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Reduced Prefrontal Efficiency for Visuospatial Working Memory in Attention-Deficit/Hyperactivity Disorder

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Objective

Visuospatial working memory impairments have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, most ADHD research has focused on the neural correlates of nonspatial mnemonic processes. This study examined brain activation and functional connectivity for visuospatial working memory in youth with and without ADHD.

Method

Twenty-four youth with ADHD and 21 age- and sex-matched healthy controls were scanned with functional magnetic resonance imaging while performing an N-back test of working memory for spatial position. Block-design analyses contrasted activation and functional connectivity separately for high (2-back) and low (1-back) working memory load conditions versus the control condition (0-back). The effect of working memory load was modeled with linear contrasts.

Results

The 2 groups performed comparably on the task and demonstrated similar patterns of frontoparietal activation, with no differences in linear gains in activation as working memory load increased. However, youth with ADHD showed greater activation in the left dorsolateral prefrontal cortex (DLPFC) and left posterior cingulate cortex (PCC), greater functional connectivity between the left DLPFC and left intraparietal sulcus, and reduced left DLPFC connectivity with left midcingulate cortex and PCC for the high load contrast compared to controls (p < .01; k > 100 voxels). Reanalysis using a more conservative statistical approach (p < .001; k > 100 voxels) yielded group differences in PCC activation and DLPFC-midcingulate connectivity.

Conclusion

Youth with ADHD show decreased efficiency of DLPFC for high-load visuospatial working memory and greater reliance on posterior spatial attention circuits to store and update spatial position than healthy control youth. Findings should be replicated in larger samples.

Section snippets

Participants

Forty-five children 9 to 15 years of age (mean = 12.78, SD = 1.94) were recruited from an industry-funded treatment study, via e-mail announcements and ads/flyers posted throughout the hospital and on online volunteer sites. All parents/children gave informed consent/assent to participate in the study, and the institutional review board of the medical school approved all study procedures. Children and parents were compensated for participation.

Participants were evaluated using the Kiddie

Participants

Demographic and clinical data are shown in Table 1. There were no group differences in age, sex, handedness, race/ethnicity, or Full-Scale IQ (all p > .20).

Behavioral Data

As shown in Table 2, there were significant main effects of load for several behavioral measures, but there were no significant main effects of group or group × load interactions.

Working Memory–Related Activation

Children with ADHD and controls had similar patterns of activation for both working memory conditions compared to the control condition in a distributed

Discussion

These findings provide evidence of functional anomalies in DLPFC associated with visuospatial working memory in youth with ADHD. Youth with ADHD performed comparably to controls on a visuospatial N-back task and demonstrated similar patterns of frontoparietal activation, indicating that the 2 groups used similar mechanisms to store and update spatial positions of visual targets. Increases in working memory load yielded linear decreases in accuracy and response speed in both groups, and were

References (53)

  • S.M. Landau et al.

    Regional specificity and practice: dynamic changes in object and spatial working memory

    Brain Res

    (2007)
  • C. Fassbender et al.

    Is there evidence for neural compensation in attention deficit hyperactivity disorder? A review of the functional neuroimaging literature

    Clin Psychol Rev

    (2006)
  • R.L. Silton et al.

    The time course of activity in dorsolateral prefrontal cortex and anterior cingulate cortex during top-down attentional control

    Neuroimage

    (2010)
  • J.M. Jansma et al.

    Specific versus nonspecific brain activity in a parametric N-back task

    Neuroimage

    (2000)
  • J. Prado et al.

    Heightened interactions between a key default-mode region and a key task-positive region are linked to suboptimal current performance but to enhanced future performance

    Neuroimage

    (2011)
  • F.X. Castellanos et al.

    Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes

    Nat Rev Neurosci

    (2002)
  • K.C. Brocki et al.

    Interrelations between executive function and symptoms of hyperactivity/impulsivity and inattention in preschoolers: a two year longitudinal study

    J Abnorm Child Psychol

    (2010)
  • E. Bora et al.

    Meta-analysis of cognitive deficits in ultra-high risk to psychosis and first-episode psychosis: do the cognitive deficits progress over, or after, the onset of psychosis?

    Schizophr Bull

    (2014)
  • M. Miller et al.

    Childhood executive function continues to predict outcomes in young adult females with and without childhood-diagnosed ADHD

    J Abnorm Child Psychol

    (2012)
  • P.S. Goldman-Rakic

    Architecture of the prefrontal cortex and the central executive

    Ann N Y Acad Sci

    (1995)
  • T.D. Wager et al.

    Neuroimaging studies of working memory: a meta-analysis

    Cogn Affect Behav Neurosci

    (2003)
  • S. Funahashi et al.

    Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex

    J Neurophysiol

    (1989)
  • M.F. Kritzer et al.

    Intrinsic circuit organization of the major layers and sublayers of the dorsolateral prefrontal cortex in the rhesus monkey

    J Compar Neurol

    (1995)
  • E.K. Miller et al.

    Neural mechanisms of visual working memory in prefrontal cortex of the macaque

    J Neurosci

    (1996)
  • M. Oliveri et al.

    Parieto-frontal interactions in visual-object and visual-spatial working memory: evidence from transcranial magnetic stimulation

    Cereb Cortex

    (2001)
  • A.F. Arnsten et al.

    The contribution of alpha 2-noradrenergic mechanisms of prefrontal cortical cognitive function. Potential significance for attention-deficit hyperactivity disorder

    Arch Gen Psychiatry

    (1996)
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    Clinical guidance is available at the end of this article.

    This article was reviewed under and accepted by deputy editor Ellen Leibenluft, MD.

    Research was supported by the Klingenstein Third Generation Foundation (A.C.B.), the Canadian Institutes of Health Research (A.C.B.), and a Mount Sinai Robin Chemers Neustein Postdoctoral Fellowship Award (A.C.B.).

    The authors thank Hanna Oltarzewska, BS, Cara Rabin, BA, and Joanne Philips, MS, of the Icahn School of Medicine for their invaluable support in data acquisition.

    Disclosure: Dr. Newcorn is a recipient of research grants from Shire and is or has been an advisor/consultant for Alcobra, Biobehavioral Diagnostics, Enzymotec, GencoSciences, Neos, Shire, and Sunovian. Drs. Bédard, Clerkin, Krone, Fan, Halperin, and Schulz report no biomedical financial interests or potential conflicts of interest.

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