Increased functional connectivity between motor and arousal brainstem nuclei and sensorimotor cortex in therapy resistant depression

The neural correlates of treatment-resistant depression (TRD) are not fully elucidated. Brainstem functional connectivity (FC) in TRD has rarely been investigated, despite the assumed role of several brainstem nuclei in depression. 23 patients and 23 sex- and age-matched healthy controls underwent resting-state functional MRI. Seed-based connectivity (SBC) was calculated for 37 brainstem seeds with motor and arousal functions. Correlations between significant FC and somatic symptom severity were computed. FC of dorsal raphe nucleus, locus coeruleus, cuneiform nucleus and periaqueductal gray to the precentral and postcentral gyrus was increased. The anterior division of the mesencephalic reticular formation showed increased FC to left frontal pole, left superior frontal gyrus and middle temporal gyrus, whereas its lateral division showed decreased FC to frontal orbital and insular cortex, compared to healthy subjects. FC of bilateral locus coeruleus to bilateral postcentral gyrus were positively correlated with depressive symptoms and the intensity of somatic symptoms. We found increased FC between brainstem and sensorimotor and frontal cortical regions in TRD patients compared to healthy controls. Increased brainstem-cortical FC appeared to be linked with depressive and somatic symptom severity.