Stimulation Of Nucleus Research Articles

The Therapeutic Potential of Non-Invasive and Invasive Cerebellar Stimulation Techniques in Hereditary Ataxias.

The degenerative ataxias comprise a heterogeneous group of inherited and acquired disorders that are characterized by a progressive cerebellar syndrome, frequently in combination with one or more extracerebellar signs. Specific disease-modifying interventions are currently not available for many of these rare conditions, which underscores the necessity of finding effective symptomatic therapies. During the past five to ten years, an increasing number of randomized controlled trials have been conducted examining the potential of different non-invasive brain stimulation techniques to induce symptomatic improvement. In addition, a few smaller studies have explored deep brain stimulation (DBS) of the dentate nucleus as an invasive means to directly modulate cerebellar output, thereby aiming to alleviate ataxia severity. In this paper, we comprehensively review the clinical and neurophysiological effects of transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and dentate nucleus DBS in patients with hereditary ataxias, as well as the presumed underlying mechanisms at the cellular and network level and perspectives for future research.

Deep Brain Stimulation of Subthalamic Nucleus Improves Quality of Life in General and Mental Health Domains in Parkinson’s Disease to the Level of the General Population

ObjectivesParkinson’s disease (PD) leads to significant impairment in quality of life (QoL) across various domains. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is known to improve motor and nonmotor symptoms in PD. The aim was to study whether STN-DBS could improve the QoL of patients with PD to the level of the general population, and to determine factors predicting better motor outcomes. Materials and MethodsThe retrospective analysis included 43 patients who underwent either primary or revision STN-DBS. Patients filled out a general QoL questionnaire (RAND 36-item health survey) before and 12 months after surgery, and scores were compared with age- and sex-adjusted national population values. In addition, motor scores were calculated using Unified Parkinson Disease Rating Scale part 3 (UPDRS 3) with the best PD medication. Levodopa equivalent daily dose (LEDD) was also collected. Changes in the QoL were compared with operation age, disease duration, and preoperative QoL. ResultsPreoperatively, patients had significantly impaired QoL in all subsections compared with that of the general population. The mean postoperative UPDRS 3 improvement was 50.0%, and reduction in LEDD was 69.0%. Statistically significant QoL improvements were found in Physical Function, Mental Health, Social Function, Vitality, and Role Physical 12 months postoperatively compared with baseline. The mean differences compared with a healthy population were not statistically significant in General Health, Mental Health, Vitality, and Role Emotional. Furthermore, disease duration was found to be negatively correlated with improvements in UPDRS 3 score, and worse preoperative QoL positively correlated with changes in Physical Function. ConclusionsPatients experienced significant QoL improvements after STN-DBS. The General Health and Mental Health of patients were postoperatively most comparable with age- and sex-adjusted population values. Moreover, earlier stimulation predicted better motor improvements, which emphasizes the importance of earlier timing of STN-DBS surgery and minimizing loss of function at a critical disease stage.

In Search of a Feedback Signal for Closed-Loop Deep Brain Stimulation: Stimulation of the Subthalamic Nucleus Reveals Altered Glutamate Dynamics in the Globus Pallidus in Anesthetized, 6-Hydroxydopamine-Treated Rats.

Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) is a surgical procedure for alleviating motor symptoms of Parkinson's Disease (PD). The pattern of DBS (e.g., the electrode pairs used and the intensity of stimulation) is usually optimized by trial and error based on a subjective evaluation of motor function. We tested the hypotheses that DBS releases glutamate in selected basal ganglia nuclei and that the creation of 6-hydroxydopamine (6-OHDA)-induced nigrostriatal lesions alters glutamate release during DBS in those basal ganglia nuclei. We studied the relationship between a pseudo-random binary sequence of DBS and glutamate levels in the STN itself or in the globus pallidus (GP) in anesthetized, control, and 6-OHDA-treated rats. We characterized the stimulus-response relationships between DBS and glutamate levels using a transfer function estimated using System Identification. Stimulation of the STN elevated glutamate levels in the GP and in the STN. Although the 6-OHDA treatment did not affect glutamate dynamics in the STN during DBS in the STN, the transfer function between DBS in the STN and glutamate levels in the GP was significantly altered by the presence or absence of 6-OHDA-induced lesions. Thus, glutamate responses in the GP in the 6-OHDA-treated animals (but not in the STN) depended on dopaminergic inputs. For this reason, measuring glutamate levels in the GP may provide a useful feedback target in a closed-loop DBS device in patients with PD since the dynamics of glutamate release in the GP during DBS seem to reflect the loss of dopaminergic neurons in the SNc.

