Brain Stimulation For Treatment Research Articles

What are the effects of pharmacological, non-invasive brain stimulation and psychological interventions, and their combination, in the treatment of post-stroke depression? A Cochrane Review summary with commentary.

Post-stroke depression (PSD) is a prevalent condition that can significantly influence the recovery process. To assess the effects of pharmacological, non-invasive brain stimulation and psychological interventions, and their combination on PSD. A summary of the Cochrane Review by Allida et al. (2023), with comments from a rehabilitation perspective. Sixty-one studies with 5831 participants were included in the Cochrane Review. Very low-certainty evidence indicated favorable treatment effects of pharmacological interventions, psychological therapies, and the combination of pharmacological intervention and non-invasive brain stimulation on PSD. Pharmacological intervention has resulted in increased side effects associated with the central nervous system and gastrointestinal system, with very low-certainty evidence. Evidence for the effectiveness of pharmacological, psychological, and combination therapies for the management of PSD is uncertain, as the quality of the evidence has been assessed as very low. Therefore, further studies with improved methods should investigate pharmacological and non-pharmacological interventions for the treatment of depression in stroke survivors.

Adolescent OCD Patient and Caregiver Perspectives on Identity, Authenticity, and Normalcy in Potential Deep Brain Stimulation Treatment.

The ongoing debate within neuroethics concerning the degree to which neuromodulation such as deep brain stimulation (DBS) changes the personality, identity, and agency (PIA) of patients has paid relatively little attention to the perspectives of prospective patients. Even less attention has been given to pediatric populations. To understand patients' views about identity changes due to DBS in obsessive-compulsive disorder (OCD), the authors conducted and analyzed semistructured interviews with adolescent patients with OCD and their parents/caregivers. Patients were asked about projected impacts to PIA generally due to DBS. All patient respondents and half of caregivers reported that DBS would impact patient self-identity in significant ways. For example, many patients expressed how DBS could positively impact identity by allowing them to explore their identities free from OCD. Others voiced concerns that DBS-related resolution of OCD might negatively impact patient agency and authenticity. Half of patients expressed that DBS may positively facilitate social access through relieving symptoms, while half indicated that DBS could increase social stigma. These views give insights into how to approach decision-making and informed consent if DBS for OCD becomes available for adolescents. They also offer insights into adolescent experiences of disability identity and "normalcy" in the context of OCD.

Deep Brain Stimulation Treatment for Genetic Parkinson's Disease: A Case Report

Parkinson's disease (PD) is the second most common neurodegenerative disease and its prevalence has been projected to double over the next 30 years. The diagnosis of PD is bradykinesia and resting tremor or rigidity. PD is a progressive neurodegenerative disease with both motor and nonmotor symptoms. There are many medical options for the treatment of PD but levodopa remains the mainstay. Deep brain stimulation (DBS) is a safe neurosurgical symptomatic treatment for eligible patients with advanced disease in whom medical therapy fails to provide adequate symptom control and a good quality of life or in whom dopaminergic drugs cause severe side effects such as dyskinesias. In this case report, a 44-year-old female patient with a history of tremor and genetic Parkinson's disease, who presented to the clinic with the complaint of excessive increase in tremor in recent years, firstly with drug treatment and then with DBS treatment is reported.

Increases in functional connectivity between the default mode network and sensorimotor network correlate with symptomatic improvement after transcranial direct current stimulation for obsessive-compulsive disorder

