toms when they ingested a MSG-containing pill but not report any

thought has become second nature in our society. A bias against

symptoms when taking placebo pills. Findings from this study

Asian foods could also be an underlying factor in the MSG uproar.

showed that in people with the reported MSG Symptom Complex,

Rarely are Doritos and Campbell’s chicken noodle soup blamed for

large doses of MSG given without food were sufficient to elicit

causing any adverse symptoms. So, the final verdict? MSG does not

symptoms [14]. Upon repeated experimentation, however, the re-

seem to be a culprit in causing neurotoxicity or the MSG Symptom

sponses were inconsistent. To explain this inconsistency, the

Complex when consumed appropriately and it can be enjoyed safe-

researchers suggested a demand bias at work [14]. The participants

ly as a flavor enhancer in a variety of cuisines across the world.

in this study were selected based on the criteria that they reported experiencing symptoms after eating MSG-containing Asian meals.

References on page 39.

Because of this, they could have interpreted that the purpose of the study was to look at the reactions to MSG consumption and unconsciously change their responses to fit their interpretation. barrier is composed of a single layer of closely packed cells called

his findings were alarming [11]. However, at the time, many did

Despite the evidence presented above indicating that MSG is safe

endothelial cells, which line the capillary walls. These cells have

not draw attention to the fact that the dosage Olney used on the

to consume, it is critical to note that there could be subgroups of

two distinct membranes, the luminal (blood-facing) membrane

mice was 50 times higher than the average MSG consumption in

people who are sensitive to MSG, and the symptoms associated

and the abluminal (brain-facing) membrane, and they contain dif-

humans [11, 8, 13]. This high dosage could be substantial enough

with the MSG Symptom Complex have been reported to be more

ferent transporters on each side to allow for the maintenance of

for the glutamate to cross the BBB, as well as impact any brain re-

prevalent in these individuals [3]. The subgroups include people

gions not protected by the BBB, resulting in the lesions observed.

with asthma and vitamin B-6 deficiency, infants, and women tak-

The findings from Olney’s study caused an increased interest in

ing contraceptives. Although there are links between these

MSG research and its reported associated symptoms. Some of these

subgroups and MSG sensitivity, no sufficient evidence exists to

symptoms include general weakness, muscle tightness and twitch-

strengthen the correlation [3].

glutamate levels in the ECF [10]. The combined effort of intestinal degradation and the protection of the BBB ensures low glutamate concentrations in the ECF, thereby preventing a glutamate overdose simply from MSG consumption.

ing, flushing, sweating and burning sensations, headaches and migraines, chest pain, palpitations, and numbness or tingling [14].

MSG ON TRIAL One of the earliest studies on MSG was conducted by John W. Olney at Washington University School of Medicine, who studied the effects of MSG in mice by injecting it under the skin [11]. Light microscopy revealed neuronal death in multiple areas of the brain, including the arcuate nucleus of the hypothalamus, neurons in the median eminence, and the subfornical organs [11]. One possible explanation for these observations could be that these brain regions lack the protection of the BBB and are thus more prone to neurotoxicity [12]. Prior to Olney’s study, there was a lack of research regarding MSG’s impact on the central nervous system, and

THE FINAL VERDICT After many years of careful investigations, the U.S. Food and Drug

In 1970, researchers at the Institute of Pharmacological Research in

Administration has marked MSG as being “generally recognized as

Milan, Italy conducted a study on the effects of MSG in healthy in-

safe” when consumed in amounts less than 30 mg per kilogram of

dividuals who did not experience symptoms after eating food

body weight [15, 16, 17]. This limit is approximately three times

containing MSG [15]. The study involved 24 participants and two

the amount of MSG that an average person would consume [8,

treatments: beef broth with and without MSG, delivered two days

13]. A common theme in most MSG research is that it rarely re-

apart. Participants then rated their symptoms associated with the

flects the way that MSG enters the human body. Studies often use

MSG Symptom Complex. The study concluded that there was no

MSG injections, MSG in liquids, or MSG pills, and they usually re-

difference between the treatments in the symptoms reported or

quire that participants fast before the experiment to control for

the frequency at which each symptom occurred [15].

other factors that could influence the results [11, 15, 14].

GREY MATTERS | issue 16

According to a meta-analysis published in 1995, the dosage and 17

Treating Pediatric Chronic Pain

painful feeling starts in your fingertips and spreads

A study conducted on patients after spinal cord injury concluded that

through your hand, radiating up your arm until it

degeneration and inflammation of axons within the spinothalamic

reaches your brain, prompting an “Ouch!” Pain is most

tract (nerves carrying pain and temperature information up from

commonly defined as “physical suffering or discomfort caused by

the spine to the thalamus) may cause spontaneous activity in intact

illness or injury,” and while this may be true, we also know from

neurons that act as a ‘central pain generator’ [3]. However, the role

first-hand experience that pain is subjective and affects people of

of the spinothalamic tract and pain receptors in chronic pain is still

all ages [1]. But if pain is so subjective, how can healthcare

unclear, and researchers have not been able to identify a biological

providers treat patients with chronic pain? The most common

pathway of this development. This lack of biological information is

treatment for chronic pain is currently pharmaceuticals, but this

the reason the field of pain medicine has turned to pharmaceuticals.

is not optimal because of the adverse side effects, abuse potential,

One of the most common reasons that adults seek medical care is

and negative impacts on neurodevelopment. A safer alternative is

chronic pain, but unfortunately, 11-40% of these patients end up

cognitive behavioral therapies (CBTs), which can provide a

becoming dependent on opioids [4]. The current opioid crisis has led

means to treat different types of pain holistically by also

to a rise in adult chronic pain research, but between 1999 and 2014,

considering psychological factors.

over 1.3 million opioid prescriptions were written to children, resulting in an annual incidence of 15% [6]. However, the prevalence of

Pain is classified as either chronic or acute, depending on how

pediatric opioid addiction is considerably lower than in adults and

long it lasts. Acute pain is shorter in duration, serves to alert the

therefore less resources have gone into pediatric chronic pain

body to a possible injury, and is driven by external stimulation of

research. Over five million adolescents undergo major surgery in the

the peripheral nervous system. Chronic pain is defined as pain

United States each year, and almost half of them report moderate to

that lasts more than 12 weeks, serves no physiological function,

severe pain in the hospital, which persists months after surgery [2].

and is driven by the central nervous system with no external

Seventeen percent of adult chronic pain patients worldwide report

stimulation [2]. There is limited knowledge on what sort of

a history of chronic pain as adolescents that persisted into adulthood [5].

treatments work for chronic pain because of its centrally driven mechanism [3]. Chronic pain most commonly manifests as headaches, abdominal pain or musculoskeletal pain [5]. Patients undergoing major surgery are at a higher risk for developing chronic pain post-surgery because of the invasive, pain-inducing nature of surgery, and this risk is specifically heightened in developing children [5]. Recovering from surgery can be an arduous process, and children are often plagued with inadequate long-term pain management [2]. The current standard of pain management in large pediatric

“Debilitating post-surgical chronic pain can affect the child’s long-term social development, intellectual functioning in an educational environment, and overall mood and self-esteem [2].”

hospitals consists first of a visit to the pre-anesthesia clinic before

TREATING PEDIATRIC CHRONIC PAIN by Meena Meyyappan art by George Song

surgery to discuss the anesthetic that will be administered to the child. After this visit, the child arrives on site the day of the surgery and meets their anesthesiologist before entering surgery.

Pain catastrophizing (the tendency to exaggerate, ruminate on,

There is no post-operative pain checkup, but the patient can elect

and feel helpless about one’s pain), sleep patterns, and anxiety

to schedule one if there is persistent pain [8]. The current practice

have been shown to be risk factors for developing chronic pain

lacks structured long-term management of chronic pain after

[2]. Studies conducted at Seattle Children’s Hospital have shown

surgical patients leave the hospital. It is difficult to develop such a

that adolescents undergoing major surgery with poorer quality of

program because pain is a subjective, psychosomatic condition

life and greater chronic pain intensity exhibit high pain

that can be managed using different methods such as physical

catastrophizing, irregular sleep patterns, and increased anxiety

therapy, CBT, and occupational therapy based on individual

before surgery [9]. The correlation of these factors has led to the

patients. To date, it is not clear what biological mechanisms are

understanding that these psychological elements play a role in

responsible for chronic pain. GREY MATTERS | issue 16

Treating Pediatric Chronic Pain

the development of post-surgical chronic pain. In order to

at Seattle Childrenâ&#x20AC;&#x2122;s Hospital, is developing an extensive post-

In a nationwide survey administered in 2011, it was found that

present a holistic treatment of pain, the relationship of these

surgical chronic pain CBT program to administer to children

minority children had significantly more debilitating pain

psychological factors to pediatric chronic pain must be extensively

undergoing major surgeries and their parents [9]. These

compared to Caucasians, girls had a higher pain intensity than

studied to develop targeted therapies. The development of more

programs consist of different modules that can be accessed by

boys, and teenagers had more compromised functioning than

CBTs to target psychological causes of chronic pain is the future

both parents and children online and followed over a period of

younger children [6]. These are important factors to consider

of chronic pain treatment [3].

months before and after surgery. The modules contain

when assessing the participant population of behavioral therapy

informational lessons on chronic pain prevention, coping

studies and the effectiveness of CBT on different demographics.

COGNITIVE BEHAVIORAL THERAPIES

mechanisms, and information about surgery, including anecdotes

There have been no studies showing the biological mechanism of

CBTs target the psychological and behavioral risk factors of

from other patients and families. Additionally, they educate patients

these relationships or how they impact the application of pain

chronic pain in adolescents [7]. They specifically emphasize the

and families about surgery, pain management techniques, and

treatments; however, there are other psychological factors that

connections between thoughts, feelings, and behaviors in terms

chronic pain [9]. Incorporating tips, references to old modules,

impact post-surgical pain in these demographics that can be

of development and pain maintenance. There are many different

and homework into these CBT programs encourages children

more readily targeted for specific groups of people.

components of a successful CBT, including psychoeducation,

and parents to practice the skills that they learned in different

self-monitoring, coping skills training for children, parent

sessions. They can increase quality of life, teach patients how to

FUTURE WORK

training, and relapse prevention. Some chronic pain CBTs focus

ease back into their normal routines after surgery, and change

Future applications for these post-surgical CBT programs could

specifically on reducing previously identified risk factors for

patientsâ&#x20AC;&#x2122; thinking about the surgical experience. These CBT

chronic pain development, such as anxiety, pain catastrophizing,

programs were initially proven to be effective in reducing pain

administration. Dr. Tonya Palermo, a psycholowgist at Seattle

and disrupted sleep. Targeting these risk factors before and after

severity in children with chronic headaches, but recent studies

Childrenâ&#x20AC;&#x2122;s Hospital, is currently doing this with WEB-MAP, a

surgery can greatly decrease the likelihood of developing post-

have shown there is a 10% or greater reduction in pain when

pain self-management program [11]. These phone-based apps

surgical chronic pain [4]. Dr. Jennifer Rabbitts, an anesthesiologist

CBTs were used in post-surgical populations in general [10].

are designed to be accessible to increasingly plugged-in youth,

integrated

into

phone-based

apps

for

outpatient

enabling them to use cognitive behavioral therapy modules remotely. This encourages increased participation and completion of modules by eliminating the need to be physically located at a

expenditures [15]. With the development of cost-effective,

laptop or desktop device. CBTs currently exist for anxiety

personalized CBTs for pain management, we can hope to reduce

disorders such as PTSD, OCD, panic disorder, generalized anxiety

the national cost of treating pediatric pain-related conditions and

disorder, social anxiety disorder, and specific phobias [12]. Other

the number of individuals living with persistent chronic pain.

