Brain Imaging Center Second Annual Symposium

October 7th, 2015 Davis Auditorium

Brain Imaging Center

Second Annual Symposium

The Leon and Norma Hess

Center for Science and Medicine

1470 Madison Ave. New York, NY, 10029

https://bic.mssm.edu

@bic_ismms

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The Brain Imaging Center at Icahn School of Medicine at Mount Sinai

Davis Auditorium (2nd floor) Hess Center for Science and Medicine

October 7, 2015

COFFEE, REGISTRATION AND POSTER SET-UP

8:30am – 9:00am

2nd floor & Seminar Room B

Free registration: https://bic.mssm.edu/blog/bicday/bicdayregistration/

OPENING REMARKS

9:00am – 9:30am

Rita Z. Goldstein PhD (Chief, Brain Imaging Center, ISMMS)

9:30am – 9:45am

Zahi A. Fayad PhD (Director, Translational and Molecular Institute, ISMMS)

KEYNOTE ADDRESS

9:45am – 10:45am

Wilson Compton MD (Deputy Director, National Institute on Drug Abuse)

‘An Update From NIDA’

10:45AM – 11:15AM COFFEE BREAK

11:15 - 12:15 SESSION 1: TECHNICAL INNOVATION MODERATORS: PRITI BALCHANDANI & JUNQUIAN (GORDON) XU

Rebecca Feldman - 7T imaging of patients with focal epilepsy who appear non-

lesional in diagnostic 1.5T and 3T MRI scans: first results (POSTER #7)

Benjamin Ely - Resting-state functional connectivity of the human habenula and its

possible role in depression (POSTER #5)

Rafael O’Halloran - U-fiber quantification in non-lesional epilepsy (POSTER #6)

Alan Seifert - Ultra-high field brainstem and cervical spinal cord imaging

Prantik Kundu - Multi-echo characterization of phasic effects of anesthesia in the

non-human primate brain (POSTER #8)

12:15 – 1:30 LUNCH

1:30 – 2:30 SESSION 2: COGNITIVE INTERVENTIONS MODERATORS: MUHAMMAD PARVAZ & ANNA ZILVERSTAND

Bryan Denny - Can people be trained to be better emotion regulators? Evidence that

longitudinal reappraisal training reduces self-reported negative emotion and amygdala

activity and increases prefrontal cortex activity in borderline personality disorder

patients

Pias Malaker - Cognitive reappraisal reduces drug-related attention-bias in cocaine

addicted individuals: an eye tracking study (POSTER #24)

Nicolas Van Dam - A novel potassium-channel modulator decreases depressive

symptomatology and increases reward response in major depressive disorder

(POSTER #26)

2:30 – 3:30 SESSION 3: MULTIMODAL AND CONNECTIVITY MODERATORS: PRANTIK KUNDU & SCOTT MOELLER

Laurel Gabard-Durnam - Stimulus-elicited connectivity influences future resting-state

connectivity in development

Seán Froudist Walsh - Prematurity-related brain injury leads to altered dopamine

function and whole brain connectivity in adult life

Anna Zilverstand - Disruption of the hubs of the connectome in cocaine addiction

3:30 -3:45 CONCLUDING REMARKS (RITA Z GOLDSTEIN PHD)

3:45 - 6:30 POSTER SESSION WITH WINE AND CHEESE RECEPTION

https://bic.mssm.edu/blog/bicday/bicdayregistration/

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Dr. Goldstein is a Professor of Psychiatry with a secondary appointment in the Department of

Neuroscience at the Icahn School of Medicine at Mount Sinai (ISMMS) in NY. Dr. Goldstein is

chief of the Brain Imaging Core (BIC) at ISMMS; she also directs the NARC

(Neuropsychoimaging of Addiction and Related Conditions) research group that uses

multimodality functional neuroimaging methods to explore the neurobiological basis of impaired

cognitive and emotional functioning in human drug addiction and other disorders of self-control.

An important application of this research is to facilitate the development of intervention

modalities that would improve treatment outcome in drug addiction and other chronically

relapsing disorders of self-regulation.

Nationally and internationally known for her neuroimaging and neuropsychological studies in

drug addiction, Dr. Goldstein formulated a theoretical model known as Impaired Response

Inhibition and Salience Attribution (iRISA). The model uses multiple neuroimaging modalities—

including MRI, EEG/ERP, PET and neuropsychological tests—to explore the neurobiological

underpinnings of iRISA in drug addiction and related conditions. Her work has contributed to the

development of relevant machine-learning algorithms for innovative analyses applied to this

multidimensional data set. Dr. Goldstein’s interests also include pharmacological fMRI,

neurofeedback using Brain Computer Interface, and brain stimulation. She has also been

exploring the contribution of individual differences, including polymorphisms in monoaminergic

genes, to addiction and aggression, with a focus on the neural mechanisms underlying

reinforcement learning, risk-taking and extinction, choice and decision-making, and self-

awareness and insight into severity of illness.

Dr. Goldstein received her B.A. degree (double major in Psychology and French), cum laude,

from Tel Aviv University, Israel, in 1992. She received her Ph.D. degree in Health Clinical

Psychology, with award of academic merit, from the University of Miami, FL, in 1999, after

completing a yearlong internship in clinical neuropsychology at the Long Island Jewish Medical

Center, NY. She then completed her post-doctorate training on a fellowship on Brain Imaging

and Alcohol Abuse from the National Institutes of Health, under the mentorship of Nora D.

Volkow (director of NIDA). Dr. Goldstein received her license in clinical psychology in 2002. Dr.

Goldstein became Assistant Scientist at the medical research department at Brookhaven

National Laboratory in 2002, advancing to the Associate position in 2004, and to a Scientist

Rita Z. Goldstein, PhD Professor of Psychiatry and Neuroscience Chief, Brain Imaging Center (BIC) Chief, Neuropsychoimaging of Addiction and Related Conditions (NARC) Research Program Icahn School of Medicine at Mount Sinai, New York, NY [email protected]

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position in 2006; tenure was awarded in 2008. Dr. Goldstein moved to the Icahn School of

Medicine in January 2013. Dr. Goldstein is also an affiliate in the departments of psychology

and biomedical engineering at State University of New York at Stony Brook. She has authored

or co-authored numerous well-cited peer-reviewed manuscripts and book chapters, focusing on

the role of the prefrontal cortex in addiction. She received multiple awards including the

prestigious Joel Elkes Research Award in 2012 and the Jacob P. Waletzky Award in 2013

(where she is now serving as member on the selection committee), becoming fellow of the

American College of Neuropsychopharmacology (ACNP) in January 2015. Goldstein’s research

has been independently funded by several federal and private agencies (including NIDA, NIMH,

and NARSAD). She is currently MPI (with BJ Casey of Weill Cornell) on the landmark study that

has been launched by the NIH, the Adolescent Brain Cognitive Development (ABCD) Study that

will follow approximately 10,000 children beginning at ages 9 to10, before they initiate drug use,

through the period of highest risk for substance use and other mental health disorders.

The creative and translational research headed by Dr. Goldstein has been recognized

throughout the field. Among recent highlights are invited talks at the EBBS-EBPS Joint Meeting,

Verona, Italy; the Gordon Conference on Alcohol & the Nervous System: Molecules, Cells,

Circuits and behavior, in Galveston, TX; and “Addiction, in theory”, meeting of the minds on

adiction, learning and decision-making in London, UK. Rita Goldstein will also chair a session at

the upcoming Society for Neuroscience on “Novel ideas and tools to enhance the

neurobiological study of drug addiction with an eye towards intervention development and

biomarker identification”, in Chicago, IL.

Dr. Goldstein became Member of the NIH Neural Basis of Psychopathology, Addictions and

Sleep Disorders (NPAS) Study Section in 2015. Mentorship of students is also of her highest

priorities. Over the years, she has mentored numerous trainees, spanning junior research

faculty, post-doc fellows to graduate, undergraduate and high-school students. Several of her

trainees received as PIs training grants from the NIH (including F32 and K01) moving on to

receiving independent funding as PIs. One of her senior PhD students was winner of the 2012

Basic Psychological Science Research Grant from APAGS. Her trainees have published >20 1st

authorship manuscripts in prestigious psychiatry and neuroscience journals (including JAMA

Psychiatry, J Neurosci, Brain, Biological Psychiatry, Cerebral Cortex, etc.).

As BIC chief Dr. Goldstein is striving to facilitate optimized research use of ISMMS’s state-of-

the-art brain imaging facilities at the Translational and Molecular Imaging Institute (TMII).