Deep brain stimulation suppresses epileptic seizures in rats via inhibition of adenosine kinase and activation of adenosine A1 receptors.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus, is an effective therapy for patients with drug-resistant epilepsy, yet, its mechanism of action remains elusive. Adenosine kinase (ADK), a key negative regulator of adenosine, is a potential modulator of epileptogenesis. DBS has been shown to increase adenosine levels, which may suppress seizures via A1 receptors (A1 Rs). We investigated whether DBS could halt disease progression and the potential involvement of adenosine mechanisms. Control group, SE (status epilepticus) group, SE-DBS group, and SE-sham-DBS group were included in this study. One week after a pilocarpine-induced status epilepticus, rats in the SE-DBS group were treated with DBS for 4 weeks. The rats were monitored by video-EEG. ADK and A1 Rs were tested with histochemistry and western blot, respectively. Compared with the SE group and SE-sham-DBS group, DBS could reduce the frequency of spontaneous recurrent seizures (SRS) and the number of interictal epileptic discharges. The DPCPX, an A1 R antagonist, reversed the effect of DBS on interictal epileptic discharges. In addition, DBS inhibited the overexpression of ADK and the downregulation of A1 Rs. The findings indicate that DBS can reduce SRS in epileptic rats via inhibition of ADK and activation of A1 Rs. A1 Rs might be a potential target of DBS for the treatment of epilepsy.

The Effects of Deep Brain Stimulation in Medial Prefrontal Cortex on Morphine Dependency and Electrical Recording of the Nucleus Accumbens

Background: Addiction is known as a gradual process leading to the uncontrolled abuse of a substance. The main problem facing the practitioners is the high rate of return among abusers after stopping substance consumption. Deep brain stimulation (DBS) is considered as one of the methods for treating stimulant substance abuse, in which an electrical current is passed, typically at frequencies above 100 Hz, through electrodes implanted surgically in the subcortical brain nuclei. Objectives: The present study aimed to investigate the effects of high-frequency DBS (HF-DBS) applied to the medial prefrontal cortex (mPFC) on the electrical response of the accumbens nucleus as well as on the motor activity and dependency in morphine-addicted male rats. Materials and Methods: Experimental rats (n = 40) were assigned to five groups (n = 8), including saline, sham, morphine, saline+DBS, and morphine+DBS groups. The rats received DBS with a frequency of 130 Hz, amplitude of 0.2 to 0.5 mA, and repeated periods of 15 minutes with an interval of 45 minutes for 3 hours during the conditioning period in the conditioned place preference (CPP) box. Then, they were treated with saline or morphine and were subjected to stereotaxic surgery for insertion of the stimulator electrode in mPFC and the recorder electrode in AC. The electrical response of AC neurons to DBS was determined by adopting the single-unit recording method. Then, the motor activities of different groups were assessed to evaluate the effects of DBS on animal movement activities. Finally, data analysis was performed using GraphPad Prism 8.1. Results: The injection of morphine enhanced the CPP score and reduced the average of spikes in the cortical neurons of the AC compared to those obtained in the sham group. These parameters were significantly decreased and increased in the animals receiving morphine+DBS compared to the morphine group, respectively. Moreover, a significant difference was observed between the morphine+DBS group and the morphine group in terms of the total traveled distance. Conclusions: The stimulation of the AC nucleus at high frequency reduced the addiction preference as well as enhanced the locomotor activity and primary neuron activity in the cortex of the AC nucleus.

Ventral intermediate nucleus deep brain stimulation for treatment-resistant focal aware motor seizures: illustrative case.

