Examining short interval intracortical inhibition with different transcranial magnetic stimulation-induced current directions in ALS.

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.

Deficits in force production during multifinger tasks demarcate cognitive dysfunction.

BACKGROUND: The multifinger force deficit (MFFD) is the decline in force generated by each finger as the number of fingers contributing to an action is increased. It has been shown to associate with cognitive status. AIMS: The aim was to establish whether a particularly challenging form of multifinger grip dynamometry, that provides minimal tactile feedback via cutaneous receptors and requires active compensation for reaction forces, will yield an MFFD that is more sensitive to cognitive status. METHODS: Associations between measures of motor function, and cognitive status (Montreal Cognitive Assessment [MoCA]) and latent components of cognitive function (derived from 11 tests using principal component analysis), were estimated cross-sectionally using generalized partial rank correlations. The participants (n = 62) were community dwelling, aged 65-87. RESULTS: Approximately half the participants were unable to complete the dynamometry task successfully. Cognitive status demarcated individuals who could perform the task from those who could not. Among those who complied with the task requirements, the MFFD was negatively correlated with MoCA scores-those with the highest MoCA scores tended to exhibit the smallest deficits, and vice versa. There were corresponding associations with latent components of cognitive function. DISCUSSION: The results support the view that neurodegenerative processes that are a feature of normal and pathological aging exert corresponding effects on expressions of motor coordination-in multifinger tasks, and cognitive sufficiency, due to their dependence on shared neural systems. CONCLUSIONS: The outcomes add weight to the assertion that deficits in force production during multifinger tasks are sensitive to cognitive dysfunction.

Consensus for experimental design in electromyography (CEDE) project: Checklist for reporting and critically appraising studies using EMG (CEDE-Check).

The diversity in electromyography (EMG) techniques and their reporting present significant challenges across multiple disciplines in research and clinical practice, where EMG is commonly used. To address these challenges and augment the reproducibility and interpretation of studies using EMG, the Consensus for Experimental Design in Electromyography (CEDE) project has developed a checklist (CEDE-Check) to assist researchers to thoroughly report their EMG methodologies. Development involved a multi-stage Delphi process with seventeen EMG experts from various disciplines. After two rounds, consensus was achieved. The final CEDE-Check consists of forty items that address four critical areas that demand precise reporting when EMG is employed: the task investigated, electrode placement, recording electrode characteristics, and acquisition and pre-processing of EMG signals. This checklist aims to guide researchers to accurately report and critically appraise EMG studies, thereby promoting a standardised critical evaluation, and greater scientific rigor in research that uses EMG signals. This approach not only aims to facilitate interpretation of study results and comparisons between studies, but it is also expected to contribute to advancing research quality and facilitate clinical and other practical applications of knowledge generated through the use of EMG.

Electroencephalographic ß-band oscillations in the sensorimotor network reflect motor symptom severity in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Resting-state electroencephalography (EEG) holds promise for assessing brain networks in amyotrophic lateral sclerosis (ALS). We investigated whether neural ß-band oscillations in the sensorimotor network could serve as an objective quantitative measure of progressive motor impairment and functional disability in ALS patients. METHODS: Resting-state EEG was recorded in 18 people with ALS and 38 age- and gender-matched healthy controls. We estimated source-localized ß-band spectral power in the sensorimotor cortex. Clinical evaluation included lower (LMN) and upper motor neuron scores, Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score, fine motor function (FMF) subscore, and progression rate. Correlations between clinical scores and ß-band power were analysed and corrected using a false discovery rate of q = 0.05. RESULTS: ß-Band power was significantly lower in people with ALS than controls (p = 0.004), and correlated with LMN score (R = -0.65, p = 0.013), FMF subscore (R = -0.53, p = 0.036), and FMF progression rate (R = 0.52, p = 0.036). CONCLUSIONS: ß-Band spectral power in the sensorimotor cortex reflects clinically evaluated motor impairment in ALS. This technology merits further investigation as a biomarker of progressive functional disability.

Cortico-muscular coherence in primary lateral sclerosis reveals abnormal cortical engagement during motor function beyond primary motor areas.

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 (ß-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.

Induction of interhemispheric facilitation by short bursts of transcranial alternating current stimulation.

