Deep Brain Stimulation Implantation Research Articles

Evaluation of DBS Timeline in Movement Disorders: A Comparison Between Genders

Deep brain stimulation (DBS) is a pivotal surgical treatment for movement disorders. However, men and women have had differing opinions and referral experiences related to DBS, leading us to assess whether a gender disparity exists in the interval from a movement disorder diagnosis to DBS usage. We performed a single-center, retrospective cohort study of 105 patients who had undergone DBS surgery for either Parkinson disease (PD) or essential tremor (ET). We compared gender differences in the median interval between the diagnosis date, DBS consultation date, and DBS surgery dates. Additionally, the patient demographics, baseline clinical characteristics, and DBS outcomes were compared between men and women. We found no significant differences between genders in the interval from the diagnosis to DBS surgery for ET or PD. At the DBS consultation for ET, the women had had significantly greater disease severity compared with the men (P= 0.029). The baseline motor impairment without medication was similar between the men and women with PD. However, female patients with PD had experienced a significantly greater reduction compared with male patients in baseline motor impairment with medication versus without medication (P= 0.042). No minority populations were represented within the female ET and PD subgroups. Our study detected no gender differences in the DBS implantation timeline but alluded to a gender-specific discrepancy in DBS referral for ET. The female patients did not have a shorter duration from the ET diagnosis to DBS, despite experiencing significantly greater baseline ET severity compared with their male counterparts. Furthermore, the women with ET more often used Medicaid insurance and were without minority representation.

Analysis of human brain tissue derived from DBS surgery

BackgroundTranscriptomic and proteomic profiling of human brain tissue is hindered by the availability of fresh samples from living patients. Postmortem samples usually represent the advanced disease stage of the patient. Furthermore, the postmortem interval can affect the transcriptomic and proteomic profiles. Therefore, fresh brain tissue samples from living patients represent a valuable resource of metabolically intact tissue. Implantation of deep brain stimulation (DBS) electrodes into the human brain is a neurosurgical treatment for, e.g., movement disorders. Here, we describe an improved approach to collecting brain tissues from surgical instruments used in implantation of DBS device for transcriptomics and proteomics analyses.MethodsSamples were extracted from guide tubes and recording electrodes used in routine DBS implantation procedure to treat patients with Parkinson’s disease, genetic dystonia and tremor. RNA sequencing was performed in tissues extracted from the recording microelectrodes and liquid chromatography-mass spectrometry (LC-MS) performed in tissues from guide tubes. To assess the performance of the current approach, the obtained datasets were compared with previously published datasets representing brain tissues.ResultsAltogether, 32,034 RNA transcripts representing the unique Ensembl gene identifiers were detected from eight samples representing both hemispheres of four patients. By using LC-MS, we identified 734 unique proteins from 31 samples collected from 14 patients. The datasets are available in the BioStudies database (accession number S-BSST667). Our results indicate that surgical instruments used in DBS installation retain brain material sufficient for protein and gene expression studies. Comparison with previously published datasets obtained with similar approach proved the robustness and reproducibility of the protocol.ConclusionsThe instruments used during routine DBS surgery are a useful source for obtaining fresh brain tissues from living patients. This approach overcomes the issues that arise from using postmortem tissues, such as the effect of postmortem interval on transcriptomic and proteomic landscape of the brain, and can be used for studying molecular aspects of DBS-treatable diseases.

Up to What Extent Does Dravet Syndrome Benefit From Neurostimulation Techniques?

