PyHFO: lightweight deep learning-powered end-to-end high-frequency oscillations analysis application.

OBJECTIVE: This study aims to develop and validate an end-to-end software platform, PyHFO, that streamlines the application of deep learning methodologies in detecting neurophysiological biomarkers for epileptogenic zones from EEG recordings. Methods: We introduced PyHFO, which enables time-efficient HFO detection algorithms like short-term energy (STE) and Montreal Neurological Institute and Hospital (MNI) detectors. It incorporates deep learning models for artifact and HFO with spike classification, designed to operate efficiently on standard computer hardware. Main results: The validation of PyHFO was conducted on three separate datasets: the first comprised solely of grid/strip electrodes, the second a combination of grid/strip and depth electrodes, and the third derived from rodent studies, which sampled the neocortex and hippocampus using depth electrodes. PyHFO demonstrated an ability to handle datasets efficiently, with optimization techniques enabling it to achieve speeds up to 50 times faster than traditional HFO detection applications. Users have the flexibility to employ our pre-trained deep learning model or use their EEG data for custom model training. Significance: PyHFO successfully bridges the computational challenge faced in applying deep learning techniques to EEG data analysis in epilepsy studies, presenting a feasible solution for both clinical and research settings. By offering a user-friendly and computationally efficient platform, PyHFO paves the way for broader adoption of advanced EEG data analysis tools in clinical practice and fosters potential for large-scale research collaborations.

Bedside clinical assessment of patients with common upper limb tremor and algorithmic approach.

The diagnostic approach for patients with tremor is challenging due to the complex and overlapping phenotypes among tremor syndromes. The first step in the evaluation of tremor is to identify the tremulous movement and exclude the tremor mimics. The second step is to classify the tremor syndrome based on the characteristics of tremor from historical clues and focused examination (Axis 1). Comprehensive tremor examinations involve the assessment of tremor in different conditions (rest, action or mixed, position or task-specific), distribution of tremor (upper limb, lower limb, head, jaw), positive signs for functional tremor (FT) if suspected (distractibility, entrainment, co-contraction), and associated neurological signs including parkinsonism, dystonic posture, cerebellar/brainstem signs, neuropathy, and cognitive impairment. A pivotal feature in this step is to determine any distinct feature of a specific isolated or combined tremor syndrome. In this review, we propose an algorithm to assess upper limb tremors. Ancillary testing should be performed if clinical evaluation is unclear. The choice of investigation depends on the types of tremors considered to narrow down the spectrum of etiology (Axis 2). Laboratory blood tests are considered for acute onset and acute worsening of tremors, while structural neuroimaging is indicated in unilateral tremors with acute onset, nonclassical presentations, and a combination of neurological symptoms. Neurophysiological study is an important tool that aids in distinguishing between tremor and myoclonus, etiology of tremor and document specific signs of FT. Treatment is mainly symptomatic based depending on the etiology of the tremor and the patient's disabilities.

Investigating cortical excitability and inhibition in patients with schizophrenia: A TMS-EEG study.

BACKGROUND: Transcranial magnetic stimulation (TMS) combined with electromyography (EMG) has widely been used as a non-invasive brain stimulation tool to assess excitation/inhibition (E/I) balance. E/I imbalance is a putative mechanism underlying symptoms in patients with schizophrenia. Combined TMS-electroencephalography (TMS-EEG) provides a detailed examination of cortical excitability to assess the pathophysiology of schizophrenia. This study aimed to investigate differences in TMS-evoked potentials (TEPs), TMS-related spectral perturbations (TRSP) and intertrial coherence (ITC) between patients with schizophrenia and healthy controls. MATERIALS AND METHODS: TMS was applied over the motor cortex during EEG recording. Differences in TEPs, TRSP and ITC between the patient and healthy subjects were analysed for all electrodes at each time point, by applying multiple independent sample t-tests with a cluster-based permutation analysis to correct for multiple comparisons. RESULTS: Patients demonstrated significantly reduced amplitudes of early and late TEP components compared to healthy controls. Patients also showed a significant reduction of early delta (50-160 ms) and theta TRSP (30-250ms),followed by a reduction in alpha and beta suppression (220-560 ms; 190-420 ms). Patients showed a reduction of both early (50-110 ms) gamma increase and later (180-230 ms) gamma suppression. Finally, the ITC was significantly lower in patients in the alpha band, from 30 to 260 ms. CONCLUSION: Our findings support the putative role of impaired GABA-receptor mediated inhibition in schizophrenia impacting excitatory neurotransmission. Further studies can usefully elucidate mechanisms underlying specific symptoms clusters using TMS-EEG biometrics.