CBTs are available for mood disorders such as depression and even substance use disorders [13,14]. Including motivational

References on page 40.

interviewing of patients in CBT may also improve outcomes and increase patient engagement [10]. Pediatric pain-related conditions are associated with 11.8 billion dollars in total health care

GREY MATTERS | issue 16

Eye Opening Epilepsy

pilepsies include a variety of disorders, characterized pri-

behaviors had been noticed by previous neurologists, Geschwind’s

marily by a disturbance in neuronal activity known as a

intense study of the topic led to significant strides in our under-

seizure [1]. One type of epilepsy that originates in the

standing of TLE [4].

temporal lobe, temporal lobe epilepsy (TLE), has potentially catalyzed some of the most famous religious experiences in history,

HISTORICAL FIGURES

perhaps due to the temporal lobe’s link to religious beliefs.

Quite a few historical figures, such as Dostoevsky, Socrates, and

Electrically stimulating the brains of TLE patients can cause differ-

most famously St. Paul, were thought to have had TLE. These ret-

ent types of hallucinations or other experiences [2]. Case studies

roactive diagnoses, derived from our increased understanding of

today reflect some symptoms and characteristics mentioned in lit-

the disease in modern patients, allow us to gain a better under-

erature about historical figures, including St. Paul and Socrates,

standing of their writings and the historical events in which they

prompting a posthumous diagnosis of TLE. While there are no

were involved. The Russian author Fyodor Dostoevsky is best

autopsies or EEGs to confirm the diagnosis, the plausibility of epi-

known for his novel, Crime and Punishment. Dostoevsky himself

leptic episodes cannot be ignored when discussing religious

likely suffered from TLE and wrote clearly about the experiences

figures. Furthermore, the link between religious epileptic events

and symptoms in one of his characters in The Idiot [5].

and location or cultural factors is supported by evidence through

Dostoevsky’s character Prince Myshkin has periods of ecstatic

international studies.

events interspersed through his dialogue, described as “his brain bursting into flame” and other phrases strongly suggestive of TLE

Temporal lobe epilepsies are categorized into partial seizures and

symptoms [5]. The amount of writing was very useful in deter-

generalized seizures based on the location of the onset area. Partial

mining the nature of Dostoevsky’s symptoms, as many of the

seizures are defined based on single hemisphere activity with a dis-

descriptions match those given by patients today. The philosopher

tinguishable onset area and then further categorized as complex

Socrates also potentially had TLE, as discussed in a case study by

partial seizures (CPS) or simple partial seizures (SPS). CPS are

Osamu Muramoto and a colleague. Socrates’s posthumous diagno-

characterized by a loss in consciousness and sometimes amnesia,

sis is based on his own writings about voices in his head that he

while patients remain conscious during SPS [3]. Among other

called “the divine sign” and other similar phrases, which were hy-

things, the temporal lobe is responsible for higher auditory and vi-

pothesized to indicate SPSs [6]. His friends described periods of

sual perception and memory and is the most common start site of

habitual unresponsiveness that would last for a significant amount

partial seizures [1, 2]. TLE comprises almost two-thirds of intrac-

of time, theorized to be a potentially recurring CPS [6].

table epilepsies, which require surgery because they cannot be managed with treatments such as antiepileptic drugs [1].

One of the most significant examples of sudden hyperreligiosity in history is St. Paul’s abrupt conversion

EYE OPENING EPILEPSY 22

Auras are also sometimes the onset of the epileptic event, and pa-

to Christianity [7]. St. Paul, initially Jewish,

tients report different sensations and disturbances in perception.

was on the road from Jerusalem to

While preictal events refer to symptoms occurring before (pre) the

Damascus to arrest Christians when he

onset of the epilepsy (ictal), auras are a form of SPS that are per-

had an apparent vision of Jesus, accom-

ceived as a variety of symptoms such as different emotions, senses,

panied by three days of blindness. There

or nausea [1]. Interictal events are those that occur between sei-

were similar accounts from a physician

zures or periods of seizures and are further characterized by

and some others on the road at the time

changes in behavior [1].

to support this. The descriptions of his fall reflect a very similar recent case,

One of the results of TLE, Geschwind Syndrome, is an interictal

where a patient with clinical and EEG

behavioral syndrome. Initially identified and qualified by Norman

features of TLE displayed occasional

Geschwind, it describes the symptoms that patients with TLE con-

grand mal seizures. This was accompa-

tinue to have between seizures [4]. Geschwind connected this

nied by symptoms of perceiving light

by Sharda Raina

disorder of the limbic system to symptoms that were displayed by

flashes and descriptions of religious ex-

art by Allegra Johnson

some of his patients, which included uncontrolled or extreme

periential emotions, supporting St.

writing, hypersexuality, and hyperreligiosity. Although these

Paul’s retroactive diagnosis [7].

GREY MATTERS | issue 16

Eye Opening Epilepsy

The nature of St. Paul’s conversion is controversial, as some argue

Japan. In one particular case, a woman who suffered from episodes

the details of his fall can be attributed to heatstroke or other possi-

of CPS had seizures accompanied by auditory hallucinations. She

ble medical issues. However, in one of his letters to the Church of

experienced a grand mal seizure when she was 17 and perceived

Corinth, St. Paul described a previous experience where he was

“the figures of God and Buddha” [8]. In Norway, a 2003 study spe-

“taken to the third heaven,” likely an ecstatic experience [7]. In an-

cifically focused on 11 TLE patients who experienced auras of

other letter, he described a “humiliating disease,” potentially the

ecstasy and found that five of the patients experienced religious

seizures or associated weakness, occurring in front of an audi-

auras [9]. In interviews, nearly every patient described the event as

ence. Although he displayed no obvious interictal behavioral

enjoyable; this is perhaps one of the reasons why historical cases

disorder, the significance of the fall—combined with his descrip-

were not seen as diseases, as the lack of negative symptoms could

tions in the letters—cannot be denied. The accounts of the fall

cause someone experiencing it at the time to believe it was divine.

and his other symptoms follow those of grand mal seizures and are thus consistent with the idea of TLE as the cause of his dras-

A UK study found a physical change correlated with hyperreligios-

tic religious conversion [7].

ity while observing 33 patients with TLE. Researchers discovered that patients displaying this symptom had significantly smaller

CURRENT DISCUSSION

right hippocampal volumes compared to other TLE patients [10].

TLE has been studied globally, with different focuses in reports

Not much is known about the neuropathology of TLE since very

from Japan, Norway, the UK, India, and Brazil—places with very

few studies look past seizures, but the association suggests a strong

diverse religious beliefs. Even places that are culturally less reli-

role for the hippocampus in religious belief and development. A

gious reflect a similar level of incidences of religious experiences

2007 study in India saw a 29% increase in religious belief after the

linked to seizures in TLE patients. In the early days of TLE re-

onset of epilepsy [11]. A Brazilian study focused specifically on

search, Geschwind responded to a statement about patients in

patients who made the sign of the cross during their epileptic

Brazil saying that the same kind of conversion would not hold

events, something more unique to the Catholic majority there

true in Texas because of different religious majorities, reflect-

[12]. They found localized right temporal lobe onset for seizures

ing an understanding of the social factors involved in these

and right hippocampal atrophy, which was consistent with the

religious conversions.

UK study [12].

A 1998 case study in Japan that reviewed 234 patients with epilep-

In order to associate the ecstatic experience with a more concrete

sy found a 1.3% incidence of related religious experiences [8].

belief, one must account for the religions or religious ideas to

These patients were found to believe in a combination of religions

which a TLE patient might feasibly be exposed. These different ar-

instead of only Buddhism or Shintoism, the traditional religions of

eas also reflect different religious majorities and levels of cultural significance associated with religion. Diagnoses of historical figures also add nuance to our current understanding of TLE. Global studies focus on various aspects of religiosity, so our knowledge of TLE must be influenced by an awareness of where studies are conducted. References on page 41.

MIND AND MATTER I

by Francisco Miralles art by Noor Al Huda Al Ghezi

t is impossible to ignore the association that exists in the mod-

Meanwhile, others may think of introspective meditation––where

ern era between meditation and the calming of one’s mind and

a specific object is chosen within the self and centered on––such as

emotions––the image of a lackadaisical hippie telling one to

loving-kindness meditation. It is no wonder that it can be difficult

just breathe might spring to mind. Recently, this association has

to navigate the question of what meditation is. A paper published

come to merit a closer look. By 2015 the estimated number of peo-

by scientist Jon Kabat-Zinn provides a more cogent interpretation

ple living with depression worldwide increased to 322 million,

of meditation [2]. Kabat-Zinn describes meditation as a way of be-

according to a 2017 report from the World Health Organization [1].

ing in which one pays attention to the contents of consciousness in

Depression is a condition characterized by feelings such as per-

the present moment by focusing on elements such as breath. This

sistent sadness, loss of interest, and fatigue that severely alter a

notion may surprise individuals, as the media often misrepresents

person’s disposition. While research on its causes and mechanisms

meditation. A common misconception is that meditation is a state

has not provided definitive conclusions, recent studies have looked

in which one relaxes and one’s mind goes completely blank. It is

into meditation as an alternative treatment to depression. These

quite the opposite; Kabat-Zinn says one’s mind can be jam-packed

studies, which explore the physiological effects of meditation on

with thought, worry, or any other mental state that may arise

the brain, provide a glimmer of hope to those in the throes of de-

when going about one’s day. What really constitutes the practice

pression. However, in order to grasp how meditation might be

of meditation is the awareness of the objects that may emerge

used to treat mental health, it is essential to understand what the

when you close your eyes to meditate, such as thoughts, emotions,

practice of meditation is and how it relates to the neuroanatomy of

and senses. It is this awareness of one’s consciousness in medita-

the depressed brain.

tion that allows for introspection, relaxation, and development of emotional intelligence [2].

