Supplemental Materials
Hyperconnectivity is a Fundamental Response to Neurological Disruption
by F. G. Hillary et al., 2014, Neuropsychology
Table S2
Connectivity Results for Moderate and Severe TBI
Studies of ROIs/subnetworks for Rest only studies in TBIAuthor / Analysis / Sample size / ROIs / Result
Arenivasetal.,2012* / Whole-braincorrelation,sub-networkanalysis,andbetween-nodeconnectionanalysis / 25TBI,17HC / MFC to PCC, MFC to
LLPC, MFC to RLPC, PCC to LLPC, PCC to RLPC, and LLPC to RLPC / -
Hillaryetal.,2011b / RSFCseed-based / 11TBI,11HCs
(2time points) / ACC, DLPFC, PCC, MedFC / +
MarquezdelaPlataetal.,2011* / Hand-drawnROI-basedcorrelation / 25TBI,16HC / Hippocampus,ACC,DLPFC / -/+
Palacios et al., 2013 / ICA, seed-based in DMN / 20 TBI, 17 HCs / DMN, Lpar
Rpar / +
Sharpetal.,2011 / ICAanddualregression,taskandrest / 20TBI,20HC / DMN,PCC / +
Studies of ROIs/subnetworks during task in TBI
Author / Analysis / Sample size / ROIs / Result
Hillaryetal.,2011a / Extendedunifiedstructuralequationmodeling / 12TBI,12HCs / PFC,Parietal,ACC / +
Kasaharaetal.,2010‡ / PPIanalysis,motortask / 12TBI,9HCs / SMA,Cb,M1 / -
Kasaharaetal.,2011‡ / PPIanalysis,workingmemorytask / 9TBI,9HCs / LIPGandRIFG, / -
Turneretal.,2011 / PLS,effectiveconnectivity / 8TBI,8HCs / PFC,Parietal / +
Whole brain analyses and Graph Theory
Author / Analysis / Sample size / ROIs / Result
Caeyenberghs et al., 2012** / Graph theory, partial correlation
motor switching task / 23 TBI, 26 HCs / Motor switching network, 22 ROIs / +
Caeyenberghs et al., 2013** / Graph theory, local-global switching task / 17 TBI, 16 HCs / Motor switching network, 22 ROIs / +
Karmonik et al., 2013 / Graph theory, delayed match-to-sample task / 12 TBI, 12 HCs / Whole brain / +
Nakamura et al., 2009 / Graph theory, Partial correlation / 6 TBI, 6 HCs
(2 time points) / Whole brain / +
Pandit et al., 2013 / Graph theory, unweighted network / 20 TBI, 21 HCs / Whole brain, PCC / -/+
*,‡=identical sample, **different data set, all 2013 subjects appear in 2012, results not duplicated for Figure 2. Note: graph theory results based upon network strength or number of connections; data included in Figure 2. Abbreviations:ACC=anteriorcingulate cortex,Cb=cerebellum,DLPFC=dorsolateralprefrontalcortex,DMN=defaultmodenetwork,ECN=executivecontrolnetwork,HC= healthycontrol,LIPG=leftinferiorparietalgyrus, LLPC=left lateral parietal cortex, M1=primarymotorcortex, MFC=medial frontal cortex, PCC=posteriorcingulatecortex,PFC=prefrontal cortex,PLS=partialleastsquares,PPI-psychophysiologicalinteraction,RIFG=rightinferiorfrontalgyrus,RLPC=right lateral parietal cortex, SMA=supplementary motorcortex,SN=saliencenetwork,TBI=moderateandseveretraumaticbraininjury.
