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Genetic Effects on the Temporal Organization of Connectome Dynamics and Associated Cognitive Functions
Genetic Effects on the Temporal Organization of Connectome Dynamics and Associated Cogniti...
Genetic Effects on the Temporal Organization of Connectome Dynamics and Associated Cognitive Functions

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자료유형  
 학위논문 서양
최종처리일시  
20260202105829
ISBN  
9798263308117
DDC  
153
저자명  
Jun, Suhnyoung.
서명/저자  
Genetic Effects on the Temporal Organization of Connectome Dynamics and Associated Cognitive Functions
발행사항  
[Sl] : University of Illinois at Urbana-Champaign, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
194 p
주기사항  
Source: Dissertations Abstracts International, Volume: 87-05, Section: B.
주기사항  
Advisor: Sadaghiani, Sepideh.
학위논문주기  
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2024.
초록/해제  
요약The brain is inherently dynamic and capable of flexibly reorganizing its functional architecture ("connectome") even in the absence of an explicit task. Such dynamic reconfigurations of the connectome play a role in shaping cognitive abilities and complex brain functions. Specifically, time-varying characteristics of the brain's functional connectome are specific to the individual and predictive of individual cognitive abilities. However, there is a critical gap in understanding which dynamic characteristics are heritable phenotypes and how inter-individual variability in such connectome dynamics could contribute to differences in cognitive abilities across people. Further, specific genetic polymorphisms that influence the heritable aspects of connectome dynamics have remained largely unknown.Therefore, the upcoming chapters are designed to achieve several objectives. Firstly, Chapter 1 explores the genetic influences on features of fMRI-derived connectome dynamics using a twin study design. Secondly, Chapter 2 identified specific genetic polymorphisms that impact fMRI-derived connectome dynamics, employing a molecular genetics study approach. Thirdly, Chapter 3 aims to delve into the genetic effects on connectome dynamics at faster timescales, utilizing source-localized EEG in conjunction with the twin study design. Lastly, Chapter 4 extends to examining the behavioral significance of heritable rapid connectome dynamics phenotypes. Collectively, our findings aim to provide a comprehensive understanding of how genetic effects impact both slow and rapid connectome dynamics, and how such dynamics in turn affect behavior.In Chapter 1, we investigated the heritability of temporal and spatial features of the functional connectome using Human Connectome Project's resting-state fMRI data. We found strong and robust evidence for heritability and cognitive association of temporal dynamic features, i.e., Fractional Occupancy (FO; the proportion of time spent in each connectome state) and Transition Probability (TP; the probability to transition between state pairs). Specifically, genetic effects explained a substantial proportion of phenotypic variance of these features (narrow-sense heritability (h2) =0.39, 95% CI= [.24,.54] for FO; h2=0.43, 95% CI= [.29,.57] for TP). Moreover, these temporal phenotypes were associated with cognitive performance. Spatial features, however, showed no robust evidence of heritability. Our findings indicate that genetic effects primarily impact how the connectome transitions across states rather than the precise spatial instantiation of the states.Building upon the findings of Chapter 1, Chapter 2 aimed to identify the specific genetic polymorphisms that shape connectome dynamics and the associated cognitive abilities. Given the widespread regulatory impact of modulatory neurotransmitters on functional connectivity, we comprehensively investigated a large set of single nucleotide polymorphisms (SNPs) of their receptors, metabolic enzymes, and transporters. We found that specific subsets of these SNPs jointly explain individual differences in temporal phenotypes of fMRI-derived connectome dynamics for which we previously established heritability in Chapter 1. Specifically, a set of cholinergic SNPs predicted Fractional Occupancy and a set of serotonergic SNPs explained Transition Probability. Together, our findings provide evidence for specific genetic effects on connectome dynamics via the regulatory impact of modulatory neurotransmitter systems.While we have established the substantial genetic effects and behavioral significance of fMRI-derived connectome dynamics throughout Chapters 1 and 2, the fMRI-derived connectome dynamics predominantly captures infra-slow ( 0.1 Hz) processes. Therefore, in Chapters 3 and 4, we studied connectome dynamics at faster timescales that are highly relevant for cognition. Specifically, in Chapter 3, we investigated the genetic effects on rapid connectome dynamics features in each canonical frequency band derived using source-space resting-state EEG. We found that temporal features were heritable, particularly, Fractional Occupancy (in theta, alpha, beta, and gamma bands) and Transition Probability (in theta, alpha, and gamma bands). Further, genetic effects explained a substantial proportion of phenotypic variance of these features: Fractional Occupancy in beta (44.3%) and gamma (39.8%) bands and Transition Probability in theta (38.4%), alpha (63.3%), beta (22.6%), and gamma (40%) bands. Consistent with the findings of Chapter 1, we did not find support for the heritability of spatial features of connectome dynamics, specifically states' Modularity and connectivity pattern.While electrophysiological connectome dynamics may be highly relevant to cognition due to their rapid (sub-second) timescale, empirical evidence for such relevance is largely lacking. In Chapter 4, we investigated the behavioral significance of rapid electrophysiological connectome dynamics using canonical correlation analysis. We found a significant relationship between the heritable features of sub-second connectome dynamics, identified in Chapter 3, and factorized cognitive performance measures. Specifically, principal components of alpha (followed by theta and gamma components) and a cognitive factor representing visuospatial processing (followed by verbal and auditory working memory) showed the most notable contribution to the relationship.Together, these chapters provide a comprehensive perspective on the genetic influences and behavioral significance of connectome dynamics across various timescales and modalities, advancing our understanding of the intricate relationship between connectome dynamics and cognition.
