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OBJECTIVE Percutaneous radiofrequency rhizotomy is a common procedure for trigeminal neuralgia (TN) that creates thermocoagulative lesions in the trigeminal ganglion. Lesioning parameters for the procedure are left to the individual surgeon’s discretion, and published guidance is primarily anecdotal. The purpose of this work was to assess the role of lesioning temperature on long-term surgical outcomes. METHODS This was a retrospective analysis of patients who underwent percutaneous radiofrequency rhizotomy from 2009 to 2020. Patient data, including demographics, disease presentation, surgical treatment, and outcomes, were collected from medical records. The primary endpoint was the recurrence of TN pain. Univariate and multivariate Cox proportional hazards regressions were used to assess the impact of chosen covariates on pain-free survival. RESULTS A total of 280 patients who had undergone 464 procedures were included in the analysis. Overall, roughly 80% of patients who underwent rhizotomy would have a recurrence within 10 years. Lower lesion temperature was predictive of longer periods without pain recurrence (HR 1.05, p < 0.001). The inclusion of lesion time, postoperative numbness, prior history of radiofrequency rhizotomy, surgeon, and multiple sclerosis as confounding variables did not affect the hazard ratio or the statistical significance of this finding. Postoperative numbness and the absence of multiple sclerosis were significant protective factors in the model. CONCLUSIONS The study findings suggest that lower lesion temperatures and, separately, postoperative numbness result in improved long-term outcomes for patients with TN who undergo percutaneous radiofrequency rhizotomies. Given the limitations of retrospective analysis, the authors suggest that a prospective multisite clinical trial testing lesion temperatures would provide definitive guidance on this issue with specific recommendations about the number needed to treat and trial design.

BackgroundTime series analysis is critical for understanding brain signals and their relationship to behavior and cognition. Cluster-based permutation tests (CBPT) are commonly used to analyze a variety of electrophysiological signals including EEG, MEG, ECoG, and sEEG data withouta prioriassumptions about specific temporal effects. However, two major limitations of CBPT include the inability to directly analyze experiments with multiple fixed effects and the inability to account for random effects (e.g. variability across subjects). Here, we propose a flexible multi-step hypothesis testing strategy using CBPT with Linear Mixed Effects Models (LMEs) and Generalized Linear Mixed Effects Models (GLMEs) that can be applied to a wide range of experimental designs and data types.MethodsWe first evaluate the statistical robustness of LMEs and GLMEs using simulated data distributions. Second, we apply a multi-step hypothesis testing strategy to analyze ERPs and broadband power signals extracted from human ECoG recordings collected during a simple image viewing experiment with image category and novelty as fixed effects. Third, we assess the statistical power differences between analyzing signals with CBPT using LMEs compared to CBPT using separate t-tests run on each fixed effect through simulations that emulate broadband power signals. Finally, we apply CBPT using GLMEs to high-gamma burst data to demonstrate the extension of the proposed method to the analysis of nonlinear data.ResultsFirst, we found that LMEs and GLMEs are robust statistical models. In simple simulations LMEs produced highly congruent results with other appropriately applied linear statistical models, but LMEs outperformed many linear statistical models in the analysis of “suboptimal” data and maintained power better than analyzing individual fixed effects with separate t-tests. GLMEs also performed similarly to other nonlinear statistical models. Second, in real world human ECoG data, LMEs performed at least as well as separate t-tests when applied to predefined time windows or when used in conjunction with CBPT. Additionally, fixed effects time courses extracted with CBPT using LMEs from group-level models of pseudo-populations replicated latency effects found in individual category-selective channels. Third, analysis of simulated broadband power signals demonstrated that CBPT using LMEs was superior to CBPT using separate t-tests in identifying time windows with significant fixed effects especially for small effect sizes. Lastly, the analysis of high-gamma burst data using CBPT with GLMEs produced results consistent with CBPT using LMEs applied to broadband power data.ConclusionsWe propose a general approach for statistical analysis of electrophysiological data using CBPT in conjunction with LMEs and GLMEs. We demonstrate that this method is robust for experiments with multiple fixed effects and applicable to the analysis of linearandnonlinear data. Our methodology maximizes the statistical power available in a dataset across multiple experimental variables while accounting for hierarchical random effects and controlling FWER across fixed effects. This approach substantially improves power and accuracy leading to better reproducibility. Additionally, CBPT using LMEs and GLMEs can be used to analyze individual channels or pseudo-population data for the comparison of functional or anatomical groups of data.Highlights● Combining CBPT with GLMEs allows statistical analysis to match experimental design.● CBPT with GLMEs accounts for subject variability and hierarchical random effects.● The proposed method maintains control of type I error, type II error, and FWER.● CBPT with GLMEs can be applied to individual channels and pseudo-population data.