Table S3
Connectivity Results for Multiple Sclerosis
3a: Studies of ROIs/subnetworks Rest OnlyAuthor / Analysis / Sample size / ROIs / Result
Basile et al., 2013 / ICA- RSFC / 34 RR, 14 SP, 25 HCs / rsfMRI, DMN
SMN / +
Bonavita et al., 2011 / ICA / 18CIRRMS,18CP RRMS,
18HCs / DMN / +/-
Faivre et al., 2012 / spatial ICA, dual regression / 13 Early RR-MS, 14 HCs / 8 resting networks / +
Gallo et al., 2012 / ICA / 16ON-MS,14nON-MS,15
HCs / VisualRSFC,Striate,Occipital / +/-
Hawellek et al., 2011 / Whole-brain covariance / 16earlystageMS,16HCs / DMN / +
Janssen / ICA, dual regression / 28 RRMS, 28 HCs / Motor, 2 visual networks / -
Koenig / RSFCseed-based / 16 MS, 16 HCs / PCC to whole brain / +
Leonardi / PCA-eigen-connectivities / 15 MS, 13 HCs / AAL atlas
90 regions / +/-
Loitfelder et al., 2012 / RSFCseed-based / 31 MS (10 CIS, 16 RR-MS, 5 SP-MS), 31 HCs / ACC / +
Rocca et al., 2012b / ICA, RSFC / 85 RR-MS, 40
HCs / SN, ECN, DMN / +/-
Roosendaal et al., 2010 / RSFCseed-based / 25MS,30HCs / Hippocampalconnections / -
Studies of ROIs/subnetworks using Task
Author / Analysis / Sample / ROIs / Result
Au duong et al., 2005a* / SEM, PASAT / 18earlystageMS,18HCs / BA46 / +/-
Au duong et al., 2005b* / Seed-based FC, PASAT / 18earlystageMS,18HCs / BA45/46 / -
Cader et al., 2006 / Task-related ROI correlations / 21RR-MS,16HCs / PFC,ACC / +/-
Cerasa et al., 2012 / PPI / 12+Cb-MS,15-CbMS,
16HCs / Cb,Parietal / -
Fera et al., 2013 / PPI- Hipp seed and memory task / 26 MS, 25 HCs / Hippocampus vs. brain / +
Forn et al., 2012 / DCM / 18CIS,15HCs / MFC,ACC,IFG,IPL / +
Helekar et al., 2010 / Voxelwise hierarchical clustering / 16 RR-MS, 21 HCs / Whole Brain during WCST / +/-
Leavitt et al., 2012 / Granger causality / 16MS,17HCs / 8task-relatedROIs,PFC / +
Rocca et al., 2012 / PPI / 17RR-MS,17benignMS,23
SP-MS,18HCs / PFC,RCb / +/-
Rocca et al., 2009a / DCM, Stroop task / 15benignMS,19HCs / Sensorimotor-RIFG,Cb / +/-
3b: Studies of Motor Networks
Author / Analysis / Sample / ROIs / Result
Ceccarelli et al., 2010 / FC analysis / 15PPMS,15HCs / Motor network / -
Cruz Gomez et al., 2013 / ICA and seed-based / 60 RRMS, 18 HCs / SMA, PMC, thalamus / +/-
Dogonowski et al., 2012** / 20-min RSFC / 42MS,30HCs / Motor RSFC and subcortical nuclei / +
Dogonowski et al., 2013** / PPI, RSFC / 27RR-MS,15SP-MS / Motor RSFC / +
Dogonowski et al., 2013** / Kendall’s coefficient of concordance / 27RR-MS,15SP-MS / Motor,
Cerebellum / -
Rocca et al., 2007 / Task-FC / 12RR-MS,14HCs / Motor network / +
Rocca et al., 2009b*** / DCM / 61MS,74HCs / SMC, SMA / +/-
Rocca et al., 2010 / DCM / 17pediatricRR-MS,16adultCIS,14adultRR-MS,10HCs / Sensorimotor network / +
Valsasina et al., 2011*** / RSFCseed-based / 61MS,74HC / Motor, sensorimotor / +
3c: Studies using Graph Theory
Author / Analysis / Sample / ROIs / Result
Gamboa et al., 2013 / Correlation matrix / 16 Early MS
20 HCs / 116 AAL atlas / na
*,**,***=identical MS samples; Abbreviations Table 2: AAL: automated anatomical labeling, ACC= anterior cingulate cortex, Cb= cerebellum, DCM=dynamic causalmodeling, DLPFC=dorsolateral prefrontal cortex, DMN=default mode network, ECN = executive control network, FC=functionalconnectivity (correlation), HC= healthy control, Hipp=hippocampus, ICA= independent components analysis, LIPG= left inferior parietal gyrus,MS=multiple sclerosis, nON-MS=non-optic neuritis multiple sclerosis, ON-MS=optic neuritis multiple sclerosis, PCC= posteriorcingulate cortex, PFC=prefrontal cortex, PMC=primary motor cortex, PPI=psychophysiological interaction, PP-MS=primary progressive MS, RIFG= right inferior frontal gyrus, RR-MS= relapsing remitting MS, RSFC=resting state functional connectivity, RSFC= resting state functional connectivity, SEM= structural equation modeling, SL= Synchronization likelihood, SMA= supplementary motor cortex, SN= salience network.