BackgroundDravet syndrome (DS) is a refractory developmental and epileptic encephalopathy (EE) with a variety of comorbidities, including cognitive impairment, autism-like behavior, speech dysfunction, and ataxia, which can seriously affect the quality of life of patients and impose a great burden on society and their families. Currently, the pharmacological therapy is patient dependent and may work or not. Neuromodulation techniques, including vagus nerve stimulation (VNS), deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), responsive neurostimulation (RNS), and chronic subthreshold cortical stimulation (CSCS), have become common adjuvant therapies for neurological diseases, but their efficacy in the treatment of DS is unknown.MethodsWe searched Web of Science, PubMed, and SpringerLink for all published cases related to the neuromodulation techniques of DS until January 15, 2022. The systematic review was supplemented with relevant articles from the references. The results reported by each study were summarized narratively.ResultsThe Web of science, PubMed and SpringerLink search yielded 258 items. A total of 16 studies published between 2016 and 2021 met the final inclusion criteria. Overall, 16 articles (109 cases) were included in this study, among which fifteen (107 patients) were involved VNS, and one (2 patients) was involved DBS. After VNS implantation, seizures were reduced to ≥50% in 60 cases (56%), seizure free were found in 8 cases (7.5%). Only two DS patients received DBS treatment, and the initial outcomes of DBS implantation were unsatisfactory. The seizures significantly improved over time for both DBS patients after the addition of antiepileptic drugs.ConclusionMore than half of the DS patients benefited from VNS, and VNS may be effective in the treatment of DS. However, it is important to note that VNS does not guarantee improvement of seizures, and there is a risk of infection and subsequent device failure. Although DBS is a safe and effective strategy for the treatment of refractory epilepsy, the role of DBS in DS needs further study, as the sample size was small. Thus far, there is no strong evidence for the role of DBS in DS.

Fully Closed Loop Test Environment for Adaptive Implantable Neural Stimulators Using Computational Models.

Implantable brain stimulation devices continue to be developed to treat and monitor brain conditions. As the complexity of these devices grows to include adaptive neuromodulation therapy, validating the operation and verifying the correctness of these systems becomes more complicated. The new complexities lie in the functioning of the device being dependent on the interaction with the patient and environmental factors such as noise and artifacts. Here, we present a hardware-in-the-loop (HIL) testing framework that employs computational models of pathological neural dynamics to test adaptive deep brain stimulation (DBS) devices prior to animal or human testing. A brain stimulation and recording electrode array is placed in the saline tank and connected to an adaptive neuromodulation system that measures and processes the synthetic signals and delivers stimulation back into the saline tank. A data acquisition system is used to detect the stimulation and provide feedback to the computational model in order to simulate the effects of stimulation on the neural dynamics. In this study, we used real-time computational models to emulate the dynamics of epileptic seizures observed in the anterior nucleus of the thalamus (ANT) in epilepsy patients and beta band (11-35 Hz) oscillations observed in the subthalamic nucleus (STN) of Parkinson's disease (PD) patients. These models simulated neuronal responses to electrical stimulation pulses and the saline tank tested hardware interactions between the detection algorithms and stimulation interference. We tested and validated the operation of adaptive DBS algorithms for seizure and beta band power suppression embedded in an implantable DBS system (Medtronic Summit RC+S). This study highlights the utility of the proposed hardware-in-the-loop framework to systematically test the adaptive DBS systems in the presence of system aggressors such as environmental noise and stimulation-induced electrical artifacts. This testing procedure can help ensure correctness and robustness of adaptive DBS devices prior to animal and human testing.

337 Neural Network Changes with Loss of Consciousness in Parkinson's Disease

INTRODUCTION: Consciousness is likely mediated by multiple parallel yet interacting cortico-subcortical recurrent networks. The pallidocortical circuit is of particular interest given the putative role of pallidum in consciousness, according to the mesocircuit model, though this has not been well studied. METHODS: We characterized changes in pallidocortical circuits in awake versus propofol-induced unconscious states in humans by directly and simultaneously recording from perirolandic cortices and the pallidum in twelve Parkinson Disease (PD) patients undergoing implantation of therapeutic deep brain stimulation (DBS) leads. RESULTS: Propofol-induced LOC resulted in power increases up to 20 Hz in globus pallidus internus (GPi), 35 Hz in globus pallidus externus (GPe), and 100 Hz in sensorimotor cortices (S1/M1). At a network level, LOC resulted in increased pallidocortical alpha coherence with increases in Granger causality (GC) in the alpha/low beta range from GPe to all other nodes. In contrast, LOC was associated with decreased network-wide beta coherence with decreased GC in the beta range from M1 to the rest of the network. CONCLUSION: These results not only confirm the LOC-related changes in pallidocortical circuitry, but GC results suggest that widely reported LOC-related increases in alpha band power emanate from GPe. These findings support a significant role of the GPe in modulating consciousness. Simultaneous LOC-related suppression of beta synchrony from M1 to other nodes suggests that distinct oscillatory frequencies can act independently, conveying unique network level activity. Given the pathophysiologic role of beta synchrony in PD, LOC-related suppresion of beta synchrony may be amplified in this patient population, but may also highlight a parallel network mediating LOC-related loss of motor control.