Adopting a translational (3T, 7T, PET/MR; human and non-human imaging), developmental and

cross-generational familial approach, BIC has been developing a standardized processing

pipelines to acquire, analyze and manage a comprehensive set of brain scans across a myriad

of neuropsychiatric disorders with the goal of accelerating the development of large-scale gene-

brain-behavior datasets essential for revolutionizing our understanding of the brain.

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Dr. Fayad serves as professor of Radiology and Medicine (Cardiology) at the Mount Sinai School of Medicine. He is

the founding Director of the Translational and Molecular Imaging Institute; Vice chair for Research, Department of

Radiology at the Icahn School of Medicine at Mount Sinai. Dr. Fayad’s interdisciplinary and discipline bridging

research - from engineering to biology and from pre-clinical to clinical investigations - has been dedicated to the

detection and prevention of cardiovascular disease with many seminal contributions in the field of multimodality

biomedical imaging (MR, CT, PET and PET/MR) and nanomedicine. He has authored more than 300 peer-reviewed

publications (h-index of 67 accessed 01/31/2015 on Thomson Reuters Web of Science), 50 book chapters, and over

400 meeting presentations. He is currently the Principal Investigator (PI) of four federal grants/contracts funded by

the National Institutes of Health’s National Heart, Lung and Blood Institute and National institute of Biomedical

Imaging and Bioengineering with a large award from NHLBI to support the Program of Excellence in Nanotechnology.

He is also PI on three new NIH sub-contracts with UCSD, Columbia and the Brigham and Women’s Hospital. In

addition, he serves as Principal Investigator of the Imaging Core of the Mount Sinai National Institute of Health

(NIH)/Clinical and Translational Science Awards (CTSA). He is a PI on a project part of the Strategically Focused

Prevention Research Network Center grant project funded by the American Heart Association (AHA) to promote

cardiovascular health among high-risk New York City children, and their parents, living in Harlem and the Bronx.

Moreover, he currently leads four pharmaceutically funded multicenter clinical trials for the evaluation of novel

cardiovascular drugs.

He is Associate Editor for the Journal of the American College of Cardiology Imaging (JACC Imaging), Section Editor

for Journal of the American College of Cardiology (JACC) and Consulting Editor for Arteriosclerosis Thrombosis and

Vascular Biology (ATVB) and past associate Editor of Magnetic Resonance in Medicine (MRM). In 2013, he became

a Charter Member, NIH Center of Scientific Review, Clinical Molecular Imaging and Probe Development Study

Section. In 2015, he chaired the Scientific Advisory Board of the Institut National de la Santé et de la Recherche

Médicale (INSERM) PARCC program at the HEGP in Paris. In 2015,

Dr. Fayad had his engineering trainings at Bradley University (BS, Electrical Engineering ’89), the Johns Hopkins

University (MS, Biomedical Engineering ‘91) and at the University of Pennsylvania (PhD. Bioengineering ’96). From

1996 to 1997 he was junior faculty in the Department of Radiology at the University of Pennsylvania. In 1997 he

joined the faculty at Mount Sinai School of Medicine.

Dr. Fayad is the recipient of multiple prestigious awards. In 2007 he was given the John Paul II Medal from Krakow,

Poland in recognition for the potential of his work on humankind. As a teacher and mentor, Dr. Fayad has been also

extremely successful. He has trained over 40 postdoctoral fellows, clinical fellows and students. His trainees have

received major awards, fellowships, and positions in academia and industry. In 2008, he received the Outstanding

Teacher Award from the International Society of Magnetic Resonance in Medicine (ISMRM) for his teaching on

cardiovascular imaging and molecular imaging. In 2009 he was awarded the title of Honorary Professor in

Nanomedicine at Aarhus University in Denmark. Recently, he was one of opening speakers at the 2011 97th Scientific

Assembly and Scientific meeting of the Radiological Society of North America (RSNA). In 2012, he was invited to

give the Henry I Russek Lecture at the 45th Anniversary of the ACCF New York Cardiovascular Symposium. In 2013,

he was elected Fellow of the International Society of Magnetic Resonance In Medicine, Magnetic Resonance

Imaging, received a Distinguished Reviewer from Magnetic Resonance in Medicine and was selected as an Academy

of Radiology Research, Distinguished Investigator In 2014 he received the Centurion Society award from his alma

matter (highest award) Bradley University for his bringing national and international credit to his alma matter. In

2014, he received the Editor’s Recognition Award, from the Journal Radiology. In 2015, he was the Dr. Joseph

Zahi A. Fayad, PhD, FAHA, FACC, FISMRM Mount Sinai Endowed Professor in Medical Imaging and

Bioengineering

Professor of Radiology and Medicine (Cardiology)

Director, Translational and Molecular Institute

Vice chair for Research, Department of Radiology

Icahn School of Medicine at Mount Sinai, New York, NY

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Dvorkin Memorial Lecturer at the Cardiac Research Day of the Mazankowski Alberta Heart Institute, University of

Alberta, Edmonton, Canada. In 2015, he became the Mount Sinai Endowed Professor in Medical Imaging and

Bioengineering. The Mount Sinai Professorships were established in 2007 by the Mount Sinai Boards of Trustees to

honor the achievements and contributions of some of Icahn School of Medicine’s most outstanding faculty. A total of

eight Mount Sinai Professorships have been awarded to date.

He is married to Monique P. Fayad, MBA and is the proud father of Chloé (13 year old) and Christophe (9 year old)

and after spending seven years in Manhattan now lives in Larchmont, runs in Central Park and participates regularly

in New York Road Runners races. He also enjoys regular sailing and stand-up paddling in Larchmont, New York,

Connecticut, Rhode Island, Cape Cod, Martha’s Vineyard, Nantucket, Caribbean Islands and beyond.

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Wilson Compton, M.D., M.P.E., a nationally known

expert on the causes and prevention of drug abuse, is the

Deputy Director of the National Institute on Drug Abuse (NIDA,)

part of the National Institutes of Health.

Dr. Compton served as the Director of NIDA’s Division of

Epidemiology, Services and Prevention Research since 2002. As

Division Director, he managed a complex research program of

national and international scope addressing the extent and

causes of drug abuse and the development of effective

prevention strategies. He has also coordinated innovative

research designed to strengthen addiction treatment services through improved organizational and

financial infrastructure. In addition, Dr. Compton has been a member of the DSM-5 Task Force and the

Substance Use Disorders Workgroup for the past five years.

"I look forward to working with Dr. Compton as NIDA responds to growing challenges in the substance

abuse research field," said NIDA Director Dr. Nora D. Volkow. "In more than a decade as a Division

Director here at NIDA, he has built a formidable team supporting research into the extent and causes of

substance abuse, with a strong focus on tobacco, prescription and illicit drug abuse. His passion is

unwavering, and his enthusiasm to use science to find improved approaches to substance abuse

management will inspire us all."

Recently, Dr. Compton has been leading an effort jointly sponsored by NIDA and the Food and Drug

Administration’s Center for Tobacco Products to field a large scale longitudinal population study to

assess the impact of new tobacco regulations. This landmark study is expected to include over 50,000

persons in the U.S. ages 12 and older with yearly data collection from study participants, including both

surveys and biological assessments of tobacco exposures, risk factors and health outcomes. He will

continue to be involved in this effort in his new role.

In October 2013, Dr. Compton was one of ten people to receive the Health and Human Services

Secretary’s Award for Meritorious Service, which recognizes employees for their sustained excellence

and for inspiring others to improve their performance. Dr. Compton was recognized for outstanding

cross-agency collaborations, linking NIDA with multiple Health and Human Services and outside agencies

to reduce tobacco use and prescription drug abuse, and to improve substance abuse prevention and

treatment systems.

Prior to joining NIDA, Dr. Compton was Associate Professor of Psychiatry and Director of the Master in

Psychiatric Epidemiology Program at Washington University in Saint Louis as well as Medical Director of

Addiction Services at the Barnes-Jewish Hospital in Saint Louis. Dr. Compton received his undergraduate

education from Amherst College. He attended medical school and completed his residency training in

psychiatry at Washington University.

