Search

Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy ( NCT05915741 ). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high degree of predictability. In patients with persistent symptoms (non-responders), predictability of the neural data remained consistently high. On the other hand, in patients who improved symptomatically (responders), predictability of the neural data was significantly diminished. This neural feature accurately classified clinical status even in patients with limited duration recordings, indicating generalizability that could facilitate therapeutic decision-making., (© 2024. The Author(s).)

Treatment-resistant depression (TRD) affects approximately 2.8 million people in the U.S. with estimated annual healthcare costs of $43.8 billion. Deep brain stimulation (DBS) is currently an investigational intervention for TRD. We used a decision-analytic model to compare cost-effectiveness of DBS to treatment-as-usual (TAU) for TRD. Because this therapy is not FDA approved or in common use, our goal was to establish an effectiveness threshold that trials would need to demonstrate for this therapy to be cost-effective. Remission and complication rates were determined from review of relevant studies. We used published utility scores to reflect quality of life after treatment. Medicare reimbursement rates and health economics data were used to approximate costs. We performed Monte Carlo (MC) simulations and probabilistic sensitivity analyses to estimate incremental cost-effectiveness ratios (ICER; USD/quality-adjusted life year [QALY]) at a 5-year time horizon. Cost-effectiveness was defined using willingness-to-pay (WTP) thresholds of $100,000/QALY and $50,000/QALY for moderate and definitive cost-effectiveness, respectively. We included 274 patients across 16 studies from 2009-2021 who underwent DBS for TRD and had ≥12 months follow-up in our model inputs. From a healthcare sector perspective, DBS using non-rechargeable devices (DBS-pc) would require 55% and 85% remission, while DBS using rechargeable devices (DBS-rc) would require 11% and 19% remission for moderate and definitive cost-effectiveness, respectively. From a societal perspective, DBS-pc would require 35% and 46% remission, while DBS-rc would require 8% and 10% remission for moderate and definitive cost-effectiveness, respectively. DBS-pc will unlikely be cost-effective at any time horizon without transformative improvements in battery longevity. If remission rates ≥8-19% are achieved, DBS-rc will likely be more cost-effective than TAU for TRD, with further increasing cost-effectiveness beyond 5 years., (© 2024. The Author(s).)

Background: Deep brain stimulation (DBS) and other neuromodulatory techniques are being increasingly utilized to treat refractory neurologic and psychiatric disorders., Objective: /Hypothesis: To better understand the circuit-level pathophysiology of treatment-resistant depression (TRD) and treat the network-level dysfunction inherent to this challenging disorder, we adopted an approach of inpatient intracranial monitoring borrowed from the epilepsy surgery field., Methods: We implanted 3 patients with 4 DBS leads (bilateral pair in both the ventral capsule/ventral striatum and subcallosal cingulate) and 10 stereo-electroencephalography (sEEG) electrodes targeting depression-relevant network regions. For surgical planning, we used an interactive, holographic visualization platform to appreciate the 3D anatomy and connectivity. In the initial surgery, we placed the DBS leads and sEEG electrodes using robotic stereotaxy. Subjects were then admitted to an inpatient monitoring unit for depression-specific neurophysiological assessments. Following these investigations, subjects returned to the OR to remove the sEEG electrodes and internalize the DBS leads to implanted pulse generators., Results: Intraoperative testing revealed positive valence responses in all 3 subjects that helped verify targeting. Given the importance of the network-based hypotheses we were testing, we required accurate adherence to the surgical plan (to engage DBS and sEEG targets) and stability of DBS lead rotational position (to ensure that stimulation field estimates of the directional leads used during inpatient monitoring were relevant chronically), both of which we confirmed (mean radial error 1.2±0.9 mm; mean rotation 3.6±2.6°)., Conclusion: This novel hybrid sEEG-DBS approach allows detailed study of the neurophysiological substrates of complex neuropsychiatric disorders., Competing Interests: Declaration of competing interest SAS is a consultant for Boston Scientific, Neuropace, Koh Young, Zimmer Biomet, Varian, Sensoria Therapeutics, and co-founder of Motif Neurotech. NP is a consultant for Boston Scientific and Abbott. WG has received donated devices from Medtronic and is a consultant for Biohaven Pharmaceuticals. SJM has served as a consultant for Alkermes, Allergan, Axsome Therapeutics, Clexio Biosciences, Engrail Therapeutics, Intra-Cellular Therapies, Janssen, Neurocrine, Perception Neurosciences, Praxis Precision Medicines, and Sage Therapeutics. CCM is a consultant for Boston Scientific; receives royalties from Hologram Consultants, Neuros Medical, and Qr8 Health; and is a shareholder in the following companies: Hologram Consultants, Surgical Information Sciences, CereGate, Autonomic Technologies, Cardionomic, Enspire DBS. All other authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Deep brain stimulation (DBS) is a widely used clinical therapy that modulates neuronal firing in subcortical structures, eliciting downstream network effects. Its effectiveness is determined by electrode geometry and location as well as adjustable stimulation parameters including pulse width, interstimulus interval, frequency, and amplitude. These parameters are often determined empirically during clinical or intraoperative programming and can be altered to an almost unlimited number of combinations. Conventional high-frequency stimulation uses a continuous high-frequency square-wave pulse (typically 130-160 Hz), but other stimulation patterns may prove efficacious, such as continuous or bursting theta-frequencies, variable frequencies, and coordinated reset stimulation. Here we summarize the current landscape and potential clinical applications for novel stimulation patterns., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Najera, Mahavadi, Khan, Boddeti, Del Bene, Walker and Bentley.)