Resection of the seizure onset zone (SOZ) is considered the gold standard for treating refractory focal aware seizures (FASs). When resective surgery is unadvisable, deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT; ANT-DBS) has been the procedure of choice. However, less than half of patients with FASs respond to ANT-DBS. The need for alternative targets to effectively treat FAS is thus evident. The authors report the case of a 39-year-old woman presenting with pharmaco-resistant focal aware motor seizures, with the SOZ located in the primary motor cortical area. She had previously undergone unsuccessful resection of the left temporoparietal operculum elsewhere. Considering the risk of new resective surgery, she was offered combined ventral intermediate nucleus (Vim)/ANT-DBS. Vim-DBS proved to be superior to ANT-DBS for seizure control (88% vs 32%), although the association of both provided the best results (97%). This is the first report on the use of the Vim as a target of DBS for the treatment of FAS. The excellent results were presumably obtained by modulation of the SOZ through Vim projections to the motor cortex. This opens a completely new avenue for treating FAS: chronic stimulation of specific thalamic nuclei.

Activation of hypothalamic-enhanced adult-born neurons restores cognitive and affective function in Alzheimer's disease.

Patients with Alzheimer's disease (AD) exhibit progressive memory loss, depression, and anxiety, accompanied by impaired adult hippocampal neurogenesis (AHN). Whether AHN can be enhanced in impaired AD brain to restore cognitive and affective function remains elusive. Here, we report that patterned optogenetic stimulation of the hypothalamic supramammillary nucleus (SuM) enhances AHN in two distinct AD mouse models, 5×FAD and 3×Tg-AD. Strikingly, the chemogenetic activation of SuM-enhanced adult-born neurons (ABNs) rescues memory and emotion deficits in these AD mice. By contrast, SuM stimulation alone or activation of ABNs without SuM modification fails to restore behavioral deficits. Furthermore, quantitative phosphoproteomics analyses reveal activation of the canonical pathways related to synaptic plasticity and microglia phagocytosis of plaques following acute chemogenetic activation of SuM-enhanced (vs. control) ABNs. Our study establishes the activity-dependent contribution of SuM-enhanced ABNs in modulating AD-related deficits and informs signaling mechanisms mediated by the activation of SuM-enhanced ABNs.

Protocolo de tratamiento del temblor esencial

Essential tremor (ET) is the most prevalent movement disorder in adults and on occasion, it can be highly debilitating. First-line treatment is pharmacological (mainly propranolol and primidone) and tends to be effective in most patients. With time, up to 50% of patients are either not going to tolerate the medication or are going to be refractory to said therapies. In the case of intolerance and/or debilitating and drugresistant tremor, botulinum toxin injections or neurosurgical procedures such as deep brain stimulation of the ventral intermediate nucleus of the thalamus or ablative procedures such as radiofrequency thalamotomy, Gamma Knife® or magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) radiosurgery may be indicated. This protocol summarizes therapeutic recommendations based on scientific evidence for the management of patients with ET.

888 Artificial Neural Network Analysis of Evoked Auditory Brainstem Responses for Prediction of Active Auditory Brainstem Implant (ABI) Electrodes in Patients With Neurofibromatosis Type II

INTRODUCTION: Auditory brainstem implantation (ABI) is used to provide auditory sensations through electric stimulation of the cochlear nucleus and is a key strategy for hearing rehabilitation in patients with neurofibromatosis type II (NF2). The exact position of the 3 by 7 electrode array with respect to the cochlear nucleus is not known, due to complex anatomy following tumor removal, procedures during surgery, potential distortions to the anatomy, and post-operative array migration, and other factors. METHODS: A retrospective study of a prospectively maintained database of ABI users with evoked brainstem responses was carried out at an academic institution. Multi-class classification was conducted using the multilayer perceptron (MLP) feed forward neural network model (FF-NN) to classify and predict the post-operative active electrodes. RESULTS: 1,177 electrodes were stimulated intraoperatively among 85 patients [females, n = 48 (56.6%)]. ABI was implanted to the right and left side in 44 patients (51.7%) and 43 patients (48.3%) respectively. The mean follow-up of ABI was 29.6 months (range, 18-33.4 months). Notably, the heat map showed that electrodes at the center and the medial end (E9-16) of the array showed higher likelihoods of being active, irrespective of right or left side. The network was trained for 500 epochs with a learning rate of 0.3 and achieved a mean classification of about 92.3%. The open accessible software for predicting the monopolar electrode stimulation postoperatively based on bipolar intraoperative stimulation can be found here at: https://hifla.org/abi CONCLUSIONS: An ideal MLP FF-NN structure was achieved and hence may result in understanding more precisely about the ABI stimulation and bringing consistency among the neurosurgeons and audiologists worldwide.