일반주제명  
Cognitive psychology
일반주제명  
Neurosciences
일반주제명  
Genetics
키워드  
Dynamic functional connectivity
키워드  
Electrophysiology
키워드  
Hidden Markov modeling
키워드  
Cognition
키워드  
Individual differences
키워드  
Canonical correlation analysis
키워드  
Heritability
키워드  
Molecular genetics
기타저자  
University of Illinois at Urbana-Champaign Psychology
기본자료저록  
Dissertations Abstracts International. 87-05B.
전자적 위치 및 접속  
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MARC

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■1001  ▼aJun,  Suhnyoung.
■24510▼aGenetic  Effects  on  the  Temporal  Organization  of  Connectome  Dynamics  and  Associated  Cognitive  Functions
■260    ▼a[Sl]▼bUniversity  of  Illinois  at  Urbana-Champaign▼c2024
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■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  87-05,  Section:  B.
■500    ▼aAdvisor:  Sadaghiani,  Sepideh.
■5021  ▼aThesis  (Ph.D.)--University  of  Illinois  at  Urbana-Champaign,  2024.
■520    ▼aThe  brain  is  inherently  dynamic  and  capable  of  flexibly  reorganizing  its  functional  architecture  ("connectome")  even  in  the  absence  of  an  explicit  task.  Such  dynamic  reconfigurations  of  the  connectome  play  a  role  in  shaping  cognitive  abilities  and  complex  brain  functions.  Specifically,  time-varying  characteristics  of  the  brain's  functional  connectome  are  specific  to  the  individual  and  predictive  of  individual  cognitive  abilities.  However,  there  is  a  critical  gap  in  understanding  which  dynamic  characteristics  are  heritable  phenotypes  and  how  inter-individual  variability  in  such  connectome  dynamics  could  contribute  to  differences  in  cognitive  abilities  across  people.  Further,  specific  genetic  polymorphisms  that  influence  the  heritable  aspects  of  connectome  dynamics  have  remained  largely  unknown.Therefore,  the  upcoming  chapters  are  designed  to  achieve  several  objectives.  Firstly,  Chapter  1  explores  the  genetic  influences  on  features  of  fMRI-derived  connectome  dynamics  using  a  twin  study  design.  Secondly,  Chapter  2  identified  specific  genetic  polymorphisms  that  impact  fMRI-derived  connectome  dynamics,  employing  a  molecular  genetics  study  approach.  Thirdly,  Chapter  3  aims  to  delve  into  the  genetic  effects  on  connectome  dynamics  at  faster  timescales,  utilizing  source-localized  EEG  in  conjunction  with  the  twin  study  design.  Lastly,  Chapter  4  extends  to  examining  the  behavioral  significance  of  heritable  rapid  connectome  dynamics  phenotypes.  Collectively,  our  findings  aim  to  provide  a  comprehensive  understanding  of  how  genetic  effects  impact  both  slow  and  rapid  connectome  dynamics,  and  how  such  dynamics  in  turn  affect  behavior.In  Chapter  1,  we  investigated  the  heritability  of  temporal  and  spatial  features  of  the  functional  connectome  using  Human  Connectome  Project's  resting-state  fMRI  data.  We  found  strong  and  robust  evidence  for  heritability  and  cognitive  association  of  temporal  dynamic  features,  i.e.,  Fractional  Occupancy  (FO;  the  proportion  of  time  spent  in  each  connectome  state)  and  Transition  Probability  (TP;  the  probability  to  transition  between  state  pairs).  Specifically,  genetic  effects  explained  a  substantial  proportion  of  phenotypic  variance  of  these  features  (narrow-sense  heritability  (h2)  =0.39,  95%  CI=  [.24,.54]  for  FO;  h2=0.43,  95%  CI=  [.29,.57]  for  TP).  Moreover,  these  temporal  phenotypes  were  associated  with  cognitive  performance.  Spatial  features,  however,  showed  no  robust  evidence  of  heritability.  Our  findings  indicate  that  genetic  effects  primarily  impact  how  the  connectome  transitions  across  states  rather  than  the  precise  spatial  instantiation  of  the  states.Building  upon  the  findings  of  Chapter  1,  Chapter  2  aimed  to  identify  the  specific  genetic  polymorphisms  that  shape  connectome  dynamics  and  the  associated  cognitive  abilities.  