Increase or Decrease of fMRI Activity in Adult Attention Deficit/ Hyperactivity Disorder: Does It Depend on Task Difficulty?

Abstract

Background: Attention deficit/hyperactivity disorder has been shown to affect working memory, and fMRI studies in children and adolescents with attention deficit/hyperactivity disorder report hypoactivation in task-related attentional networks. However, studies with adult attention deficit/hyperactivity disorder patients addressing this issue as well as the effects of clinically valid methylphenidate treatment are scarce. This study contributes to closing this gap.

Methods: Thirty-five adult patients were randomized to 6 weeks of double-blind placebo or methylphenidate treatment. Patients completed an fMRI n-back working memory task both before and after the assigned treatment, and matched healthy controls were tested and compared to the untreated patients.

Results: There were no whole-brain differences between any of the groups. However, when specified regions of interest were investigated, the patient group showed enhanced BOLD responses in dorsal and ventral areas before treatment. This increase was correlated with performance across all participants and with attention deficit/hyperactivity disorder symptoms in the patient group. Furthermore, we found an effect of treatment in the right superior frontal gyrus, with methylphenidate-treated patients exhibiting increased activation, which was absent in the placebo-treated patients.

Conclusions: Our results indicate distinct activation differences between untreated adult attention deficit/hyperactivity disorder patients and matched healthy controls during a working memory task. These differences might reflect compensatory efforts by the patients, who are performing at the same level as the healthy controls. We furthermore found a positive effect of methylphenidate on the activation of a frontal region of interest. These observations contribute to a more thorough understanding of adult attention deficit/hyperactivity disorder and provide impulses for the evaluation of therapy-related changes.

Keywords: adult attention deficit/hyperactivity disorder; clinical trial; fMRI; methylphenidate; working memory.

Figure 1.

CONSORT flow diagram illustrating the ADHD patients’ progress through the study.

Figure 2.

Significantly activated voxels found in the whole brain analysis with P _FWE < .05 (5 voxels extent threshold) for the contrast 2-back minus 0-back in the patient group (top) and the healthy control group (bottom).

Figure 3.

Clusters found in the ROI analysis that showed significantly greater peak voxel activation for the contrast 2-back minus 0-back in the patient group (ADHD) compared to the healthy control group (HC) in the (A) left anterior intraparietal sulcus (IPS) and in the (B) right inferior/ middle frontal gyrus (IFG/MFG) as well as mean contrast estimates and standard error of measurement for these two clusters (C). *Significantly different, P ≤ .05.