503 Stimulation of the Paraventricular Nucleus Activates Brown Adipose Tissue via Local GABA Release: A Novel Target for the Treatment of Obesity

INTRODUCTION: Sympathetic activation of brown adipose tissue (BAT) has shown significant promise in preclinical studies to elicit long term weight loss and reversal of type 2 diabetes however it is inhibited in obese individuals. METHODS: Rats were anesthetized and monitored for body temperature, BAT temperature, expired CO2, mean arterial pressure, and heart rate. Postganglionic BAT sympathetic nerve activity (SNA) was recorded from the interscapular BAT pad. Stimulating electrode and micropipette were placed steroeotactically in the PVN. Stimulation pulses at an intensity of 100 µA at 100 Hz for 5 minutes were delivered. Changes in BAT SNA and physiology were compared with and without stereotactically injected 500 µM bicuculline, a GABAA receptor antagonist. RESULTS: Stimulation of the PVN increased BAT SNA compared to no stimulation (411.7 ± 75.8% baseline vs 98.18 ± 1.4% baseline n = 5; P < 0.05) along with BAT temperature (35.8 ± 0.8°C vs 34.2 ± 0.7°C, n = 5, P < 0.001), expired CO2 (4.7 ± 0.6% vs 4.2 ± 0.5%, n = 5, P < 0.05) indicating increased metabolic rate. There was no change in blood pressure, body temperature, or paw temperature suggesting no change in sympathetic tone. Heart rate increased (476 ± 21 bpm vs 429 ± 23 bpm, n = 5, P < 0.01) consistent with increased metabolic demand. Microinjection of 500 µM bicuculline into the PVN prevented stimulated activation of BAT SNA. CONCLUSIONS: Stimulation of the PVN increases BAT activation and basal metabolic activity in the absence of cold-stimulus with minimal off-target effects on systemic sympathetic tone and may be a viable therapeutic target for stimulation of BAT activity to treat obesity and type 2 diabetes.

Effects of deep brain stimulation frequency on eye movements and cognitive control

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson’s disease (PD). Varying the frequency DBS has differential effects on axial and distal limb functions, suggesting differing modulation of relevant pathways. The STN is also a critical node in oculomotor and associative networks, but the effect of stimulation frequency on these networks remains unknown. This study aimed to investigate the effects of 80 hz vs. 130 Hz frequency STN-DBS on eye movements and executive control. Twenty-one STN-DBS PD patients receiving 130 Hz vs. 80 Hz stimulation were compared to a healthy control group (n = 16). All participants were tested twice in a double-blind manner. We examined prosaccades (latency and gain) and antisaccades (latency of correct and incorrect antisaccades, error rate and gain of the correct antisaccades). Executive function was tested with the Stroop task. The motor condition was assessed using Unified Parkinson’s Disease Rating Scale part III. The antisaccadic error rate was higher in patients (p = 0.0113), more so in patients on 80 Hz compared to 130 Hz (p = 0.001) stimulation. The differences between patients and controls and between frequencies for all other eye-movements or cognitive measures were not statistically significant. We show that 80 Hz STN-DBS in PD reduces the ability to maintain stable fixation but does not alter inhibition, resulting in a higher antisaccade error rate presumably due to less efficient fixation, without altering the motor state. This provides a wider range of stimulation parameters that can reduce specific DBS-related effects without affecting motor outcomes.

