EEG-based biomarkers for optimizing deep brain stimulation contact configuration in Parkinson's disease.

Objective: Subthalamic deep brain stimulation (STN-DBS) is a neurosurgical therapy to treat Parkinson's disease (PD). Optimal therapeutic outcomes are not achieved in all patients due to increased DBS technological complexity; programming time constraints; and delayed clinical response of some symptoms. To streamline the programming process, biomarkers could be used to accurately predict the most effective stimulation configuration. Therefore, we investigated if DBS-evoked potentials (EPs) combined with imaging to perform prediction analyses could predict the best contact configuration. Methods: In 10 patients, EPs were recorded in response to stimulation at 10 Hz for 50 s on each DBS-contact. In two patients, we recorded from both hemispheres, resulting in recordings from a total of 12 hemispheres. A monopolar review was performed by stimulating on each contact and measuring the therapeutic window. CT and MRI data were collected. Prediction models were created to assess how well the EPs and imaging could predict the best contact configuration. Results: EPs at 3 ms and at 10 ms were recorded. The prediction models showed that EPs can be combined with imaging data to predict the best contact configuration and hence, significantly outperformed random contact selection during a monopolar review. Conclusion: EPs can predict the best contact configuration. Ultimately, these prediction tools could be implemented into daily practice to ease the DBS programming of PD patients.

Understanding Neuromodulation Pathways in tDCS: Brain Stem Recordings in Rat During Trigeminal Nerve Direct Current Stimulation.

Background: Recent evidence suggests that transcranial direct current stimulation (tDCS) indirectly influences brain activity through cranial nerve pathways, particularly the trigeminal nerve. However, the electrophysiological effects of direct current (DC) stimulation on the trigeminal nerve (DC-TNS) and its impact on trigeminal nuclei remain unknown. These nuclei exert control over brainstem centers regulating neurotransmitter release, such as serotonin and norepinephrine, potentially affecting global brain activity. Objectives: To investigate how DC-TNS impacts neuronal activity in the principal sensory nucleus (NVsnpr) and the mesencephalic nucleus of the trigeminal nerve (MeV). Methods: Twenty male Sprague Dawley rats (n=10 each nucleus) were anesthetized with urethane. DC stimulation, ranging from 0.5 to 3 mA, targeted the trigeminal nerve's marginal branch. Simultaneously, single-unit electrophysiological recordings were obtained using a 32-channel silicon probe, comprising three one-minute intervals: pre-stimulation, DC stimulation, and post-stimulation. Xylocaine was administered to block the trigeminal nerve as a control. Results: DC-TNS significantly increased neuronal spiking activity in both NVsnpr and MeV, returning to baseline during the post-stimulation phase. When the trigeminal nerve was blocked with xylocaine, the robust 3 mA trigeminal nerve DC stimulation failed to induce increased spiking activity in the trigeminal nuclei. Conclusion: Our results offer initial empirical support for trigeminal nuclei activity modulation via DC-TNS. This discovery supports the hypothesis that cranial nerve pathways may play a pivotal role in mediating tDCS effects, setting the stage for further exploration into the complex interplay between peripheral nerves and neural modulation techniques. Highlights: Direct current stimulation of the trigeminal nerve (DC-TNS) modulates neural activity in rat NVsnpr and MeV.Xylocaine administration reversibly blocks the DC-TNS effect on neural responses.Trigeminal nerve stimulation should be considered a possible mechanism of action of tDCS.