Interhemispheric facilitation (IHF) describes potentiation of motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) over primary motor cortex (M1), when they are preceded (3-6 ms) by conditioning TMS below motor threshold (MT) delivered over the opposite M1. This effect is however obtained only when the conditioning stimulation is sufficiently circumscribed. In paired associative protocols, (500 ms) bursts of 140 Hz transcranial alternating current stimulation (tACS) interact with the state of neural circuits in the opposite hemisphere in a similar manner to sub-threshold TMS. We hypothesised that tACS applied over M1 would elevate the amplitudes of MEPs elicited by suprathreshold TMS applied 6 ms later over the opposite M1. Thirty healthy right-handed participants were tested. In a control condition, MEPs were recorded in right flexor carpi radialis (rFCR) following 120% resting MT TMS over left M1. In 11 experimental conditions, 1 mA (peak-to-peak) 140 Hz (30, 100, 500 ms) or 670 Hz (6, 12, 100, 500 ms) tACS, or 100-640 Hz (6, 12, 100, 500 ms) transcranial random noise stimulation (tRNS), was delivered over right M1, 6 ms in advance of the TMS. IHF was obtained by conditioning with 30 ms (but not 100 or 500 ms) 140 Hz tACS. The magnitude of IHF (12% increase; d = 0.56 (0.21-0.98)) was within the range reported for dual-coil TMS studies. Conditioning by 670 Hz tACS or tRNS had no effect. Our findings indicate that short bursts of 140 Hz tACS, applied over M1, have distributed effects similar to those of subthreshold TMS.

Consensus for experimental design in electromyography (CEDE) project: Single motor unit matrix.

The analysis of single motor unit (SMU) activity provides the foundation from which information about the neural strategies underlying the control of muscle force can be identified, due to the one-to-one association between the action potentials generated by an alpha motor neuron and those received by the innervated muscle fibers. Such a powerful assessment has been conventionally performed with invasive electrodes (i.e., intramuscular electromyography (EMG)), however, recent advances in signal processing techniques have enabled the identification of single motor unit (SMU) activity in high-density surface electromyography (HDsEMG) recordings. This matrix, developed by the Consensus for Experimental Design in Electromyography (CEDE) project, provides recommendations for the recording and analysis of SMU activity with both invasive (needle and fine-wire EMG) and non-invasive (HDsEMG) SMU identification methods, summarizing their advantages and disadvantages when used during different testing conditions. Recommendations for the analysis and reporting of discharge rate and peripheral (i.e., muscle fiber conduction velocity) SMU properties are also provided. The results of the Delphi process to reach consensus are contained in an appendix. This matrix is intended to help researchers to collect, report, and interpret SMU data in the context of both research and clinical applications.

Deficits in rate of force production during multifinger tasks are associated with cognitive status.

OBJECTIVES: The multifinger force deficit (MFFD) is the decline in force generated by an individual finger as the number of fingers contributing to the action is increased. It has been proposed that as a measure of neural sufficiency rather than muscle status, it provides a means of detecting individuals at risk of cognitive decline. Age-related deficits in central neural drive exert a disproportionate impact on the rate at which force can be generated. We examined whether a MFFD derived from the maximum rate at which force is generated, is more sensitive to individual differences in cognitive status, than one calculated using the maximum level of force. METHODS: Monotonic associations between each of two variants of the MFFD, and cognition (measured with the Montreal Cognitive Assessment), were estimated cross sectionally using generalized partial rank correlations, in which age, level of education and degree of handedness were included as covariates. The participants (n=26) were community dwelling adults aged 66-87. RESULTS: The MFFD derived using the maximum rate of force development was negatively associated with cognitive status. The association for the MFFD based on the maximum level of force, was not statistically reliable. The associations with cognitive status obtained for both variants of the MFFD were of greater magnitude than those reported previously for standard grip strength dynamometry. CONCLUSION: The sensitivity with which the MFFD detects risk of cognitive decline may be enhanced by using the maximum rate of force developed by each finger, rather than the maximum force generated by each finger.

Consensus for experimental design in electromyography (CEDE) project: High-density surface electromyography matrix.

