Stereotactic Frame-based Targeting of the Posterior Fossa: A systematic workflow for the Leksell G Frame.

Introduction Cerebellar deep brain stimulation (DBS) is gaining traction as a potential treatment for movement disorders and stroke and there is renewed interest in the cerebellum as a target for neuromodulation. Despite the safety and accuracy of frame-based approaches to the posterior fossa, unconventional stereotactic frame placement may be necessary to allow for low posterior fossa trajectories. Current literature lacks a comprehensive protocol detailing inverted frame placement and targeting.

Thalamic Local Field Potentials and Closed-Loop Deep Brain Stimulation in Orthostatic Tremor.

Background: Orthostatic tremor (OT) is a rare movement disorder characterized by a feeling of unsteadiness and a high-frequency tremor in the legs (13-18 Hz) relieved by sitting or walking.

Objectives: The aims were to study the brain electrophysiology captured chronically in a person with medication-refractory OT while standing and walking and in the semi-recumbent position using bilateral ventral intermedius nucleus deep brain stimulation (DBS) (Medtronic Percept PC) and to describe the clinical use of closed-loop DBS.

Methods: A sensing survey was used to capture baseline local field potentials (LFPs) while standing.

Clinico-physiological correlates of Parkinson's disease from multi-resolution basal ganglia recordings.

Parkinson's disease (PD) has been associated with pathological neural activity within the basal ganglia. Herein, we analyzed resting-state single-neuron and local field potential (LFP) activities from people with PD who underwent awake deep brain stimulation surgery of the subthalamic nucleus (STN; n = 125) or globus pallidus internus (GPi; n = 44), and correlated rate-based and oscillatory features with UPDRSIII off-medication subscores. Rate-based single-neuron features did not correlate with PD symptoms.

Interrogating basal ganglia circuit function in people with Parkinson's disease and dystonia.

Background: The dichotomy between the hypo- versus hyperkinetic nature of Parkinson's disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. In this study, we investigated differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections.

Methods: Using microelectrode recording data collected from the GPi during deep brain stimulation surgery, we compared neuronal spiketrain features between people with PD and those with dystonia, as well as correlated neuronal features with respective clinical scores.

Lateralized Subthalamic Stimulation for Axial Dysfunction in Parkinson's Disease: Exploratory Outcomes and Open-Label Extension.

Background: A randomized trial suggested that reducing left-sided subthalamic stimulation amplitude could improve axial dysfunction.

Objectives: To explore open-label tolerability and associations between trial outcomes and asymmetry data.

Methods: We collected adverse events in trial participants treated with open-label lateralized settings for ≥3 months.

Probabilistic Refinement of Focused Ultrasound Thalamotomy Targeting for Parkinson's Disease Tremor.

Background: There remains high variability in clinical outcomes when the same magnetic resonance image-guided focused ultrasound (MRgFUS) thalamotomy target is used for both essential tremor (ET) and tremor-dominant Parkinson's disease (TDPD).

Objective: Our goal is to refine the MRgFUS thalamotomy target for TDPD versus ET.

Methods: We retrospectively performed voxel-wise efficacy and structural connectivity mapping using 3-12-month post-procedure hand tremor scores for a multicenter cohort of 32 TDPD patients and a previously published cohort of 79 ET patients, and 24-hour T1-weighted post-MRgFUS brain images.

Disease-associated mutations in C-terminus of HSP70 interacting protein (CHIP) impair its ability to negatively regulate mitophagy.

C-terminus of HSP70 interacting protein (CHIP) is an E3 ubiquitin ligase and HSP70 cochaperone. Mutations in the CHIP encoding gene are the cause of two neurodegenerative conditions: spinocerebellar ataxia autosomal dominant type 48 (SCA48) and autosomal recessive type 16 (SCAR16). The mechanisms underlying CHIP-associated diseases are currently unknown.