Anatomical damages in the spinal nerve roots and the spinal cord after brachial plexus injury: descriptive study from a cohort of consecutive patients who underwent DREZ-lesioning for pain-practical implications.

BACKGROUND: Systematic descriptions of anatomical damage after brachial plexus injury (BPI) at the intradural level have been scarcely reported in detail. However, considering these damages, not only in the spinal nerve roots but also in the spinal cord itself, is crucial in determining the appropriate surgical approach to restore upper limb function and address refractory pain. Therefore, the authors present a descriptive study focusing on intradural findings observed during microsurgical DREZ-lesioning. METHODS: This study enrolled 19 consecutive patients under the same protocol. Microsurgical observation through exposure of C4 to Th1 medullary segments allowed to describe the lesions in spinal nerve roots, meninges, and spinal cord. Electrical stimulation of the ventral roots checked the muscle responses. RESULTS: Extensive damage was observed among the 114 explored roots (six roots per patient), with only 21 (18.4%) ventral (VR) and 17 (14.9%) dorsal (DR) roots retaining all rootlets intact. Damage distribution varied, with the most frequent impairments in C6 VRs (18 patients) and the least in Th1 VRs (14 patients), while in all the 19 patients for the C6 DRs (the most frequently impaired) and in 14 patients for Th1 DRs (the less impaired). C4 roots were found damaged in 12 patients. Total or partial avulsions affected 63.3% and 69.8% of DRs and VRs, respectively, while 15.8% and 14.0% of the 114 DRs and VRs were atrophic, maintaining muscle responses to stimulation in half of those VRs. Pseudomeningoceles were present in 11 patients but absent in 46% of avulsed roots. Adhesive arachnoiditis was noted in 12 patients, and dorsal horn parenchymal alterations in 10. CONCLUSIONS: Knowledge of intradural lesions post-BPI helps in guiding surgical indications for repair and functional neurosurgery for pain control.

Contributions of narrow- and broad-spiking prefrontal and parietal neurons on working memory tasks.

Neurons that generate persistent activity in the primate dorsolateral prefrontal and posterior parietal cortex have been shown to be predictive of behavior in working memory tasks, though subtle differences between them have been observed in how information is represented. The role of different neuron types in each of these areas has not been investigated at depth. We thus compared the activity of neurons classified as narrow-spiking, putative interneurons, and broad-spiking, putative pyramidal neurons, recorded from the dorsolateral prefrontal and posterior parietal cortex of male monkeys, to analyze their role in the maintenance of working memory. Our results demonstrate that narrow-spiking neurons are active during a range of tasks and generate persistent activity during the delay period over which stimuli need to be maintained in memory. Furthermore, the activity of narrow-spiking neurons was predictive of the subject's recall no less than that of broad-spiking neurons, which are exclusively projection neurons in the cortex. Our results show that putative interneurons play an active role during the maintenance of working memory and shed light onto the fundamental neural circuits that determine subjects' memories and judgments.

A revised approach for electrodiagnosis-based severity classification in carpal tunnel syndrome.

BACKGROUND: An electrodiagnostic evaluation is conducted to diagnose carpal tunnel syndrome (CTS) and evaluate its severity. OBJECTIVE: This study proposes a revised approach for classifying the severity of electrophysiological findings for patients with CTS. METHODS: This retrospective cross-sectional study included patients with CTS confirmed through electrodiagnostic evaluations. Based on the Stevens' classification, the patients were divided into three groups (mild/moderate/severe). A new intermediate group was defined to identify patients with normal motor nerve conduction studies and abnormal electromyographic results. CTS pain was evaluated using a numeric rate scale. Physical examinations and sonographic evaluation were performed to detect anatomical abnormalities. RESULTS: Overall, 1,069 CTS hands of 850 CTS patients were included. The mean age was 57.9 ± 10.8 years, and 336 (39.5%) were men. There were 522 (48.8%) mild cases; 281 (26.3%) moderate cases; and 266 (24.9%) severe cases. In the severe group, 49 cases were reclassified into the intermediate group. The median cross-sectional area in the intermediate group significantly differed from that in the severe group. However, the pain score significantly differed from that of the moderate group. CONCLUSION: The intermediate CTS group showed clinical features that were intermediate to those of the moderate and severe CTS groups.