BackgroundNon-invasive neuromodulation is a promising intervention for obsessive-compulsive disorder (OCD), although its neurobiological mechanisms of action are still poorly understood. Recent evidence suggests that abnormalities in the connectivity of the default mode network (DMN) and the supplementary motor area (SMA) with other brain regions and networks are involved in OCD pathophysiology. We examined if transcranial direct current stimulation (tDCS) alters these connectivity patterns and if they correlate with symptom improvement in treatment-resistant OCD. MethodsIn 23 patients from a larger clinical trial (comparing active tDCS to sham) who underwent pre- and post-treatment MRI scans, we assessed resting-state functional MRI (rs-fMRI) data. The treatment involved 30-minute daily tDCS sessions for four weeks (weekdays only), with the cathode over the SMA and the anode over the left deltoid. We conducted whole-brain connectivity analysis comparing active tDCS-treated to sham-treated patients. ResultsWe found that active tDCS, but not sham, led to connectivity increasing between the DMN and the bilateral pre/postcentral gyri (p = 0.004, FDR corrected) and temporal-auditory areas plus the SMA (p = 0.028, FDR corrected). Also, symptom improvement was directly associated with connectivity increasing between the left lateral sensorimotor network and the left precuneus (r = 0.589, p = 0.034). LimitationsLimited sample size (23 participants with resting-state neuroimaging), inability to analyze specific OCD symptom dimensions (e.g., harm, sexual/religious, symmetry/checking, cleaning/contamination). ConclusionsThese data offer novel information concerning functional connectivity changes associated with non-invasive neuromodulation interventions in OCD and can guide new brain stimulation interventions in the framework of personalized interventions.

Retracted: Measuring Subthalamic Nucleus Volume of Parkinson's Patients and Evaluating Its Relationship with Clinical Scales at Pre- and Postdeep Brain Stimulation Treatment: A Magnetic Resonance Imaging Study.

[This retracts the article DOI: 10.1155/2021/6646416.].

Fighting fair: community perspectives on the fairness of performance enhancement in esports.

This study aims to explore community perspectives on enhancer usage in competitive gaming and esports, focusing on the perception of fairness and concerns about various potential performance enhancers. We conducted both qualitative and quantitative surveys to understand the competitive gaming community's opinions on different types of performance enhancers and their potential impact on esports. A thematic analysis was performed to identify key themes in how players rationalize their opinions. The gaming community differentiates between potential performance enhancers based on how problematic they are for the esports scene, with the most concern surrounding hard drugs, pharmaceuticals, and brain stimulation interventions. Participants who are more invested in competitive gaming tend to be more sceptical of enhancers and express greater concerns. Four themes were identified in the thematic analysis: (1) risk, (2) morality, (3) enhancer effects, and (4) regulation. To increase acceptance and perceived legitimacy in decision-making, it is recommended that regulators engage a variety of stakeholders in transparent decision-making processes when forming tournament rules and regulations. This will help address the fragmented regulatory landscape and prevent potential differences in the perception of tournament winners based on the governing body supervising the competition.

Is it more effective for anhedonia and avolition? A systematic review and meta-analysis of non-invasive brain stimulation interventions for negative symptoms in schizophrenia.

Noninvasive brain stimulation (NIBS) techniques are a promising tool for treating the negative symptoms of schizophrenia. Growing evidence suggests that different dimensions of negative symptoms have partly distinct underlying pathophysiological mechanisms. Previous randomized controlled trials (RCTs) have shown inconsistent impacts of NIBS across dimensions. This systematic review and meta-analysis evaluated the effects of NIBS on general negative symptoms, and on specific domains, including blunted affect, alogia, asociality, anhedonia, and avolition. PubMed, Web of Science, Embase, Cochrane CENTRAL, PsycINFO, OpenGrey, and Clinicaltrials.gov from the first date available to October, 2023. Among 1049 studies, we identified eight high-quality RCTs. NIBS significantly affects general negative symptoms (SMD = -0.54, 95% CI [-0.88, -0.21]) and all five domains (SMD = -0.32 to -0.63). Among dimensions, better effects have been shown for improvement of avolition (SMD = -0.47, 95% CI [-0.81, -0.13]) and anhedonia (SMD = -0.63, 95% CI [-0.98, -0.28]). Subgroup analyses of studies that applied once daily stimulation or >10 sessions showed significantly reduced negative symptom severity. NIBS exerts distinct effects across multiple dimensions of negative symptom, with treatment effects related to stimulation frequency and total sessions. These results need to be confirmed in dedicated studies.

Novel Approaches for the Treatment of Post-Traumatic Stress Disorder: A Systematic Review of Non-Invasive Brain Stimulation Interventions and Insights from Clinical Trials.

