Relationship of prefrontal cortex activity with anhedonia and cognitive function in major depressive disorder: an fNIRS study.

Background: Major depressive disorder (MDD) is associated with deficits in cognitive function, thought to be related to underlying decreased hedonic experiences. Further research is needed to fully elucidate the role of functional brain activity in this relationship. In this study, we investigated the neurofunctional correlate of the interplay between cognitive function and hedonic experiences in medication-free MDD using functional near-infrared spectroscopy (fNIRS).

Methods: We examine differences of brain activation corresponding to the verbal fluency test (VFT) between MDD patients and healthy controls (HCs). Fifty-six MDD patients and 35 HCs underwent fMRI scanning while performing the VFT. In exploratory analyses, cognitive performance, as assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB), four dimensions of hedonic processing (desire, motivation, effort, and consummatory pleasure) measured by the Dimensional Anhedonia Rating Scale (DARS), and relative changes in oxygenated hemoglobin concentration during the VFT were compared across groups.

Results: Patients with MDD demonstrated impairments in sustained attention and working memory, accompanied by lower total and subscale scores on the DARS. Compared to healthy controls, MDD patients exhibited reduced activation in the prefrontal cortex (PFC) during the VFT task (t = 2.32 to 4.77, < 0.001 to 0.02, FDR corrected). DARS motivation, desire, and total scores as well as sustained attention, were positively correlated with activation in the dorsolateral PFC and Broca's area ( < 0.05, FDR corrected).

Conclusions: These findings indicate that changes in prefrontal lobe oxygenated hemoglobin levels, a region implicated in hedonic motivation and cognitive function, may serve as potential biomarkers for interventions targeting individuals with MDD. Our results corroborate the clinical consensus that the prefrontal cortex is a primary target for non-invasive neuromodulatory treatments for depression.