High-density surface electromyography (HDsEMG) can be used to measure the spatial distribution of electrical muscle activity over the skin. As this distribution is associated with the generation and propagation of muscle fiber action potentials, HDsEMG is processed to extract information on regional muscle activation, muscle fiber characteristics and behaviour of individual motor units. This matrix, developed by the Consensus for Experimental Design in Electromyography (CEDE) project, summarizes recommendations on the use of HDsEMG in experimental studies. For each application, recommendations are included regarding electrode montage, electrode type and configuration, electrode location and orientation, data analysis, and interpretation. Cautions and reporting standards are also included. The steps of the Delphi process to reach consensus are contained in an appendix. This matrix is intended to help researchers when collecting, reporting, and interpreting HDsEMG data. It is hoped that this document will be used to generate new empirical evidence to improve how HDsEMG is used in research and in clinical applications.

Neural mechanisms mediating cross education: With additional considerations for the ageing brain.

CALVERT, G.H.M., and CARSON, R.G. Neural mechanisms mediating cross education: With additional considerations for the ageing brain. NEUROSCI BIOBEHAV REV 21(1) XXX-XXX, 2021. - Cross education (CE) is the process whereby a regimen of unilateral limb training engenders bilateral improvements in motor function. The contralateral gains thus derived may impart therapeutic benefits for patients with unilateral deficits arising from orthopaedic injury or stroke. Despite this prospective therapeutic utility, there is little consensus concerning its mechanistic basis. The precise means through which the neuroanatomical structures and cellular processes that mediate CE may be influenced by age-related neurodegeneration are also almost entirely unknown. Notwithstanding the increased incidence of unilateral impairment in later life, age-related variations in the expression of CE have been examined only infrequently. In this narrative review, we consider several mechanisms which may mediate the expression of CE with specific reference to the ageing CNS. We focus on the adaptive potential of cellular processes that are subserved by a specific set of neuroanatomical pathways including: the corticospinal tract, corticoreticulospinal projections, transcallosal fibres, and thalamocortical radiations. This analysis may inform the development of interventions that exploit the therapeutic utility of CE training in older persons.

Consensus for experimental design in electromyography (CEDE) project: Terminology matrix.

Consensus on the definition of common terms in electromyography (EMG) research promotes consistency in the EMG literature and facilitates the integration of research across the field. This paper presents a matrix developed within the Consensus for Experimental Design in Electromyography (CEDE) project, providing definitions for terms used in the EMG literature. The definitions for physiological and technical terms that are common in EMG research are included in two tables, with key information on each definition provided in a comment section. A brief outline of some basic principles for recording and analyzing EMG is included in an appendix, to provide researchers new to EMG with background and context for understanding the definitions of physiological and technical terms. This terminology matrix can be used as a reference to aid researchers new to EMG in reviewing the EMG literature.

Sarcopenia and Neuroscience: Learning to Communicate.

In the 1990s and early 2000s, the common definition for sarcopenia was age-related loss of skeletal muscle, and low levels of muscle mass were central to sarcopenia diagnosis. In more recent consensus definitions, however, low muscle strength displaces low muscle mass as a defining feature of sarcopenia. The change stems from growing evidence that muscle weakness is a better predictor of adverse health outcomes (eg, mobility limitations) than muscle mass. This evidence accompanies an emerging recognition that central neural mechanisms are critical determinants of age-related changes in strength and mobility that can occur independently of variations in muscle mass. However, strikingly little practical attention is typically given to the potential role of the central nervous system in the etiology or remediation of sarcopenia (ie, low muscle function). In this article, we provide an overview of some mechanisms that mediate neural regulation of muscle contraction and control, and highlight the specific contributions of neural hypoexcitability, dopaminergic dysfunction, and degradation of functional and structural brain connectivity in relation to sarcopenia. We aim to enhance the lines of communication between the domains of sarcopenia and neuroscience. We believe that appreciation of the neural regulation of muscle contraction and control is fundamental to understanding sarcopenia and to developing targeted therapeutic strategies for its treatment.

A Bayesian approach to analysing cortico-cortical associative stimulation induced increases in the excitability of corticospinal projections in humans.