Reinterpreting published tDCS results in terms of a cranial and cervical nerve co-stimulation mechanism.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation method that has been used to alter cognition in hundreds of experiments. During tDCS, a low-amplitude current is delivered via scalp electrodes to create a weak electric field in the brain. The weak electric field causes membrane polarization in cortical neurons directly under the scalp electrodes. It is generally assumed that this mechanism causes the observed effects of tDCS on cognition. However, it was recently shown that some tDCS effects are not caused by the electric field in the brain but rather via co-stimulation of cranial and cervical nerves in the scalp that also have neuromodulatory effects that can influence cognition. This peripheral nerve co-stimulation mechanism is not controlled for in tDCS experiments that use the standard sham condition. In light of this new evidence, results from previous tDCS experiments could be reinterpreted in terms of a peripheral nerve co-stimulation mechanism. Here, we selected six publications that reported tDCS effects on cognition and attributed the effects to the electric field in the brain directly under the electrode. We then posed the question: given the known neuromodulatory effects of cranial and cervical nerve stimulation, could the reported results also be understood in terms of tDCS peripheral nerve co-stimulation? We present our re-interpretation of these results as a way to stimulate debate within the neuromodulation field and as a food-for-thought for researchers designing new tDCS experiments.

Deep brain stimulation for the treatment of Alzheimer's disease: A systematic review and meta-analysis.

Background: One of the experimental neuromodulation techniques being researched for the treatment of Alzheimer's disease (AD) is deep brain stimulation (DBS). To evaluate the effectiveness of DBS in AD, we performed a systematic review and meta-analysis of the available evidence. Methods: From the inception through December 2021, the following databases were searched: Medline via PubMed, Scopus, Embase, Cochrane Library, and Web of Science. The search phrases used were "Alzheimer's disease," "AD," "deep brain stimulation," and "DBS." The information from the included articles was gathered using a standardized data-collecting form. In the included papers, the Cochrane Collaboration methodology was used to evaluate the risk of bias. A fixed-effects model was used to conduct the meta-analysis. Results: Only five distinct publications and 6 different comparisons (one study consisted of two phases) were included out of the initial 524 papers that were recruited. DBS had no impact on the cognitive ability in patients with AD [0.116 SMD, 95% confidence interval (CI), -0.236 to 0.469, p = 0.518]. The studies' overall heterogeneity was not significant (κ2 = 6.23, T 2 = 0.053, df = 5, I 2 = 19.76%, p = 0.284). According to subgroup analysis, the fornix-DBS did not improve cognitive function in patients with AD (0.145 SMD, 95%CI, -0.246 to 0.537, p = 0.467). Unfavorable neurological and non-neurological outcomes were also reported. Conclusion: The inconsistencies and heterogeneity of the included publications in various target and age groups of a small number of AD patients were brought to light by this meta-analysis. To determine if DBS is useful in the treatment of AD, further studies with larger sample sizes and randomized, double-blinded, sham-controlled designs are required.

Acute stimulation with symmetric biphasic pulses induces less ataxia compared to cathodic pulses in DBS for essential tremor.

BACKGROUND: Symmetric biphasic pulses have been shown to acutely increase the therapeutic window of ventralis intermedius deep brain stimulation (Vim-DBS) for essential tremor (ET) compared to cathodic pulses. Acute supratherapeutic stimulation can induce ataxic side effects in Vim-DBS. OBJECTIVE: To investigate the effect on tremor, ataxia and dysarthria of 3 h of biphasic stimulation in patients with DBS for ET. METHODS: A randomized, doubled-blind, cross-over design was used to compare standard cathodic pulses with symmetric biphasic pulses (anode-first) during a 3-h period per pulse shape. During each 3-h period, all stimulation parameters were identical, except for the pulse shape. Tremor (Fahn-Tolosa-Marin Tremor Rating Scale), ataxia (International Cooperative Ataxia Rating Scale) and speech (acoustic and perceptual measures) were assessed hourly during the 3-h periods. RESULTS: Twelve ET patients were included. During the 3-h stimulation period, tremor control was equivalent between the two pulse shapes. Biphasic pulses elicited significantly less ataxia than cathodic pulses (p = 0.006). Diadochokinesis rate of speech was better for the biphasic pulse (p = 0.048), but other measures for dysarthria were not significantly different between the pulses. CONCLUSION: Symmetric biphasic pulses induce less ataxia than conventional pulses after 3 h of stimulation DBS in ET patients.

Electrophysiologic Evidence That Directional Deep Brain Stimulation Activates Distinct Neural Circuits in Patients With Parkinson Disease.