Asleep deep brain stimulation with intraoperative magnetic resonance guidance: a single-institution experience.

Deep brain stimulation (DBS) is traditionally performed on an awake patient with intraoperative recordings and test stimulation. DBS performed under general anesthesia with intraoperative MRI (iMRI) has demonstrated high target accuracy, reduced operative time, direct confirmation of target placement, and the ability to place electrodes without cessation of medications. The authors describe their initial experience with using iMRI to perform asleep DBS and discuss the procedural and radiological outcomes of this procedure. All DBS electrodes were implanted under general anesthesia by a single surgeon by using a neuronavigation system with 3-T iMRI guidance. Clinical outcomes, operative duration, complications, and accuracy were retrospectively analyzed. In total, 103 patients treated from 2015 to 2019 were included, and all but 1 patient underwent bilateral implantation. Indications included Parkinson's disease (PD) (65% of patients), essential tremor (ET) (29%), dystonia (5%), and refractory epilepsy (1%). Targets included the globus pallidus pars internus (12.62% of patients), subthalamic nucleus (56.31%), ventral intermedius nucleus of the thalamus (30%), and anterior nucleus of the thalamus (1%). Technically accurate lead placement (radial error ≤ 1 mm) was obtained for 98% of leads, with a mean (95% CI) radial error of 0.50 (0.46-0.54) mm; all leads were placed with a single pass. Predicted radial error was an excellent predictor of real radial error, underestimating real error by only a mean (95% CI) of 0.16 (0.12-0.20) mm. Accuracy remained high irrespective of surgeon experience, but procedure time decreased significantly with increasing institutional and surgeon experience (p = 0.007), with a mean procedure duration of 3.65 hours. Complications included 1 case of intracranial hemorrhage (asymptomatic) and 1 case of venous infarction (symptomatic), and 2 patients had infection at the internal pulse generator site. The mean ± SD voltage was 2.92 ± 0.83 V bilaterally at 1-year follow-up. Analysis of long-term clinical efficacy demonstrated consistent postoperative improvement in clinical symptoms, as well as decreased drug doses across all indications and follow-up time points, including mean decrease in levodopa-equivalent daily dose by 53.57% (p < 0.0001) in PD patients and mean decrease in primidone dose by 61.33% (p < 0.032) in ET patients at 1-year follow-up. A total of 205 leads were placed in 103 patients by a single surgeon under iMRI guidance with few operative complications. Operative time trended downward with increasing institutional experience, and technical accuracy of radiographic lead placement was consistently high. Asleep DBS implantation with iMRI appears to be a safe and effective alternative to standard awake procedures.

421 Coherence Between the Subthalamic Nucleus and the Primary Motor Cortex in Patients With Parkinson's Disease

INTRODUCTION: DBS is established as a safe and effective treatment for Parkinson’s Disease (PD). The development of second generation stimulators based on closed loop systems is dependent upon deeper understanding of the cortical control of motricity and its coupling with STN oscillations. METHODS: Experimental study on human subjects involving 10 patients with idiopathic PD with indication for deep brain stimulation implants into the STN. Primary motor area of the hands were identified preoperatively with fMRI. Corkscrew electrodes were implanted in the scalp to obtain C3-Cz and C4-Cz derivations of the EEG. Needle electrodes were implanted into the thenar and hypothenar muscles of both hands to record motor evoked potentials and voluntary myoelectric activity. At the time of implantation of the definitive macro-electrodes, the best contacts were connected to the electrophysiological monitoring device to record STN local field potentials (LFP) from 1 side at a time. During the next 3 minutes, the patient was asked to perform closing and opening movements of the hand contralateral to the implant. Simultaneously recordings of hand-EMG, EEG signals from M1, and STN field potentials were acquired for off line analysis. RESULTS: Our data indicate that during epochs of hand movements, theta and beta range components of the EEG related to M1 were significantly increased as compared with rest epochs. Additionally, we demonstrated that, during movement, the cross correlation between STN-LFP and M1 significantly increased (p &lt; 0.001). CONCLUSION: Movement control is highly dependent upon theta and beta EEG components and upon a high coherence between STN and M1 specifically occurring during movement. The development of closed-loop stimulation devices should consider this physiology to reach better results.

