OBJECTIVE:To develop a high-density electrode system that defines the locations of surface electrodes to record neural activity of the human cervical spinal cord; standardizing high-density electrospinography (HD-ESG) recording methodology. METHODOLOGY:An electrode placement system (SC10X/U) was designed to divide the electrode space over the cervical and upper thoracic spinal cord, inspired by 10/10 EEG system. As proof of concept, a 64-channel system derived from SC10X/U was utilised to record the spinal evoked potentials in response to median nerve stimulation in ten healthy participants. RESULTS:SC10-X/U defines 76 surface electrode positions relative to anatomical references. It features a unique 10/10 system-compatible nomenclature for the locations. SC10X/U-derived HD-ESG system successfully recorded evoked spinal responses. Significant N13 and P9 potentials were observed. A post-stimulation latency of 13.2 ± 1.1 ms was observed for N13 spinal-potential. Topographic map of the N13 potential indicated an epicentre at C5-C7 dorsal-vertebral levels. CONCLUSION:The system defines electrode locations to promote standardized recordings across individuals and research centres. The evoked potentials recorded using the system conformed to the existing neurophysiological and neuroanatomical literature.s. SIGNIFICANCE:The proposed system addresses the gap of non-standardized multi-channel recording of neural signals from the upper spinal cord, facilitating reliable and reproducible recordings.

Abstract Brain microstates are a well-established method for the dynamic analysis of resting-state electroencephalogram (EEG). We observed four quasi-stable, transient and reoccurring resting-state topographies in the high density EEG data (128 electrodes, 3x2 min recording blocks). The four microstates were reliably observed across conditions: individuals with Amyotrophic lateral sclerosis (ALS) (n = 99) versus age-matched healthy controls (HC, n = 78). To improve the understanding of the neural mechanisms underlying microstates, we estimated the sources of microstates topographies. A general linear model was applied to predict the microstate sequence based on EEG-estimated source space time courses. High reproducibility across participants of influential brain sources led to the identification of four microstate specific networks. Some brain regions contributed to several microstate networks, which may indicate that these regions (including the precuneus, the superior frontal gyrus and the hippocampus) are functional neuronal ‘hubs’ of connection. Additionally, distinct source patterns were observed between ALS patients and healthy controls, highlighting potential functional changes in the brain networks in ALS.

Objective: To design and develop a high-density (HD) electrode system that describes the position of surface electrodes for recording electrophysiological signals from the human cervical spinal cord. The system is intended to standardize experimental recordings and facilitate the subsequent analysis of evoked and spontaneous spinal cord neural activity, using high-density electrospinography (HD-ESG). Method: The proposed system (SC10-X/U) describes the locations of up to 76 channels with a unique nomenclature, where the division of the spinal cord (SC) electrode space was inspired by the EEG 10-10 system. As proof of concept, spinal evoked potentials in response to median nerve stimulation at the wrist were recorded from 10 participants and characterized based on a 64-channel derivation from the SC10-X/U system. Results: Following the design criteria, the SC10-X/U defines 76 electrode positions and its configuration. HD-ESG system was utilized to successfully record evoked spinal responses and significant N13 and P9 potential were observed in response to the stimulation. The spinal N13 potential had a latency of 13.2 +- 1.1ms (mean +- SD) after stimulation. A topographic map of the N13 electro-spinal activity using the 64-channel recording system revealed an epicentre at C5-C7 dorsal-vertebral locations (ML4 - ML6 electrodes). Conclusion: The proposed SC10-X/U system will facilitate standardized recording and analysis of high-density ESG signals from the human cervical spinal cord. The system defines electrode locations to promote standardization across different individuals, studies, and clinical and research centres. The HD-ESG evoked potentials recorded using the proposed system were comparable to those observed in previous non-HD studies. The presented topographic maps conform to known neurophysiological and neuroanatomical findings. This served to validate the design and development of the electrode system and patch for future studies. ### Competing Interest Statement The authors have declared no competing interest.

