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单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,Task-based fMRI,basic principles and applications,刘一军,北京大学 工学院 生物医学工程系,北大脑健康科学及工程中心,&,Departments of Psychiatry&Neuroscience,,,McKnight Brain Institute,,,University of Florida,1,Methodology&Applications,Oxygenation,Volume,(,VASO,),Time,(,Current MRI,),(,FSE,),(,SWI,),(,ASL,),(,DWI,),2,f,MRI-FMRI,“Structure”,:anatomical,f,MRI-FMRI,compositional,biochemical,etc.,结构,:,解剖,、形态、组织组成,生化特性,Activation,:localized brain activity changes,激活,:,功能,定位、神经活动变化,Modularity,:functional connectivity/network imaging,连接,:,功能,调制、网络成像,Dynamics,:time dependence(short-or long-term)/causal,动态,:,时间,效应、动力学(如:药动力学等),(研究对象四个层面),3,f,MRI:Localization,(,功能定位),Talairach Coordinates,X=-48,Z=32,6.0,t,2.5,Br,(Left M1 Mouth Region/BA4),M1,Wn,SMA,4,Functional,Volume Modeling,(FVM),Multiple Studies,(tasks);,Multiple Centers,(groups),f,MRI-Assisted Neurosurgery,5,fMRI,任务设计的基本原则,一般要求:,对照控制,随机性,重复性,均衡性,两个重要原则:,1、拒绝一个假设(Null Hypothesis),2、得到显著效应(或产生显著差异)。,6,fMRI,任务基本概念与类型,基本类型:,1.组块(Blocked),2.事件相关(Event-Related),快速事件,慢速事件,3.混合设计,两个重要思想:,1、临床 意义;,2、分析方法的匹配。,7,Analysis Methods,Dependent,Block,Event-Related,time,time,Independent,?,time,Memory consolidation;,Mood induction;,Drug intervention;,Nutrition;,Spontaneous events.,TCA Model/Liu,2000,8,fMRI,新范式与实验设计,从结构到功能,从基础到临床,从简单到复杂,9,Insula,举例,1,10,举例,2,:最近的一项研究结果,Yuan et al,(,PloSOne,,,2011,),The problematic Internet use(PIU),restructures the brain in adolescents,11,背景:,Previous studies provided scientific evidences of the,brains ability to reshape itself with experience.However,to,date the structural effects of problematic Internet use(PIU),or Internet addiction disorder(IAD)on cortical thickness,among adolescents are not well known.,研究方法:,High-resolution MRI VBM/FreeSurfer,;,adolescents with PIU and age-,education-and gender-,matched controls were acquired.The color-word Stroop task,was adopted to assess the executive function.The cortical,thickness measurement method was employed to investigate,alterations of cortical thickness in individuals with PIU.,12,13,2:Motor cortex;7-lingual cortex,10:Orbito-frontal cortex,14,15,16,The findings,implicated that PIU was tied to,physical changes in the cortical thickness of the,adolescents brain.The finger movement and motor,imagery related brain regions were thicker in,adolescents with PIU;however,the regions,implicated in executive function and visual-language,processing were thinner.-,Yuan et al,(,2011,),17,举例,3,basal,timing,counting,18,-3,0,33,fMRI scan 1,BACs measure,-5,35(mins),tasks,tasks,fMRI scan 2,3(hours),Effects of Low-dose Alcohol on Neural Timing,Alcohol Beverage,(0.25 g/kg),Time(min),0,-5,-5,30,0,Alcohol,BOLD signal(%),+5,Virtual,Traffic-light,timing tasks,19,Timing,odd ball design,T=4 seconds,20,Counting,odd ball design,21,Response Accuracy,Reaction Time(ms),A,85%,90%,100%,Pre-Drink,Counting,Post-Drink,Timing,(N=8),B,500,700,600,800,95%,900,Pre-Drink,Counting,Post-Drink,Timing,(N=8),Fig.3 Behavioral Data,Behavioral data,22,Task Rest,Task,Rest,32,25,10,5,0,Time(min):,Methods,METHODS,0.25g EtOH per Kg body weight,approx 1 shot of 80 Pf Vodka in