Connectivity and Multimodal Imaging

Stimulus-elicited connectivity influences future resting-state connectivity in

development

L. Gabard-Durnam*, D.G. Gee* , B. Goff, J. Flannery, E. Telzer, K. Humphreys, D. Lumian, D.S. Fareri,

C. Caldera & N. Tottenham

Although the functional architecture of the brain is indexed by resting-state connectivity networks, little is

currently known about the mechanisms through which these networks assemble into stable mature

patterns. The current study examined how both stimulus-driven and resting-state functional connections of

the human brain emerge over development at the systems level to form the robust connectivity observed in

adulthood. Using a sequential design following 4-23 year olds over a 2-year period, we examined the

predictive associations between stimulus-driven and resting-state connectivity in amygdala and medial

prefrontal cortex (mPFC) circuitry as an exemplar case (given its protracted developmental timeframe). Age-

related changes in amygdala functional connectivity converged on the same region of mPFC when elicited

by emotional stimuli and when measured at rest. Prospective analyses showed that the magnitude of an

individual’s stimulus-driven connectivity unidirectionally predicted resting-state functional connectivity two

years later, over and above previous resting-state measures, age, and motion indices. These findings suggest

that resting-state functional architecture may arise from phasic patterns of functional connectivity elicited

by environmental stimuli over the course of development on the order of years.

Page 7Second Annual BIC Symposium October 7 2015


Prematurity-related brain injury leads to altered dopamine function and

whole brain connectivity in adult life.

Seán Froudist-Walsh 1,2,3 Vyacheslav Karolis 2 Michael Bloomfield 3 Flavio Dell'Acqua 2

Federico Turkheimer 2 Shitij Kapur 2 Robin Murray 2 Oliver Howes 2,3* Chiara Nosarti 2*

1 Icahn School of Medicine at Mount Sinai

2 Institute of Psychiatry, King's College London

3 MRC Clinical Sciences Centre, Imperial College London

*contributed equally to this work

The dopaminergic system is involved in the development of functional cognitive networks during normal

neurodevelopment. Converging evidence has identified cognitive deficits and altered structural connectivity

in individuals born very preterm (VPT). We hypothesized that presynaptic dopamine synthesis capacity

would be altered in the caudate nucleus, which is a common site of injury in these individuals and that this

would be related to altered development of whole-brain structural networks.

One hundred and sixteen individuals (56/60 from the VPT/control groups, respectively) underwent

structural and diffusion-weighted MRI scanning on a 3T GE Signa scanner (GE). Thirty-eight individuals also

underwent F-DOPA PET scans on a Siemens ECAT/EXACT3D PET scanner.scans (25/13 from VPT/Control).

Dopamine synthesis capacity (Ki) was assessed in the caudate nucleus. Whole-brain structural connectivity

matrices were created using damped Richardson-Lucy spherical deconvolution tractography, the rich club

index of brain organisational structure was assessed and the effect of lesions to randomly selected

connections on the brainâ€™s connectional structure was quantified.

VPT adults had reduced presynaptic dopamine synthesis capacity in the caudate (p = 0.011). Individuals born

VPT had a higher rich club index than controls. Simulated lesion analysis and logistic regression classification

revealed an altered role of fronto-basal ganglia connections in preterm, with 75% classification accuracy on

this measure alone.

Dopamine synthesis capacity in the caudate was negatively correlated with rich club index (r = -0.375, p =

0.020) and with connectivity-based classifier confidence (r = -0.565, p = 0.0002).

This is the first study in humans to show that early brain injury can affect the dopamine system in

adulthood. This is also the first study to show a strong relationship between dopamine function and altered

neurodevelopment of whole-brain connectivity.



Disruption of the hubs of the connectome in cocaine addiction

Zilverstand 1, O’Halloran 1,2, Kundu 1,2, Parvaz 1, Gan 1, Alia-Klein 1, Goldstein 1

1 Department of Psychiatry, Mount Sinai

2 Department of Radiology, Mount Sinai

Brain networks or ‘connectomes’ are organized around highly connected processing ‘hubs’, which are

essential for efficient information processing. Disruptions of these hubs have been linked to impairments in

multiple neuropsychiatric disorders, demonstrating that structural microlesions in hub regions predict

disruptions in resting-state functional connectivity. We therefore aim to investigate if the connectome in

cocaine addiction shows disruptions specifically in brain processing hubs, and if these disruptions are

predicted by structural microlesions. We acquired structural, diffusion-weighted and functional resting-state

data in cocaine addicted individuals (n=30) and healthy controls (n=33), matched on race, gender and

intelligence. Per individual, a whole-brain functional connectome was derived from resting-state data by

parcellating the data using an anatomical template and computing bivariate correlations between all

regions. A structural connectome was derived from diffusion-weighted data using the same template,

counting the number of fiber tracts between regions. To assess for regional microlesions, volume

differences within each anatomical region were computed by voxel-based morphometry. Functional and

structural connectomes of cocaine addicted were contrasted with controls’ (p<0.05, uncorrected). Cocaine

addicted individuals showed disruptions of resting-state connectivity in processing hubs, such as the

anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (dlPFC), hippocampus, putamen and caudate,

previously implicated across neuropsychiatric disorders. The ACC, dlPFC, and hippocampus also showed

disruption of the structural connectome. Ongoing work is to determine the impact of regional anatomical

abnormalities.


Technical Innovations

7T Imaging of patients with focal epilepsy who appear non-lesional in

diagnostic 1.5T and 3T MRI scans: first results

Rebecca E Feldman , Hadrien Dyvorne , Bradley N Delman , Madeline C Fields,

Lara V Marcuse and Priti Balchandani

Objective: Magnetic resonance imaging (MRI) plays a vital role in the preoperative localization and

characterization of epileptogenic abnormalities. We report the results of a study designed to assess the

value of 7 Tesla (7T) MRI to reveal epileptogenic foci in patients with focal epilepsy who have non-lesional

clinical MRI scans. Non-invasive localization of the seizure focus would assist in surgical planning as well as

facilitate a better understanding of the disease.

Methods: 20 patients with focal epilepsy, who were non-lesional at clinical field strengths and 15 healthy

controls, were recruited for the 7T imaging study. The MRI protocol consisted of: 4 sequences acquired

perpendicular to the hippocampus: MP-RAGE, MP2RAGE, T2 TSE, and FLAIR; and 2 sequences acquired

axially: Susceptibility weighted imaging (SWI) and T2 TSE. The images were read by a neuroradiologist, and

the findings were reported to the epileptologists.

Results: A total of 6 patients were found to have significant abnormalities likely related to their epilepsy.

The information provided by the SWI sequence was instrumental in guiding more targeted inspection of the

other structural images and aiding in lesion identification. In 2 of these patients, the findings directly

impacted the surgical plan and the post-surgical prognosis. There were multiple other findings of

questionable significance found in both patients with epilepsy and healthy controls.

Conclusion: The information revealed by the improved resolution and contrast provided by the 7T scanner

will be valuable in improving surgical planning for epilepsy and in providing new insights into the etiology of

the disease.

Poster

# 7



Resting-state functional connectivity of the human habenula

and its possible role in depression

Benjamin A. Ely, Junqian (Gordon) Xu, Joo-won Kim, Wayne K. Goodman, Kyle A. Lapidus,

Vilma Gabbay, Emily R. Stern

Introduction: The habenula (Hb) plays an important role in reward and punishment processing in many

species by inhibiting midbrain monoamine signaling; in particular, Hb-mediated decreases in ventral

tegmental area (VTA) dopamine release are associated with depressive phenotypes. However, the small size

of the Hb has limited its in vivo characterization to date. Using a unique, high-resolution neuroimaging

dataset, we therefore examined Hb resting-state whole-brain functional connectivity and its relationship to

depressive symptomatology.

Methods: Data were acquired from 50 healthy young adults (25 high, 25 low depression scores) in the

Human Connectome Project public release. A novel semi-automated segmentation and anatomical-to-

functional resolution interpolation approach was used to generate seeds for connectivity analyses.

Connectivity maps were generated for the entire cohort and contrast of high vs. low depression groups.

Results: In the entire cohort, the Hb exhibited functional connectivity with the VTA, brainstem, posterior

insula, dorsolateral prefrontal cortex, and posterior cingulate, as well as several thalamic and sensorimotor

areas. High and low depression groups differed in Hb connectivity with several cortical regions, including the

posterior and dorsal anterior cingulate.

Conclusions: Consistent with animal electrophysiological research, we found Hb functional connectivity with

the VTA and brainstem, supporting the notion of a similar role regulating monoamine circuitry in humans.

The Hb also demonstrated connectivity with numerous executive control and sensorimotor processing

areas. Interestingly, subjects with high depression scores exhibited altered Hb connectivity with cingulate

regions previously linked to depression, suggesting the relationship between these regions as a potential

target for future research and treatment.