OBJECTIVES: Deep brain stimulation (DBS) delivered via multicontact leads implanted in the basal ganglia is an established therapy to treat Parkinson disease (PD). However, the different neural circuits that can be modulated through stimulation on different DBS contacts are poorly understood. Evidence shows that electrically stimulating the subthalamic nucleus (STN) causes a therapeutic effect through antidromic activation of the hyperdirect pathway-a monosynaptic connection from the cortex to the STN. Recent studies suggest that stimulating the substantia nigra pars reticulata (SNr) may improve gait. The advent of directional DBS leads now provides a spatially precise means to probe these neural circuits and better understand how DBS affects distinct neural networks. MATERIALS AND METHODS: We measured cortical evoked potentials (EPs) using electroencephalography (EEG) in response to low-frequency DBS using the different directional DBS contacts in eight patients with PD. RESULTS: A short-latency EP at 3 milliseconds originating from the primary motor cortex appeared largest in amplitude when stimulating DBS contacts closest to the dorsolateral STN (p < 0.001). A long-latency EP at 10 milliseconds originating from the premotor cortex appeared strongest for DBS contacts closest to the SNr (p < 0.0001). CONCLUSIONS: Our results show that at the individual patient level, electrical stimulation of different nuclei produces distinct EP signatures. Our approach could be used to identify the functional location of each DBS contact and thus help patient-specific DBS programming. CLINICAL TRIAL REGISTRATION: The ClinicalTrials.gov registration number for the study is NCT04658641.

Epicranial Direct Current Stimulation Suppresses Harmaline Tremor in Rats.

INTRODUCTION: Essential tremor (ET) is the most common neurologic movement disorder worldwide. It is characterized by a postural tremor, mostly in the upper extremities, causing difficulties in daily activities that may lead to social exclusion. Some patients with ET do not respond well to or do not tolerate medication. Thus, deep brain stimulation can be offered. In a recent study, we proposed a novel neuromodulation technique called epicranial current stimulation (ECS) that works in a minimally invasive way by placing the electrodes subcutaneously under the skin and directly over the skull. In this study, we investigated the feasibility of using epicranial direct current stimulation (EDCS) to suppress tremor in a rat harmaline ET model. MATERIALS AND METHODS: In experiment 1, seven Sprague Dawley rats were implanted with ECS electrodes placed over the motor cortex (MC) and the cerebellum to investigate whether stimulating between them could suppress tremor. In experiments 2 and 3, eight rats were implanted with ECS electrodes placed over the MC, cerebellum, and the rostral skull to separate the effects on tremor caused by stimulating each target. During each experiment, the rats were injected with harmaline, which induced tremor that was quantified using an accelerometer. EDCS was then applied through the different electrode configurations to evaluate their tremor suppression effectiveness. RESULTS: Results from experiment 1 showed that MCcathode-Cerebellaranode suppressed tremor compared with stimulation-OFF but MCanode-Cerebellarcathode did not. Furthermore, experiments 2 and 3 showed that it was the cerebellar anodal electrode that was driving tremor suppression. CONCLUSION: Cerebellar EDCS suppressed harmaline tremor in rats in a polarity-dependent manner. EDCS could be a promising neuromodulation method for patients with ET.

Interphase Gaps in Symmetric Biphasic Pulses Reduce the Therapeutic Window in Ventral Intermediate Nucleus of the Thalamus-Deep Brain Stimulation for Essential Tremor.

INTRODUCTION: Symmetric biphasic pulses enlarge the therapeutic window in thalamic deep brain stimulation in patients with essential tremor. Adding an interphase gap to these symmetric biphasic pulses may further affect the therapeutic window. MATERIALS AND METHODS: Nine patients (16 hemispheres) were included in this study. Biphasic pulses (anodic phase first) with interphase gaps of 0, 10, 20, 50, and 100 µs were tested, in random order. The outcome parameters were the therapeutic threshold (TT) and side-effect threshold (SET), and thus also the therapeutic window (TW). RESULTS: Increasing interphase gaps lowered both SET and TT (linear mixed-effects model; p < 0.001 and p < 0.001). Because SET decreased predominantly, increasing interphase gaps resulted in smaller TWs (linear mixed-effects model; p < 0.001). DISCUSSION AND CONCLUSIONS: Introducing an interphase gap in a symmetric biphasic pulse may lead to less selectivity in fiber or neuronal activation. Our findings show that, in the context of anode-first biphasic pulses, the use of zero-interphase gaps results in the largest TW. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT05177900.