a 200mL,cocktail diluted with diet 7-up,Scanner:Siemens,3 Tesla,Software:IFIS,e-Prime&Brain Voyager,Tasks:Counting&Timing,6 seconds Vs.4 seconds,23,TABLES,Table I.Pre-Drink Brain Activation:Timing Counting,Region,Supplementary Motor Area,Cerebellum,Cerebellum,Inferior Parietal Lobe,Insula,Insula,Medial Frontal Gyrus,Middle Frontal Gyrus,Middle Frontal Gyrus,Superior Frontal Gyrus,VL of Thalamus,BA,6,-,-,40,-,-,6,10/46,9,9,-,Side,R,L,L,R,R,L,M,R,L,R,M,x,43,-32,-32,48,33,-38,1,33,-29,23,-14,y,4,-76,-52,-47,16,15,8,44,50,49,-14,z,24,-25,-32,32,7,5,51,20,18,28,17,Size,519,1222,278,472,800,2659,1184,910,2641,1139,242,t-score,6.35,6.38,6.25,6.15,6.54,6.68,6.28,6.43,6.71,6.17,5.97,P,(corr.)200 voxels are shown.BA=Brodmanns Area.Size=number,of 1mm,3,voxels.X,Y,and Z refer to Talairach coordinates(Talairach J and Tournoux P,1988).,24,Imaging Data of Pre-Drink State:,Timing Counting,-,+,25,Imaging Data of Timing Task,Post Drink Pre-Drink,The findings,provide additional insight,regarding the acute cognitive and,psychomotor impairments that result,from exposure to a low dose of alcohol.,-,Nelson et al,(,2011,),JMRI,27,28,A or B?,ICCS2010,29,ICCS2010,举例,4,30,ICCS2010,31,-From,Lang,1999,IAPS Rating/AdSAM(PAD),3530,Not at all,Extremely,1,2,3,4,5,Surprised,Fearful,Angry,Sad,Disgusted,Happy,_,_,_,_,_,_,Cross validation,ICCS2010,3789,32,Morris/Liu,2009,Using AdSAM as Constraints,ICCS2010,33,Morris/Liu,HBM,2009,ICCS2010,34,Reference:,Mapping a Multidimensional Emotion in Response to Television,Commercials,Jon D.Morris,1,2*,Nelson J.Klahr,2,3,Feng Shen,1,Jorge Villegas,1,Paul Wright,2,3,Guojun He,2,3,and Yijun Liu,2,3*,Morris/Liu,HBM,2009,Emotion dissociation at,different dimensions,35,36,Smoke-Craving Stimuli,High,Medium,Low,37,38,L,R,A novel paradigm,Temporal Symmetry,of brain response to the changing face,vs.,Spatial symmetry,39,Faces in the Picture,The Self-Portrait of,A.Drer,The difference between the two,hemispheres is reflected in the face.,(,symmetry or asymmetry,),40,Two continuous events both physically(e.g.,temporally,)and psychologically(emotionally),related.,Noticing the changes of facial expression of others,well represents such a sequential process but having,social context.,In particular,changing face is a,reversible,process.,The change of facial expression,41,Procedure,Visual Stimulation,Recognition of emotional facial expressions(Ekman)with a,paired-block,design,.,Subjects,Healthy volunteers(n=10,6 f/4m,23 38 yrs,right-handed):,Psychological and Psychophysiological Measurements:,1.Disgust scaling questionnaire(Rozin);,2.Skin conductance(SC5-SA/Contact Precision,Psylab).,MRI,Scanner:3.0 T Signa(GE).,EPI BOLD Sequence:TE/TR/FA=25 ms/,1500 ms,/70,0,;17 axial slices,8 mm thick;,FOV=24 x 24 cm,2,;Encodings=64x64.,Image Processing:MEDX,SN,TCA and,in-home,programs in MATLAB.,42,Paired-Block Design,Each Run six episodes(e.g.ND,NN,DN,NF,NN,FN).,Three runs for each subject.,43,(From Neutral to Disgust),The Face Changing,Z=63 mm,61,59,57,55,35,53,33,51,31,49,29,47,27,45,25,43,23,41,21,39,19,37,17,-29,-25,-27,-31,-33,P0.01,15,13,11,9,7,5,3,1,-1,-3,-15,-17,-5,-21,-23,-7,-9,-19,-11,-13,NC,vs.,Target,Control,44,Asymmetry,Left,(Neutral