Functional MRI: techniques and applications. Susan Bookheimer, Ph.D. UCLA Center for Cognitive Neurosciences

Transcription

1 Functional MRI: techniques and applications Susan Bookheimer, Ph.D. UCLA Center for Cognitive Neurosciences

2 none Disclosures

3 Outline Basis of fmri signal; how it works, what it measures fmri experimental design New techniques Clinical applications Research applications

4 Introduction to Functional Imaging Neurovascular Coupling: Increased local brain activity leads to: Increased glucose utilization Increased cerebral blood flow Increased cerebral blood volume Minimal increase in oxygen utilization Increased deoxyhemoglobin concentration

5 Functional Magnetic Resonance Imaging (FMRI) MRI scanning of brain function (vs. structure) An indirect measure of increased regional cerebral blood flow during neural activity During increased brain activity, MRI signal intensity ( brightness ) increases with the increase in oxyhemoglobin concentration Tells us which brain regions are working during task performance

6 Principles of fmri Indirect measure of blood flow Measures changes in magnetic susceptibility due to change in ratio of oxygenated vs. deoxygenated blood that accompanies increased neural activity Relative measure change across states (rest, activity) of arbitrary units of signal intensity

7 Change in oxyhemoglobin concentration during increase blood flow

8 Visual Stimulation in Occipital cortex

9 Time Series analysis: Changes in MRI signal intensity during activation

10 Assumptions in fmri Assumes relatively intact blood flow response Permits relative, activation based measurements only Requires adequate task performance

11 fmri techniques Fast- scanning: Echoplanar (EPI) imaging Gradient echo EPI: susceptibility weighted Spin echo or asymmetric spin echo EPI Spiral Arterial spin labeling

12 Hemodynamic response to activation tasks

13 Image processing Image reconstruction into a time series of volumes Test the extent to which the MR signal intensity conforms to the predicted hemodynamic response Present results in an accessible format

14 Practical issues Getting people in the scanner Stimulus presentation Head motion restraint Mathematical correction (eg AIR)

15 MRI Scanner

16 MRI Compatible Video Goggles

17 Conceptual and methodogical aspects of experimental design There are two aspects of fmri design that are important to distinguish Conceptual design How do we design tasks to properly measure the processes of interest? The issues here are very similar to those in cognitive psychology Methodological design How can we construct a task paradigm to optimize our ability to measure the effects of interest, within the specific constraints of the fmri scanning environment?

18 fmri experimental design: A basic plan Define mental process to examine Define tasks to manipulate that process Measure fmri data during tasks Compare fmri data between tasks

19 Hierarchical Ex B - } Ex A - } Control Tailored Baseline Ex A > Ctl A Ex B > Ctl B >} Factorial Designs Ex A Common baseline Control Ex B Parametric A< A < A < A Ex B Ex A Mixed, Nested Designs Parallel > > Ex A Selective attention A B C A B C A B C Ex B Ex A Ex B AxB Conjunction Designs Priming/Adaptation Designs

20 The subtraction method Acquire data under two conditions These conditions putatively differ only in the cognitive process of interest Compare brain images acquired during those conditions Regions of difference reflect activation due to the subtracted process of interest Petersen et al., 1988

21 Hierarchical subtraction example from Petersen, 1991 Rest Control Auditory words vs. rest: A1, word recognition centers Visual words vs rest: visual areas, word form areas Reading or repeating words vs passive words: motor areas Generating words vs. repeating: semantic (language) areas - } - } Sensory Motor - } Semantic

22 Experimental design models Hierarchical designs Eg: Peterson et al language study Sensory control (see words) Output control (read words aloud) Language task (generate associates) Use a cognitive subtraction model Equate demands on all factors except one Rely on theory of additive factors active areas remain the same throughout the hierarchy

23 Common Baseline Ex A Ex B One level of hierarchy Control Test for violation of additivity assumption Allows you to see common areas active for A and B Assumes A and B have similar psychometric properties (ie, level of difficulty, variation, and distribution in the population) Need additional approach to see unique areas

24 HOUSE

25 Directed Attention Models All stimuli identical in all conditions Direct attention towards different features Implicit or explicit Assumes process is modified by directed attention Assumes passive processing does not capture your variable of interest

26 Example: implicit selective attention with parallel comparisons Subjects hear pairs of sentences. Task: judge if the sentences mean the same thing Implicit Manipulation: sentences differ on semantic or syntactic basis The boy went to the store- The boy went to the market The city is east of the lake. East of the city is the lake Comparisons: Common baseline: each vs. rest Parallel comparisons: semantic vs syntax and reverse

27 EG Corbetta et al

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32 Selective attention to shape, color, motion

33 Implicit Directed attenion EG Dapretto et al Instructions are the same; process required to reach a response differs Syntax vs semantics: sentence comprehension task. Do the sentences mean the same thing (Y N) The boy has gone to the market. The boy has gone to the store The city is east of the lake. East of the lake is the city.