A novel tDCS control condition using optimized anesthetic gel to block peripheral nerve input.

Background: Recent studies indicate that some transcranial direct current stimulation (tDCS) effects may be caused by indirect stimulation of peripheral nerves in the scalp rather than the electric field in the brain. To address this, we developed a novel tDCS control condition in which peripheral input is blocked using topical anesthetics. We developed a compounded anesthetic gel containing benzocaine and lidocaine (BL10) that blocks peripheral input during tDCS. Methods: In a blinded randomized cross-over study of 18 healthy volunteers (M/F), we compared the gel's efficacy to EMLA and an inert placebo gel. Subjects used a visual analog scale (VAS) to rate the stimulation sensation in the scalp produced by 10 s of 2 mA tDCS every 2 min during 1 h. In an additional in-vitro experiment, the effect of a DC current on gel resistivity and temperature was investigated. Results: Both the BL10 and EMLA gel, lowered the stimulation sensations compared to the placebo gel. The BL10 gel showed a tendency to work faster than the EMLA gel with reported sensations for the BL10 gel being lower than for EMLA for the first 30 min. The DC current caused a drastic increase in gel resistivity for the EMLA gel, while it did not affect gel resistivity for the BL10 and placebo gel, nor did it affect gel temperature. Conclusions: Topical anesthetics reduce stimulation sensations by blocking peripheral nerve input during tDCS. The BL10 gel tends to work faster and is more electrically stable than EMLA gel. Clinical trial registration: The study is registered at ClinicalTrials.gov with name "Understanding the Neural Mechanisms Behind tDCS" and number NCT04577677.

Aligning Dentato-Rubro-Thalamic Tract and Subthalamic Nucleus Targets in a Patient with Comorbid Essential Tremor and Parkinson's Disease: Case Report.

Deep brain stimulation is an established treatment option for both essential tremor (ET) and Parkinson's disease (PD), although typically targeting different brain structures. Some patients are diagnosed with comorbid ET and PD. Selecting the optimal stimulation target in these patients is challenging. We present a patient with comorbid ET and PD in whom we used bilaterally a single parietal trajectory to align the dentato-rubro-thalamic tract and the subthalamic nucleus. Although parietal trajectories are challenging, we reached satisfactory outcomes for both conditions without complications. Single-electrode deep brain stimulation of the dentato-rubro-thalamic tract and the subthalamic nucleus through a parietal approach may represent a feasible treatment option in this patient group.

Deep brain stimulation and spinal cord stimulation for orthostatic tremor: A systematic review.

BACKGROUND: Orthostatic tremor is a rare and debilitating movement disorder. Its first-line treatment is pharmacological. For pharmaco-refractory patients, surgical treatment options such as deep brain stimulation (DBS) and spinal cord stimulation (SCS) have been investigated recently. OBJECTIVES: We conducted a systematic review of all published outcome and safety data on DBS and SCS for orthostatic tremor patients. METHODS: We searched Pubmed and Embase for studies describing orthostatic tremor patients treated with DBS or SCS. We collected all available outcome and safety data and our primary endpoint was the change in unsupported stance duration 1 year postoperatively (±6 months). RESULTS: We included 15 studies, reporting on 32 orthostatic tremor patients who underwent DBS, 4 patients SCS and 2 both. The ventral intermediate nucleus and the zona incerta were targeted in 25/34 and 9/34 DBS cases, respectively. The median stance time at 1 year follow-up was 240 s compared to 30 s pre-operatively (p < 0.001). Stimulation-induced side effects occurred in the majority of patients, but were often transient. Bilateral stimulation appeared more effective than unilateral and stimulation settings were comparable to thalamic DBS for essential tremor. There were insufficient data available to draw meaningful conclusions on the long-term effects of DBS. Due to insufficient data, no conclusions could be drawn on the effects of SCS on orthostatic tremor. CONCLUSION: DBS may be effective to increase stance time in orthostatic tremor patients in the first year, but further research is necessary to evaluate the long-term effects and the role of spinal cord stimulation.

