Utility of diffusion tensor imaging and generalized q-sampling imaging for predicting short-term clinical effect of deep brain stimulation in Parkinson's disease.

PURPOSE: To assess whether diffusion tensor imaging (DTI) and generalized q-sampling imaging (GQI) metrics could preoperatively predict the clinical outcome of deep brain stimulation (DBS) in patients with Parkinson's disease (PD). METHODS: In this single-center retrospective study, from September 2021 to March 2023, preoperative DTI and GQI examinations of 44 patients who underwent DBS surgery, were analyzed. To evaluate motor functions, the Unified Parkinson's Disease Rating Scale (UPDRS) during on- and off-medication and Parkinson's Disease Questionnaire-39 (PDQ-39) scales were used before and three months after DBS surgery. The study population was divided into two groups according to the improvement rate of scales: ≥ 50% and < 50%. Five target regions, reported to be affected in PD, were investigated. The parameters having statistically significant difference were subjected to a receiver operating characteristic (ROC) analysis. RESULTS: Quantitative anisotropy (qa) values from globus pallidus externus, globus pallidus internus (qa_Gpi), and substantia nigra exhibited significant distributional difference between groups in terms of the improvement rate of UPDRS-3 scale during on-medication (p = 0.003, p = 0.0003, and p = 0.0008, respectively). In ROC analysis, the best parameter in predicting DBS response included qa_Gpi with a cut-off value of 0.01370 achieved an area under the ROC curve, accuracy, sensitivity, and specificity of 0.810, 73%, 62.5%, and 85%, respectively. Optimal cut-off values of ≥ 0.01864 and ≤ 0.01162 yielded a sensitivity and specificity of 100%, respectively. CONCLUSION: The imaging parameters acquired from GQI, particularly qa_Gpi, may have the ability to non-invasively predict the clinical outcome of DBS surgery.

Lead-free dual-frequency ultrasound implants for wireless, biphasic deep brain stimulation.

Ultrasound-driven bioelectronics could offer a wireless scheme with sustainable power supply; however, current ultrasound implantable systems present critical challenges in biocompatibility and harvesting performance related to lead/lead-free piezoelectric materials and devices. Here, we report a lead-free dual-frequency ultrasound implants for wireless, biphasic deep brain stimulation, which integrates two developed lead-free sandwich porous 1-3-type piezoelectric composite elements with enhanced harvesting performance in a flexible printed circuit board. The implant is ultrasonically powered through a portable external dual-frequency transducer and generates programmable biphasic stimulus pulses in clinically relevant frequencies. Furthermore, we demonstrate ultrasound-driven implants for long-term biosafety therapy in deep brain stimulation through an epileptic rodent model. With biocompatibility and improved electrical performance, the lead-free materials and devices presented here could provide a promising platform for developing implantable ultrasonic electronics in the future.

Subthalamic nucleus synchronization between beta band local field potential and single-unit activity in Parkinson's disease.

Local field potential (LFP) oscillations in the beta band (13-30 Hz) in the subthalamic nucleus (STN) of Parkinson's disease patients have been implicated in disease severity and treatment response. The relationship between single-neuron activity in the STN and regional beta power changes remains unclear. We used spike-triggered average (STA) to assess beta synchronization in STN. Beta power and STA magnitude at the beta frequency range were compared in three conditions: STN versus other subcortical structures, dorsal versus ventral STN, and high versus low beta power STN recordings. Magnitude of STA-LFP was greater within the STN compared to extra-STN structures along the trajectory path, despite no difference in percentage of the total power. Within the STN, there was a higher percent beta power in dorsal compared to ventral STN but no difference in STA-LFP magnitude. Further refining the comparison to high versus low beta peak power recordings inside the STN to evaluate if single-unit activity synchronized more strongly with beta band activity in areas of high beta power resulted in a significantly higher STA magnitude for areas of high beta power. Overall, these results suggest that STN single units strongly synchronize to beta activity, particularly units in areas of high beta power.

Role of Functional neurosurgery in Improving Patient Outcomes in Epilepsy, Movement Disorders, and Chronic Pain.