to Disgust),Right,Z=-15 mm,(Disgust to Neutral),45,Different Emotions,(Neutral to Disgust),(Neutral to,Fear,),Left,Right,Z=-15 mm,Hippocampus,46,Temporal Symmetry,Left,The blue(,red,)line delineates the brain activation during the recognition of the change from,neutral(,emotional,)face to emotional(,neutral,)face.Pink areas indicate the overlaid activation.,NC:Caudate Nucleus(,corpus,).,Z=21 mm,NC,Z=21 mm,NC,Right,47,The symmetry activation(common to both the directional changes and,both disgust and fear)in the basal ganglia,especially the caudate,nucleus(NC),and the hippocampus(Hi)is consistent with the role of,the NC in gating sensory inputs,and the role of the Hi in encoding or,abstracting sensory inputs for learning and memory.,Based on the above assumptions,we further hypothesize that,there is parallel processing between,emotional encoding,(equivalent to,the implicit processing in facial recognition)at the Hi,which may be,associated with past experience,and,sensory gating,(equivalent to the,explicit processing)at the NC during emotional experience.As,predicted,we found that,in OCD,there is mis-matched activation,between the NC and the Hi during disgust perception but not during,fear perception.,Implication,48,Sensory or Emotional?,“Autism is a most private world,I turned finally,not to categorize or consider their faces,but to see,how they came to terms with them and how they,asserted their independence and individuality”,-from,About Face,by,J Cole,Clinical Implication,49,50,#,#,51,52,53,Characteristics,Gender(male/female),Age(years),Education years,Illness Duration,SMFQ Score,SCARED Score,MDD(n=18),8/10,15.78,1.20,9.2/1.1,6 months,16.67,5.44,44.3919.10,HC(n=18),8/10,16.2,0.9,9.5/0.8,3.56,3.55,14.8910.61,P,value,0.99,0.413,0.311*,0.000*,0.000*,MDD,Major Depression Disorder.HC,Healthy Control group.SMFQ,Short Mood and Feeling,Questionnaire.Unless otherwise indicated,data are shown as mean,SD.,The P value was obtained by Pearson 2 two-tailed test.,*The P value was obtained by a two-sample two-tailed,t,test.,Jiao et al(unpublished),Example:Granger causality analysis in resting-state fMRI,study of adolescent depression,Table 1.Demographic characteristics and clinical variables,54,Differences in the resting-state activity levels estimated by,ALFF,between the adolescent with MDD and healthy subjects,ALFF:amplitude of low-frequency fluctuation(,Zang et al,),55,Differential distributions of the ALFF and the,enlarged frontal vs.(para)limbic-striatal imbalance,in adolescent MDD,56,ALFF,as a neurobiomarker of adolescent,depression symptoms(SMFQ),57,Casey 2008,Testing a hypothesis based on a development model,Jiao et al PloSOne,58,An implication of the dlPFCs role in,rTMS,treatment of depression,ALFF-based Granger network analysis,59,Depressive,Brain,60,An implication of the dlPFCs role in,rTMS,treatment of medication,resistant depression,61,L,R,A summary:GCA methods and its potential applications,Voxel wise(conditional GCA),ROI-based(energy-based),System-wise(block GCA),asymmetric,baseline information flow between,the brain hemispheres,?,62,
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