Subthalamic Nucleus Deep Brain Stimulation Restores Motor and Sensorimotor Cortical Neuronal Oscillatory Activity in the Free-Moving 6-Hydroxydopamine Lesion Rat Parkinson Model

ObjectivesEnhanced beta oscillations in cortical-basal ganglia (BG) thalamic circuitries have been linked to clinical symptoms of Parkinson’s disease. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces beta band activity in BG regions, whereas little is known about activity in cortical regions. In this study, we investigated the effect of STN DBS on the spectral power of oscillatory activity in the motor cortex (MCtx) and sensorimotor cortex (SMCtx) by recording via an electrocorticogram (ECoG) array in free-moving 6-hydroxydopamine (6-OHDA) lesioned rats and sham-lesioned controls. Materials and MethodsMale Sprague–Dawley rats (250–350 g) were injected either with 6-OHDA or with saline in the right medial forebrain bundle, under general anesthesia. A stimulation electrode was then implanted in the ipsilateral STN, and an ECoG array was placed subdurally above the MCtx and SMCtx areas. Six days after the second surgery, the free-moving rats were individually recorded in three conditions: 1) basal activity, 2) during STN DBS, and 3) directly after STN DBS. ResultsIn 6-OHDA-lesioned rats (N = 8), the relative power of theta band activity was reduced, whereas activity of broad-range beta band (12–30 Hz) along with two different subbeta bands, that is, low (12–30 Hz) and high (20–30 Hz) beta band and gamma band, was higher in MCtx and SMCtx than in sham-lesioned controls (N = 7). This was, to some extent, reverted toward control level by STN DBS during and after stimulation. No major differences were found between contacts of the electrode grid or between MCtx and SMCtx. ConclusionLoss of nigrostriatal dopamine leads to abnormal oscillatory activity in both MCtx and SMCtx, which is compensated by STN stimulation, suggesting that parkinsonism-related oscillations in the cortex and BG are linked through their anatomic connections.

Application of current steering with MICC directional lead in STN-DBS for Parkinson’s disease

BackgroundDeep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely performed for medically refractory Parkinson's disease (PD). Recent new technology of the multiple independent current control (MICC) with the directional lead provides both vertical and horizontal current steering on purposes. Consequently, MICC directional lead allows fine stimulation adjustment tailoring the condition of the individual patient. It is also expected to avoid stimulation induced adverse effects. MethodsWe retrospectively investigated the situation of current steering and the reason for doing so 3-month and 1-year after surgery in 80 patients who underwent bilateral STN-DBS for PD using MICC directional lead. ResultsIn 160 leads of 80 patients, current steering was used in 39 leads (24%) 3-month after surgery, but in 80 leads (50%) 1-year after surgery. As for the reason, vertical steering was used in 7 leads (4%) and horizontal steering was used in 28 leads (18%) to explore better stimulation effect for cardinal symptoms of PD. In addition, vertical steering was used for improving dyskinesia in 40 leads (25%) and alleviating tremor in 5 leads (3%). Horizontal steering was also used for avoiding adverse effects in 15 leads (9%), most of which were used to alleviate the symptoms of excessive stimulation of pyramidal tract. ConclusionsCurrent steering with the MICC directional lead was actually utilized in STN-DBS to explore more precise control of motor symptoms and also useful to avoid stimulation-induced adverse effect. Current steering is especially used in the later period after introduction of DBS.

Comparison of Two Electrode Placement Methods in Transcranial Direct Current Stimulation for Parkinson's Disease

