Effective connectivity between deep brain stimulation targets in individuals with treatment-resistant depression

Abstract

The therapeutic effect of deep brain stimulation on patients with treatment-resistant depression is strongly dependent on the connectivity of the stimulation region with other regions associated with depression. The aims of this study are to characterize the effective connectivity between the brain regions playing important roles in depression and further investigate the underlying pathophysiological mechanisms of treatment-resistant depression and the mechanisms involving deep brain stimulation. Thirty-three individuals with treatment-resistant depression and twenty-nine healthy control subjects were examined. All subjects underwent resting-state functional magnetic resonance imaging scanning. The coupling parameters reflecting the causal interactions among deep brain stimulation targets and medial prefrontal cortex were estimated using spectral dynamic causal modeling. Our results showed that compared to the healthy control subjects, in the left hemisphere of treatment-resistant depression patients, the nucleus accumbens was inhibited by the inferior thalamic peduncle and excited the ventral caudate and the subcallosal cingulate gyrus, which in turn excited the lateral habenula. In the right hemisphere, lateral habenula inhibited ventral caudate and nucleus accumbens, both of which inhibited inferior thalamic peduncle, which in turn inhibited cingulate gyrus. ventral caudate excited lateral habenula and cingulate gyrus, which excited medial prefrontal cortex. Furthermore, these effective connectivity links varied between males and females, and left and right hemispheres. Our findings suggest that intrinsic excitatory/inhibitory connections between deep brain stimulation targets are impaired in treatment-resistant depression patients and that these connections are sex dependent and hemispherically lateralized. This knowledge can help to better understand the underlying mechanisms of treatment-resistant depression, and along with tractography, structural imaging, and other relevant clinical information, may assist to determine the appropriate region for deep brain stimulation therapy in each treatment-resistant depression patient.

The Habenula in Mood Disorders: A Scoping Review of Human Studies

“…Another one used a seed-to-voxel analysis where voxels within specific ROIs were considered in addition to ROI-to-ROI analyses (Jung et al, 2022). Three studies exclusively performed ROI-to-ROI analyses (Amiri et al, 2023;Gosnell et al, 2019;Poblete et al, 2022). Lastly, two studies opted for network analysis (Amiri et al, 2021;Zhu et al, 2019), which is a framework that envisions the brain as an intricate network.…”

“…One study found that when DBS of the SCC was turned on, RSFC between the whole habenula and a cluster in the ACC was higher than when it was turned off (Elias et al, 2022). Another study, using dynamic causal modeling to model effective connectivity, provided evidence suggesting that in the left hemisphere, connections from the SCC to the habenula were excitatory in the TRD group, whereas they were inhibitory in HCs (Amiri et al, 2023). Overall, because of the great methodological diversity among the studies, no clear pattern emerges from these studies.…”