Relationship of brain edema after deep brain stimulation surgery with motor and cognitive function

BackgroundSome patients with Parkinson's disease (PD) develop peri-lead brain edema after deep brain stimulation (DBS) surgery. The influence of edema on neurological function is not well characterized. We investigated the relationship of brain edema after DBS surgery with motor and cognitive function. MethodsThirteen patients with PD (6 males and 7 females; mean age: 61.2 years) who underwent bilateral subthalamic nucleus (STN) DBS surgery were included. All patients underwent magnetic resonance imaging (MRI) examination on day 6 post-DBS surgery. The volume of edema was measured either in the frontal white matter or STN on fluid attenuated inversion recovery (FLAIR) images. We examined the relationship between these volumes and changes in cognitive and motor function. ResultsPatients were divided into those with frontal subcortical edema (FE) ≥3,000 mm3 (FE + group; n = 7) and <3,000 mm3 (FE–group; n = 6). In the FE + group, the postoperative Mini-Mental State Examination score worsened by 2.4 points after one week compared with that immediately before surgery, while that in the FE-group worsened only by 0.2 points (p = 0.038). On comparing patients with peri-STN edema (SE) ≥1,000 mm3 (SE + group; n = 3) and those with SE < 1,000 mm3 (SE-group; n = 10) showed that frequency of DBS tuning in the early postoperative period of the SE + group was lesser than that in the SE-group. ConclusionsDevelopment of FE after DBS surgery was related to transient cognitive decline. On the other hand, SE seemed associated with altered motor function and reduces the requirement for tuning in the initial period after DBS implantation.

The need to be alert to complications of peri-lead cerebral edema caused by deep brain stimulation implantation: Asystematic literature review and meta-analysis study.

BackgroundThe compatibility of deep brain stimulation (DBS) hardware and MRI scans has greatly improved the diagnostic rate of postoperative peri‐lead edema (PLE). However, the etiology, incidence, and prognostic outcomes of this complication have not been established.ObjectiveThe incidence of PLE and associated symptoms, the process of occurrence and progression of this complication, as well as treatment strategies were evaluated.MethodsWe conducted a Preferred Reporting Items for Systematic Reviews and Meta‐Analyses compliant systematic review of all studies that reported on incidences of PLE and associated symptoms after DBS implantation. Through systematic literature review, we evaluated its causes, neuropsychiatric symptoms, duration, treatment methods, and prognostic outcomes.ResultsOur search retrieved 10 articles, including 5 articles on PLE and 10 articles on symptomatic PLE. The incidence of PLE was 35.8% (95% CI: 17.0%–54.6%), while the incidence of symptomatic PLE was 3.1% (95% CI: 1.5%–4.7%) accounting for 8.7% of PLE.ConclusionsThis complication is not as rare as previously reported. Therefore, it requires significant attention after DBS implantation. The correlation between its causes, duration, symptoms, and the area involved in edema should be assessed in long‐term prospective clinical studies with large sample sizes.

Case report on ear numbness following deep brain stimulation implantation.

Introduction and importanceDeep brain stimulation (DBS) implantation is a neurosurgical procedure in which electrodes are implanted in the brain. Complications that may occur include wound infection, issues with the DBS hardware, and others. This case report presents a patient who suffered ear numbness following DBS implantation.Case presentationA 50-year-old man presented with resting tremors in both hands. He reported that his handwriting had worsened and his movements had slowed. Physical examination revealed rigidity and postural instability. The patient was diagnosed with Parkinson's disease and a bilateral subthalamic nucleus DBS implantation was scheduled combined with the patient's medication all this time. Patient's symptoms showed improvement after the procedure. However, the patient complained of ear numbness and occasional pain in the area around his ear. We observed the patient over the next 3 months and the symptoms eventually resolved without any medication and intervention.Clinical discussionEar numbness is a rare complication that occasionally occurs after DBS implantation. This complication occurs because the tunneling track's proximity to the great auricular nerve and the lesser occipital nerve can result in accidental damage to either one or both of these nerves during subcutaneous tunneling.ConclusionWe suggest a simple procedure to avoid neural injury while maintaining the course of the tunneling in which the tunnel is created below the periosteum rather than at the subcutaneous level.

Both subthalamic and pallidal deep brain stimulation are effective for GNAO1-associated dystonia: three case reports and a literature review.

