Practical considerations in epilepsy neurostimulation.

Neuromodulation is a key therapeutic tool for clinicians managing patients with drug-resistant epilepsy. Multiple devices are available with long-term follow-up and real-world experience. The aim of this review is to give a practical summary of available neuromodulation techniques to guide the selection of modalities, focusing on patient selection for devices, common approaches and techniques for initiation of programming, and outpatient management issues. Vagus nerve stimulation (VNS), deep brain stimulation of the anterior nucleus of the thalamus (DBS-ANT), and responsive neurostimulation (RNS) are all supported by randomized controlled trials that show safety and a significant impact on seizure reduction, as well as a suggestion of reduction in the risk of sudden unexplained death in epilepsy (SUDEP). Significant seizure reductions are observed after 3 months for DBS, RNS, and VNS in randomized controlled trials, and efficacy appears to improve with time out to 7 to 10 years of follow-up for all modalities, albeit in uncontrolled follow-up or retrospective studies. A significant number of patients experience seizure-free intervals of 6 months or more with all three modalities. Number and location of epileptogenic foci are important factors affecting efficacy, and together with comorbidities such as severe mood or sleep disorders, may influence the choice of modality. Programming has evolved-DBS is typically initiated at lower current/voltage than used in the pivotal trial, whereas target charge density is lower with RNS, however generalizable optimal parameters are yet to be defined. Noninvasive brain stimulation is an emerging stimulation modality, although it is currently not used widely. In summary, clinical practice has evolved from those established in pivotal trials. Guidance is now available for clinicians who wish to expand their approach, and choice of neuromodulation technique may be tailored to individual patients based on their epilepsy characteristics, risk tolerance, and preferences.

Deep brain stimulation of the supero-lateral branch of the medial forebrain bundle does not lead to changes in personality in patients suffering from severe depression.

BACKGROUND: Reports of changes in patients' social behavior during deep brain stimulation (DBS) raised the question whether DBS induces changes in personality. This study explored if (1) DBS is associated with changes in personality in patients suffering from treatment-resistant depression (TRD), (2) how personality dimensions and depression are associated, and (3) if TRD patients' self-ratings of personality are valid. METHODS: TRD patients were assessed before DBS (n = 30), 6 months (t2, n = 21), 2 (t3, n = 17) and 5 years (t4, n = 11) after the initiation of DBS of the supero-lateral branch of the medial forebrain bundle (slMFB-DBS). Personality was measured with the NEO-Five-Factor Inventory (NEO-FFI), depression severity with Hamilton (HDRS), and Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Personality dimensions did not change with slMFB-DBS compared with baseline. Extraversion was negatively correlated with HDRS28 (r = -0.48, p < 0.05) and MADRS (r = -0.45, p < 0.05) at t2. Inter-rater reliability was high for the NEO-FFI at baseline (Cronbach's α = 0.74) and at t4 (α = 0.65). Extraversion [t(29) = -5.20; p < 0.001] and openness to experience [t(29) = -6.96; p < 0.001] differed statistically significant from the normative sample, and did not predict the antidepressant response. CONCLUSIONS: slMFB-DBS was not associated with a change in personality. The severity of depression was associated with extraversion. Personality of TRD patients differed from the healthy population and did not change with response, indicating a possible scar effect. Self-ratings of personality seem valid to assess personality during TRD.

Critical review evaluating the pig as a model for human nutritional physiology.

