Six unmedicated, right-handed male adults diagnosed with ADHD who had current and childhood histories of inattention, impulsivity, and hyperactivity but no other lifetime axis I diagnoses were studied. The comparison group comprised six healthy men matched in age and general intelligence who had no lifetime axis I diagnosis. The mean ages of the men with ADHD was 28.5 years (SD=8.9), and the mean age of the men without ADHD was 25.7 (SD=5.2). Screenings included the ADHD Rating Scale
(4); review of developmental, family, educational, and social characteristics, drug and alcohol use (drug use was confirmed by urinalysis), and occupational histories; SCL-90-R; neurological examination; Wechsler Adult Intelligence Scale—Revised; and Wide Range Achievement Test—Revised. The men with ADHD fulfilled at least eight of 14 items of the DSM-III-R criteria during both childhood and at the time of imaging. Diagnoses were confirmed by using scores on the ADHD Rating Scale
(4), which was completed by participants, their parents, and significant others, who also rated the subjects’ current and/or childhood functioning
(5). The men with ADHD endorsed at least 10 of 14 items rating current behavior
(4), and all had scores of 12 or greater when rated by a parent (or a family friend for one subject) on the Conners Abbreviated Symptom Questionnaire
(5). Participants with learning disabilities were excluded from both groups. Three of the men with ADHD had a childhood ADHD diagnosis. Two men with ADHD had taken methylphenidate during childhood but had been methylphenidate-free for 2 and 10 years, respectively, before the study. All subjects provided written informed consent.
The Paced Auditory Serial Addition Task
(6) was administered to engage working memory. Single-digit numbers were presented binaurally every 2.4 seconds. Subjects added each number to the preceding number. Subjects also vocalized random numbers during a self-paced number-generation control condition to correct for the contribution of arousal, auditory stimulation, verbal production, and short-term (nonworking) memory to the rCBF changes related to the auditory addition task.
PET imaging occurred on 2 consecutive days; conditions of day 1 were replicated on day 2. Subjects completed two resting, number-generation, and addition task conditions per day, for a total of 12 scans. A Siemens 921 PET scanner acquired 90-second scans in three-dimensional mode after bolus intravenous administration of 25 mCi of
[
15O]H
2O. T
1-weighted transaxial spin echo magnetic resonance images (repetition time=650 msec, echo time=20 msec) of brain structure were obtained for coregistration to PET images
(7).
Scans were fit to an atlas centered in Talairach and Tournoux coordinates. PET images were smoothed to a final isotropic resolution of 11.8 mm full width at half maximum and normalized by proportionate scaling of global activity. Alterations in rCBF were identified in a pixel-by-pixel comparison using a four-way analysis of variance (ANOVA) to generate t statistic images accounting for differences between factors of day, task, subject, and repetitions.
The difference (p<0.005) between number-generation versus addition task images isolated the neural correlates of working memory. Differences over time among the four addition task images were compared in an omnibus F test with a threshold of p<0.005.