Frontal asymmetry as a core feature of major depression: a functional near-infrared spectroscopy study

Frontal asymmetry plays a major role in depression. However, patients with treatment-resistant depression (TRD) have widespread hypofrontality. We investigated whether patients with TRD have a characteristic frontal activation pattern in functional near-infrared spectroscopy (fNIRS) findings and how the frontal cortex responds to different levels of cognitive tasks.We enrolled 27 right-handed patients with TRD, 27 patients without TRD and 27 healthy controls. We used multichannel fNIRS to evaluate activation of the bilateral dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC) and left motor area in response to 3 tasks: finger tapping, a low cognitive-load motor task; verbal fluency, a moderate cognitive-load task; and a dual task involving simultaneous finger tapping and verbal fluency, a high cognitive-load task.We found significant between-group differences in left DLPFC activation for all 3 tasks. The healthy controls had cortical activation in the left motor area during finger tapping and the bilateral frontal cortex during the dual task. However, patients without TRD had right VLPFC activation during finger tapping and left DLPFC activation during the dual task. Patients with TRD had bilateral DLPFC activation during finger tapping but exhibited increased bilateral VLPFC and left motor area activation during verbal fluency and increased left motor area activation during the dual task. In healthy controls and patients without TRD, we found that the right VLPFC was positively correlated with depression severity.Our cohort included only patients with late-onset depression.We found different patterns of abnormal frontal activation between patients with and without TRD. In patients without TRD, the right prefrontal cortex (PFC) was recruited during simple motor tasks. However, in patients with TRD, the bilateral PFC was recruited during simple tasks and motor cortical resources were used compensatorily during PFC-demanding complex cognitive tasks.