Using fMRI to Evaluate Working Using fMRI to Evaluate Working Memory Function of FASDMemory Function of FASD

Krisztina Malisza, PhDKrisztina Malisza, PhDInstitute for Biodiagnostics Institute for Biodiagnostics

National Research Council of CanadaNational Research Council of Canada

What are we trying to do?What are we trying to do?

Neural Activity In Response to task

WhereDetection

How MuchQuantify

What do we measure with fMRI?What do we measure with fMRI?

BrainActivity

Metabolism

Blood Flow

O2

O2

What do we measure with fMRI?What do we measure with fMRI?

BrainActivity

Metabolism

Blood Flow

O2

O2

dHb

dHb

Deoxyhemoglobin causes a variation in the local magnetic field on a macroscale

What do we measure with fMRI?What do we measure with fMRI?

BrainActivity

Metabolism

Blood Flow

O2

O2

dHb

dHb

T2*

T2*

T2* - transverse relaxation caused by variations in local field on a macroscale

What do we measure with fMRI?What do we measure with fMRI?

BrainActivity

Metabolism

Blood Flow

O2

O2

dHb

dHb

T2*

T2*

MR Signal

MR Signal

What do we measure with fMRI?What do we measure with fMRI?

BrainActivity

Metabolism

Blood Flow

O2

O2

dHb

dHb

T2*

T2*

MR Signal

MR Signal

fMRI Data AcquisitionfMRI Data AcquisitionHemodynamic Response FunctionHemodynamic Response Function

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fMRI Data AcquisitionfMRI Data AcquisitionBlock DesignBlock Design

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fMRI BackgroundfMRI Background

Physiological effects relating to changes in neuronal activity cause changes in the MR signal intensity

By imaging a volume of the brain or spinal cord repeatedly during alternated “rest” and “task” periods, we can detect where the signal intensity changed in relation to the activity

Objectives:• To determine FASD child/adult brain function

in areas of attention, spatial memory and working memory

• Develop MRI based techniques to aid diagnosis of FASD

• To determine if there are different regions of fMRI activity in subjects with FASD than controls using a working memory task

MethodsMethodsSubjects:

Child Control n=15 Child FASD n=14

Adult Control n=10 Adult FASD n=10

fMRI

1.5T GE Signa LX MRI system

• Gradient-Echo Echo Planar Imaging (EPI)

• 3 activation states alternated with 4 rest states (NR=56)

N-BackTasksN-BackTasks(n=0) Simple (2 1 4 3)(n=0) Simple (2 1 4 3)

(n=1) One-back (NR 2 1 4)(n=1) One-back (NR 2 1 4)

(n=2) Two-back (NR NR 2 1)(n=2) Two-back (NR NR 2 1)

(n=1) Blank (NR 2 NR 4)(n=1) Blank (NR 2 NR 4)

N-BackTasksN-BackTasks

MethodsMethods• 4 fMRI tasks:

Saccadic eye movement Finger movement Working memory (spatial, object) Procedural learning Attention

HUMAN BRAIN: PREFRONTAL CORTEX

A. Spatial working memory A. Spatial working memory B. Spatial working memory, performance of self-ordered tasks B. Spatial working memory, performance of self-ordered tasks C. Spatial, object and verbal working memory, self-ordered C. Spatial, object and verbal working memory, self-ordered tasks, analytic reasoning tasks, analytic reasoning D. Object working memory, analytic reasoning D. Object working memory, analytic reasoning

Scientific American, August 1997

Lobes of the Cerebral CortexLobes of the Cerebral Cortex

Prefrontal cortex (DLPFC)working memory

•Anterior cingulate attention, response selection

•Parietal lobe discrimination, memory, spatial perception

•InsulaVisceral function, integrates autonomic infoConnections to temporal & parietal lobeResponse inhibition/selection Executive function

Brain RegionsBrain Regions

Data AnalysisData Analysis

50% correct responses on fMRI tasks

Children (FASD: Control): Blank: 9:141-Back: 7:13

Adults (FASD: Control): Blank: 10:101-Back: 6:9

SPM 99 (computer program)

Images corrected for motion, normalised to a adult or child template then smoothed

Individual activations in more difficult tasks (n=1) subtracted from simple (n=0) task

Activations displayed on a T1 template

Data AnalysisData Analysis

Open bars: Controls; Filled bars: FAS participants

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Combined adult and child fMRI task performance

AdultsAdults

Blank - simple

FASD (25y,F)

Control (26y, F)

P=0.01

P=0.01

P=0.05

P=0.01

P=0.05

FASD (26y,F)

AdultsAdults

1-back - simple

P=0.01

P=0.05

P=0.01

P=0.05

FASD, 26y and 25y, F

Control, 26y, F

Mean Response Times Mean Response Times L

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Simple 1-back blank 2-backTask

