Neural Correlates of Symptom Improvement Following Stimulant Treatment in Adults with Attention-Deficit/Hyperactivity Disorder

Abstract

Objective: The purposes of this study were to examine the impact of 3 weeks of amphetamine administration on intrinsic connectome-wide connectivity patterns in adults with attention-deficit/hyperactivity disorder (ADHD) and explore the association between stimulant-induced symptom improvement and functional connectivity alteration. Methods: Participants included 19 adults (age 20-55 years) diagnosed with ADHD using the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria per the Adult Clinician Diagnostic Scale taking part in amphetamine trials. For each patient, two 6-minute resting-state functional magnetic resonance imaging (R-fMRI) scans were acquired at baseline and after treatment. A fully data-driven multivariate analytic approach (i.e., multivariate distance matrix regression [MDMR]) was applied to R-fMRI data to characterize the distributed pharmacological effects in the entire functional connectome. Clinical efficacy was assessed using ADHD rating scale with adult prompts and the Adult Self-Report Scale v1.1 Symptom Checklist. We linked stimulant-induced functional connectivity changes to symptom amelioration using Spearman's correlation. Results: Three weeks of administration of a stimulant significantly reduced ADHD symptoms. MDMR-based analyses on RfMRI data highlighted the left dorsolateral prefrontal cortex (DLPFC, a key cognitive control region) and the medial prefrontal cortex (MPFC, the anterior core of default network) whose distributed patterns of functional connectivity across the entire brain were altered by psychostimulants. Follow-up intrinsic functional connectivity revealed that stimulants specifically decreased the positive functional connectivity between DLPFC-insula, DLPFC-anterior cingulate cortex, and MPFC-insula. Importantly, these functional connectivity changes are associated with symptom improvement. Conclusion: These results suggested that ADHD is associated with increased functional integration or decreased functional segregation between core regions of cognitive control, default, and salience networks. The apparent normalization of intrinsic functional interaction in these circuits (i.e., increased functional segregation) may underlie the clinical benefits produced by 3 weeks of amphetamine treatment.

Abnormal Resting-State Functional Connectivity of Insular Subregions and Disrupted Correlation with Working Memory in Adults with Attention Deficit/Hyperactivity Disorder

“…The results are also in line with recent resting-state studies examining SN abnormality in patients with ADHD ( 16 , 72 ). Another study found that the improvement of ADHD symptom improvement in adults with ADHD by taking in amphetamine was linked to altered insula-medial prefrontal cortex (a core part of DMN) connectivity ( 73 ). These consistent results may suggest that the abnormal salience stimuli allocation procedure mediated by the AI, might be involved in the cognitive and EFs.…”

Distinct effects of childhood ADHD and cannabis use on brain functional architecture in young adults

“…First is that while recruiting from the MTA sample provided a unique and invaluable opportunity to assess brain functional architecture in individuals with childhood ADHD who have been followed longitudinally since middle childhood, our final sample, once divided into 4 groups, was relatively small. Consequently, even though studies have shown that acute (An et al, 2013, Cary et al, 2016, Hong et al, 2015, Yang et al, 2016) and long-term (Battel et al, 2016) stimulant treatment can alter network functional connectivity in ADHD, we were unable to leverage the rich longitudinal phenotypic data available for MTA participants (e.g., treatment received, symptom trajectories) due to the prohibitively small samples remaining once participants were stratified accordingly. Future analyses of data collected as part of the larger MTA study will examine important questions related to the effects of cumulative exposure to ADHD medications over time on neurocognitive performance and brain function; unfortunately such questions could not be addressed in the current study.…”

Aberrant Temporal Connectivity in Persons at Clinical High Risk for Psychosis

“…Whole-brain analyses using MDMR have been used in different cohorts including pediatric samples (72), individuals with Attention Deficit/Hyperactivity Disorder (40, 73), cohorts with psychosis-spectrum symptoms (35) as well as depression and post-traumatic stress disorder (74). Compared to classic seed-based analyses, MDMR has the advantage of using information from all voxels in order to identify “hot spots” of dysconnectivity.…”