Short-latency afferent inhibition and its relationship to covert sensory and motor hand impairment in multiple sclerosis.

OBJECTIVE: To investigate sensorimotor integration by quantifying short-latency afferent inhibition (SAI) in people with MS who experience manual dexterity problems compared to controls. METHODS: 22 people with MS with self-reported manual dexterity problems and 10 sex and age-matched controls were assessed using various upper extremity clinical tests. SAI was assessed by a transcranial magnetic stimulation pulse over the primary motor cortex preceded by peripheral nerve stimulation to the median nerve at 6 interstimulus intervals 2 - 8 ms longer than individualized N20 latencies. RESULTS: Although within normal limits, persons with MS exhibited significantly slower Nine Hole Peg Test performance and pinch strength in the dominant hand. They also exhibited greater sensory impairment (monofilament test) in the dominant hand. Persons with MS showed significantly greater disinhibition of SAI in the dominant hand compared to controls, which was significantly correlated with weaker pinch strength. CONCLUSION: Reduced SAI in people with MS, particularly in the dominant hand, signifies disruptions in cortical cholinergic inhibitory activity and is associated with lower pinch strength. SIGNIFICANCE: Evaluating changes in SAI may offer insight into the disrupted cortical cholinergic inhibitory activity that contributes to sensorimotor disintegration, potentially advancing disease management in persons with MS.

Multiple sclerosis-related heat sensitivity linked to absence of DMT prescription and subjective hand impairment but not autonomic or corticospinal dysfunction.

OBJECTIVES: Heat sensitivity (HS) describes a temporary worsening of multiple sclerosis (MS) symptoms with increased body temperature. The pathophysiology may relate to central nervous system conduction deficits and autonomic dysfunction. We conducted deep clinical phenotyping of a cohort of persons with MS to identify predictors of HS. METHODS: We recruited 59 MS participants with HS or No HS. Participants self-reported symptom severity (Hospital Anxiety and Depression Scale, Multiple Sclerosis Impact Scale, and fatigue visual analog scale) and underwent maximal exercise and transcranial magnetic stimulation testing to characterize autonomic and corticospinal function. We examined associations with HS using binomial logistic regression. RESULTS: People with HS (36/59) had significantly greater disability, depression, fatigue, and physical and psychological functional effects of MS. They also had significantly lower corticospinal excitability but not conduction. After controlling for disease-modifying therapy (DMT), disability, and disease type, self-reported difficulty using hands in everyday tasks was significantly associated with a large increase in the odds of HS. Autonomic and corticospinal dysfunction were not associated with HS. Lack of DMT use alone was also associated with a large increase in the odds of HS. DISCUSSION: Following a comprehensive assessment of plausible contributors to HS, HS was most strongly associated with lack of a DMT prescription and self-reported hand dysfunction. Surprisingly, objective measurement of autonomic and corticospinal integrity did not contribute to HS.

Probing the Brain-Body Connection Using Transcranial Magnetic Stimulation (TMS): Validating a Promising Tool to Provide Biomarkers of Neuroplasticity and Central Nervous System Function.

Transcranial magnetic stimulation (TMS) is a non-invasive method used to investigate neurophysiological integrity of the human neuromotor system. We describe in detail, the methodology of a single pulse TMS protocol that was performed in a large cohort of people (n = 110) with multiple sclerosis (MS). The aim was to establish and validate a core-set of TMS variables that predicted typical MS clinical outcomes: walking speed, hand dexterity, fatigue, and cognitive processing speed. We provide a brief and simple methodological pipeline to examine excitatory and inhibitory corticospinal mechanisms in MS that map to clinical status. Delayed and longer ipsilateral silent period (a measure of transcallosal inhibition; the influence of one brain hemisphere's activity over the other), longer cortical silent period (suggestive of greater corticospinal inhibition via GABA) and higher resting motor threshold (lower corticospinal excitability) most strongly related to clinical outcomes, especially when measured in the hemisphere corresponding to the weaker hand. Greater interhemispheric asymmetry (imbalance between hemispheres) correlated with poorer performance in the greatest number of clinical outcomes. We also show, not surprisingly, that TMS variables related more strongly to motor outcomes than non-motor outcomes. As it was validated in a large sample of patients with varying severities of central nervous system dysfunction, the protocol described herein can be used by investigators and clinicians alike to investigate the role of TMS as a biomarker in MS and other central nervous system disorders.

Higher Quadriceps Roller Massage Forces Do Not Amplify Range-of-Motion Increases nor Impair Strength and Jump Performance.

Grabow, L, Young, JD, Alcock, LR, Quigley, PJ, Byrne, JM, Granacher, U, Skarabot, J, and Behm, DG. Higher quadriceps roller massage forces do not amplify range-of-motion increases nor impair strength and jump performance. J Strength Cond Res 32(11): 3059-3069, 2018-Roller massage (RM) has been reported to increase range of motion (ROM) without subsequent performance decrements. However, the effects of different rolling forces have not been examined. The purpose of this study was to compare the effects of sham (RMsham), moderate (RMmod), and high (RMhigh) RM forces, calculated relative to the individuals' pain perception, on ROM, strength, and jump parameters. Sixteen healthy individuals (27 ± 4 years) participated in this study. The intervention involved three 60-second quadriceps RM bouts with RMlow (3.9/10 ± 0.64 rating of perceived pain [RPP]), RMmod (6.2/10 ± 0.64 RPP), and RMhigh (8.2/10 ± 0.44 RPP) pain conditions, respectively. A within-subject design was used to assess dependent variables (active and passive knee flexion ROM, single-leg drop jump [DJ] height, DJ contact time, DJ performance index, maximum voluntary isometric contraction [MVIC] force, and force produced in the first 200 milliseconds [F200] of the knee extensors and flexors). A 2-way repeated measures analysis of variance showed a main effect of testing time in active (p < 0.001, d = 2.54) and passive (p < 0.001, d = 3.22) ROM. Independent of the RM forces, active and passive ROM increased by 7.0% (p = 0.03, d = 2.25) and 15.4% (p < 0.001, d = 3.73) from premeasure to postmeasure, respectively. Drop jump and MVIC parameters were unaffected from pretest to posttest (p > 0.05, d = 0.33-0.84). Roller massage can be efficiently used to increase ROM without substantial pain and without subsequent performance impairments.

Phase- and Workload-Dependent Changes in Corticospinal Excitability to the Biceps and Triceps Brachii during Arm Cycling.

This is the first study to examine corticospinal excitability (CSE) to antagonistic muscle groups during arm cycling. Transcranial magnetic stimulation (TMS) of the motor cortex and transmastoid electrical stimulation (TMES) of the corticospinal tract were used to assess changes in supraspinal and spinal excitability, respectively. TMS induced motor evoked potentials (MEPs) and TMES induced cervicomedullary evoked potentials (CMEPs) were recorded from the biceps and triceps brachii at two positions, mid-elbow flexion and extension, while cycling at 5% and 15% of peak power output. While phase-dependent modulation of MEP and CMEP amplitudes occurred in the biceps brachii, there was no difference between flexion and extension for MEP amplitudes in the triceps brachii and CMEP amplitudes were higher during flexion than extension. Furthermore, MEP amplitudes in both biceps and triceps brachii increased with increased workload. CMEP amplitudes increased with higher workloads in the triceps brachii, but not biceps brachii, though the pattern of change in CMEPs was similar to MEPs. Differences between changes in CSE between the biceps and triceps brachii suggest that these antagonistic muscles may be under different neural control during arm cycling. Putative mechanisms are discussed.