Long-Term Efficacy and Resting-State Functional Magnetic Resonance Imaging Changes of Deep Brain Stimulation in the Lateral Habenula Nucleus for Treatment-Resistant Bipolar Disorder.

BACKGROUND: To explore the long-term efficacy and resting-state functional magnetic resonance imaging (fMRI) changes of lateral habenula nucleus (LHb) deep brain stimulation (DBS; LHb-DBS) for treatment-resistant bipolar disorder (TRBD). METHODS: An 18-year-old woman with TRBD received bilateral LHb-DBS. We assessed changes in Hamilton Depression Scale-17 (HDRS-17), Bech-Rafaelsen Melancholia Scale (BRMS), Hamilton Anxiety Scale (HAMA), and Pittsburgh Sleep Quality Scale (PSQI) scores from preoperative baseline to postoperative continuous 24-month follow-up. Brain activity and resting-state functional connectivity (rsFC) were examined off-stimulation at 0.6 and 15 months post-LHb-DBS. Overall improvement and adverse events were analyzed. RESULTS: Continuous 24-month follow-up showed average improvements from baseline of 65.33%, 54.90%, 63.33%, and 48.72% for HDRS-17, BRMS, HAMA, and PSQI scores, respectively. At the final follow-up, improvement was 96.00%, 88.24%, 84.85%, and 69.23%, respectively. Resting-state fMRI results revealed an increase in fractional amplitude of low-frequency fluctuations (fALFF) within the putamen, ventral tegmental area (VTA), and substantia nigra pars compacta (SNc) over 15 months of continuous bilateral LHb stimulation when DBS was off. From baseline to 15 months, fALFF in the putamen, VTA, and SNc increased by 1.68%, 6.36%, and 1.10%, respectively. Consistently reduction in rsFC was observed between the left nucleus accumbens (NAcc) and left hippocampus. Over the 15 months of continuous stimulation, rsFC decreased by 72% from baseline. CONCLUSIONS: Long-term LHb-DBS can control symptoms and improve the quality of life in patients with TRBD. This may be attributed to an increase in fALFF in the putamen, VTA, and SNc, and a reduction in rsFC between the left NAcc and left hippocampus.