Functional Magnetic Resonance Imaging

Carol A. Seger

Psychology

Molecular, Cellular, and Integrative Neuroscience

Michael Thaut

Music, Theater, and Dance and MCIN

Outline

• Overview of fMRI

• Our lab’s research questions

• Open imaging issues in fMRI– Spatial normalization and interindividual

comparisons– Functional connectivity analyses

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fMRI: what are we measuring?BOLD imaging

– Blood oxygenation level dependent contrast. • Ratio of deoxyhemoglobin to oxyhemoglobin• Essentially reflects blood flow (hemodynamic response)

– Hemodynamic response characteristics• Tightly coupled to neural activity. • Slow• Additive

• Inherently comparative method

Steps in fMRI

• Design• Image acquisition

– Anatomical images– Functional images

• Across multiple tasks

• Preprocessing– Slice timing correction– Temporal smoothing– Motion correction– Spatial smoothing– Normalization to template

brain

• Statistical analyses– Deconvolution of BOLD

signal– Voxel wise statistical

analyses comparing BOLD signal to task

• Correction for multiple comparisons

– Functional connectivity analyses

• Data visualization– False color overlay onto

anatomical images– Cortex inflation

Introduction to my research questions

• “The roles of corticostriatal loops in human learning and cognition”– Corticostriatal loops and the basal ganglia– Human stimulus-outcome learning

• Michael Thaut, Music Therapy.• Rhythm and tempo processing, and its

interactions with human motor performance.

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Basal Ganglia:A Striatum 1. Caudate a. head b. body/tail 2. Putamen 3. Ventral striatum /

nucleus accumbensB Output nuclei SNc, GPi

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Visual Loop

Motor Loop

Executive Loop

MotivationalLoop

TemporalCortex /VentrolateralPrefrontal

GPi / SNr

Thalamus

Caudate:Body/Tail

Orbito-Frontal /AnteriorCingulate

GPi / SNr

Thalamus

VentralStriatum

DorsolateralPrefrontal /PosteriorParietal

GPi / SNr

Thalamus

Caudate:Head

Premotor /SMA /Somato-sensory

GPi / SNr

Thalamus

Putamen

Motivational Executive Visual Motor

Parallel Corticostriatal Loops

Associative Modificed from Lawrence et al, 1998

Stimulus-outcome learning

Learn to respond to a particular stimulus or situation withAn appropriate response that will result in an appropriateOutcome

Many different tasks Instrumental conditioningArbitrary motor response learningCategorization

Example study:Visual categorization taskFocus on the visual loop

Method: Typical Learning TaskTrial:

Right0

2500…

3500 ms

3000

• View stimulus• Make response

– Button press indicating category

• Receive feedback– “Right” or “Wrong”

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8 faces, 8 houses.Event related analyses

deconvolve BOLD on each trial.compare different types of trials

face trials vs house trialscorrectly categorized vs error

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Basal Ganglia:Activity in the body of the caudate associated with correct categorization

Visual Cortex:Activity in the fusiformGyrus associated withProcessing faces.FFA - Fusiform face area

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Activation within the visual corticostriatalLoop during categorization of faces.

Thaut lab

Spatial normalization and Interindividual comparisons

• Variability in brain size and shape across people

• Special issues in normalizing the basal ganglia.

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SPM: 1. 12 parameter affine

registration2. Registration using a spatial

transformation model consisting of a linear combination of low-spatial frequency discrete cosine transform functions

--> 1176 df

Functional Connectivity

• Anatomical Connectivity measurements– Diffusion Tensor Imaging

• Functional Connectivity measurements– Model free approaches– Model based approaches

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Diffusion Tensor Imaging

White mattermyelinated axons connecting brain regions.

Basal ganglia: Verifying corticostriatal loop anatomy in humansExamine individual differences in anatomical connectivity

Principles of Functional Brain Organisation

1) Functional specialisation (Localism)Assumption of functionally specialised brain regions

General Connectivity Analysis

Voxel time series

StimulationParadigm

‘Functional Localisation’

comparison

1.

Region A

Region B

comparison

‘Inter-regional Connectivity’

2.

stimulus

ON OFF

Functional Connectivity Overview

Step 1 : Postulation of Model

- postulation of a hypothetical model of inter-regional interactions

- should be based on known anatomical connections

Numerical Version: Structural Equations

y1 = b13 x + b13 y2

y2 = b23 y3

y = B x

Slide 10

Functional Connectivity in fMRI

- defined as ‘temporal coherence between spatially remote neuro-physiological events’

(Friston et al., 1993)

- generally assed by correlation coefficients between brain regions

- simplest form of function connectivity equals bivariate correlation coefficient

A

B

r(a,b)? If r significant then

A and B functionally connected

Model freeFunctional connectivity

• Generally start with a seed region, then identify other regions using various methods– Correlation

• Principal component analysis• Partial least squares analysis

– Granger causality mapping• Vector Autoregressive modeling

– Coherence analysis• Spectral methods• Fourier analysis or wavelets

Example connectivity maps

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Granger Causal ModelingRed: seed regionGreen: preceeds / predicts seedBlue: follows / predicted by seed

Coherence analysisCircle: Seed in motor cortex

Granger Causality analysisSeed region Fusiform Face Area • predicted body/tail of the caudate activity • 8 / 8 subjects

RH

LH

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Corticostriatal interaction during categorization

y3

y1

y2

b13

b23

b12

Numerical Version: Structural Equations

y1 = b13 x + b13 y2

y2 = b23 y3

y = B x

Path Coefficients =strength of effective connection

y3

y1

y2

0.3

0.8

0.2

Model Bases Analyses:Structural Equation Modeling

Summary - Future Directions

• Continue our work on corticostriatal loops in human learning and cognition.

• Anatomical Spatial Normalization• Functional Connectivity• Other imaging issues

– Comparisons across patient groups– Better ways to deconvolve blood flow measures

• Funded by NIMH

Blocked Design20-60 sec

• Consecutive, rapid presentation for long duration.• Use overlap to build a larger signal.• Advantages:

•Simple analysis.•Optimal for detection.

20-60 sec fixation

HRF

trials

Additivity of the hemodynamic response

1 2 3

W. W. Norton

What does the basal ganglia do?1. Modulatory system2. Selection or gating of responses --- extending to strategies, etc. Accounts for symptoms of Parkinson’s and Huntington’s diseases