Poster

# 5



U-fiber quantification in non-lesional epilepsy

Rafael O’Halloran, Priti Balchandani

Introduction: In patients with non-lesional epilepsy it is challenging to identify the zone of epilepsy onset in

standard imaging approaches. Recent work suggests that it may be possible to determine the zone of

epilepsy onset by identifying areas with reduced density of u-fibers [1]. U-fibers, or subcortical arcuate

fibers, connect neighboring cortical region and provide inhibitory control. It is hypothesized that lack of

inhibition due to lower numbers of u-fibers may contribute to the onset of epilepsy in affected tissues.

Supporting this hypothesis, recent work in a epileptic baboons suggests that there is a lack of neurons in

motor areas that may be explained by lack of u-fibers in these areas.

Methods: Two control subjects and two patients with non-lesional epilepsy underwent 7T MRI consisting of

a T1-weighted MP2RAGE sequence and high-angular-resolved diffusion-weighted dMRI. Fiber orientation

distributions for tractography were obtained from the corrected diffusion-weighted images by spherical

deconvolution. Tractograpy was performed using the iFOD2 algorithm implemented in MRTRIX3 to obtain

100 million fibers seeded from the grey-white matter border. U-fibers were identified based on their length

being longer than 3 cm and the distance between the ends being shorter than their length over pi (Figure 1).

Quantitative U-fiber density maps were obtained by dividing track density maps of the u-fibers by track

density maps of all the tracks.

Results and Conclusion: Preliminary data suggest that lower densities of u-fibers may be present in patients

non-lesional epilepsy (Figure 2). Future work will be focused on quantitative assessment of the differences

in healthy controls and patients as well as quantifying asymmetries in u-fiber distributions to identify

epilepsy onset zones. When the clinical data become available we wil lbe able to compare predicted versus

actual epilepsy onset zones.

Poster

# 6



Ultra-high field brainstem and cervical spinal cord imaging

Alan C. Seifert, Bei Zhang, Joo-Won Kim, and Junqian Xu

The cervical spinal cord, together with supraspinal brainstem circuits, conveys important sensorimotor

information between the cortex and body. However, delineation of the brainstem nuclei and cervical spinal

cord grey matter, let alone examination of their functional roles, has been challenging at conventional field

strength due to their small sizes. Recently, we have designed and constructed a two-panel (anterior-

posterior) ultra-high field (7T) radiofrequency (RF) coil with 4 transceive (Tx/Rx) and 18 receive (Rx)

elements that overcomes the limitations of existing 7T cervical spinal cord coils, allows the peak RF transmit

power (B1+) to be localized near the spinal cord and brainstem, and achieves excellent receive sensitivity

and large superior-inferior coverage. To demonstrate the performance of this coil for 7T brainstem and

cervical spinal cord imaging, axial GRE images with 0.30 x 0.30 x 3.00 mm resolution were acquired at

multiple locations spanning from the midbrain to the distal medulla (Fig. 1) and C1 to C7 spinal cord

segments (Fig. 2) with exquisite anatomical detail. A sagittal GRE image of the brainstem and cervical spinal

cord was also acquired with a 300 x 197 mm field of view (FOV) at 0.78 x 0.78 x 3.00 mm resolution. B1+

efficiency was mapped using the double-angle method. Additionally, our two- sided 22 channel coil allows

focusing of peak B1+ to adapt to the depth of the subject’s cervical spinal cord beneath the body surface.

This coil array enables high-resolution structural and functional MRI covering both the brainstem and spinal

cord at 7T.



Multi-echo characterization of phasic effects of anesthesia in the non-human

primate brain

Prantik Kundu, Christienne Damatac, Jamie Nagy, Ciorana Roman Ortiz,

Seán Froudist Walsh, Paula Croxson

Introduction: Phasic brain activity is characterized by complex time courses expressing multiple frequencies

and transitions between frequency profiles over time (i.e. non-stationarity). In contrast, the brain activity

that can currently be studied using functional neuroimaging is evoked either by repetitive blocks or single

events, or heavily filtered time series of fixed frequency range (e.g. 0.01Hz-0.1Hz). Due to high levels of

noise including drift and head motion, activity time courses serve mainly as a basis for correlational analysis

and statistical parametric mapping of functional localization - not for directly characterizing temporal

activity. Realizing this key limitation, we implemented blood oxygenation level dependent functional MRI

(BOLD fMRI) with multi-echo acquisition for imaging NMR signal decay, such that signal validation and noise

reduction are offloaded into the decay domain and both space and time domains are freed for

characterization and analysis. We propose here to fully realize this methodology as a means for general

study of phasic brain activity.

Methods: We developed a strategy for imaging phasic activity at high-resolution and high signal-to-noise

ratio, using an innovative combination of ultra-high field MRI (7T), a new transmit receive-array head coil, a

new multi-band multi-echo functional MRI (fMRI) pulse sequence, and an advanced application of multi-

echo analysis to remove artifacts across the spectral range. This imaging strategy, called wide-spectrum

(WS)-fMRI was applied in an experiment to detect phasic activity from modulations in the depth of

isoflurane anesthesia in a macaque monkey model over a continuous hour of fMRI.

Results: Preliminary data demonstrated whole-brain WS-fMRI at 1.5mm isotropic spatial resolution and 1.8s

temporal resolution yielding temporal signal-to-noise ratio (tSNR) for BOLD time series being 300-700 (25th

to 75th percentiles) without spatial smoothing or temporal bandpass filtering. This compares to

conventional fMRI yielding tSNR of 60-100 after extensive filtering and smoothing. We then functionally

localized phasic activity as modulated by anesthesia, then used the differences in latencies between

regional cortical and subcortical phasic changes to assess hypotheses from prior meta-analyses on causal

mechanisms of anesthesia-induced loss of consciousness. We then design analyses for systematically

characterizing phasic activity using time-frequency transforms, then associated different phasic activity to

distinct temporal models.

Discussion: These innovations will greatly expand the domains of brain activity studied with fMRI, and open

a new frontier in the characterization of healthy brain function, disorders, and functional recovery.

Poster

# 8


Cognitive Interventions

Can people be trained to be better emotion regulators? Evidence that longitudinal

reappraisal training reduces self-reported negative emotion and amygdala activity

and increases prefrontal cortex activity in borderline personality disorder patients

Bryan T. Denny 1, Jin Fan 1,2,3, Xun Liu 4, Kevin N. Ochsner 5, Sarah Jo Mayson 1,

Liza Rimsky 1, Antonia McMaster 1, Heather Alexander 1, Antonia S. New 1,6,

Marianne Goodman 1,6, Larry J. Siever 1,6, Harold W. Koenigsberg 1,6

1 Department of Psychiatry, Icahn School of Medicine at Mount Sinai

2 Department of Neuroscience, Icahn School of Medicine at Mount Sinai

3 Department of Psychology, Queens College, City University of New York

4 Institute of Psychology, Chinese Academy of Sciences

5 Department of Psychology, Columbia University

6 James J Peters VA Medical Center

Substantial research has indicated the effectiveness of engaging reappraisal in order to reduce self-reported

negative emotion via recruitment of prefrontal cortex and down-regulation of amygdala activity in

individual sessions. However, there has been far less research into whether focused longitudinal training in

reappraisal strategies can yield adaptive changes in brain and behavior over time, both in healthy

populations and in populations for whom emotion regulation often fails. Borderline personality disorder

(BPD) is the prototypical disorder involving emotion dysregulation. In this study, we assessed whether and

via what neural mechanisms BPD patients could be trained to enhance reappraisal and reduce self-reported

negative emotion via psychological distancing, which involves viewing stimuli as an impartial, objective

observer. At each of five sessions, 14 BPD and 16 healthy control (HC) participants were shown negative

social emotional images and given instructions to reappraise their responses to half ('Reappraise') and to

look and respond naturally at the other half ('Look'). Emotion self-reports were obtained after each image

presentation. Sessions 1-5 were spaced 1-2 days apart and afforded training through practice on novel

images. fMRI data were acquired at Sessions 1 and 5. We found that BPD patients showed reductions in

negative emotion self-reports over time. BPD patients also showed increasing attenuation of amygdala

activity due to reappraisal (Reappraise Negative) relative to responding naturally (Look Negative) over time

in a manner not attributable to habituation. Further, with training, BPD patients showed increased

reappraisal-related recruitment of dorsolateral prefrontal cortex, a region engaged during reappraisal in

HC's in this and prior studies. Taken together, these data represent the first evidence that longitudinal

reappraisal training can normalize reappraisal-related neural activity in any patient population.


