FREE ELECTRONIC LIBRARY - Abstract, dissertation, book

Pages:   || 2 | 3 | 4 | 5 |   ...   | 15 |

«DEPARTMENT OF PHYSIOLOGY Unsupervised characterization of human brain networks that are involved in emotional processing and regulation THESIS ...»

-- [ Page 1 ] --





Unsupervised characterization of human brain networks that are

involved in emotional processing and regulation




October 2015 This work was carried out under the academic supervision of Talma Hendler Professor of Psychiatry and Psychology School of Psychological Science, Sagol School of Neuroscience, Faculty of Medicine Tel-Aviv University Director, Functional Brain Center, Wohl Institute for Advanced Imaging, Tel-Aviv Sourasky Medical Center AND Ron Shamir Professor of Computer Sciences Blavatnik School of Computer Science Tel-Aviv University Dedicated with gratitude to my parents and entire family for their love and encouragement, and especially to Oded, Shachar and Ofek. Without your love and support I would not have completed this thesis.


I wish to start by thanking my Yoga professor Orit Sen-Gupta, who by beautifully sharing her knowledge of the Yogic philosophy of the mind, inspired me to go on this quest. I wish to thank my advisors Prof. Talma Hendler and Prof. Ron Shamir who made it possible for me.

I also wish to thank my fellow students in the lab at Wohl Institute for Advances Imaging at the Tel-Aviv Sourasky Medical Center as well as in the lab for Computational Genomics at Tel-Aviv University for their help and support all through my PhD. Especially I would like to thank Michal Ballas-Gruberger and Haggai Sharon for their invaluable support and inspiration; Eti Ben Simon, David Amar, Sharon Vaisvase, Tamar Lin and Gadi Gilam for productive collaboration; Gal Raz, Shahar Jamshy, Ilana Podlipsky and Yael Yaakov for helpful discussions.

Thanks  This work was supported by the Israeli ministry of Science and Technology



2. Introduction

2.1The resting Brain

2.2 Experience related fingerprint in resting state fMRI

2.3 Neural traces of Inter-individual differences in handling emotionally-challenging experiences

2.4 Methods for studying variability in resting state functional connectivity

3. Research Objectives

4. General methods and materials

4.1 Functional MRI

4.1.1 Background

4.1.2 fMRI acquisition

4.1.3 fMRI preprocessing and parcellation

4.1.4 Cross correlation functional connectivity analysis

4.2 Behavioral measures of affective response

4.3 Comparing neural measures against behavioral and other physiological measures...... 26 5. Improving interpretation of large-scale changes in resting state networks 27

5.1 Background

5.2 Methods

5.3 Results

5.4 Discussion

6.............Characterizing changes in resting-state networks induced by a psychological perturbation

6.1 Background

6.2 Case study 1: Characterizing changes in resting-state networks induced by acute social stress

6.2.1 Specific Background

6.2.2 Specific materials and methods

6.2.3 Results

6.2.4 Discussion – study 1

6.3 Case study 2: Characterizing changes in resting-state networks following an anger inducing social interaction

6.3.1 Specific Background

6.3.2 Specific materials and methods

6.3.3 Results

6.3.4 Discussion- study 2

6.4 Joint Discussion


Ch aracterizing changes in resting-state networks following a physiological perturbation 83

7.1 Background

7.2 Specific materials and methods

7.3 Results

7.4 Discussion

8. Concluding Discussion

8.1 Overview of the results

8.2. Methodological insights and contributions

8.2. Study Limitations



OF AND Figure 5-1: Two examples that demonstrate the difference between the two approaches to connectivity enrichment significance

Figure 5-2: RichMind results visualization for case study 1

Figure 5-3: RichMind results visualization for case study 2

Figure 6-1: An illustration of data-driven univariate rsFC analysis.

Figure 6-2:: Psychological response to stress on experimental timeline.

Figure 6-3:: Significant rsFC changes following stress

Figure 6-4: A graph representation of the enrichment analysis results

Figure 6-5: Results of inter-group rsFC change comparison

Figure 6-6: Experimental procedure of case study 2

Figure 6-7: An illustration of the global rsFC analysis steps

Figure 6-8: rsFC changes identified flowing UG

Figure 6-9: Association between overall rAmy rsFC and behavioural measures.................. 80 Figure 7-1: Results of pairwise univariate rsFC analysis seeded in parcels 165 and 148...... 93 Figure 7-2: association between SD –induced rsFC change and behavioral measures........ 94 Figure 7-3: Accuracy rates of LOOCV analysis presented as a function of number of used features (k)

Figure 7-4: LOOCV top-ranking features

Figure 7-5: Annotations used in enrichment analysis

Figure 7-6: SD-induced changes in modular organization.