Neural signatures of indirect pathway activity during subthalamic stimulation in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) produces an electrophysiological signature called evoked resonant neural activity (ERNA); a high-frequency oscillation that has been linked to treatment efficacy. However, the single-neuron and synaptic bases of ERNA are unsubstantiated. This study proposes that ERNA is a subcortical neuronal circuit signature of DBS-mediated engagement of the basal ganglia indirect pathway network.

Mitophagy Upregulation Occurs Early in the Neurodegenerative Process Mediated by α-Synuclein.

Parkinson's disease (PD) is a progressive neurogenerative movement disorder characterized by dopaminergic cell death within the substantia nigra pars compacta (SNpc) due to the aggregation-prone protein α-synuclein. Accumulation of α-synuclein is implicated in mitochondrial dysfunction and disruption of the autophagic turnover of mitochondria, or mitophagy, which is an essential quality control mechanism proposed to preserve mitochondrial fidelity in response to aging and stress. Yet, the precise relationship between α-synuclein accumulation, mitochondrial autophagy, and dopaminergic cell loss remains unresolved.

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.

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.

Comprehensive characterization of intracranial hemorrhage in deep brain stimulation: a systematic review of literature from 1987 to 2023.

Objective: Deep brain stimulation (DBS) is an effective treatment for medically refractory movement disorders and other neurological conditions. To comprehensively characterize the prevalence, locations, timing of detection, clinical effects, and risk factors of DBS-related intracranial hemorrhage (ICH), the authors performed a systematic review of the published literature.

Methods: PubMed, EMBASE, and Web of Science were searched using 2 concepts: cerebral hemorrhage and brain stimulation, with filters for English, human studies, and publication dates 1980-2023.

MRI-Guided Focused Ultrasound for the Treatment of Dystonia: A Narrative Review.

Contemporary surgical management of dystonia includes neuromodulation via deep brain stimulation (DBS) or ablative techniques such as radiofrequency (RF) ablation. MRI-guided focused ultrasound (MRgFUS) is an emerging modality that uses high-intensity ultrasound to precisely ablate targets in the brain; this is incisionless, potentially avoiding the surgical risks of a burr hole and transcortical tract to reach the anatomical target. There is some evidence of efficacy in essential tremor and Parkinson's disease (PD), but, to date, there is no study aggregating the evidence of MRgFUS in dystonia.

Dopaminergic Cell Replacement for Parkinson's Disease: Addressing the Intracranial Delivery Hurdle.

Parkinson's disease (PD) is an increasingly prevalent neurological disorder, affecting more than 8.5 million individuals worldwide. α-Synucleinopathy in PD is considered to cause dopaminergic neuronal loss in the substantia nigra, resulting in characteristic motor dysfunction that is the target for current medical and surgical therapies.

Another Step Forward for Freezing of Gait in Parkinson's Disease.

The study "A spinal cord neuroprosthesis for locomotor deficits due to Parkinson's disease" by Milekovic et al. introduces a novel neuroprosthesis for treating locomotor deficits in late-stage Parkinson's disease (PD). This approach employs an epidural spinal array targeting dorsal roots and electromyography to create a spatiotemporal map of muscle activation, aiming to restore natural gait patterns.

Subthalamic and pallidal neurons are modulated during externally cued movements in Parkinson's disease.

External sensory cues can reduce freezing of gait in people with Parkinson's disease (PD), yet the role of the basal ganglia in these movements is unclear. We used microelectrode recordings to examine modulations in single unit (SU) and oscillatory local field potentials (LFP) during auditory-cued rhythmic pedaling movements of the feet. We tested five blocks of increasing cue frequencies (1 Hz, 1.

Economic Evaluations Comparing Deep Brain Stimulation to Best Medical Therapy for Movement Disorders: A Meta-Analysis.

Background: Movement disorders (Parkinson's disease, essential tremor, primary dystonia) are a debilitating group of conditions that are progressive in nature. The mainstay of treatment is best medical therapy; however, a number of surgical therapies are available, including deep brain stimulation. Economic evaluations are an important aspect of evidence to inform decision makers regarding funding allocated to these therapies.