Transcutaneous electrical nerve inhibition using medium frequency alternating current.

Transcutaneous medium-frequency alternating electrical current is defined as an alternating current between 1 and 10 kHz and is capable of producing an instant, reversible block. This study aims to evaluate the efficacy of sensory perception and force production of the index and middle finger after transcutaneous medium-frequency alternating electrical current stimulation of the distal median nerve. A single-center prospective interventional cohort study was conducted in adult healthy volunteers at the Jessa Hospital, Hasselt, Belgium. Two different electrodes (PALS & 3M) were placed on the distal median nerve, which was located using a Sonosite X-Porte Ultrasound transducer, with the first electrode being placed on the skin at the level of the transverse carpal ligament and the second electrode 7 cm proximally to the first electrode. The tactile sensation was evaluated with Semmes-Weinstein monofilament test and sensation of pressure/pain was evaluated with an algometer. Peak force production was assessed with an electronic dynamometer. All measurements were performed at baseline and tMFAEC stimulation frequencies of 2 and 10 kHz in a randomized manner. Statistical analysis was performed with a one-way ANOVA with repeated measures test or a Friedman rank sum test, followed by the Wilcoxon signed rank test adjusted with Bonferroni correction. A p-value < 0.05 was considered statistically significant. From 9 to 13th of April 2021, 25 healthy volunteers were included in the Jessa Hospital, Hasselt, Belgium. A statistically significant reduction in tactile sensation during 2 kHz and 10 kHz stimulation compared to baseline was observed (2.89 ± 0.22 (PALS2); 3.35 ± 0.25 (3M2) and 2.14 ± 0.12 (PALS10); 2.38 ± 0.12 (3M10) versus - 1.75 ± 0.09 (baseline), p < 0.0001). 3M electrodes showed a tendency towards the elevation of pressure pain threshold compared to baseline. No significant difference in mean peak forces of the index and middle fingers after transcutaneous medium-frequency alternating electrical current stimulation with 2 and 10 kHz was found. This study demonstrates that transcutaneous medium-frequency alternating electrical current stimulation on the distal median nerve inhibits tactile sensory nerve activity in the index and middle finger when stimulation of 2 kHz and, to a lesser extent, 10 kHz was applied. A reduction of motor nerve activity was not observed but force production measurements may be prone to error.Trial registration: clinicaltrials.gov on 01/04/2021. NCT-Number: NCT04827173.

Frequency-Specific Modulation of Slow-Wave Neural Oscillations via Weak Exogeneous Extracellular Fields Reveals a Resonance Pattern.

Single neurons often exhibit endogenous oscillatory activity centered around a specific frequency band. Transcranial alternating current stimulation (tACS) can generate a weak oscillating extracellular field in the brain that causes subthreshold membrane potential shifts that can affect spike timing at the single neuron level. Many studies have now shown that the endogenous oscillation can be entrained when the tACS frequency matches that of the exogenous extracellular field. However, the effect of tACS on the amplitude of the endogenous oscillation has been less well studied. We investigated this by using exogenous extracellular fields to modulate slow-wave neural oscillations in the ketamine anesthetized male Wistar rat. We applied spatially broad extracellular fields of different frequencies while recording spiking activity from single neurons. The effect of the exogenous extracellular field on the slow-wave neural oscillation amplitude (NOA) followed a resonance pattern: large modulations were observed when the extracellular frequency matched the endogenous frequency of the neuron, while extracellular fields with frequencies far away from the endogenous frequency had little effect. No changes in spike-rate were observed for any of the extracellular fields applied. Our results demonstrate that in addition to the previously reported entrainment and Arnold tongue patterns, weak oscillating extracellular fields modulate the amplitude of the endogenous neural oscillation without any changes in spike-rate, and that this modulation follows a frequency-specific resonance pattern.SIGNIFICANCE STATEMENT Neural activity often oscillates around specific endogenous frequencies. Transcranial alternating current stimulation (tACS) is a neuromodulation method which biases spike-times and alter endogenous activity. Most tACS studies focus on entrainment effects which occur when tACS and endogenous neural frequencies are matched. In this study we varied the frequency of the applied tACS and investigated its effect on amplitude of the neural oscillation. Our results revealed a resonance pattern where tACS frequencies close to the endogenous frequency caused an increase in neural oscillation amplitude (NOA) specifically at the applied tACS frequency, while applying tACS frequencies farther away caused little or no change in NOA. Furthermore, applying tACS at differing frequencies caused the amplitude of the neural oscillation at the prestimulation endogenous frequency to decrease.

