A single-center, open-label trial on convenience and complications of rechargeable implantable pulse generators for spinal cord stimulation: The Recharge Pain Trial.

Rechargeable implantable pulse generators (r-IPGs) have been available for spinal cord stimulation (SCS) claiming to offer a longer service life but demanding continuous monitoring and regular recharging by the patients. The aim of the study (DRKS00021281; Apr 7th, 2020) was to assess the convenience, safety, and acceptance of r-IPGs and their effect on patient lives under long-term therapy. Standardized questionnaires were sent to all chronic pain patients with a r-IPG at the time of trial. Primary endpoint was the overall convenience of the charging process on an ordinal scale from "very hard" (1 point) to "very easy" (5 points). Secondary endpoints were charge burden (min/week), rates of user confidence and complications (failed recharges, interruptions of therapy). Endpoints were analyzed for several subgroups. Data sets n = 40 (42% return rate) were eligible for analysis. Patient age was 57.2 ± 12.6 (mean ± standard deviation) years with the r-IPG being implanted for 52.1 ± 32.6 months. The overall convenience of recharging was evaluated as "easy" (4 points). The charge burden was 112.7 ± 139 min/week. 92% of the patients felt confident recharging the neurostimulator. 37.5% of patients reported failed recharges. 28.9% of patients experienced unintended interruptions of stimulation. Subgroup analysis only showed a significant impact on overall convenience for different models of stimulators (p < 0.05). Overall, SCS patients feel confident handling a r-IPG at high rates of convenience and acceptable effort despite high rates of usage-related complications. Further technical improvements for r-IPGs are needed.

Spatial Filtering of Electroencephalography Reduces Artifacts and Enhances Signals Related to Spinal Cord Stimulation (SCS).

OBJECTIVES: How spinal cord stimulation (SCS) in its different modes suppresses pain is poorly understood. Mechanisms of action may reside locally in the spinal cord, but also involve a larger network including subcortical and cortical brain structures. Tonic, burst, and high-frequency modes of SCS can, in principle, entrain distinct temporal activity patterns in this network, but finally have to yield specific effects on pain suppression. Here, we employ high-density electroencephalography (EEG) and recently developed spatial filtering techniques to reduce SCS artifacts and to enhance EEG signals specifically related to neuromodulation by SCS. MATERIALS AND METHODS: We recorded high-density resting-state EEGs in patients suffering from pain of various etiologies under different modes of SCS. We established a pipeline for the robust spectral analysis of oscillatory brain activity during SCS, which includes spatial filtering for attenuation of pulse artifacts and enhancement of brain activity potentially modulated by SCS. RESULTS: In sensor regions responsive to SCS, neuromodulation strongly reduced activity in the theta and low alpha range (6-10 Hz) in all SCS modes. Results were consistent in all patients, and in accordance with thalamocortical dysrhythmia hypothesis of pain. Only in the tonic mode showing paresthesia as side effect, SCS also consistently and strongly reduced high-gamma activity (>84 Hz). CONCLUSIONS: EEG spectral analysis combined with spatial filtering allows for a spatially and temporally specific assessment of SCS-related, neuromodulatory EEG activity, and may help to disentangle therapeutic and side effects of SCS.

Investigating the temporal dynamics of electroencephalogram (EEG) microstates using recurrent neural networks.

Electroencephalogram (EEG) microstates that represent quasi-stable, global neuronal activity are considered as the building blocks of brain dynamics. Therefore, the analysis of microstate sequences is a promising approach to understand fast brain dynamics that underlie various mental processes. Recent studies suggest that EEG microstate sequences are non-Markovian and nonstationary, highlighting the importance of the sequential flow of information between different brain states. These findings inspired us to model these sequences using Recurrent Neural Networks (RNNs) consisting of long-short-term-memory (LSTM) units to capture the complex temporal dependencies. Using an LSTM-based auto encoder framework and different encoding schemes, we modeled the microstate sequences at multiple time scales (200-2,000 ms) aiming to capture stably recurring microstate patterns within and across subjects. We show that RNNs can learn underlying microstate patterns with high accuracy and that the microstate trajectories are subject invariant at shorter time scales (≤400 ms) and reproducible across sessions. Significant drop in the reconstruction accuracy was observed for longer sequence lengths of 2,000 ms. These findings indirectly corroborate earlier studies which indicated that EEG microstate sequences exhibit long-range dependencies with finite memory content. Furthermore, we find that the latent representations learned by the RNNs are sensitive to external stimulation such as stress while the conventional univariate microstate measures (e.g., occurrence, mean duration, etc.) fail to capture such changes in brain dynamics. While RNNs cannot be configured to identify the specific discriminating patterns, they have the potential for learning the underlying temporal dynamics and are sensitive to sequence aberrations characterized by changes in metal processes. Empowered with the macroscopic understanding of the temporal dynamics that extends beyond short-term interactions, RNNs offer a reliable alternative for exploring system level brain dynamics using EEG microstate sequences.

Transcranial magnetic stimulation for obsessive-compulsive disorder and post-traumatic stress disorder: A comprehensive systematic review and analysis of therapeutic benefits, cortical targets, and psychopathophysiological mechanisms.

