Role of the Cerebellum in the Construction of Functional and Geometrical Spaces.

The perceptual and motor systems appear to have a set of movement primitives that exhibit certain geometric and kinematic invariances. Complex patterns and mental representations can be produced by (re)combining some simple motor elements in various ways using basic operations, transformations, and respecting a set of laws referred to as kinematic laws of motion. For example, point-to-point hand movements are characterized by straight hand paths with single-peaked-bell-shaped velocity profiles, whereas hand speed profiles for curved trajectories are often irregular and more variable, with speed valleys and inflections extrema occurring at the peak curvature. Curvature and speed are generically related by the 2/3 power law. Mathematically, such laws can be deduced from a combination of Euclidean, affine, and equi-affine geometries, whose neural correlates have been partially detected in various brain areas including the cerebellum and the basal ganglia. The cerebellum has been found to play an important role in the control of coordination, balance, posture, and timing over the past years. It is also assumed that the cerebellum computes forward internal models in relationship with specific cortical and subcortical brain regions but its motor relationship with the perceptual space is unclear. A renewed interest in the geometrical and spatial role of the cerebellum may enable a better understanding of its specific contribution to the action-perception loop and behavior's adaptation. In this sense, we complete this overview with an innovative theoretical framework that describes a possible implementation and selection by the cerebellum of geometries adhering to different mathematical laws.

Detection of atypical attentional behaviors in young subjects.

BACKGROUND: Vigilance ability refers to the accuracy and speed with which a person performs a cognitive-motor task, either voluntarily (endogenous mode) or following a warning stimulus (exogenous mode). In the context of a force production task, our study focuses on the impact of the states of vigilance by proposing an original approach that allows distinguishing between good (inlier) and poor (outlier) participants. We assume that the use of an external signal and duration of the temporal preparation (foreperiod) increase the speed and the precision of motor responses. Our objective is particularly challenging in the context of a limited dataset with a high level of noise. NEW METHOD: Our original methodological approach consists of coupling the RANSAC (RANdom SAmple Consensus) algorithm with a statistical machine learning algorithm to handle noise. COMPARISON WITH EXISTING METHODS: Our clustering approach, based on the coupling of RANSAC methodology with ensemble classifiers, overcomes the limitations of conventional supervised algorithms that are either not robust to outliers (such as K-Nearest Neighbors) and/or not adapted to few-shot learning (such as Support Vector Machines and Artificial Neural Networks). RESULTS: The clustering results were validated in terms of reaction time distributions and force error distributions with respect to participant groups. We show that the use of an external signal and duration of the temporal preparation (foreperiod) increase the speed and the precision of motor responses. CONCLUSION: Our study has allowed us to detect atypical attentional patterns and succeeds in separating the inliers from the outliers.

Influence of Mental Training of Attentional Control on Autonomic Arousal Within the Framework of the Temporal Preparation of a Force Task.

While temporal preparation has frequently been examined through the manipulation of foreperiods, the role of force level during temporal preparation remains underexplored. In our study, we propose to manipulate mental training of attentional control in order to shed light on the role of the force level and autonomic nervous system in the temporal preparation of an action. Forty subjects, divided into mental training group (n = 20) and without mental training group (n = 20), participated in this study. The influence of the attentional control and force levels on the autonomic nervous system were measured using the skin conductance response and the heart rate variability; the accuracy of the motor responses was measured using a method derived from machine learning. Behaviorally, only the mental training group reinforced its motor and attentional control. When using short foreperiod durations and high force level, motor and attentional control decreased, consistent with the dominant sympathetic system. This resulted in an increased anticipation rate of responses with a higher reaction time compared to the long foreperiods duration and low force level, in which the reaction time significantly decreased, with enhancement of the expected force level, showing consistency with the dominant parasympathetic system. Interestingly, results revealed a predictive relationship between the sympathovagal balance and motor and attentional control during the long foreperiods and low force level. Finally, results demonstrate that attentional mental training leads to the reinforcement of interactions between the autonomic nervous system and attentional processes which are involved in the temporal preparation of a force task.

Shared and Unique Disease Pathways in Amyotrophic Lateral Sclerosis and Parkinson's Disease Unveiled in Peripheral Blood Mononuclear Cells.