Current Steering Using Multiple Independent Current Control Deep Brain Stimulation Technology Results in Distinct Neurophysiological Responses in Parkinson's Disease Patients.

Background: Deep brain stimulation (DBS) is an effective neuromodulation therapy to treat people with medication-refractory Parkinson's disease (PD). However, the neural networks affected by DBS are not yet fully understood. Recent studies show that stimulating on different DBS-contacts using a single current source results in distinct EEG-based evoked potentials (EPs), with a peak at 3 ms (P3) associated with dorsolateral subthalamic nucleus stimulation and a peak at 10 ms associated with substantia nigra stimulation. Multiple independent current control (MICC) technology allows the center of the electric field to be moved in between two adjacent DBS-contacts, offering a potential advantage in spatial precision. Objective: Determine if MICC precision targeting results in distinct neurophysiological responses recorded via EEG. Materials and Methods: We recorded cortical EPs in five hemispheres (four PD patients) using EEG whilst employing MICC to move the electric field from the most dorsal DBS-contact to the most ventral in 15 incremental steps. Results: The center of the electric field location had a significant effect on both the P3 and P10 amplitude in all hemispheres where a peak was detected (P3, detected in 4 of 5 hemispheres, p < 0.0001; P10, detected in 5 of 5 hemispheres, p < 0.0001). Post hoc analysis indicated furthermore that MICC technology can significantly refine the resolution of steering. Conclusion: Using MICC to incrementally move the center of the electric field to locations between adjacent DBS-contacts resulted in significantly different neurophysiological responses that may allow further precision of the programming of individual patients.

Detection of tACS Entrainment Critically Depends on Epoch Length.

Neural entrainment is the phase synchronization of a population of neurons to an external rhythmic stimulus such as applied in the context of transcranial alternating current stimulation (tACS). tACS can cause profound effects on human behavior. However, there remain a significant number of studies that find no behavioral effect when tACS is applied to human subjects. To investigate this discrepancy, we applied time sensitive phase lock value (PLV) based analysis to single unit data from the rat motor cortex. The analysis revealed that detection of neural entrainment depends critically on the epoch length within which spiking information is accumulated. Increasing the epoch length allowed for detection of progressively weaker levels of neural entrainment. Based on this single unit analysis, we hypothesized that tACS effects on human behavior would be more easily detected in a behavior paradigm which utilizes longer epoch lengths. We tested this by using tACS to entrain tremor in patients and healthy volunteers. When the behavioral data were analyzed using short duration epochs tremor entrainment effects were not detectable. However, as the epoch length was progressively increased, weak tremor entrainment became detectable. These results suggest that tACS behavioral paradigms that rely on the accumulation of information over long epoch lengths will tend to be successful at detecting behavior effects. However, tACS paradigms that rely on short epoch lengths are less likely to detect effects.

A systematic review and meta-analysis of transcranial direct-current stimulation effects on cognitive function in patients with Alzheimer's disease.