Background:Mutations in the G-protein subunit alpha o1 (GNAO1) gene have recently been shown to be involved in the pathogenesis of early infantile epileptic encephalopathy and movement disorders. The clinical manifestations of GNAO1-associated movement disorders are highly heterogeneous. However, the genotype–phenotype correlations in this disease remain unclear, and the treatments for GNAO1-associated movement disorders are still limited.Objective:The objective of this study was to explore diagnostic and therapeutic strategies for GNAO1-associated movement disorders.Methods:This study describes the cases of three Chinese patients who had shown severe and progressive dystonia in the absence of epilepsy since early childhood. We performed genetic analyses in these patients. Patients 1 and 2 underwent globus pallidus internus (GPi) deep brain stimulation (DBS) implantation, and Patient 3 underwent subthalamic nucleus (STN) DBS implantation. In addition, on the basis of a literature review, we summarized and discussed the clinical characteristics and outcomes after DBS surgery for all reported patients with GNAO1-associated movement disorders.Results:Whole-exome sequencing (WES) analysis revealed de novo variants in the GNAO1 gene for all three patients, including a splice-site variant (c.724–8G > A) in Patients 1 and 3 and a novel heterozygous missense variant (c.124G > A; p. Gly42Arg) in Patient 2. Both GPi and STN DBS were effective in improving the dystonia symptoms of all three patients.Conclusion:DBS is effective in ameliorating motor symptoms in patients with GNAO1-associated movement disorders, and both STN DBS and GPi DBS should be considered promptly for patients with sustained refractory GNAO1-associated dystonia.

Novelty-induced frontal-STN networks in Parkinson's disease.

Novelty detection is a primitive subcomponent of cognitive control that can be deficient in Parkinson's disease (PD) patients. Here, we studied the corticostriatal mechanisms underlying novelty-response deficits. In participants with PD, we recorded from cortical circuits with scalp-based electroencephalography (EEG) and from subcortical circuits using intraoperative neurophysiology during surgeries for implantation of deep brain stimulation (DBS) electrodes. We report three major results. First, novel auditory stimuli triggered midfrontal low-frequency rhythms; of these, 1-4 Hz "delta" rhythms were linked to novelty-associated slowing, whereas 4-7 Hz "theta" rhythms were specifically attenuated in PD. Second, 32% of subthalamic nucleus (STN) neurons were response-modulated; nearly all (94%) of these were also modulated by novel stimuli. Third, response-modulated STN neurons were coherent with midfrontal 1-4 Hz activity. These findings link scalp-based measurements of neural activity with neuronal activity in the STN. Our results provide insight into midfrontal cognitive control mechanisms and how purported hyperdirect frontobasal ganglia circuits evaluate new information.

Deep Brain Stimulation and Treatment Outcomes of Young- and Late-Onset (≤55 Years) Parkinson's Disease: A Population-Based Study.

Background: No studies have reported the rate of motor complications (MC) and response to medical and surgical treatment in a population-based cohort of young-onset Parkinson's Disease (YOPD) patients and a cohort of sex-matched late-onset Parkinson's Disease (LOPD).Objective: To assess the outcomes of dopaminergic treatment in YOPD and LOPD, explore treatment-induced MC, medical adjustment, and rate of deep brain stimulation (DBS).Methods: We used the expanded Rochester Epidemiology Project (eREP) to investigate a population-based cohort of YOPD between 2010 and 2015 in 7 counties in Minnesota. Cases with onset ≤55 years of age were included as YOPD. An additional sex-matched cohort of LOPD (onset at ≥56 years of age) was included for comparison. All medical records were reviewed to confirm the diagnoses.Results: In the seven counties 2010–15, there were 28 YOPD patients, which were matched with a LOPD cohort. Sixteen (57%) YOPD had MC, as compared to 9 (32%) LOPD. In YOPD, 9 had motor fluctuations (MF) and Levodopa-induced dyskinesia (LID) together, whereas 3 had LID only and 4 MF only. In LOPD, 3 had MF and LID, 3 MF only, and 3 LID only. Following medical treatment for MC, 6/16 YOPD (38%) and 3/9 (33%) LOPD had symptoms resolution. In YOPD, 11/16 (69%) were considered for DBS implantation, in LOPD they were 2/9 (22%), but only 7 (6 YOPD and 1 LOPD) underwent the procedure. YOPD had significantly higher rates in both DBS candidacy and DBS surgery (respectively, p = 0.03 and p = 0.04). Among DBS-YOPD, 5/6 (83%) had positive motor response to the surgery; the LOPD case had a poor response. We report the population-based incidence of both YOPD with motor complications and YOPD undergoing DBS, which were 1.17 and 0.44 cases per 100,000 person-years, respectively.Conclusion: Fifty-seven percent of our YOPD patients and 32% of the LOPD had motor complications. Roughly half of both YOPD and LOPD were treatment resistant. YOPD had higher rates of DBS candidacy and surgery. Six YOPD and 1 LOPD underwent DBS implantation and most of them had a positive motor response after the surgery.

