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Cingulate dynamics track depression recovery with deep brain stimulation.

ABSTRACT: Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD)¹. However, achieving stable recovery is unpredictable², typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting³. We currently lack objective brain-based biomarkers to guide clinical decisions by distinguishing natural transient mood fluctuations from situations requiring intervention. To address this gap, we used a new device enabling electrophysiology recording to deliver SCC DBS to ten TRD participants (ClinicalTrials.gov identifier NCT01984710). At the study endpoint of 24 weeks, 90% of participants demonstrated robust clinical response, and 70% achieved remission. Using SCC local field potentials available from six participants, we deployed an explainable artificial intelligence approach to identify SCC local field potential changes indicating the patient's current clinical state. This biomarker is distinct from transient stimulation effects, sensitive to therapeutic adjustments and accurate at capturing individual recovery states. Variable recovery trajectories are predicted by the degree of preoperative damage to the structural integrity and functional connectivity within the targeted white matter treatment network, and are matched by objective facial expression changes detected using data-driven video analysis. Our results demonstrate the utility of objective biomarkers in the management of personalized SCC DBS and provide new insight into the relationship between multifaceted (functional, anatomical and behavioural) features of TRD pathology, motivating further research into causes of variability in depression treatment.

SUBMITTER: Alagapan S

PROVIDER: S-EPMC10550829 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Cingulate dynamics track depression recovery with deep brain stimulation.

Alagapan Sankaraleengam S Choi Ki Sueng KS Heisig Stephen S Riva-Posse Patricio P Crowell Andrea A Tiruvadi Vineet V Obatusin Mosadoluwa M Veerakumar Ashan A Waters Allison C AC Gross Robert E RE Quinn Sinead S Denison Lydia L O'Shaughnessy Matthew M Connor Marissa M Canal Gregory G Cha Jungho J Hershenberg Rachel R Nauvel Tanya T Isbaine Faical F Afzal Muhammad Furqan MF Figee Martijn M Kopell Brian H BH Butera Robert R Mayberg Helen S HS Rozell Christopher J CJ

Nature 20230920 7981

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD)1. However, achieving stable recovery is unpredictable2, typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting3. We currently lack objective brain-based biomarkers to guide clinical decisions by distinguishing natural transient mood fluctuations f ...[more]

PMID: 37730990

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Project description:ContextDeep brain stimulation (DBS) may be an effective intervention for treatment-resistant depression (TRD), but available data are limited.ObjectiveTo assess the efficacy and safety of subcallosal cingulate DBS in patients with TRD with either major depressive disorder (MDD) or bipolar II disorder (BP).DesignOpen-label trial with a sham lead-in phase.SettingAcademic medical center. Patients Men and women aged 18 to 70 years with a moderate-to-severe major depressive episode after at least 4 adequate antidepressant treatments. Ten patients with MDD and 7 with BP were enrolled from a total of 323 patients screened. Intervention Deep brain stimulation electrodes were implanted bilaterally in the subcallosal cingulate white matter. Patients received single-blind sham stimulation for 4 weeks followed by active stimulation for 24 weeks. Patients then entered a single-blind discontinuation phase; this phase was stopped after the first 3 patients because of ethical concerns. Patients were evaluated for up to 2 years after the onset of active stimulation.Main outcome measuresChange in depression severity and functioning over time, and response and remission rates after 24 weeks were the primary efficacy end points; secondary efficacy end points were 1 year and 2 years of active stimulation.ResultsA significant decrease in depression and increase in function were associated with chronic stimulation. Remission and response were seen in 3 patients (18%) and 7 (41%) after 24 weeks (n = 17), 5 (36%) and 5 (36%) after 1 year (n = 14), and 7 (58%) and 11 (92%) after 2 years (n = 12) of active stimulation. No patient achieving remission experienced a spontaneous relapse. Efficacy was similar for patients with MDD and those with BP. Chronic DBS was safe and well tolerated, and no hypomanic or manic episodes occurred. A modest sham stimulation effect was found, likely due to a decrease in depression after the surgical intervention but prior to entering the sham phase.ConclusionsThe findings of this study support the long-term safety and antidepressant efficacy of subcallosal cingulate DBS for TRD and suggest equivalent safety and efficacy for TRD in patients with BP. Trial Registration clinicaltrials.gov Identifier: NCT00367003.

