Strength-trained adults demonstrate greater corticoreticular activation versus untrained controls.

The rapid increase in strength following strength-training involves neural adaptations, however, their specific localisation remains elusive. Prior focus on corticospinal responses prompts this study to explore the understudied cortical/subcortical adaptations, particularly cortico-reticulospinal tract responses, comparing healthy strength-trained adults to untrained peers. Fifteen chronically strength-trained individuals (≥2 years of training, mean age: 24 ± 7 years) were compared with 11 age-matched untrained participants (mean age: 26 ± 8 years). Assessments included maximal voluntary force (MVF), corticospinal excitability using transcranial magnetic stimulation (TMS), spinal excitability (cervicomedullary stimulation), voluntary activation (VA) and reticulospinal tract (RST) excitability, utilizing StartReact responses and ipsilateral motor-evoked potentials (iMEPs) for the flexor carpi radialis muscle. Trained participants had higher normalized MVF (6.4 ± 1.1 N/kg) than the untrained participants (4.8 ± 1.3 N/kg) (p = .003). Intracortical facilitation was higher in the strength-trained group (156 ± 49%) (p = .02), along with greater VA (98 ± 3.2%) (p = .002). The strength-trained group displayed reduced short-interval-intracortical inhibition (88 ± 8.0%) compared with the untrained group (69 ± 17.5%) (p < .001). Strength-trained individuals exhibited a greater normalized rate of force development (38.8 ± 10.1 N·s-1/kg) (p < .009), greater reticulospinal gain (2.5 ± 1.4) (p = .02) and higher ipsilateral-to-contralateral MEP ratios compared with the untrained group (p = .03). Strength-trained individuals displayed greater excitability within the intrinsic connections of the primary motor cortex and the RST. These results suggest greater synaptic input from the descending cortico-reticulospinal tract to α-motoneurons in strength-trained individuals, thereby contributing to the observed increase in VA and MVF.

Short-Latency Afferent Inhibition Correlates with Stage of Disease in Parkinson's Patients.

BACKGROUND: Sensory-motor decoupling at the cortical level involving cholinergic circuitry has also been reported in Parkinson's Disease (PD). Short-latency afferent inhibition (SAI) is a transcranial magnetic stimulation (TMS) paradigm that has been used previously to probe cortical cholinergic circuits in well-characterised subgroups of patients with PD. In the current study, we compared SAI in a cohort of PD patients at various stages of disease and explored correlations between SAI and various clinical measures of disease severity. METHODS: The modified Hoehn and Yahr (H&Y) scale was used to stage disease in 22 patients with PD. Motor and cognitive function were assessed using the MDS-UPDRS (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale) part III and MoCA (Montreal Cognitive Assessment) score, respectively. Objective gait assessment was performed using an electronic walkway (GAITRite®). SAI was measured as the average percentage inhibition of test motor-evoked potentials (MEPs) conditioned by electrical stimulation of the contralateral median nerve at the wrist. RESULTS: SAI was significantly reduced in patients with advanced PD (H&Y stage 3) compared to early PD patients (H&Y stage 1) on pairwise comparison. The visuospatial executive function and orientation domains of cognition demonstrated significant negative associations with SAI. CONCLUSION: Cortical sensory-motor integration is progressively diminished as disease progresses. The observation that a reduction in SAI is associated with a reduction in cognitive function possibly reflects the progressive involvement of cortical cholinergic circuits in PD with increasing motor stage. Future longitudinal studies are necessary to confirm this preliminary result.

Comparing Stop Signal Reaction Times in Alzheimer's and Parkinson's Disease.

