The impact of methylphenidate on choice impulsivity is inversely associated with corpus callosum fiber integrity across sexes

Background: Choice impulsivity represents preference towards smaller immediate rewards over larger delayed rewards. Extensive literature demonstrates that choice impulsivity can be manipulated using dopaminergic agonists such as methylphenidate (MPH), and that females exhibit elevated choice impulsivity compared to males. Sex differences are also frequently reported with respect to brain white matter (WM) fiber integrity. It has yet to be determined whether sex differences also exist in the impact of MPH on choice impulsivity, and whether these putative differences are accounted for by the integrity of differential WM fibers. Methods: Forty-eight healthy young adults completed the delay discounting (DD) task twice during MRI-DTI scans after receiving either MPH or placebo in a double-blind, placebo-controlled, within-subject design. WM fiber integrity was assessed using automated fiber quantification (AFQ) and tract-based spatial statistics (TBSS). Results: Compared to placebo, MPH yielded significantly reduced choice impulsivity in males but not in females. DTI data revealed reduced integrity in multiple WM fibers in females compared to males. Interestingly, the impact of MPH on choice impulsivity was negatively associated with fiber integrity in the forceps major of the corpus callosum for males only and positively associated with fiber integrity in the forceps minor of the corpus callosum for females only. Conclusions: Taken together, results uncover sex-specific effects of MPH on choice impulsivity, accounted for by inverse associations between choice impulsivity under MPH and the structural integrity of distinct segments of the corpus callosum. These findings highlight the need to consider sex differences in the neurobiological mechanisms of impulsivity.