Recent evidence supports an association between amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). Indeed, prospective population-based studies demonstrated that about one-third of ALS patients develop parkinsonian (PK) signs, even though different neuronal circuitries are involved. In this context, proteomics represents a valuable tool to identify unique and shared pathological pathways. Here, we used two-dimensional electrophoresis to obtain the proteomic profile of peripheral blood mononuclear cells (PBMCs) from PD and ALS patients including a small cohort of ALS patients with parkinsonian signs (ALS-PK). After the removal of protein spots correlating with confounding factors, we applied a sparse partial least square discriminant analysis followed by recursive feature elimination to obtain two protein classifiers able to discriminate (i) PD and ALS patients (30 spots) and (ii) ALS-PK patients among all ALS subjects (20 spots). Functionally, the glycolysis pathway was significantly overrepresented in the first signature, while extracellular interactions and intracellular signaling were enriched in the second signature. These results represent molecular evidence at the periphery for the classification of ALS-PK as ALS patients that manifest parkinsonian signs, rather than comorbid patients suffering from both ALS and PD. Moreover, we confirmed that low levels of fibrinogen in PBMCs is a characteristic feature of PD, also when compared with another movement disorder. Collectively, we provide evidence that peripheral protein signatures are a tool to differentially investigate neurodegenerative diseases and highlight altered biochemical pathways.

Dysfunction of basal ganglia functional connectivity associated with subjective and cognitive fatigue in multiple sclerosis.

Objectives: Central fatigue is one of the most common symptoms in multiple sclerosis (MS). It has a profound impact on quality of life and a negative effect on cognition. Despite its widespread impact, fatigue is poorly understood and very difficult to measure. Whilst the basal ganglia has been implicated in fatigue the nature of its role and involvement with fatigue is still unclear. The aim of the present study was to establish the role of the basal ganglia in MS fatigue using functional connectivity measures. Methods: The present study examined the functional connectivity (FC) of the basal ganglia in a functional MRI study with 40 female participants with MS (mean age = 49.98 (SD = 9.65) years) and 40 female age-matched (mean age = 49.95 (SD = 9.59) years) healthy controls (HC). To measure fatigue the study employed the subjective self-report Fatigue Severity Scale and a performance measure of cognitive fatigue using an alertness-motor paradigm. To distinguish physical and central fatigue force measurements were also recorded. Results: The results suggest that decreased local FC within the basal ganglia plays a key role in cognitive fatigue in MS. Increased global FC between the basal ganglia and the cortex may sub serve a compensatory mechanism to reduce the impact of fatigue in MS. Conclusion: The current study is the first to show that basal ganglia functional connectivity is associated with both subjective and objective fatigue in MS. In addition, the local FC of the basal ganglia during fatigue inducing tasks could provide a neurophysiological biomarker of fatigue.

Human Exteroception during Object Handling with an Upper Limb Exoskeleton.

Upper limb exoskeletons may confer significant mechanical advantages across a range of tasks. The potential consequences of the exoskeleton upon the user's sensorimotor capacities however, remain poorly understood. The purpose of this study was to examine how the physical coupling of the user's arm to an upper limb exoskeleton influenced the perception of handheld objects. In the experimental protocol, participants were required to estimate the length of a series of bars held in their dominant right hand, in the absence of visual feedback. Their performance in conditions with an exoskeleton fixed to the forearm and upper arm was compared to conditions without the upper limb exoskeleton. Experiment 1 was designed to verify the effects of attaching an exoskeleton to the upper limb, with object handling limited to rotations of the wrist only. Experiment 2 was designed to verify the effects of the structure, and its mass, with combined movements of the wrist, elbow, and shoulder. Statistical analysis indicated that movements performed with the exoskeleton did not significantly affect perception of the handheld object in experiment 1 (BF01 = 2.3) or experiment 2 (BF01 = 4.3). These findings suggest that while the integration of an exoskeleton complexifies the architecture of the upper limb effector, this does not necessarily impede transmission of the mechanical information required for human exteroception.

Plasma CHI3L1 in Amyotrophic Lateral Sclerosis: A Potential Differential Diagnostic Biomarker.