Functional neurosurgery encompasses surgical procedures geared towards treating movement disorders (such as Parkinson's disease and essential tremor), drug-resistant epilepsy, and various types of pain disorders. It is one of the most rapidly expanding fields within neurosurgery and utilizes both traditional open surgical methods such as open temporal lobectomy for epilepsy as well as neuromodulation-based treatments such as implanting brain or nerve stimulation devices. This review outlines the role functional neurosurgery plays in treatment of epilepsy, movement disorders, and pain, and how it is being implemented at the University of Missouri by the Department of Neurosurgery.

Speech, voice, and language outcomes following deep brain stimulation: A systematic review.

BACKGROUND: Deep brain stimulation (DBS) reliably ameliorates cardinal motor symptoms in Parkinson's disease (PD) and essential tremor (ET). However, the effects of DBS on speech, voice and language have been inconsistent and have not been examined comprehensively in a single study. OBJECTIVE: We conducted a systematic analysis of literature by reviewing studies that examined the effects of DBS on speech, voice and language in PD and ET. METHODS: A total of 675 publications were retrieved from PubMed, Embase, CINHAL, Web of Science, Cochrane Library and Scopus databases. Based on our selection criteria, 90 papers were included in our analysis. The selected publications were categorized into four subcategories: Fluency, Word production, Articulation and phonology and Voice quality. RESULTS: The results suggested a long-term decline in verbal fluency, with more studies reporting deficits in phonemic fluency than semantic fluency following DBS. Additionally, high frequency stimulation, left-sided and bilateral DBS were associated with worse verbal fluency outcomes. Naming improved in the short-term following DBS-ON compared to DBS-OFF, with no long-term differences between the two conditions. Bilateral and low-frequency DBS demonstrated a relative improvement for phonation and articulation. Nonetheless, long-term DBS exacerbated phonation and articulation deficits. The effect of DBS on voice was highly variable, with both improvements and deterioration in different measures of voice. CONCLUSION: This was the first study that aimed to combine the outcome of speech, voice, and language following DBS in a single systematic review. The findings revealed a heterogeneous pattern of results for speech, voice, and language across DBS studies, and provided directions for future studies.

Letter to editor: gender gap in deep brain stimulation for Parkinson's disease: preliminary results of a retrospective study.

This letter addresses important considerations for enhancing the research on the gender gap in deep brain stimulation (DBS) for Parkinson's disease. While acknowledging the commendable efforts of the study's authors, we highlight several areas that warrant further attention to maximize the research's yield and applicability. Specifically, we emphasize the need for a more diverse cohort to enhance the generalizability of findings, inclusion of a control group for comprehensive evaluation, utilization of additional assessment tools to mitigate bias, incorporation of qualitative data for a holistic understanding, and evaluation of long-term outcomes beyond short follow-up durations. Addressing these considerations would strengthen the validity, applicability, and impact of research findings in this crucial area of study.

Protocol for combined N-of-1 trials to assess cerebellar neurostimulation for movement disorders in children and young adults with dyskinetic cerebral palsy.

BACKGROUND: Movement and tone disorders in children and young adults with cerebral palsy are a great source of disability. Deep brain stimulation (DBS) of basal ganglia targets has a major role in the treatment of isolated dystonias, but its efficacy in dyskinetic cerebral palsy (DCP) is lower, due to structural basal ganglia and thalamic damage and lack of improvement of comorbid choreoathetosis and spasticity. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a significant role in dystonia network models, and small studies have shown promise of dentate stimulation in improving CP-related movement and tone disorders. METHODS: Ten children and young adults with DCP and disabling movement disorders with or without spasticity will undergo bilateral DBS in the dorsal dentate nucleus, with the most distal contact ending in the superior cerebellar peduncle. We will implant Medtronic Percept, a bidirectional neurostimulator that can sense and store brain activity and deliver DBS therapy. The efficacy of cerebellar DBS in improving quality of life and motor outcomes will be tested by a series of N-of-1 clinical trials. Each N-of-1 trial will consist of three blocks, each consisting of one month of effective stimulation and one month of sham stimulation in a random order with weekly motor and quality of life scales as primary and secondary outcomes. In addition, we will characterize abnormal patterns of cerebellar oscillatory activity measured by local field potentials from the intracranial electrodes related to clinical assessments and wearable monitors. Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS. DISCUSSION: Our goal is to test a cerebellar neuromodulation therapy that produces meaningful changes in function and well-being for people with CP, obtain a mechanistic understanding of the underlying brain network disorder, and identify physiological and imaging-based predictors of outcomes useful in planning further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT06122675, first registered November 7, 2023.