The present review examines the pig as a model for physiological studies in human subjects related to nutrient sensing, appetite regulation, gut barrier function, intestinal microbiota and nutritional neuroscience. The nutrient-sensing mechanisms regarding acids (sour), carbohydrates (sweet), glutamic acid (umami) and fatty acids are conserved between humans and pigs. In contrast, pigs show limited perception of high-intensity sweeteners and NaCl and sense a wider array of amino acids than humans. Differences on bitter taste may reflect the adaptation to ecosystems. In relation to appetite regulation, plasma concentrations of cholecystokinin and glucagon-like peptide-1 are similar in pigs and humans, while peptide YY in pigs is ten to twenty times higher and ghrelin two to five times lower than in humans. Pigs are an excellent model for human studies for vagal nerve function related to the hormonal regulation of food intake. Similarly, the study of gut barrier functions reveals conserved defence mechanisms between the two species particularly in functional permeability. However, human data are scant for some of the defence systems and nutritional programming. The pig model has been valuable for studying the changes in human microbiota following nutritional interventions. In particular, the use of human flora-associated pigs is a useful model for infants, but the long-term stability of the implanted human microbiota in pigs remains to be investigated. The similarity of the pig and human brain anatomy and development is paradigmatic. Brain explorations and therapies described in pig, when compared with available human data, highlight their value in nutritional neuroscience, particularly regarding functional neuroimaging techniques.

Deep brain stimulation and suicide attempts in treatment-resistant patients: a case report and neuroethical analysis.

This case presents the situation of a 66-year-old woman diagnosed with Multiple System Atrophy Parkinsonian Type who underwent deep brain stimulation (DBS) therapy and subsequently made two suicide attempts. Despite receiving treatment and extensive psychotherapy, her condition did not improve, leading to suicidal behavior over the course of a year. Notably, she held unrealistic beliefs about the effectiveness of DBS therapy, expressing dissatisfaction with its outcomes. Family dynamics were complex, with the patient concealing her psychological distress while coping with her worsening health condition. This severe distress culminated in two suicide attempts within a relatively short timeframe. Our psychiatric team promptly intervened, implementing a suicidality protocol and adjusting her medication regimen. Despite a documented prevalence of suicidal ideation and attempts post-DBS in the literature, the exact causes remain uncertain, with the suggested involvement of neuroimmune or neurological pathways. This case contributes to scientific understanding by shedding light on suicide attempts following ineffective DBS interventions, emphasizing the patient's right to be informed about potential suicide risks and the possibility of assisted suicide through a neuroethical analysis. Therefore, our case underlines the importance of psychiatric evaluation and intervention in DBS patients to prevent further suicidality, focusing on a multidisciplinary approach tailored to the patient's autonomy and neuroethical principles.

Local Field Potentials in Deep Brain Stimulation: Investigation of the Most Cited Articles.

Objective: Deep brain stimulation (DBS) allows for direct electrical stimulation of neural circuitry and recording of local field potentials (LFPs). A bibliometric analysis can be implemented to identify studies that have shaped a research field and influenced future study; however, no such analysis investigating the implementation of LFPs in DBS has been performed. The objective of the present study was to identify the most highly cited articles pertaining to DBS LFPs to identify and evaluate the research that has contributed the most to this growing field. Methods: The Science Citation Index of the Web of Science was implemented to identify the top 84 most cited articles pertaining to DBS LFPs. Information regarding the publication, including author information and study aims, was extracted. Results: The most highly cited articles had had a mean of 109 citations and had been published between 2002 and 2019, with a mode in 2016. The articles had predominantly investigated the subthalamic nucleus (68% of clinical studies) in humans (83.8% of clinical studies). The studies of humans had recruited a mean of 12.5 subjects. Most of the identified articles (56.0%) had reported class III clinical evidence. Conclusions: The implementation of DBS LFPs is a novel field that is rapidly growing. However, a need exists for more studies with larger patient cohorts and more randomized controlled trials to further elucidate the benefits of this technology. These results will allow for the identification and recognition of the most influential studies pertaining to DBS LFPs, appreciation of the current and future research trends, and inform us regarding areas warranting further investigation.

Corticospinal circuit neuroplasticity may involve silent synapses: Implications for functional recovery facilitated by neuromodulation after spinal cord injury.