Central pain disorders, such as central post-stroke pain, remain clinically challenging to treat, despite many decades of pharmacological advances and the evolution of neuromodulation. For treatment refractory cases, previous studies have highlighted some benefits of cortical stimulation. Recent advances in new targets for pain and the optimization of neuromodulation encouraged our group to develop a dual cortical target approach paired with Bayesian optimization to provide a personalized treatment. Here, we present a case report of a woman who developed left-sided facial pain after multiple thalamic strokes. All previous pharmacologic and interventional treatments failed to mitigate the pain, leaving her incapacitated due to pain and medication side effects. She subsequently underwent a single burr hole for placement of motor cortex (M1) and dorsolateral prefrontal cortex (dlPFC) paddles for stimulation with externalization. By using Bayesian optimization to find optimal stimulation parameters and stimulation sites, we were able to reduce pain from an 8.5/10 to a 0/10 during a 5-day inpatient stay, with pain staying at or below a 2/10 one-month post-procedure. We found optimal treatment to be simultaneous stimulation of M1 and dlPFC without any evidence of seizure induction. In addition, we found no worsening in cognitive performance during a working memory task with dlPFC stimulation. This personalized approach using Bayesian optimization may provide a new foundation for treating central pain and other functional disorders through systematic evaluation of stimulation parameters.

Epidural spinal cord stimulation (eSCS) has shown promise for restoring some volitional motor control after spinal cord injury (SCI). Maximizing therapeutic response requires effective spatial stimulation generated through careful configuration of anodes and cathodes on the eSCS lead. By exploring the way the spatial distribution of low frequency stimulation affects muscle activation patterns, we investigated the spatial specificity of stimulation-evoked responses for targeted muscle groups for restoration after chronic SCI (cSCI) in participants in the Epidural Stimulation After Neurologic Damage (E-STAND) trial.Fifteen participants with Abbreviated Injury Scale A cSCI from the E-STAND study were evaluated with a wide range of bipolar spatial patterns. Surface electromyography captured stimulation-evoked responses from the rectus abdominis (RA), intercostal, paraspinal, iliopsoas, rectus femoris (RF), tibialis anterior (TA), extensor hallucis longus (EHL), and gastrocnemius muscle groups bilaterally. Peak-to-peak amplitudes were analyzed for each pulse across muscles. Stimulation patterns with dipoles parallel (vertical configurations), perpendicular (horizontal configurations), and oblique (diagonal configurations) relative to the rostral-caudal axis were evaluated.Cathodic stimulation in the transverse plane indicated ipsilaterally biased activation in RA, intercostal, paraspinal, iliopsoas, RF, TA, EHL, and gastrocnemius muscles (p 0.05). We found that caudal cathodic stimulation was significantly more activating only in the RF and EHL muscle groups than in the rostral (p 0.037 and p 0.006, respectively). Oblique stimulation was found to be more activating in the RA, intercostal, paraspinal, iliopsoas, and TA muscle groups than in the transverse (p 0.05).Cathodic stimulation provides uniform specificity for targeting laterality. Few muscle groups responded specifically to variation in rostral/caudal stimulation, and oblique stimulation improved stimulation responses when compared with horizontal configurations. These relations may enable tailored targeting of muscle groups, but the surprising amount of variation observed suggests that monitoring these evoked muscle responses will play a key role in this tailoring process.The Clinicaltrials.gov registration number for the study is NCT03026816.

Visual review of intracranial electroencephalography (iEEG) is often an essential component for defining the zone of resection for epilepsy surgery. Unsupervised approaches using machine and deep learning are being employed to identify seizure onset zones (SOZs). This prompts a more comprehensive understanding of the reliability of visual review as a reference standard. We sought to summarize existing evidence on the reliability of visual review of iEEG in defining the SOZ for patients undergoing surgical workup and understand its implications for algorithm accuracy for SOZ prediction. We performed a systematic literature review on the reliability of determining the SOZ by visual inspection of iEEG in accordance with best practices. Searches included MEDLINE, Embase, Cochrane Library, and Web of Science on May 8, 2022. We included studies with a quantitative reliability assessment within or between observers. Risk of bias assessment was performed with QUADAS-2. A model was developed to estimate the effect of Cohen kappa on the maximum possible accuracy for any algorithm detecting the SOZ. Two thousand three hundred thirty-eight articles were identified and evaluated, of which one met inclusion criteria. This study assessed reliability between two reviewers for 10 patients with temporal lobe epilepsy and found a kappa of .80. These limited data were used to model the maximum accuracy of automated methods. For a hypothetical algorithm that is 100% accurate to the ground truth, the maximum accuracy modeled with a Cohen kappa of .8 ranged from .60 to .85 (F-2). The reliability of reviewing iEEG to localize the SOZ has been evaluated only in a small sample of patients with methodologic limitations. The ability of any algorithm to estimate the SOZ is notably limited by the reliability of iEEG interpretation. We acknowledge practical limitations of rigorous reliability analysis, and we propose design characteristics and study questions to further investigate reliability.