Neurophysiological Characteristics in Type II and Type III 5q Spinal Muscular Atrophy Patients: Impact of Nusinersen Treatment.

Objective: This study aimed to observe the neurophysiological characteristics of type II and type III 5q spinal muscular atrophy (SMA) patients and the changes in peripheral motor nerve electrophysiology after Nusinersen treatment, as well as the influencing factors. Methods: This single-center retrospective case-control study collected clinical data and peripheral motor nerve CMAP parameters from 42 5qSMA patients and 42 healthy controls at the Second Affiliated Hospital of Xi'an Jiaotong University (January 2021 to December 2022). It evaluated changes in motor function and CMAP amplitude before and after Nusinersen treatment. Results: Our investigation encompassed all symptomatic and genetically confirmed SMA patients, consisting of 32 type II and 10 type III cases, with a median age of 57 months (29.5 to 96 months). Comparative analysis with healthy controls revealed substantial reductions in CMAP amplitudes across various nerves in both type II and type III patients. Despite the administration of Nusinersen treatment for 6 or 14 months to the entire cohort, discernible alterations in motor nerve amplitudes were not observed, except for a significant improvement in younger patients (≤36 months) at the 14-month mark. Further scrutiny within the type II subgroup unveiled that individuals with a disease duration ≤12 months experienced a noteworthy upswing in femoral nerve amplitude, a statistically significant difference when compared to those with >12 months of disease duration. Conclusion: Motor nerve amplitudes were significantly decreased in type II and type III 5q SMA patients compared to healthy controls. Nusinersen treatment showed better improvement in motor nerve amplitudes in younger age groups and those with shorter disease duration, indicating a treatment-time dependence.

Effects of bi-hemispheric anodal transcranial direct current stimulation on soccer player performance: a triple-blinded, controlled, and randomized study.

The search for increased performance and physical performance are linked to the use of ergogenic resources. The vertical jump is one of the measures commonly used to evaluate the performance of lower limbs in athletes. Transcranial direct current stimulation (tDCS) is a non-invasive, safe, economically viable technique that can modulate cortical excitability, which can influence the increase in the performance of athletes in general. This study aimed to investigate whether the use of tDCS on the primary motor cortex (M1) improves the performance of soccer players. A cross-sectional study was conducted. Twenty-seven players were randomized into three groups: Active tDCS group (n = 9), Sham group (n = 9), and control group (n = 9). Stimulation was applied at 2 mA for 15 min using a cephalic mount. Visual Pain Scale (VAS) and Subjective Recovery Scale (SRS) were monitored before and after tDCS. In addition, the participants performed the Countermovement Jump (CMJ) before and after the stimulation intercalated with Heart Rate (HR) and Rating of Perceived Exertion (RPE CR-10). No differences were found in any of the performance variables analyzed (p > 0.05) nor in the responses of HR (p > 0.05), RPE (p > 0.05), VAS (p > 0.05), and SRS (p > 0.05) between groups. The tDCS in M1 did not change the performance of the vertical jump, and there was no improvement in the subjective scales. New studies should also be developed with different stimulus intensities in different cortical areas and sports modalities.

Chronic Visual Abnormality in an Elderly Patient With Temporal Lobe Epilepsy.

A 79-year-old woman visited our department for chronic visual field abnormalities with a floating sensation for two months. Neurological and ophthalmologic examinations yielded normal results, except for brain MRI indicating left hippocampal atrophy. Cognitive function tests were normal. EEG revealed frequent spikes and slow waves in the left frontotemporal region, corroborated by reduced accumulation in 123I-iomazenil single photon emission computed tomography. A diagnosis of temporal lobe epilepsy was established, and treatment with lacosamide resulted in a remarkable improvement in symptoms and EEG findings. Mild focal seizures from the temporal region might cause mild impaired awareness, resulting in the patient's report as a sensation of uncertainty between the self and the outside world, mimicking ophthalmologic abnormalities. The repeated nature of the seizures contributed to the absence of the term "transient" in symptom description. Diagnosing epilepsy in the elderly proves challenging due to nonspecific complaints.