Spinal cord injury (SCI) leads to devastating physical consequences, such as severe sensorimotor dysfunction even lifetime disability, by damaging the corticospinal system. The conventional opinion that SCI is intractable due to the poor regeneration of neurons in the adult central nervous system (CNS) needs to be revisited as the CNS is capable of considerable plasticity, which underlie recovery from neural injury. Substantial spontaneous neuroplasticity has been demonstrated in the corticospinal motor circuitry following SCI. Some of these plastic changes appear to be beneficial while others are detrimental toward locomotor function recovery after SCI. The beneficial corticospinal plasticity in the spared corticospinal circuits can be harnessed therapeutically by multiple contemporary neuromodulatory approaches, especially the electrical stimulation-based modalities, in an activity-dependent manner to improve functional outcomes in post-SCI rehabilitation. Silent synapse generation and unsilencing contribute to profound neuroplasticity that is implicated in a variety of neurological disorders, thus they may be involved in the corticospinal motor circuit neuroplasticity following SCI. Exploring the underlying mechanisms of silent synapse-mediated neuroplasticity in the corticospinal motor circuitry that may be exploited by neuromodulation will inform a novel direction for optimizing therapeutic repair strategies and rehabilitative interventions in SCI patients.

Peri-lead edema and local field potential correlation in post-surgery subthalamic nucleus deep brain stimulation patients.

Implanting deep brain stimulation (DBS) electrodes in patients with Parkinson's disease often results in the appearance of a non-infectious, delayed-onset edema that disappears over time. However, the time window between the DBS electrode and DBS stimulating device implant is often used to record local field potentials (LFPs) which are used both to better understand basal ganglia pathophysiology and to improve DBS therapy. In this work, we investigated whether the presence of post-surgery edema correlates with the quality of LFP recordings in eight patients with advanced Parkinson's disease implanted with subthalamic DBS electrodes. The magnetic resonance scans of the brain after 8.5 ± 1.5 days from the implantation surgery were segmented and the peri-electrode edema volume was calculated for both brain hemispheres. We found a correlation (ρ = -0.81, p < 0.0218, Spearman's correlation coefficient) between left side local field potentials of the low beta band (11-20 Hz) and the edema volume of the same side. No other significant differences between the hemispheres were found. Despite the limited sample size, our results suggest that the effect on LFPs may be related to the edema localization, thus indicating a mechanism involving brain networks instead of a simple change in the electrode-tissue interface.

Asking questions that matter - Question prompt lists as tools for improving the consent process for neurotechnology clinical trials.

Implantable neurotechnology devices such as Brain Computer Interfaces (BCIs) and Deep Brain Stimulators (DBS) are an increasing part of treating or exploring potential treatments for neurological and psychiatric disorders. While only a few devices are approved, many promising prospects for future devices are under investigation. The decision to participate in a clinical trial can be challenging, given a variety of risks to be taken into consideration. During the consent process, prospective participants might lack the language to consider those risks, feel unprepared, or simply not know what questions to ask. One tool to help empower participants to play a more active role during the consent process is a Question Prompt List (QPL). QPLs are communication tools that can prompt participants and patients to articulate potential concerns. They offer a structured list of disease, treatment, or research intervention-specific questions that research participants can use as support for question asking. While QPLs have been studied as tools for improving the consent process during cancer treatment, in this paper, we suggest they would be helpful in neurotechnology research, and offer an example of a QPL as a template for an informed consent tool in neurotechnology device trials.

Utility of routine surface electrophysiology to screen for functional tremor prior to surgical treatment of essential tremor.