Multiple studies have corroborated restored volitional motor control after motor-complete spinal cord injury (SCI) through the use of spinal cord stimulation (SCS/eSCS) but rigorous quantitative descriptions have been lacking. Using a structured surface electromyogram based (sEMG) task with and without SCS during the Epidural Stimulation After Neurological Damage (ESTAND) study in participants with chronic, motor and sensory complete SCI, we investigated muscle activity complexity and muscle synergies to better characterize neuro-muscular control.In addition, competition exists between the task and neural origin hypotheses underlying muscle synergies, and this analysis in humans with motor and sensory complete chronic injury provided an opportunity to test these hypotheses. Muscle activity complexity was computed with Higuchi Fractal Dimensional analysis (HFD), and muscle synergies were estimated using non-negative matrix factorization (NNMF) in six participants with AIS A chronic SCI. We found that the complexity of muscle activity is immediately reduced with SCS in the SCI participants. We also found that over the follow-up sessions, the muscle synergy structure of the SCI participants became more defined, and the number of synergies decreased over time, indicating improved coordination between the muscle groups. Lastly, we found that the muscle synergies were restored with SCS, supporting the neural hypothesis of muscle synergies. We conclude that SCS restores muscle movements and muscle synergies that are distinct from healthy, able-bodied controls.

It has been over 1 year since we observed the policing of the George Floyd protests in the United States [R. R. Hardeman, E. M. Medina, R. W. Boyd, N. Engl. J. Med. 383, 197–199 (2020)]. Multiple injury reports emerged in medical journals, and the scientific community called for law enforcement to discontinue the use of less-lethal weapons [E. A. Kaske et al. , N. Engl. J. Med . 384, 774–775 (2021) and K. A. Olson et al. , N. Engl. J. Med. 383, 1081–1083 (2020)]. Despite progress in research, policy change has not followed a similar pace. Although the reasoning for this discrepancy is multifactorial, failure to use appropriate language may be one contributing factor to the challenges faced in updating policies and practices. Here, we detail how language has the potential to influence thinking and decision-making, we discuss how the language of less-lethal weapons minimizes harm, and we provide a framework for naming conventions that acknowledges harm.

Lead migration (LM) after spinal cord stimulation (SCS) implantation surgery is the most common device-related complication. Our study of lead and implantable pulse generator (IPG) migration using a large administrative claims data base aims to understand rates, risk factors, and outcomes after SCS implantation.This retrospective cohort study used the IBM® MarketScan® (Armonk, NY) Commercial and Medicare Supplemental Databases from 2016 to 2018. Adult patients who underwent SCS surgical procedures with at least 90 days of follow-up were identified using Current Procedural Terminology (CPT®) codes. Patients with LM and IPG migration after SCS surgery were identified using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10 CM) codes. Patients who underwent revision surgery after SCS implantation were identified using the CPT codes and ICD-10 CM codes. In addition, patient characteristics associated with LM or IPG migration, the temporal relationship of migration diagnosis, and revision surgery were evaluated in the cohort. Continuous outcomes were compared between groups using the two-sample Student t-test. The Fisher exact test was used to compare categorical outcomes between groups.A total of 7322 patients (64.4% percutaneous SCS) underwent SCS surgery during the study period. A total of 141 patients (1.9%) had LM or IPG migration. Of those, 116 patients (1.6%) had LM only; 18 patients (0.2%) had IPG migration; and seven patients (0.1%) had LM and IPG migration. The mean duration for migration diagnosis after initial SCS implantation was 168 (±163.1) days. The mean duration to revision surgery after the migration diagnosis was 12.3 (±35.2) days only. Most patients with migration (105, 74.5%) underwent revision surgery. Only younger age (p = 0.02) was associated with migration in this study.LM and pulse generator migration that required revision surgery occurred in a small proportion of patients who underwent SCS surgical procedures.

