Impact of Preoperative Cognition on Motor Improvement in Bilateral Subthalamic Nucleus-Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVE: This study aimed to assess the influence of preoperative cognition on postoperative motor and nonmotor outcomes in patients with Parkinson disease (PD) after deep brain stimulation (DBS). MATERIALS AND METHODS: A retrospective study was performed in subjects with PD with bilateral subthalamic DBS. Preoperative cognition was indexed by Parkinson's Disease-Cognitive Rating Scale (PD-CRS) and global neuropsychological evaluation (NPE) scores. The primary outcome was change from baseline to postoperative off-drug Movement Disorders Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part 3 score. Secondary outcomes included change from baseline to postoperative MDS-UPDRS part 1 subscores. RESULTS: The study included 226 subjects; 176 patients (77.9%) had normal cognition (PD-NC); 48 (21.2%) had mild cognitive impairment (MCI), and two (0.9%) had PD dementia. Proportional change (-41.4% vs -52.2%, p = 0.013) in off-drug MDS-UPDRS part 3 score was smaller in PD-MCI than in PD-NC. PD-CRS (Pearson's r = 0.236, p < 0.001) and NPE (Pearson's r = 0.219, p < 0.001) scores displayed a positive correlation with proportional change in off-drug MDS-UPDRS part 3 score. Worse PD-CRS scores were related to larger improvements in MDS-UPDRS part 1.2 (hallucinations) (Pearson's r = 0.135, p = 0.045). CONCLUSIONS: DBS induces a clinically meaningful motor improvement in patients with cognitive impairment and PD, but the improvement may be smaller than in patients who are not cognitively affected. Further research into the risk-benefit balance of DBS in people with PD and cognitive dysfunction is warranted.

Can Neuromodulation Improve Sleep and Psychiatric Symptoms?

PURPOSE OF REVIEW: In this review, we evaluate recent studies that employ neuromodulation, in the form of non-invasive brain stimulation, to improve sleep in both healthy participants, and patients with psychiatric disorders. We review studies using transcranial electrical stimulation, transcranial magnetic stimulation, and closed-loop auditory stimulation, and consider both subjective and objective measures of sleep improvement. RECENT FINDINGS: Neuromodulation can alter neuronal activity underlying sleep. However, few studies utilizing neuromodulation report improvements in objective measures of sleep. Enhancements in subjective measures of sleep quality are replicable, however, many studies conducted in this field suffer from methodological limitations, and the placebo effect is robust. Currently, evidence that neuromodulation can effectively enhance sleep is lacking. For the field to advance, methodological issues must be resolved, and the full range of objective measures of sleep architecture, alongside subjective measures of sleep quality, must be reported. Additionally, validation of effective modulation of neuronal activity should be done with neuroimaging.

Cognitive phenotyping of GBA1-Parkinson's disease: A study on deep brain stimulation outcomes.

BACKGROUND: Heterozygous variants in the glucocerebrosidase (GBA1) gene are the most common genetic risk factor for Parkinson's Disease (PD). GBA1-PD patients exhibit earlier disease onset, severe motor impairment, and heightened cognitive decline. Deep Brain Stimulation (DBS) offers motor improvement for PD patients, but its cognitive effects, particularly in GBA1-PD, are debated. METHODS: This study involved 96 PD patients who underwent subthalamic nucleus DBS at Hospital de la Santa Creu i Sant Pau between 2004 and 2023. Clinical and neuropsychological assessments were conducted pre- and post-surgery, focusing on Mattis Dementia Rating Scale (MDRS) and Frontal Systems Behavior Scale (FrSBe). Patients were categorized into GBA1-PD and non-GBA1-PD groups, with non-GBA1-PD further divided into cognitive fast-progressors and slow-progressors. RESULTS: GBA1 variants were present in 13.5 % of patients. GBA1-PD patients showed greater cognitive decline over time, particularly in attention, conceptualization, and memory, compared to non-GBA1-PD. Non-GBA1-PD fast-progressors exhibited significant cognitive deterioration in initiation and conceptualization within the first year post-DBS. Motor outcomes improved similarly across all groups, but slow-progressors showed a greater reduction in Levodopa Equivalent Daily Dose (LEDD). CONCLUSIONS: GBA1-PD patients experience more rapid cognitive decline, particularly in posterior-cortical and fronto-striatal functions. Additionally, a subset of non-GBA1-PD patients shows significant early cognitive decline post-DBS, especially in executive functions. Baseline MDRS scores do not predict cognitive outcomes, highlighting the need for further research to refine prognostic tools. Despite cognitive challenges, GBA1-PD patients benefit from DBS in terms of motor outcomes, underscoring the importance of individualized assessments for DBS suitability, regardless of genetic status.