(1) Background: Motor neuron diseases (MNDs) are fatal neurodegenerative diseases. Biomarkers could help with defining patients' prognoses and stratifications. Besides neurofilaments, chitinases are a promising family of possible biomarkers which correlate with neuroinflammatory status. We evaluated the plasmatic levels of CHI3L1 in MNDs, MND mimics, and healthy controls (HCs). (2) Methods: We used a sandwich ELISA to quantify the CHI3L1 in plasma samples from 44 MND patients, 7 hereditary spastic paraplegia (HSP) patients, 9 MND mimics, and 19 HCs. We also collected a ALSFRSr scale, MRC scale, spirometry, mutational status, progression rate (PR), blood sampling, and neuropsychological evaluation. (3) Results: The plasma levels of the CHI3L1 were different among groups (p = 0.005). Particularly, the MND mimics showed higher CHI3L1 levels compared with the MND patients and HCs. The CHI3L1 levels did not differ among PMA, PLS, and ALS, and we did not find a correlation among the CHI3L1 levels and clinical scores, spirometry parameters, PR, and neuropsychological features. Of note, the red blood cell count and haemoglobin was correlated with the CHI3L1 levels (respectively, p < 0.001, r = 0.63; p = 0.022, and r = 0.52). (4) Conclusions: The CHI3L1 plasma levels were increased in the MND mimics cohort compared with MNDs group. The increase of CHI3L1 in neuroinflammatory processes could explain our findings. We confirmed that the CHI3L1 plasma levels did not allow for differentiation between ALS and HCs, nor were they correlated with neuropsychological impairment.

SOMAscan Proteomics Identifies Novel Plasma Proteins in Amyotrophic Lateral Sclerosis Patients.

Amyotrophic lateral sclerosis (ALS) is a complex disease characterized by the interplay of genetic and environmental factors for which, despite decades of intense research, diagnosis remains rather delayed, and most therapeutic options fail. Therefore, unravelling other potential pathogenetic mechanisms and searching for reliable markers are high priorities. In the present study, we employ the SOMAscan assay, an aptamer-based proteomic technology, to determine the circulating proteomic profile of ALS patients. The expression levels of ~1300 proteins were assessed in plasma, and 42 proteins with statistically significant differential expression between ALS patients and healthy controls were identified. Among these, four were upregulated proteins, Thymus- and activation-regulated chemokine, metalloproteinase inhibitor 3 and nidogen 1 and 2 were selected and validated by enzyme-linked immunosorbent assays in an overlapping cohort of patients. Following statistical analyses, different expression patterns of these proteins were observed in the familial and sporadic ALS patients. The proteins identified in this study might provide insight into ALS pathogenesis and represent potential candidates to develop novel targeted therapies.

Phenotype Analysis of Fused in Sarcoma Mutations in Amyotrophic Lateral Sclerosis.

Background and Objectives: Pathogenic variations in fused in sarcoma (FUS) are among the most common genetic causes of amyotrophic lateral sclerosis (ALS) worldwide. They are supposedly characterized by a homogeneous pure motor phenotype with early-onset and short disease duration. However, a few FUS-mutated cases with a very late disease onset and slow progression have been reported. To analyze genotype-phenotype correlations and identify the prognostic factors in FUS-ALS cases. Methods: We identified and cross-sectionally analyzed 22 FUS-ALS patient histories from a single-center cohort of 2,615 genetically tested patients and reviewed 289 previously published FUS-ALS cases. Survival analysis was performed by Kaplan-Meier survival curves, followed by the log-rank test and multivariate Cox analysis. Results: Survival of FUS-ALS is age-dependent: In our cohort, early-onset cases had a rapid disease progression and short survival (p = 0.000003) while the outcome of FUS-mutated patients with mid-to-late onset did not differ from non-FUS-ALS patients (p = 0.437). Meta-analysis of literature data confirmed this trend (p = 0.00003). This survival pattern is not observed in other ALS-related genes in our series. We clustered FUS-ALS patients in 3 phenotypes: (1) axial ALS, with upper cervical and dropped-head onset in mid-to-late adulthood; (2) benign ALS, usually with a late-onset and slow disease progression; and (3) juvenile ALS, often with bulbar onset and preceded by learning disability or mild mental retardation. Those phenotypes arise from different mutations. Discussion: We observed specific genotype-phenotype correlations of FUS-ALS and identified age at onset as the most critical prognostic factor. Our results demonstrated that FUS mutations underlie a specific subtype of ALS and enable a careful stratification of newly diagnosed FUS-ALS cases for clinical course and potential therapeutic windows. This will be crucial in the light of incoming gene-specific therapy.