Table 5-1 – RichMind results for case study 1

Table 5-2 - RichMind results for case study 2

Table 6-1 – Lobe-based enrichment analysis results

Table 6-2 – ENRICHMENT-inducing parcel pairs:

Table 7-1 – Results of univariate overall rsFC analysis

Table 7-2 – Results of pairwise univariate rsFC analysis seeded in parcels 165 and 148..... 91 Table 7-3 - Parcel pairs that were selected as features in all 17 iterations of LOOCV (k=24) analysis

Table 7-4: Modules identified via modularity analysis on group-level rsFC matrices............. 97


(4-1) Pearson Correlation Coeficient

(4-2) Fisher Transformation

(4-3) Spearman Correlation Coeficient

(5-1) Hyper-Geometric score

(7-1) Classificationn success

(7-2) Classification accuracy

(7-3) Classification accuracy p-value

(7-4) Jaccard Score

Abbreviations and symbols

Brain regions: Anterior Cingulate Cortex (ACC); Amygdala (Amy);

Basolateral Amygdala (BLA); Inferior Frontal Gyrus (IFG); Prefrontal Cortex (PFC); dorsolateral PFC (DPLFC); Superior temporal sulcus (STS); Posterior cingulate cortex (PCC); Visual network (VN); Default-mode network (DMN);

Fronto-parietal control network (FPCN); Sub-lobular (SL); Auditory network (AN); Executive control network (ECN); Ventral attention network (VAN);

Dorsal attention network (DAN); Sensory-motor network (SMN) Brain imaging and physiology: Functional Magnetic Resonance Imaging (fMRI); Magnetic Resonance Imaging (MRI); Electroencephalogram (EEG);

General Electric (GE); repetition time (TR); Region Of Interest (ROI); field potential (LFP); Heart rate (HR); Heart rate variability (HRV);

Electrocardiogram (ECG);

Others: Post-traumatic Stress Disorder (PTSD); Functional Connectivity (FC), Resting State (rs); Leave-one-out cross validation (LOOCV); Ultimatum-game (UG); Trier Social Stress Test (TSST); Degree preserving permutation (DPP);

Hypergeometric (HG); inter-subject correlation (ISC); Automated Anatomic Labeling (AAL)

1. ABSTRACT Background In the past decade and a half, the neuroscience community has learned that during rest, ongoing energy consuming activity takes place in the brain. When focusing on low frequencies, this activity is highly correlated within known functional networks. Although these correlated fluctuations are generally maintained over time, they were shown to vary with changes in cognitive and emotional states, and were suggested to hold information on individual history of interaction with the world as well as a priori cognitive and emotional biases.

Exploration of variability in resting-state (rs) neural functional connectivity (FC) through functional magnetic resonance imaging (fMRI) has been traditionally performed using hypothesis-driven analysis while focusing on one or a few predefined seed regions. This approach can reveal only a fraction of the actual phenomenon as it relies on prior knowledge of the putative functional network structure. An alternative approach is to conduct a whole-brain voxel-wise analysis, which is computationally expensive and sensitive to noise. A possible compromise is to define a set of regions of interest (ROIs) that provide good coverage of the brain. Such dimensionality reduction allows conducting wholebrain rsFC analysis while treating the data as a collection of independent connections and performing statistical analyses of each connection separately.

Alternatively, multivariate techniques evaluate the relationship between the entire connectome matrices and their associated phenotypic variables in a single statistical test. While powerful, such analysis does not reveal information on the involvement of individual connections.

Despite the methodological progress in studying variability in rsFC patters, to date findings that are obtained from large-scale rsFC analysis are mostly interpreted by a qualitative comparison to known neural maps which are is based on existing literature. Such methodology does not use statistical tools for interpretation, and holds the risk of reporting false positive results and missing important findings. In order to perform this interpretation rigorously one must address it statistically. A natural way to do this is by testing whether a link between two known brain regions or functional networks is significantly more prevalent in the results than would be expected by chance (i.e. enriched).

Analysis of enrichment has long been used in the field of Bioinformatics, and is the acceptable way for characterizing large sets of genes that emerge from data driven genomic analysis.

This work uses rsfMRI to examine the way in which different types of emotionally challenging experiences affect patterns of neural coactivation in subsequent resting periods. This is done using several approaches for largescale rsFC analysis in combination with enrichment analysis as an established manner for interpretation. Assuming that rsFC holds information on individual tendencies as well as on prior experience, we examined inter-individual differences in these patterns and their relation to various behavioral measures of emotional reactivity and regulation. We hypothesized that emotionally challenging experiences will induce large scale changes in patterns of fMRI rsFC. We further expected these changes to be associated with subjective measures of emotional experience.


