Methylphenidate normalizes resting-state brain dysfunction in boys with attention deficit hyperactivity disorder

Abstract

We used resting-state functional magnetic resonance imaging (RS-fMRI) to investigate the acute effects of methylphenidate hydrochloride (MPH) on spontaneous brain activity in children with attention deficit hyperactivity disorder (ADHD). In all, 23 boys with ADHD were scanned twice, under either 10 mg dose of MPH or placebo, in a randomized, cross-over, counterbalanced placebo-controlled design. 32 Matched healthy controls were scanned once for comparison. Seven of the 23 ADHD boys participated in a follow-up 8-week MPH treatment. A regional homogeneity (ReHo) method was applied to characterize the local synchronization of spontaneous brain activity. ADHD boys under placebo compared with controls showed decreased ReHo in bilateral dorsolateral prefrontal cortices and increased ReHo in bilateral sensorimotor and parieto-visual cortices. Relative to placebo, MPH upregulated ReHo in bilateral ventral prefrontal cortices and cerebellar vermis, and downregulated ReHo in right parietal and visual areas that overlapped with the abnormally enhanced activities. When under MPH, ReHo differences between patients and controls were no longer observed. The preliminary prediction analysis revealed that the decreased ReHo in right parietal cortex after the acute MPH was positively correlated with the decreased symptom scores after the 8-week MPH treatment in the seven patients. We show that an acute dose of MPH normalized all fronto-parieto-cerebellar dysfunctions in boys with ADHD during the resting state. Preliminary findings furthermore suggest the potential of RS-fMRI as a prognostic imaging tool to identify response to MPH treatment.

Figure 1

Clusters showing significant ReHo differences between ADHD group under placebo condition and control group. The cold colors indicate lower ReHo in ADHD group under placebo than control group, while the warm colors mean vice versa; all clusters P<0.05 (corrected). Left in the figure indicates the right side of the brain.

Figure 2

Clusters showing significant ReHo differences between MPH condition and placebo condition in the ADHD group. The cold colors indicate lower ReHo in MPH condition than placebo condition, while the warm colors mean vice versa; all clusters P<0.05 (corrected). Left in the figure indicates the right side of the brain.

Figure 3

The ReHo decrease after the acute MPH administration in right postcentral gyrus and superior parietal lobe was negatively correlated with the eighth-week score of ADHD RS-IV in the seven patients, covarying for the baseline score. (a) Voxel-wise correlation map: the cluster is located in BA 5/3/7 with 37 voxels (MNI coordinates of the peak voxel: 12, –42, 69). Left in the figure indicates the right side of the brain. (b) The scatter plot showed the positive correlation between the decreased mean ReHo with single-dose MPH extracted from the above cluster and the decreased score after 8-week MPH treatment: r=0.79, P=0.04.