Feasibility Of Deep Brain Stimulation Research Articles

Safety and feasibility clinical trial of nucleus accumbens deep brain stimulation for treatment-refractory opioid use disorder.

There were more than 107,000 drug overdose deaths in the US in 2021, the most ever recorded. Despite advances in behavioral and pharmacological treatments, over 50% of those receiving treatment for opioid use disorder (OUD) experience drug use recurrence (relapse). Given the prevalence of OUD and other substance use disorders (SUDs), the high rate of drug use recurrence, and the number of drug overdose deaths, novel treatment strategies are desperately needed. The objective of this study was to evaluate the safety and feasibility of deep brain stimulation (DBS) targeting the nucleus accumbens (NAc)/ventral capsule (VC) and potential impact on outcomes in individuals with treatment-refractory OUD. A prospective, open-label, single-arm study was conducted among participants with longstanding treatment-refractory OUD (along with other co-occurring SUDs) who underwent DBS in the NAc/VC. The primary study endpoint was safety; secondary/exploratory outcomes included opioid and other substance use, substance craving, and emotional symptoms throughout follow-up and 18FDG-PET neuroimaging. Four male participants were enrolled and all tolerated DBS surgery well with no serious adverse events (AEs) and no device- or stimulation-related AEs. Two participants sustained complete substance abstinence for > 1150 and > 520 days, respectively, with significant post-DBS reductions in substance craving, anxiety, and depression. One participant experienced post-DBS drug use recurrences with reduced frequency and severity. The DBS system was explanted in one participant due to noncompliance with treatment requirements and the study protocol. 18FDG-PET neuroimaging revealed increased glucose metabolism in the frontal regions for the participants with sustained abstinence only. DBS of the NAc/VC was safe, feasible, and can potentially reduce substance use, craving, and emotional symptoms in those with treatment-refractory OUD. A randomized, sham-controlled trial in a larger cohort of patients is being initiated.

Cerebellar deep brain stimulation for chronic post-stroke motor rehabilitation: a phase I trial

Upper-extremity impairment after stroke remains a major therapeutic challenge and a target of neuromodulation treatment efforts. In this open-label, non-randomized phase I trial, we applied deep brain stimulation to the cerebellar dentate nucleus combined with renewed physical rehabilitation to promote functional reorganization of ipsilesional cortex in 12 individuals with persistent (1–3 years), moderate-to-severe upper-extremity impairment. No serious perioperative or stimulation-related adverse events were encountered, with participants demonstrating a seven-point median improvement on the Upper-Extremity Fugl-Meyer Assessment. All individuals who enrolled with partial preservation of distal motor function exceeded minimal clinically important difference regardless of time since stroke, with a median improvement of 15 Upper-Extremity Fugl-Meyer Assessment points. These robust functional gains were directly correlated with cortical reorganization evidenced by increased ipsilesional metabolism. Our findings support the safety and feasibility of deep brain stimulation to the cerebellar dentate nucleus as a promising tool for modulation of late-stage neuroplasticity for functional recovery and the need for larger clinical trials. ClinicalTrials.gov registration: NCT02835443.

A Protocol to Investigate Deep Brain Stimulation for Refractory Tinnitus: From Rat Model to the Set-Up of a Human Pilot Study

Chronic tinnitus can have an immense impact on quality of life. Despite recent treatment advances, many tinnitus patients remain refractory to them. Preclinical and clinical evidence suggests that deep brain stimulation (DBS) is a promising treatment to suppress tinnitus. In rats, it has been shown in multiple regions of the auditory pathway that DBS can have an alleviating effect on tinnitus. The thalamic medial geniculate body (MGB) takes a key position in the tinnitus network, shows pathophysiological hallmarks of tinnitus, and is readily accessible using stereotaxy. Here, a protocol is described to evaluate the safety and test the therapeutic effects of DBS in the MGB in severe tinnitus sufferers. Bilateral DBS of the MGB will be applied in a future study in six patients with severe and refractory tinnitus. A double-blinded, randomized 2 × 2 crossover design (stimulation ON and OFF) will be applied, followed by a period of six months of open-label follow-up. The primary focus is to assess safety and feasibility (acceptability). Secondary outcomes assess a potential treatment effect and include tinnitus severity measured by the Tinnitus Functional Index (TFI), tinnitus loudness and distress, hearing, cognitive and psychological functions, quality of life, and neurophysiological characteristics. This protocol carefully balances risks and benefits and takes ethical considerations into account. This study will explore the safety and feasibility of DBS in severe refractory tinnitus, through extensive assessment of clinical and neurophysiological outcome measures. Additionally, important insights into the underlying mechanism of tinnitus and hearing function might be revealed. ClinicalTrials.gov NCT03976908 (6 June 2019).