Purpose: Therapeutic electrical stimulation of deep brain structures, such as the subthalamic nucleus and the Globus Pallidus (GP), is widely accepted as a treatment tool for patients with Parkinson's Disease (PD). Electrical stimulation of the cerebral cortex with electrodes or transcranial stimulation can increase motor function among PD patients. The present study aimed to evaluate the effects of non-invasive cortical stimulation with simulation of transcranial Direct Current Stimulation (tDCS) technique on parts of the basal ganglia among PD patients.
 Materials and Methods: tDCS was simulated using two different electrode placement methods (anodal stimulation of the primary motor cortex (M1) and anodal stimulation of the Dorsolateral Prefrontal Cortex (DLPFC)) and We evaluated the excitation procedure in the target area based on the excitation current distribution in GP and Subthalamic Nucleus according to the patient's condition in both electrode methods. All simulations were performed using head Magnetic Resonance Imaging (MRI) images of four people with PD. Also, according to the excitation current distribution obtained from the previous step, we studied how the excitation current distributed in the target areas is affected by using a model of the basal ganglia so that based on the membrane potential of each excitation in these areas, in all four patients, we compare both electrode-installation methods in a functional way. The effectiveness of brain stimulation was also studied using a basal ganglia model. Considering the membrane potential of GP and Subthalamic Nucleus regions, the effectiveness of each electrode placement method was evaluated in the Basal Ganglia (BG) model.
 Results: According to the results, direct current stimulation was propagated through electrodes placed on the scalp throughout the model. Also, anodal stimulation of the M1 had a better stimulation of GP and subthalamic nucleus than anodal stimulation of the DLPFC.
 Conclusion: Although, the procedures for performing tDCS and invasive brain stimulation in PD are different, the results show that this treatment can be appropriate and improve motor function in patients with PD.

Comparing the effects of transcranial alternating current and temporal interference (tTIS) electric stimulation through whole-brain mapping of c-Fos immunoreactivity.

The analysis of the topography of brain neuromodulation following transcranial alternating current (AC) stimulation is relevant for defining strategies directed to specific nuclei stimulation in patients. Among the different procedures of AC stimulation, temporal interference (tTIS) is a novel method for non-invasive neuromodulation of specific deep brain targets. However, little information is currently available about its tissue effects and its activation topography in in vivo animal models. After a single session (30 min, 0.12 mA) of transcranial alternate current (2,000 Hz; ES/AC group) or tTIS (2,000/2,010 Hz; Es/tTIS group) stimulation, rat brains were explored by whole-brain mapping analysis of c-Fos immunostained serial sections. For this analysis, we used two mapping methods, namely density-to-color processed channels (independent component analysis (ICA) and graphical representation (MATLAB) of morphometrical and densitometrical values obtained by density threshold segmentation. In addition, to assess tissue effects, alternate serial sections were stained for glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba1), and Nissl. AC stimulation induced a mild superficial increase in c-Fos immunoreactivity. However, tTIS stimulation globally decreased the number of c-Fos-positive neurons and increased blood brain barrier cell immunoreactivity. tTIS also had a stronger effect around the electrode placement area and preserved neuronal activation better in restricted areas of the deep brain (directional stimulation). The enhanced activation of intramural blood vessels' cells and perivascular astrocytes suggests that low-frequency interference (10 Hz) may also have a trophic effect.

Patterns of neural activity and clinical outcomes in a juvenile Huntington's Disease patient undergoing Deep Brain Stimulation of the subthalamic nucleus

BackgroundHuntington's disease (HD) is a hereditary neurodegenerative disease leading to cognitive and motor impairment. HD depends on basal ganglia dysfunctions, but the role of subthalamic nucleus (STN) neurons is not completely known. Drug-resistant motor symptoms of HD can be alleviated by neuromodulation of the basal ganglia through Deep Brain Stimulation (DBS) of STN. DBS target selection is supported by intra-operative microelectrode recordings (MER). MER have been previously used to characterize neural dynamics of STN in several movement disorders and can provide information on firing patterns underlying HD. MethodsWe analyzed MER data acquired during bilateral DBS of STN in a juvenile HD female patient with hypokinetic motor symptoms (generalized dystonia, stiffness, and severe gait impairment). Firing patterns of STN in HD were characterized by isolating single neuron activities (n = 23) and measuring their regularity, bursting, and oscillatory behavior. Multi-unit activity recordings spectrum was used to estimate the presence of network oscillations. ResultsSTN neurons displayed irregular dynamics and intense and sparse bursting. Only 3/23 neurons presented oscillatory activity. However, network oscillations were detected, in particular in the beta (12–30 Hz) band. After bilateral STN-DBS surgery, the Unified Huntington's Disease Rating Scale decreased from 60 to 54. ConclusionsThe most salient difference between HD and other movement disorders in STN activity is the presence of a weakly synchronized oscillatory mode, in which oscillations are evident at the network level but not at the single neuron level.