Vagus nerve stimulation (VNS): recent advances and future directions.

PURPOSE: Vagus nerve stimulation (VNS) is emerging as a unique and potent intervention, particularly within neurology and psychiatry. The clinical value of VNS continues to grow, while the development of noninvasive options promises to change a landscape that is already quickly evolving. In this review, we highlight recent progress in the field and offer readers a glimpse of the future for this bright and promising modality. METHODS: We compiled a narrative review of VNS literature using PubMed and organized the discussion by disease states with approved indications (epilepsy, depression, obesity, post-stroke motor rehabilitation, headache), followed by a section highlighting novel, exploratory areas of VNS research. In each section, we summarized the current role, recent advancements, and future directions of VNS in the treatment of each disease. RESULTS: The field continues to gain appreciation for the clinical potential of this modality. VNS was initially developed for treatment-resistant epilepsy, with the first depression studies following shortly thereafter. Overall, VNS has gained approval or clearance in the treatment of medication-refractory epilepsy, treatment-resistant depression, obesity, migraine/cluster headache, and post-stroke motor rehabilitation. CONCLUSION: Noninvasive VNS represents an opportunity to bridge the translational gap between preclinical and clinical paradigms and may offer the same therapeutic potential as invasive VNS. Further investigation into how VNS parameters modulate behavior and biology, as well as how to translate noninvasive options into the clinical arena, are crucial next steps for researchers and clinicians studying VNS.

Deep brain stimulation for post-stroke rehabilitation in Pakistan.

Stroke has a high prevalence in Pakistan, at an alarming rate of 250 per 100 000 people. Although various treatment options are available, they are not ideal for Pakistan due to their high cost, restricted availability, and time sensitivity. In 1997, the FDA-approved deep brain stimulation (DBS) for Parkinson's disease and it was first performed in Pakistan in 2014. DBS has also proved effective for restoring post-stroke mobility, according to a trial from August 2023. DBS has the potential to revolutionize post-stroke rehabilitation in Pakistan; however, further research is required into its effectiveness and its limitations must be addressed first.

A historical perspective on the neurobiology of speech and language: from the 19th century to the present.

In this essay, we review 19th century conceptions on the neurobiology of speech and language, including the pioneer work of Franz Gall, Jean-Baptiste Bouillaud, Simon Alexandre Ernest Aubertin, Marc Dax, Paul Broca, and Carl Wernicke. We examine how these early investigations, anchored in the study of neurological disorders, have broadened their scope via neuropsychological and psycholinguistic theories and models. Then, we discuss how major technological advances have led to an important paradigm shift, through which the study of the brain slowly detached from the study of disease to become the study of individuals of all ages, with or without brain pathology or language disorders. The profusion of neuroimaging studies that were conducted in the past four decades, inquiring into various aspects of language have complemented-and often challenged-classical views on language production. Our understanding of the "motor speech center," for instance, has been entirely transformed. The notion of cerebral dominance has also been revisited. We end this paper by discussing the challenges and controversies of 21st century neurobiology of speech and language as well as modern views of the neural architecture supporting speech and language functions.

Neuromodulation effect of temporal interference stimulation based on network computational model.