Use of Topical Vancomycin Powder to Reduce Surgical Site Infections after Deep Brain Stimulation Surgery: UCSF Experience and Meta-Analysis

Objective: Surgical site infection (SSI) is the most common serious complication of deep brain stimulation (DBS) implantation surgery. Here, we report a single-surgeon experience on the efficacy of topical, intrawound vancomycin powder (VP) in reducing SSI for DBS surgery and present the first systematic review and meta-analysis examining the effect of topical vancomycin on SSI in patients after DBS surgery. Methods: For the retrospective review, all unique patients undergoing DBS surgery at UCSF for new hardware implantation or internal pulse generator (IPG) replacement by a single surgeon from September 2013 to March 2019, with at least 1 year of follow-up data, were included. For the meta-analysis, we included all primary studies that compared SSIs with and without application of topical vancomycin in DBS surgeries. Results: 368 unique patients met inclusion criteria; 195 patients received topical VP (VP group) and 173 did not (control). 99/195 patients in the VP group underwent new DBS implantation and 96/195 had IPG replacement. 71/173 patients in the control group had new DBS implantation and 102/173 had IPG replacement. There were 10 total cases of SSI: 4 patients from the VP group (3 new implants and 1 IPG replacement) and 6 patients from the control group (3 new implants and 3 IPG replacements), resulting in SSI rates of 2.1 and 3.5%, respectively (p value = 0.337). Including our retrospective analysis, 6 studies met inclusion criteria for the systematic review and meta-analysis. In the 4 studies that examined primary DBS implants, 479 total patients received topical VP and 436 did not; mean odds ratio for SSI with topical vancomycin was 0.802 (95% confidence interval [CI] 0.175–3.678). Across the 5 studies that examined IPG implantations or replacements, 606 total patients received topical VP while 1,173 patients did not; mean odds ratio for SSI with topical vancomycin was 0.492 (95% CI 0.164–1.475). In either case, topical VP application did not significantly decrease risk of SSI. Conclusion: Surgical infections after DBS surgery are uncommon events, with studies demonstrating mixed results on whether topical vancomycin reduces this risk. Our single-institution retrospective analysis and systematic review of prior studies both demonstrated no significant SSI rate reduction with topical VP. This is likely due to low baseline SSI rates, resulting in a small effect size for prevention. Given the cost-effectiveness, simplicity, and low risk, topical, intrawound VP remains a treatment option to further reduce risk of SSI, particularly in settings with higher baseline infection rates.

Machine learning algorithm for decoding multiple subthalamic spike trains for speech brain–machine interfaces

Objective. The goal of this study is to decode the electrical activity of single neurons in the human subthalamic nucleus (STN) to infer the speech features that a person articulated, heard or imagined. We also aim to evaluate the amount of subthalamic neurons required for high accuracy decoding suitable for real-life speech brain-machine interfaces (BMI). Approach. We intraoperatively recorded single-neuron activity in the STN of 21 neurosurgical patients with Parkinson’s disease undergoing implantation of deep brain stimulator while patients produced, perceived or imagined the five monophthongal vowel sounds. Our decoder is based on machine learning algorithms that dynamically learn specific features of the speech-related firing patterns. Main results. In an extensive comparison of algorithms, our sparse decoder (‘SpaDe’), based on sparse decomposition of the high dimensional neuronal feature space, outperformed the other algorithms in all three conditions: production, perception and imagery. For speech production, our algorithm, Spade, predicted all vowels correctly (accuracy: 100%; chance level: 20%). For perception accuracy was 96%, and for imagery: 88%. The accuracy of Spade showed a linear behavior in the amount of neurons for the perception data, and even faster for production or imagery. Significance. Our study demonstrates that the information encoded by single neurons in the STN about the production, perception and imagery of speech is suitable for high-accuracy decoding. It is therefore an important step towards BMIs for restoration of speech faculties that bears an enormous potential to alleviate the suffering of completely paralyzed (‘locked-in’) patients and allow them to communicate again with their environment. Moreover, our research indicates how many subthalamic neurons may be necessary to achieve each level of decoding accuracy, which is of supreme importance for a neurosurgeon planning the implantation of a speech BMI.