Background: Patients with functional tremor may be clinically misdiagnosed as "medication-refractory" essential tremor (ET) and referred for surgical treatment. Electrophysiology can screen for functional tremor and avoid inappropriate surgery. Objective: To report the utility of surface electrophysiology (SEMG) to screen for functional tremor in patients referred for ET surgery. Methods: Retrospective review of consecutive ET patients referred to the Mayo Clinic DBS clinic over 1.5 years. Included subjects had a clinical diagnosis of medication-refractory ET and completed presurgical workup including routine SEMG tremor study. Results: Of 87 subjects, 9 (10%) were clinically suspected of functional tremor by the DBS neurologist. Electrophysiology confirmed functional tremor features in 7/9 and ET in the other 2/9; and newly identified 5 additional cases of functional tremor. There were 12 total confirmed cases of functional tremor: isolated in 1, and mixed functional tremor and ET in 11. Of 11 mixed patients, 6 with mild functional overlay were approved for surgery. The remaining 5 patients with moderate-severe functional overlay and the single patient with isolated functional tremor were referred to the functional tremor motor retraining program. Of these, 1 patient with mixed tremor had residual disabling organic ET after program completion and was later approved for surgery. Thus, 5/87 patients (6%) avoided unnecessary surgery. Conclusions: Functional tremor may frequently overlay "medication-refractory" ET amongst patients referred for surgery, affecting 1 of 7 patients in our quaternary referral DBS center. Electrophysiology studies are useful to routinely screen patients and prevent unnecessary surgery.

PELP: Accounting for Missing Data in Neural Time Series by Periodic Estimation of Lost Packets.

Recent advances in wireless data transmission technology have the potential to revolutionize clinical neuroscience. Today sensing-capable electrical stimulators, known as "bidirectional devices", are used to acquire chronic brain activity from humans in natural environments. However, with wireless transmission come potential failures in data transmission, and not all available devices correctly account for missing data or provide precise timing for when data losses occur. Our inability to precisely reconstruct time-domain neural signals makes it difficult to apply subsequent neural signal processing techniques and analyses. Here, our goal was to accurately reconstruct time-domain neural signals impacted by data loss during wireless transmission. Towards this end, we developed a method termed Periodic Estimation of Lost Packets (PELP). PELP leverages the highly periodic nature of stimulation artifacts to precisely determine when data losses occur. Using simulated stimulation waveforms added to human EEG data, we show that PELP is robust to a range of stimulation waveforms and noise characteristics. Then, we applied PELP to local field potential (LFP) recordings collected using an implantable, bidirectional DBS platform operating at various telemetry bandwidths. By effectively accounting for the timing of missing data, PELP enables the analysis of neural time series data collected via wireless transmission-a prerequisite for better understanding the brain-behavior relationships underlying neurological and psychiatric disorders.

The Power of Access in Parkinson's Disease Care: A Retrospective Review of Telehealth Uptake During the COVID-19 Pandemic.

Objective: The onset of the COVID-19 pandemic in March of 2020 forced a rapid pivot to telehealth and compelled a use-case experiment in specialty telehealth neurology movement disorders care. The aims of this study were to quantify the potential benefit of telehealth as an option to the Parkinson's disease community as shown by the first 9 months of the COVID-19 pandemic, and to quantify the potential impact of the absence of a deep brain stimulation (DBS) telehealth option on DBS patient follow-up. Methods: New patient visits to the Inova Parkinson's and Movement Disorder's Center from April to December 2020 (9 months) were retrospectively reviewed for telehealth vs. in-person, demographics (age, gender, race, primary insurance), chief complaint, prior movement disorders specialist (MDS) consultation, imaging tests ordered, and distance/travel time from primary zip code to clinic. Additionally, DBS programming visit volume from April to December 2020 was compared to DBS programming visit volume from April to December 2019. Results: Of the 1,097 new patients seen, 85% were via telehealth (N = 932) and 15% in person (N = 165). In the telehealth cohort, 97.75% had not consulted with an MDS before (N = 911), vs. 87.9% of in-person (N = 145). Age range was 61.8 +/- 17.9 years (telehealth), 68.8 +/- 16.0 years (in-person). Racial breakdown for telehealth was 60.7% White (N = 566), 10.4% Black (N = 97), 7.4% Asian (N = 69) and 4.5% Hispanic (N = 42); in-person was 70.9% White (N = 117), 5.5% Black (N = 9), 7.9% Asian (N = 13) and 5.5% Hispanic (N = 9). Top 5 consultation reasons, top 10 primary insurance providers and imaging studies ordered between the two cohorts were similar. Distance/travel time between primary zip code and clinic were 33.8 +/- 104.8 miles and 42.2 +/- 93.4 min (telehealth) vs. 38.1 +/- 114.7 miles and 44.1 +/- 97.6 min (in-person). DBS programming visits dropped 24.8% compared to the same period the year before (254 visits to 191 visits). Conclusion: Telehealth-based new patient visits to a Movement Disorders Center appeared successful at increasing access to specialty care. The minimal difference in supporting data highlights the potential parity to in-person visits. With no telehealth option for DBS visits, a significant drop-off was seen in routine DBS management.