Deep brain stimulation (DBS) has long been the conventional method for targeting deep brain structures, but noninvasive alternatives like transcranial Temporal Interference Stimulation (tTIS) are gaining traction. Research has shown that alternating current influences brain oscillations through neural modulation. Understanding how neurons respond to the stimulus envelope, particularly considering tTIS's high-frequency carrier, is vital for elucidating its mechanism of neuronal engagement. This study aims to explore the focal effects of tTIS across varying amplitudes and modulation depths in different brain regions. An excitatory-inhibitory network using the Izhikevich neuron model was employed to investigate responses to tTIS and compare them with transcranial Alternating Current Stimulation (tACS). We utilized a multi-scale model that integrates brain tissue modeling and network computational modeling to gain insights into the neuromodulatory effects of tTIS on the human brain. By analyzing the parametric space, we delved into phase, amplitude, and frequency entrainment to elucidate how tTIS modulates endogenous alpha oscillations. Our findings highlight a significant difference in current intensity requirements between tTIS and tACS, with tTIS requiring notably higher intensity. We observed distinct network entrainment patterns, primarily due to tTIS's high-frequency component, whereas tACS exhibited harmonic entrainment that tTIS lacked. Spatial resolution analysis of tTIS, conducted via computational modeling and brain field distribution at a 13 Hz stimulation frequency, revealed modulation in deep brain areas, with minimal effects on the surface. Notably, we observed increased power within intrinsic and stimulation bands beneath the electrodes, attributed to the high stimulus signal amplitude. Additionally, Phase Locking Value (PLV) showed slight increments in non-deep areas. Our analysis indicates focal stimulation using tTIS, prompting further investigation into the necessity of high amplitudes to significantly affect deep brain regions, which warrants validation through clinical experiments.

Machine learning for the localization of Subthalamic Nucleus during deep brain stimulation surgery: a systematic review and Meta-analysis.

INTRODUCTION: Delineating subthalamic nucleus (STN) boundaries using microelectrode recordings (MER) and trajectory history is a valuable resource for neurosurgeons, aiding in the accurate and efficient positioning of deep brain stimulation (DBS) electrodes within the STN. Here, we aimed to assess the application of artificial intelligence, specifically Hidden Markov Models (HMM), in the context of STN localization. METHODS: A comprehensive search strategy was employed, encompassing electronic databases, including PubMed, EuroPMC, and MEDLINE. This search strategy entailed a combination of controlled vocabulary (e.g., MeSH terms) and free-text keywords pertaining to "artificial intelligence," "machine learning," "deep learning," and "deep brain stimulation." Inclusion criteria were applied to studies reporting the utilization of HMM for predicting outcomes in DBS, based on structured patient-level health data, and published in the English language. RESULTS: This systematic review incorporated a total of 14 studies. Various machine learning compared wavelet feature to proposed features in diagnosing the STN, with the HMM yielding a diagnostic odds ratio (DOR) of 838.677 (95% CI: 203.309-3459.645). Similarly, the K-Nearest Neighbors (KNN) model produced parameter estimates, including a diagnostic odds ratio of 25.151 (95% CI: 12.270-51.555). Meanwhile, the support vector machine (SVM) model exhibited parameter estimates, with a DOR of 13.959 (95% CI: 10.436-18.671). CONCLUSIONS: MER data demonstrates significant variability in neural activity, with studies employing a wide range of methodologies. Machine learning plays a crucial role in aiding STN diagnosis, though its accuracy varies across different approaches.

Deep brain stimulation for Tourette's syndrome.