Project description:ImportanceThe clinical utility of monitoring behavioral changes during intraoperative testing of subcallosal cingulate deep brain stimulation is unknown.ObjectiveTo characterize the structural connectivity correlates of deep brain stimulation-evoked behavioral effects using probabilistic tractography in depression.Design, setting, and participantsCategorization of acute behavioral effects was conducted in 9 adults undergoing deep brain stimulation implantation surgery for chronic treatment-resistant depression in a randomized and blinded testing session at Emory University. Patients were studied from September 1, 2011, through June 30, 2013. Post hoc analyses of the structural tractography patterns mediating distinct categories of evoked behavioral effects were defined, including the best response overall. Data analyses were performed from May 1 through July 1, 2015.Main outcomes and measuresCategorization of stimulation-induced transient behavioral effects and delineation of the shared white matter tracts mediating response subtypes.ResultsAmong the 9 patients, 72 active and 36 sham trials were recorded. The following stereotypical behavior patterns were identified: changes in interoceptive (noted changes in body state in 30 of 72 active and 4 of 36 sham trials) and in exteroceptive (shift in attention from patient to others in 9 of 72 active and 0 sham trials) awareness. The best response was a combination of exteroceptive and interoceptive changes at a single left contact for all 9 patients. Structural connectivity showed that the best response contacts had a pattern of connections to the bilateral ventromedial frontal cortex (via forceps minor and left uncinate fasciculus) and to the cingulate cortex (via left cingulum bundle), whereas behaviorally salient but nonbest contacts had only cingulate involvement. The involvement of the 3 white matter bundles during stimulation of the best contacts suggests a mechanism for the observed transient "depression switch."Conclusions and relevanceThis analysis of transient behavior changes during intraoperative deep brain stimulation of the subcallosal cingulate and the subsequent identification of unique connectivity patterns may provide a biomarker of a rapid-onset depression switch to guide surgical implantation and to refine and optimize algorithms for the selection of contacts in long-term stimulation for treatment-resistant depression.

Project description:BackgroundDeep brain stimulation (DBS) of the subcallosal cingulate (SCC) is an emerging experimental therapy for treatment-resistant depression. New developments in SCC DBS surgical targeting are focused on identifying specific axonal pathways for stimulation that are estimated from preoperatively collected diffusion-weighted imaging (DWI) data. However, brain shift induced by opening burr holes in the skull may alter the position of the target pathways.ObjectivesQuantify the effect of electrode location deviations on tractographic representations for stimulating the target pathways using longitudinal clinical imaging datasets.MethodsPreoperative MRI and DWI data (planned) were coregistered with postoperative MRI (1 day, near-term) and CT (3 weeks, long-term) data. Brain shift was measured with anatomical control points. Electrode models corresponding to the planned, near-term, and long-term locations were defined in each hemisphere of 15 patients. Tractography analyses were performed using estimated stimulation volumes as seeds centered on the different electrode positions.ResultsMean brain shift of 2.2 mm was observed in the near-term for the frontal pole, which resolved in the long-term. However, electrode displacements from the planned stereotactic target location were observed in the anterior-superior direction in both the near-term (mean left electrode shift: 0.43 mm, mean right electrode shift: 0.99 mm) and long-term (mean left electrode shift: 1.02 mm, mean right electrode shift: 1.47 mm). DBS electrodes implanted in the right hemisphere (second-side operated) were more displaced from the plan than those in the left hemisphere. These displacements resulted in 3.6% decrease in pathway activation between the electrode and the ventral striatum, but 2.7% increase in the frontal pole connection, compared to the plan. Remitters from six-month chronic stimulation had less variance in pathway activation patterns than the non-remitters.ConclusionsBrain shift is an important concern for SCC DBS surgical targeting and can impact connectomic analyses.

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Cingulate dynamics track depression recovery with deep brain stimulation.

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Cingulate dynamics track depression recovery with deep brain stimulation.

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