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hyperactivity disorder: A PET study
NeuroImage
11, Number
5, 2000,
Part 2 of 2 Parts 1 D E .cI;L”
DISORDERS - NEUROLOGY
Effects of Familiarity and Methylphenidate on the Neural Correlates of Working Memory in Attention Deficit/Hyperactivity Disorder: A PET Study J.B. Schweitzer*,
D.O. Lee?, J.M. Hoffman&
C.F. Zinkt,
M. Ning*, S.T. Grafton@, C.D. KiltsS
*Maryland Psychiatric Research Center, University of Maryland, Baltimore, MD iDepartment
of Psychiatry, Emory University, Atlanta, GA
$National Cancer Institute, Bethesda, MD $Center for Cognitive Neuroscience, Dartmouth University, Hanover, NH Introduction Attention deficit/hyperactivity disorder (ADHD) is a disorder commonly characterized by persistent inattention and/or excessive motor restlessness and impulsive behavior. It is now recognized that children and adults with ADHD exhibit deficits in working memory (1,2), and that such impairments are ameliorated by treatment with methylphenidate (3). Familiarity with tasks and situations has also been shown to increase ADHD symptomatology, rather than improve performance (4). The aim of the present study was to determine 1) the effect of familiarity on rCBF patterns in subjects with ADHD and 2) the effect of methylphenidate on those patterns. Methods Nine right-handed men who met criteria for ADHD, combined type (DSM-IV & the ADHD Rating Scales) were imaged during an unmedicated condition and (8/9 subjects) during a methylphenidate condition. The methylphenidate images were acquired after subjects demonstrated 3 weeks of stable behavioral ratings on an optimal dose of medication. On the day of the methylphenidate condition, subjects ingested the medication approximately 45 min before the first working memory scan. Subjects had no other lifetime Axis I diagnosis or learning disability. [150]Hz0 PET studies were acquired for each subject during three working memory trials in the unmedicated and medication conditions. Subjects performed the working memory task for four additional practice trials between the first and second acquisition and for four additional practice trials between the second and third PET acquisition. The Paced Auditory Serial Addition Task (PASAT) was used as the working memory test. During the PASAT, subjects listened to the presentation of a random number between 1 and 9 every 2.0 set and added each number to the preceding number (e.g., 6, 3, 2 = 9,5). Changes in ICBF over time between the three PASAT images were compared on a voxel-wise basis by analysis of covariance (ANCOVA) with a statistical threshold of p < 0.01 and a Z score threshold of 2.33. Results Subjects demonstrated a significant improvement Practice did not improve performance on the PASAT practice resulted in decreases in activation in bilateral cingulate, cuneus, and Rt. postcentral gyrua. During temporal areas (BA 37, 21, 20) and in the thalamus. the Lt. hippocampus, precuneus. Rt. occipital lobe
on PASAT performance during the methylphenidate condition (p < 0.002). for the ADHD subjects in either condition. During the unmedicated condition, temporal areas (BA 20,21,22) and increases in activation in the Rt. posterior the medicated condition, practice resulted in decreases in activation in bilateral Practice resulted in increases in activation during the medication condition in (BA 19), and Lt. precentral gyrus (BA 6).
Conclusions Unlike traditional models of learning with normal volunteers. practice or familiarity with a task does not necessarily lead to improvement in performance in subjects with ADHD. While practice with a task resulted in no improvement in performance it did result in a shifting of rCBF activity in temporal to occipital areas in both the unmedicated and medicated conditions. This shift may he reflective of a change from more verbally-based strategies (e.g.. verbally rehearsing the last digit given during the PASAT) to visual strategies as familiarity with the task increased. The hippocampal activations found only during rhe methylphenidate condition suggest that this structure plays a role in the overall improvement in performance on the PASAT References I 2. 3. 4.