Neuromodulation Treatments of Pathological Anxiety in Anxiety Disorders, Stressor-Related Disorders, and Major Depressive Disorder: A Dimensional Systematic Review and Meta-Analysis.

Background: Pathological anxiety is responsible for major functional impairments and resistance to conventional treatments in anxiety disorders (ADs), posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Focal neuromodulation therapies such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) are being developed to treat those disorders. Methods: We performed a dimensional systematic review and meta-analysis to assess the evidence of the efficacy of TMS, tDCS and DBS in reducing anxiety symptoms across ADs, PTSD and MDD. Reports were identified through systematic searches in PubMed/Medline, Scopus and Cochrane library (inception to November 2020), followed by review according to the PRISMA guidelines. Controlled clinical trials examining the effectiveness of brain stimulation techniques on generic anxiety symptoms in patients with ADs, PTSD or MDD were selected. Results: Nineteen studies (RCTs) met inclusion criteria, which included 589 participants. Overall, focal brain activity modulation interventions were associated with greater reduction of anxiety levels than controls [SMD: -0.56 (95% CI, -0.93 to-0.20, I 2 = 77%]. Subgroup analyses revealed positive effects for TMS across disorders, and of focal neuromodulation in generalized anxiety disorder and PTSD. Rates of clinical responses and remission were higher in the active conditions. However, the risk of bias was high in most studies. Conclusions: There is moderate quality evidence for the efficacy of neuromodulation in treating pathological anxiety. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=233084, identifier: PROSPERO CRD42021233084. It was submitted on January 29th, 2021, and registered on March 1st, 2021. No amendment was made to the recorded protocol. A change was applied for the subgroup analyses based on target brain regions, we added the putative nature (excitatory/inhibitory) of brain activity modulation.

Effectiveness of Thalamic Ventralis Oralis Anterior and Posterior Nuclei Deep Brain Stimulation for Posttraumatic Dystonia.

Herein we report that the ventralis oralis anterior and posterior (Voa/Vop) nuclei of the thalamus may be effective alternative targets for deep brain stimulation (DBS) to improve posttraumatic dystonia when the globus pallidus interna is traumatically damaged. This patient presented at age 35 years with a clinical diagnosis of posttraumatic cervical and bilateral upper limb acquired dystonia resulting from intracerebral and intraventricular hemorrhage after a motorcycle accident at age 19 years. Due to a right globus pallidus interna traumatic lesion, conventional DBS targeting of the inferior basal ganglia was not possible; thus, the alternative Voa/Vop nuclei target was implanted. The patient realized significant benefit and at last follow-up 3 years postoperatively continued to endorse marked benefit and improvement of dystonia symptoms with minimal adverse effects from bilateral DBS implantation in the alternative targets of the Voa/Vop nuclei of the thalamus.

Hyperostosis in Combination With Low Skull Density Ratio: A Potential Contraindication for Magnetic Resonance Imaging-Guided Focused Ultrasound Thalamotomy.