The word meditation has a different definition depending on the context. For example, some may think of active meditation forms

Considering these positive attributes, what impacts on the brain

such as Kundalini yoga, where movement is the object of focus.

does meditation have that could alleviate symptoms of depression? The answer begins with a description of what we know of the mechanisms of depression. Studies have shown that depressed people display hyperactivity of the amygdala and loss of volume in the hippocampus [3, 4, 5]. The hyperactivity of the amygdala is correlated with the emotional responses of depressed patients, whose reactions to positive stimuli are negligible and reactions to negative stimuli are extreme [9]. Moreover, there is an established correlation between the atrophy of the hippocampus and increased depressive symptoms [5]. With these relationships in mind, let’s look at how meditation has been found to affect these same areas of the brain. In recent years, studies on meditation have established links between its practice and changes in the hippocampus and amygdala, a glimmer of hope in potentially treating depression. One study published by Eileen Luders of the UCLA Department of Neurology

GREY MATTERS | issue 16

Mind and Matter

Luders’s study at UCLA, the studies conducted by Holzel and her

may not only alter the structure of the brain itself, but also its func-

team also point to the potential of meditation in changing the brain

tion and offer a way to aid depressed persons in search of

in ways that could help patients with depression.

treatment options. It is important to note that 10-30% of the world’s depressed population does not respond to the typical trial of

The studies above show that the practice of meditation could aid in

antidepressants; this statistic shows the need to look into other via-

painting a better picture of what the treatment of depression

ble treatments of depression, such as meditation [10]. Issues such as

might be in coming years. However, the studies referred to should

treatment-resistant depression currently cast a shadow over the field

be taken with a grain of salt. There are many factors to account for

of psychiatry and neuroscience, a shadow that re-

when establishing causal relationships between meditation and changes in the brain’s anatomy, such as the sub-

search regarding meditation and depression could shine a light on in coming years.

jectivity and various forms of meditation. There are numerous practices considered to be med-

References on page 41.

itation that all vary significantly, such as Kundalini yoga and loving-kindness meditation.

When

further

exploring

meditation, it is important to keep in mind that these differences in meditative forms could produce differences in results, from physiological to psychological. While the research has yet to overcome this limitation, it may be possible to take into account this variation by studying these many practices of meditation. Another limitation is the subjectivity of the meditative experience, as it is impossible to look at the world through the eyes sought to evaluate how long-term meditative practice affects the

stress reduction (MBSR) program. Twenty-seven participants were re-

of someone else. This undeniable fact must be kept

anatomy of the brain [6]. The team recruited 22 long-term active

cruited to the study, all of whom underwent the full eight-week

in mind as scientists in the field delve further into the

meditation practitioners and 22 controls. In order to evaluate

MBSR program. These participants then had multiple MRI scans

relationship between meditation and depression.

changes in the brain’s anatomy, the researchers used magnetic res-

taken in the week prior and in the two weeks after the intervention

onance imaging (MRI) to obtain images of the participants’ brains

that were later compared to assess for differences in the density of the

The data recorded by Holzel and Luders in their respec-

and create models of the participants’ cerebrums, which were com-

amygdala’s gray matter after the MBSR intervention. In their analy-

tive studies show that there is a correlation between

pared to locate any disparities in their anatomy [6]. When

ses of the MRI data, the team found that the gray matter density of

the practice of meditation and changes in the

comparing the two groups, the team found that meditators and

the amygdala had decreased with meditation, an observation that co-

brain, specifically an enlargement of the

controls did not differ in total brain or gray matter volume.

incided with participants’ self-reported decreases in stress levels [7].

hippocampal gray matter and a reduction in the size of the amygdala.

However, the meditators had larger volumes of gray matter in the hippocampus, a region responsible for functions such as emotional

Holzel and her team further researched the changes in the brain

These studies provide a hint that,

regulation and memory consolidation, in comparison to the con-

that could be facilitated by meditative practices in the years follow-

due to the changes in the brain

trols [6]. The implications of these results are significant: they point

ing the above study [8]. In a 2011 study, Holzel aimed to find objective

induced by meditation, sus-

to the possibility of using meditation to combat the atrophy of the

measurements of changes in the brain’s anatomy that could under-

tained meditative practice

hippocampus that is characteristic of depression.

lie the benefits associated with meditation. Sixteen individuals were

could possibly counter the

recruited to undergo the MBSR program, while another 19 were

physiological symptoms of

Another study that looked into meditation’s effect on neuroanato-

recruited to be controls. The 16 that participated in the program

the depressed brain, specif-

my was carried out by Britta Holzel of the Bender Institute of

also had their brain scanned using MRI two weeks prior to and

ically the atrophy of the

Neuroimaging [7]. Holzel’s team sought to explore how the amyg-

two weeks after the intervention. The MBSR group exhibited an

hippocampal region and

dala’s gray matter density changed following an eight-week training

increase in hippocampal gray matter by the end of the study, in

the hyperactivity of the

program in mindfulness meditation called the mindfulness-based

contrast to a lack of changes found in the control group [8]. Like

amygdala.

GREY MATTERS | issue 16

Meditation GREY MATTERS | issue 16

Stand Up For Your Brain

STAND UP FOR YOUR BRAIN by Neha Krishnam art by Angelique Guina

o sit or to stand—a debate many rarely think about due

shows, exercise isn’t enough—prolonged sitting is an independent

to the prominence of sedentary lifestyles. Many of our

factor [8]. Despite healthy choices, extended periods of sitting are

daily activities involve sitting, such as being in front of a

still associated with cancer, disease, and obesity.

computer for hours or attending lectures. Previous studies have shown that sitting for a long time can increase the risk of develop-

THE NEURAL EFFECTS OF SITTING

thinnest medial temporal lobes). Atrophy of the MTL usually

ing cardiovascular diseases or diabetes, but new studies emphasize

It is known that long stretches of sitting can contribute to detri-

occurs with aging, resulting in impaired memory and even

that sitting can be bad for your brain as well [1]. The phrase “sit-

mental health problems and ultimately increased mortality rates.

Alzheimer’s disease. This study highlights the possible rela-

ting is the new smoking,” coined by James Levine, a professor of

However, harmful effects in the brain due to these seated periods

tion of sedentary behavior to the development of Alzheimer’s

medicine at the Mayo Clinic, is a fairly extreme comparison [2]. So

have only recently gained attention [6]. Many people believe that

disease. The authors hypothesized that a 25% reduction in

why don’t we take the harmful effects of sitting and the benefits of

exercise can cancel out sedentary behavior and thus tend to re-

sedentary behavior could reduce the prevalence of

standing more seriously?

main mostly seated throughout the day, only getting up for meals

Alzheimer’s by about one million cases across the globe.

and their commutes. Contrary to that belief, new research sug-

The researchers’ concluding statements suggest that more

SEDENTARY BEHAVIOR

gests that exercise is not enough to counteract the harmful effect

time spent sitting may result in a lack of thickness of the

Since a constant supply of blood is essential for the brain to func-

that sitting has on the brain’s health.

MTL in general and in the entorhinal cortex, the parahippocampal cortex, and the subiculum—areas that all aid in memory and

tion, temporary slowing of cerebral blood flow (such as during sitting) can negatively affect a person’s thinking and memory [3].

Researchers at UCLA studied how sedentary behavior influences

learning [9]. However, the study did not identify a correlation be-

Meanwhile, long-term declines in brain blood flow are linked to

brain health, especially in regions of the brain that are critical to

tween the thickness of the MTL and physical activity, suggesting

STAND UP FOR YOUR BRAIN

higher risks for some neurodegenerative diseases, including de-

memory formation [9]. Dr. Prabha Siddharth and her team

that exercise cannot undo the damage from continuous sitting [9].

People like to say, “Give your brain a break and stand up for a lit-

mentia [4]. A study published in the British Journal of Sports

showed that sedentary behavior is associated with reduced thick-

Instead, reducing the amount of sitting that people do may be a

tle.” Excessive sitting is correlated with a number of adverse

Medicine proposed that those who are continuously seated have a

ness of the medial temporal lobe (MTL), which houses the

more effective intervention.

effects, ranging from obesity to cancer to impaired learning.

higher chance of disease than those who stand up and move their

hippocampus, a part of the brain critical to learning and memory.

Many people believe that they can make it up through exercise, Science continues to suggest that standing can make people better

but research shows that exercise alone does not cancel out these

thinkers. A popular test, known as the Stroop Test, measures a

adverse effects. Prolonged sitting is its own factor—it needs to be

Prolonged sitting does not just affect the brain but other parts of

person’s selective attention capacity and skills as well as process-

countered with consistent muscle movement, such as walking or

the body as well. Researchers suggest that continuous sitting re-

ing speed [10]. The test requires the participant to read the name

even standing—throughout the day. People do not often think

of a color written on papers of a different color. For example, a

about the benefits of standing when presented with an easier op-

person would have to respond “yellow” if the word “yellow” were

tion. So, if you are reading this while sitting at your computer, try

written on a green paper. This specific study measured whether

standing up. It may work wonders for your brain.

muscles, such as by walking [5].

sults in a lack of muscle movement and that this sedentary behavior, properly defined as a “distinct class of behaviors, unrelated to exercise,” promotes overall poor health [5]. The University of Queensland also found that people who stood fre-

“The phrase “sitting is the new smoking,” coined by James Levine, a professor of medicine at the Mayo Clinic, is a fairly extreme comparison.”

standing or sitting enabled a quicker response. To do this, researchers had two groups of sitting participants and two groups of

quently had lower levels of blood fats. It is important to note that it was the frequency of standing, not the duration, that counted

The thinner the MTL, the more learning and memory are nega-

standing participants. The results showed that the people who

[6]. Prolonged sitting not only results in an increased risk of dis-

tively impacted. Furthermore, researchers asked a group of 35

stood responded faster than those who sat by approximately 120

ease but also back strain, causing chronic pain and blood clots [3].

healthy people, ages 45 to 70, about their activity levels and the

milliseconds [10]. This number may seem extremely small; how-

The Journal of the National Cancer Institute also reported that

average number of hours spent sitting per day, then performed

ever, it is important to remember the many things the human brain

sedentary behavior was associated with a 24% greater risk of de-

MRI scans. They found that the thickness of the MTL was in-

needs to interpret throughout the day. When all of that is taken

veloping colon cancer, a 32% higher risk of endometrial cancer,

versely correlated with how sedentary the participants were (i.e.

into account, the tiny number is compounded, possibly creating a

and a 21% increased risk of lung cancer [7]. However, as research

participants who reported sitting for longer periods had the

significant difference in reaction time when sitting versus standing.

GREY MATTERS | issue 16

References on page 42.

GREY MATTERS | issue 16

Mind Your Language

processing are exclusively triggered by speech sounds. This suggests

structure acting as a short-term memory bank for all phonetic

that there is a brain structure acting as some sort of filter that removes

stimuli and another that responds specifically to information the

non-speech sounds from the system of language processing. It turns

listener recognizes and comprehends [6].

out that this filtration consists of a complex series of interactions between brain structures in and around the auditory cortices [3].

