Neural Correlates of Symptom Improvement Following Stimulant Treatment in Adults
with Attention-Deficit/Hyperactivity Disorder, Zhen Yang, PhD, Clare Kelly, PhD, Francisco X. Castellanos, MD, Terry Leon, MS, Michael P. Milham, MD, PhD, and Lenard A. Adler, MD
JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY, p. 1–10,DOI: 10.1089/cap.2015.0243

Several prior studies have examined effects of stimulant medications on functional connectivity during resting state fMRI (R-fMRI). This study appears to be the first study to examine effects of ADHD treatment on functional connectivity in adults. Nineteen adults with ADHD were received two, six minute R-fMRI scans at baseline and after three weeks of single-blind treatment with amphetamine (mixed amphetamine salts (MAS) or lisdexamfetamine (LDX)).

A comparison group of healthy controls (HC) was scanned once at baseline. Potential amphetamine effects on the entire connectome relating to R-fMRI were examined through a data driven analytic approach. Clinical effects of amphetamines on ADHD symptoms were examined via the prompted ADHD Rating Scale (ADHD-RS) administered by a clinician and the Adult Self Report Scale (ASRS) v1.1 Symptom Checklist. MAS and LDX both significantly improved ADHD symptoms on the ADHD-RS and ASRS. Functional connectivity analyses showed that stimulants altered multivariate connectivity in medial prefrontal cortex (MPFC)/paracingulate gyrus and the dorsolateral PFC. Seed based correlation analyses were defined for the left DLPFC and bilateral MPFC. Functional connectivity analyses showed that amphetamines decreased positive functional connectivity between: a) left DLPFC and bilateral dorsal ACC, right insula and left insula and b) bilateral MPFC. These reductions in functional connectivity led to a pattern of function similar to the healthy controls, which is important as the increased functional segregation of these units may be involved in the improvement with amphetamine treatment. Although these results cannot be directly translated into the clinic, they hold open the promise that, in the future, imaging methodologies may be useful for either predicting or tracking treatment response.