Since its approval in treating a number of movement disorders, magnetic resonance imaging-guided focused ultrasound (MRgFUS) has been adopted rapidly as one of the standard treatment modalities internationally. However, the efficiency of the energy delivered by the ultrasonic waves is largely determined by the highly variable bone morphology and density characteristics of the skull. One of the widely accepted indices used to facilitate patient selection is the skull density ratio (SDR). Earlier literature suggested that an SDR of less than 0.4 would be unfavorable for MRgFUS treatment. Some prior studies have excluded patients with hyperostosis. However, there is little published data regarding the impact of other skull features such as hyperostosis on treatment success. We present the case of a 66-year-old man with medically refractory essential tremor who had an SDR of 0.38 and extensive hyperostosis frontalis interna and underwent attempted MRgFUS thalamotomy treatment. However, intraoperatively the treatment was unsuccessful in generating sufficiently elevated temperature to create a lesion of the usual desired volume, and as expected, there was minimal clinical improvement. For comparison, we also summarize a case series of 4 other patients with an SDR of less than 0.4 who had successful outcomes. We believe that SDR should not be used as the only means of selecting patients for MRgFUS. Instead, important factors such as hyperostosis should be taken into consideration for patient selection and pretreatment counseling.

The antidepressant effect of nucleus accumbens deep brain stimulation is mediated by parvalbumin-positive interneurons in the dorsal dentate gyrus.

The nucleus accumbens (NAc) is a crucial region in the reward circuit and is related to anhedonia, the pivotal symptom of major depression disorder (MDD). Deep brain stimulation (DBS) of NAc has been identified as an effective treatment for severe refractory major depression; however, the underlying mechanism of NAc-DBS in MDD treatment remains elusive. Using the chronic unpredictable mild stress (CUMS) mouse model, we found NAc-DBS rescued depression-like behaviors, and reversed high gamma oscillation reduction and neurogenesis impairment in the dorsal dentate gyrus. Inactivation of parvalbumin (PV)-positive interneurons (PVI) in the dorsal DG led to depression-like behavior and decreased adult neurogenesis. Further investigation elucidated the VTA-DG GABAergic projection and CA1-NAc projection might jointly participate in NAc-DBS therapeutic mechanism. Disinhibition of the VTA-DG GABAergic projection had an antidepressant effect, and inhibition of the CA1-NAc projection reduced the antidepressant effect of DBS-NAc. Moreover, disinhibiting the VTA-DG GABAergic projection or activating the CA1-NAc projection could increase PVI activity in the dorsal DG. These results showed PVI in the dorsal DG as an essential target in depression and NAc-DBS antidepressant mechanisms.

Global Variability in Deep Brain Stimulation Practices for Parkinson's Disease.

INTRODUCTION: Deep brain stimulation (DBS) has become a standard treatment option for select patients with Parkinson's disease (PD). The selection process and surgical procedures employed have, to date, not been standardized. METHODS: A comprehensive 58-question web-based survey was developed with a focus on DBS referral practices and peri-operative management. The survey was distributed to the Parkinson's Foundation Centers of Excellence, members of the International Parkinson's Disease and Movement Disorders Society, and the Parkinson Study Group (Functional Neurosurgery Working Group) between December 2015 and May 2016. RESULTS: There were 207 individual respondents (20% response rate) drawn from 59 countries and 6 continents, of whom 64% received formal training in DBS. Thirteen percent of centers reported that DBS could proceed despite a confidence level of < 50% for PD diagnosis. A case-based approach to DBS candidacy was applied in 51.3% of centers without a cut-off for levodopa-responsiveness. Surprisingly, 33% of centers regularly used imaging for diagnostic confirmation of idiopathic PD. Thirty-one percent of centers reported that neuropsychological evaluation did not affect DBS target selection. Approximately half of the respondents reported determination of DBS candidacy based on a multidisciplinary committee evaluation and 1/3 rd reported that a committee was used for target selection. Eight percent of respondents felt that psychosocial factors should not impact DBS candidacy nor site selection. Involvement of allied health professionals in the preoperative process was sparse. There was high variability in preoperative education about DBS outcome expectations. Approximately half of the respondents did not utilize a "default brain target," though STN was used more commonly than GPi. Specific DBS procedure techniques applied, as well as follow-up timelines, were highly variable. CONCLUSION: Results revealed high variability on the best approaches for DBS candidate selection, brain target selection, procedure type, and postoperative practices. Cognitive and mood assessments were underutilized. There was low reliance on multidisciplinary teams or psychosocial factors to impact the decision-making process. There were small but significant differences in practice across global regions, especially regarding multidisciplinary teams. The wide variability of responses across multiple facets of DBS care highlights the need for prospective studies to inform evidence-based guidelines.