Neuroscience fundamentals relevant to neuromodulation: Neurobiology of deep brain stimulation in Parkinson's disease.

Deep Brain Stimulation (DBS) has become a pivotal therapeutic approach for Parkinson's Disease (PD) and various neuropsychiatric conditions, impacting over 200,000 patients. Despite its widespread application, the intricate mechanisms behind DBS remain a subject of ongoing investigation. This article provides an overview of the current knowledge surrounding the local, circuit, and neurobiochemical effects of DBS, focusing on the subthalamic nucleus (STN) as a key target in PD management. The local effects of DBS, once thought to mimic a reversible lesion, now reveal a more nuanced interplay with myelinated axons, neurotransmitter release, and the surrounding microenvironment. Circuit effects illuminate the modulation of oscillatory activities within the basal ganglia and emphasize communication between the STN and the primary motor cortex. Neurobiochemical effects, encompassing changes in dopamine levels and epigenetic modifications, add further complexity to the DBS landscape. Finally, within the context of understanding the mechanisms of DBS in PD, the article highlights the controversial question of whether DBS exerts disease-modifying effects in PD. While preclinical evidence suggests neuroprotective potential, clinical trials such as EARLYSTIM face challenges in assessing long-term disease modification due to enrollment timing and methodology limitations. The discussion underscores the need for robust biomarkers and large-scale prospective trials to conclusively determine DBS's potential as a disease-modifying therapy in PD.

Dissecting deep brain stimulation evoked neural activity in the basal ganglia.

Deep brain stimulation (DBS) is an established therapeutic tool for the treatment of Parkinson's disease (PD). The mechanisms of DBS for PD are likely rooted in modulation of the subthalamo-pallidal network. However, it can be difficult to electrophysiologically interrogate that network in human patients. The recent identification of large amplitude evoked potential (EP) oscillations from DBS in the subthalamic nucleus (STN) or globus pallidus internus (GPi) are providing new scientific opportunities to expand understanding of human basal ganglia network activity. In turn, the goal of this review is to provide a summary of DBS-induced EPs in the basal ganglia and attempt to explain various components of the EP waveforms from their likely network origins. Our analyses suggest that DBS-induced antidromic activation of globus pallidus externus (GPe) is a key driver of these oscillatory EPs, independent of stimulation location (i.e. STN or GPi). This suggests a potentially more important role for GPe in the mechanisms of DBS for PD than typically assumed. And from a practical perspective, DBS EPs are poised to become clinically useful electrophysiological biomarker signals for verification of DBS target engagement.

Diffusion and functional MRI in surgical neuromodulation.

Surgical neuromodulation has witnessed significant progress in recent decades. Notably, deep brain stimulation (DBS), delivered precisely within therapeutic targets, has revolutionized the treatment of medication-refractory movement disorders and is now expanding for refractory psychiatric disorders, refractory epilepsy, and post-stroke motor recovery. In parallel, the advent of incisionless treatment with focused ultrasound ablation (FUSA) can offer patients life-changing symptomatic relief. Recent research has underscored the potential to further optimize DBS and FUSA outcomes by conceptualizing the therapeutic targets as critical nodes embedded within specific brain networks instead of strictly anatomical structures. This paradigm shift was facilitated by integrating two imaging modalities used regularly in brain connectomics research: diffusion MRI (dMRI) and functional MRI (fMRI). These advanced imaging techniques have helped optimize the targeting and programming techniques of surgical neuromodulation, all while holding immense promise for investigations into treating other neurological and psychiatric conditions. This review aims to provide a fundamental background of advanced imaging for clinicians and scientists, exploring the synergy between current and future approaches to neuromodulation as they relate to dMRI and fMRI capabilities. Focused research in this area is required to optimize existing, functional neurosurgical treatments while serving to build an investigative infrastructure to unlock novel targets to alleviate the burden of other neurological and psychiatric disorders.

