Biology subjects

Figee, M.

Publications and source records attributed to Figee, M..

4 recordsLinked to original sources

bioRxiv2025

Dopamine and serotonin transients predict depressive symptom relief following deep brain stimulation of human subcallosal cingulate cortex

Recent advances in deep brain stimulation (DBS) of the subcallosal cingulate (SCC) show promise in mitigating the symptoms of treatment-resistant depression (TRD) in humans1-3. Monoamines, such as dopamine and serotonin, mediate the effects of pharmacological treatments of depression. However, their roles in recovery following DBS remain elusive, largely due to technical limitations of measuring these neurotransmitters in the living human brain. Here, by leveraging machine learning-enhanced electrochemistry4-7, we show that dopamine and serotonin signaling following DBS to the SCC predicted later depressive symptom relief in humans with TRD. We found that both dopamine and serotonin levels increased following subtherapeutic intraoperative SCC stimulation, with each neurotransmitter showing selective responses to distinct decision-making tasks. Furthermore, acute dopamine increases predicted later mood improvements during a social decision-making task, while serotonin enhancement predicted faster responses during a non-social learning task longitudinally. Critically, changes in dopamine and serotonin levels during the social decision-making task jointly predicted depressive symptom remission at 6-month follow-up. These findings illustrate the contribution of both dopamine and serotonin signaling in predicting behavioral improvement and depressive symptom remission in humans with TRD. Such neurochemical plasticity may serve as potential mechanistic biomarkers for SCC DBS mechanism and TRD treatment response. Significance statementO_LIDopamine and serotonin levels increased following acute DBS to the SCC in humans. C_LIO_LIAcute dopamine and serotonin changes predicted later mood and response speed changes. C_LIO_LISustained TRD recovery was predicted by acute increases in both dopamine and serotonin estimates. C_LI

neuroscience↗

bioRxiv2025

Longitudinal Changes in Cortical Response Dynamics with Deep Brain Stimulation to the Subcallosal Cingulate for Treatment-Resistant Depression

Deep brain stimulation (DBS) of the subcallosal cingulate cortex (SCC) is a promising intervention for treatment-resistant depression, yet objective biomarkers that track recovery remain limited. This study examined longitudinal changes in stimulation-evoked potentials (SEPs) to characterize how SCC-driven cortical communication evolves during treatment. Ten patients across three SCC-DBS trials underwent high-density EEG recordings at 4 and 24 weeks. SEP features were extracted from source-localized SCC signals and related to clinical outcomes and fractional anisotropy (FA) of midcingulate cingulum. Cortical responses showed a consistent reduction in latency and an increase in magnitude over time, indicating faster and stronger electrocortical signaling with chronic stimulation. Higher baseline midcingulate FA predicted greater latency acceleration, linking SEP timing to white-matter integrity. These findings identify temporal SEP dynamics as candidate mechanistic biomarkers that reflect circuit engagement during SCC-DBS and offer a pathway toward physiology-guided optimization of neuromodulation for depression. HighlightsO_LIReduced latency of stimulation evoked potential after 6 months of DBS C_LIO_LILarger cortical evoked response to single pulse perturbation after 6 months of DBS C_LIO_LIBaseline myelin integrity in MCC predicts magnitude of change in EP latency C_LI

neuroscience↗

bioRxiv2023

Neural Interoceptive Processing is Modulated by Deep Brain Stimulation for Treatment Resistant Depression

BackgroundA critical advance in depression research is to clarify the hypothesized role of interoceptive processing in neural mechanisms of treatment efficacy. This study tests whether cortical interoceptive processing, as indexed by the heartbeat-evoked potential (HEP), is modulated by deep brain stimulation (DBS) to the subcallosal cingulate (SCC) for treatment resistant depression (TRD). MethodsEight patients with TRD were enrolled in a study of SCC DBS safety and efficacy. Electroencephalography (EEG) and symptom severity measures were sampled in a laboratory setting over the course of a six-month treatment protocol. The primary outcome measure was an EEG-derived HEP, which reflects cortical processing of heartbeat sensation. Cluster-based permutation analyses were used to test the effect of stimulation and time in treatment on the HEP. The change in signal magnitude after treatment was correlated with change in depression severity as measured by the 17-item Hamilton Depression Rating Scale. ResultsHEP amplitude was greater after 24 weeks of treatment (t(7)=-4.40, p=.003, g=-1.38, 95% Cl [-2.3, -0.42]), and this change was inversely correlated with latency of treatment response (rho = -0.75, 95% Cl [-0.95, -0.11], p=.03). An acute effect of DBS was also observed, but as a decrease in HEP amplitude (t(6) =6.66, p<.001, g=2.19, 95% Cl [0.81, 3.54]). HEP differences were most pronounced over left posterior sensors from 405-425 ms post-stimulus. ConclusionBrain-based evidence substantiates a theorized link between interoception and depression, and suggests an interoceptive contribution to the mechanism of treatment efficacy with deep brain stimulation for severe depression.

neuroscience↗

bioRxiv2019

Deep brain stimulation modulates directional frontolimbic connectivity in obsessive-compulsive disorder

Deep brain stimulation (DBS) is effective for patients with treatment-refractory obsessive-compulsive disorder. DBS of the ventral anterior limb of the internal capsule (vALIC) rapidly improves mood and anxiety with optimal stimulation parameters. To understand these rapid effects of vALIC-DBS, we studied functional interactions within the affective amygdala circuit. We compared resting state functional magnetic resonance imaging data during chronic stimulation versus one week of stimulation discontinuation in patients, and obtained two resting state scans from matched healthy volunteers to account for test-retest effects. Imaging data were analyzed using functional connectivity analysis and dynamic causal modelling. Improvement in mood and anxiety following DBS was associated with reduced amygdala-insula functional connectivity. Directional connectivity analysis revealed that DBS increased the impact of the ventromedial prefrontal cortex on the amygdala, and decreased the impact of the amygdala on the insula. These results highlight the importance of the amygdala circuit in the pathophysiology of OCD, and suggest a neural systems model through which negative mood and anxiety are modulated by vALIC-DBS for OCD and possibly other psychiatric disorders.\n\nOne Sentence SummaryDeep brain stimulation improves mood and anxiety in obsessive-compulsive disorder by altering connectivity between the amygdala, insula and prefrontal cortex.

neuroscience↗