Cognitive Interventions

Cognitive reappraisal reduces drug-related attention-bias in cocaine addicted

individuals: an eye tracking study

Pias Malaker, Muhammad A. Parvaz, Nelly Alia-Klein, Rita Z. Goldstein

Enhanced attention afforded to drugs and drug-related cues, and at the expense of other reinforcers, is a

common manifestation in drug addiction. Reappraisal techniques have successfully been used to reduce this

drug-related attention-bias among addicted individuals. However, little is known about the effects of

reappraisal on gaze duration (GD), a direct measure of initial and motivated attention to salient stimuli, and

on subsequent drug craving in individuals with cocaine use disorder (iCUD). In this study, 21 iCUD and 21

healthy controls (HC) passively viewed drug and neutral pictures and were instructed to either continue

looking at the cue (‘look’) or decrease their emotional reactivity to the cue using cognitive reappraisal

(‘reappraise’). Following each instructional segment, side-by-side images of the drug and neutral cues were

presented while GD was recorded; craving was assessed by self-reports of drug wanting every fourth trial.

Results indicate that unlike HC, iCUD demonstrated marginally diminished GD to drug-related cues (relative

to neutral cues) following the ‘reappraise’ compared to the ‘look’ condition (p=0.1); such greater reduction

in attention-bias was associated with reduced wanting of cocaine, specifically following the ‘reappraisal’

relative to ‘look’ trials, and with less withdrawal symptoms. Taken together, these findings indicate that

cognitive reappraisal may reduce craving by decreasing GD directed at drug-related cues, and that this

effect could be best utilized in interventions with iCUD who are outside of acute withdrawal.

Poster

# 24

A novel potassium-channel modulator decreases depressive symptomatology

and increases reward response in major depressive disorder.

Nicholas T. Van Dam, Marin Kautz, Allyson K. Friedman, Ming-Hu Han, Eric J. Nestler,

Dennis S. Charney, Dan V. Iosifescu, James W. Murrough

Preclinical models have shown that an abnormally elevated firing rate of dopamine neurons in the ventral

tegmental area, projecting to the nucleus accumbens/ventral striatum, characterizes susceptibility to

depression-like behavior, while resiliency is characterized by homeostatic up-regulation of KCNQ-type

potassium channels. The potentiation of KCNQ channels counters the maladaptive effects of stress, and thus

may be a fundamentally novel therapeutic approach to stress-related conditions, like depression. In

preliminary analysis of an ongoing, open-label trial of Ezogabine, a selective modulator of KCNQ ion

channels, 8 patients with depression (47±11 years; 75% male) completed an incentive flanker task (IFT),

while functional MRI data was acquired, before and after 10 weeks of pharmacotherapy. The IFT, much like

the monetary incentive delay task, permits examination of both the anticipatory and consummatory phases

of reward. Patients not only showed a significant, large decrease in depression on the Montgomery-Asberg

Depression Rating scale (T1-M=27.4±4.0, T2-M=15.1±8.6, t(7)=3.70, p=0.007, d=1.83), they also showed

reward-circuit increases from pre-treatment to post-treatment in neural response to both the anticipatory

and consummatory phases of reward. Notable changes were observed in the striatum, ventromedial

prefrontal cortex, and dorsal anterior cingulate cortex, among other regions. These results suggest that the

active up-regulation of KCNQ-type potassium channels, observed in resilient animals, may be a feasible

target for treating stress-related illness in humans.

Poster

# 26


Poster Session

A new BIC tool! Introducing Nipype neuroimaging pipelines

Anvi K. Vora, MD

Background: There are many brain imaging softwares, but different algorithms, file formats, capabilities.

Nipype is a lightweight, scriptable system, wraps multiple brain imaging softwares, with a common language

(as opposed to shell scripting, matlab, etc), made by developers at Harvard and MIT. We have made effort

toward making this resource available on Minerva for general use by the BIC community.

Subject matter: Nipype is made to combine the capabilities of various imaging softwares, including:

• AFNI

• SPM

• BRAINS

• Mrtrix

• Camino-TrackVis

• FSL

• Dcm2nii

• Camino

• FreeSurfer

• And more…

This presentation on Nipype will include a brief overview of its use, and some capability that it can provide

to the users.

Poster

# 1


Poster Session

Dimensional traits of psychosis associated with NMDA receptor

GRIN2B polymorphism: an exploratory candidate-gene association study

Anvi K. Vora, Antonia S. New, Erin A. Hazlett Qiaoping Yuan, Zhifeng Zhou, Colin Hodgkinson,

David Goldman, Larry J. Siever, Panos Roussos, M. Mercedes Perez-Rodriguez

Background: Schizotypy is a construct believed to capture the underlying genetic

vulnerability to schizophrenia. However, few studies have investigated the genetic underpinnings of

dimensional schizotypy. This is an exploratory case-control candidate gene association study examining the

relationship between single nucleotide polymorphisms (SNPs) and multiple schizotypy dimensions in a

sample enriched for dimensional schizotypy and schizotypal personality disorder.

Methods: 472 subjects were assessed with the Schizotypal Personality Questionnaire (SPQ). 1,536 SNPs

from 130 genes were genotyped using a custom Illumina SNP array chip. Principal component analysis was

used to cluster SPQ variables. Linear regression was performed using PLINK, to test for associations between

schizotypy symptoms and candidate SNPs. Logistic regression was used to test for associations between the

SNPs and the diagnosis of schizotypal personality disorder versus controls.

Results: A significant relationship was found between rs4763361 SNP that is positioned within the NMDA

receptor (GRIN2B), for dimensional schizotypy traits related to disorganized symptoms (p=1.358e-05), which

remained significant after Bonferroni Correction. There were no significant associations between any of the

SNPs and the categorical diagnosis of schizotypal personality disorder.

Conclusions: This study indicates that polymorphisms related to NMDA pathways may have an impact on

dimensional traits of psychosis, particularly related to disorganized symptomatology.

Poster

# 2


Poster Session

Hippocampus subfield segmentation at 7T MRI in patients with

major depressive disorder: first results

Judy Alper, Hadrien Dyvorne, Jason Bini, Bradley Delman, James Murrough,

Priti Balchandani

Major depressive disorder (MDD) is a disabling illness of very high prevalence worldwide. There is a need to

better understand the underlying pathophysiology of MDD for enhanced treatment design and efficiency.

Previous studies have shown an association between the volumes of hippocampus subregions and MDD.

Using the 7 Tesla MRI scanner to acquire the data for volumetric analysis can allow for more accurate

volumetric measurements due to higher contrast and resolution compared to lower field strength. This

study aims to demonstrate the feasibility of hippocampal subfield segmentation for MDD patients at 7T

using high-resolution anatomical T2-weighted MRI. We also perform a preliminary analysis to evaluate

differences in subfield volumes between healthy subjects and MDD patients. Five MDD patients (ages 40-55

years) and five healthy controls (ages 34-46 years) were enrolled in this study and underwent an MRI scan at

7T. Manual segmentation was performed in OsiriX, using high-resolution 7T T2 TSE (0.45x0.45x2 mm3)

images by the same trained image analyst. The subfields delineated were CA1, CA2 3, CA4 DG, choroid

plexus, inferior lateral ventricle (ILV), presubiculum, and subiculum. A comparison of the MDD patients to

the healthy controls was done in each of the seven subregion mean volumes and total hippocampus mean

volumes measured. P values were calculated to examine the significance of the volumetric differences. The

volumetric difference measured in the ILV has a significant p value and has a greater volume in patients

than controls. This measurement is supported by previous MDD studies and may suggest a link between

MDD and ILV dilation. Significant volumetric differences were not observed in the other hippocampus

subfields. Identifying a correlation between MDD and hippocampus subfield volumes can lead to new

biomarkers of the disease with applications in diagnostics and treatment.

Poster

# 3


Poster Session

Reliability of human habenula segmentation using myelin content

Joo-won Kim and Junqian Xu

Translational and Molecular Imaging Institute, Department of Radiology,

Icahn School of Medicine at Mount Sinai, New York, NY

The habenula, a pair of small nuclei located at the dorsal medial thalamus and next to the third ventricle, is

an important midbrain structure related to aversion and reward system regulation. Recently, we have

developed an objective semi-automated human habenula segmentation algorithm based on subcortical

myelin contrast. Here we evaluated the intra-scanner (i.e. test-retest) reliability of the proposed habenula

segmentation algorithm. Repeated T1w and T2w structural scans (0.7 mm isotropic resolution) from twenty-

seven healthy young adults were acquired in two different days from the Human Connectome Project (HCP).