1) Develop improved means for characterizing and interpreting large-scale changes in FC patterns of rsfMRI data.

2) Data-driven investigation of rsFC modulations following several different types of “emotional challenge”.

3) Identify inter-individual differences in rsFC modulations that correspond to inter-individual differences in measures of affective experience.

Methods To evaluate enrichment within sets of neural positions we adopted the statistical hyper-geometric test. We used the same test to evaluate enrichment within sets of neural connections, however for this case we added an additional nonparametric permutation test, which accounts for uneven levels of FC in different brain areas. Both tests were integrated into the RichMind Matlab package.

Given a collection of findings (neural positions or connections), and a known neural mapping, RichMind tests for enrichment in the input, and provides both statistical reports and brain visualization of the identified enrichments. The software was validated on two previously published studies, the first conducted on healthy participants viewing emotion-inducing film clips, and the second on participants with amnestic mild cognitive impairment.

Next, we analyzed data recorded before and after three different emotionally– challenging paradigms: a social-stress induction task, an anger-provoking interpersonal conflict task (the ultimatum game; UG) and a night without sleep (i.e.

sleep deprivation; SD). In all three cases a pre-defined functional parcellation was applied on the data before analysis for dimensionality reduction. We used a univariate analysis approach to identify rsFC changes. In the sleep deprivation study we used a combination of univariate analysis with multivariate approaches of leave-one-out cross validation (LOOCV) and modularity analysis, due to the small sample size. Large-scale findings were characterized using enrichment analysis. Emotional experience was measured using a number of self-reported questionnaires, and in some cases also using a physiological measure of heart-rate and heart-rate variability.

Main results Following the Trier social stress test we identified a large-scale rsFC change across the brain, which included strengthening of thalamo-cortical connectivity alongside a weakening of cross-hemispheral parieto-temporal connectivity.

These alterations were associated with change in subjective stress reports.

Integrating report-based information on stress sustainment 20 minutes post induction revealed a single significant rsFC change between the right basolateral amygdala (BLA) and the precuneus, which inversely predicted the level of subjective recovery. A parcel centered in the right amygdala demonstrated differential rsFC also following the inter-personal conflict task.

Specifically, it showed increased rsFC with a single parcel centered in the right inferior frontal gyrus. Baseline levels of overall rsFC of that parcel were positively correlated with subsequent subject gain in UG as well as reported anger following the game.

Pages:   || 2 | 3 | 4 | 5 |   ...   | 15 |

Similar works:

«IN THE CIRCUIT COURT OF THE NINTH JUDICIAL CIRCUIT, IN AND FOR ORANGE COUNTY, FLORIDA ROSE HEALTHCARE CENTER, INC., f/k/a Rose Chiropractic Centre, P.A., a/a/o Jitendra Kumar Pandya, Appellant, v. CASE NO.: CVA1 09-24 Lower Court Case No.: 2006-CC-7465-O INFINITY INSURANCE COMPANY and Leader Insurance Company, n/k/a INFINITY AUTO INSURANCE COMPANY, Appellees. / Appeal from the County Court, for Orange County, Antoinette Plogstedt, Judge. Aaryn Fuller, Esquire, for Appellant. Patrick D. Hinchey,...»

«Effect of US and Graston on Muscle Contraction THE EFFECT OF THERAPEUTIC ULTRASOUND AND INSTRUMENT ASSISTED SOFT TISSUE MOBILIZATION ON MUSCLE CONTRACTION OF THE LUMBAR MULTIFIDUS MEASURED BY ULTRASOUND IMAGING _ An Independent Research Presented to The Faculty of the College of Health Professions & Social Work Florida Gulf Coast University In Partial Fulfillment of the Requirement for the Degree of Doctor of Physical Therapy _ By Madeline R. Holman and Curtis Caldwell Effect of US and Graston...»

«Рекомендаци международной ассоциации дентальной травмы по диагностике и методам лечения травм зубов. Часть 3. Травмы зубов молочного прикуса¹ Составители русскоязычной версии: Russian Editors: Maria Plotnikov^,Leon Bilder*, Liran Levin§ ^ Rambam Health Care Campus, Faculty of Medicine, Technion IIT, Haifa, Israel. *Department of Periodontology,...»