Background: A number of stereotactic platforms are available for performing deep brain stimulation (DBS) lead implantation. Robot-assisted stereotaxy has emerged more recently demonstrating comparable accuracy and shorter operating room times compared with conventional frame-based systems., Objective: To compare the accuracy of our streamlined robotic DBS workflow with data in the literature from frame-based and frameless systems., Methods: We retrospectively reviewed 126 consecutive DBS lead placement procedures using a robotic stereotactic platform. Indications included Parkinson disease (n = 94), essential tremor (n = 21), obsessive compulsive disorder (n = 7), and dystonia (n = 4). Procedures were performed using a stereotactic frame for fixation and the frame pins as skull fiducials for robot registration. We used intraoperative fluoroscopic computed tomography for registration and postplacement verification., Results: The mean radial error for the target point was 1.06 mm (SD: 0.55 mm, range 0.04-2.80 mm) on intraoperative fluoroscopic computed tomography. The mean operative time for an asleep, bilateral implant without implantable pulse generator placement was 238 minutes (SD: 52 minutes), and skin-to-skin procedure time was 116 minutes (SD: 42 minutes)., Conclusion: We describe a streamlined workflow for DBS lead placement using robot-assisted stereotaxy with a comparable accuracy profile. Obviating the need for checking and switching coordinates, as is standard for frame-based DBS, also reduces the chance for human error and facilitates training., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Objective: Deep brain stimulation (DBS) for Parkinson disease (PD) is traditionally performed with awake intraoperative testing and/or microelectrode recording. Recently, however, the procedure has been increasingly performed under general anesthesia with image-based verification. The authors sought to compare structural and functional networks engaged by awake and asleep PD-DBS of the subthalamic nucleus (STN) and correlate them with clinical outcomes., Methods: Levodopa equivalent daily dose (LEDD), pre- and postoperative motor scores on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III), and total electrical energy delivered (TEED) at 6 months were retroactively assessed in patients with PD who received implants of bilateral DBS leads. In subset analysis, implanted electrodes were reconstructed using the Lead-DBS toolbox. Volumes of tissue activated (VTAs) were used as seed points in group volumetric and connectivity analysis., Results: The clinical courses of 122 patients (52 asleep, 70 awake) were reviewed. Operating room and procedure times were significantly shorter in asleep cases. LEDD reduction, MDS-UPDRS III score improvement, and TEED at the 6-month follow-up did not differ between groups. In subset analysis (n = 40), proximity of active contact, VTA overlap, and desired network fiber counts with motor STN correlated with lower DBS energy requirement and improved motor scores. Discriminative structural fiber tracts involving supplementary motor area, thalamus, and brainstem were associated with optimal clinical improvement. Areas of highest structural and functional connectivity with VTAs did not significantly differ between the two groups., Conclusions: Compared to awake STN DBS, asleep procedures can achieve similarly optimal targeting-based on clinical outcomes, electrode placement, and connectivity estimates-in more efficient procedures and shorter operating room times.

Objective: Stereotactic radiosurgical capsulotomy (SRS-C) is an effective neurosurgical option for patients with treatment-resistant obsessive-compulsive disorder (TROCD). Unlike other procedures such as deep brain stimulation and radiofrequency ablation, the cost-effectiveness of SRS-C for TROCD has not been investigated. The authors herein report the first cost-effectiveness analysis of SRS-C for TROCD., Methods: Using a decision analytic model, the authors compared the cost-effectiveness of SRS-C to treatment as usual (TAU) for TROCD. Treatment response and complication rates were derived from a review of relevant clinical trials. Published algorithms were used to convert Yale-Brown Obsessive Compulsive Scale scores into utility scores reflecting improvements in quality of life. Costs were approached from the healthcare sector perspective and were drawn from Medicare reimbursement rates and available healthcare economics data. A Monte Carlo simulation and probabilistic sensitivity analysis were performed to estimate the incremental cost-effectiveness ratio., Results: One hundred fifty-eight TROCD patients across 9 studies who had undergone SRS-C and had at least 36 months of follow-up were included in the model. Compared to TAU, SRS-C was more cost-effective, with an estimated incremental cost-effectiveness ratio of $28,960 per quality-adjusted life year (QALY) gained. Within the 3-year time horizon, net QALYs gained were greater in the SRS-C group than the TAU group by 0.27 (95% CI 0.2698-0.2702, p < 0.0001). At willingness-to-pay thresholds of $50,000 and $100,000 per QALY, the Monte Carlo simulation revealed that SRS-C was more cost-effective than TAU in 83% and 100% of iterations, respectively., Conclusions: Compared to TAU, SRS-C for TROCD is more cost-effective under a range of possible cost and effectiveness values.

