brain imaging center second annual symposium
TRANSCRIPT
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
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
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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
Connectivity and Multimodal Imaging
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 brain’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.
Page 8Second Annual BIC Symposium October 7 2015
Connectivity and Multimodal Imaging
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.
Page 9Second Annual BIC Symposium October 7 2015
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
Page 10Second Annual BIC Symposium October 7 2015
Technical Innovations
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
Page 11Second Annual BIC Symposium October 7 2015
Technical Innovations
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
Page 12Second Annual BIC Symposium October 7 2015
Technical Innovations
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.
Page 13Second Annual BIC Symposium October 7 2015
Technical Innovations
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
Page 14Second Annual BIC Symposium October 7 2015
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.
Page 15Second Annual BIC Symposium October 7 2015
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
Page 16Second Annual BIC Symposium October 7 2015
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
Page 17Second Annual BIC Symposium October 7 2015
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
Page 18Second Annual BIC Symposium October 7 2015
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
Page 19Second Annual BIC Symposium October 7 2015
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 experi- mental
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
Page 20Second Annual BIC Symposium October 7 2015
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
Page 21Second Annual BIC Symposium October 7 2015
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
Page 22Second Annual BIC Symposium October 7 2015
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
Page 23Second Annual BIC Symposium October 7 2015
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
Page 24Second Annual BIC Symposium October 7 2015
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
Page 25Second Annual BIC Symposium October 7 2015
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 ≥ 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 ≤ r ≤ .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
Page 26Second Annual BIC Symposium October 7 2015
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
Page 27Second Annual BIC Symposium October 7 2015
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
Page 28Second Annual BIC Symposium October 7 2015
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 Alzheimer’s disease,
multiple sclerosis, and normal age-related cognitive decline.
Poster
# 22
Page 29Second Annual BIC Symposium October 7 2015
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
Page 30Second Annual BIC Symposium October 7 2015