Insights into COVID-19 pathophysiology from a longitudinal multisystem report during acute infection.

The Coronavirus disease 2019 (COVID-19), an illness caused by a SARS-CoV-2 viral infection, has been associated with neurological and neuropsychiatric disorders, revealing its impact beyond the respiratory system. Most related research involved individuals with post-acute or persistent symptoms of COVID-19, also referred to as long COVID or Post-Acute Sequelae of COVID-19 (PASC). In this longitudinal unique report, we aimed to describe the acute supraspinal and corticospinal changes and functional alterations induced by a COVID-19 infection using neuroimaging, neurophysiological and clinical assessment of a participant during acute infection, as compared to three other visits where the participant had no COVID-19. The results favor a multisystem impairment, impacting cortical activity, functional connectivity, and corticospinal excitability, as well as motor and cardiovascular function. The report suggests pathophysiological alteration and impairment already present at the acute stage, that if resolved tend to lead to a full clinical recovery. Such results could be also insightful into PASC symptomatology.

Corticospinal inhibition investigated in relation to upper extremity motor function in cervical spinal cord injury.

OBJECTIVE: Corticospinal inhibitory mechanisms are relevant to functional recovery but remain poorly understood after spinal cord injury (SCI). Post-injury characteristics of contralateral silent period (CSP), a measure of corticospinal inhibition evaluated using transcranial magnetic stimulation (TMS), is inconsistent in literature. We envisioned that investigating CSP across muscles with varying degrees of weakness may be a reasonable approach to resolve inconsistencies and elucidate the relevance of corticospinal inhibition for upper extremity function following SCI. METHODS: We studied 27 adults with chronic C1-C8 SCI (age 48.8 ± 16.1 years, 3 females) and 16 able-bodied participants (age 33.2 ± 11.8 years, 9 females). CSP characteristics were assessed across biceps (muscle power = 3-5) and triceps (muscle power = 1-3) representing stronger and weaker muscles, respectively. We assessed functional abilities using the Capabilities of the Upper Extremity Test (CUE-T). RESULTS: Participants with chronic SCI had prolonged CSPs for biceps but delayed and diminished CSPs for triceps compared to able-bodied participants. Early-onset CSPs for biceps and longer, deeper CSPs for triceps correlated with better CUE-T scores. CONCLUSIONS: Corticospinal inhibition is pronounced for stronger biceps but diminished for weaker triceps muscle in SCI indicating innervation relative to the level of injury matters in the study of CSP. SIGNIFICANCE: Nevertheless, corticospinal inhibition or CSP holds relevance for upper extremity function following SCI.

Safety and effects of a therapeutic 15 Hz rTMS protocol administered at different suprathreshold intensities in able-bodied individuals.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) remains a promising strategy for neurorehabilitation. The stimulation intensity (SI) influences the aftereffects observed. Here, we examined whether single sessions of a 15 Hz rTMS protocol, administered at suprathreshold SI, can be safely administered to able-bodied (AB) individuals. Six right-handed men were included in this pilot study. HF-rTMS was delivered over the right M1, in 10 trains of 75 biphasic stimuli at 15 Hz, at 105-120% of the individual resting motor threshold (RMT). To assess safety, electromyography (EMG) was monitored to control for signs of spread of excitation and brief EMG burst (BEB) after stimulation. Additionally, TMS side effects questionnaires and the numeric rating scale (NRS) were administered during each session. We assessed corticospinal excitability (CSE) and motor performance changes with measures of resting (rMEP) and active (aMEP) motor evoked potential and grip strength and box and blocks test (BBT) scores, respectively. Overall, the sessions were tolerated and feasible without any pain development. However, EMG analysis during 15 Hz rTMS administration revealed increased BEB frequency with SI. Statistical models revealed an increase of CSE at rest (rMEP) but not during active muscle contraction (aMEP). No linear relationship was observed between 15 Hz rTMS SI and rMEP increase. No significant changes were highlighted for motor performance measures. Although feasible and tolerable by the AB individuals tested, the results demonstrate that when administered at suprathreshold intensities (≥ 105% RMT) the 15 Hz rTMS protocol reveals signs of persistent excitation, suggesting that safety precautions and close monitoring of participants should be performed when testing such combinations of high-intensity and high-frequency stimulation protocols. The results also give insight into the nonlinear existent relationship between the SI and HF-rTMS effects on CSE.NEW & NOTEWORTHY The results of this pilot study show the effects of a therapeutically promising 15 Hz repetitive transcranial magnetic stimulation (rTMS) protocol, administered at different suprathreshold intensities in able-bodied individuals. Although tolerable and feasible with a neuromodulatory potential, 15 Hz rTMS might result in persistent excitability that needs to be closely monitored if administered at suprathreshold stimulation intensity. These results reaffirm the importance of feasibility studies, especially in translational animal-to-human research.