Images were processed with the HCP PreFreeSurfer pipeline and myelin maps were generated using T1w to

T2w ratio. The previously proposed habenula segmentation algorithm, consisting of multi steps

(thresholding, region growing, geometric constraints, and partial volume estimation), was applied to

estimate habenula volumes. Relative differences were calculated. Twenty-six out of twenty-seven pairs of

data were successfully segmented (one subject’s T1w image had very low contrast). The mean ± standard

deviation of left/right habenula volumes of the test and retest data were 20.11 ± 3.11 / 20.36 ± 3.52 mm2

and 18.78 ± 3.33 and 19.64 ± 3.92 mm2, respectively (Fig. 1C). The relative differences of the test and retest

results for the left and right habenula were 16 ± 11% and 14 ± 10%, respectively. Our proposed habenula

segmentation based on subcortical myelin contrast achieves promising intra-scanner (test-retest) reliability.

Investigation of the reproducibility and accuracy of the proposed segmentation scheme could lead to

further optimization of the segmentation algorithm.

Poster

# 4

Dynamic brain functional connectivity with change-point estimation

Jaehee Kim (Duksung University), DuBois Bowman (Columbia University)

Functional magnetic resonance imaging (fMRI) data sets are large and characterized by complex

dependence structures driven by highly sophisticated neurophysiology and aspects of the experimental

designs. fMRI studies often include multiple sessions, and temporal dependencies may persist between the

corresponding estimates of mean neural activity. Further, spatial correlations between brain activity

measurements in different locations are often present in fMRI data. We develop a method that leverages

the special structure of our covariance model, enabling relatively fast and efficient change-point estimation.

Using our proposed method, we analyze fMRI data from a study of MDD patients.

Poster

# 9


Poster Session

Brain activity and connectivity associated with empathetic anticipation

of another’s pain

Tuyen Mallela, Tingting Wu, Thomas Zhou, Alexander Dufford, Tehila Eilam-Stock,

Matthew Yuen, Patrick R. Hof & Jin Fan

While the anticipation of self-directed pain has been well-studied, there is still limited information about the

anticipation of pain that is directed towards others. We used a combination of functional magnetic

resonance imaging and psychophysiological measures to examine the dissociation of neural and

physiological empathetic responses to the observation of another’s pain versus the anticipation of another’s

pain. Participants were presented with video clips of a hand or foot in situations of pain, anticipatory

(imminent) pain, and no pain, and they were asked to evaluate whether the person depicted was

experiencing pain or no pain while functional and physiological data were recorded. Results indicated that

both the observation and anticipation of pain in another recruited regions that are commonly attributed to

mentalization and perspective-taking, including the temporoparietal junction, anterior cingulate cortex,

anterior insula, and superior temporal sulcus, but that the observation of pain condition elicited stronger

activity in these areas. The most significant region that exhibited greater activity during the anticipation of

pain than during its observation was the posterior cingulate cortex (PCC). A region-of-interest analysis

showed that it was less deactivated than the other two conditions, and a psychophysiological interaction

analysis showed significant interactions between the PCC and precuneus.

Poster

# 10

Better prediction of Parkinson’s Disease using a new measure

of whole-brain network activity

Ben Cassidy, Daniel Drake, Victor Solo, DuBois Bowman

Non-invasive neuroimaging of brain activity has enormous potential to provide biomarkers for neurological

diseases, to identify disease onset before standard clinical symptoms are observed. One approach is to treat

brain activity as a network and identify abnormal interactions between brain regions. In this work we

demonstrate a new statistical framework to rigorously identify interactions between brain regions using

Functional Magnetic Resonance Imaging data. This task is challenging due to the large number of

interactions between regions encompassing the whole brain, the need to account for the complicated

physiological processes inherent in the brain, as well as the difficulty distinguishing between direct and

indirect interactions. Our method is the first to deal with all these issues simultaneously. Equally

importantly, our method is suitable for estimating brain activity networks from individual scanning sessions

of a single person, which would be necessary for future clinical applications. We show our method gives

remarkably improved performance in distinguishing between Parkinson’s Disease and healthy brain activity,

compared to the current standard method for identifying brain activity networks.

Poster

# 11


Poster Session

Multimodal imaging signatures of Parkinson’s Disease

F. DuBois Bowman 1, Daniel F. Drake 1 and Daniel E. Huddleston 2

1 Columbia University

2 Emory University

Parkinson's disease (PD) is a complex neurodegenerative disorder that manifests through hallmark motor

symptoms, often accompanied by a range of non-motor symptoms. There is a putative delay between the

onset of the neurodegenerative process, marked by the death of dopamine-producing cells, and the onset

of motor symptoms, creating an urgent need to develop biomarkers that may yield early PD detection.

Neuroimaging offers a non-invasive approach to examining the potential utility of a vast number of

functional and structural brain characteristics as biomarkers. We present a statistical framework for

analyzing neuroimaging data from multiple MRI modalities (including anatomical, structural, and functional

MRI) to determine features that reliably distinguish PD patients from healthy control (HC) subjects. Our

approach builds on elastic net to perform regularization and variable selection, but introduces additional

criteria designed to enhance parsimony and reproducibility. We apply our method to data from 42 subjects

(28 PD patients and 14 HC). Out of tens of thousands of possible features, we identify six distinct three-

feature models that reliably separate PD patients from HC, highlighting brain regions that are implicated in

the neurodegenerative PD process.

Poster

# 12

White matter pathways in 3 deep brain stimulation targets

for Parkinson’s Disease

Rafael O’Halloran, Brian Kopell

In deep brain stimulation (DBS) for the treatment of Parkinson’s Disease electrodes inserted near grey

matter targets, including the caudal zona incerta (cZI), subthalamic nucleus (STN) and globus pallidus

internus (GPi). It is increasingly recognized that proximity to key white matter pathways may be important

for efficacy and perhaps for avoiding unwanted side effects like gate impairment and cognitive impairment.

In order to better understand the white matter connectivity in these regions we performed tractography

from the target regions in 3 groups of patients with implants in the cZI, STN and GPi. Preliminary data from

the STN group show expected patterns of connectivity. Differences in connectivity can be appreciated from

preliminary data in subjects with 3 targets: cZI, STN and GPi. While more work is needed to determine how

to interpret and us this methodology in planning treatment, connectivity analysis appears to be a useful way

to reduce data complexity and present the most relevant features to surgeons.

Poster

# 13


Poster Session

A comprehensive probabilistic tractography study in sibling pairs

discordant for bipolar disorder

Emma Sprooten, Emma E Knowles, D Reese McKay, Samuel R Mathias, Jennifer Barrett,

Margaret S Brumbaugh, Stefanie Landa, Lindsay Cyr, Peter Kochunov, Anderson M Winkler,

Godfrey D Pearlson, Sophia Frangou, David C Glahn

Diffusion tensor imaging (DTI) studies have repeatedly shown reductions in fractional anisotropy (FA) in

bipolar patients and their unaffected siblings. Using TBSS, we have previously shown widespread FA

reductions in patients and their unaffected relatives. Here, we investigated whether similar effects can be

observed using probabilistic tractography of 18 major fiber tracts. Diffusion-weighted MR images were

acquired for 99 patients, 70 of their non-bipolar siblings and 56 healthy controls on a Siemens Allegra 3T

scanner (TR/TE=6300/81ms, 1.7x1.7x3.0mm, b=800s/mm2, 55 gradient directions). Images were

preprocessed using FSL tools. BedpostX was applied with a 2 fiber model. We applied TRACULA, a global

probabilistic tractography algorithm that uses Freesurfer segmentations to incorporate anatomical

knowledge in the prior probability function. Tract segmentations were visually checked those that clearly

deviated from their expected trajectory were excluded. Average FA was extracted from the 18 tracts. We

applied mixed model regressions with hemisphere and tract as within-subject factors, diagnostic group and

sex as fixed factor, and age and age2 as covariates. In the sibling-patient comparison, family was added as

additional within-subject factor. Considering all tracts simultaneously, there was an overall difference

between patients and controls (p=0.03, T=2.23). In separate mixed models for each tract, only FA in the

superior longitudinal fasciculus was significantly reduced in patients (p=0.005, T=2.95) at a Bonferroni-

corrected α. FA was not significantly reduced in siblings compared to controls in any of the tracts, although

was a trend for an effect in the corpus callosum (p=0.05; T=1.96). Our data confirm the presence of subtle

but global FA reductions in patients with bipolar disorder, which are most pronounced in the superior

longitudinal fasciculus. Unaffected siblings may display more subtle and more restricted reductions.