Repeated pairing of transcranial magnetic stimulation (TMS) over left and right primary motor cortex (M1), at intensities sufficient to generate descending volleys, produces sustained increases in corticospinal excitability. In other paired associative stimulation (PAS) protocols, in which peripheral afferent stimulation is the first element, changes in corticospinal excitability achieved when the second stimulus consists of brief bursts of transcranial alternating current stimulation (tACS), are comparable to those obtained if TMS is used instead (McNickle and Carson 2015). The present aim was to determine whether associative effects are induced when the first stimulus of a cortico-cortical pair is tACS, or alternatively subthreshold TMS. Bursts of tACS (500 ms; 140 Hz; 1 mA) were associated (180 stimulus pairs) with single magnetic stimuli (120% resting motor threshold rMT) delivered over the opposite (left) M1. The tACS ended 6 ms prior to the TMS. In a separate condition, TMS (55% rMT) was delivered to right M1 6 ms before (120% rMT) TMS was applied over left M1. In a sham condition, TMS (120% rMT) was delivered to left M1 only. The limitations of null hypothesis significance testing are well documented. We therefore employed Bayes factors to assess evidence in support of experimental hypotheses-defined precisely in terms of predicted effect sizes, that these two novel variants of PAS increase corticospinal excitability. Although both interventions induced sustained (~ 20-30 min) increases in corticospinal excitability, the evidence in support of the experimental hypotheses (over specified alternatives) was generally greater for the paired TMS-TMS than the tACS-TMS conditions.

Neuromuscular electrical stimulation-promoted plasticity of the human brain.

The application of neuromuscular electrical stimulation (NMES) to paretic limbs has demonstrated utility for motor rehabilitation following brain injury. When NMES is delivered to a mixed peripheral nerve, typically both efferent and afferent fibres are recruited. Muscle contractions brought about by the excitation of motor neurons are often used to compensate for disability by assisting actions such as the formation of hand aperture, or by preventing others including foot drop. In this context, exogenous stimulation provides a direct substitute for endogenous neural drive. The goal of the present narrative review is to describe the means through which NMES may also promote sustained adaptations within central motor pathways, leading ultimately to increases in (intrinsic) functional capacity. There is an obvious practical motivation, in that detailed knowledge concerning the mechanisms of adaptation has the potential to inform neurorehabilitation practice. In addition, responses to NMES provide a means of studying CNS plasticity at a systems level in humans. We summarize the fundamental aspects of NMES, focusing on the forms that are employed most commonly in clinical and experimental practice. Specific attention is devoted to adjuvant techniques that further promote adaptive responses to NMES thereby offering the prospect of increased therapeutic potential. The emergent theme is that an association with centrally initiated neural activity, whether this is generated in the context of NMES triggered by efferent drive or via indirect methods such as mental imagery, may in some circumstances promote the physiological changes that can be induced through peripheral electrical stimulation.

Altered supraspinal motor networks in survivors of poliomyelitis: A cortico-muscular coherence study.

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 cortico-muscular (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.

Probing interhemispheric dorsal premotor-primary motor cortex interactions with threshold hunting transcranial magnetic stimulation.

OBJECTIVE: To characterise the effect of altering transcranial magnetic stimulation parameters on the magnitude of interhemispheric inhibition (IHI) from dorsal premotor (PMd) to primary motor cortex (M1). METHOD: We used a fully automated adaptive threshold hunting paradigm to quantify PMd-M1 IHI across a range of conditioning stimulus (CS) intensities (90%, 110%, 130% of resting motor threshold, rMT) and interstimulus intervals (ISIs) (8, 10, 40 ms). M1-M1 IHI was examined with CS intensities of 110%, 120%, and 130% rMT and ISIs of 10 and 40 ms. Two test coil orientations (inducing posterior-anterior or anterior-posterior current) were used. RESULTS: PMd-M1 IHI was obtained consistently with posterior-anterior (but not anterior-posterior) test stimuli and increased with CS intensity. M1-M1 IHI was expressed across all conditions and increased with CS intensity when posterior-anterior but not anterior-posterior induced current was used. CONCLUSIONS: The expression of PMd-M1 IHI is contingent on test coil orientation (requiring posterior-anterior induced current) and increases as a function of CS intensity. The expression of M1-M1 IHI is not dependent on test coil orientation. SIGNIFICANCE: We defined a range of parameters that elicit reliable PMd-M1 IHI. This (threshold hunting) methodology may provide a means to quantify premotor-motor pathology and reveal novel quantitative biomarkers.