The role of the nucleus basalis of Meynert in neuromodulation therapy: a systematic review from the perspective of neural network oscillations.

As a crucial component of the cerebral cholinergic system and the Papez circuit in the basal forebrain, dysfunction of the nucleus basalis of Meynert (NBM) is associated with various neurodegenerative disorders. However, no drugs, including existing cholinesterase inhibitors, have been shown to reverse this dysfunction. Due to advancements in neuromodulation technology, researchers are exploring the use of deep brain stimulation (DBS) therapy targeting the NBM (NBM-DBS) to treat mental and neurological disorders as well as the related mechanisms. Herein, we provided an update on the research progress on cognition-related neural network oscillations and complex anatomical and projective relationships between the NBM and other cognitive structures and circuits. Furthermore, we reviewed previous animal studies of NBM lesions, NBM-DBS models, and clinical case studies to summarize the important functions of the NBM in neuromodulation. In addition to elucidating the mechanism of the NBM neural network, future research should focus on to other types of neurons in the NBM, despite the fact that cholinergic neurons are still the key target for cell type-specific activation by DBS.

Neurophysiological findings in conus medullaris infarction-a case report and systematic review of the literature.

INTRODUCTION: Conus medullaris infarction (CMI) is a rare vascular phenomenon that has been scarcely reported in the literature. While previous studies have described the clinical and radiological features of CMI, little attention has been paid to its associated neurophysiological findings. METHODS: We present a case of idiopathic CMI and its neurophysiological findings, then present our findings from a systematic review of other reports of CMI with neurophysiological features found via PubMed search. RESULTS: Nine articles describing ten cases of CMI with associated neurophysiological data were found, in addition to our case. Out of all 11 cases, 7 cases (64%) had absent F-waves on the first nerve conduction study (NCS) performed as early as 4 h after onset, 5 of whom demonstrated reappearance of F-waves on subsequent follow-up NCS. Seven patients (64%) had diminished compound muscle action potentials (CMAPs), which was usually detectable on NCS performed between day 8 and day 18 of onset. None of them showed recovery of CMAPs in follow-up studies. Four patients (36%) had absent H-reflexes and two patients (18%) had sensory abnormalities. Electromyography (EMG) was reported in seven patients (64%), showing reduced recruitment as early as day 1 of onset, and denervation potentials as early as 4 weeks after onset. CONCLUSION: Absent F-waves and diminished CMAPs are the most common NCS abnormalities in CMI. Absent F-waves are detectable very early but tend to recover on subsequent NCS, while diminished CMAPs are detectable later but do not seem to resolve. Further research to determine the utility of neurophysiological studies in CMI diagnosis and prognostication is needed.

New stimulation procedures for language mapping in stereo-EEG.

OBJECTIVE: Cortical intracerebral electrical stimulation is an important tool for language mapping in the presurgical work-up of patients with drug-resistant focal epilepsy. Language mapping with stereo-electroencephalography (EEG) is usually performed by high-frequency stimulations (HFS: 50 Hz), whereas low-frequency stimulations (LFS: 1 Hz) are usually considered useful for primary cortices mapping. Little is known in literature about "intermediate" frequencies (IFS: 6-15 Hz). Our objective is to explore the clinical usefulness of IFS in language mapping and identify factors, beyond the electrical parameters, that impact the mapping. METHODS: We studied 23 patients submitted to stereo-EEG for presurgical evaluation. Language mapping was performed in the anterior, posterior and/or basal language region of the dominant hemisphere for language. We included all contact positions within these regions stimulated by HFS (50 Hz, 5 s, 1-3 mA) and IFS (6-15 Hz, 15 s, 5 mA). We compared the capability of both stimulation methods to induce a language deficit without afterdischarges (ADs), and we analyzed factors related to clinical examination, region, and stimulation technique by multivariate analysis. RESULTS: A total of 211 stimulations (98 HFS, 113 IFS) in 70 cortical sites within the anterior (84 stimulations), posterior (137), and basal language region (60) were included. IFS induced more frequently language deficits not associated to AD compared to HFS (37.1% vs 25.7%, p = .0043), whereas HFS provoked more diffuse AD (34.7% vs 15.0%, p = .001). Investigating multiple language functions increased the probability of revealing a deficit (odds ratio [OR] 3.16, p = .0016), independently of the stimulation method. SIGNIFICANCE: IFS are valuable for language mapping, thereby improving the probability of inducing a clinical deficit not accompanied by an AD. The completeness of the clinical examination independently affects the sensitivity of the mapping. IFS are a new tool with potential usefulness for the cortical mapping of other associative cortical regions.