First-line treatments for post-traumatic stress disorder (PTSD) encompass a wide range of pharmacotherapies and psychotherapies. However, many patients fail to respond to such interventions, highlighting the need for novel approaches. Due to its ability to modulate cortical activity, non-invasive brain stimulation (NIBS) could represent a valuable therapeutic tool. Therefore, the aim of this systematic review is to summarize and discuss the existing evidence on the ameliorative effects of NIBS on PTSD and comorbid anxiety and depressive symptoms. Our goal is also to debate the effectiveness of an integrated approach characterized by the combination of NIBS and psychotherapy. This search was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines in the PubMed, PsycINFO, PsycARTICLES, PSYINDEX, MEDLINE, and ERIC databases. Overall, 31 studies met the eligibility criteria, yielding a total of 26 clinical trials employing transcranial magnetic stimulation (TMS) and 5 making use of transcranial direct-current stimulation (tDCS). From these studies, it emerged that NIBS consistently reduced overall PTSD symptoms' severity as well as comorbid anxiety and depressive symptoms. Moreover, we speculate that combining NIBS with prolonged exposure or cognitive processing therapy might represent a promising therapeutic approach for consistently ameliorating subjects' clinical conditions.

The Linguistic-Cognitive Profile in an Adult Population with Parkinson's Disease and Deep Brain Stimulation: A Comparative Study.

Introduction. Individuals with Parkinson's disease (PD) exhibit general impairments, particularly non-motor symptoms that are related to language, communication, and cognition processes. People with this disease may undergo a surgical intervention for the placement of a deep brain stimulation device, which improves their motor symptoms. However, this type of intervention leads to a decline in their linguistic and cognitive abilities that becomes increasingly noticeable as the disease progresses. Objective. The objective of this research was to compare the performance and linguistic-cognitive profile of individuals with Parkinson's disease who underwent deep brain stimulation treatment based on the stage of the disease. Method. A total of 60 participants who were diagnosed with PD by their reference hospital were selected. These participants were divided into three groups based on the stage of the disease that they were in, forming three groups: a Stage I group (n = 20), a Stage II group (n = 20), and a Stage III group (n = 20). The linguistic-cognitive profile was assessed using the MoCA, ACE-III, and MetAphas tests. The design of this study was established as a quasi-experimental, cross-sectional investigation, and statistical analysis was performed using MANOVA to compare the scores between the study groups. Results. The results indicate that individuals in Stage I exhibit better linguistic and cognitive performance compared to the other groups of participants in Stage II and Stage III, with statistically significant differences (p < 0.05). Conclusion. In conclusion, the progression of PD leads to significant linguistic and cognitive decline in individuals with this disease who have a deep brain stimulation device, greatly limiting the autonomy and quality of life for people with PD.

Efficacy of non-invasive brain stimulation for post-stroke dysphagia: a meta-analysis.

Given the potential harms of dysphagia after stroke, we noticed the possibility of non-invasive brain stimulation treatments in the management process. The meta-analysis search for articles published before May 2023 in databases. We used STATA 12.0 software to compute the standard mean difference (SMD) and 95% confidence intervals (CI). The study showed a greater improvement in swallowing function in post-stroke dysphagia given transcranial direct current stimulation (tDCS) immediately after treatment, compared to those given sham tDCS (SMD = 2.99, 95% CI = 1.86-4.11). The study showed a greater improvement in swallowing function in post-stroke dysphagia given tDCS some days after treatment, compared to those given sham tDCS (SMD = 2.01, 95% CI = 0.87-3.16). The study showed a greater improvement in swallowing function in post-stroke dysphagia given repetitive transcranial magnetic stimulation (rTMS) immediately after treatment, compared to those given sham rTMS (SMD = 4.17, 95% CI = 3.11-5.23). The study showed a greater improvement in swallowing function in post-stroke dysphagia given rTMS some days after treatment, compared to those given sham rTMS (SMD = 1.77, 95% CI = 0.94-2.60). In conclusion, our study showed the beneficial effects of non-invasive brain stimulation on difficulty swallowing for stroke patients and speculated about the potential application of non-invasive brain stimulation on post-stroke dysphagia improvement.