Table S3a
Connectivity Results for DAT and MCI Studies Examining Whole-Brain Connectivity Using Graph Theory
Table 3a: Graph Theory in AD and MCIAuthor / Analysis / Sample size / ROIs / Result
Chen et al., 2013 / Graph theory / 30 AD, 30 HCs / 116 (Talairach) / -
Minati et al., 2014 / ICA.; graph theory / 49 MCI, 32 HCs / 742 regions / -
Sanz-Arigita et al., 2010 / Pair-wise synchronization, graph theory / 18 mild AD, 21 HCs / Whole brain, Frontal cortices / -
Supekar et al., 2008 / Graph theory / 21 AD, 18 HCs / Whole brain / -
Wang, J. et al., 2013 / Graph theory / 37 aMCI, 47 HCs / DMN, Whole brain / -
Wang, L. et al., 2013 / Episodic memory task, graph theory / 25 MCI, 26 HCs / DMN / -
Xia et al., 2013 / Graph theory; seed-voxel / 32 AD, 38 HCs / posteromedial cortex (PMC) / +/-
Yao et al., 2010 / Graph theory / 113 MCI, 91 AD, 98 HCs / Whole brain, Frontal, Posterior / +/-*
Zhao et al., 2012 / Graph theory / 33 AD, 20 HCs / Whole brain, DMN / +/-
Note: increasedpathlengthinterpretedasconnectivityloss; data not included in Figure 2.AbbreviationsTable3a:AD=Alzheimer’s disease,DMN=defaultmode network,FTLD=frontotemporallobe dementia,RSFC=restingstatefunctionalconnectivity.