«February 9, 2012 Robin E. Jensen 1 CURRICULUM VITAE Robin E. Jensen Assistant Professor, Department of Communication University of Utah Languages and Communication Bldg, Room 2400 Telephone: (801) 581-6889 255 South Central Campus Drive Fax: (801) 585-6255 Salt Lake City, UT 84112 E-mail: r.e.jensen@utah.edu Education Ph.D. University of Illinois, Urbana-Champaign Communication Concentration: Rhetoric; Health Communication Graduate Minor: Gender and Women’s Studies Degree awarded: May 2007...»

«Adenoviral infectivity of Exfoliated Viable Cells in Urine: Implications for the Detection of Bladder Cancer Anuradha Murali*, Laura Kasman *, Christina Voelkel-Johnson§ Department of Microbiology & Immunology, Medical University of South Carolina, Charleston SC, 29425, USA *These authors contributed equally to this work § Corresponding author Email addresses: AM: muraliak@musc.edu LK: kasmanl@musc.edu CVJ: johnsocv@musc.edu -1Abstract Background Bladder cancer, the 6th most common malignancy...»

«Factors affecting speech reception in fluctuating noise and reverberation The research described in this thesis was carried out within the EMGO Research Institute, at the ENT/Audiology Department of the VU University Medical Center in Amsterdam, The Netherlands. This project was supported by the Heinsius-Houbolt Foundation, The Netherlands.Cover: In Search of Meaning #1 An Art and Science Collaboration Artist Lylie Fisher http://www.lyliefisher.com The cover displays a work of art inspired by...»

«Australia’s mothers and babies 2011 PERINATAL STATISTICS SERIES Number 28 Australia’s mothers and babies Z. Li, R. Zeki, L. Hilder & E. A. Sullivan Australian Institute of Health and Welfare Canberra Cat. no. PER 59 The Australian Institute of Health and Welfare is a major national agency which provides reliable, regular and relevant information and statistics on Australia’s health and welfare. The Institute’s mission is authoritative information and statistics to promote better health...»

«Health Transition Review, Supplement to Volume 7, 1997, 361-375 ‘Main’ girlfriends, girlfriends, marriage, and money: the social context of HIV risk behaviour in sub-Saharan Africa * Dominique Meekers a and Anne-Emmanuèle Calvès b a Department of Population Dynamics, School of Hygiene and Public Health, Johns Hopkins University b Département de Démographie, Université de Montréal Among the elements important for an understanding of sexual behaviour and the prevalence of STDs are the...»

«How Allocated Cost and Space Charges Are Calculated at the University of Pennsylvania June 2013 Introduction The financial administration of the University is governed by a Responsibility Center Management (RCM) model, in which a Responsibility Center is an organizational unit that is expected to develop and to adhere to a balanced budget. The four types of Responsibility Centers in the University are: Schools, Resource Centers, Auxiliary Enterprises, and Administrative Service Centers. RCM...»

«Forage Fish The more common fish species identified as forage fish within Washington State include Pacific herring (Clupea harengus pallasi), surf smelt (Hypomesus pretiosus), Pacific sand lance (Ammodytes hexapterus), and northern anchovy (Engraulis mordax). Less common smelt, including longfin smelt, night smelt and rainbow smelt are generally grouped with surf smelt for management purposes, although their biology may be somewhat different. Anadromous forage fish, such as eulachon or the...»

«ICSSPE/CIEPSS Hanns-Braun-Straße, Friesenhaus II 14053 Berlin, Germany, Tel.: +49 30 311 0232 15, Fax: +49 30 311 0232 29 ICSSPE BULLETIN TABLE OF CONTENTS Table of Contents PUBLISHER'S STATEMENT FOREWORD Editorial Ben Weinberg President's Message Margaret Talbot Welcome New Members FEATURE: Perspectives on Front Line Care for Mild Traumatic Brain Injury in Sport (MTBI): Position Statements, Policies and Guidelines Introduction Carl R. Cramer Commentary Frank Conidi Position Statement: Sports...»

«HANDBOOK OF MASTER OF MEDICAL PHYSICS (M MED PHYSICS) An Institute of Physics and Engineering in Medicine (IPEM), United Kingdom, accredited programme 1. INTRODUCTION Technological advances and development in medicine, particularly in radiology, radiotherapy and nuclear medicine have created a demand for qualified personnel to support the current progress in the country. In 1998 the University of Malaya launched the Master of Medical Physics programme to meet the growing need of qualified...»

<<  HOME   |    CONTACTS
2016 www.abstract.xlibx.info - Free e-library - Abstract, dissertation, book

Materials of this site are available for review, all rights belong to their respective owners.
If you do not agree with the fact that your material is placed on this site, please, email us, we will within 1-2 business days delete him.