A review on Parkinson’s disease symptoms before and after deep brain stimulation treatment

Introduction: Parkinson’s disease (PD), followed by Alzheimer’s disease, is the most common progressive neurodegenerative disease. Tremors, rigidity, akinesia, and disorders are common PD symptoms. Over the last few decades, deep brain stimulation (DBS) of the subthalamic nucleus has become a standard treatment for advanced PD. The aim of this systematic review paper is to see the difference between the symptoms of PD before and after DBS. Methods: We conducted a literature search using PubMed and Google Scholar. We chose research from the past 10 years. We retrieved 64 papers, and seven duplicated papers were removed. We reviewed the abstract for the remaining 57 papers which led to the selection of 29 papers. After applying inclusion and exclusion criteria for the remaining 29 papers, 23 papers in the English language were chosen for our review. Results: Five Randomized Clinical Trials (RCTs) studied the outcomes of DBS and eight RCTs about effects on posture and motor function. Four RCTs investigated the effects on gait and balance, two on tremors, and the remaining two on posture. The effects of DBS on speech and language were compared in two RCTs. Three studies looked at cognitive performance. One RCT studied sleeping versus awake DBS on PD. These studies showed that with DBS treatment, there was significant improvement in posture, motor function, gait, balance, speech, and language. However, more studies are required for the further analysis on dysphagia and urinary dysfunction. Conclusion: Our study contributed to a better understanding of the advantages of DBS for a range of symptoms, but it concluded that additional RCT on dysphagia and urinary dysfunction was required to reach a reliable conclusion. More research is required to determine the effects of DBS on different motor and non-motor PD symptoms to standardize treatment.

Towards automated sleep-stage classification for adaptive deep brain stimulation targeting sleep in patients with Parkinson’s disease

Sleep dysfunction affects over 90% of Parkinson’s disease patients. Recently, subthalamic nucleus deep brain stimulation has shown promise for alleviating sleep dysfunction. We previously showed that a single-layer neural network could classify sleep stages from local field potential recordings in Parkinson’s disease patients. However, it was unable to categorise non-rapid eye movement into its different sub-stages. Here we employ a larger hidden layer network architecture to distinguish the substages of non-rapid eye movement with reasonable accuracy, up to 88% for the lightest substage and 92% for deeper substages. Using Shapley attribution analysis on local field potential frequency bands, we show that low gamma and high beta are more important to model decisions than other frequency bands. These results suggest that the proposed neural network-based classifier can be employed for deep brain stimulation treatment in commercially available devices with lower local field potential sampling frequencies.

Multifractal characteristics of neuronal activity of the &lt;i&gt; globus pallidus &lt;/i&gt; in patients with dystonia