Table S3b-c
Connectivity Results for AD Examining ROI and Subnetworks and Task
Table 3b:Studies of Rest Only connectivity in ADAuthor / Analysis / Sample size / ROIs / Result
Agosta et al., 2012 / RSFCseed-based / 13AD,12MCI,13HC / DMN, Frontoparietal, ECN, SN / +/-
Allen et al., 2007 / RSFCseed-based / 8AD,8HCs / Hippocampus, Frontal / -
Balthazar et al., 2013 / RSFC, ICA / 20AD,17HCs / DMN, SN / +/-
Binnewijzend et al., 2012 / ICA, dual regression / 39AD,23MCI,43
HCs / DMN, Precuneus, PCC / -
Chhatwal et al., 2013 / ICA / 15 AD, 37 HCs / DMN / -
Ciftci et al., 2011^ / RSFC, minimum spanning tree / 13AD,14young HC,
14old HC / PCC, Precuneus, Hippocampus / -
Cole et al., 2011 / RSFCseed-based / 14AD,15HC / Pain networks, R DLPFC / +
Damoiseaux et al., 2012 / ICA, dual regression / 21AD,18HCs / Subdivisions of the DMN / +/-
Galvin et al., 2011 / RSFCseed-based / 88total-longitudinal(15DLB,35AD,38HCs) / Precuneus / -
Gili et al., 2011 / ICA / 11AD,10MCI,
10HCs / DMN / -
Greicius et al., 2004 / ICA / 13AD,14YHCs,14
HCs / DMN, PCC
Hippocampus / +/-
Jones et al., 2011 / ICA and seed-based analyses / 28AD,56hc / aDMN, pDMN, seed analyses w/ medFC and precuneus / +/-
Kim et al., 2013^ / RSFCseed-based / 13AD,14HCs / Hippocampus and Precuneus / -
Li et al., 2013 / ICA / 14AD,16HCs / DMN, DAN / +/-
Liu et al., 2013 / RSFCseed-based,
graph theory / 18 severe AD, 17 mild AD, 18 MCI, 21 HC / DMN / -
Song et al., 2013 / ICA / 35 AD, 18 aMCI, 21 HC / DMN, AN, LFP, Pcu, RFP, SMN, VN / -
Wang, K. et al., 2007 / RSFC – whole brain / 14 AD, 14 HCs / Whole brain, PCC / +/-
Wang, L. et al., 2006 / RSFCseed-based / 13 AD, 13 HCs / Hippocampus / +/-
Wang, Z. et al., 2013 / RSFC, hierarchical ICA clustering analysis / 32 AD, 38 HC / IPL subregions / +/-
Wu et al., 2011* / ICA, Bayesian modeling / 15AD,16HCs / DMN / -
Yao et al., 2013 / RSFCseed-based / 35 AD, 27 MCI, 27 HC / Amygdala / -
Zamboni et al., 2013 / Probabilistic ICA
Task and Rest / 30 AD, 25 MCI, 25 HC / Hippocampus / +/-
Zhang et al., 2009 / RSFCseed-based / 18AD,16HCs / PCC / +/-
Zhang et al., 2010 / RSFCseed-based / 46AD,16HCs / DMN, PCC / +/-
Zhou et al., 2008 / ICA / 11AD,10MCI,13
HCs / DMN / -
Zhou et al., 2010 / ICA / 12AD,12FTD,12
HCs / DMN, PCC, Salience network / -
Zhou et al., 2013 / RSFCseed-based / 35 AD, 27 MCI, 27 HCs / Thalamus / +/-
Zhu et al., 2013 / RSFCseed-based / 10AD,11aMCI,12
HCs / Precuneus, PCC / -
Table 3c: Studies of ROIs/subnetworks during task in AD
Author / Analysis / Sample size / ROIs / Result
Franciotti et al., 2013 / ICA, Granger causal modeling / 18Lewy,18AD,15
HCs / DMN, PCC / -
Genon et al., 2012 / PPI, ICA / 32AD,17HCs / Precuneus, PCC / -
Li et al., 2012 / ICA., Verbal fluency task / 15 AD, 16 HCs / Dorsal and Ventral Attention networks, CC, MPFC / -
Liu et al., 2012 / ICA, granger causality / 18AD,18HCs / RSNs, DMN, Auditory network / +/-
Miao et al., 2011 / Granger causal modeling / 15AD,12youngHCs,
16oldHCs, / DMN, PCC, medFC, IPL / -
Ries et al., 2012! / PPI analysis, memory self-appraisal task / 12AD,12HCs / Med FC / -
Rombouts et al., 2009 / Tensorial probabilistic ICA / 18 AD, 28 MCI, 41 HCs / Motor, Visual, Cognitive networks and DMN during face encoding task / -
Rytsar et al., 2011 / DCM / 14 AD, 16 HCs / V1, V3 / -
Schwindt et al., 2012 / RSFC, visual task / 16 AD, 18 HCs / DMN / -
Song et al., 2013 / ICA / 35 AD, 18 aMCI, 21 HC / DMN, AN, LFP, Pcu, RFP, SMN, VN / -
Wen et al., 2013* / Power spectral analysis and Granger Causal modeling / 15AD,16HCs / DMN / -
Note: all “Results” for AD samples only, for studies including AD & MCI samples, MCI findings presented below. *=identical samples included only once in Figure 2.