O130 / #985 NUCLEUS ACCUMBENS DEEP BRAIN STIMULATION (DBS) FOR OPIOID USE DISORDER: PRELIMINARY RESULTS OF SAFETY, FEASIBILITY, AND EFFICACY CLINICAL TRIAL: TRACK 2: BRAIN STIMULATION

Novel treatments for refractory opioid use disorder (OUD) are needed given high treatment failure rates and associated overdose deaths. We initiated an FDA-approved and US National Institute on Drug Abuse (NIDA) sponsored clinical trial to evaluate the safety and feasibility of deep brain stimulation (DBS) of the Nucleus Accumbens (NAc) and ventral anterior internal capsule (VC) for treatment-refractory OUD.

Efficacy and feasibility of deep brain stimulation for patients with depression: A protocol for systematic review and meta-analysis.

Background:Previous meta-analyses have examined the clinical efficacy and acceptability of deep brain stimulation (DBS) compared with sham therapy or paired active therapy. However, the absence of head-to-head clinical trials with some treatment comparisons creates uncertainty for decision makers. Thus, to provide new evidence-based medical evidence for clinical treatment, we undertook a meta-analysis to assess the efficacy and safety of DBS in patients with depression based on high-quality randomized controlled studies.Methods:The protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement guidelines. PubMed/Medline and EMBASE will be searched before May 2021 for all studies, using various combinations of the following free text and key terms: deep brain stimulation; depression; random. No language restrictions will be applied. The method of data extraction will follow the approach outlined by the Cochrane Handbook for Systematic Reviews of Interventions. Review Manager software 5.3 is used for the meta-analysis. The quality of randomized trials will be assessed by Cochrane risk of bias tool for randomized controlled trials.Results:The results of our review will be reported strictly following the PRISMA criteria and the review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings.OSF registration number:10.17605/OSF.IO/Q5B3S.

A systematic review of endovascular stent-electrode arrays, a minimally invasive approach to brain-machine interfaces.

The goal of this study was to systematically review the feasibility and safety of minimally invasive neurovascular approaches to brain-machine interfaces (BMIs). A systematic literature review was performed using the PubMed database for studies published between 1986 and 2019. All studies assessing endovascular neural interfaces were included. Additional studies were selected based on review of references of selected articles and review articles. Of the 53 total articles identified in the original literature search, 12 studies were ultimately selected. An additional 10 articles were included from other sources, resulting in a total of 22 studies included in this systematic review. This includes primarily preclinical studies comparing endovascular electrode recordings with subdural and epidural electrodes, as well as studies evaluating stent-electrode gauge and material type. In addition, several clinical studies are also included. Endovascular stent-electrode arrays provide a minimally invasive approach to BMIs. Stent-electrode placement has been shown to be both efficacious and safe, although further data are necessary to draw comparisons between subdural and epidural electrode measurements given the heterogeneity of the studies included. Greater access to deep-seated brain regions is now more feasible with stent-electrode arrays; however, further validation is needed in large clinical trials to optimize this neural interface. This includes the determination of ideal electrode material type, venous versus arterial approaches, the feasibility of deep brain stimulation, and more streamlined computational decoding techniques.