Transcranial direct-current stimulation (tDCS) appears to enhance cognitive function in Alzheimer's disease (AD). Accordingly, over the last two decades, the number of studies using tDCS for AD has grown. This study aimed to provide a quantitative assessment of the efficacy of tDCS in improving cognitive function in patients with AD. We systematically searched the literature until May 2021 to identify relevant publications for inclusion in our systematic review and meta-analysis. Eligible studies were sham-controlled trials assessing the impacts of anodal or cathodal tDCS on cognitive function in patients with AD. The outcome measure of this study was the effects of tDCS on distinct cognitive domains including memory, attention, and global cognitive function. The initial search yielded a total of 323 records. Five other articles were found using manual search of the databases. Of these, 13 publications (14 different studies) with a total of 211 patients of various degrees of AD severity underwent meta-analysis. Meta-analysis revealed the non-significant effects of tDCS on attention (0.425 SMD, 95% CI, -0.254 to 1.104, p = 0.220), and significant positive impacts on the amelioration of general cognitive measures (1.640 SMD, 95% CI, 0.782 to 2.498, p < 0.000), and memory (1.031 SMD, 95% CI, 0.688 to 1.373, p < 0.000) dysfunction in patients with AD. However, the heterogeneity of the studies were high in all subdomains of cognition (Ï°2 = 22.810, T2 = 0.552, d.f. = 5, I2 = 78.80%, p < 0.000 for attention, Ï°2 = 96.29, T2 = 1.727, d.f. = 10, I2 = 89.61%, p < 0.000 for general cognition, and Ï°2 = 7.253, T2 = 0.085, d.f. = 5, I2 = 31.06%, p = 0.203 for memory). Improved memory and general cognitive function in patients with AD was shown in this meta-analysis. However, due to the small number of studies and the high heterogeneity of the data, more high-quality studies using standardized parameters and measures are needed before tDCS can be considered as a treatment for AD.

Anodic and symmetric biphasic pulses enlarge the therapeutic window in deep brain stimulation for essential tremor.

BACKGROUND: Since the inception of DBS, cathodic pulses have been used. OBJECTIVE: To investigate the effect of anodic and symmetric biphasic pulses on the therapeutic window (TW) in essential tremor (ET) patients. METHODS: A randomized, doubled-blinded, cross-over design was used to test the effect of cathodic, anodic and symmetric biphasic pulses (cathode-first and anode-first) on the TW in an acute clinical setting. TW was defined as the difference between the minimal stimulation amplitude provoking side effects and minimal stimulation amplitude inducing tremor arrest. RESULTS: 9 ET patients (10 hemispheres) were included. Anodic stimulation induced a significantly larger TW compared to cathodic stimulation (p = 0.008). Symmetric biphasic stimulation also widened the TW compared to cathodic stimulation for both cathode- (p = 0.047) and anode-first (p = 0.008) biphasic pulses. For both anodic and biphasic pulses, the effect on TW was mainly driven by the change in side effect threshold. The order of the phases in the biphasic pulse had a significant effect on the side effect threshold (p = 0.039), with biphasic-anode first having the highest value. All pulse shapes were safe in the acute setting. CONCLUSION: Anodic and symmetric biphasic pulses increase TW in ET patients.

Objective evaluation of stimulation artefact removal techniques in the context of neural spike sorting.

Objective. We present a framework to objectively test and compare stimulation artefact removal techniques in the context of neural spike sorting.Approach. To this end, we used realistic hybrid ground-truth spiking data, with superimposed artefacts fromin vivorecordings. We used the framework to evaluate and compare several techniques: blanking, template subtraction by averaging, linear regression, and a multi-channel Wiener filter (MWF).Main results. Our study demonstrates that blanking and template subtraction result in a poorer spike sorting performance than linear regression and MWF, while the latter two perform similarly. Finally, to validate the conclusions found from the hybrid evaluation framework, we also performed a qualitative analysis onin vivorecordings without artificial manipulations.Significance. Our framework allows direct quantification of the impact of the residual artefact on the spike sorting accuracy, thereby allowing for a more objective and more relevant comparison compared to indirect signal quality metrics that are estimated from the signal statistics. Furthermore, the availability of a ground truth in the form of single-unit spiking activity also facilitates a better estimation of such signal quality metrics.