High-Frequency rTMS Combined with Task-Specific Hand Motor Training Modulates Corticospinal Plasticity in Motor Complete Spinal Cord Injury: A case report.

Since its first use in spinal cord injury (SCI) in the early 2000s [1], high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) demonstrated a capacity to modulate corticospinal excitability (CSE) and motor performance. Studies focused on individuals with incomplete SCI. Here, we examined the feasibility of a 15-day therapeutic stimulation protocol combining HF-rTMS with task-specific motor training targeting the weaker hand in an individual with early chronic complete SCI. In this case report, we present evidence of progressive increase of CSE at rest and during muscle activation, and decreased cortical inhibition, associated with a trend toward improvement in pinch function of the weaker hand. These promising findings need to be confirmed in a larger population. Clinical Relevance- These preliminary results are promising and demonstrate the importance of a large number of training session repetitions to induce consistent changes relevant to the recovery after a complete SCI.

Stimulation Parameters Used During Repetitive Transcranial Magnetic Stimulation for Motor Recovery and Corticospinal Excitability Modulation in SCI: A Scoping Review.

There is a growing interest in non-invasive stimulation interventions as treatment strategies to improve functional outcomes and recovery after spinal cord injury (SCI). Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulatory intervention which has the potential to reinforce the residual spinal and supraspinal pathways and induce plasticity. Recent reviews have highlighted the therapeutic potential and the beneficial effects of rTMS on motor function, spasticity, and corticospinal excitability modulation in SCI individuals. For this scoping review, we focus on the stimulation parameters used in 20 rTMS protocols. We extracted the rTMS parameters from 16 published rTMS studies involving SCI individuals and were able to infer preliminary associations between specific parameters and the effects observed. Future investigations will need to consider timing, intervention duration and dosage (in terms of number of sessions and number of pulses) that may depend on the stage, the level, and the severity of the injury. There is a need for more real vs. sham rTMS studies, reporting similar designs with sufficient information for replication, to achieve a significant level of evidence regarding the use of rTMS in SCI.

Controlling for lesions, kinematics and physiological noise: impact on fMRI results of spastic post-stroke patients.

Functional magnetic resonance imaging (fMRI) is a widely used technique for assessing brain function in both healthy and pathological populations. Some factors, such as motion, physiological noise and lesion presence, can contribute to signal change and confound the fMRI data, but fMRI data processing techniques have been developed to correct for these confounding effects. Fifteen spastic subacute stroke patients underwent fMRI while performing a highly controlled task (i.e. passive extension of their affected and unaffected wrists). We investigated the impact on activation maps of lesion masking during preprocessing and first- and second-level analyses, and of adding wrist extension amplitudes and physiological data as regressors using the Statistical Parametric Mapping toolbox (SPM12). We observed a significant decrease in sensorimotor region activation after the addition of lesion masks and movement/physiological regressors during the processing of stroke patients' fMRI data. Our results demonstrate that:•The unified segmentation routine results in good normalization accuracy when dealing with stroke lesions regardless of their size;•Adding a group lesion mask during the second-level analysis seems to be a suitable option when none of the patients have lesions in target regions. Otherwise, no masking is acceptable;•Movement amplitude is a significant contributor to the sensorimotor activation observed during passive wrist extension in spastic stroke patients;•Movement features and physiological noise are relevant factors when interpreting for sensorimotor activation in studies of the motor system in patients with brain lesions. They can be added as nuisance covariates during large patient groups' analyses.

Kinematic parameters obtained with the ArmeoSpring for upper-limb assessment after stroke: a reliability and learning effect study for guiding parameter use.

