using fmri to evaluate working memory function of fasd krisztina malisza, phd institute for...
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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
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What are we trying to do?What are we trying to do?
Neural Activity In Response to task
WhereDetection
How MuchQuantify
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What do we measure with fMRI?What do we measure with fMRI?
BrainActivity
Metabolism
Blood Flow
O2
O2
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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
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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
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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
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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
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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 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
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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
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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)
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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)
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(n=1) Blank (NR 2 NR 4)(n=1) Blank (NR 2 NR 4)
N-BackTasksN-BackTasks
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MethodsMethods• 4 fMRI tasks:
Saccadic eye movement Finger movement Working memory (spatial, object) Procedural learning Attention
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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
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Lobes of the Cerebral CortexLobes of the Cerebral Cortex
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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
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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
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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
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Open bars: Controls; Filled bars: FAS participants
1A
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Task
% C
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Task
% N
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Task
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Task
% In
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Combined adult and child fMRI task performance
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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)
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AdultsAdults
1-back - simple
P=0.01
P=0.05
P=0.01
P=0.05
FASD, 26y and 25y, F
Control, 26y, F
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Mean Response Times Mean Response Times L
aten
cy (
s)
Simple 1-back blank 2-backTask
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7***
***
******
Adult ControlAdult FAS
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Incorrect and No responsesIncorrect and No responses
simple 1-back blank 2-back
Task
Ave
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Adult ControlAdult FAS
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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
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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
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Response timesResponse times
simple 1-back blank 2-back
Tasks
Lat
ency
(s)
0
0.1
0.2
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Child FASChild control
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Ave
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Tasksimple 1-back blank 2-back
Incorrect and No responsesIncorrect and No responses
0
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Child FASChild Control
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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
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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
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Self Ordered Pointing
Group
FASControl
Me
an
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ors
20
18
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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
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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
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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
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CPT: Latency of Correct Responses
Group
FASControl
Me
an
late
ncy
(s)
.70
.60
.50
.40
.30
.20
.10
0.00
*
Group, F(1,14) = 10.14, p<.01
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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.
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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
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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