Dystonia is a movement disorder characterized by involuntary muscle contractions resulting in anomalous postures, often accompanied by dystonic tremors. Among the indicative dystonic postures is an involuntary tonic tilt or rotation of the head. Currently, the etiology and pathogenesis of the disease remain theories. Currently, only low-frequency (theta-alpha) oscillations in the globus pallidus are regarded as the possible biomarker of pathological activity in dystonia. In many patients with dystonia, the absence of rhythmic neuronal activity in the basal ganglia renders this biomarker unusable for surgical treatment of the disease. Additionally, the mechanisms underlying the rearrangement of temporary patterns of neural activity that result in pathological symptoms remain unclear. We propose that the appearance of these pathological rhythms is associated with the reduction of dynamic complexity in the pattern of neural activity within the globus pallidus. We aim to use multifractal analysis in this study to evaluate changes in the globus pallidus neural activity pattern’s dynamic complexity and their correlation with the clinical manifestations of dystonia. The study examined the electrical activity of the globus pallidus in 23 patients receiving deep brain stimulation (DBS) treatment. We used the microelectrode registration technique and local field potential (LFP) registration during intraoperative neuron monitoring to precisely identify the specific locations of the external and internal segments of the globus pallidus (GPe and GPi). In four patients, an additional postoperative recording of local field potentials (LFP) was conducted while performing DBS and vibrational impact on the neck muscles. A neurologist evaluated the patients to determine the severity of the disease using the Burke-Fahn-Mardsen Dystonia Rating Scale (BFMDRS). The LEAD DBS software package was employed for postoperative reconstruction of the DBS stimulating electrode positions and for simulating the optimal stimulation zone, selected by the neurologist (i.e., volume of tissue activated, VTA). Subsequently, we identified the region that presented the most significant variation in multifractal spectrum parameters following DBS to understand its correlation with the optimal VTA. A total of 745 local potential records were analyzed, with 433 in GPe and 312 in GPi. The severity of dystonia was found to be correlated with the parameters of the multifractal spectrum (rho: –0.5630882, p=0.005149 for GPe and rho: –0.5180609, p=0.01133 for GPi). Moreover, as the dystonia severity increased along the BFMDRS scale, the multifractal spectrum became narrower and more asymmetric. In post-surgery recordings, we observed changes in the shape of the multifractal spectrum during DBS stimulation or vibration. In particular, when exposed, the multifractal spectrum significantly widened, and its symmetry was restored. We identified the region with the greatest alteration in the width of the multifractal spectrum following DBS and discovered that this region considerably intersected or fully matched the neurologist’s chosen zone for optimal DBS stimulation. We demonstrated that multifractal analysis can serve as an ancillary approach to evaluate the extent of proprioceptive feedback impairment and as a biomarker of dystonia. The noteworthy and substantial correlation with dystonia severity underscores the considerable potential of multifractal spectrum features as a biomarker of dystonia. Additionally, the overlapping areas with the most significant DBS impact and the widest variation in the multifractal spectrum in DBS can be used as a tool for identifying the most favorable region for DBS stimulation.

A perspective on translating genomic discoveries into targets for brain-machine interface and deep brain stimulation devices.

Mental illnesses have a huge impact on individuals, families, and society, so there is a growing need for more efficient treatments. In this context, brain-computer interface (BCI) technology has the potential to revolutionize the options for neuropsychiatric therapies. However, the development of BCI-based therapies faces enormous challenges, such as power dissipation constraints, lack of credible feedback mechanisms, uncertainty of which brain areas and frequencies to target, and even which patients to treat. Some of these setbacks are due to the large gap in our understanding of brain function. In recent years, large-scale genomic analyses uncovered an unprecedented amount of information regarding the biology of the altered brain function observed across the psychopathology spectrum. We believe findings from genetic studies can be useful to refine BCI technology to develop novel treatment options for mental illnesses. Here, we assess the latest advancements in both fields, the possibilities that can be generated from their intersection, and the challenges that these research areas will need to address to ensure that translational efforts can lead to effective and reliable interventions. Specifically, starting from highlighting the overlap between mechanisms uncovered by large-scale genetic studies and the current targets of deep brain stimulation treatments, we describe the steps that could help to translate genomic discoveries into BCI targets. Because these two research areas have not been previously presented together, the present article can provide a novel perspective for scientists with different research backgrounds. This article is categorized under: Neurological Diseases > Genetics/Genomics/Epigenetics Neurological Diseases > Biomedical Engineering.

Disparities in Access to Deep Brain Stimulation and Responsive Neurostimulation Approaches to Drug-Resistant Epilepsy