BACKGROUND: To investigate the relative contributions of cerebral cortex and basal ganglia to movement stopping, we tested the optimum combination Stop Signal Reaction Time (ocSSRT) and median visual reaction time (RT) in patients with Alzheimer's disease (AD) and Parkinson's disease (PD) and compared values with data from healthy controls. METHODS: Thirty-five PD patients, 22 AD patients, and 29 healthy controls were recruited to this study. RT and ocSSRT were measured using a hand-held battery-operated electronic box through a stop signal paradigm. RESULT: The mean ocSSRT was found to be 309 ms, 368 ms, and 265 ms in AD, PD, and healthy controls, respectively, and significantly prolonged in PD compared to healthy controls (p = 0.001). The ocSSRT but not RT could separate AD from PD patients (p = 0.022). CONCLUSION: Our data suggest that subcortical networks encompassing dopaminergic pathways in the basal ganglia play a more important role than cortical networks in movement-stopping. Combining ocSSRT with other putative indices or biomarkers of AD (and other dementias) could increase the accuracy of early diagnosis.

Differential modulation of corticomotor excitability in older compared to young adults following a single bout of strength -exercise.

Evidence shows corticomotor plasticity diminishes with age. Nevertheless, whether strength-training, a proven intervention that induces corticomotor plasticity in younger adults, also takes effect in older adults, remains untested. This study examined the effect of a single-session of strength-exercise on corticomotor plasticity in older and younger adults. Thirteen older adults (72.3 ± 6.5 years) and eleven younger adults (29.9 ± 6.9 years), novice to strength-exercise, participated. Strength-exercise involved four sets of 6-8 repetitions of a dumbbell biceps curl at 70-75% of their one-repetition maximum (1-RM). Muscle strength, cortical, corticomotor and spinal excitability, before and up to 60-minutes after the strength-exercise session were assessed. We observed significant changes over time (p < 0.05) and an interaction between time and age group (p < 0.05) indicating a decrease in corticomotor excitability (18% p < 0.05) for older adults at 30- and 60-minutes post strength-exercise and an increase (26% and 40%, all p < 0.05) in younger adults at the same time points. Voluntary activation (VA) declined in older adults immediately post and 60-minutes post strength-exercise (36% and 25%, all p < 0.05). Exercise had no effect on the cortical silent period (cSP) in older adults however, in young adults cSP durations were shorter at both 30- and 60- minute time points (17% 30-minute post and 9% 60-minute post, p < 0.05). There were no differences in short-interval cortical inhibition (SICI) or intracortical facilitation (ICF) between groups. Although the corticomotor responses to strength-exercise were different within groups, overall, the neural responses seem to be independent of age.

Identifying the role of the reticulospinal tract for strength and motor recovery: A scoping review of nonhuman and human studies.

In addition to the established postural control role of the reticulospinal tract (RST), there has been an increasing interest on its involvement in strength, motor recovery, and other gross motor functions. However, there are no reviews that have systematically assessed the overall motor function of the RST. Therefore, we aimed to determine the role of the RST underpinning motor function and recovery. We performed a literature search using Ovid Medline, Embase, CINAHL Plus, and Scopus to retrieve papers using key words for RST, strength, and motor recovery. Human and animal studies which assessed the role of RST were included. Studies were screened and 32 eligible studies were included for the final analysis. Of these, 21 of them were human studies while the remaining were on monkeys and rats. Seven experimental animal studies and four human studies provided evidence for the involvement of the RST in motor recovery, while two experimental animal studies and eight human studies provided evidence for strength gain. The RST influenced gross motor function in two experimental animal studies and five human studies. Overall, the RST has an important role for motor recovery, gross motor function and at least in part, underpins strength gain. The role of RST for strength gain in healthy people and its involvement in spasticity in a clinical population has been limitedly described. Further studies are required to ascertain the role of the RST's role in enhancing strength and its contribution to the development of spasticity.

Determining the cortical, spinal and muscular adaptations to strength-training in older adults: A systematic review and meta-analysis.