Transcranial magnetic stimulation (TMS) is a safe non-invasive treatment technique. We systematically reviewed randomised controlled trials (RCTs) applying TMS in obsessive compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) to analyse its therapeutic benefits and explore the relationship between cortical target and psychopathophysiology. We included 47 randomised controlled trials (35 for OCD) and found a 22.7 % symptom improvement for OCD and 29.4 % for PTSD. Eight cortical targets were investigated for OCD and four for PTSD, yielding similar results. Bilateral dlPFC-TMS exhibited the greatest symptom change (32.3 % for OCD, N = 4 studies; 35.7 % for PTSD, N = 1 studies), followed by right dlPFC-TMS (24.4 % for OCD, N = 8; 26.7 % for PTSD, N = 10), and left dlPFC-TMS (22.9 % for OCD, N = 6; 23.1 % for PTSD, N = 1). mPFC-TMS showed promising results, although evidence is limited (N = 2 studies each for OCD and PTSD) and findings for PTSD were conflicting. Despite clinical improvement, reviewed reports lacked a consistent and solid rationale for cortical target selection, revealing a gap in TMS research that complicates the interpretation of findings and hinders TMS development and optimisation. Future research should adopt a hypothesis-driven approach rather than relying solely on correlations from imaging studies, integrating neurobiological processes with affective, behavioural, and cognitive states, thereby doing justice to the complexity of human experience and mental illness.

Questionnaire-based approach to evaluate the convenience of rechargeable extracorporeal pulse generators for wireless spinal cord stimulation.

Spinal cord stimulation (SCS) has been utilized for more than 50 years to treat refractory neuropathic pain. Currently, SCS systems with fully implantable pulse generators (IPGs) represent the standard. New wireless extracorporeal SCS (wSCS) devices without IPGs promise higher levels of comfort and convenience for patients. However, to date there are no studies on how charging and using this wSCS system affects patients and their therapy. This study is the first questionnaire-based survey on this topic focusing on patient experience. The trial was a single arm, open-label and mono-centric phase IV study. Standardized questionnaires were sent to all patients with a wSCS device in use at the time of trial. The primary endpoint was the convenience of the charging and wearing process scored on an ordinal scale from "very hard" (1) to "very easy" (5). Secondary endpoints included time needed for charging, the duration of stimulation per day and complication rates. Questionnaires of 6 out of 9 patients were returned and eligible for data analysis. The mean age of patients was 61.3 ± 6.7 (± SD) years. The duration of therapy was 20.3 ± 15.9 months (mean ± SD). The mean duration of daily stimulation was 17 ± 5.9 h (mean ± SD). n = 5 patients rated the overall convenience as "easy" (4) and n = 3 patients evaluated the effort of the charging process and wearing of the wSCS device as "low" (4). n = 5 patients considered the wearing and charging process as active participation in their therapy. n = 5 patients would choose an extracorporeal device again over a conventional SCS system. Early or late surgical complications did not occur in this patient collective. Overall, patients felt confident using extracorporeal wSCS devices without any complications. Effort to maintain therapy with this system was rated as low.

Deep brain stimulation for obsessive-compulsive disorder: A systematic review of randomised controlled trials.

Deep brain stimulation (DBS) is considered a promising intervention for treatment-resistant obsessive-compulsive disorder (trOCD). We conducted a systematic search to investigate the efficacy and safety of DBS for OCD. Primary outcomes included the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), adverse events (AE), and quality of life. We assessed affective state, global functioning, cognition, and tolerability as secondary outcomes. Eight studies comprising 80 patients with trOCD were analysed both individually and collectively. We found a pooled mean reduction in Y-BOCS of 38.68 %, indicating DBS could be considered an effective therapy for trOCD. Most AE were mild and transient, however there were five severe surgery-related AE: intracerebral haemorrhage in three patients and infection in two. Mood-related serious AE were one completed suicide, three suicide attempts in two patients, and suicidal thoughts and depression in four. Despite this, affective state improved following stimulation. Despite being limited by significant heterogeneity across studies, our review has shown DBS to be an effective treatment in otherwise trOCD. There is a need to standardise study methodology in future research.

fMRI Revealed Reduced Amygdala Activation after Nx4 in Mildly to Moderately Stressed Healthy Volunteers in a Randomized, Placebo-Controlled, Cross-Over Trial.

Social stress contributes to major societal health burdens, such as anxiety disorders and nervousness. Nx4 has been found to modulate stress responses. We investigated whether dampening of such responses is associated with neuronal correlates in brain regions involved in stress and anxiety. In a randomized, placebo-controlled, double-blind, cross-over trial, 39 healthy males took a single dose (three tablets) of either placebo or Nx4, 40 to 60 minutes before an fMRI scan session. We here report on drug effects on amygdala responses during a face-matching task, which was performed during a complex test battery further including resting-state brain connectivity and a social stress experiment. The first of the Primary Outcomes, defined in a hierarchical order, concerned reduced amygdala effects after intake of verum compared to placebo. We found a statistically significant reduction in differential activations in the left amygdala for the contrast negative faces versus forms during verum versus placebo condition. Our results indicate that effects of Nx4 can be monitored in the brain. Previously noted effects on stress responses may thus be modulated by affective brain regions including the amygdala.