Barkley R. Murphy K. Kwasnik D. Journal of Attention Disorders, 1996; 1:41-54 Mariani M, Barkley R.A. Developmental Neuropsycholgy, 1997;13: 11 l-129 Tannock R, Ickowicz A, Schachar R. J Am Acad Child Adolesc Psychiatry, 1995;34:886-896 Schweitzer J. Sulzer-Azaroff B. J Child Psych and Psych Allied Disciplines, 1996;36:671-686
S172
11, Number
5, 2000,
Part 2 of 2 Parts 1 D E .cI;L”
DISORDERS - NEUROLOGY
Effects of Familiarity and Methylphenidate on the Neural Correlates of Working Memory in Attention Deficit/Hyperactivity Disorder: A PET Study J.B. Schweitzer*,
D.O. Lee?, J.M. Hoffman&
C.F. Zinkt,
M. Ning*, S.T. Grafton@, C.D. KiltsS
*Maryland Psychiatric Research Center, University of Maryland, Baltimore, MD iDepartment
of Psychiatry, Emory University, Atlanta, GA
$National Cancer Institute, Bethesda, MD $Center for Cognitive Neuroscience, Dartmouth University, Hanover, NH Introduction Attention deficit/hyperactivity disorder (ADHD) is a disorder commonly characterized by persistent inattention and/or excessive motor restlessness and impulsive behavior. It is now recognized that children and adults with ADHD exhibit deficits in working memory (1,2), and that such impairments are ameliorated by treatment with methylphenidate (3). Familiarity with tasks and situations has also been shown to increase ADHD symptomatology, rather than improve performance (4). The aim of the present study was to determine 1) the effect of familiarity on rCBF patterns in subjects with ADHD and 2) the effect of methylphenidate on those patterns. Methods Nine right-handed men who met criteria for ADHD, combined type (DSM-IV & the ADHD Rating Scales) were imaged during an unmedicated condition and (8/9 subjects) during a methylphenidate condition. The methylphenidate images were acquired after subjects demonstrated 3 weeks of stable behavioral ratings on an optimal dose of medication. On the day of the methylphenidate condition, subjects ingested the medication approximately 45 min before the first working memory scan. Subjects had no other lifetime Axis I diagnosis or learning disability. [150]Hz0 PET studies were acquired for each subject during three working memory trials in the unmedicated and medication conditions. Subjects performed the working memory task for four additional practice trials between the first and second acquisition and for four additional practice trials between the second and third PET acquisition. The Paced Auditory Serial Addition Task (PASAT) was used as the working memory test. During the PASAT, subjects listened to the presentation of a random number between 1 and 9 every 2.0 set and added each number to the preceding number (e.g., 6, 3, 2 = 9,5). Changes in ICBF over time between the three PASAT images were compared on a voxel-wise basis by analysis of covariance (ANCOVA) with a statistical threshold of p < 0.01 and a Z score threshold of 2.33. Results Subjects demonstrated a significant improvement Practice did not improve performance on the PASAT practice resulted in decreases in activation in bilateral cingulate, cuneus, and Rt. postcentral gyrua. During temporal areas (BA 37, 21, 20) and in the thalamus. the Lt. hippocampus, precuneus. Rt. occipital lobe
on PASAT performance during the methylphenidate condition (p < 0.002). for the ADHD subjects in either condition. During the unmedicated condition, temporal areas (BA 20,21,22) and increases in activation in the Rt. posterior the medicated condition, practice resulted in decreases in activation in bilateral Practice resulted in increases in activation during the medication condition in (BA 19), and Lt. precentral gyrus (BA 6).
Conclusions Unlike traditional models of learning with normal volunteers. practice or familiarity with a task does not necessarily lead to improvement in performance in subjects with ADHD. While practice with a task resulted in no improvement in performance it did result in a shifting of rCBF activity in temporal to occipital areas in both the unmedicated and medicated conditions. This shift may he reflective of a change from more verbally-based strategies (e.g.. verbally rehearsing the last digit given during the PASAT) to visual strategies as familiarity with the task increased. The hippocampal activations found only during rhe methylphenidate condition suggest that this structure plays a role in the overall improvement in performance on the PASAT References I 2. 3. 4.
Barkley R. Murphy K. Kwasnik D. Journal of Attention Disorders, 1996; 1:41-54 Mariani M, Barkley R.A. Developmental Neuropsycholgy, 1997;13: 11 l-129 Tannock R, Ickowicz A, Schachar R. J Am Acad Child Adolesc Psychiatry, 1995;34:886-896 Schweitzer J. Sulzer-Azaroff B. J Child Psych and Psych Allied Disciplines, 1996;36:671-686
S172