Habenular Involvement in Response to Subcallosal Cingulate Deep Brain Stimulation for Depression

Gavin J B Elias; Jürgen Germann; Aaron Loh; Alexandre Boutet; Aditya Pancholi; Michelle E Beyn; Venkat Bhat; D Blake Woodside; Peter Giacobbe; Sidney H Kennedy; Andres M Lozano

doi:10.3389/fpsyt.2022.810777

Habenular Involvement in Response to Subcallosal Cingulate Deep Brain Stimulation for Depression

Front Psychiatry. 2022 Feb 4:13:810777. doi: 10.3389/fpsyt.2022.810777. eCollection 2022.

Authors

Gavin J B Elias¹, Jürgen Germann¹, Aaron Loh¹, Alexandre Boutet^{1

2}, Aditya Pancholi¹, Michelle E Beyn¹, Venkat Bhat³, D Blake Woodside⁴, Peter Giacobbe⁵, Sidney H Kennedy^{4

6}, Andres M Lozano^{1

6}

Affiliations

¹ Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, ON, Canada.
² Joint Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.
³ Centre for Mental Health and Krembil Research Centre, University Health Network, Toronto, ON, Canada.
⁴ Centre for Mental Health, University Health Network, Toronto, ON, Canada.
⁵ Department of Psychiatry, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, ON, Canada.
⁶ Krembil Research Institute, University of Toronto, Toronto, ON, Canada.

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 p _Bonferroni < 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.

Keywords: deep brain stimulation; depression; habenula; neuroimaging; neuromodulation; treatment biomarker.