Tourette's syndrome is a neuropsychiatric disorder characterized by formidable motor and vocal tics. Many individuals also present with comorbid neuropsychiatric conditions. Though patients often benefit from pharmacological and behavioral therapies, a subset of individuals develop severe, treatment-resistant symptoms that might necessitate more invasive interventions, such as Deep Brain Stimulation (DBS). DBS, particularly targeting regions like the globus pallidus internus (GPi) and the centromedian-parafascicular complex (CM-Pf) of the thalamus, has demonstrated effectiveness in reducing tic severity and improving quality of life. This review outlines the mechanism, clinical efficacy, and long-term outcome of DBS in TS. Results from clinical studies reveal significant reductions in tics. However, success with DBS is variable depending on a number of factors, including target selection and electrode placement. The use of DBS has ethical considerations, which include risks to the surgical procedure, the need for full and complete informed consent, and questions about the implications of such treatment on cognitive and emotional growth. Long-term follow-up will be required to ensure appropriate patient outcomes and complication management. Additional research and ethical debate will be needed with advancing DBS technology to ensure responsible and equitable treatment. This paper narratively summarizes the surgical options available for TS, with a focus on the current status of DBS in the management of the disease.

Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment Reduces Variability in Brain Function in Schizophrenia: Data From a Double-Blind, Randomized, Sham-Controlled Trial.

BACKGROUND/HYPOTHESIS: There is increasing awareness of interindividual variability in brain function, with potentially major implications for repetitive transcranial magnetic stimulation (rTMS) efficacy. We perform a secondary analysis using data from a double-blind randomized controlled 4-week trial of 20 Hz active versus sham rTMS to dorsolateral prefrontal cortex (DLPFC) during a working memory task in participants with schizophrenia. We hypothesized that rTMS would change local functional activity and variability in the active group compared with sham. STUDY DESIGN: 83 participants were randomized in the original trial, and offered neuroimaging pre- and post-treatment. Of those who successfully completed both scans (n = 57), rigorous quality control left n = 42 (active/sham: n = 19/23), who were included in this analysis. Working memory-evoked activity during an N-Back (3-Back vs 1-Back) task was contrasted. Changes in local brain activity were examined from an 8 mm ROI around the rTMS coordinates. Individual variability was examined as the mean correlational distance (MCD) in brain activity pattern from each participant to others within the same group. RESULTS: We observed an increase in task-evoked left DLPFC activity in the active group compared with sham (F1,36 = 5.83, False Discovery Rate (FDR))-corrected P = .04). Although whole-brain activation patterns were similar in both groups, active rTMS reduced the MCD in activation pattern compared with sham (F1,36 = 32.57, P < .0001). Reduction in MCD was associated with improvements in attention performance (F1,16 = 14.82, P = .0014, uncorrected). CONCLUSIONS: Active rTMS to DLPFC reduces individual variability of brain function in people with schizophrenia. Given that individual variability is typically higher in schizophrenia patients compared with controls, such reduction may "normalize" brain function during higher-order cognitive processing.

Evaluating a motor progression connectivity model across Parkinson's disease stages.

BACKGROUND: Stimulation of a specific site in the dorsolateral subthalamic nucleus (STN) was recently associated with slower motor progression in Parkinson's Disease (PD), based on the deep brain stimulation (DBS) in early-stage PD pilot clinical trial. Here, subject-level visualizations are presented of this early-stage PD dataset to further describe the relationship between active contacts and motor progression. This study also evaluates whether stimulation of the sweet spot and connectivity model associated with slower motor progression is also associated with improvements in long-term motor outcomes in patients with advanced-stage PD. METHODS: Active contacts of the early-stage PD cohort (N = 14) were analyzed alongside the degree of two-year motor progression. Sweet spot and connectivity models derived from the early-stage PD cohort were then used to determine how well they can estimate the variance in long-term motor outcomes in an independent STN-DBS cohort of advanced-stage PD patients (N = 29). RESULTS: In early-stage PD, proximity of stimulation to the dorsolateral STN was associated with slower motor progression. In advanced-stage PD, stimulation proximity to the early PD connectivity model and sweet spot were associated with better long-term motor outcomes (R = 0.60, P < 0.001; R = 0.37, P = 0.046, respectively). CONCLUSIONS: Results suggest stimulation of a specific site in the dorsolateral STN is associated with both slower motor progression and long-term motor improvements in PD.