There are observable decreases in muscle strength as a result of ageing that occur from the age of 40, which are thought to occur as a result of changes within the neuromuscular system. Strength-training in older adults is a suitable intervention that may counteract the age-related loss in force production. The neuromuscular adaptations (i.e., cortical, spinal and muscular) to strength-training in older adults are largely equivocal and a systematic review with meta-analysis will serve to clarify the present circumstances regarding the benefits of strength-training in older adults. 20 studies entered the meta-analysis and were analysed using a random-effects model. A best evidence synthesis that included 36 studies was performed for variables that had insufficient data for meta-analysis. One study entered both. There was strong evidence that strength-training increases maximal force production, rate of force development and muscle activation in older adults. There was limited evidence for strength-training to improve voluntary-activation, the volitional-wave and spinal excitability, but strong evidence for increased muscle mass. The findings suggest that strength-training performed between 2 and 12 weeks increases strength, rate of force development and muscle activation, which likely improves motoneurone excitability by increased motor unit recruitment and improved discharge rates.

Is peripheral alpha synuclein a marker for gait velocity in Parkinson's disease?

BACKGROUND: The extent of gait abnormality is non-uniform across motor phenotypes of Parkinson's disease (PD). The biological basis of this heterogeneity remains intriguing. Moreover, the relationship of gait impairment with various neurodegenerative protein markers in PD is not well established. OBJECTIVES: Here, we aimed to explore the interplay between gait parameters and specific serum protein markers in PD. METHODS: A total of 62 PD patients were consecutively recruited. Blood samples and gait data were acquired from 37 and 34 patients respectively. Two-dimensional spatio-temporal gait parameters were estimated using an electronic walkway (GAITRite®, CIR Systems Inc., USA). Serum phosphorylated alpha synuclein (p-Ser129-a-syn) and total a-syn levels were measured using commercially available ELISA kit. Data was analyzed using SPSS Version 20 (IBM). RESULTS: We found that phosphorylated a-syn levels were significantly higher in PD patients with postural instability and gait difficulty compared to tremor dominant variant. Significant reduction in gait velocity was also observed with increasing levels of this pathological form of a-syn. Regression modelling showed that phosphorylated a-syn is an independent predictor of gait velocity. DISCUSSION: Our findings indicate that concentrations of peripheral p-Ser129-a-syn but not total a-syn could be a potential contributor of gait impairment in PD. Further investigation on the systemic role of phosphorylated a-syn on gait would bridge the gap between central and peripheral mechanisms underlying phenotypic variability in PD.

A longitudinal quantitative analysis of gait in patients with SCA-12.

INTRODUCTION: Spinocerebellar ataxia type 12 (SCA 12) is characterized by late onset tremor, ataxia and pyramidal signs. Parkinsonism and cognitive decline may appear with time. It is considered as slowly progressive but temporal evolution of symptoms has not been reported. METHOD: We report the evolution of symptoms in three SCA12 patients followed over a range of 5-6 years. We focused on the evolution of gait abnormality as it becomes the most disabling symptom as disease advances. Two-dimensional gait parameters were studied using an electronic walkway at various time points to measure objective changes in gait. RESULT: All patients presented with tremor in the upper extremity at baseline which progressed non-uniformly over the years. Progression of gait variability measures of step length, stance time and step time were also observed. CONCLUSION: Gait characteristics such as variability may precede clinical gait abnormality and could serve as a sensitive marker for disease progression for better therapeutic intervention in disease management. Future studies with larger sample size should be undertaken to conclusively validate this observation.

Semantic Fluency Predicts Gait Velocity in PSP.

Context: Progressive supranuclear palsy (PSP) is a large-scale network disease resulting in variable signs and symptoms including gait impairment and higher order cognitive dysfunction. Despite few studies showing the association of falls and cognitive dysfunction, the existing literature is yet to establish the exact relationship of discrete characteristics of gait with cognitive function in PSP. Aims: In this cross-sectional study, we aimed to characterize and explore the relationship of these two apparently distinct physiological phenomena in patients with PSP and across its different variants. Methods and Material: Quantitative assessment of two-dimensional gait parameters was measured using an electronic walkway (GAITRite®). Dementia Rating Scale-2 was used to assess global as well as higher order cognitive functions. Statistical Analysis Used: A regression model was used to interpret results. Results: We observed that the variability domain of gait was significantly impaired in PSP patients with severe cognitive impairment compared to that of intact cognition. Moreover, initiation/perseveration (I/P), a higher order cognitive process, and one of its specific components, i.e., complex verbal task (ß = 2.39, P < 0.001), significantly predict gait velocity in PSP [F (1, 40) = 16.102, P < 0.001]. Conclusions: Our findings indicate that the severity of cognitive functions affects gait variability, which might lead to frequent falls as observed in PSP. Furthermore, semantic fluency task of I/P function may act as a predictor of gait velocity. We suspect that higher order cognitive dysfunction through the damage of frontal lobe structure including dorsolateral prefrontal cortex or related network may influence gait in PSP.