In the case of signed languages, the input information does not consist of auditory signals. Instead, when signers receive an

MIND your LANGUAGE art and writing by Carina Kill

When the brain first perceives any kind of sound, a part of the

incoming linguistic stimulus, it first activates their primary visual

temporal lobe located in one of the most highly-developed parts of

cortex, located in the back of the brain [7]. Intriguingly, in the same

the human brain is activated [3]. Milliseconds after this region is

way that a hearing person’s brain filters through speech and non-

stimulated, the auditory cortices in both the left and right

speech sounds, signers show different right-side brain activity when

hemisphere of the brain begin to show activity. Although acting in

seeing a gesture and seeing a sign [8]. For example, if someone were

concert, the two hemispheres have actually been shown to function

to pantomime the action of sweeping the floor, it would elicit

very differently [4]. The left auditory cortex reacts most strongly to

different brain activity than the signed sentence “I am sweeping the

speech sounds, while the right more accurately detects tonal and

floor” in the receiving signer’s brain. This implies the same sort of

pitch differences across all types of sounds. This interaction is important

linguistic filter posited by those who study spoken languages [9].

because processing language requires both the detection of spoken

Although it is suspected that two separate pathways are also

words and an understanding of the intonation patterns that may

responsible for the filtration in signed languages, the research on

include clues about their possible meanings. This can be illustrated

linguistic processes in the deaf brain is still in its infancy, although

in English when someone makes a non-question statement sound

rapidly advancing [7].

like a question by raising their pitch at the end of the sentence. The importance of tone can be demonstrated even further in actual tonal

Because sign language relies on the visual world, there are many

languages like Chinese where, for example, the word “ma” can mean

characteristics unique to sign languages that are not present in

“hemp plant” when said with a rising tone but “mother” when said

spoken languages, but the similarities reach far deeper. When

with a flat tone. The two hemispheres of the brain work together to

first exploring sign language in the brain, researchers turned to

sort through this incoming auditory information before passing it

the right hemisphere due to its role in visuospatial processes like

on to the parts of the brain associated with syntactic (structure-

facial recognition.

based) and semantic (meaning-based) comprehension. Several studies found that the rear right hemisphere was indeed It was recently discovered that incoming auditory information

activated by the presence of incoming signed input [8]. A couple

follows two separate paths to the second area of language processing,

studies then compared this highlighted area in native American Sign Language (ASL) users and people who learned ASL later in

ne of the most fundamental things separating humans

processing in the brain is based on three crucial concepts:

which is also in the temporal lobe [5]. When any sort of complex

from all other species on Earth is our ability to use

recognizing an incoming signal, decoding the signal, and ultimately

sound with varying pitches and contours is heard, the first path

language. While other living things may be able to

establishing comprehension. Despite the recent blossoming of the

activates. These types of sounds are defined as any sound

communicate brief signals with various sounds or chemicals, the

field, there is still considerable debate over how exactly the brain

complex enough to possibly be interpreted as speech. Because

complexity and variability of human language is unique to our

goes from receiving input to understanding the message it carries.

spoken languages contain a multitude of varying sound signals, this area is not activated by singular sounds, but only by more

species alone. The capacity for language is often directly linked to the higher-order thinking that enables humans to create, evaluate,

The understanding of a phrase can be broken down into three major

complicated combinations [6]. The second pathway activates

and analyze. Because of this, the study of how language is

steps: accepting input information, processing the structure of the

only when the incoming speech signals are intelligible to

structured in the brain has been growing rapidly as technology

incoming information, and finally comprehending the meaning of

the listener [5]. This is related to how you can

advances [1]. The formal study of language began as far back as

the phrase [3]. Each of these steps can in turn be broken down into

recognize when a foreign language is being spoken

200 years ago. Major language changes were spreading across the

several substeps within certain geographic locations in the brain.

despite not knowing all of the sounds in the foreign

ancient world, and it was necessary for people to learn these

For spoken languages, the primary auditory cortices serve as the

inventory, but when you hear your own language you

changes in order to participate in the advancing society [2].

main regions for the first step of language processing by

hear the separation of words and can comprehend the

However, it has only been over the past few decades that scientists

recognizing and accepting input information. Interestingly, while the

meanings effortlessly, almost subconsciously. That is because

have had the technology needed to gain insight into the

auditory cortices are activated by speech and non-speech sounds

the two types of information travel through different pathways

neurological basis of language [2]. The understanding of language

alike, the areas of the brain relating to the last two steps of language

in the brain. This difference suggests that perhaps there is a brain

GREY MATTERS | issue 16

Mind Your Language

life. Interestingly, they found the same area of the right hemisphere

are merely a series of complex gestures [10]. In actuality, signed

For example, the person could be presented with two

to be significantly more active in the native users who learned sign

languages possess all of the same syntactic complexities and rules

sentences: “the boy runs” and “the runs boy.” The second

language before a certain age. The age cutoff for this brain activity

that define spoken languages and thus share a lot of the neural

phrase would be considered ungrammatical

aligns exactly with the critical period for language learning that

pathways involved with language processing after the initial

because the word “runs” does not work

had previously only been defined for hearing people [8]. This

input step. Once information from the visual or auditory input

as an adjective when English word-order

research implicates this portion of the right hemisphere in the first

has been delivered to the left-side temporal lobe, the brain begins

rules are applied. This can also be

step of signed language processing: accepting input information.

the modality-independent part of language processing: decoding

extended to signed languages, which rely on

But after this step, the same neurological areas activate in deaf and

the structure of the incoming phrase [9].

facial

hearing people alike, implying a shared system for processing structural and meaning-based information [7].

expressions

and

subtle

head

movements to establish grammatical function. Currently there are many hypotheses concerning how the brain is

In this case, scientists present deaf signers with a sign

able to sort through and deconstruct sentence structure, likely due to

accompanied by a head movement or facial expression that is

The syntactic and semantic levels of signed language processing

the staggering array of possible structures and rule combinations the

not normally there, effectively interrupting the same syntactic

are nearly identical to those seen in the brains of people using

human species is capable of mastering. There are about 7,000

assignment process [14]. By incorrectly using a word, researchers

spoken language. The differences that are occasionally found

languages being used currently, and although certain general

are able to interrupt the first part of sentence parsing, the word-

After the brain takes in the auditory or visual information and

usually trace back to the physical modality of signing, or how

structures are common, each language has its own intricacies [11].

category assignment, and observe the resulting effect on the

processes the phrase’s structure, all in a matter of milliseconds, it

signed languages consist of visual linguistic input, necessitating

Linguists define sentence structure based on where the crucial

word-relationship assignment [3]. This type of experiment shows

begins the third step of language processing: integrating the

visuospatial

components of the sentence—subject, verb, and object—must

especially increased activity in the top part of the temporal lobe,

multiple levels of information into one coherent message based

involvement [7]. It was actually the

appear. English is an SVO (subject, verb, object) language because

which hints at the region’s involvement in sorting out initial

on word meaning and usage. Over the past 15 years, research into

similarities between spoken and signed

sentences in English must be built according to this general

syntactic relationships.

the neurolinguistic separation between syntactic and semantic

languages regarding left-hemisphere

structure. For example, “She loves him” (SVO) would be considered

brain activity that helped disprove

a correct statement to an English speaker, but “Him she loves” (OSV)

The second type of experiment used to study the decoding of

revolve around the idea that all information processed up until

the misconception that sign languages

would seem strange and ungrammatical. There is at least one

phrase structure involves the use of artificial grammar. In these

this point needs to somehow be combined. This unsurprisingly

language in use today to account for nearly every possible

experiments, people learn a new set of grammar rules designed by

means that the majority of the previously discussed neural

combination of structure rules, and some languages with no well-

researchers, and then are tested on how well they can apply them.

regions play a role during the integration process [3]. The most

defined word order at all. Yet each community is linguistically

This process lets researchers gain insight into the areas of the brain

current model suggests that the temporal lobe can be broken into

developed and can communicate equally well. Word order is thus a

concerned with phrase-structure rule assignments. At the same

two parts, one remembering the structure of the incoming

common feature of language that can lead to different syntactic

time, researchers are able to study syntactic functions without the

phrasal information and the other dealing with any ambiguity

the

right

hemisphere’s

processes has split into several categories. These categories

structures with the same semantic interpretations [12]. In order to

that could be present in the sentence. This separation is based on

fully comprehend phrases, then, the human brain must somehow be

activation in the front part of the temporal lobe that is unaffected

able to assign meaning to each word in the phrase in a way that makes sense syntactically. The region of the temporal lobe to which the auditory and visual cortices deliver information is currently being targeted for the investigation of this phenomenon.

The temporal lobe is most commonly associated with the processing of auditory information and memory encoding. It is also associated with emotion processing, language, and some aspects of visual perception.

by fake words as long as the overall structure is correct. For example, in the sentence “the linkish dropner borked quastically,” none of the words are real words. But an English speaker is still able to identify which word is functioning as the noun, verb, etc., which alone lets them determine if the phrase is grammatical

One leading hypothesis to explain the phenomenon is that

or not. This again demonstrates that syntax is processed

shortly after processing the auditory or visual information, the

separately from word meaning. The back art of the temporal

brain begins decoding the phrase structure by assigning each

influence of word meaning. The participants’ ability to

lobe is the neural region observed to be increasingly active as the

word in the phrase to a category. These categories consist of the

successfully process made-up structure rules lets researchers

ambiguity of the phrase increases [3].

basic word-category distinctions (nouns, verbs, adjectives, etc.).

deduce whether sentence structure and word meaning are stored

The near-immediate next step is to reveal the subtler relationships

separately in the brain. Certain artificial grammar experiments

Ambiguity can arise when words are used grammatically but

between the words (i.e. which adjective describes which noun).

like these highlight activation in the same top part of the

have many possible correct meanings. This phenomenon is

Scientists have been able to observe separate brain activity during

temporal lobe but also show increased brain activity in the frontal

responsible for making certain phrases funny. The joke, “How do

these two distinct phases of language comprehension using two

lobe. Nearly all neurological research exploring the sorting of

you make a turtle fast? Stop feeding it.” is humorous because the

main kinds of experiments. The first type of experiment involves

language supports the idea that sentences are first parsed into

word “fast” is acting in an ambiguous way. In this context, the

comparing brain activity when people are given syntactically

categories and then almost simultaneously organized into a sort

word “fast” could mean speed but is later revealed to mean lack of

valid sentences versus sentences with incorrect word orders [13].

of tree that delineates the words’ relationships to each other [3].