Given  the  widespread  regulatory  impact  of  modulatory  neurotransmitters  on  functional  connectivity,  we  comprehensively  investigated  a  large  set  of  single  nucleotide  polymorphisms  (SNPs)  of  their  receptors,  metabolic  enzymes,  and  transporters.  We  found  that  specific  subsets  of  these  SNPs  jointly  explain  individual  differences  in  temporal  phenotypes  of  fMRI-derived  connectome  dynamics  for  which  we  previously  established  heritability  in  Chapter  1.  Specifically,  a  set  of  cholinergic  SNPs  predicted  Fractional  Occupancy  and  a  set  of  serotonergic  SNPs  explained  Transition  Probability.  Together,  our  findings  provide  evidence  for  specific  genetic  effects  on  connectome  dynamics  via  the  regulatory  impact  of  modulatory  neurotransmitter  systems.While  we  have  established  the  substantial  genetic  effects  and  behavioral  significance  of  fMRI-derived  connectome  dynamics  throughout  Chapters  1  and  2,  the  fMRI-derived  connectome  dynamics  predominantly  captures  infra-slow  (  0.1  Hz)  processes.  Therefore,  in  Chapters  3  and  4,  we  studied  connectome  dynamics  at  faster  timescales  that  are  highly  relevant  for  cognition.  Specifically,  in  Chapter  3,  we  investigated  the  genetic  effects  on  rapid  connectome  dynamics  features  in  each  canonical  frequency  band  derived  using  source-space  resting-state  EEG.  We  found  that  temporal  features  were  heritable,  particularly,  Fractional  Occupancy  (in  theta,  alpha,  beta,  and  gamma  bands)  and  Transition  Probability  (in  theta,  alpha,  and  gamma  bands).  Further,  genetic  effects  explained  a  substantial  proportion  of  phenotypic  variance  of  these  features:  Fractional  Occupancy  in  beta  (44.3%)  and  gamma  (39.8%)  bands  and  Transition  Probability  in  theta  (38.4%),  alpha  (63.3%),  beta  (22.6%),  and  gamma  (40%)  bands.  Consistent  with  the  findings  of  Chapter  1,  we  did  not  find  support  for  the  heritability  of  spatial  features  of  connectome  dynamics,  specifically  states'  Modularity  and  connectivity  pattern.While  electrophysiological  connectome  dynamics  may  be  highly  relevant  to  cognition  due  to  their  rapid  (sub-second)  timescale,  empirical  evidence  for  such  relevance  is  largely  lacking.  In  Chapter  4,  we  investigated  the  behavioral  significance  of  rapid  electrophysiological  connectome  dynamics  using  canonical  correlation  analysis.  We  found  a  significant  relationship  between  the  heritable  features  of  sub-second  connectome  dynamics,  identified  in  Chapter  3,  and  factorized  cognitive  performance  measures.  Specifically,  principal  components  of  alpha  (followed  by  theta  and  gamma  components)  and  a  cognitive  factor  representing  visuospatial  processing  (followed  by  verbal  and  auditory  working  memory)  showed  the  most  notable  contribution  to  the  relationship.Together,  these  chapters  provide  a  comprehensive  perspective  on  the  genetic  influences  and  behavioral  significance  of  connectome  dynamics  across  various  timescales  and  modalities,  advancing  our  understanding  of  the  intricate  relationship  between  connectome  dynamics  and  cognition.
■590    ▼aSchool  code:  0090.
■650  4▼aCognitive  psychology
■650  4▼aNeurosciences
■650  4▼aGenetics
■653    ▼aDynamic  functional  connectivity
■653    ▼aElectrophysiology
■653    ▼aHidden  Markov  modeling
■653    ▼aCognition
■653    ▼aIndividual  differences
■653    ▼aCanonical  correlation  analysis
■653    ▼aHeritability
■653    ▼aMolecular  genetics
■690    ▼a0633
■690    ▼a0317
■690    ▼a0369
■71020▼aUniversity  of  Illinois  at  Urbana-Champaign▼bPsychology.
■7730  ▼tDissertations  Abstracts  International▼g87-05B.
■790    ▼a0090
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17361300▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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