Unraveling the threads of stability: A review of the neurophysiology of postural control in Parkinson's disease.

Postural instability is a detrimental and often treatment-refractory symptom of Parkinson's disease. While many existing studies quantify the biomechanical deficits among various postural domains (static, anticipatory, and reactive) in this population, less is known regarding the neural network dysfunctions underlying these phenomena. This review will summarize current studies on the cortical and subcortical neural activities during postural responses in healthy subjects and those with Parkinson's disease. We will also review the effects of current therapies, including neuromodulation and feedback-based wearable devices, on postural instability symptoms. With recent advances in implantable devices that allow chronic, ambulatory neural data collection from patients with Parkinson's disease, combined with sensors that can quantify biomechanical measurements of postural responses, future work using these devices will enable better understanding of the neural mechanisms of postural control. Bridging this knowledge gap will be the critical first step towards developing novel neuromodulatory interventions to enhance the treatment of postural instability in Parkinson's disease.

Neurophysiological characterization of oropharyngeal dysphagia in older patients.

OBJECTIVE: To characterize swallowing biomechanics and neurophysiology in older patients with oropharyngeal dysphagia (OD). METHODS: Observational study in 12 young healthy volunteers (HV), 9 older HV (OHV) and 12 older patients with OD with no previous diseases causing OD (OOD). Swallowing biomechanics were measured by videofluoroscopy, neurophysiology with pharyngeal sensory (pSEP) and motor evoked-potentials (pMEP) to intrapharyngeal electrical and transcranial magnetic stimulation (TMS), respectively, and salivary neuropeptides with enzyme-linked immunosorbent assay (ELISA). RESULTS: 83.3% of OOD patients had unsafe swallows (Penetration-Aspiration scale = 4.3 ± 2.1; p < 0.0001) with delayed time to laryngeal vestibule closure (362.5 ± 73.3 ms; p < 0.0001) compared to both HV groups. OOD patients had: (a) higher pharyngeal sensory threshold (p = 0.009) and delayed pSEP P1 and N2 latencies (p < 0.05 vs HV) to electrical stimulus; and (b) higher pharyngeal motor thresholds to TMS in both hemispheres (p < 0.05) and delayed pMEPs latencies (right, p < 0.0001 HV vs OHV/OOD; left, p < 0.0001 HV vs OHV/OOD). CONCLUSIONS: OOD patients have unsafe swallow and delayed swallowing biomechanics, pharyngeal hypoesthesia with disrupted conduction of pharyngeal sensory inputs, and reduced excitability and delayed cortical motor response. SIGNIFICANCE: These findings suggest new elements in the pathophysiology of aging-associated OD and herald new and more specific neurorehabilitation treatments for these patients.

Walter Eichler and his role in the development of electroneurography.

Walter Eichler (1904-1942) performed the first in situ nerve conduction studies in humans. Eichler's work has been largely overlooked and there have been no biographical accounts written of him. His 1937 paper, Über die Ableitung der Aktionspotentiale vom menschlichen Nerven in situ (On the recording of the action potentials from human nerves in situ) was translated and reviewed. Archival material was obtained on his career that was housed predominantly at the University of Freiburg im Breisgau. He had memberships in Nazi organizations but did not appear to be politically active. During his brief career, he constructed novel equipment and established seminal principles for performing nerve conductions on humans. The authors repeated his experiment in the ulnar nerve, which duplicated Eichler's findings. His recordings were quite remarkable given advances in technology. In summary, the Eichler paper is the first study in the development of in situ clinical electroneurography in humans. Many of his procedural observations are still fundamental in the current practice of electroneurography. As best can be determined, his study in humans did not appear ethically compromised. Although Eichler's personal background remains open to question, his paper is a seminal study in the history and development of clinical electroneurography.Abbreviations: AP: Action potential; C: Capacitor; CNP: Compound nerve potential; DC: Direct current; E1: Preferred term for active electrode; E2: Preferred term for reference electrode; NSDÄB: Nationalsozialistische Deutsche NSD-Ärtzebund (National Socialist German Doctors' League; NSDAP: Nationalsozialistische Deutsche Arbeiterpartei (National Socialist German Workers' Party/ Nazi Party); SS: Schutzstaffel (Protective Echelon or Squad of the Nazi party).