food. As ambiguity increases, so does activity in the posterior

GREY MATTERS | issue 16

Changing Focus: ADHD in Women

Other studies have also found Broca’s region to be highly recruited

CHANGING FOCUS:

when people were asked to learn artificial grammar rules, suggesting that it plays a role not only in using, but also acquiring, complex language structures. Both of these ideas are backed by research that demonstrates that Broca’s area may be involved in sequence processing more generally. This is supported by research that suggests that Broca’s area may contribute to a person’s working memory, defined as the short-term storage of information for relatively immediate use [17]. It would make sense that to process a

ADHD IN WOMEN

complex sentence a person would need to store some amount of information while processing the rest, but scientists have found contradictory evidence on this basis. Some patients with brain injury demonstrated a link between working memory capacity and

by Sophia Anderson

complex sentence comprehension while others did not. So, it is

art by Sarah Wells

possible that Broca’s area is involved with sentence comprehension, but it is also likely that other areas of the brain are involved in ways area of the temporal lobe. This region also shows

increased

activity

with increasing complexity of verbs and number of prepositional phrases (for example, “the dog barked” versus “the dog jumped and barked from the porch at the cat in the tree above”) [3]. Other studies unrelated to language have demonstrated the latter region of the temporal lobe is involved with several other types of information integration, from audiovisual stimuli to face recognition and more, which means its implication in language processing is well-supported [15].

yet to be discovered [17]. Because neurolinguistic research is currently experiencing rapid evolution, the discovery of each of these regions’ involvements is really just the tip of the iceberg. The study of language is an ironic concept at its core in that we need to use language to study language. It has long been proposed that the very things that make us human are fundamentally based on language. Thinking about things in complex and analytical ways has enabled humans to develop the many elaborate societies that exist today. Without language, the communication of these highly developed, complex ideas becomes impossible, as demonstrated

half-cleaned room, an almost-done math assignment,

equipment!” A dynamic like this extending through someone’s

people, can develop basic communication skills, but they are

only the first part of a book report, and a notebook filled with

life can cause personal trouble, but there is more to the situation

normally limited to gestures and lack the linguistic skills necessary

incomplete drawings. She doesn’t always remember to text her

than its consequences. This woman is not careless, but instead

to communicate intricate thoughts and messages. Because of the

friends back and slowly they stop texting her. Her teachers fre-

demonstrates symptoms of attention deficit and hyperactivity

universality of communication, the discoveries made in the field of

quently comment that she would do well if she would “apply

disorder, or ADHD.

linguistics reach far deeper than the field itself. The neurological

herself,” but she can’t seem to get her head out of the clouds. Her

basis of language in humans is only now beginning to be unveiled

parents wonder why she does not seem to hear what they say

ADHD has a massive impact on the daily lives of many women. A

due to crucial technological advancements, and the next century

during dinner. School doesn’t interest her, and she doesn’t un-

common misconception, however, is that ADHD is a male-domi-

will bring countless more discoveries.

derstand why other people can do well while she struggles. As

nated condition and does not impact many women or persist into

she gets older, she finds methods to make sure she doesn’t fall be-

adulthood in women. This idea is being debunked with a new un-

hind in school, but it’s a constant struggle to balance these with her

derstanding that girls and women do experience this disorder at

personal relationships. She is more likely than others to develop

rates similar to boys and men, and around 64% of them continue to

depression, anxiety, or even a substance abuse disorder due to

struggle with ADHD into adulthood [1]. Males and females often

stress. It is often hard for her to prioritize tasks or make decisions

show vastly different symptoms, making it harder for females with

because she doesn’t always have a voice in her head telling her

ADHD to receive a timely and life-changing diagnosis, if they are

“Finish your work!” like others do. Instead, sometimes the voice in

diagnosed at all [2]. When ADHD in women is noticed, it’s often

by the hindered communication skills of those deprived of linguistic input in their formative years [18]. Those lacking sufficient linguistic input, like children who are severely abused and isolated,

In addition to the temporal lobe, the frontal lobe has been shown to play a major role in the third step of phrase processing (the combination of syntactic and meaning-based information to form a complete message) [3]. Broca’s area, a region in the frontal lobe, has been particularly interesting to scientists trying to narrow down how the brain accomplishes such a complex process. Researchers have been able to make a direct link between Broca’s area and several of the most important language processing steps. One wellestablished link exists between Broca’s area and syntactic complexity [16]. Broca’s area, like the posterior temporal lobe, also shows increased activity as sentences get increasingly complex and more

or deaf people surrounded by exclusively non-signing, hearing

References on page 42.

difficult to process. This makes sense when considering symptoms of damage to Broca’s area, wherein people lose their advanced language skills but retain comprehension of much simpler phrases and word meanings [16].

GREY MATTERS | issue 16

icture a twelve-year-old girl. She’s always losing her home-

her head will tell her something outlandish, like “Research saltwa-

work. Whenever she starts a project she ends up with a

ter aquariums and then buy two hundred dollars’ worth of fish and

GREY MATTERS | issue 16

Changing Focus: ADHD in Women

stigmatized and almost universally misunderstood. Part of this

used in models of ADHD. This creates a gap in research pertaining

especially in school-age children, perpetuating the idea of ADHD

gratification of a video game outweighs cleaning, and scrolling

confusion comes from the various expressions of ADHD in differ-

to women. Because of this gap and the subsequent research em-

as a predominantly male disorder and discouraging women from

through Instagram or shopping on Amazon is more interesting

ent people and at different ages.

phasis on boys and men with ADHD, women with the disorder

seeking specific treatment later in life. This difference in symp-

than homework. Most people do find video games, shopping, or

often go through their childhoods and much of their adult lives

toms is partially explained by neurological differences between

social media more fun than cleaning or work, but the problem

On a basic level, there are three distinct kinds of ADHD: hyperac-

without a diagnosis to explain their symptoms. Our direct under-

men and women with ADHD.

comes when someone with ADHD cannot mentally prioritize the

tive (ADHD-H), inattentive (ADHD-I), and combined (ADHD-C),

standings of diagnosing ADHD and the long-term impact of

mundane, but necessary, tasks of living. This helps explain the ten-

which shows both inattentive and hyperactive traits. People with

ADHD focus mainly on men, making it difficult to apply to wom-

dency of women with ADHD to “check out” of day-to-day life as

ADHD-I present symptoms that include frequent careless mis-

en who have a very different set of neurological causes and cultural

many of them may find it boring or unstimulating.

takes, not being able to finish tasks, forgetting important events

expectations tied to the disorder. The gendered difference in ex-

and projects, and not speaking when spoken to. They may day-

pression requires better screening methods, more research, and

The variability in symptoms and, consequently, diagnosis also has

dream as a way to escape boredom or interrupt conversations with

increased societal awareness for women and girls with ADHD to

an effect on long-term outcomes for women and men. Women

unrelated comments. Conversely, people who have ADHD-H may

prevent devastating social and emotional repercussions.

move around inappropriately, talk excessively, are unable to wait

“Current studies of diagnosed children suggest that most elementary-age girls who are diagnosed with ADHD present ADHD-I, possibly because of social norms stifling expression of the other subtypes. “

with ADHD carry the disorder into adulthood between 44% and 62% of the time, based on self-reports of issues in the context of

their turn, fidget, and interrupt conversations. These actions

There are especially pervasive social problems around recognizing

match the diagnostic criteria governed by the fifth revision of the

and diagnosing school-age girls who have ADHD [4]. Literature is

American Psychiatric Association’s Diagnostic and Statistical

conflicted on whether or not women are more likely to have the

Manual of Mental Disorders (DSM-5). Unlike most of the other

less-diagnosed ADHD-I, but this may be a barrier to treatment

most dangerous when the patient does not receive treatment for

DSM-5 criteria for diagnosing mental disorders, these criteria

since people with ADHD-H or -C are more likely to be diagnosed

the underlying condition of ADHD. There is a long list of potential

were formulated to diagnose children, and they don’t always cap-

at a young age and are therefore overrepresented in studies.

Although most symptoms are common between men and women,

comorbidities, most of which have been observed separately in

ture the nuances and struggles that adults with ADHD experience

Unfortunately, this means we know much more about people with

brain differences point to a less known and critical difference in

multiple studies. Common risks include increased liability for anx-

[2]. Beyond that, many adults with ADHD have comorbid disor-

ADHD-H and –C than those with ADHD-I who have subtler

the neurological causes of ADHD in men versus women.

iety disorders, personality disorders such as borderline personality

ders like substance abuse, depression, borderline personality

symptoms. Furthermore, societal expectations for girls to be quiet-

According to a study conducted at the University of Wollongong

disorder and schizophrenia, bipolar disorder, and rejection-sensi-

disorder, or generalized anxiety disorder [7, 8]. These conditions

er and less rowdy or disruptive during class may create a dynamic

with a sample of 16 men and 16 women with ADHD diagnosed in

tive dysphoria [7, 8]. Outside of the mental health realm, there is

have symptoms that frequently overlap with problems created by

that stifles common ADHD-H or -C symptoms in young girls. The

childhood and a sex-matched control group, men with ADHD

an increased risk of sexually transmitted infections and single par-

ADHD, like an unstable personal life, forgetfulness, anxiety, and

impact of different types of ADHD on teachers’ decisions to refer

have significantly reduced beta and increased theta brain waves

enthood and a decreased likelihood of graduating high school and

volatile emotions. Doctors might see the anxiety caused by not re-

students to doctors was tested by researchers with the NHS Trust

when compared to gender-, age-, and IQ-matched pairs [5]. Beta

college [9, 10]. These do not always happen because of ADHD, and

membering important events, or depression from difficulties

in the United Kingdom. Using a sample of 169 out of 186 elemen-

waves facilitate active thinking and the ability to resist movement.

they do not happen to all people who have the disorder, but there

forming appropriate social bonds, and treat those issues without

tary schools, researchers sent questionnaires containing vignettes

Theta waves allow for increased short-term memory and the abili-

is a greater incidence especially with untreated ADHD. If a woman

recognizing that, depending on the cause, the underlying factor

of children with either ADHD-I or -C for teachers to read. The vi-

ty to process and respond to stimuli. This increased ability to

in particular has many of these conditions along with any symp-

may be ADHD.

gnettes described behaviors common to each type of ADHD and

process and respond tends to be associated with the inability to fil-

toms of ADHD, there is a high chance that she suffers from some

emphasized the problems the hypothetical students had with mak-

ter through stimuli: everything receives the same importance and

form of this disorder. It might be helpful for her to have an ap-

ing satisfactory progress in school. They found that teachers were

emotional investment, whether it be planning for an important

pointment with a psychiatrist, because even if it does not lead to a

equally likely to recognize ADHD-C and -I in male and female

work meeting or choosing a tropical fish in a pet store. The differ-

diagnosis of ADHD, it could unearth one of the comorbid disor-

populations in laboratory settings. However, they recommended

ences in brain waves help to explain the hyperactivity shown in

ders, which could then be treated as a first-line of defense.