Differential Effects of Cerebellar Transcranial Direct Current Stimulation with Gait Training on Functional Mobility, Balance, and Ataxia Symptoms.

Cerebellar transcranial direct current stimulation (ctDCS) has emerged as a promising, non-invasive, and safe neuromodulatory intervention capable of reducing ataxia symptoms and restoring cerebellum-motor connectivity. However, previous studies have only applied ctDCS in isolation, without association with specific training. This study aimed to assess the effect of ctDCS combined with gait training on functional mobility, balance, and symptoms and severity of ataxia. A randomized, triple-blind, sham-controlled, bi-center clinical trial was conducted with forty-four adults with cerebellar ataxia. Volunteers were randomized to receive five daily sessions of either real ctDCS (n = 11; 2 mA for 25 min) or sham ctDCS (n = 11) during gait training. Functional mobility, balance, and symptoms and severity of ataxia were assessed using the Time Up and Go test, the MiniBESTest, and the Scale for the Assessment and Rating of Ataxia (SARA), respectively, before and after the interventions. Both groups showed improvement in functional mobility, but there was no significant difference between the ctDCS and sham groups. However, the ctDCS group demonstrated significant improvements in cerebellar ataxia severity as reflected by SARA scores, particularly in tests of stance, sitting, speech disturbance, nose-finger test, and heel-shin slide test. Notably, no improvements were observed in balance. This study indicates that while ctDCS combined with gait training may improve specific symptoms of cerebellar ataxia, it does not significantly enhance overall functional mobility compared to sham treatment.

Olfactory bulb stimulation mitigates Alzheimer's-like disease progression.

BACKGROUND: Deep brain stimulation (DBS) has demonstrated potential in mitigating Alzheimer's disease (AD). However, the invasive nature of DBS presents challenges for its application. The olfactory bulb (OB), showing early AD-related changes and extensive connections with memory regions, offers an attractive entry point for intervention, potentially restoring normal activity in deteriorating memory circuits. AIMS: Our study examined the impact of electrically stimulating the OB on working memory as well as pathological and electrophysiological alterations in the OB, medial prefrontal cortex, hippocampus, and entorhinal cortex in amyloid beta (Aß) AD model rats. METHODS: Male Wistar rats underwent surgery for electrode implantation in brain regions, inducing Alzheimer's-like disease. Bilateral olfactory bulb (OB) electrical stimulation was performed for 1 hour daily to the OB of stimulation group animals for 18 consecutive days, followed by the evaluations of histological, behavioral, and local field potential signal processing. RESULTS: OB stimulation counteracted Aß plaque accumulation and prevented AD-induced working memory impairments. Furthermore, it prompted an increase in power across diverse frequency bands and enhanced functional connectivity, particularly in the gamma band, within the investigated regions during a working memory task. CONCLUSION: This preclinical investigation highlights the potential of olfactory pathway-based brain stimulation to modulate the activity of deep-seated memory networks for AD treatment. Importantly, the accessibility of this pathway via the nasal cavity lays the groundwork for the development of minimally invasive approaches targeting the olfactory pathway for brain modulation.

Stereotactic radiofrequency lesioning of caudal zona incerta for parkinsonian tremor.

This video showcases stereotactic radiofrequency lesioning of the caudal zona incerta (CZi) for parkinsonian tremor in a 70-year-old patient. The preoperative evaluation, including imaging and frame placement, is detailed. The surgical procedure involves meticulous targeting and trajectory planning. Intraoperative stimulation is utilized for motor response assessment. Two temporary lesioning phases precede the final procedure at 75°C. The postoperative CT scan highlights the lesion site. Immediate tremor relief is observed postoperatively, with the effect persisting at the 1-month follow-up. Supporting readings underscore the efficacy and safety of CZi for tremor management. The video can be found here: https://stream.cadmore.media/r10.3171/2024.7.FOCVID2462.

