ADHD and cannabis use in young adults examined using fMRI of a Go/NoGo task

Abstract

Children diagnosed with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for substance abuse. Response inhibition is a hallmark of ADHD, yet the combined effects of ADHD and regular substance use on neural networks associated with response inhibition are unknown. Task-based functional Magnetic Resonance Imaging (fMRI) data from young adults with childhood ADHD with (n = 25) and without (n = 25) cannabis use ≥ monthly in the past year were compared with a local normative comparison group (LNCG) with (n = 11) and without (n = 12) cannabis use. Go/NoGo behavioral and fMRI data were evaluated for main and interaction effects of ADHD diagnosis and cannabis use. ADHD participants made significantly more commission errors on NoGo trials than controls. ADHD participants also had less frontoparietal and frontostriatal activity, independent of cannabis use. No main effects of cannabis use on response inhibition or functional brain activation were observed. An interaction of ADHD diagnosis and cannabis use was found in the right hippocampus and cerebellar vermis, with increased recruitment of these regions in cannabis-using controls during correct response inhibition. ADHD participants had impaired response inhibition combined with less fronto-parietal/striatal activity, regardless of cannabis use history. Cannabis use did not impact behavioral response inhibition. Cannabis use was associated with hippocampal and cerebellar activation, areas rich in cannabinoid receptors, in LNCG but not ADHD participants. This may reflect recruitment of compensatory circuitry in cannabis using controls but not ADHD participants. Future studies targeting hippocampal and cerebellar-dependent function in these groups may provide further insight into how this circuitry is altered by ADHD and cannabis use.

Keywords: ADHD; Cannabis; Go/NoGo; Inhibition; Marijuana; fMRI.

Fig. 1. In-scanner behavioral performance

A main effect of ADHD diagnosis was observed with a higher likelihood of false positives associated with ADHD (left, p<.05), irrespective of cannabis use history.

Fig. 2. Main effect of ADHD diagnosis during an inhibition (NoGo>Go) task

Cortical network differences are primarily right lateralized and include frontal and parietal regions, which are reduced in subjects with history of childhood ADHD. No regions of activation were significantly greater in ADHD than LNCG subjects.

Fig. 3. Main effect of ADHD diagnosis: group map and anatomically defined subcortical ROI boxplot

Significant clusters of hypoactivation in ADHD subcortical cortices include right caudate, thalamus and accumbens (left). Further native space analyses confirmed right caudate hypoactivation in ADHD (right) participants along with right putamen and left pallidum.

Fig. 4. Interaction effects of cannabis use and ADHD diagnosis

Significant regions of marijuana use by ADHD diagnosis interaction effects included right hippocampus, right cerebellum/vermis and lingual gyrus.

Fig. 5. Task Breakdown of Interaction Effects

Individually, ADHD and cannabis use both attenuate hippocampal and cerebellar deactivation NoGo>Go seen in “normal” controls (LNCG, non-users), but in combination, do not effect NoGo>Go activation. Interaction effects during inhibition are dominated by the NoGo condition.