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Thalamo-Cortical Activation and Connectivity During Response Preparation in Adults With Persistent and Remitted ADHD
Suzanne M. Clerkin, Ph.D., M.S.C.R.; Kurt P. Schulz, Ph.D.; Olga G. Berwid, Ph.D.; Jin Fan, Ph.D.; Jeffrey H. Newcorn, M.D.; Cheuk Y. Tang, Ph.D.; Jeffrey M. Halperin, Ph.D.
Am J Psychiatry 2013;170:1011-1019. doi:10.1176/appi.ajp.2013.12070880
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Dr. Newcorn has received grant support from Eli Lilly, Ortho-McNeil-Janssen, and Shire and advisory or consulting fees from Alcobra, Biobehavioral Diagnostics, Eli Lilly, Neos, Shionogi and Otsuka, and Shire. The other authors report no financial relationships with commercial interests.

Supported by NIMH (R01MH060698 to J.M.H. and K01MH070892 to K.P.S.) and by NIH (5KL2RR029885 to S.M.C.).

From the Departments of Psychiatry and Radiology, Icahn School of Medicine at Mount Sinai, and the Department of Psychology, Queens College, City University of New York.

Address correspondence to Dr. Clerkin (suzanne.clerkin@mssm.edu).

Copyright © 2013 by the American Psychiatric Association

Received July 05, 2012; Revised November 08, 2012; Revised January 12, 2013; Revised March 06, 2013; Accepted March 13, 2013.

Abstract

Objective  The neural correlates of stimulus-driven processes, such as response preparation, have been posited to be associated with the onset of attention deficit hyperactivity disorder (ADHD) while being distinct from the neural mechanisms associated with recovery. The authors tested this hypothesis in adults with remitted and persistent ADHD.

Method  Thirty-eight young adults who were diagnosed with combined-type ADHD in childhood (probands) and 32 carefully matched comparison subjects were followed longitudinally and scanned with functional MRI while performing an event-related cued reaction time task. Probands were characterized as individuals with persistent or remitted ADHD. Differences in thalamo-cortical activation and functional connectivity during response preparation between comparison subjects and probands and between individuals with persistent ADHD and those with remitted ADHD were assessed by contrasting neural activation and functional connectivity during cue or noncue events.

Results  Probands exhibited less cue-related activation than comparison subjects in the thalamus, anterior cingulate cortex, supplementary motor area, inferior parietal lobe, and dorsolateral prefrontal cortex despite similar overall patterns of activation. There were no differences in activation between individuals in the remitted ADHD group and those in the persistent ADHD group in any hypothesized regions. However, cue-related functional connectivity between the right thalamus and brainstem was greater in comparison subjects relative to probands, and cue-related connectivity was greater between the right thalamus and prefrontal regions in individuals with remitted ADHD relative to those with persistent ADHD.

Conclusions  Decreased thalamo-cortical activation during response preparation was present in adults diagnosed with ADHD in childhood regardless of symptom remission in adulthood, and may be partly driven by less functional coordination between the brainstem and thalamus. Greater functional integration of the thalamo-cortical network might parallel symptom recovery.

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FIGURE 1. Regions of Significantly Greater Activation for the Cue-Noncue Contrast in a Study of Response Preparation in ADHDa

a Images are from comparison subjects (panel A), probands (panel B), and comparison subjects minus probands (panel C). The significance threshold was set at p<0.01, with an extent threshold at 100 voxels.

FIGURE 2. Functional Connectivity During Cues and Noncues in a Study of Response Preparation in ADHDa

a Panel A depicts significantly greater functional connectivity during cues relative to noncues for comparison subjects than probands between the right thalamus (mask shown in red) and the brainstem at the level of the pons (x=2, y=−26, z=−34). Panel B depicts significantly greater functional connectivity during cues relative to noncues for individuals with remitted ADHD than those with persistent ADHD between the right thalamus (mask shown in red) and the prefrontal cortex, including the left (x=−38, y=44, z=14) and right (x=38, y=36, z=22) frontopolar cortex (Brodmann’s area [BA] 10) and the left (x=−46, y=46, z=10) dorsolateral prefrontal cortex (BA 46). The significance threshold was set at p<0.01, with an extent threshold at 100 voxels.

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TABLE 1.Clinical and Demographic Characteristics in a Study of Thalamo-Cortical Activation and Connectivity During Response Preparation in ADHD
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TABLE 2.Sample Performance in a Study of Thalamo-Cortical Activation and Connectivity During Response Preparation in ADHD
Table Footer Note

a Times in milliseconds.

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TABLE 3.Group Differences in Brain Activation During Response Preparationa
Table Footer Note

a BA=Brodmann’s area; MNI=Montreal Neurological Institute. Significance at p<0.01, with the extent threshold fixed at 100 voxels.

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