boys, more so than girls, with ADHD-I receive medical treatment

men with ADHD [5]. Men might be more prone to become inter-

Although these conditions are often treatable, they have massive

in their classrooms outside of the experiment. In other words, al-

ested in many different things rapidly or do things without

repercussions for those who suffer from them, even with proper

though they knew the potential educational and social

thinking them through. This is a sharp contrast to women with

interventions. This includes a higher mortality rate, especially for

repercussions for both ADHD-I and -C, teachers did not recom-

ADHD, who on average have statistically insignificant differences

women who have ADHD as well as comorbid disorders, and peo-

mend treatment for both types when they appeared in girls, as

in brain waves to a matched control group of women with the

ple who were diagnosed in adulthood [11]. This demonstrates the

opposed to higher treatment recommendation rates for their male

same ages and IQs [6]. However, they show significantly lower

gendered barrier to appropriate treatment resulting from the stig-

The complex etiology of ADHD leaves many researchers not

peers. Current studies of diagnosed children suggest that most ele-

arousal. In this context, arousal refers to the gain of stimulation

ma around female mental health and the overriding belief that

knowing where to start or what to focus on. Many of them choose

mentary-age girls who are diagnosed with ADHD present

and satisfaction from daily activities. Women with ADHD have

ADHD is predominantly a male disorder.

to corroborate older studies that focus on men and boys or simply

ADHD-I, possibly because of social norms stifling expression of

lower arousal levels, which was measured by their skin’s electrical

base their research off of older male-focused studies because these

the other subtypes. Boys, especially those with ADHD-H or -C, are

conductance, than matched controls. Practically, this means they

To dispel this stigma around women with ADHD, medical jour-

groups have more evidence to inform their work [3]. Even in ani-

more disruptive to class because of the visibility of their symptoms

experience less enjoyment and satisfaction from normal activities.

nals and medical schools need to reframe the disorder as something

mal research, historically, male animals were nearly exclusively

[4]. This leads to a lack of correct diagnosis and treatment,

A lack of “arousal” from daily life could mean that the immediate

that presents in many different forms and often persists into

DSM-5 is a collective manual consisting of definitions and classifications for over 297 mental disorders. The DSM-5 serves as primal authority for psychiatric diagnoses in the US.

GREY MATTERS | issue 16

medical treatment, but these numbers do not include undiagnosed people or patients with fewer than five out of the nine diagnosable criteria—not enough to reach a full diagnosis. Comorbidities are

GREY MATTERS | issue 16

Changing Focus: ADHD in Women

REFERENCES

adulthood [1]. Schools should implement a more rigorous screening program for at-risk children, which would help children gain the therapy and treatment to develop socially, emotionally, and academically with their classmates. Addressing problems that come with impulsivity and poor decision-making skills may decrease the

EXPRESS BEFORE YOU TEST

risk for certain comorbid disorders, like anxiety and depression, in

by Elise Stefanou, art by Nina Chen | page 6

CODE OF CONDUCT: BAYESIAN PREDICTIVE CODING

adolescence and adulthood. The real and devastating effects of this neurological and psychological disorder are often swept away with an insistence that if patients simply “worked harder” or “focused more,” they would not be in their situations. Common social expectations of women (with or without ADHD) to perform as domestic partners, coupled with careers and the stressors of everyday life, can be overwhelming to the point of reducing their ability to do well in any of these areas [1]. We need to dispel the idea that women and girls are not susceptible to ADHD, and that ADHD-I is less damaging than more visible subtypes. Improving evidence-based diagnostics and treatments, regardless of gender, would likely lead to a higher instance of ADHD diagnosis in women, allowing them to access appropriate care before they begin to suffer from the negative effects associated with the disorder. This, partnered with breaking down mental health stigmas and traditional female social roles, would give women with ADHD a fighting chance at succeeding in the same environments as their peers, male or female. References on page 43.

GREY MATTERS | issue 16

1. Faigley, L. (1986). Competing theories of process: A critique and a proposal. College English, 8(6), 527-542. 2. Pennebaker, J. W. (1997). Writing about emotional experiences as a therapeutic process. Psychological Science, 8(3), 162-166. 3. Pennebaker, J. W. & Beall, S. K. (1986). Confronting a traumatic event: Toward an understanding of inhibition and disease. Journal of Abnormal Psychology, 95(3), 274-281. 4. DiMenichi, B. C., Lempert, K. M., Bejjani, C., & Tricomi, E. (2018). Writing about past failures attenuates cortisol responses and sustained attention deficits following psychosocial stress. Frontiers in Behavioral Neuroscience, 12(45), 1-9. doi: 10.3389/fnbeh.2018.00045 5. Klein, K. & Boals, A. (2001). Expressive writing can increase working memory capacity. Journal of Experimental Psychology, 130(3), 520-533. doi: 10.1037//0096-344S.130.3.520 6. Memarian, N., Torre, J. B., Haltom, K. E., Stanton, A. L., & Lieberman, M. D. (2017). Neural activity during affect labeling predicts expressive writing effects on well-being: GLM and SVM approaches. Social Cognitive and Affective Neuroscience, 12(9), 1437-1447. doi: 10.1093/scan/nsx084 7. Ramirez, G. & Beilock, S. L. (2011). Writing about testing worries boosts exam performance in the classroom. Science, 331, 211-213. doi: 10.1126/science.1199427 8. Shen, L., Yang, L., Zhang, J., & Zhang, M. (2018). Benefits of expressive writing in reducing test anxiety: A randomized controlled trial in Chinese samples. Public Library of Science One, 13(2). doi: 10.1371/journal.pone.0191779 9. Ayers, S., et al. (2018). Evaluation of expressive writing for postpartum health: a randomised controlled trial. Journal of Behavioral Medicine, 41(5), 614-626. doi: 10.1007/ s10865-018-9970-3 10. Lu, Q., Gallagher, M. W., Loh, A., & Young, L. (2018). Expressive writing intervention improves quality of life among Chinese-American breast cancer survivors: A randomized controlled trial. Annals of Behavioral Medicine, 52(11), 952-962. doi: 10.1093/abm/kax067 11. Tonarelli, A., et al. (2018). Expressive writing. A tool to help health workers of palliative care. Acta BioMedica, 89(6-S), 3542. doi: 10.23750/abm.v89i6-S.7452

by Kathryn Stangret, art by Kat Ramus | page 10 1. Spratling, M.W. (2017). A review of predictive coding algorithms, Brain and Cognition, 112, 92-97, doi.org/10.1016/j. bandc.2015.11.003. 2. Jacobs, R. A., & Kruschke, J. K. (2010). Bayesian learning theory applied to human cognition. Wiley Interdisciplinary Reviews: Cognitive Science, 2, 8–21. doi.org/10.1002/wcs.80. 3. Parr, T., Rees, G., and Friston, K.J. (2018). Computational Neuropsychology and Bayesian Inference. Frontiers in Human Neuroscience, 12:61. doi.org/10.3389/fnhum.2018.00061. 4. Aitchison, L., Lengyel, M. (2017). With or without you: predictive coding and Bayesian inference in the brain. Current Opinion in Neurobiology, 46, 219-227. doi.org/10.1016/j. conb.2017.08.010. 5. Sterzer, P., et al. (2018). The Predictive Coding Account of Psychosis. Biological psychiatry, 84(9), 634-643. doi. org/10.1016/j.biopsych.2018.05.015. 6. Kruschke, J.K. & Liddell, T.M. (2018). Bayesian data analysis for newcomers. Psychonomic Bulletin & Review, 25(1), 155177. doi.org/10.3758/s13423-017-1272-1. 7. Doyle, D.C. (1890). Sherlock Holmes Gives a Demonstration. The Sign of Four (pp. 68). Chicago. 8. Ghahramani, Z. (2015). Probabilistic machine learning and artificial intelligence. Nature, 521, 452-459. doi:10.1038/ nature14541.

WITH A GRAIN OF SALT: THE MSG MENACE by Xuan Nhi Nguyen, art by Fiona Seung | page 14 1. Sand, J. (2005). A Short History of MSG: Good Science, Bad Science, and Taste Cultures. Gastronomica,5(4), 38-49. doi:10.1525/gfc.2005.5.4.38 2. Kwok, R. H., MD. (1968). Chinese-Restaurant Syndrome. New England Journal of Medicine,278(14), 796-796. doi:10.1056/ nejm196805162782014 3. Raiten, D., Talbot, J., & Fisher, K. (1995). Analysis of adverse reactions to monosodium glutamate (MSG). The Journal of Nutrition, 125(11), xiv, xxi, xxii, 9, 83-86. 4. McCaghren, T.J.. (1968) Chinese-Restaurant Syndrome. The New England Journal of Medicine, 278(20), 1122-1124. 5. Kikunae, I. (2002). New seasonings. Chemical Senses, 27(9),

GREY MATTERS | issue 16

REFERENCES

847-849. doi:10.1093/chemse/27.9.847 6. Sano, C. (2009). History of glutamate production. The American Journal of Clinical Nutrition, 90(3), 728S-732S. doi:10.3945/ajcn.2009.27462F 7. Kazmi, Z., Fatima, I., Perveen, S., & Malik, S. (2017). Monosodium glutamate: Review on clinical reports. International Journal of Food Properties, 20(Sup2), 1807-1815. doi:10.1080/10942912.2017.1295260 8. Rhodes, J., Titherley, A.C., Norman, J.A., Wood, R., Lord, D.W. (1991). A survey of the monosodium glutamate content of foods and an estimation of the dietary intake of monosodium glutamate. Food Additives and Contaminants, 8(5), 663-672. 9. Dong, X., Wang, Y., & Qin, Z. (2009). Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases. Acta Pharmacologica Sinica, 30(4), 379-387. doi:10.1038/aps.2009.24 10. Hawkins, Richard A. (2009). The blood-brain barrier and glutamate. American Journal of Clinical Nutrition, 90(3), 867S-874S. doi:10.3945/ajcn.2009.27462BB 11. Olney, J. (1969). Brain Lesions, Obesity, and Other Disturbances in Mice Treated with Monosodium Glutamate. Science, 164(3880), 719-721. 12. Morita, S., & Miyata, S. (2013). Accessibility of low-molecular-mass molecules to the median eminence and arcuate hypothalamic nucleus of adult mouse. Cell Biochemistry and Function, 31(8), 668-677. doi:10.1002/cbf.2953 13. Walpole, S. C., Prieto-Merino, D., Edwards, P., Cleland, J., Stevens, G., & Roberts, I. (2012). The weight of nations: An estimation of adult human biomass. BMC Public Health, 12(439). doi:10.1186/1471-2458-12-439 14. Geha, Beiser, Ren, Patterson, Greenberger, Grammer, . . . Saxon. (2000). Multicenter, double-blind, placebo-controlled, multiple-challenge evaluation of reported reactions to monosodium glutamate. The Journal of Allergy and Clinical Immunology, 106(5), 973-980. doi:10.1067/mai.2000.110794 15. P. L. Morselli, & S. Garattini. (1970). Monosodium Glutamate and the Chinese Restaurant Syndrome. Nature, 227(5258), 611-612. doi:10.1038/227611a0 16. Center for Food Safety and Applied Nutrition. (2012). Food Additives & Ingredients - Questions and Answers on Monosodium glutamate (MSG). Retrieved from https://www. fda.gov/food/ingredientspackaginglabeling/foodadditivesingredients/ucm328728.htm 17. Mortensen, A., Aguilar, F., Crebelli, R., Di Domenico, A., Dusemund, B., Frutos, M., . . . Lambré, C. (2017). Re‐evaluation of glutamic acid (E 620), sodium glutamate (E 621), potassium glutamate (E 622), calcium glutamate (E 623),

ammonium glutamate (E 624) and magnesium glutamate (E 625) as food additives. EFSA Journal, 15(7), N/a. doi:10.2903/j. efsa.2017.4910

