Methylphenidate modulates activity within cognitive neural networks of patients with post-stroke major depression: A placebo-controlled fMRI study

Rajamannar Ramasubbu¹, Bradley G Goodyear²

¹Departments of Psychiatry and Clinical Neurosciences; ²Department of Radiology and Clinical Neurosciences, University of Calgary, Hotchkiss Brain Institute, Calgary, AB, Canada

Background: Methylphenidate (MP) is a dopamine- and noradrenaline-enhancing agent beneficial for post-stroke depression (PSD) and stroke recovery due to its therapeutic effects on cognition, motivation, and mood; however, the neural mechanisms underlying its clinical effects remain unknown. This study used functional magnetic resonance imaging (fMRI) to investigate the effect of MP on brain activity in response to cognitive tasks in patients with PSD.

Methods: Nine stroke outpatients with DSM IV defined major depression underwent fMRI during two cognitive tasks (2-back and serial subtraction) on four occasions, on the first and third day of a three-day treatment of MP and placebo. Nine healthy control (HC) subjects matched for age and sex scanned during a single session served as normative data for comparison. The main outcome measure was cognitive task-dependent brain activity.

Results: For the 2-back task, left prefrontal, right parietal, posterior cingulate, and temporal and bilateral cerebellar regions exhibited significantly greater activity during the MP condition relative to placebo. Less activity was detected in rostral prefrontal and left parietal regions. For serial subtraction, greater activity was detected in medial prefrontal, biparietal, bitemporal, posterior cingulate, and bilateral cerebellar regions, as well as thalamus, putamen, and insula. Further, underactivation observed during the placebo condition relative to HC improved or reversed during MP treatment. No significant differences in behavioral measures were found between MP and placebo conditions or between patients and HC.

Conclusions: Short-term MP treatment may improve and normalize activity in cognitive neuronal networks in patients with PSD.

Keywords: methylphenidate, post-stroke depression, functional MRI, cognition