Post-ictal Rhythmic Thalamic Activity of the Centromedian Nucleus.

Deep brain stimulation of the centromedian nucleus of the thalamus (CMN) to treat drug-resistant epilepsy has been of interest for decades. However, little is known about the electrophysiological activity of the CMN during seizures. We describe a novel CMN EEG finding associated with seizure: post-ictal rhythmic thalamic activity. Five patients with drug-resistant epilepsy of unknown etiology with focal onset seizures underwent stereoelectroencephalography monitoring as part of evaluation for potential resective surgery or neuromodulation. Two patients had previously undergone complete corpus callosotomy and vagus nerve stimulation. A standardized plan for implantation included targets in the bilateral CMN. Each patient had frontal onset seizures, and two patients had additional insular, parietal, or mesial temporal onset seizures. Contacts of CMN were involved synchronously or rapidly after onset in most recorded seizures, particularly those with frontal onset. Focal onset hemiclonic and bilateral tonic-clonic seizures spread to involve cortical contacts with high-amplitude rhythmic spiking followed by abrupt offset with diffuse voltage attenuation. A post-ictal rhythmic 1.5 to 2.5 Hz delta frequency pattern, post-ictal rhythmic thalamic activity, emerged in CMN contacts amid the suppression of background activity in cortical contacts. In the two patients with corpus callosotomy, unilateral seizure spread and ipsilateral post-ictal rhythmic thalamic activity were observed. We observed post-ictal rhythmic thalamic activity in five patients with stereoelectroencephalography monitoring of the CMN with convulsive seizures. This rhythm appears late in ictal evolution and may signal an important role of the CMN in seizure termination. Furthermore, this rhythm may help identify CMN involvement in the epileptic network.

Depression Scores following Ventral Intermediate Nucleus Deep Brain Stimulation for Essential Tremor: A Meta-Analysis

Background: Essential tremor (ET) patients present with both motor and non-motor symptoms including depression. Although deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) is used to treat motor symptoms of ET, there is no consensus as to how VIM DBS influences non-motor symptoms, specifically depression. Objective: The objective of this study was to conduct a meta-analysis of available studies investigating change in pre- to postoperative depression scores as measured by Beck Depression Inventory (BDI) in ET patients receiving VIM DBS. Methods: Inclusion criteria were randomized control trials or observational studies of patients undergoing unilateral/bilateral VIM DBS. Non-ET patients, case reports, patients <18 years old, only non-VIM electrode placement, non-English articles, and abstracts were excluded. The primary outcome was change in BDI score from the preoperative time point to the last available follow-up. Pooled estimates of overall effect for BDI standardized mean difference were calculated using random effects models with the inverse variance method. Results: Seven studies divided into eight cohorts for a total of 281 ET patients met inclusion criteria. Pooled preoperative BDI score was 12.44 (95% CI [6.63–18.25]). A statistically significant decrease in depression scores was observed postoperatively (SMD = −0.29, 95% CI [−0.46 to −0.13], p = 0.0006). Pooled postoperative BDI score was 9.18 (95% CI [4.98–13.38]). A supplementary analysis which included an additional study with an estimated standard deviation at last follow-up was conducted. There was also a statistically significant decrease in depression postoperatively (9 cohorts, n = 352, SMD = −0.31, 95% CI [−0.46 to −0.16], p < 0.0001). Conclusions: Both quantitative and qualitative analyses of the existing literature suggest that VIM DBS improves depression postoperatively among ET patients. These results may guide surgical risk-benefit analysis and counseling for ET patients undergoing VIM DBS.

DBS of the ANT for refractory epilepsy: A single center experience of seizure reduction, side effects and neuropsychological outcomes.