The zona incerta system: Involvement in Parkinson's disease.

Parkinson's disease (PD) is characterized by degeneration of the nigrostriatal dopamine system, resulting in progressive motor and nonmotor symptoms. Although most studies have focused on the basal ganglia network, recent evidence suggests that the zona incerta (ZI), a subthalamic structure composed of 4 neurochemically defined regions, is emerging as a therapeutic target in PD. This review summarizes the clinical and animal studies that indicate the importance of ZI in PD. Human clinical studies have shown that subthalamotomy or deep brain stimulation (DBS) of the ZI alleviates muscle rigidity, bradykinesia, tremors and speech dysfunction in patients with PD. Researchers have also studied the impact of DBS of the ZI on nonmotor signs such as pain, anxiety, and depression. Animal studies combining optogenetics, chemogenetics, behavioral assays, and neural activity recordings reveal the functional roles of ZI GABAergic and glutamatergic neurons in locomotion, gait, and coordination of the symptoms of PD, all of which are discussed in this review. Controversies and possible future studies are also discussed.

The dorsomedial prefrontal cortex promotes self-control by inhibiting the egocentric perspective.

The dorsomedial prefrontal cortex (dmPFC) plays a crucial role in social cognitive functions, including perspective-taking. Although perspective-taking has been linked to self-control, the mechanism by which the dmPFC might facilitate self-control remains unclear. Using the multimodal neuroimaging dataset from the Human Connectome Project (Study 1, N =978 adults), we established a reliable association between the dmPFC and self-control, as measured by discounting rate-the tendency to prefer smaller, immediate rewards over larger, delayed ones. Experiments (Study 2, N = 36 adults) involving high-definition transcranial direct current stimulation showed that anodal stimulation of the dmPFC reduces the discounting of delayed rewards and decreases the congruency effect in egocentric but not allocentric perspective in the visual perspective-taking tasks. These findings suggest that the dmPFC promotes self-control by inhibiting the egocentric perspective, offering new insights into the neural underpinnings of self-control and perspective-taking, and opening new avenues for interventions targeting disorders characterized by impaired self-regulation.

Non-Invasive Brain Stimulation Beyond the Motor Cortex: A Systematic Review and Meta-Analysis Exploring Effects on Quantitative Sensory Testing in Clinical Pain.

BACKGROUND: Non-invasive brain stimulation (NIBS) has been investigated increasingly as a means of treating pain. The effectiveness of NIBS in the treatment of pain has traditionally focused upon protocols targeting the primary motor cortex (M1). However, over time, the effectiveness of M1 NIBS has been attributed to effects on interconnected cortical and subcortical sites rather than M1 itself. While previous reviews have demonstrated the effectiveness of non-M1 NIBS in improving subjective reports of pain intensity, the neurophysiological mechanisms underlying these effects remain incompletely understood. As chronic pain is associated with pain hypersensitivity and impaired endogenous descending pain modulation, it is plausible that non-M1 NIBS promotes analgesic effects by influencing these processes. OBJECTIVE: The aim of this systematic review and meta-analysis was therefore to evaluate the effect of NIBS over non-M1 sites on quantitative sensory testing measures in clinical pain populations. METHODS: A systematic search of electronic databases was conducted from inception to January 2024. Included articles (13trials, n = 565 participants) were appraised using PEDro and GRADE and a random effects model was used to meta-analyse outcomes where possible. RESULTS: A small number of studies found that NIBS applied to DLPFC may improve pain modulation in patients with fibromyalgia, and that stimulation of the posterior superior insula and prefrontal cortex could improve pain sensitivity in chronic neuropathic and osteoarthritic pain, respectively. However, findings varied between studies and there remains a paucity of primary research. CONCLUSION: This review indicates that current literature does not provide clear evidence that NIBS over non-M1 sites influences pain processing.

Impact of the combination of virtual reality and noninvasive brain stimulation on the upper limb motor function of stroke patients: a systematic review and meta-analysis.