BackgroundEpilepsy affects 1% to 2% of the global population, and those who are resistant to medical treatment may be candidates for neuromodulation. In select populations, brain stimulation approaches including deep brain stimulation (DBS) and responsive neurostimulation (RNS) are used. Although studies have shown that patients from Black, Hispanic, lower income, and rural communities have less access to epilepsy care and have lower rates of epilepsy surgery, disparities in the use of brain stimulation for epilepsy treatment are currently not known. Materials and MethodsWe queried the US National Inpatient Sample data base from January 1, 2014 to December 31, 2019 for all patients discharged with an International Classification of Diseases (ICD) Ninth Revision or ICD Tenth Revision diagnosis of drug-resistant epilepsy. Among these patients discharged, the rates of brain stimulation treatment, including DBS and RNS, were reported in each subgroup of race, ethnicity, and insurance. To generate national estimates, all analyses were weighted. ResultsA total of 237,895 patients discharged with drug-resistant epilepsy were identified, of whom 4,925 (2.1%) received brain stimulation treatment for drug-resistant epilepsy. Black patients (n = 420, 0.9%, odds ratio [OR] = 0.51, 95% CI [0.40, 0.64]) were less likely to receive brain stimulation treatment than were White patients (n = 3300, 2.4%). There was no significant difference between Asian (n = 105, 2.3%, OR = 0.80, 95% CI [0.53, 1.33]) and Hispanic (n = 655, 2.6%, OR = 0.95, 95% CI [0.77, 1.17]) patients and White patients. No significant difference was observed between female (n = 2515, 2.1%, OR = 1.02, 95% CI [0.89, 1.17]) and male (n = 2410, 2.0%) patients either. Patients with Medicare (n = 1150, 1.2%, OR = 0.69, 95% CI [0.57, 0.84]) or Medicaid (n = 1150, 1.8%, OR = 0.52, 95% CI [0.44, 0.62]) were less likely to receive brain stimulation treatment than were those with private insurance as the primary payer (n = 2370, 3.9%). ConclusionsWe discovered significant disparities in the use of brain stimulation treatments for drug-resistant epilepsy based on race and insurance status. More research will be required to determine the cause of these disparities.

Neurotechnological solutions for post-traumatic stress disorder: A perspective review and concept proposal.

Post-traumatic stress disorder (PTSD) is an anxiety condition caused by exposure to severe trauma. It is characterised by nightmares, flashbacks, hyper-vigilance and avoidance behaviour. These all lead to impaired functioning reducing quality of life. PTSD affects 2-5% of the population globally. Most sufferers cannot access effective treatment, leading to impaired psychological functioning reducing quality of life. Eye movement desensitisation and reprocessing (EMDR) is a non-invasive brain stimulation treatment that has shown significant clinical effectiveness in PTSD. Another treatment modality, that is, trauma-focused cognitive behavioural therapy is also an effective intervention. However, both evidence-based treatments are significantly resource intensive as they need trained therapists to deliver them. A concept of a neuro-digital tool for development is proposed to put to clinical practice of delivering EMDR to improve availability, efficiency and effectiveness of treatment. The evidence in using new technologies to measure sleep, geolocation and conversational analysis of social media to report objective outcome measures is explored. If achieved, this can be fed back to users with data anonymously collated to evaluate and improve the tool. Coproduction would be at the heart of product development so that the tool is acceptable and accessible to people with the condition.

Use of Connectomes in Deep Brain Stimulation for the Treatment of Obsessive-Compulsive Disorder

AbstractObsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by the performance of repetitive behaviors in response to an obsession, which currently ranks as the tenth cause of disability in the world. Patients who are refractory to conventional treatment are candidates for the neurosurgical treatment of deep brain stimulation (DBS). In this procedure, electrodes are implanted in specific anatomical brain targets. The present systematic literature review aimed to describe the main connectomes and associate them with their respective targets involved in DBS for the treatment of OCD, to understand the connectomes related to OCD and their contributions to DBS, and to describe the main targets used in DBS surgery for OCD. Based on the present results, the stimulated targets that showed better clinical outcomes were the anterior limb of the internal capsule, the nucleus accumbens, the subthalamic nucleus, and the ventral capsule/striatal capsule. The target associated with the worst clinical results was the posterior limb of the anterior commissure. The variable stimulation of certain regions of the brain determines different clinical results. However, an individualized investigation of the OCD patient is essential for choosing the best target for DBS.