TREATING PEDIATRIC CHRONIC PAIN by Meena Meyyappan, art by George Song | page 18 1. Pain [Def. 1]. (n.d.). In Dictionary.com. 2. Rabbitts, J. A., Zhou, C., Groenewald, C. B., Durkin, L., & Palermo, T. M. (2015). Trajectories of postsurgical pain in children. Pain,156(11), 2383-2389. doi:10.1097/j. pain.0000000000000281 3. Wasner, G., Lee, B. B., Engel, S., & Mclachlan, E. (2008). Residual spinothalamic tract pathways predict development of central pain after spinal cord injury. Brain, 131(9), 2387-2400. doi:10.1093/brain/awn169 4. Dahlhamer, J., Lucas, J., Zelaya, C., Nahin, R., Mackey, S., Debar, L., . . . Helmick, C. (2018). Prevalence of Chronic Pain and High-Impact Chronic Pain Among Adults — United States, 2016. MMWR. Morbidity and Mortality Weekly Report, 67(36), 1001-1006. doi:10.15585/mmwr.mm6736a2 5. Friedrichsdorf, S., Giordano, J., Dakoji, K. D., Warmuth, A., Daughtry, C., & Schulz, C. (2016). Chronic Pain in Children and Adolescents: Diagnosis and Treatment of Primary Pain Disorders in Head, Abdomen, Muscles and Joints. Children, 3(4), 42. doi:10.3390/children3040042 6. Evans, S., Taub, R., Tsao, J. C., Meldrum, M., & Zeltzer, L. K. (2010). Sociodemographic factors in a pediatric chronic pain clinic: The roles of age, sex and minority status in pain and health characteristics. Journal of pain management, 3(3), 273–281. 7. Palermo, T. M. (2012). The Evidence Base for CognitiveBehavioral Therapy for Pediatric Chronic Pain. Cognitive-Behavioral Therapy for Chronic Pain in Children and Adolescents, 25-38. doi:10.1093/ med:psych/9780199763979.003.0003 8. Gupta, A., & Gupta, N. (2010). Setting up and functioning of a preanaesthetic clinic. Indian Journal of Anaesthesia, 54(6), 504. doi:10.4103/0019-5049.72638 9. Rabbitts, J. A., Aaron, R. V., Fisher, E., Lang, E. A., Bridgwater, C., Tai, G. G., & Palermo, T. M. (2017). Long-Term Pain and Recovery After Major Pediatric Surgery: A Qualitative Study With Teens, Parents, and Perioperative Care Providers. The Journal of Pain, 18(7), 778-786. doi:10.1016/j. jpain.2017.02.423

GREY MATTERS | issue 16

10. Hart, S. L., & Hart, T. A. (2010). The Future of Cognitive Behavioral Interventions Within Behavioral Medicine. Journal of Cognitive Psychotherapy, 24(4), 344-353. doi:10.1891/0889-8391.24.4.344 11. Palermo, T. M., Vega, R. D., Dudeney, J., Murray, C., & Law, E. (2018). Mobile health intervention for self-management of adolescent chronic pain (WebMAP mobile): Protocol for a hybrid effectiveness-implementation cluster randomized controlled trial. Contemporary Clinical Trials, 74, 55-60. doi:10.1016/j.cct.2018.10.003 12. Kaczkurkin, A. N., & Foa, E. B. (2015). Cognitive-behavioral therapy for anxiety disorders: an update on the empirical evidence. Dialogues in clinical neuroscience, 17(3), 337–346. 13. Driessen, E., & Hollon, S. D. (2010). Cognitive Behavioral Therapy for Mood Disorders: Efficacy, Moderators and Mediators. Psychiatric Clinics of North America,33(3), 537555. doi:10.1016/j.psc.2010.04.005 14. McHugh, R. K., Hearon, B. A., & Otto, M. W. (2010). Cognitive behavioral therapy for substance use disorders. The Psychiatric clinics of North America, 33(3), 511–525. doi:10.1016/j.psc.2010.04.012 15. Groenewald, C. B., Wright, D. R., & Palermo, T. M. (2015). Health care expenditures associated with pediatric pain-related conditions in the United States. Pain,156(5), 951-957. doi:10.1097/j.pain.0000000000000137

Divine?” Journal of Medical Humanities 35.3 (2014): 241-55. Web. 6. Muramoto, Osamu, and Walter G. Englert. “Socrates and Temporal Lobe Epilepsy: A Pathographic Diagnosis 2,400 Years Later.” Epilepsia 47.3 (2006): 652-54. Web. 7. Landsborough, D. “St Paul and Temporal Lobe Epilepsy.” Journal of Neurology, Neurosurgery & Psychiatry50.6 (1987): 659-64. Web. 8. Ogata, A. & Miyakawa, T. Religious experiences in epileptic patients with a focus on ictus-related episodes. Psychiatry and Clinical Neurosciences 52, 321–325 (1998). https://doi. org/10.1046/j.1440-1819.1998.00397.x 9. Åsheim Hansen, B., & Brodtkorb, E. (2003). Partial epilepsy with “ecstatic” seizures. Epilepsy and Behavior, 4(6), 667-673. https://doi.org/10.1016/j.yebeh.2003.09.009 10. Wuerfel, Krishnamoorthy, Brown, Lemieux, Koepp, Tebartz Van Elst, and Trimble. “Religiosity Is Associated with Hippocampal but Not Amygdala Volumes in Patients with Refractory Epilepsy.” Journal of Neurology, Neurosurgery and Psychiatry 75.4 (2004): 640-642. Web. 11. Khwaja, Geeta, Ashish Duggal, Amit Kulkarni, Neera Chaudhry, Meena Gupta, Debashish Chowdhury, and Vikram Bohra. “Recurrent Prolonged Fugue States as the Sole Manifestation of Epileptic Seizures.” Annals of Indian Academy of Neurology 16.4 (2013): 561-64. Web. 12. Tedrus, G. M. A. S., Fonseca, L. C., Fagundes, T. M. & da Silva, G. L. Religiosity aspects in patients with epilepsy. Epilepsy & Behavior 50, 67–70 (2015). https://doi.org/10.1016/j. yebeh.2015.06.003

EYE OPENING EPILEPSY by Sharda Raina, art by Allegra Johnson | page 22 1. Blair, R. D. G. Temporal lobe epilepsy semiology. Epilepsy research and treatment 2012, 751510–751510 (2012). doi: 10.1155/2012/751510 2. Gloor, P., Olivier, A., Quesney, L., Andermann, F., & Horowitz, S. (1982). The role of the limbic system in experiential phenomena of temporal lobe epilepsy. Annals of Neurology, 12(2), 129-144. 3. Kumar A, Sharma S. Seizure, Simple Partial. [Updated 2018 Dec 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan. 4. Devinsky, J. & Schachter, S. Norman Geschwind’s contribution to the understanding of behavioral changes in temporal lobe epilepsy: The February 1974 lecture. Epilepsy & Behavior 15, 417–424 (2009). https://doi.org/10.1016/j.yebeh.2009.06.006 5. McCrae, Niall, and Rob Whitley. “Exaltation in Temporal Lobe Epilepsy: Neuropsychiatric Symptom or Portal to the

MIND AND MATTER by Francisco Miralles, art by Noor Al Huda Al Ghezi | page 25 1. Depression and Other Common Mental Disorders: Global Health Estimates. Geneva: World Health Organization; 2017. License: CC BY-NC-SA 3.0 IGO. 2. Kabat-Zinn, J. (2015). Meditation—It’s Not What You Think. Mindfulness,6(2), 393-395. doi:10.1007/s12671-015-0393-8 3. Drevets, W., Videen, T., Price, J., Preskorn, S., Carmichael, S., & Raichle, M. (1992). A functional anatomical study of unipolar depression. The Journal of Neuroscience,12(9), 3628-3641. doi:10.1523/jneurosci.12-09-03628.1992 4. Sheline, Y. I. (2000). 3D MRI studies of neuroanatomic changes in unipolar major depression: The role of stress and medical comorbidity. Biological Psychiatry,48(8), 791-800. doi:10.1016/ s0006-3223(00)00994-x 5. Campbell, S., & MacQueen, G. (2004). The role of the

GREY MATTERS | issue 16

REFERENCES

hippocampus in the pathophysiology of major depression. Journal of Psychiatry & Neuroscience, 29(6), 417-426. 6. Luders, E., Toga, A. W., Lepore, N., & Gaser, C. (2009). The underlying anatomical correlates of long-term meditation: Larger hippocampal and frontal volumes of gray matter. NeuroImage,45(3), 672-678. doi:10.1016/j. neuroimage.2008.12.061 7. Hölzel, B. K., Carmody, J., Evans, K. C., Hoge, E. A., Dusek, J. A., Morgan, L., . . . Lazar, S. W. (2009). Stress reduction correlates with structural changes in the amygdala. Social Cognitive and Affective Neuroscience,5(1), 11-17. doi:10.1093/ scan/nsp034 8. Hölzel, B. K., Carmody, J., Vangel, M., Congleton, C., Yerramsetti, S. M., Gard, T., & Lazar, S. W. (2011). Mindfulness practice leads to increases in regional brain gray matter density. Psychiatry Research: Neuroimaging,191(1), 3643. doi:10.1016/j.pscychresns.2010.08.006 9. Murray, E. A., Wise, S. P., & Drevets, W. C. (2011). Localization of Dysfunction in Major Depressive Disorder: Prefrontal Cortex and Amygdala. Biological Psychiatry,69(12). doi:10.1016/j.biopsych.2010.09.041 10. Depression. (2018, March 22). Retrieved from http://www. who.int/news-room/fact-sheets/detail/depression