Neurosurgical neuromodulation therapy for psychiatric disorders.

Psychiatric disorders are among the leading contributors to global disease burden and disability. A significant portion of patients with psychiatric disorders remain treatment-refractory to best available therapy. With insights from the neurocircuitry of psychiatric disorders and extensive experience of neuromodulation with deep brain stimulation (DBS) in movement disorders, DBS is increasingly being considered to modulate the neural network in psychiatric disorders. Currently, obsessive-compulsive disorder (OCD) is the only U.S. FDA (United States Food and Drug Administration) approved DBS indication for psychiatric disorders. Medically refractory depression, addiction, and other psychiatric disorders are being explored for DBS neuromodulation. Studies evaluating DBS for psychiatric disorders are promising but lack larger, controlled studies. This paper presents a brief review and the current state of DBS and other neurosurgical neuromodulation therapies for OCD and other psychiatric disorders. We also present a brief review of MR-guided Focused Ultrasound (MRgFUS), a novel form of neurosurgical neuromodulation, which can target deep subcortical structures similar to DBS, but in a noninvasive fashion. Early experiences of neurosurgical neuromodulation therapies, including MRgFUS neuromodulation are encouraging in psychiatric disorders; however, they remain investigational. Currently, DBS and VNS are the only FDA approved neurosurgical neuromodulation options in properly selected cases of OCD and depression, respectively.

Multi-timescale neuromodulation strategy for closed-loop deep brain stimulation in Parkinson's disease.

Objective.Beta triggered closed-loop deep brain stimulation (DBS) shows great potential for improving the efficacy while reducing side effect for Parkinson's disease. However, there remain great challenges due to the dynamics and stochasticity of neural activities. In this study, we aimed to tune the amplitude of beta oscillations with different time scales taking into account influence of inherent variations in the basal ganglia-thalamus-cortical circuit.Approach. A dynamic basal ganglia-thalamus-cortical mean-field model was established to emulate the medication rhythm. Then, a dynamic target model was designed to embody the multi-timescale dynamic of beta power with milliseconds, seconds and minutes. Moreover, we proposed a closed-loop DBS strategy based on a proportional-integral-differential (PID) controller with the dynamic control target. In addition, the bounds of stimulation amplitude increments and different parameters of the dynamic target were considered to meet the clinical constraints. The performance of the proposed closed-loop strategy, including beta power modulation accuracy, mean stimulation amplitude, and stimulation variation were calculated to determine the PID parameters and evaluate neuromodulation performance in the computational dynamic mean-field model.Main results. The Results show that the dynamic basal ganglia-thalamus-cortical mean-field model simulated the medication rhythm with the fasted and the slowest rate. The dynamic control target reflected the temporal variation in beta power from milliseconds to minutes. With the proposed closed-loop strategy, the beta power tracked the dynamic target with a smoother stimulation sequence compared with closed-loop DBS with the constant target. Furthermore, the beta power could be modulated to track the control target under different long-term targets, modulation strengths, and bounds of the stimulation increment.Significance. This work provides a new method of closed-loop DBS for multi-timescale beta power modulation with clinical constraints.

Subthalamic stimulation modulates context-dependent effects of beta bursts during fine motor control.