Motor imagery in amyotrophic lateral Sclerosis: An fMRI study of postural control.

BACKGROUND: The functional reorganization of brain networks sustaining gait is poorly characterized in amyotrophic lateral sclerosis (ALS) despite ample evidence of progressive disconnection between brain regions. The main objective of this fMRI study is to assess gait imagery-specific networks in ALS patients using dynamic causal modeling (DCM) complemented by parametric empirical Bayes (PEB) framework. METHOD: Seventeen lower motor neuron predominant (LMNp) ALS patients, fourteen upper motor neuron predominant (UMNp) ALS patients and fourteen healthy controls participated in this study. Each subject performed a dual motor imagery task: normal and precision gait. The Movement Imagery Questionnaire (MIQ-rs) and imagery time (IT) were used to evaluate gait imagery in each participant. In a neurobiological computational model, the circuits involved in imagined gait and postural control were investigated by modelling the relationship between normal/precision gait and connection strengths. RESULTS: Behavioral results showed significant increase in IT in UMNp patients compared to healthy controls (Pcorrected < 0.05) and LMNp (Pcorrected < 0.05). During precision gait, healthy controls activate the model's circuits involved in the imagined gait and postural control. In UMNp, decreased connectivity (inhibition) from basal ganglia (BG) to supplementary motor area (SMA) and from SMA to posterior parietal cortex (PPC) is observed. Contrary to healthy controls, DCM detects no cerebellar-PPC connectivity in neither UMNp nor LMNp ALS. During precision gait, bilateral connectivity (excitability) between SMA and BG is observed in the LMNp group contrary to UMNp and healthy controls. CONCLUSIONS: Our findings demonstrate the utility of implementing both DCM and PEB to characterize connectivity patterns in specific patient phenotypes. Our approach enables the identification of specific circuits involved in postural deficits, and our findings suggest a putative excitatory-inhibitory imbalance. More broadly, our data demonstrate how clinical manifestations are underpinned by network-specific disconnection phenomena in ALS.

Theoretical discrimination index of postural instability in amyotrophic lateral sclerosis.

To assess the usefulness of a theoretical postural instability discrimination index (PIth) in amyotrophic lateral sclerosis (ALS). Prospective regression analyzes were performed to identify the biomechanical determinants of postural instability unrelated to lower limb motor deficits from gait initiation factors. PIth was constructed using a logit function of biomechanical determinants. Discriminatory performance and performance differences were tested. Backward displacement of the pression center (APAamplitude) and active vertical braking of the mass center (Braking-index) were the biomechanical determinants of postural instability. PIth = - 0.13 × APAamplitude - 0.12 × Braking-index + 5.67, (P < 0.0001, RSquare = 0.6119). OR (APAamplitude) and OR (Braking-index) were 0.878 and 0.887, respectively, i.e., for a decrease of 10 mm in APAamplitude or 10% in Braking-index, the postural instability risk was 11.391 or 11.274 times higher, respectively. PIth had the highest discriminatory performance (AUC 0.953) with a decision threshold value [Formula: see text] 0.587, a sensitivity of 90.91%, and a specificity of 83.87%, significantly increasing the sensitivity by 11.11%. PIth, as objective clinical integrator of gait initiation biomechanical processes significantly involved in dynamic postural control, was a reliable and performing discrimination index of postural instability with a significant increased sensitivity, and may be useful for a personalized approach to postural instability in ALS.

Effects of intracellular calcium accumulation on proteins encoded by the major genes underlying amyotrophic lateral sclerosis.