Objective: To establish if induced current direction across the motor cortex alters the sensitivity of transcranial magnetic stimulation (TMS)-evoked short-interval intracortical inhibition (SICI) as an ALS biomarker. Methods: Threshold tracking-TMS was undertaken in 35 people with ALS and 39 controls. Using a coil orientation which induces posterior-anterior (PA)-directed current across the motor cortex, SICI (1 ms and 3 ms interstimulus intervals) and intracortical facilitation (ICF, 10 ms interstimulus interval) were recorded. SICI3ms was also recorded using a coil orientation which induces anterior-posterior (AP)directed current across the motor cortex. Results: At group level, SICI3ms-PA (AUROC = 0.7), SICI3ms-AP (AUROC = 0.8) and SICI1ms (AUROC = 0.66) were substantially lower in those with ALS, although there was considerable interindividual heterogeneity. Averaging across interstimulus intervals (ISIs) marginally improved SICIPA sensitivity (AUROC = 0.76). Averaging SICI values across ISIs and orientations into a single SICI measure did not substantially improve sensitivity (AUROC = 0.81) compared to SICI3ms-AP alone. SICI3ms-AP and SICI3ms-PA did not significantly correlate (rho = 0.19, p = 0.313), while SICI1ms-PA and SICI3ms-PA did (rho = 0.37, p = 0.006). Further, those with ALS with the lowest SICI3ms-PA were not those with the lowest SICI3ms-AP. ICF was similar between groups (AUROC = 0.50). Conclusions: SICIPA and SICIAP are uncorrelated measures of motor cortical inhibitory functions which are useful as distinct, unequally affected, measures of disinhibition in ALS. Significance: Examining both SICIPA and SICIAP may facilitate more comprehensive characterisation of motor cortical disinhibition in ALS. (c) 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Amyotrophic lateral sclerosis (ALS) is a multisystem neurodegenerative disorder characterized by progressive motor decline. Studies of electroencephalographic (EEG) activity during rest and motor execution have captured network changes in ALS. However, the nature of network-level impairment in the pre-motor activity in ALS remains unclear. Assessing the (dys)function of motor networks engaged prior to motor output is essential for understanding the motor pathophysiology in ALS. We recorded EEG in 22 people with ALS (PwALS) and 16 age-matched healthy controls during rest and isometric pincer-grip tasks. EEG spectral power and coherence were calculated during rest, pre-motor stage, and motor execution. In PwALS, significantly higher event-related spectral perturbations were observed compared to controls over electrodes representing a) contralateral prefrontal and parietal regions in theta band during pre-motor stage, b) contralateral parietal and ipsilateral motor regions in high-beta band during motor execution. Similarly, spectral coherence revealed abnormal EEG connectivity within 1) sensorimotor network during rest in theta band, 2) (pre)motor networks during pre-motor stage in low-alpha and high-beta bands, 3) Fronto-parietal networks during execution in high-beta band. Furthermore, the abnormal EEG connectivity during rest and execution (but not during pre-motor stage) showed significant negative correlation with clinical ALS-functional-rating-scale scores. Combining abnormal EEG connectivity from rest, pre-motor, and execution stages provided more powerful discrimination between patients and controls with a uniquely higher contribution of measures pertaining to the pre-motor stage. The results indicate that pre-motor functional activity reflects a different and unique aspect of network impairment, with potential for inclusion as biomarker candidates in ALS.

Amyotrophic lateral sclerosis (ALS) is characterised primarily by motor system degeneration, with clinical evidence of cognitive and behavioural change in up to 50% of cases. We have shown previously that resting-state EEG captures the dysfunction in motor and cognitive networks in ALS. However, the longitudinal development of the network-level dysfunction patterns remains unclear, particularly in the networks related to cognitive-behavioural functions. We examined 124 ALS individuals with 128-channel resting-state EEG recordings, categorised by cognitive impairment (ALSci, n = 27), behavioural impairment (ALSbi, n = 58), or non-impaired (ALSncbi, n = 53). Using linear mixed-effects models, we characterised the general and phenotype-specific longitudinal changes in brain network, and their association with cognitive performance, fine motor symptoms, and survival. We observed significant decline in \(\theta\)-band spectral power over time in the temporal region along with increased \({\gamma }_{l}\)-band power in the fronto-temporal region in the ALS group. ALSncbi participants showed widespread β-band synchrony decrease, while ALSci participants exhibited increased co-modulation correlated with verbal fluency decline. Longitudinal network-level changes varied between ALS subgroups, correlating with motor, cognitive, and behavioural decline. Spectral EEG measures can longitudinally track abnormal network patterns, serving as a candidate stratification tool for clinical trials and personalized treatments in ALS.

Primary lateral sclerosis (PLS) is a slowly progressing disorder, which is characterized primarily by the degeneration of upper motor neurons (UMNs) in the primary motor area (M1). It is not yet clear how the function of sensorimotor networks beyond M1 are affected by PLS. The aim of this study was to use cortico-muscular coherence (CMC) to characterize the oscillatory drives between cortical regions and muscles during a motor task in PLS and to examine the relationship between CMC and the level of clinical impairment. We recorded EEG and EMG from hand muscles in 16 participants with PLS and 18 controls during a pincer-grip task. In PLS, higher CMC was observed over contralateral-M1 (α- and γ-band) and ipsilateral-M1 (β-band) compared with controls. Significant correlations between clinically assessed UMN scores and CMC measures showed that higher clinical impairment was associated with lower CMC over contralateral-M1/frontal areas, higher CMC over parietal area, and both higher and lower CMC (in different bands) over ipsilateral-M1. The results suggest an atypical engagement of both contralateral and ipsilateral M1 during motor activity in PLS, indicating the presence of pathogenic and/or adaptive/compensatory alterations in neural activity. The findings demonstrate the potential of CMC for identifying dysfunction within the sensorimotor networks in PLS.