Increasing evidence suggests a considerable role of pre-movement beta bursts for motor control and its impairment in Parkinson's disease. However, whether beta bursts occur during precise and prolonged movements and if they affect fine motor control remains unclear. To investigate the role of within-movement beta bursts for fine motor control, we here combine invasive electrophysiological recordings and clinical deep brain stimulation in the subthalamic nucleus in 19 patients with Parkinson's disease performing a context-varying task that comprised template-guided and free spiral drawing. We determined beta bursts in narrow frequency bands around patient-specific peaks and assessed burst amplitude, duration, and their immediate impact on drawing speed. We reveal that beta bursts occur during the execution of drawing movements with reduced duration and amplitude in comparison to rest. Exclusively when drawing freely, they parallel reductions in acceleration. Deep brain stimulation increases the acceleration around beta bursts in addition to a general increase in drawing velocity and improvements of clinical function. These results provide evidence for a diverse and task-specific role of subthalamic beta bursts for fine motor control in Parkinson's disease; suggesting that pathological beta bursts act in a context dependent manner, which can be targeted by clinical deep brain stimulation.

Prefrontal-subthalamic theta signaling mediates delayed responses during conflict processing.

While medial frontal cortex (MFC) and subthalamic nucleus (STN) have been implicated in conflict monitoring and action inhibition, respectively, an integrated understanding of the spatiotemporal and spectral interaction of these nodes and how they interact with motor cortex (M1) to definitively modify motor behavior during conflict is lacking. We recorded neural signals intracranially across presupplementary motor area (preSMA), M1, STN, and globus pallidus internus (GPi), during a flanker task in 20 patients undergoing deep brain stimulation implantation surgery for Parkinson disease or dystonia. Conflict is associated with sequential and causal increases in local theta power from preSMA to STN to M1 with movement delays directly correlated with increased STN theta power, indicating preSMA is the MFC locus that monitors conflict and signals STN to implement a 'break.' Transmission of theta from STN-to-M1 subsequently results in a transient increase in M1-to-GPi beta flow immediately prior to movement, modulating the motor network to actuate the conflict-related action inhibition (i.e., delayed response). Action regulation during conflict relies on two distinct circuits, the conflict-related theta and movement-related beta networks, that are separated spatially, spectrally, and temporally, but which interact dynamically to mediate motor performance, highlighting complex parallel yet interacting networks regulating movement.

Effects of deep brain stimulation on dopamine D2 receptor binding in patients with treatment-refractory depression.

BACKGROUND: Depression is a chronic psychiatric disorder related to diminished dopaminergic neurotransmission. Deep brain stimulation (DBS) has shown effectiveness in treating patients with treatment-refractory depression (TRD). This study aimed to evaluate the effect of DBS on dopamine D2 receptor binding in patients with TRD. METHODS: Six patients with TRD were treated with bed nucleus of the stria terminalis (BNST)-nucleus accumbens (NAc) DBS were recruited. Ultra-high sensitivity [11C]raclopride dynamic total-body positron emission tomography (PET) imaging was used to assess the brain D2 receptor binding. Each patient underwent a [11C]raclopride PET scan for 60-min under DBS OFF and DBS ON, respectively. A simplified reference tissue model was used to generate parametric images of binding potential (BPND) with the cerebellum as reference tissue. RESULTS: Depression and anxiety symptoms improved after 3-6 months of DBS treatment. Compared with two-day-nonstimulated conditions, one-day BNST-NAc DBS decreased [11C]raclopride BPND in the amygdala (15.9 %, p < 0.01), caudate nucleus (15.4 %, p < 0.0001) and substantia nigra (10.8 %, p < 0.01). LIMITATIONS: This study was limited to the small sample size and lack of a healthy control group. CONCLUSIONS: Chronic BNST-NAc DBS improved depression and anxiety symptoms, and short-term stimulation decreased D2 receptor binding in the amygdala, caudate nucleus, and substantia nigra. The findings suggest that DBS relieves depression and anxiety symptoms possibly by regulating the dopaminergic system.

Emerging therapies for childhood-onset movement disorders.