Poster

# 14


Poster Session

Does sex matter? A meta-analysis of higher cognitive function

Jamie Nagy, Christienne Damatac, Mark Baxter, Peter Rudebeck, Paula Croxson

The rates of psychiatric disorders are markedly different between men and women. Dysfunction within

brain structures involved in higher cognitive function, such as the hippocampus and prefrontal cortex, is

apparent in psychiatric disorders. These structures have also been suggested to differ in size between the

sexes indicating that such differences could contribute to differential rates of psychiatric disorders.

However, the paucity of data on sex differences in behavior and brain structure in animal models used to

investigate the neural mechanisms of neuropsychiatric disease makes it difficult to address the potential

contribution of sex to these disorders.

We carried out a re-analysis of behavioral data from a large cohort of macaque monkeys from two

behavioral tasks testing higher cognitive function and dependent on interactions between prefrontal cortex

and temporal cortex: one of episodic memory and one of strategy implementation. We combined data from

animals in several experiments tested under identical task conditions and examined the data by looking at

sex as a factor. Our analysis did not show an effect of sex on episodic memory (45 males, 11 females) or

strategy implementation (19 males, 6 females). We additionally carried out an anatomical analysis using

high-resolution T1-weighted structural MRI images acquired from a 3-Tesla scanner (12 males, 9 females).

Because we did not find sex differences in our tasks nor in hippocampal volume/whole brain volume ratios,

our research suggests that these behavioral and neuroanatomical measures may be employed in

experimental studies with macaques without concerns of confounding effects of sex.

Poster

# 15


Poster Session

Sex-differences in grey matter volume in cocaine use disorder:

a voxel-based morphometric study

Preston-Campbell, R.N., Gan, G., Zilverstand A., Moeller, S.J.,Parvaz, M.A.,

Alia-Klein, N., Goldstein, R.Z.

Structural imaging studies have demonstrated reductions in grey matter volume (GMV) in prefrontal cortical

(PFC) [including orbitofrontal cortex (OFC)] and subcortical limbic regions in individuals with cocaine use

disorders (iCUD). However, most research has focused on men. A more sex-balanced study could help clarify

the mechanisms underlying the differential severity of addiction in iCUD (women>men).

Twenty-two iCUD (13M/9F) and 25 demographically matched healthy controls (12M/13F) underwent MRI

(3T Skyra), providing T1-weighted anatomical images acquired with a 3D MPRAGE sequence. Baseline

craving was also assessed.

Independent and interactive effects of diagnosis and sex on GMV were examined using a whole-brain 2

(diagnosis: iCUD, control) x 2 (sex: M, F) ANOVA in SPM8. Follow-up comparisons were conducted using t-

tests within groups. Clusters with >20 contiguous voxels, with a Puncorr<0.005 search threshold, were

considered significant.

Consistent with prior studies, relative to healthy controls, iCUD had reduced GMV in the bilateral OFC.

Follow-up comparisons within groups showed: (A) Within females, iCUD had lower GMV than healthy

controls in the right superior and right mid frontal gyrus (BA 8,9) and left OFC (BA 11). Within men, iCUD had

lower GMV than healthy controls in the right ventromedial PFC. (B) Within iCUD, women had greater GMV

than men in the bilateral amygdala and dorsal anterior cingulate cortex (BA 24). In female iCUD only, such

higher left amygdala GMV correlated with more baseline craving, driven by a higher likelihood of using

cocaine in a drug environment.

This study suggests that OFC morphological differences between iCUD and healthy controls may be driven

by females. Within the iCUD, differences in the amygdala could be marking changes in the brain's

stress/alarm system, culminating in aversive states such as craving. Future longitudinal studies can test

whether such effects reflect a predisposition to drug use in women and/or morphologic changes secondary

to chronic drug use that are accentuated in women.

Poster

# 16


Poster Session

Vascular disease in cocaine addicted individuals

K. Bachi, V. Mani, R.Z. Goldstein, Z.A. Fayad, N. Alia-Klein

Cocaine, a powerful vasoconstrictor and a nonspecific voltage gated sodium channel blocker, induces an

immune response including cytokine elevations. Individuals with cocaine use disorder (iCUD) show

functional brain impairments that are potentially mediated by vascular pathology including inflammation.

We hypothesized that iCUD are prone to vascular inflammation despite having no history of vascular and/or

cardiovascular disease (CVD). Therefore, we imaged the common carotid arteries with PET/MR for

inflammation markers (18F-FDG) and anatomical indices (MR) in 10 iCUD (mean age, SE: 50.7, 1.6). Results

were compared with an older population at risk for CVD (64.6, .96). Individuals with CUD had inflamed

plaque in arteries measured by target-to-background ratio (TBR) [TBRmax, Right (mean, SE: 1.89, .12) Left

(1.7, .11); TBR â‰¥ 1.6 is considered inflamed plaque] and larger vessel wall area (mm2; 38.45, 1.48 versus

32.28, 1.43, t(8)=3.34, p=.01) and thickness (mm; 1.63, .03 versus 1.27, .04, t(8)=8.84, p<.001). These

markers correlated significantly with cocaine use indices where the more severe the CUD the greater the

carotid abnormalities (.53 â‰¤ r â‰¤ .81, p<.01). Thus, results demonstrate carotid disease markers in

iCUD and have clinical significance for combating silent disease progression. Given the importance to brain

perfusion (the carotid arteries channel the majority of blood flow to the brain), our future studies will

explore the associations between these carotid abnormalities with brain impairments in iCUD.

Poster

# 17

Structural MRI and PET in the diagnosis of chronic traumatic encephalopathy:

study of a retired NFL player

Mariel Pullman, Corey Fernandez, Jennifer Short, Karin Knesaurek, Ash Rafique,

Lale Kostakoglu, Barry Jordan, Wayne Gordon, Kristen Dams-O’Connor, James Stone,

Sam Gandy, Patrick Hof, Dara Dickstein.

Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease resulting from repetitive brain

trauma. CTE is currently diagnosed definitively postmortem, and studies are needed to facilitate detection

during life. We describe the clinical case of a 39-year-old retired National Football League player with a

history of 22 concussions and cognitive complaint. Evaluation included neurologic and neuropsychological

assessment, structural MRI, [18F]-Florbetapir amyloid and [18F]-T807 tau PET imaging. Additional

neuropsychological data from 2010 and a structural MRI from 2011 allowed for longitudinal analysis of

neuropsychological performance, cortical thickness, and subcortical volumes. Cognitive performance

declined during the 5-year period in the domains of executive functioning, verbal fluency, and fine motor

skills. Performance was below average on tests of narrative memory and naming, but average or higher in

other memory and language tests. In longitudinal structural analysis, left frontal cortex, lateral temporal

cortex and the basal ganglia showed greatest decreases, with apparent sparing of medial temporal lobe

structures. PET imaging was negative for amyloid plaques but revealed possible diffuse tau binding,

consistent with postmortem patterns of tau deposition in CTE, although interpretation of this novel ligand is

unclear. These data may inform future diagnostic criteria for CTE in living patients.

Poster

# 18


Poster Session

Should we trust oxytocin? An ultra-high field fMRI study of

trust reinforcement learning and Bayesian expectations under oxytocin

J.S. Ide, S. Nedic, K.F. Wong, E.A. Lawson, B.C. Dickerson, G. LaCamera,

L.R. Mujica-Parodi

Oxytocin (OT) is an endogenous neuropeptide that plays an important role in pair bonding and social

interaction, and is thought to increase trust and reduce fear. It has attracted great attention from the media

and the researchers as a potential treatment for illnesses characterized by social and emotional deficits,

such as autism spectrum disorders and anxiety. Several large-scale clinical trials using OT are underway,

nevertheless outcomes remain inconclusive and effects on the brain circuits unknown. Some studies show

that OT does not always increase trust or social reward learning, and may increase anxiety in certain

circumstances. In a series of randomized, placebo-controlled crossover experiments of single dose OT

(0.54IU/Kg) in healthy men, we characterize the reinforcement learning of trust in a mechanistic way by

analyzing OT’s effects on brain circuits underling decision making at an individual-subject level. We employ

ultra-high field functional MRI (7T), combined with an iterative reward-learning task involving trust, and

computational framework that models learning, expectation and behavior, and associates these with

dynamic interactions between regions involved in the formation of trust: nucleus accumbens, amygdala,

and OFC. Our findings suggest that OT may actually inhibit learning and behavioral adaptation through its

effects on the reward circuit. We show that behavioral measures related to trust correlate with functional

and effective connectivity between amygdala and OFC.