The aetiology of Amyotrophic Lateral Sclerosis (ALS) is still poorly understood. The discovery of genetic forms of ALS pointed out the mechanisms underlying this pathology, but also showed how complex these mechanisms are. Excitotoxicity is strongly suspected to play a role in ALS pathogenesis. Excitotoxicity is defined as neuron damage due to excessive intake of calcium ions (Ca2+) by the cell. This study aims to find a relationship between the proteins coded by the most relevant genes associated with ALS and intracellular Ca2+ accumulation. In detail, the profile of eight proteins (TDP-43, C9orf72, p62/sequestosome-1, matrin-3, VCP, FUS, SOD1 and profilin-1), was analysed in three different cell types induced to raise their cytoplasmic amount of Ca2+. Intracellular Ca2+ accumulation causes a decrease in the levels of TDP-43, C9orf72, matrin3, VCP, FUS, SOD1 and profilin-1 and an increase in those of p62/sequestosome-1. These events are associated with the proteolytic action of two proteases, calpains and caspases, as well as with the activation of autophagy. Interestingly, Ca2+ appears to both favour and hinder autophagy. Understanding how and why calpain-mediated proteolysis and autophagy, which are physiological processes, become pathological may elucidate the mechanisms responsible for ALS and help discover new therapeutic targets.

A novel splice site FUS mutation in a familial ALS case: effects on protein expression.

Objective: To investigate the impact of a novel heterozygous FUS mutation in the acceptor splice site of intron 14 (c.1542 - 1 g > t) on protein expression in Peripheral Blood Mononuclear Cells (PBMC) from a familial ALS patient. Methods: PBMC were isolated for mRNA analysis (cDNA synthesis, sequencing and one-step RT-PCR), Western Immunoblot (WI), and Immunofluorescence (IF). Results: cDNA analysis revealed the skipping of exon 15 and a premature stop codon at c.228. RT-PCR showed reduced FUS mRNA by more than half compared to a healthy control (HC) and an ALS patient without genetic mutations (wtALS). In WI FUS band intensity in the proband was 30-50% compared to HC and wtALS. An antibody expected to detect only the wild-type protein did not reveal any reduction of FUS band intensity compared to the other antibodies. IF showed no difference among HC, wtALS, and the proband. Discussion: The reduction of FUS mRNA and protein in PBMC suggests the absence of the truncated protein, probably due to nonsense-mediated decay, leading to loss of function.

Defective cyclophilin A induces TDP-43 proteinopathy: implications for amyotrophic lateral sclerosis and frontotemporal dementia.

Aggregation and cytoplasmic mislocalization of TDP-43 are pathological hallmarks of amyotrophic lateral sclerosis and frontotemporal dementia spectrum. However, the molecular mechanism by which TDP-43 aggregates form and cause neurodegeneration remains poorly understood. Cyclophilin A, also known as peptidyl-prolyl cis-trans isomerase A (PPIA), is a foldase and molecular chaperone. We previously found that PPIA interacts with TDP-43 and governs some of its functions, and its deficiency accelerates disease in a mouse model of amyotrophic lateral sclerosis. Here we characterized PPIA knock-out mice throughout their lifespan and found that they develop a neurodegenerative disease with key behavioural features of frontotemporal dementia, marked TDP-43 pathology and late-onset motor dysfunction. In the mouse brain, deficient PPIA induces mislocalization and aggregation of the GTP-binding nuclear protein Ran, a PPIA interactor and a master regulator of nucleocytoplasmic transport, also for TDP-43. Moreover, in absence of PPIA, TDP-43 autoregulation is perturbed and TDP-43 and proteins involved in synaptic function are downregulated, leading to impairment of synaptic plasticity. Finally, we found that PPIA was downregulated in several patients with amyotrophic lateral sclerosis and amyotrophic lateral sclerosis-frontotemporal dementia, and identified a PPIA loss-of-function mutation in a patient with sporadic amyotrophic lateral sclerosis . The mutant PPIA has low stability, altered structure and impaired interaction with TDP-43. These findings strongly implicate that defective PPIA function causes TDP-43 mislocalization and dysfunction and should be considered in future therapeutic approaches.

The heterozygous deletion c.1509_1510delAG in exon 14 of FUS causes an aggressive childhood-onset ALS with cognitive impairment.