34 Dapretto and Bookheimer, Neuron, 1999

35 Parametric designs Employs continuous variation in a stimulus/task parameter E.g., working memory load, stimulus contrast Inference: Modulation of activity reflects sensitivity to the modulated parameter

36 Boynton et al., 1996

37 Cohen et al., 1996

38 Priming/adaptation designs Presentation of an item multiple times leads to changes in activity Usually decreased activity upon repetition Inference: Regions showing decreased activity are sensitive to (i.e. represent) whatever stimulus features were repeated Requires version of pure modulation assumption Assumes that processing of specific features is reduced but that the task is otherwise qualitatively the same

39 Can adaptation fmri characterize neural representations? Two stimuli: can neurons tell the difference? A voxel containing neurons that respond to all politicians, irrespective of party A voxel containing some specifically Democratic neurons, and other specifically Republican neurons. From R. Raizada

40 Neural adaptation to repeated stimuli does show the difference: What counts as repetition for neurons in a voxel? It s a politician Same neurons, adapting: It s a politician again It s a Republican From R. Raizada Different, fresh neurons: It s a Democrat

41 Timing

42 BLOCKED: Blocked vs. Event-Related fmri SPACED MIXED TRIAL: RAPID MIXED TRIAL: From R. Buckner, HBM2001

43 Experimental Paradigm Match Label Control Block Length = 32.5 sec Total Scan Time = 4:53 min

44 Match Affect Label Affect From Hariri et al 1999 Susan Y. Bookheimer, Ph.D. Hariri et al., 1999

45 Event-Related Designs Event-related or single trial experiments Have stimuli presented 1 at a time rather than in blocks Adjust for the hemodynamic response function Bin like stimuli, obtain averaged HRF Compare HRFs across stimulus types Long ISI studies (15 seconds) allow for complete relaxation of HRF (implicit resting control) Short ISI studies model additive response of like stimuli and adjust

46 Directed vs. averted gaze

47 Event-Related fmri Design TR = 3 s Optimized Random Sequence (Wager & Nichols 2003) TR = 3 s 2 s + 2 s + ISI = ms Jitter = ms + 2 s

48 Episodic Retrieval: R-K Distinction (Eldridge, Knowlton et al 2000) Remember (R) - recognition with conscious recollection Episodic memory Know (K) - recognition without recollection Non-episodic memory

49 Left Hippocampus Anatomic ROI

50 Two-Group Designs Two-group designs Hypothesis: groups differ in activation vs control comparisons Different from resting state differences ala FDG Performance confounds

51 % correct High-Functioning AutisticBoys Accuracy Normal Adults Match Label Control

52 Directed vs. averted gaze

53 TD: Directed vs Averted Gaze (negative emotions) Amygdala, hippocampus, Medial PFC, lateral PFC Visual and HC

54 ASD Visual and HC No task modulation

55 Between-group direct comparisons Direct TD > ASD Averted TD > ASD

56 Functional Connectivity in fmri

57 Functional Connectivity

58 Imaging Genetics Growing Field Examines differences in brain structure/function/connectivity as a result of possessing different genetic polymorphisms Usually chosen for conferring risk for a disorder Imaging differences seen in normal populations with different, common polymorphisms in the absence of obvious behavioral or phenotypic differences

59 fmri in normal subjects with genetic risk for AD Bookheimer, Small, et al, NEJM 2000 Purpose: use fmri to identify changes in brain function prior to significant cognitive decline; predict outcome APOE-3 vs E-4 extremely healthy older volunteers (X=63.5; N=30) Memory stress-test in cognitively normal elderly Memorize unrelated word pairs justice-club Scans compare learning/retrieval vs. control

60 Group Analysis: Effect of Genotype

61 5HTT and imaging

62 Amygdala response: 5HTT short allele > Long allele Cohort 1 Cohort 2

63 Applications Mapping normal functions: within group Clinical applications: between group designs Surgical planning AD/AD risk Drug interventions Psychiatric disorders

64 Clinical Applications: Neurosurgical planning Goal: Identify critical areas Task specificity issues Disruption by the lesion Language performance

65 Stimulation Points- 1 cm Recording Strips

66 Language Tasks Object Naming Finding a name; expression Used in OR; alternate forms; reveals Broca s area and Basal temporal language area Auditory Naming Smell with this nose Color of grass green Finding a name; comprehension, expression

67 Conjunction Analysis Within task, repeat conditions (3 times) Across tasks, find areas of overlap Perform separately for receptive, expressive tasks Allows low magnitude activations that are consistent to show.

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69 Areas of conjunction

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71 Pharmaco- fmri Use fmri to identify brain changes associated with treatment Eg, Acetylcholine agonist treatment may improve memory in AD fmri Pre- and post-treatment with Aricept

72 Donepezil Treatment- Mild AD Pre-Treatment Post-Treatment Related Paired-Associate Learning vs. Rest

73 fmri in Psychiatric populations Panic disorder Social anxiety ADHD Autism Bipolar

74 Panic Disorder- symptom provocation

75 Social Anxiety and amygdala arousal Guyer et al, Arch Gen Psychiatry (11): Simulated online chat in social anxiety and control adolescents

76 Amygdala hyperarousal in social anxiety disordered children

77 Susan Y. Bookheimer, Ph.D. Disgust and Threat Responses in OCD (Shapira et al, Biol Psychiatry. 2003) Disgust Threat Control OCD

78 Susan Y. Bookheimer, Ph.D. Bipolar Disorder- Mania Altshuler et al 2005

79 Summary Numerous applications for fmri in translational research Elucidate normal brain systems Help identify circuits impaired in patient populations Numerous new techniques