Objective: Magnetoencephalography (MEG) is a useful component of the presurgical evaluation of patients with epilepsy. Due to its high spatiotemporal resolution, MEG often provides additional information to the clinician when forming hypotheses about the epileptogenic zone (EZ). Because of the increasing utilization of stereo-electroencephalography (sEEG), MEG clusters are used to guide sEEG electrode targeting with increasing frequency. However, there are no predefined features of an MEG cluster that predict ictal activity. This study aims to determine which MEG cluster characteristics are predictive of the EZ., Methods: The authors retrospectively analyzed all patients who had an MEG study (2017-2021) and underwent subsequent sEEG evaluation. MEG dipoles and sEEG electrodes were reconstructed in the same coordinate space to calculate overlap among individual contacts on electrodes and MEG clusters. MEG cluster features-including number of dipoles, proximity, angle, density, magnitude, confidence parameters, and brain region-were used to predict ictal activity in sEEG. Logistic regression was used to identify important cluster features and to train a binary classifier to predict ictal activity., Results: Across 40 included patients, 196 electrodes (42.2%) sampled MEG clusters. Electrodes that sampled MEG clusters had higher rates of ictal and interictal activity than those that did not sample MEG clusters (ictal 68.4% vs 39.8%, p < 0.001; interictal 71.9% vs 44.6%, p < 0.001). Logistic regression revealed that the number of dipoles (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.04-1.14, t = 3.43) and confidence volume (OR 0.02, 95% CI 0.00-0.86, t = -2.032) were predictive of ictal activity. This model was predictive of ictal activity with 77.3% accuracy (sensitivity = 80%, specificity = 74%, C-statistic = 0.81). Using only the number of dipoles had a predictive accuracy of 75%, whereas a threshold between 14 and 17 dipoles in a cluster detected ictal activity with 75.9%-85.2% sensitivity., Conclusions: MEG clusters with approximately 14 or more dipoles are strong predictors of ictal activity and may be useful in the preoperative planning of sEEG implantation.

Approximately 2%-3% of the population suffers from obsessive-compulsive disorder (OCD). Several brain regions have been implicated in the pathophysiology of OCD, but their various contributions remain unclear. We examined changes in structural and functional neuroimaging before and after a variety of therapeutic interventions as an index into identifying the underlying networks involved. We identified 64 studies from 1990 to 2020 comparing pretreatment and post-treatment imaging of patients with OCD, including metabolic and perfusion, neurochemical, structural, functional and connectivity-based modalities. Treatment class included pharmacotherapy, cognitive-behavioural therapy/exposure and response prevention, stereotactic lesions, deep brain stimulation and transcranial magnetic stimulation. Changes in several brain regions are consistent and correspond with treatment response despite the heterogeneity in treatments and neuroimaging modalities. Most notable are decreases in metabolism and perfusion of the caudate, anterior cingulate cortex, thalamus and regions of prefrontal cortex (PFC) including the orbitofrontal cortex (OFC), dorsolateral PFC (DLPFC), ventromedial PFC (VMPFC) and ventrolateral PFC (VLPFC). Modulating activity within regions of the cortico-striato-thalamo-cortical system may be a common therapeutic mechanism across treatments. We identify future needs and current knowledge gaps that can be mitigated by implementing integrative methods. Future studies should incorporate a systematic, analytical approach to testing objective correlates of treatment response to better understand neurophysiological mechanisms of dysfunction., Competing Interests: Competing interests: KB reports a patent pending unrelated to the submitted work. ES reports personal fees from Elsevier, personal fees from Wiley, personal fees from Oxford, personal fees from American Psychological Association, personal fees from Jessica Kingsley, personal fees from Springer, personal fees from Lawrence Erlbaum, personal fees from Levo Therapeutics, personal fees from International OCD Foundation, grants from NIH, grants from Texas Higher Education Coordinating Board, grants from Greater Houston Community Foundation, grants from Red Cross, grants from Rebuild Texas, all outside the submitted work. HBS reports royalties from UpToDate and Cambridge University Press, and research support of multisite industry sponsored trial of investigational drug for OCD from Biohaven Pharmaceutical, and a stipend from American Medical Association for role as Associate Editor of JAMA Psychiatry. WKG reports grants from NIH, grants from McNair Foundation, grants and personal fees from Biohaven Pharmaceutical, personal fees from Neurocrine Biosciences, other from Medtronic, all outside the submitted work. SAS reports consulting agreements with Boston Scientific, Neuropace, Abbott, and Zimmer Biomet. The remaining authors report there are no competing interests., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)