We report a case of childhood-onset ALS with a FUS gene mutation presenting cognitive impairment and a rapid clinical progression. The patient, an 11-year-old girl, presented with right distal upper limb weakness and mild intellectual disability at the Griffith Mental Development Scales. The disease rapidly worsened and the patient became tetraplegic and bed-ridden 2 years after symptom onset. A c.1509_1510delAG mutation in exon 14 of the FUS gene was detected, resulting in a predicted truncated protein, p.G504Wfs*12, lacking the nuclear localization signal. The levels of FUS mRNA in the proband were not significantly different compared to controls. Western immunoblot analysis showed that one antibody (500-526) detected in the proband ~50% of the amount of FUS protein compared to controls, while 3 other antibodies (2-27, 400-450 and FUS C-terminal), which recognize both wild type and the mutated FUS, detected 60% to 75% of the amount of the protein. These findings indicate that p.G504Wfs*12 FUS is more prone to undergo post-translational modification respect to wild type FUS.

Improving Health of People With Multiple Sclerosis From a Multicenter Randomized Controlled Study in Parallel Groups: Preliminary Results on the Efficacy of a Mindfulness Intervention and Intention Implementation Associated With a Physical Activity Program.

Objectives: The objective of this study is to investigate the efficacy of psychological Interventions - Mindfulness or Implementation Intention - associated with a Physical Activity program, delivered via internet, in reducing Multiple Sclerosis symptoms. Method: Thirty-five adults were randomly assigned to one of the three groups: a Mindfulness-Based Intervention group (N = 12), Implementation Intention group (N = 11), and a Control Group (N = 12). All the groups received the same Physical Activity program. The Mindfulness condition group received daily training in the form of pre-recorded sessions while the Implementation group elaborated their specific plans once a week. Mobility, fatigue, and the impact of the disease on the patient's life were measured. Two measurement times are carried out in pre-post intervention, at baseline and after eight weeks. Results: Overall, after 8 weeks intervention, results show that there was a significant increase in Walking distance in the three groups. In addition, the within-group analysis showed a statistically significant improvement between pre and post intervention on the physical component of the Disease Impact scale in the Implementation Intention group (p = 0.023) with large effect size, in the Mindfulness-Based Intervention group (p = 0.008) with a medium effect size and in the control group (p = 0.028) with small effect size. In the Implementation Intention group, all physical, psychosocial and cognitive Fatigue Impact subscales scores decreased significantly (p = 0.022, p = 0.023, and p = 0.012, respectively) and the physical component was statistically and negatively correlated (r = -0.745; p = 0.008) when Implementation Intention group practice a mild to moderate physical activity. In the Mindfulness-Based Intervention group, the physical component (MFIS) showed a statistically significant improvement (p = 0.028) but no correlation with moderate-to-vigorous physical activity (MVPA); the control group outcomes did not reveal any significant change. Conclusion: The results of this study are very encouraging and show the feasibility of Mindfulness interventions associated with physical activity to improve the health of people with MS. Further study should assess Mindfulness interventions tailored to MS condition and using both hedonic and eudemonic measures of happiness.

Neural Correlates of Motor Imagery of Gait in Amyotrophic Lateral Sclerosis.

BACKGROUND: Gait impairment is poorly characterized in amyotrophic lateral sclerosis (ALS), despite increasing evidence of extrapyramidal and cerebellar dysfunction. Gait impairment adds to the considerable motor disability of ALS patients and requires targeted multidisciplinary interventions. PURPOSE: To assess gait imagery-specific networks and functional adaptation in ALS. STUDY TYPE: Prospective. POPULATION: Seventeen ALS patients with lower motor neuron predominant (LMNp) disability, 14 patients with upper motor neurons predominant (UMNp) disease, and 14 healthy controls were included. FIELD STRENGTH/SEQUENCES: 3T / gradient echo echo planar (GE-EPI). ASSESSMENT: Subjects performed a dual motor imagery task: normal and precision gait. The Movement Imagery Questionnaire - Revised Second Version (MIQ-rs) was used to appraise movement imagery in each participant. Study group-specific activation patterns were evaluated during motor imagery of gait. Additional generalized psychophysiological interaction analyses were carried out using the supplementary motor area, caudate, cerebellum, and superior parietal lobule as seed regions. STATISTICAL TESTS: Repeated-measures analysis of variance (ANOVA) was used to compare time imagery and MIQ-rs scores between groups. Size effects were also reported as partial eta squared (η2). One-way ANOVA was performed to explore differences in terms of connexions during motor imagery tasks. RESULTS: A significant increase in imagery time in UMNp patients compared to controls (P < 0.05) and LMNp (P < 0.05) during imagined gait was demonstrated. UMNp patients exhibited altered supplementary motor area, precentral gyrus, superior parietal lobule, and dorsolateral prefrontal cortex activation and increased orbitofrontal (pFDR(False Discovery Rate) < 0.05), posterior parietal (pFDR < 0.05) caudate (pFDR < 0.05), and cerebellar (pFDR < 0.05) signal during imagined locomotion. Increased effective connectivity of the striato-cerebellar and parieto-cerebellar circuits was also demonstrated. Additional activation was detected in the insula and cingulate cortex. DATA CONCLUSION: Enhanced striato- and parieto-cerebellar networks in UMNp ALS patients are likely to represent a compensatory response to impaired postural control. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 5.