Recent electroencephalography (EEG) studies have shown that patterns of brain activity can be used to differentiate amyotrophic lateral sclerosis (ALS) and control groups. These differences can be interrogated by examining EEG microstates, which are distinct, reoccurring topographies of the scalp's electrical potentials. Quantifying the temporal properties of the four canonical microstates can elucidate how the dynamics of functional brain networks are altered in neurological conditions. Here we have analysed the properties of microstates to detect and quantify signal-based abnormality in ALS. High-density resting-state EEG data from 129 people with ALS and 78 HC were recorded longitudinally over a 24-month period. EEG topographies were extracted at instances of peak global field power to identify four microstate classes (labelled A-D) using K-means clustering. Each EEG topography was retrospectively associated with a microstate class based on global map dissimilarity. Changes in microstate properties over the course of the disease were assessed in people with ALS and compared with changes in clinical scores. The topographies of microstate classes remained consistent across participants and conditions. Differences were observed in coverage, occurrence, duration, and transition probabilities between ALS and control groups. The duration of microstate class B and coverage of microstate class C correlated with lower limb functional decline. The transition probabilities A to D, C to B and C to B also correlated with cognitive decline (total ECAS) in those with cognitive and behavioural impairments. Microstate characteristics also significantly changed over the course of the disease. Examining the temporal dependencies in the sequences of microstates revealed that the symmetry and stationarity of transition matrices were increased in people with late-stage ALS. These alterations in the properties of EEG microstates in ALS may reflect abnormalities within the sensory network and higher-order networks. Microstate properties could also prospectively predict symptom progression in those with cognitive impairments.

Neural oscillations, or brain rhythms, fluctuate in a manner reflecting ongoing behavior. Whether these fluctuations are instrumental or epiphenomenal to the behavior remains elusive. Attempts to experimentally manipulate neural oscillations exogenously using noninvasive brain stimulation have shown some promise, but difficulty with tailoring stimulation parameters to individuals has hindered progress in this field. We demonstrate here using electroencephalography (EEG) neurofeedback in a brain-computer interface that human participants (n = 44) learned over multiple sessions across a 6-day period to self-regulate their Beta rhythm (13-20 Hz), either up or down, over the right inferior frontal cortex. Training to downregulate Beta was more effective than training to upregulate Beta. The modulation was evident only during neurofeedback task performance but did not lead to offline alteration of Beta rhythm characteristics at rest, nor to changes in subsequent cognitive behavior. Likewise, a control group (n = 38) who underwent training to up or downregulate the Alpha rhythm (8-12 Hz) did not exhibit behavioral changes. Although the right frontal Beta rhythm has been repeatedly implicated as a key component of the brain's inhibitory control system, the present data suggest that its manipulation offline prior to cognitive task performance does not result in behavioral change in healthy individuals. Whether this form of neurofeedback training could serve as a useful therapeutic target for disorders with dysfunctional inhibitory control as their basis remains to be tested in a context where performance is abnormally poor and neural dynamics are different.

Objective: Poliomyelitis results in changes to the anterior horn cell. The full extent of cortical network changes in the motor physiology of polio survivors has not been established. Our aim was to investigate how focal degeneration of the lower motor neurons (LMN) in infancy/childhood affects motor network connectivity in adult survivors of polio. Methods: Surface electroencephalography (EEG) and electromyography (EMG) were recorded during an isometric pincer grip task in 25 patients and 11 healthy controls. Spectral signal analysis of corticomuscular (EEG-EMG) coherence (CMC) was used to identify the cortical regions that are functionally synchronous and connected to the periphery during the pincer grip task. Results: A pattern of CMC was noted in polio survivors that was not present in healthy individuals. Significant CMC in low gamma frequency bands (30-47 Hz) was observed in frontal and parietal regions. Conclusion: These findings imply a differential engagement of cortical networks in polio survivors that extends beyond the motor cortex and suggest a disease-related functional reorganisation of the cortical motor network. Significance: This research has implications for other similar LMN conditions, including spinal muscular atrophy (SMA). CMC has potential in future clinical trials as a biomarker of altered function in motor networks in post-polio syndrome, SMA, and other related conditions. (C) 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.

We studied the brain microstates as a wellestablished method for dynamic resting-state analysis of electroencephalogram (EEG), to assess the functional changes in the brain networks in Amyotrophic lateral sclerosis (ALS). Clinical Relevance— EEG microstates changes can reflect the disrupted functional balance between motor and cognitive networks in ALS and act as a potential neurophysiological marker of the disease subtypes and progression.

Monday, April 27April 14, 2020Free AccessCortico-Muscular Coherence Patterns in Spinal Muscular Atrophy (2318)Amina Coffey, Saroj Bista, Matthew Mitchell, Rosie Giglia, Richard Carson, Madeleine Lowery, Mark Heverin, Peter Bede, Bahman Nasseroleslami, and Orla HardimanAuthors Info & AffiliationsApril 14, 2020 issue94 (15_supplement)https://doi.org/10.1212/WNL.94.15_supplement.2318 Letters to the Editor

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