PURPOSE OF REVIEW: We highlight novel and emerging therapies in the treatment of childhood-onset movement disorders. We structured this review by therapeutic entity (small molecule drugs, RNA-targeted therapeutics, gene replacement therapy, and neuromodulation), recognizing that there are two main approaches to treatment: symptomatic (based on phenomenology) and molecular mechanism-based therapy or 'precision medicine' (which is disease-modifying). RECENT FINDINGS: We highlight reports of new small molecule drugs for Tourette syndrome, Friedreich's ataxia and Rett syndrome. We also discuss developments in gene therapy for aromatic l-amino acid decarboxylase deficiency and hereditary spastic paraplegia, as well as current work exploring optimization of deep brain stimulation and lesioning with focused ultrasound. SUMMARY: Childhood-onset movement disorders have traditionally been treated symptomatically based on phenomenology, but focus has recently shifted toward targeted molecular mechanism-based therapeutics. The development of precision therapies is driven by increasing capabilities for genetic testing and a better delineation of the underlying disease mechanisms. We highlight novel and exciting approaches to the treatment of genetic childhood-onset movement disorders while also discussing general challenges in therapy development for rare diseases. We provide a framework for molecular mechanism-based treatment approaches, a summary of specific treatments for various movement disorders, and a clinical trial readiness framework.

Covid-19 in Parkinson's Disease treated by drugs or brain stimulation / COVID-19 en la enfermedad de Parkinson tratada con fármacos o estimulación cerebral

Purpose: Covid-19 has affected all people, especially those with chronic diseases, including Parkinson's Disease (PD). Covid-19 may affect both motor and neuropsychiatric symptoms of PD patients. We intend to evaluate different aspects of Covid-19 impact on PD patients. Methods: 647 PD patients were evaluated in terms of PD-related and Covid-19-related clinical presentations in addition to past medical history during the pandemic through an online questioner. They were compared with an age-matched control group consist of 673 individuals and a sample of the normal population consist of 1215 individuals. Results: The prevalence of Covid-19 in PD patients was 11.28%. The mortality was 1.23% among PD patients. The prevalence of Covid-19 in PD patients who undergone Deep Brain Stimulation (DBS) was 18.18%. No significant association was found between the duration of disease and the prevalence of Covid-19. A statistically significant higher prevalence of Covid-19 in PD patients who had direct contact with SARS-CoV-19 infected individuals was found. No statistically significant association has been found between the worsening of motor symptoms and Covid-19. PD patients and the normal population may differ in the prevalence of some psychological disorders, including anxiety and sleeping disorders, and Covid-19 may affect the psychological status. Conclusion: PD patients possibly follow tighter preventive protocols, which lead to lower prevalence and severity of Covid-19 and its consequences in these patients. Although it seems Covid-19 does not affect motor and psychological aspects of PD as much as it was expected, more accurate evaluations are suggested in order to clarify such effects.(AU)

Objetivo: La COVID-19 ha afectado a toda la población, especialmente a aquellos con enfermedades crónicas, incluyendo a los pacientes con enfermedad de Parkinson (EP). La COVID-19 puede empeorar tanto los signos motores como los síntomas neuropsiquiátricos de los pacientes con EP. El objetivo de este estudio es evaluar diferentes aspectos del impacto de la COVID-19 en los pacientes con EP. Métodos: A través de un cuestionario virtual se evaluó a 647 pacientes con EP de acuerdo con sus presentaciones clínicas relacionadas con la EP y con la COVID-19, además de la historia médica previa durante la pandemia. Se compararon con un grupo de controles sanos de la misma edad que constaba de 673 individuos y una muestra de la población general de 1.215 individuos. Resultados: La prevalencia de la COVID-19 en pacientes con EP fue del 11,28%. La mortalidad fue del 1,23% entre los pacientes con EP. La prevalencia de COVID-19 en pacientes con EP con estimulación cerebral profunda fue del 18,18%. No se encontró una asociación significativa entre la duración de la enfermedad y la prevalencia de COVID-19. Se halló una prevalencia mayor de COVID-19 que fue estadísticamente significativa en pacientes con EP que tuvieron contacto directo con personas infectadas con SARS-CoV-2. No se encontró una asociación estadísticamente significativa entre el empeoramiento de los signos motores y la COVID-19. Los pacientes con EP y la población general podrían diferir en la prevalencia de algunos trastornos psicológicos, incluidos los trastornos de ansiedad y del sueño, y la COVID-19 podría afectar al estado psicológico. Conclusión: Los pacientes con EP posiblemente sigan protocolos preventivos más estrictos, lo que conduce a una menor prevalencia y gravedad de COVID-19 y de sus consecuencias en estos pacientes.(AU)

