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Using fMRI to Evaluate Working Memory Function of FASD

Using fMRI to Evaluate Working Memory Function of FASD. Krisztina Malisza, PhD Institute for Biodiagnostics National Research Council of Canada. What are we trying to do?. Neural Activity In Response to task. Where Detection. How Much Quantify. What do we measure with fMRI?.

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Using fMRI to Evaluate Working Memory Function of FASD

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  1. Using fMRI to Evaluate Working Memory Function of FASD Krisztina Malisza, PhD Institute for Biodiagnostics National Research Council of Canada

  2. What are we trying to do? Neural Activity In Response to task Where Detection How Much Quantify

  3. What do we measure with fMRI? Metabolism O2 Brain Activity Blood Flow O2

  4. What do we measure with fMRI? Metabolism O2 dHb Deoxyhemoglobin causes a variation in the local magnetic field on a macroscale Brain Activity Blood Flow O2 dHb

  5. What do we measure with fMRI? Metabolism O2 dHb T2* Brain Activity Blood Flow O2 dHb T2* • T2* - transverse relaxation caused by variations in local field on a macroscale

  6. What do we measure with fMRI? Metabolism O2 dHb T2* MR Signal Brain Activity Blood Flow O2 dHb T2* MR Signal

  7. What do we measure with fMRI? Metabolism O2 dHb T2* MR Signal Brain Activity Blood Flow O2 dHb T2* MR Signal

  8. fMRI Data AcquisitionHemodynamic Response Function

  9. fMRI Data AcquisitionBlock Design

  10. fMRI Data AcquisitionBlock Design

  11. fMRI 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

  12. 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

  13. Methods • Subjects: • 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)

  14. N-BackTasks (n=0) Simple (2 1 4 3) (n=1) One-back (NR 2 1 4) (n=2) Two-back (NR NR 2 1)

  15. N-BackTasks (n=1) Blank (NR 2 NR 4)

  16. Methods • 4 fMRI tasks: • Saccadic eye movement • Finger movement • Working memory (spatial, object) • Procedural learning • Attention

  17. HUMAN BRAIN: PREFRONTAL CORTEX A. Spatial working memory B. Spatial working memory, performance of self-ordered tasks C. Spatial, object and verbal working memory, self-ordered tasks, analytic reasoning D. Object working memory, analytic reasoning Scientific American, August 1997

  18. Lobes of the Cerebral Cortex

  19. Brain Regions • Prefrontal cortex (DLPFC) • working memory • Anterior cingulate • attention, response selection • Parietal lobe • discrimination, memory, spatial perception • Insula • Visceral function, integrates autonomic info • Connections to temporal & parietal lobe • Response inhibition/selection • Executive function

  20. Data Analysis •  50% correct responses on fMRI tasks • Children (FASD: Control): • Blank: 9:14 • 1-Back: 7:13 • Adults (FASD: Control): • Blank: 10:10 • 1-Back: 6:9

  21. Data Analysis • 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

  22. Combined adult and child fMRI task performance Open bars: Controls; Filled bars: FAS participants

  23. FASD (25y,F) FASD (26y,F) Adults P=0.01 P=0.01 P=0.05 Control (26y, F) P=0.01 P=0.05 Blank - simple

  24. Adults FASD, 26y and 25y, F P=0.01 P=0.05 Control, 26y, F P=0.01 P=0.05 1-back - simple

  25. Mean Response Times 0.7 Adult Control *** Adult FAS *** 0.6 *** 0.5 *** 0.4 Latency (s) 0.3 0.2 0.1 0 Simple 1-back blank 2-back Task

  26. Incorrect and No responses 10 Adult Control 9 Adult FAS 8 7 6 Average Number of Incorrect and No Responses 5 4 3 ** 2 * 1 0 simple 1-back blank 2-back Task

  27. S51 – FASD (11y, F) S45 – FASD (11y (just), F) Children P=0.01 P=0.01 P=0.01 P=0.01 S32 Control (11 y, F) S47 Control (10 y, F) Blank - simple

  28. Children S51 – FASD (11y, F) S45 – FASD (11y (just), F) P=0.01 P=0.01 P=0.01 P=0.01 S32 Control (11 y, F) S47 Control (10 y, F) 1-back - simple

  29. Response times Child control 0.7 Child FAS 0.6 *** ** 0.5 0.4 Latency (s) 0.3 0.2 0.1 0 simple 1-back blank 2-back Tasks

  30. Incorrect and No responses Child Control ** 14 Child FAS 12 * 10 ** 8 Average Number of Incorrect and No Responses 6 * 4 2 0 simple 1-back blank 2-back Task

  31. fMRI 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

  32. Self-Ordered Pointing • Test of visual working memory and strategic memory • Presented with n sets of n pictures (n = 6, 8, 10 or 12) • In each sheet of a given set, S must touch a different picture

  33. Wisconsin Card Sorting Task • Successful performance requires • Planning ability • Cognitive flexibility • Working memory • Response inhibition • Concept formation and reasoning Kolb & Whishaw, 2001, p.541

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

  35. Continuous Performance Task • Detect the presence of targets in a series of trials that include distractors • Measures: • # correct responses • correct response latency • probability of a hit • probability of a false alarm

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

  37. 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.

  38. Conclusions • Adults and children with FASD show impaired performance relative to age- and sex-matched controls, on tasks tapping into executive function, sustained attention, and visual working memory • Significant latency of response for FASD subjects compared to controls – but both groups paying attention!! • Not all exposed individuals show deficits • Studying unique neuroanatomical & neuropsychological profile of individuals with FASD is important for design of assessment tools, and development of support and intervention programs for patients and their families • fMRI may prove helpful in this regard

  39. Acknowledgements IBD - Ms A. Allman, Dr. D. Shiloff U of M, Psychology – Dr. L. Jakobson HSC – Dr. A. Chudley, Dr. S. Longstaffe child life specialists Ms D. Kuypers Ms S. Treichel Financial support Manitoba Medical Services Foundation Ava-Ann Allman- Women in Engineering and Science (WES) Award -NRC

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