Proceedings of the Eighth Annual Deep Brain Stimulation Think Tank: Advances in Optogenetics, Ethical Issues Affecting DBS Research, Neuromodulatory Approaches for Depression, Adaptive Neurostimulation, and Emerging DBS Technologies.

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field. The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer's disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank.

Sleep-Aware Adaptive Deep Brain Stimulation Control: Chronic Use at Home With Dual Independent Linear Discriminate Detectors.

Adaptive deep brain stimulation (aDBS) is a promising new technology with increasing use in experimental trials to treat a diverse array of indications such as movement disorders (Parkinson's disease, essential tremor), psychiatric disorders (depression, OCD), chronic pain and epilepsy. In many aDBS trials, a neural biomarker of interest is compared with a predefined threshold and stimulation amplitude is adjusted accordingly. Across indications and implant locations, potential biomarkers are greatly influenced by sleep. Successful chronic embedded adaptive detectors must incorporate a strategy to account for sleep, to avoid unwanted or unexpected algorithm behavior. Here, we show a dual algorithm design with two independent detectors, one used to track sleep state (wake/sleep) and the other used to track parkinsonian motor state (medication-induced fluctuations). Across six hemispheres (four patients) and 47 days, our detector successfully transitioned to sleep mode while patients were sleeping, and resumed motor state tracking when patients were awake. Designing "sleep aware" aDBS algorithms may prove crucial for deployment of clinically effective fully embedded aDBS algorithms.

Corrigendum: Proceedings of the Eighth Annual Deep Brain Stimulation Think Tank: Advances in Optogenetics, Ethical Issues Affecting DBS Research, Neuromodulatory Approaches for Depression, Adaptive Neurostimulation, and Emerging DBS Technologies.

[This corrects the article DOI: 10.3389/fnhum.2021.644593.].

People With Parkinson's Disease and Freezing of Gait Show Abnormal Low Frequency Activity of Antagonistic Leg Muscles.

OBJECTIVE: Freezing of gait is detrimental to patients with idiopathic Parkinson's disease (PD). Its pathophysiology represents a multilevel failure of motor processing in the cortical, subcortical, and brainstem circuits, ultimately resulting in ineffective motor output of the spinal pattern generator. Electrophysiological studies pointed to abnormalities of oscillatory activity in freezers that covered a broad frequency range including the theta, alpha, and beta bands. We explored muscular frequency domain activity with respect to freezing, and used deep brain stimulation to modulate these rhythms thereby evaluating the supraspinal contributions to spinal motor neuron activity. METHODS: We analyzed 9 PD freezers and 16 healthy controls (HC). We studied the patients after overnight withdrawal of dopaminergic medication with stimulation off, stimulation of the subthalamic nucleus (STN-DBSonly) or the substantia nigra pars reticulate (SNr-DBSonly), respectively. Patients performed a walking paradigm passing a narrow obstacle. We analyzed the frequency-domain spectra of the tibialis anterior (TA) and gastrocnemius (GA) muscles in 'regular gait' and during the 'freezing' episodes. RESULTS: In stimulation off, PD freezers showed increased muscle activity of the alpha and low-beta band compared to HC in both TA and GA. This activity increase was present during straight walking and during the freezes to similar extent. STN- but not SNr-DBS decreased this activity and paralleled the clinical improvement of freezing. CONCLUSION: We found increased muscle activation of the alpha and lower beta band in PD freezers compared to HC, and this was attenuated with STN-DBS. Future studies may use combined recordings of local field potentials, electroencephalography (EEG), and electromyography (EMG) to interrogate the supraspinal circuit mechanisms of the pathological activation pattern of the spinal pattern generator.