Asleep versus awake GPi DBS surgery for Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: Patients with Parkinson's Disease (PD) who receive either asleep image-guided subthalamic nucleus deep brain stimulation (DBS) or the traditional awake technique have comparable motor outcomes. However, there are fewer studies regarding which technique should be chosen for globus pallidus internus (GPi) DBS. This systematic review and meta-analysis aims to compare the accuracy of lead placement and motor outcomes of asleep versus awake GPi DBS PD population. METHODS: We systematically searched PubMed, Embase, and Cochrane for studies comparing asleep vs. awake GPi DBS lead placement in patients with PD. Outcomes were spatial accuracy of lead placement, measured by radial error between intended and actual location, motor improvement measured using (UPDRS III), and postoperative stimulation parameters. Statistical analysis was performed with Review Manager 5.1.7. and OpenMeta [Analyst]. RESULTS: Three studies met inclusion criteria with a total of 247 patients. Asleep DBS was used to treat 192 (77.7 %) patients. Follow-up ranged from 6 to 48 months. Radial error was not statistically different between groups (MD -0.49 mm; 95 % CI -1.0 to 0.02; I2 = 86 %; p = 0.06), with a tendency for higher target accuracy with the asleep technique. There was no significant difference between groups in change on motor function, as measured by UPDRS III, from pre- to postoperative (MD 8.30 %; 95 % CI -4.78 to 21.37; I2 = 67 %, p = 0.2). There was a significant difference in postoperative stimulation voltage, with the asleep group requiring less voltage than the awake group (MD -0.27 V; 95 % CI -0.46 to - 0.08; I2 = 0 %; p = 0.006). CONCLUSION: Our meta-analysis indicates that asleep image-guided GPi DBS presents a statistical tendency suggesting superior target accuracy when compared with the awake standard technique. Differences in change in motor function were not statistically significant between groups.

Auditory oddball responses in the human subthalamic nucleus and substantia nigra pars reticulata.

The auditory oddball is a mainstay in research on attention, novelty, and sensory prediction. How this task engages subcortical structures like the subthalamic nucleus and substantia nigra pars reticulata is unclear. We administered an auditory OB task while recording single unit activity (35 units) and local field potentials (57 recordings) from the subthalamic nucleus and substantia nigra pars reticulata of 30 patients with Parkinson's disease undergoing deep brain stimulation surgery. We found tone modulated and oddball modulated units in both regions. Population activity differentiated oddball from standard trials from 200 ms to 1000 ms after the tone in both regions. In the substantia nigra, beta band activity in the local field potential was decreased following oddball tones. The oddball related activity we observe may underlie attention, sensory prediction, or surprise-induced motor suppression.

Preventing Shift from Pneumocephalus During Deep Brain Stimulation Surgery: Don't Give Up the 'Fork in the Brain'.

Clinical vignette: We present the case of a patient who developed intra-operative pneumocephalus during left globus pallidus internus deep brain stimulation (DBS) placement for Parkinson's disease (PD). Microelectrode recording (MER) revealed that we were anterior and lateral to the intended target. Clinical dilemma: Clinically, we suspected brain shift from pneumocephalus. Removal of the guide-tube for readjustment of the brain target would have resulted in the introduction of movement resulting from brain shift and from displacement from the planned trajectory. Clinical solution: We elected to leave the guide-tube cannula in place and to pass the final DBS lead into a channel that was located posterior-medially from the center microelectrode pass. Gap in knowledge: Surgical techniques which can be employed to minimize brain shift in the operating room setting are critical for reduction in variation of the final DBS lead placement. Pneumocephalus after dural opening is one potential cause of brain shift. The recognition that the removal of a guide-tube cannula could worsen brain shift creates an opportunity for an intraoperative team to maintain the advantage of the 'fork' in the brain provided by the initial procedure's requirement of guide-tube placement.