Table S3d-e
Connectivity Results for MCI Examining ROI and Subnetworks and Task
Table 3d: Studies of ROIs/subnetworks in MCIAuthor / Method
Analysis / Sample size / ROIs / Result
Agosta et al., 2012 / RSFC / 13 AD,12 MCI, 13HC / DMN, Frontoparietal, ECN, SN / -
Bai et al., 2008 / Regional homogeneity / 20 aMCI, 20 HCs / DMN, PCC, RIPL, R fusiform, Putamen / +/-
Bai et al., 2009b* / RSFCseed-based / 30 aMCI;26hcs / PCC and whole brain / +/-
Bai et al., 2011a** / ICA / 26 aMCI, 18 HCs / PCC, Precuneus / +
Bai et al., 2011b** / RSFCseed-based / 26 aMCI, 18 HCs / Cerebellum / -
Bai et al., 2011c** / RSFC-whole brain correlation / 26 aMCI, 18 HCs / Frontal, Subcortical / +/-
Bai et al., 2012** / ICA, cross-correlation / 26 aMCI, 18 HCs / Self-referencing network / +
Bokde et al., 2006 / Linear correlation coefficient / 16 MCI, 19 HCs / Right middle frontal gyrus / +/-
Binnewijzend et al., 2012 / ICA, dual regression / 39 AD, 23 MCI, 43 HCs / DMN, Precuneus, PCC / nd
Das et al., 2013 / RSFCseed-based / 17 MCI, 31 HCs / Medial temporal lobe / +/-
Dong et al., 2012 / RSFCseed-based / 8 MCI ,8 SA,8 UA / DMN / +/-
Drzezg et al., 2011 / RSFC-whole brain correlation / 12 PIB+, 12 PIB-, 13 PIB+/MCI / Whole brain connectivity / -
Esposito et al., 2013 / self-organizing ICA / 13 MCI, 24 HCs / DMN, SMN, IPL, SMG / +
Feng et al., 2012 / RSFC-whole brain correlation / 12 MCI, 12 HCs / Whole brain / +/-
Gili et al., 2011 / ICA / 11 AD, 10 MCI,
10 HCs / DMN / -
Gour et al., 2011 / ICA / 13 MCI, 12 HCs / Anterior temporal network, DMN, ECN / +
Han et al., 2012 / RSFCseed-based / 40 MCI, 40 HCs / PCC / +/-
Jin et al., 2012 / ICA / 8 MCI,8 HCs / DMN / +/-
Li et al., 2013 / ICA. / 17 aMCI, 17 HC / DMN / -
Liang et al., 2012*** / RSFCseed-based / 14 MCI,14 HCs / DLPFC to IPC, IPS, AG, SG / +/-
Liang et al., 2011*** / RSFCseed-based / 14 MCI,14 HCs / DMN, ECN, SN / +/-
Liu et al., 2013 / RSFCseed-based,
graph theory / 18 severe AD, 17 mild AD, 18 MCI, 21 HC / DMN / +/-
Qi et al., 2010*** / ICA / 14 MCI,14 HCs / DMN / +/-
Rombouts et al., 2009 / Tensorial probabilistic ICA / 18 AD, 28 MCI, 41 HCs / Motor, Visual, Cognitive networks, DMN / -
Song et al., 2013 / ICA. / 35 AD, 18 aMCI, 21 HC / RSNs: DMN, AN, LFP, Pcu, RFP, SMN, VN / -
Sorg et al., 2007 / ICA / 24 aMCI, 16 HCs / DMN, Hippocampus, PCC / -
Wang Y et al., 2013 / ICA / 18 MCI, 23 CC, 16 HCs / DMN, Hippocampus / -
Wang, Z. et al.,. 2011*** / RSFCseed-based / 14 MCI,14 HCs / Hippocampus / +/-
Wang, Z. et al., 2012a *** / RSFCseed-based / 14 MCI,14 HCs / Thalamus / +/-