Modifying surgical implantation of deep brain stimulation leads significantly reduces RF-induced heating during 3 T MRI.

Radiofrequency (RF) heating of tissue during magnetic resonance imaging (MRI) is a known safety risk in the presence of active implantable medical devices (AIMDs). As a result, access to MRI is limited for patients with these implants including those with deep brain stimulation (DBS) systems. Numerous factors contribute to excessive RF tissue heating at the DBS lead-tip, most notable being the trajectory of the lead. Phantom studies have demonstrated that looping the extracranial portion of the DBS lead at the surgical burr hole reduces the heating at the lead-tip; however, clinical implementation of this technique is challenging due to surgical constraints. As such, the intended looped trajectory is usually different from what is implanted in patients. To date, no data is available to quantify the extent by which surgical trajectory modification reduces RF heating of DBS leads compared to the typical surgical approach. In this work, we measured RF heating of a commercial DBS system during 3 T MRI, where the trajectory of the lead and extension cable mimicked lead trajectories constructed from postoperative CT images of 13 patients undergoing modified DBS surgery and 2 patients with unmodified trajectories. Two manually created trajectories mimicking typical heating cases seen in the literature were also evaluated. We found that modified lead trajectories reduced the average heating by 3-folds compared to unmodified lead trajectories.Clinical Relevance- This study evaluates the performance of a surgical modification in the routing of DBS leads in reducing RF-induced heating during MRI at 3 T.

Impaired Timing of Speech-Related Neurons in the Subthalamic Nucleus of Parkinson Disease Patients Suffering Speech Disorders.

Our previous study found degradation to subthalamic neuronal encoding of speech features in Parkinson disease (PD) patients suffering from speech disorders. To find how timing of speech-related neuronal firing changes in PD patients with speech disorders compared to PD patients without speech disorders. During the implantation of deep brain stimulator (DBS), we recorded the activity of single neurons in the subthalamic nucleus (STN) of 18 neurosurgical patients with PD while they articulated, listened to, or imagined articulation of 5 vowel sounds, each following a beep. We compared subthalamic activity of PD patients with (n=10) vs without speech disorders. In this comparison, patients with speech disorders had longer reaction times and shorter lengths of articulation. Their speech-related neuronal activity preceding speech onset (planning) was delayed relative to the beep, but the time between this activity and the emission of speech sound was similar. Notwithstanding, speech-related neuronal activity following the onset of speech (feedback) was delayed when computed relative to the onset. Only in these patients was the time lag of planning neurons significantly correlated with the reaction time. Neuronal activity in patients with speech disorders was delayed during imagined articulation of vowel sounds but earlier during speech perception. Our findings indicate that longer reaction times in patients with speech disorders are due to STN or earlier activity of the speech control network. This is a first step in locating the source(s) of PD delays within this network and is therefore of utmost importance for future treatment of speech disorders.

Effect of bilateral deep brain stimulation on the subthalamic nucleus on patients with Parkinson's disease: An observational and non-blinded study