BACKGROUND: Stroke frequently results in upper limb motor dysfunction, with traditional therapies often failing to yield sufficient improvements. Emerging technologies such as virtual reality (VR) and noninvasive brain stimulation (NIBS) present promising new rehabilitation possibilities. OBJECTIVES: This study systematically reviews and meta-analyses the effectiveness of VR and NIBS in improving upper limb motor function in stroke patients. METHODS: Registered with PROSPERO (CRD42023494220) and adhering to the PRISMA guidelines, this study conducted a thorough search of databases including PubMed, MEDLINE, PEDro, REHABDATA, EMBASE, Web of Science, Cochrane, CNKI, Wanfang, and VIP from 2000 to December 1, 2023, to identify relevant studies. The inclusion criterion was stroke patients receiving combined VR and NIBS treatment, while exclusion criteria were studies with incomplete articles and data. The risk of bias was assessed using the Cochrane Collaboration tool. Statistical analysis was performed using Stata SE 15.0, employing either a fixed-effects model or a random-effects model based on the level of heterogeneity. RESULTS: A total of 11 studies involving 493 participants were included, showing a significant improvement in Fugl-Meyer Assessment Upper Extremity (FMA-UE) scores in the combined treatment group compared to the control group (SMD = 0.85, 95% CI [0.40, 1.31], p = 0.017). The Modified Ashworth Scale (MAS) scores significantly decreased (SMD = - 0.51, 95% CI [- 0.83, - 0.20], p = 0.032), the Modified Barthel Index (MBI) scores significantly increased (SMD = 0.97, 95% CI [0.76, 1.17], p = 0.004), and the Wolf Motor Function Test (WMFT) scores also significantly increased (SMD = 0.36, 95% CI [0.08, 0.64], p = 0.021). Subgroup analysis indicated that the duration of treatment influenced the outcomes in daily living activities. CONCLUSIONS: The combination of VR and NIBS demonstrates significant improvements in upper limb motor function in stroke patients. The duration of treatment plays a critical role in influencing the outcomes, particularly in activities of daily living. This systematic review has limitations, including language bias, unclear randomization descriptions, potential study omissions, and insufficient follow-up periods. Future studies should focus on exploring long-term effects and optimizing treatment duration to maximize the benefits of combined VR and NIBS therapy.

Combination of or Transition between Deep Brain Stimulation and Responsive Neurostimulation for the Treatment of Drug-Resistant Epilepsy.

INTRODUCTION: Neuromodulation is an important treatment modality for patients with drug-resistant epilepsy who are not candidates for resective or ablative procedures. However, randomized controlled trials and real-world studies reveal that a subset of patients will experience minimal reduction or even an increase in seizure frequency after neuromodulation. We describe our experience with patients who undergo a second intracranial neuromodulation procedure after unsatisfactory initial response to intracranial neuromodulation. METHODS: We performed a retrospective chart review to identify all patients who had undergone deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) or responsive neurostimulation (RNS), followed by additional intracranial neuromodulatory procedures, with at least 12 months of follow-up. Demographic and clinical data, including seizure frequencies, were collected. RESULTS: All patients had temporal lobe epilepsy. Six patients were treated with concurrent ANT DBS and temporal lobe RNS, and 3 patients transitioned between neuromodulation systems. Of the patients treated concurrently with ANT DBS and temporal lobe RNS, 5 of the 6 patients experienced additional reduction in seizure frequency after adding a second neuromodulation system. Of the patients who switched between neuromodulation modalities, all patients experienced further reduction in seizure frequency. CONCLUSIONS: For patients who do not experience adequate benefit from initial therapy with ANT DBS or temporal lobe RNS, the addition of a neuromodulation system or switching to a different form of neuromodulation may allow for additional reduction in seizure frequency. Larger studies will need to be performed to understand whether the use of multiple systems concurrently leads to improved clinical results in patients who are initially treatment resistant to neuromodulation.