Evaluation of the antiseizure efficacy, side effects and neuropsychological effects of Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT). ANT-DBS is a treatment option for patients with difficult-to-treat epilepsy. Though several works outline the cognitive and/or mood effects of ANT-DBS for the treatment of epilepsy, data on the intersection between antiseizure efficacy, cognitive and undesired effects are scarce. We retrospectively analyzed the data of our cohort of 13 patients. Post-implantation seizure frequencies were measured at 6 months, 12 months and last follow-up, as well as averaged throughout follow-up. These values were then compared with mean seizure frequencies in the 6 months before implantation. To address acute cognitive effects of DBS a baseline assessment was performed after implantation and before stimulation, and a follow-up assessment was conducted under DBS. The long-term effects of DBS on cognition were assessed by comparing the preoperative neuropsychological profile with a long-term follow-up under DBS. In the entire cohort, 54.5% of patients were responders, with an average seizure reduction of 73.6%. One of these patients achieved temporary seizure freedom and near-total seizure reduction during the entire follow-up. Seizure reduction of <50% was achieved in 3 patients. Non-responders suffered an average seizure increase of 27.3%. Eight of twenty-two active electrodes (36,4%) were off-target. Two of our patients had both electrodes implanted off-target. When removing these two patients from the analysis and averaging seizure frequency during the entire follow-up period, four patients (44.4%) were responders and three experienced a seizure reduction of <50%. Intolerable side effects arose in 5 patients, mostly psychiatric. Regarding acute cognitive effects of DBS, only one patient showed a significant decline in executive functions. Long-term neuropsychological effects included significant intraindividual changes in verbal learning and memory. Figural memory, attention and executive functions, confrontative naming and mental rotation were mostly unchanged, and improved in few cases. In our cohort, more than half of patients were responders. Psychiatric side effects seem to have been more prevalent compared to other published cohorts. This may be partially explained by a relatively high occurrence of off-target electrodes.

Frameless Robot-Assisted Asleep Centromedian Thalamic Nucleus Deep Brain Stimulation Surgery in Patients with Drug-Resistant Epilepsy: Technical Description and Short-Term Clinical Results.

This purpose of this work is to give a detailed description of a surgical technique for frameless robot-assisted asleep deep brain stimulation (DBS) of the centromedian thalamic nucleus (CMT) in drug-resistant epilepsy (DRE). Ten consecutively enrolled patients who underwent CMT-DBS were included in the study. The FreeSurfer "Thalamic Kernel Segmentation" module and experience target coordinates were used for locating the CMT, and quantitative susceptibility mapping (QSM) images were used to check the target. The patient's head was secured with a head clip, and electrode implantation was performed with the assistance of the neurosurgical robot Sinovation®. After opening the dura, the burr hole was continuously flushed with physiological saline to stop air from entering the skull. All procedures were performed under general anesthesia without intraoperative microelectrode recording (MER). The mean age of the patients at surgery and onset of seizures was 22years (range 11-41years) and 11years (range 1-21years), respectively. The median duration of seizures before CMT-DBS surgery was 10years (2-26years). CMT was successfully segmented, and its position was verified by experience target coordinates and QSM images in all ten patients. The mean surgical time for bilateral CMT-DBS in this cohort was 165 ± 18min. The mean pneumocephalus volume was 2 cm3. The median absolute errors in the x-, y-, and z-axes were 0.7mm, 0.5mm, and 0.9mm, respectively. The median Euclidean distance (ED) and radial error (RE) was 1.3 ± 0.5mm and 1.0 ± 0.3mm, respectively. No significant difference was found between right- and left-sided electrodes regarding the RE nor the ED. After a mean 12-month follow-up, the average reduction in seizures was 61%, and six patients experienced a ≥ 50% reduction in seizures, including one patient who had no seizures after the operation. All patients tolerated the anesthesia operation, and no permanent or serious complications were reported. Frameless robot-assisted asleep surgery is a precise and safe approach for placing CMT electrodes in patients with DRE, shortening the surgery time. The segmentation of the thalamic nuclei enables the precise location of the CMT, and the flow of physiological saline to seal the burr holes is a good way to reduce the influx of air. CMT-DBS is an effective method to reduce seizures.