Is Deep Brain Stimulation still an option for tremor recurrence after Focused Ultrasound thalamotomy? A case report

With the development of MRI-guided focused ultrasound (FUS), there is an ongoing renewal of interest for ablative procedures as a surgical option for tremor disorders. One of the main criticisms regarding FUS thalamotomy is the potential recurrence of tremor symptoms during follow-up. In case of tremor reappearance, repeating the ultrasound ablation may represent a reasonable option. However, tremor is often perceived as a highly disabling condition and patients may be reluctant to undergo the same unsuccessful treatment again. In this context, few data are available about the feasibility of Deep Brain Stimulation (DBS) in case of tremor recurrence after FUS. Moreover, concerns exist that FUS lesioning could preclude or limit the effectiveness of future DBS. Here we present the case of a 73-year-old right-handed man with a disabling, right-hand, mixed tremor recurring after initial successful FUS thalamotomy and that was properly managed in the end with thalamic Deep Brain Stimulation. Our case suggests that DBS and FUS thalamotomy are not mutually exclusive, but rather they represent complementary tools in the surgical approach to tremor.

Feasibility of Deep Brain Stimulation as a Novel Treatment for Refractory Opioid Use Disorder

Feasibility of Deep Brain Stimulation as a Novel Treatment for Refractory Opioid Use Disorder

Feasibility of deep brain stimulation for controlling the lower urinary tract functions: An animal study

ObjectiveTo evaluate the feasibility of deep brain stimulation (DBS) and compare the potential of four DBS targets in rats for regulating bladder activity: the periaqueductal gray (PAG), locus coeruleus (LC), rostral pontine reticular nucleus (PnO), and pedunculopontine tegmental nucleus (PPTg). MethodsA bipolar stimulating electrode was implanted. The effects of DBS on the inhibition and activation of micturition reflexes were investigated by using isovolumetric intravesical pressure recordings. ResultsPAG DBS at 2–2.5 V, PnO DBS at 2–2.5 V, and PPTg DBS at 1.75–2.5 V nearly completely inhibited reflexive isovolumetric bladder contractions. By contrast, LC DBS at 1.75 and 2 V slightly augmented reflexive isovolumetric bladder contractions in rats. DBSs on PnO and PPTg at higher intensities (2.5–5 V) demonstrated a higher success rate and larger contraction area evocation in activating bladder contractions in a partially filled bladder. DBS targeting the PPTg was most efficient in suppressing reflexive isovolumetric bladder contractions. ConclusionPPTg DBS demonstrated stable results and high potency for controlling bladder contractions. PPTg might be a promising DBS target for developing new neuromodulatory approaches for the treatment of bladder dysfunctions. SignificanceDBS could be a potential approach to manage bladder function under various conditions.

High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models.

Approximately one quarter of individuals with an autism spectrum disorder (ASD) display self-injurious behavior (SIB) ranging from head banging to self-directed biting and punching. Sometimes, these behaviors are extreme and unresponsive to pharmacological and behavioral therapies. We have found electroconvulsive therapy (ECT) can produce life-changing results, with more than 90% suppression of SIB frequency. However, these patients typically require frequent maintenance ECT (mECT), as often as every 5 days, to sustain the improvement gained during the acute course. Long-term consequences of such frequent mECT started as early as childhood in some cases are unknown. Accordingly, there is a need for alternative forms of chronic stimulation for these patients. To explore the feasibility of deep brain stimulation (DBS) for intractable SIB seen in some patients with an ASD, we utilized two genetically distinct mouse models demonstrating excessive self-grooming, namely the Viaat-Mecp2(-/y) and Shank3B(-/-) lines, and administered high-frequency stimulation (HFS) via implanted electrodes at the subthalamic nucleus (STN-HFS). We found that STN-HFS significantly suppressed excessive self-grooming in both genetic lines. Suppression occurs both acutely when stimulation is switched on, and persists for several days after HFS is stopped. This effect was not explained by a change in locomotor activity, which was unaffected by STN-HFS. Likewise, social interaction deficits were not corrected by STN-HFS. Our data show STN-HFS suppresses excessive self-grooming in two autism-like mouse models, raising the possibility DBS might be used to treat intractable SIB associated with ASDs. Further studies are required to explore the circuitry engaged by STN-HFS, as well as other potential stimulation sites. Such studies might also yield clues about pathways, which could be modulated by non-invasive stimulatory techniques.