ObjectiveThis study analyzed the influence of subthalamic nucleus deep brain stimulation (DBS) in motor parameters and patients' quality of life with Parkinson's disease (PD) evaluated before and after 12 months of the surgical procedure. MethodsA cohort of 20 patients with PD who underwent DBS implantation in the subthalamic nucleus was included. Pre and on-DBS postoperative data in on and off-medication periods related to motor functions and quality of life, from the application of validated scales, were collected to verify possible relationships between changes in these parameters and the surgical procedure. ResultsA significant decrease in the Hoehn and Yahr scale disease stage and in the levodopa equivalent dose (p < 0.001) was verified in the off-medication period when we compared baseline and post-12 months data. A significant decrease in dyskinesias (p = 0.009) was observed during the on-medication period by evaluating the UDysRS scale. Concerning motor functions verified through the UPDRS-III scale, it was obtained a significant reduction in total scores (p = 0.001), besides a decrease in rigidity scores for upper and lower limbs (p < 0.05) during the on-medication period. During the off-medication period, scores of UPDRS-III demonstrated a significant decrease, except for the ones related to speech and amplitude of resting tremor. Regarding the quality-of-life assessment, scores obtained from PDQ-39 showed that, after 12 months of electrode implantation, there was a significant decrease in mobility, daily living activity, and stigma parameters (p < 0.05). ConclusionsResults obtained allow us to conclude that DBS of the subthalamic nucleus in patients with PD improves motor function in both on and off-medication periods, improvement of the disease stage in the off-medication period, with no change in the on-medication period, also an improvement in the patient's self-reported quality of life and a significant reduction in the dose of L-DOPA.

Reducing Ataxic Side Effects from Ventral Intermediate Nucleus of the Thalamus Deep Brain Stimulation Implantation in Essential Tremor: Potential Advantages of Directional Stimulation

Objective: The aim of the study was to retrospectively evaluate the effect of directional deep brain stimulation (DBS) on ataxia in an essential tremor patient population. Materials and Methods: A retrospective chart review of documented Scale for Assessment and Rating of Ataxia (SARA) scores were analyzed using a case-control design. All subjects we evaluated were treated at a single, tertiary care academic center. We reviewed 14 patients who underwent bilateral ventral intermediate nucleus of the thalamus (VIM) implantation with microelectrode recording, with electrodeposition and segmented contact orientation confirmed via postoperative computed tomography. The main outcome was to determine change in ataxia scores between directional versus monopolar circumferential stimulation. Results: Fourteen patients (9 males, median age at implantation 69 [range 63–82]) underwent surgery between October 2017 and July 2020 at the UNC Movement Disorders Center. SARA scores between directional stimulation and monopolar circumferential stimulation demonstrated a significant reduction in total scores with best possible segmented stimulation (n = 13, p < 0.0001, 95% confidence interval [CI] −3.496 to −6.789). This difference remained statistically significant even after removing the SARA tremor subscore (n = 13, p < 0.0001, 95% CI −3.155 to −6.274). In line with prior reports, SARA score changes from the preoperative state were generally worsened when applying monopolar circumferential stimulation bilaterally (n = 13, p = 0.655; 95% CI −2.836 to 4.359), but improved with directional stimulation (n = 13, p = 0.010; 95% CI −1.216 to −7.547). Conclusion: This retrospective analysis appears to show evidence for improved outcomes through directional stimulation in bilateral VIM DBS implantation with reduction of ataxic side effects that have traditionally plagued postoperative results, all while providing optimized tremor reduction via stimulation.

Safety and image quality at 7T MRI for deep brain stimulation systems: Ex vivo study with lead-only and full-systems.

Ultra-high field MRI at 7 T can produce much better visualization of sub-cortical structures compared to lower field, which can greatly help target verification as well as overall treatment monitoring for patients with deep brain stimulation (DBS) implants. However, use of 7 T MRI for such patients is currently contra-indicated by guidelines from the device manufacturers due to the safety issues. The aim of this study was to provide an assessment of safety and image quality of ultra-high field magnetic resonance imaging at 7 T in patients with deep brain stimulation implants. We performed experiments with both lead-only and complete DBS systems implanted in anthropomorphic phantoms. RF heating was measured for 43 unique patient-derived device configurations. Magnetic force measurements were performed according to ASTM F2052 test method, and device integrity was assessed before and after experiments. Finally, we assessed electrode artifact in a cadaveric brain implanted with an isolated DBS lead. RF heating remained below 2°C, similar to a fever, with the 95% confidence interval between 0.38°C-0.52°C. Magnetic forces were well below forces imposed by gravity, and thus not a source of concern. No device malfunctioning was observed due to interference from MRI fields. Electrode artifact was most noticeable on MPRAGE and T2*GRE sequences, while it was minimized on T2-TSE images. Our work provides the safety assessment of ultra-high field MRI at 7 T in patients with DBS implants. Our results suggest that 7 T MRI may be performed safely in patients with DBS implants for specific implant models and MRI hardware.