Task-dependent modulation of corticospinal excitability and inhibition following strength training.

This study determined whether there are task-dependent differences in cortical excitability following different types of strength training. Transcranial magnetic stimulation (TMS) measured corticospinal excitability (CSE) and intracortical inhibition (ICI) of the biceps brachii muscle in 42 healthy subjects that were randomised to either paced-strength-training (PST, n = 11), self-paced strength-training (SPST, n = 11), isometric strength-training (IST, n = 10) or to a control group (n = 10). Single-pulse and paired-pulse TMS were applied prior to and following 4-weeks of strength-training. PST increased CSE compared to SPST, IST and the control group (all P < 0.05). ICI was only reduced (60%) following PST. Dynamic strength increased by 18 and 25% following PST and SPST, whilst isometric strength increased by 20% following IST. There were no associations between the behavioural outcome measures and the change in CSE and ICI. The corticospinal responses to strength-training are task-dependent, which is a new finding. Strength-training that is performed slowly could promote use-dependent plasticity in populations with reduced volitional drive, such as during periods of limb immobilization, musculoskeletal injury or stroke.

Determining the Sites of Neural Adaptations to Resistance Training: A Systematic Review and Meta-analysis.

BACKGROUND: Resistance-training causes changes in the central nervous system (CNS); however, the sites of these adaptations remain unclear. OBJECTIVE: To determine sites of neural adaptation to resistance-training by conducting a systematic review and meta-analysis on the cortical and subcortical responses to resistance-training. METHODS: Evidence from randomized controlled trials (RCTs) that focused on neural adaptations to resistance-training was pooled to assess effect estimates for changes in strength, cortical, and subcortical adaptations. RESULTS: The magnitude of strength gain in 30 RCTs (n = 623) reported a standardised mean difference (SMD) of 0.67 (95% CI 0.41, 0.94; P < 0.001) that measured at least one cortical/subcortical neural adaptation which included: motor-evoked potentials (MEP; 19 studies); silent period (SP; 7 studies); short-interval intracortical inhibition (SICI; 7 studies); cervicomedullary evoked potentials (CMEP; 1 study); transcranial magnetic stimulation voluntary activation (VATMS; 2 studies); H-reflex (10 studies); and V-wave amplitudes (5 studies). The MEP amplitude during voluntary contraction was greater following resistance-training (SMD 0.55; 95% CI 0.27, 0.84; P < 0.001, n = 271), but remained unchanged during rest (SMD 0.49; 95% CI -0.68, 1.66; P = 0.41, n = 114). Both SP (SMD 0.65; 95% CI 0.29, 1.01; P < 0.001, n = 184) and active SICI (SMD 0.68; 95% CI 0.14, 1.23; P = 0.01, n = 102) decreased, but resting SICI remained unchanged (SMD 0.26; 95% CI - 0.29, 0.81; P = 0.35, n = 52). Resistance-training improved neural drive as measured by V-wave amplitude (SMD 0.62; 95% CI 0.14, 1.10; P = 0.01, n = 101), but H-reflex at rest (SMD 0.16; 95% CI - 0.36, 0.68; P = 0.56; n = 57), during contraction (SMD 0.15; 95% CI - 0.18, 0.48; P = 0.38, n = 142) and VATMS (MD 1.41; 95% CI - 4.37, 7.20; P = 0.63, n = 44) remained unchanged. CONCLUSION: There are subtle neural adaptations following resistance-training involving both cortical and subcortical adaptations that act to increase motoneurone activation and likely contribute to the training-related increase in muscle strength.