Exercise, Cognition, and Cannabis Use in Adolescents

Heavy and/or chronic cannabis use has been associated with neurocognitive impairment and decline, often in domains such as memory and executive functioning. On the other hand, exercise has been linked to positive effects on brain and cognitive health across the lifespan, as well as to better substance use outcomes. Despite this, little is known about the ways in which exercise could help prevent or ameliorate adverse cannabis-related outcomes among adolescents. Through three separate studies, the current dissertation examines interrelations among exercise, cognition, and cannabis use in children and adolescents in an effort to determine whether exercise can prevent or ameliorate cannabis-related cognitive decline and other adverse outcomes. The first study examined whether exercise ameliorates cannabis-related declines in episodic memory in a sample of 401 adolescents. Results from multivariate latent growth curve models replicated findings that greater frequency of cannabis use is associated with declines in episodic memory. However, neither initial levels nor change in exercise moderated these associations. The second study examined associations between exercise and cannabis-related outcomes (e.g., cannabis use frequency, cannabis use disorder, cannabis-related problems) after a 6-month period, and tested the mediating role of exercise effects on decision-making in a sample of 387 adolescents. Results from prospective mediation analyses revealed that more exercise predicted greater cannabis use frequency, but not cannabis use disorder or problems. There was no evidence of a mediating role for decision-making in the associations between exercise and cannabis-related outcomes, and positive effects of exercise on decision-making were better accounted for by demographics. The third study examined cross-sectional associations between exercise, task-related brain activation, and executive functioning in a sample of 7,733 preadolescent children. Results from cross-sectional mediation analyses indicated that the association between exercise and executive functioning was largely accounted for by sociodemographic factors, and did not support a mediating role for task-related activation of frontoparietal and salience networks. Together, findings suggest that effects of exercise on neurocognitive functioning in pediatric populations are small, may be more readily observed within the domain of executive functioning, and may be better explained by sociodemographic characteristics

Neural response to monetary loss among youth with disruptive behavior disorders and callous-unemotional traits in the ABCD study

Etiological models highlight reduced punishment sensitivity as a core risk factor for disruptive behavior disorders (DBD) and callous-unemotional (CU) traits. The current study examined neural sensitivity to the anticipation and receipt of loss, one key aspect of punishment sensitivity, among youth with DBD, comparing those with and without CU traits. Data were obtained from the Adolescent Brain and Cognitive Development (ABCD)SM Study (N = 11,874; Mage = 9.51; 48% female). Loss-related fMRI activity during the monetary incentive delay task was examined across 16 empirically-derived a priori brain regions (e.g., striatum, amygdala, insula, anterior cingulate cortex, medial prefrontal cortex) and compared across the following groups: (1) typically developing (n = 693); (2) DBD (n = 995), subdivided into those (3) with CU traits (DBD + CU, n = 198), and (4) without CU traits (DBD-only, n = 276). Latent variable modeling was also employed to examine network-level activity. There were no significant between-group differences in brain activity to loss anticipation or receipt. Null findings were confirmed with and without covariates, using alternative grouping approaches, and in dimensional models. Network-level analyses also demonstrated comparable activity across groups during loss anticipation and receipt. Findings suggest that differences in punishment sensitivity among youth with DBD are unrelated to loss anticipation or receipt. More precise characterizations of other aspects punishment sensitivity are needed to understand risk for DBD and CU traits

Reduced Functional Connectivity of Default Mode and Set-Maintenance Networks in Ornithine Transcarbamylase Deficiency

<div><p>Background and Purpose</p><p>Ornithine transcarbamylase deficiency (OTCD) is an X-chromosome linked urea cycle disorder (UCD) that causes hyperammonemic episodes leading to white matter injury and impairments in executive functioning, working memory, and motor planning. This study aims to investigate differences in functional connectivity of two resting-state networks—default mode and set-maintenance—between OTCD patients and healthy controls.</p><p>Methods</p><p>Sixteen patients with partial OTCD and twenty-two control participants underwent a resting-state scan using 3T fMRI. Combining independent component analysis (ICA) and region-of-interest (ROI) analyses, we identified the nodes that comprised each network in each group, and assessed internodal connectivity.</p><p>Results</p><p>Group comparisons revealed reduced functional connectivity in the default mode network (DMN) of OTCD patients, particularly between the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) node and bilateral inferior parietal lobule (IPL), as well as between the ACC/mPFC node and the posterior cingulate cortex (PCC) node. Patients also showed reduced connectivity in the set-maintenance network, especially between right anterior insula/frontal operculum (aI/fO) node and bilateral superior frontal gyrus (SFG), as well as between the right aI/fO and ACC and between the ACC and right SFG.</p><p>Conclusion</p><p>Internodal functional connectivity in the DMN and set-maintenance network is reduced in patients with partial OTCD compared to controls, most likely due to hyperammonemia-related white matter damage. Because several of the affected areas are involved in executive functioning, it is postulated that this reduced connectivity is an underlying cause of the deficits OTCD patients display in this cognitive domain.</p></div

DMN.

<p>The default mode network of both subject groups is composed of an ACC/mPFC node, a PCC/precuneus node, and bilateral IPL nodes.</p

ROI Analyses Results.

<p>A) Z-scores reflecting degree of functional connectivity between pairs of ROIs in the Control group. B) Z-scores reflecting degree of functional connectivity between pairs of ROIs in OTCD patient group. C) Controls have significantly greater set-maintenance functional connectivity than OTCD patients between ACC node and bilateral SFG.</p

Participant Demographics.

<p>✦✦These values reflect the framewise displacement of patients after the exclusion of 3 OTCD patients due to excessive head motion (<i>N</i> = 13).</p><p>Participant Demographics.</p