Poster

# 19

Higher intrinsic amygdala activity levels are associated with

poorer cognitive functions in HIV+ adults

Uraina Clark PhD, Rachal Hegde BS, Susan Morgello MD

The amygdalae play an important role in higher-order cognitive functions. Abnormalities in amygdalae

morphometry have been associated with increased cognitive impairment in HIV+ adults. Yet, the relation

between amygdalae function and HIV-associated cognitive impairment has not been investigated

previously. The current study was conducted to evaluate the relation between intrinsic amygdala activity

and cognitive functions in HIV+ adults. A brief cognitive battery assessing executive functioning (EF) abilities

was administered to 27 HIV+ and 16 HIV-negative control (HC) participants. Resting-state fMRI data were

obtained for 26 HIV+ and 14 HC participants. The fractional amplitude of low-frequency fluctuations (fALFF)

within the right and left amygdala was calculated as a measure of intrinsic amygdala activity. HIV+ adults

exhibited poorer EF abilities than HC (t=2.18, p=.036). Intrinsic amygdalae activity (fALFF) was higher in HIV+

relative to HC, particularly in the right amygdala (F=4.32, p=.046, ηp2=.12). Across the entire sample, higher

right amygdala activity was associated with poorer EF abilities (r= -.38, p=.028). This association was strongly

driven by effects within the HIV+ group (r= -.40, p=.076). We report preliminary evidence that HIV+ adults

exhibit increased intrinsic amygdala activity, which is associated with increased EF impairment. This effect

may be mediated by co-occurring disruptions in frontal-lobe regions responsible for higher-order cognitive

functions. Future investigations will examine intrinsic activity within frontal-subcortical networks to better

understand the neural substrates of cognitive impairment in HIV+ adults.

Poster

# 20


Poster Session

Using verbal fluency to probe drug-related attention bias

across abstinence in cocaine addiction

Shasha Lin, Muhammad A. Parvaz, Thomas Maloney, Scott J. Moeller,

Nelly Alia-Klein, Rita Z. Goldstein

Drug-related attention bias is modulated by abstinence, but its trajectory as a function of abstinence

duration is not well-understood. We assessed such attention bias in individuals with cocaine use disorder

(iCUD, n=143) varying in abstinence duration, as well as in matched healthy controls (HC, n=95), using the

drug fluency task as a behavioral probe (adapted from the classic semantic fluency task; Goldstein, Woicik,

Lukasik, Maloney & Volkow, 2007). The iCUD were grouped by length of abstinence: 0 to 6 days (n=93), 1

week to 1 month (n=23), 1 month to 4 months (n=15), and 4 months to 1 year (n=12), closely paralleling

time windows used previously in preclinical and human studies. An ANOVA across the HC and 4 iCUD groups

on the percentage of drug fluency task responses over total responses in both the drug fluency task and the

classic semantic fluency task showed a significant inverted U-shaped quadratic trend (Fig. 1, F(1,233)=9.2,

p<.01), indicating the intensification of attention bias at the beginning of abstinence and its eventual

dissipation after 4 months. These results converge with previous molecular and neuroanatomical studies

(e.g., Grimm et al., 2003) that suggest an initial incubation and later decline of cue-induced craving. This

study delineated the trajectory of drug-related attention bias over the course of abstinence. Future studies

can use neuroimaging techniques (e.g., EEG, MRI, PET) to examine the neural basis of this drug fluency

effect with more equal-sized sample groups and in a longitudinal within-subjects design.

Poster

# 21


Poster Session

Structural network changes associated with cognitive training in memory

Christienne Damatac, Jamie Nagy, Lazar Fleysher, Rafael O’Halloran, Paula Croxson

Age and pathologically related cognitive decline correlate with changes in brain structure and connectivity.

Magnetic resonance imaging (MRI) can not only measure these changes, but also those induced by training.

Previous human studies have demonstrated short-term effects of motor training on both gray matter

volume and white matter integrity. However, there's yet to be a longitudinal study that demonstrates gray

and white matter long-term changes from cognitive training. We investigated effects of specific cognitive

training on gray and white matter plasticity, measured by MRI in macaque monkeys.

We trained 3 monkeys in a two-object discrimination learning task that caused them to form a

discrimination learning set (DLS), reliant on frontal-temporal connections, while 3 control monkeys were

trained in a task that involved concurrent discrimination learning (CDL), which utilizes only temporal lobe

structures. We subsequently assessed transfer of learning to untrained tasks of episodic memory and

reversal learning. High-resolution structural (MP2RAGE, 0.5mm isotropic voxels) and diffusion-weighted

imaging (DWI) (68 directions, 1.0mm isotropic voxels) scans were performed on a 3 Tesla Siemens Skyra MRI

scanner using a custom-built 8-channel head coil before and after each stage of cognitive training. Metrics

assessing white matter integrity (e.g. fractional anisotropy and mean diffusivity) and gray matter volume

were computed using FSL (www.fmrib.ox.ac.uk/fsl).

DLS-trained monkeys learned more quickly than CDL-trained monkeys. Comparison of pre- and post-training

MRI data revealed cognitive training-associated changes in gray matter volume and fractional anisotropy.

Thus, MRI can be used to monitor structural and functional changes in the brain associated with cognitive

training and may aid in the translation of cognitive training into therapies for Alzheimerâ€™s disease,

multiple sclerosis, and normal age-related cognitive decline.

Poster

# 22


Poster Session

Neural predictors and moderators of treatment response to

social skills groups for children with autism spectrum disorder

Karim Ibrahim, Latha Soorya, Sarah Soffes, Danielle Halpern, Joseph Buxbaum,

Alexander Kolevzon, and Ting Wang

Social skills training using a cognitive-behavioral (CBT) approach has been shown to be effective in

improving social behavior deficits in children with ASD. However, little is known about patterns of brain

activity that predict and correlate with response to treatment. We examined whether baseline brain activity

was associated with response to social skills treatment in verbally fluent children with ASD. Children ages

8-11 were randomized to CBT or a facilitated play comparison group. Behavioral assessments and fMRI were

conducted at baseline and endpoint (12 weeks). While undergoing fMRI, children viewed emotionally

expressive faces with direct or averted gaze. Regression analyses were conducted to evaluate the

relationship between baseline brain activity and changes in social cognition and behavior. Across groups,

baseline activity in the left FG was significantly correlated with improvement in social awareness on the

Social Responsiveness Scale. Activity in the right FG moderated changes in social awareness for the CBT

group. Across groups, baseline activity in the right FG predicted improvement on a social cognition measure

following treatment. Overall, these results show that baseline activity in the FG, or a more typical neural

response to faces, was associated with children who demonstrated the greatest improvement in measures

of social awareness and social cognition following treatment.

Funded by NIMH, NARSAD, and Autism Speaks.

Poster

# 23

Feedback-related negativity tracks anhedonia – not depression - in

individuals with cocaine use disorders

Naomi Spilka BA, Muhammad Parvaz PhD, Vilma Gabbay MD, Rita Z. Goldstein PhD.

Anhedonia, defined as a loss of interest or pleasure in all or most of an individual’s activities, is a behavioral

manifestation of dysregulated dopamine activity in the mesocorticolimbic reward circuit, which is a hallmark

of drug addiction. Feedback-related negativity (FN) is a scalp-based elecroencephalography (EEG) derived

marker that is linked with corticostriatal dopamine activity, previously used to track reward sensitivity in

health and in various psychopathologies. Therefore, in this study, we hypothesized that FN amplitude can

be used to specifically track state anhedonia in individuals with cocaine use disorder (iCUD). Fifty-five iCUD

completed a probabilistic gambling-type game where they predicted a win (gain 60₵) or a loss (lose 30₵) on

a trial-by-trial basis; the FN was scored during the feedback informing participants of the outcome of these

predictions. Our data revealed that unlike FN response to loss, iCUD demonstrated increased FN amplitude

in response to a win feedback, which was associated with decreased state anhedonia (r=-.440; p< .001) and

depression (r=-.307; p< .023). Importantly, a linear regression analysis showed that only anhedonia

contributed significant variance (23%) to the FN amplitude as compared to overall depression (.1%), current

abstinence (.3%) and lifetime duration of cocaine use (1.3%). These results show that the FN amplitude in

response to win feedback objectively tracks state anhedonia above and beyond the contributions of

depression, severity and recency of drug use. Future studies may explore this relationship in other

psychopathologies mediated by dopaminergic dysregulation such as mood disorders and schizophrenia.

Poster

# 25


Documents

Brain Imaging Center Second Annual Symposium