Alpha peak frequency-based Brainmarker-I as a method to stratify to pharmacotherapy and brain stimulation treatments in depression

Biomarkers predicting treatment outcome in major depressive disorder could enhance clinical improvement. Here this observational and prospective accuracy study investigates whether an age- and sex-normalized electroencephalography biomarker, based on the individual alpha frequency (iAF), can successfully stratify patients to different interventions such as repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT). Differential iAF directions were explored for sertraline, as well as rTMS (N = 196) and ECT (N = 41). A blinded out-of-sample validation (EMBARC; N = 240) replicated the previously found association between low iAF and better sertraline response. The subgroup of patients with an iAF around 10 Hz had a higher remission rate following 10 Hz rTMS compared with the group level, while the high-iAF subgroup had highest remission to 1 Hz rTMS and the low-iAF subgroup to ECT. Blinded out-of-sample validations for 1 Hz (N = 39) and ECT (N = 51) corroborated these findings. The present study suggests a clinically actionable electroencephalography biomarker that can successfully stratify between various antidepressant treatments.

Applicability of clinical genetic testing for deep brain stimulation treatment in monogenic Parkinson's disease and monogenic dystonia: a multidisciplinary team perspective.

In this perspective article, we highlight the possible applicability of genetic testing in Parkinson's disease and dystonia patients treated with deep brain stimulation (DBS). DBS, a neuromodulatory technique employing electrical stimulation, has historically targeted motor symptoms in advanced PD and dystonia, yet its precise mechanisms remain elusive. Genetic insights have emerged as potential determinants of DBS efficacy. Known PD genes such as GBA, SNCA, LRRK2, and PRKN are most studied, even though further studies are required to make firm conclusions. Variable outcomes depending on genotype is present in genetic dystonia, as DYT-TOR1A, NBIA/DYTPANK2, DYT-SCGE and X-linked dystonia-parkinsonism have demonstrated promising outcomes following GPi-DBS, while varying outcomes have been documented in DYT-THAP1. We present two clinical vignettes that illustrate the applicability of genetics in clinical practice, with one PD patient with compound GBA mutations and one GNAL dystonia patient. Integrating genetic testing into clinical practice is pivotal, particularly with advancements in next-generation sequencing. However, there is a clear need for further research, especially in rarer monogenic forms. Our perspective is that applying genetics in PD and dystonia is possible today, and despite challenges, it has the potential to refine patient selection and enhance treatment outcomes.

Selective Activation of Subthalamic Nucleus Output Quantitatively Scales Movements.

The subthalamic nucleus (STN) is a common target for deep brain stimulation (DBS) treatments of Parkinsonian motor symptoms. According to the dominant model, the STN output can suppress movement by enhancing inhibitory basal ganglia (BG) output via the indirect pathway, and disrupting STN output using DBS can restore movement in Parkinson's patients. But the mechanisms underlying STN DBS remain poorly understood, as previous studies usually relied on electrical stimulation, which cannot selectively target STN output neurons. Here, we selectively stimulated STN projection neurons using optogenetics and quantified behavior in male and female mice using 3D motion capture. STN stimulation resulted in movements with short latencies (10-15 ms). A single pulse of light was sufficient to generate movement, and there was a highly linear relationship between stimulation frequency and kinematic measures. Unilateral stimulation caused movement in the ipsiversive direction (toward the side of stimulation) and quantitatively determined head yaw and head roll, while stimulation of either STN raises the head (pitch). Bilateral stimulation does not cause turning but raised the head twice as high as unilateral stimulation of either STN. Optogenetic stimulation increased the firing rate of STN neurons in a frequency-dependent manner, and the increased firing is responsible for stimulation-induced movements. Finally, stimulation of the STN's projection to the brainstem mesencephalic locomotor region was sufficient to reproduce the behavioral effects of STN stimulation. These results question the common assumption that the STN suppresses movement, and instead suggest that STN output can precisely specify action parameters via direct projections to the brainstem.SIGNIFICANCE STATEMENT Our results question the common assumption that the subthalamic nucleus (STN) suppresses movement, and instead suggest that STN output can precisely specify action parameters via direct projections to the brainstem.