BACKGROUND: After stroke, kinematic measures obtained with non-robotic and robotic devices are highly recommended to precisely quantify the sensorimotor impairments of the upper-extremity and select the most relevant therapeutic strategies. Although the ArmeoSpring exoskeleton has demonstrated its effectiveness in stroke motor rehabilitation, its interest as an assessment tool has not been sufficiently documented. The aim of this study was to investigate the psychometric properties of selected kinematic parameters obtained with the ArmeoSpring in post-stroke patients. METHODS: This study involved 30 post-stroke patients (mean age = 54.5 ± 16.4 years; time post-stroke = 14.7 ± 26.7 weeks; Upper-Extremity Fugl-Meyer Score (UE-FMS) = 40.7 ± 14.5/66) who participated in 3 assessment sessions, each consisting of 10 repetitions of the 'horizontal catch' exercise. Five kinematic parameters (task and movement time, hand path ratio, peak velocity, number of peak velocity) and a global Score were computed from raw ArmeoSpring' data. Learning effect and retention were analyzed using a 2-way repeated-measures ANOVA, and reliability was investigated using the intra-class correlation coefficient (ICC) and minimal detectable change (MDC). RESULTS: We observed significant inter- and intra-session learning effects for most parameters except peak velocity. The measures performed in sessions 2 and 3 were significantly different from those of session 1. No additional significant difference was observed after the first 6 trials of each session and successful retention was also highlighted for all the parameters. Relative reliability was moderate to excellent for all the parameters, and MDC values expressed in percentage ranged from 42.6 to 102.8%. CONCLUSIONS: After a familiarization session, the ArmeoSpring can be used to reliably and sensitively assess motor impairment and intervention effects on motor learning processes after a stroke. Trial registration The study was approved by the local hospital ethics committee in September 2016 and was registered under number 05-0916.

Cross-Modal Functional Connectivity of the Premotor Cortex Reflects Residual Motor Output After Stroke.

Stroke is known to cause widespread activation and connectivity changes resulting in different levels of functional impairment. Recovery of motor functions is thought to rely mainly on reorganizations within the sensorimotor cortex, but increasing attention is being paid to other cerebral regions. To investigate the motor task-related functional connectivity (FC) of the ipsilesional premotor cortex (PMC) and its relation to residual motor output after stroke in a population of mostly poorly recoverd patients. Twenty-four stroke patients (23 right handed, mean age = 52.4 ± 12.6 years) with varying levels of motor deficits underwent functional magnetic resonance imaging while performing different motor tasks (passive mobilization, motor execution, and motor imagery of an extension movement of the unaffected hand [UH] or affected hand [AH]). For the different motor tasks, analyses of cerebral activation and task-related FC of the ipsilesional lateral sensorimotor network (SMN), and particularly the premotor cortex (PMC), were performed. Compared with UH data, FC of the ipsilesional lateral SMN during the passive or active motor tasks involving the AH was decreased with regions of the ipsilesional SMN and was increased with regions of the bilateral frontal and the ipsilesional posterior parietal cortices such as the precuneus (Pcu). During passive wrist mobilization, FC between the ipsilesional PMC and the contralesional SMN was negatively correlated with residual motor function, whereas that with nonmotor regions such as the bilateral Pcu and the contralesional dorsolateral prefrontal cortex was positively correlated with the residual motor function. Cross-modal FC of the ipsilesional PMC may reflect compensation strategies after stroke. The results emphasize the importance of the PMC and other nonmotor regions as prominent nodes involved in reorganization processes after a stroke.

Action, observation or imitation of virtual hand movement affect differently regions of the mirror neuron system and the default mode network.

Virtual reality (VR)-based paradigms use visual stimuli that can modulate visuo-motor networks leading to the stimulation of brain circuits. The aims of this study were to compare the changes in blood-oxygenation level dependent (BOLD) signal when watching and imitating moving real (RH) and virtual hands (VH) in 11 healthy participants (HP). No differences were found between the observation of RH or VH making this VR-based experiment a promising tool for rehabilitation protocols. VH-imitation involved more the ventral premotor cortex (vPMC) as part of the mirror neuron system (MNS) compared to execution and VH-observation conditions. The dorsal-anterior Precuneus (da-Pcu) as part of the Precuneus/posterior Cingulate Cortex (Pcu/pCC) complex, a key node of the Default Mode Network (DMN), was also less deactivated and therefore more involved. These results may reflect the dual visuo-motor roles for the vPMC and the implication of the da-Pcu in the reallocation of attentional and neural resources for bimodal task management. The ventral Pcu/pCC was deactivated regardless of the condition confirming its role in self-reference processes. Imitation of VH stimuli can then modulate the activation of specific areas including those belonging to the MNS and the DMN.