Neurovascular compression (NVC) has been the primary hypothesis for the underlying mechanism of classical trigeminal neuralgia (TN). However, a substantial body of literature has emerged highlighting notable exceptions to this hypothesis. The purpose of this study is to assess the reliability and diagnostic accuracy of high resolution, high contrast MRI-determined neurovascular contact for TN.We performed a retrospective, randomized, and blinded parallel characterization of neurovascular interaction and diagnosis in a population of TN patients and controls using four expert reviewers. Performance statistics were calculated, as well as assessments for generalizability using shuffled bootstraps.Fair to moderate agreement (ICC: 0.32-0.68) about diagnosis between reviewers was observed using MRIs from 47 TN patients and 47 controls. On average reviewers performed no better than chance when diagnosing participants, with an accuracy of 0.57 (95% CI 0.40, 0.59) per patient.While MRI is useful in determining structural causes in secondary TN, expert reviewers do no better to only slightly better than chance with distinguishing TN with MRI, despite moderate agreement. Further, the causal role of NVC for TN is not clear, limiting the applicability of MRI to diagnose or prognosticate treatment of TN.

IntroductionCortical spreading depolarisation (CSD) is characterised by a near-complete loss of the ionic membrane potential of cortical neurons and glia propagating across the cerebral cortex, which generates a transient suppression of spontaneous neuronal activity. CSDs have become a recognised phenomenon that imparts ongoing secondary insults after brain injury. Studies delineating CSD generation and propagation in humans after traumatic brain injury (TBI) are lacking. Therefore, this study aims to determine the feasibility of using a multistrip electrode array to identify CSDs and characterise their propagation in space and time after TBI.Methods and analysisThis pilot, prospective observational study will enrol patients with TBI requiring therapeutic craniotomy or craniectomy. Subdural electrodes will be placed for continuous electrocorticography monitoring for seizures and CSDs as a research procedure, with surrogate informed consent obtained preoperatively. The propagation of CSDs relative to structural brain pathology will be mapped using reconstructed CT and electrophysiological cross-correlations. The novel use of multiple subdural strip electrodes in conjunction with brain morphometric segmentation is hypothesised to provide sufficient spatial information to characterise CSD propagation across the cerebral cortex and identify cortical foci giving rise to CSDs.Ethics and disseminationEthical approval for the study was obtained from the Hennepin Healthcare Research Institute’s ethics committee, HSR 17-4400, 25 October 2017 to present. Study findings will be submitted for publication in peer-reviewed journals and presented at scientific conferences.Trial registration numberNCT03321370.

IntroductionSpinal cord injury (SCI) leads to significant changes in morbidity, mortality and quality of life (QOL). Currently, there are no effective therapies to restore function after chronic SCI. Preliminary studies have indicated that epidural spinal cord stimulation (eSCS) is a promising therapy to improve motor control and autonomic function for patients with chronic SCI. The aim of this study is to assess the effects of tonic eSCS after chronic SCI on quantitative outcomes of volitional movement and cardiovascular function. Our secondary objective is to optimise spinal cord stimulation parameters for volitional movement.Methods and analysisThe Epidural Stimulation After Neurologic Damage (ESTAND) trial is a phase II single-site self-controlled trial of epidural stimulation with the goal of restoring volitional movement and autonomic function after motor complete SCI. Participants undergo epidural stimulator implantation and are followed up over 15 months while completing at-home, mobile application-based movement testing. The primary outcome measure integrates quantity of volitional movement and similarity to normal controls using the volitional response index (VRI) and the modified Brain Motor Control Assessment. The mobile application is a custom-designed platform to support participant response and a kinematic task to optimise the settings for each participant. The application optimises stimulation settings by evaluating the parameter space using movement data collected from the tablet application and accelerometers. A subgroup of participants with cardiovascular dysautonomia are included for optimisation of blood pressure stabilisation. Indirect effects of stimulation on cardiovascular function, pain, sexual function, bowel/bladder, QOL and psychiatric measures are analysed to assess generalisability of this targeted intervention.Ethics and disseminationThis study has been approved after full review by the Minneapolis Medical Research Foundation Institutional Review Board and by the Minneapolis VA Health Care System. This project has received Food and Drug Administration investigational device exemption approval. Trial results will be disseminated through peer-reviewed publications, conference presentations and seminars.Trial registration numberNCT03026816.

In order to prevent influx of highly enriched nuclear material throu-gh border checkpoints, new advanced detection schemes need to be developed. Typical issues faced in this context are sources with very low emission against a dominating natural background radiation. Sources are expected to be small and shielded and hence cannot be detected from measurements of radiation levels alone. We consider collimated and Compton-type measurements and propose a detection method that relies on the geometric singularity of small sources to distinguish them from the more uniform background. The method is characterized by high sensitivity and specificity and allows for assigning confidence probabilities of detection. The validity of our approach can be justified using properties of related techniques from medical imaging. Results of numerical simulations are presented for collimated and Compton-type measurements. The 2D case is considered in detail.