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Adult ControlAdult FAS

Incorrect and No responsesIncorrect and No responses

simple 1-back blank 2-back

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Adult ControlAdult FAS

ChildrenChildrenS51 – FASD (11y, F)S45 – FASD (11y (just), F)

Blank - simpleS32 Control (11 y, F)S47 Control (10 y, F)

P=0.01

P=0.01

P=0.01

P=0.01

ChildrenChildren

1-back - simpleS32 Control (11 y, F)S47 Control (10 y, F)

S51 – FASD (11y, F)S45 – FASD (11y (just), F)

P=0.01

P=0.01

P=0.01

P=0.01

Response timesResponse times

simple 1-back blank 2-back

Tasks

Lat

ency

(s)

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Child FASChild control

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Child FASChild Control

fMRI ConclusionsfMRI Conclusions

Adults & Children

• Consistent activations in brain regions associated with working memory (DLPFC) and attention (cingulate)

• Controls - increase in frontal activity with increasing task difficulty; not as consistent in FASD

• FASD – greater inferior frontal activation than controls • Controls – activation in insula; very little if any in FASD

promising preliminary results - full study required

Self-Ordered PointingSelf-Ordered Pointing

Test of visual working Test of visual working memory and strategic memory and strategic memorymemory

Presented with Presented with nn sets of sets of nn pictures pictures

((nn = 6, 8, 10 or 12) = 6, 8, 10 or 12)

In each sheet of a given In each sheet of a given set, S must touch a set, S must touch a different picture different picture

Self Ordered Pointing

Group

FASControl

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Wisconsin Card Sorting TaskWisconsin Card Sorting Task

Successful performance requiresSuccessful performance requires» Planning abilityPlanning ability» Cognitive flexibilityCognitive flexibility» Working memoryWorking memory» Response inhibitionResponse inhibition» Concept formation and reasoningConcept formation and reasoning

Kolb & Whishaw, 2001, p.541

WCST Measure Control FAS

Perseverative Responses SS

111.0 (17.5)

93.4 (34.8)

Perseverative Errors SS 108.7(14.4)

91.5(31.6)

Nonperseverative Errors SS * 105.4(7.4)

92.3 (15.6)

% Conceptual Level Responses SS **

104.7(7.8)

88.0 (17.3)

Number of Categories ** 5.9(0.4)

3.9(1.8)

* p<.10; ** p<.05

Continuous Performance TaskContinuous Performance Task

Detect the presence of targets in a series of trials that include distractors

Measures: – # correct responses# correct responses– correct response latencycorrect response latency– probability of a hitprobability of a hit– probability of a false alarmprobability of a false alarm

CPT: Latency of Correct Responses

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FASControl

Me

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late

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.60

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.20

.10

0.00

*

Group, F(1,14) = 10.14, p<.01

CPT

• Age main effect: Children performed worse than adults on all 4 indicies

• Group main effect: FAS performed similarly to controls on all measures except mean latencies of correct responses

significantly longer than controls p <0.01

Indicates that group differences on other measures were unlikely due to group differences in ability to remain on task.

ConclusionsConclusions Adults and children with FASD show impaired performance Adults and children with FASD show impaired performance

relative to age- and sex-matched controls, on tasks tapping into relative to age- and sex-matched controls, on tasks tapping into executive function, sustained attention, and visual working executive function, sustained attention, and visual working memorymemory

Significant latency of response for FASD subjects compared to Significant latency of response for FASD subjects compared to controls – but both groups paying attention!!controls – but both groups paying attention!!

Not all exposed individuals show deficitsNot all exposed individuals show deficits Studying unique neuroanatomical & neuropsychological Studying unique neuroanatomical & neuropsychological

profile of individuals with FASD is important for design of profile of individuals with FASD is important for design of assessment tools, and development of support and intervention assessment tools, and development of support and intervention programs for patients and their familiesprograms for patients and their families

fMRI may prove helpful in this regardfMRI may prove helpful in this regard

AcknowledgementsAcknowledgementsIBD - IBD - Ms A. Allman, Dr. D. ShiloffMs A. Allman, Dr. D. ShiloffU of M, Psychology –U of M, Psychology – Dr. L. Jakobson Dr. L. JakobsonHSC – HSC – Dr. A. Chudley, Dr. S. Longstaffe Dr. A. Chudley, Dr. S. Longstaffe

child life specialistschild life specialistsMs D. KuypersMs D. KuypersMs S. TreichelMs S. Treichel

Financial supportFinancial supportManitoba Medical Services Foundation Manitoba Medical Services Foundation Ava-Ann AllmanAva-Ann Allman - Women in Engineering and Science - Women in Engineering and Science

(WES) Award -NRC (WES) Award -NRC