Stand Up for your brain

30-40. doi:10.1016/j.amepre.2013.09.009 6. Stamatakis, E., Ekelund, U., Ding, D., Hamer, M., Bauman, A. E., & Lee, I. (2018). Is the time right for quantitative public health guidelines on sitting? A narrative review of sedentary behaviour research paradigms and findings. British Journal of Sports Medicine,53(6), 377-382. doi:10.1136/ bjsports-2018-099131 7. Sudholz, B., Timperio, A., Ridgers, N. D., Dunstan, D. W., Baldock, R., Holland, B., & Salmon, J. (2016). The Impact and Feasibility of Introducing Height-Adjustable Desks on Adolescents’ Sitting in a Secondary School Classroom. AIMS Public Health,3(2), 274-287. doi:10.3934/ publichealth.2016.2.274 8. Biddle, S. J., Pearson, N., Ross, G. M., & Braithwaite, R. (2010). Tracking of sedentary behaviours of young people: A systematic review. Preventive Medicine,51(5), 345-351. doi:10.1016/j. ypmed.2010.07.018 9. Siddarth, P., Burggren, A. C., Eyre, H. A., Small, G. W., & Merrill, D. A. (2018). Sedentary behavior associated with reduced medial temporal lobe thickness in middle-aged and older adults. Plos One,13(4). doi:10.1371/journal.pone.0195549 10. Rosenbaum, D., Mama, Y., & Algom, D. (2018). Stand by Your Stroop: Standing Up Enhances Selective Attention and Cognitive Control. Psychological Science,29(6), 1023-1024. doi:10.1177/0956797618772298

by Neha Krishnam, art by Angelique Guina | page 28 1. Pulsford, R. M., Stamatakis, E., Britton, A. R., Brunner, E. J., & Hillsdon, M. M. (2013). Sitting behavior and obesity: evidence from the Whitehall II study. American Journal of Preventive Medicine, 44(2), 132–138. doi:10.1016/j.amepre.2012.10.009 2. Levine, J. A. (2014). The Chairman’s Curse: Lethal Sitting. Mayo Clinic Proceedings, 89(8), 1030-1032. doi:10.1016/j. mayocp.2014.07.001 3. Fantini, S., Sassaroli, A., Tgavalekos, K. T., & Kornbluth, J. (2016). Cerebral blood flow and autoregulation: Current measurement techniques and prospects for noninvasive optical methods. Neurophotonics,3(3), 031411. doi:10.1117/1. nph.3.3.031411 4. Mehta, R. K., Shortz, A. E., & Benden, M. E. (2015). Standing Up for Learning: A Pilot Investigation on the Neurocognitive Benefits of Stand-Biased School Desks. International Journal of Environmental Research and Public Health, 13(1), ijerph13010059. doi:10.3390/ijerph13010059 5. Neuhaus, M., Healy, G. N., Dunstan, D. W., Owen, N., & Eakin, E. G. (2014). Workplace Sitting and Height-Adjustable Workstations. American Journal of Preventive Medicine,46(1),

Mind your language art and writing by Carina Kill | page 30 1. Campbell, L., “The History of Linguistics.” The Handbook of Linguistics, 30 Nov. 2007, doi:10.1111/b.9781405102520.2002.00006.x. 2. Chang, E.F., et al. “Contemporary Model of Language Organization: an Overview for Neurosurgeons.” Journal of Neurosurgery, Feb. 2015, pp. 250–261., doi:10.3171/2014.10. jns132647. 3. Friederici, A. D. “The Brain Basis of Language Processing: From Structure to Function.” Physiological Reviews, vol. 91, no. 4, 1 Oct. 2011, pp. 1357–1392., doi:10.1152/ physrev.00006.2011. 4. Hickok, G., “The Cortical Organization of Speech Processing: Feedback Control and Predictive Coding the Context of a Dual-Stream Model.” Journal of Communication Disorders, vol. 45, no. 6, 2012, pp. 393–402., doi:10.1016/j. jcomdis.2012.06.004.

GREY MATTERS | issue 16

5. Upadhyay, J., et al. “Effective and Structural Connectivity in the Human Auditory Cortex.” Journal of Neuroscience, vol. 28, no. 13, 2008, pp. 3341–3349., doi:10.1523/ jneurosci.4434-07.2008. 6. Griffiths, Timothy D., and Warren J. D.. “The Planum Temporale as a Computational Hub.” Trends in Neurosciences, vol. 25, no. 7, 11 Oct. 2002, pp. 348–353., doi:10.1016/ s0166-2236(02)02191-4. 7. Hickok, G., Bellugi, U., & Klima, E. S. (2001). Sign Language in the Brain. Scientific American, 284(6), 58-65. doi:10.1038/ scientificamerican0601-58 8. Neville, H. J., Bavelier, D., Corina, D., Rauschecker, J., Karni, A., Lalwani, A., . . . Turner, R. (1998). Cerebral organization for language in deaf and hearing subjects: Biological constraints and effects of experience. Proceedings of the National Academy of Sciences, 95(3), 922-929. doi:10.1073/ pnas.95.3.922 9. Fromkin, V. A. (1988). Sign Languages: Evidence for Language Universals and the Linguistic Capacity of the Human Brain. Sign Language Studies, 1059(1), 115-127. doi:10.1353/ sls.1988.0027 10. Campbell, R., MacSweeney, M., & Waters, D. (2008). Sign Language and the Brain: A Review. Journal of Deaf Studies and Deaf Education, 13(1), 3-20. doi: 10.1093/deafed/enm035. 11. Gell M., Murray R., Merritt. (2011). “The origin and evolution of word order.” Proceedings of the National Academy of Sciences of the United States of America. 108., doi: 17290-5. 10.1073/pnas.1113716108. 12. Dryer, M. S. “On the Six-Way Word Order Typology.” Studies in Language, vol. 37, no. 2, 2013, pp. 267–301., doi:10.1075/ sl.37.2.02dry 13. Bornkessel, I., and Schlesewsky, M., “The Extended Argument Dependency Model: A Neurocognitive Approach to Sentence Comprehension across Languages.” Psychological Review, vol. 113, no. 4, Oct. 2006, pp. 787–821., doi:10.1037/0033-295x.113.4.787. 14. Grossman, R. B., & Shepard-Kegl, J. A. (2006). To Capture a Face: A Novel Technique for the Analysis and Quantification of Facial Expressions in American Sign Language. Sign Language Studies, 6(3), 273-305. doi:10.1353/sls.2006.0018 15. Shen, W., et al. “The Roles of the Temporal Lobe in Creative Insight: an Integrated Review.” Thinking & Reasoning, vol. 23, no. 4, 2017, pp. 321–375., doi:10.1080/13546783.2017.130888. 16. Embick, D., et al. “A Syntactic Specialization for Brocas Area.” Proceedings of the National Academy of Sciences 97, no. 11 (2000): 6150-154. doi:10.1073/pnas.100098897. 17. Rogalsky, C., “Brocas Area, Sentence Comprehension, and Working Memory: an FMRI Study.” Frontiers in Human

Neuroscience, vol. 2, 2008, doi:10.3389/neuro.09.014.2008. 18. Macsweeney, M., et al. “Phonological Processing in Deaf Signers and the Impact of Age of First Language Acquisition.” NeuroImage, vol. 40, no. 3, 2008, pp. 1369–1379., doi:10.1016/j.neuroimage.2007.12.047.

CHANGING FOCUS: ADHD IN WOMEN by Sophia Anderson, art by Sarah Wells | page XX 1. Guelzow, B. T., Loya, F., & Hinshaw, S. P. (2016). How Persistent is ADHD into Adulthood? Informant Report and Diagnostic Thresholds in a Female Sample. Journal of Abnormal Child Psychology, 45(2), 301-312. doi:10.1007/ s10802-016-0174-4 2. Waite, R. (2007). Women and attention deficit disorders: A great burden overlooked. Journal of the American Academy of Nurse Practitioners, 19(3), 116-125. doi:10.1111/j.1745-7599.2006.00203.x 3. Valera, E. M., Brown, A., Biederman, J., Faraone, S. V., Makris, N., Monuteaux, M. C., . . . Seidman, L. J. (2010). Sex Differences in the Functional Neuroanatomy of Working Memory in Adults With ADHD. American Journal of Psychiatry, 167(1), 86-94. doi:10.1176/appi.ajp.2009.09020249 4. Moldavsky, M., Groenewald, C., Owen, V., & Sayal, K. (2012). Teachers’ recognition of children with ADHD: Role of subtype and gender. Child and Adolescent Mental Health, 18(1), 18-23. doi:10.1111/j.1475-3588.2012.00653.x 5. Dupuy, F. E., Clarke, A. R., Barry, R. J., Mccarthy, R., & Selikowitz, M. (2016). Women are different to men: EEG differences in DSM-5 Adult Attention-Deficit/Hyperactivity Disorder. International Journal of Psychophysiology, 108, 6. doi:10.1016/j.ijpsycho.2016.07.018 6. Hermens, D. F., Williams, L. M., Lazzaro, I., Whitmont, S., Melkonian, D., & Gordon, E. (2004). Sex differences in adult ADHD: A double dissociation in brain activity and autonomic arousal. Biological Psychology, 66(3), 221-233. doi:10.1016/j. biopsycho.2003.10.006 7. Solberg, B. S., Halmøy, A., & Engeland, A. (2017). Gender differences in psychiatric comorbidity: A population-based study of 40 000 adults with attention deficit hyperactivity disorder. Acta Psychiatrica Scandinavica, 137(3), 176-186. doi:10.1111/ acps.12845 8. Cortese, S., Faraone, S. V., Bernardi, S., Wang, S., & Blanco, C. (2016). Gender Differences in Adult Attention-Deficit/ Hyperactivity Disorder. The Journal of Clinical Psychiatry, 77(04). doi:10.4088/jcp.14m09630

GREY MATTERS | issue 16

REFERENCES 9. Chen, M., Hsu, J., & Huang, K. (2018). Sexually Transmitted Infection Among Adolescents and Young Adults With Attention-Deficit/Hyperactivity Disorder: A Nationwide Longitudinal Study. Journal of the American Academy of Child & Adolescent Psychiatry, 57(1), 48-53. doi:10.1016/j. jaac.2017.09.438 10. Ahmad, S., Hinshaw, S. P., & Owens, E. (2016). 41.2 Adult Functional And Psychiatric Outcomes Among Women With Childhood Attention-Deficit/hyperactivity Disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 55(10). doi:10.1016/j.jaac.2016.07.361 11. Dalsgaard, S., Dr, Ostergaard, S., Dr, Leckman, J., PhD, Mortensen, P., PhD, & Pedersen, M., MSc. (2016). Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: A nationwide cohort study. The Lancet. doi:https://doi.org/10.1016/S0140-6736(14)61684-6

GREY MATTERS | issue 16

Grey Matters Journal is funded, in part, by the generous support of the departments of Pharmacology, Psychology, Physiology & Biophysics, the Neurobiology major, and the College of Arts & Sciences at the University of Washington. We are also extremely grateful for the contributions of our readers. Your donations make this publication possible. To support Grey Matters and further our mission, visit: www.greymattersjournal.com