Electrophysiology and 3D-imaging reveal properties of human intracardiac neurons and increased excitability with atrial fibrillation.

Altered autonomic input to the heart plays a major role in atrial fibrillation (AF). Autonomic neurons termed ganglionated plexi (GP) are clustered on the heart surface to provide the last point of neural control of cardiac function. To date the properties of GP neurons in humans are unknown. Here we have addressed this knowledge gap in human GP neuron structure and physiology in patients with and without AF. Human right atrial GP neurons embedded in epicardial adipose tissue were excised during open heart surgery performed on both non-AF and AF patients and then characterised physiologically by whole cell patch clamp techniques. Structural analysis was also performed after fixation at both the single cell and at the entire GP levels via three-dimensional confocal imaging. Human GP neurons were found to exhibit unique properties and structural complexity with branched neurite outgrowth. Significant differences in excitability were revealed between AF and non-AF GP neurons as measured by lower current to induce action potential firing, a reduced occurrence of low action potential firing rates, decreased accommodation and increased synaptic density. Visualisation of entire GPs showed almost all neurons are cholinergic with a small proportion of noradrenergic and dual phenotype neurons. Phenotypic distribution differences occurred with AF including decreased cholinergic and dual phenotype neurons, and increased noradrenergic neurons. These data show both functional and structural differences occur between GP neurons from patients with and without AF, highlighting that cellular plasticity occurs in neural input to the heart that could alter autonomic influence on atrial function. KEY POINTS: The autonomic nervous system plays a critical role in regulating heart rhythm and the initiation of AF; however, the structural and functional properties of human autonomic neurons in the autonomic ganglionated plexi (GP) remain unknown. Here we perform the first whole cell patch clamp electrophysiological and large tissue confocal imaging analysis of these neurons from patients with and without AF. Our data show human GP neurons are functionally and structurally complex. Measurements of action potential kinetics show higher excitability in GP neurons from AF patients as measured by lower current to induce action potential firing, reduced low firing action potential rates, and decreased action potential accommodation. Confocal imaging shows increased synaptic density and noradrenergic phenotypes in patients with AF. Both functional and structural differences occur in GP neurons from patients with AF that could alter autonomic influence on atrial rhythm.

Contribution of basal ganglia activity to REM sleep disorder in Parkinson's disease.

BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder (RBD) is one of the most common sleep problems and represents a key prodromal marker in Parkinson's disease (PD). It remains unclear whether and how basal ganglia nuclei, structures that are directly involved in the pathology of PD, are implicated in the occurrence of RBD. METHOD: Here, in parallel with whole-night video polysomnography, we recorded local field potentials from two major basal ganglia structures, the globus pallidus internus and subthalamic nucleus, in two cohorts of patients with PD who had varied severity of RBD. Basal ganglia oscillatory patterns during RBD and REM sleep without atonia were analysed and compared with another age-matched cohort of patients with dystonia that served as controls. RESULTS: We found that beta power in both basal ganglia nuclei was specifically elevated during REM sleep without atonia in patients with PD, but not in dystonia. Basal ganglia beta power during REM sleep positively correlated with the extent of atonia loss, with beta elevation preceding the activation of chin electromyogram activities by ~200 ms. The connectivity between basal ganglia beta power and chin muscular activities during REM sleep was significantly correlated with the clinical severity of RBD in PD. CONCLUSIONS: These findings support that basal ganglia activities are associated with if not directly contribute to the occurrence of RBD in PD. Our study expands the understanding of the role basal ganglia played in RBD and may foster improved therapies for RBD by interrupting the basal ganglia-muscular communication during REM sleep in PD.