Wang, Z. et al., 2012b*** / RSFCseed-based / 14 MCI,14 HCs / PCC / +/-
Xie et la., 2012* / RSFCseed-based / 30 aMCI, 26 HCs / Insula / +/-
Xie et al., 2013 / RSFCseed-based / 18 LLD, 17 aMCI, 12 LLD & aMCI, 25 HC / Hippocampus / -
Yao et al., 2013 / RSFCseed-based / 35 AD, 27 MCI, 27 HC / Amygdala / nd
Yi et al., 2012 / Functional connectivity density / 26 MCI, 28 HCs / DMN / -
Zamboni et al., 2013 / Probabilistic ICA., correlation, rest and task / 30 AD, 25 MCI, 25 HC / Hippocampus
Zhu et al., 2013 / DICCCOL, functional connectome / 10 MCI, 24 at-risk MCI, 10 HCs / DTI derived ROIs for functional connectomes / +/-
Zhu et al., 2013 / RSFCseed-based / 10 AD, 11 aMCI, 12 HCs / Precuneus, PCC / nd
Zhou et al., 2013 / RSFCseed-based / 35 AD, 27 MCI, 27 HCs / Thalamus / +/-
Zhou et al., 2008 / ICA / 11 AD, 10 MCI, 13 HCs / DMN / -
Table 3e: Studies of ROIs/subnetworks during task in MCI
Author / Analysis / Sample size / ROIs / Result
Bai et al., 2009a / Cross-correlation / 28 aMCI, 23 HCs / Memory-related networks, Hippocampus / +/-
Jacobs et al., 2012 / Granger causal methods / 18 MCI,18 HCs / Parietal connectivity / +/-
Liu et al., 2012 / ICA, multivariate granger causal modeling / 16 MCI, 18 HCs / 8 RSNs / +/-
Neufang et al., 2011 / DCM / 15 pAD, 16 healthy elderly / Cingulo-fronto-parietal network / -
Yan et al., 2013 / ICA, Granger causal modeling / 18 aMCI, 18 HCs / DMN / +/-
Note:all“Results”forMCIsamplesonly,forstudiesincludingADMCIsamples,ADfindingspresentedabove.*,**,***=identical samples,findingsincludedonlyonceinFigure 2.AbbreviationsforTable3a-d:ACC=anteriorcingulatecortex,AD=Alzheimer’s disease, AG: angular gyrus, aMCI=amnesticmildcognitiveimpairment,DLB=dementiawithLewybodies,DLPFC=dorsolateralprefrontalcortex, DMN=defaultmodenetwork,ECN=executivecontrolnetwork,FC=functionalconnectivity(correlation),fMRI=functionalmagnetic resonanceimaging,HC=healthycontrol,ICA=independentcomponentsanalysis, IPC= inferior parietal cortex, IPS= intra-parietal sulcus, LIPG=leftinferiorparietalgyrus,nd=no difference,pAD=prodromalAD,PCC=posteriorcingulatecortex,PET=positronemissiontomography,PFC=prefrontalcortex,PPI-psychophysiologicalinteraction,PP-MS=primaryprogressiveMS,RIFG=Rightinferiorfrontalgyrus,RIPL=rightinferiorparietal lobule,RR-MS=relapsingremittingMS, RSFC= resting state functional connectivity; SA=successfulaging,SEM=structuralequationmodeling, SICE=sparseinversecovarianceestimates, SG=supramarginal gyrus, SL=Synchronizationlikelihood,SMA=supplementarymotorcortex,SN=salience network,V1,V3:visualcortex,UA:usualaging.