Catechol-O-methyltransferase polymorphism is associated with the cortico-cerebellar functional connectivity of executive function in children with attention-deficit/hyperactivity disorder

Abstract

The cerebellum, although traditionally considered a motor structure, has been increasingly recognized to play a role in regulating executive function, the dysfunction of which is a factor in attention-deficit/hyperactivity disorder (ADHD). Additionally, catechol-O-methyltransferase (COMT) polymorphism has been reported to be associated with executive function. We examined whether the cortico-cerebellar executive function network is altered in children with ADHD and whether COMT polymorphism is associated with the altered network. Thirty-one children with ADHD and thirty age- and IQ-matched typically developing (TD) controls underwent resting-state functional MRI, and functional connectivity of executive function-related Crus I/II in the cerebellum was analysed. COMT Val158Met genotype data were also obtained from children with ADHD. Relative to TD controls, children with ADHD showed significantly lower functional connectivity of the right Crus I/II with the left dorsolateral prefrontal cortex. Additionally, the functional connectivity of children with ADHD was modulated by COMT polymorphism, with Met-carriers exhibiting significantly lower functional connectivity than the Val/Val genotype. These results suggest the existence of variations, such as ethnic differences, in COMT genetic effects on the cortico-cerebellar executive function network. These variations contribute to heterogeneity in ADHD. Further neuroimaging genetics study might lead to the development of fundamental therapies that target ADHD pathophysiology.

Functional network connectivity changes in children with attention‐deficit hyperactivity disorder: A resting‐state fMRI study

“…In the current study, the results revealed that the DC values of the ADHD group were higher than normal controls in the bilateral middle cingulate gyrus. The cingulate gyrus is thought to play an important role in executive control (Mizuno et al (2017)). The middle cingulate gyrus is related to cognitive processing, such as the detection of errors or conflicts, as well as negative conditional reflexes and the prediction and awareness of pain.…”

Intrinsic brain activity associated with eye gaze during mother–child interaction

“…26, GE Healthcare, Milwaukee, WI, USA) with a standard head coil (8-channnel HD Brain, GE Healthcare). Resting-state functional images were acquired with a T2*-weighted gradient-echo echoplanar imaging (EPI) sequence 60,61 . Each volume consisted of 40 slices, with a thickness of 3.5 mm and a 0.5-mm gap, to cover the entire brain.…”

“…The field of view was 192 × 192 mm, and the matrix size was 64 × 64, yielding volume dimensions of 3 × 3 mm. A total of 192 volumes were acquired for an imaging time of 7 min 42 s 60,61 . The participants were instructed to remain awake but to close their eyes and think of nothing in particular.…”

“…Head movement was minimized by the placement of memory-foam pillows around the head. A T1-weighted anatomical dataset was obtained from each participant using a magnetization-prepared rapid acquisition gradient echo sequence (voxel size 1 × 1 × 1 mm, TE = 1.996 ms, TR = 6.38 ms, TI = 600 ms, flip angle = 11°, total scan time = 4 min 50 s) 60,61 .…”

“…The signal from each slice was realigned temporally to that obtained from the middle slice using "sinc" interpolation. To control for motion confounding in our data, we investigated the effects of head motion by computing the mean frame-to-frame root mean square motion and FD obtained during the realignment process 61 . Next, high-resolution T1 images were coregistered to functional images via a nonlinear image registration approach and segmented using a new segment algorithm with diffeomorphic anatomical registration through the exponentiated lie algebra technique 63 .…”