Abstract
The habenula (Hb) is a small, evolutionarily conserved epithalamic structure implicated in functions such as reward and mood regulation. Prior imaging work suggests that Hb's structural and functional properties may relate to treatment response in depression and other mood disorders. We used multimodal MRI techniques to investigate the potential involvement of Hb in response to subcallosal cingulate area deep brain stimulation (SCC-DBS) for treatment-resistant mood disorders. Using an automated segmentation technique, we compared Hb volume at baseline and at a subsequent post-operative timepoint (4.4 ± 3.0 years after surgery) in a cohort of 32 patients who received SCC-DBS. Clinical response to treatment (≥50% decrease in HAMD-17 from baseline to 12 months post-operation) was significantly associated with longitudinal Hb volume change: responders tended to have increased Hb volume over time, while non-responders showed decreased Hb volume (t = 2.4, p = 0.021). We additionally used functional MRI (fMRI) in a subcohort of SCC-DBS patients (n = 12) to investigate immediate within-patient changes in Hb functional connectivity associated with SCC-DBS stimulation. Active DBS was significantly associated with increased Hb connectivity to several prefrontal and corticolimbic regions (TFCE-adjusted pBonferroni < 0.0001), many of which have been previously implicated in the neurocircuitry of depression. Taken together, our results suggest that Hb may play an important role in the antidepressant effect of SCC-DBS.
Highlights
The habenula (Hb) is a small, bilateral, and highly evolutionarily preserved structure situated in the epithalamus [1, 2]
The present study employed multimodal MRI techniques to investigate the involvement of the habenula (Hb) in clinical response to subcallosal cingulate area deep brain stimulation (SCC-Deep brain stimulation (DBS))
Evidence supporting such an involvement was observed in two ways: (i) longitudinal Hb volume change following DBS treatment differed in SCC-DBS responders compared to non-responders; (ii) active SCC-DBS stimulation acutely modulated Hb’s functional connectivity to a number of regions that are implicated in brain-wide depression networks [54,55,56,57]
Summary
The habenula (Hb) is a small, bilateral, and highly evolutionarily preserved structure situated in the epithalamus [1, 2]. Volumetric studies in humans have likewise detected altered habenula volume in individuals with depression, bipolar disorder, schizophrenia, and autism spectrum disorder [12, 19, 22, 23]. Hb volume changes have been observed in bipolar disorder (BD) and major depressive disorder (MDD) patients who received pharmacotherapy but not in medication-naïve patients [23]. Other studies report response-related changes in Hb functional connectivity in MDD, patients following treatment with electroconvulsive therapy [24] or ketamine [24, 25]. Baseline structural and functional Hb connectivity patterns have been shown to predict response (75% sensitivity; 72% specificity) to inpatient treatment in a large MDD cohort [26]
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