Effects of Mental Effort on Premotor Muscle Activity and Maximal Grip Force.

The present study sought to evaluate how mental effort modulates premotor activity within forearm muscles in the context of an isometric grasping task. Muscle activity of the flexor digitorum superficialis (FDS) and extensor digitorum communis (EDC) was recorded during the application of maximum grip forces in nineteen healthy adult subjects. Each subject was examined under two experimental conditions: 1) spontaneous initiation of grasp (SI) and 2) focused concentration preceding the initiation of grasp (CA). Two novel parameters, the mean premotor duration (MPD) and the mean premotor power (MPP) were used to distinguish patterns of muscle activity. Here we tested the hypothesis was maximal grip strength is primed by muscle activity during the premotor phase. Our results demonstrate that MPD for each muscle group was significantly longer in the CA condition than for the SI condition (BF10 = 491497) and that MPP was significantly greater in EDC than in FDS (BF10 = 4305). Furthermore, both the MPD and MPP of the EDC were significantly correlated with maximum grip force. These results suggest that the increase of premotor activity consequent to the mental effort (focused concentration) may support internal biomechanical and physiological mechanisms which serve to enhance patterns of neuromuscular synergies.

Partial sleep deprivation affects endurance performance and psychophysiological responses during 12-minute self-paced running exercise.

PURPOSE: This study aimed to investigate the effects of partial sleep deprivation (PSD) on physical performance and psychophysiological responses during 12-minute self-paced running exercise. METHODS: Twenty runners (20.8±1.1 years, 70.6±4.9 kg, 175.1±3.9 cm) performed, in a randomized order, two running self-paced field exercises after a normal sleep night (CONT, bedtime from 22:30 h to 06:30 h) and one night of PSD (bedtime from 00:30 h to 04:30 h). Core temperature and motivation were recorded before exercise. Speed, covered distance, heart rate (HR), rating of perceived exertion (RPE) and respiratory parameters (i.e., minute ventilation (VE), oxygen uptake (VO2) and carbon dioxide production (VCO2)) were assessed during exercise. Blood lactate concentration [La] was assessed 2 min after exercise. Simple reaction time (SRT), mood and barrage test (BT) were assessed before and after exercise. RESULTS: Higher RPE (p=0.01, d=0.90) and lower physical performance (i.e., p=0.001, d=0.59 for running speed and p=0.01, d=0.7 and Δ (%)=-6% for covered distance), following PSD, were obtained compared to CONT. Similarly, PSD attenuated core temperature (p=0.01, d=0.84), HR (p=0.006, ɳp2=0.45), VE (p=0.001, ɳp2=0.73), VO2 (p=0.001, ɳp2=0.96), BT (p<0.0005, ɳp2=0.86), SRT (p=0.0009, ɳp2=0.44) and mood (p<0.0005). However, VCO2, [La] and motivation score were not affected by sleep conditions. CONCLUSION: The decrease of running performance and the increase of physical discomfort after PSD could be the origin of the lower cardio-respiratory responses to the 12-minute self-paced exercise. Effective strategies should be introduced to overcome the deterioration of physical performance and physiological responses after PSD.