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Brainstem dysfunctions are very common in Multiple Sclerosis (MS) and are a critical predictive factor for future disability. Brainstem functionality can be explored with blink reflexes, subcortical responses consisting in a blink following a peripheral stimulation. Some reflexes are already employed in clinical practice, such as Trigeminal Blink Reflex (TBR). Here we propose for the first time in MS the exploration of Hand Blink Reflex (HBR), which size is modulated by the proximity of the stimulated hand to the face, reflecting the extension of the peripersonal space. The aim of this work is to test whether Machine Learning (ML) techniques could be used in combination with neurophysiological measurements such as TBR and HBR to improve their clinical information and potentially favour the early detection of brainstem dysfunctionality. HBR and TBR were recorded from a group of People with MS (PwMS) with Relapsing-Remitting form and from a healthy control group. Two AdaBoost classifiers were trained with TBR and HBR features each, for a binary classification task between PwMS and Controls. Both classifiers were able to identify PwMS with an accuracy comparable and even higher than clinicians. Our results indicate that ML techniques could represent a tool for clinicians for investigating brainstem functionality in MS. Also, HBR could be promising when applied in clinical practice, providing additional information about the integrity of brainstem circuits potentially favouring early diagnosis. [ABSTRACT FROM AUTHOR]

Background: Hand dexterity impairment is a key feature of disability in people with primary progressive multiple sclerosis (PPMS). So far, ocrelizumab, a recombinant humanized monoclonal antibody that selectively depletes CD20-expressing B cells, is the only therapy approved for PPMS and recent analysis reported its ability to reduce the risk of upper limb disability progression. However, the neural mechanisms underlying hand impairment in PPMS and the brain networks behind the effect of ocrelizumab on manual dexterity are not fully understood. Objective: Main aims of our study were: (i) to investigate neurophysiological and behavioural correlates of hand function impairment in subjects with PPMS, and (ii) to use neurophysiologic and behavioural measures to track the effects of ocrelizumab therapy on manual dexterity. Methods: Seventeen PPMS patients and 17 healthy-controls underwent routine neurophysiological protocols assessing the integrity of cortico-spinal and somatosensory pathways and advanced transcranial magnetic stimulation (TMS) protocols evaluating inhibitory (short and long interval intracortical inhibition, short-latency afferent inhibition) and facilitatory (motor thresholds, intracortical facilitation, short-interval intracortical facilitation) circuits in the primary motor cortex. All subjects also underwent behavioural analysis of hand dexterity by means of nine-hole peg test and finger movement analysis, and hand strength with handgrip and three-point pinch test. Neurophysiological and clinical assessments of hand functionality were also performed after 1 year of ocrelizumab therapy. Results: At baseline PPMS patients displayed a significant impairment of hand dexterity and strength compared to healthy controls (all p < 0.03). Neurophysiological study disclosed prolonged latencies of standard somatosensory and motor evoked potentials (all p < 0.025) and an overall reduction of intracortical excitability at TMS protocols, involving both excitatory and inhibitory circuits. Importantly, hand dexterity impairment, indexed by delayed 9HPT, correlated with TMS protocols investigating cortical sensorimotor integration (short-latency afferent inhibition, SAI), p = 0.009. Both parameters, 9HPT (p = 0.01) and SAI (p = 0.01), displayed a significant improvement after 1 year of therapy with ocrelizumab. Conclusion: Intracortical sensorimotor networks are involved in hand dexterity dysfunction of PPMS. Ocrelizumab therapy displays a beneficial effect on hand dexterity impairment most likely through intracortical networks implicated in fast sensorimotor integration. [ABSTRACT FROM AUTHOR]

Visual processing of emotional stimuli has been shown to engage complex cortical and subcortical networks, but it is still unclear how it affects sensorimotor integration processes. To fill this gap, here, we used a TMS protocol named short-latency afferent inhibition (SAI), capturing sensorimotor interactions, while healthy participants were observing emotional body language (EBL) and International Affective Picture System (IAPS) stimuli. Participants were presented with emotional (fear- and happiness-related) or non-emotional (neutral) EBL and IAPS stimuli while SAI was tested at 120 ms and 300 ms after pictures presentation. At the earlier time point (120 ms), we found that fear-related EBL and IAPS stimuli selectively enhanced SAI as indexed by the greater inhibitory effect of somatosensory afferents on motor excitability. Larger early SAI enhancement was associated with lower scores at the Behavioural Inhibition Scale (BIS). At the later time point (300 ms), we found a generalized SAI decrease for all kind of stimuli (fear, happiness or neutral). Because the SAI index reflects integrative activity of cholinergic sensorimotor circuits, our findings suggest greater sensitivity of such circuits during early (120 ms) processing of threat-related information. Moreover, the correlation with BIS score may suggest increased attention and sensory vigilance in participants with greater anxiety-related dispositions. In conclusion, the results of this study show that sensorimotor inhibition is rapidly enhanced while processing threatening stimuli and that SAI protocol might be a valuable option in evaluating emotional-motor interactions in physiological and pathological conditions. [ABSTRACT FROM AUTHOR]

Time-of-day influences both physical and mental performances. Its impact on motor learning is, however, not well established yet. Here, using a finger tapping-task, we investigated the time-of-day effect on skill acquisition (i.e., immediately after a physical or mental practice session) and consolidation (i.e., 24 h later). Two groups (one physical and one mental) were trained in the morning (10 a.m.) and two others (one physical and one mental) in the afternoon (3 p.m.). We found an enhancement of motor skill following both types of practice, whatever the time of the day, with a better acquisition for the physical than the mental group. Interestingly, there was a better consolidation for both groups when the training session was scheduled in the afternoon. Overall, our results indicate that the time-of-day positively influences motor skill consolidation and thus must be considered to optimize training protocols in sport and clinical domains to potentiate motor learning. [ABSTRACT FROM AUTHOR]

Circle-line drawing paradigm is used to study bimanual coupling. In the standard paradigm, subjects are asked to draw circles with one hand and lines with the other hand; the influence of the concomitant tasks results in two "elliptical" figures. Here we tested whether proprioceptive information evoked by muscle vibration inducing a proprioceptive illusion (PI) of movement at central level, was able to affect the contralateral hand drawing circles or lines. A multisite 80 Hz-muscle vibration paradigm was used to induce the illusion of circle- and line-drawing on the right hand of 15 healthy participants. During muscle vibration, subjects had to draw a congruent or an incongruent figure with the left hand. The ovalization induced by PI was compared with Real and Motor Imagery conditions, which already have proved to induce bimanual coupling. We showed that the ovalization of a perceived circle over a line drawing during PI was comparable to that observed in Real and Motor Imagery condition. This finding indicates that PI can induce bimanual coupling, and proprioceptive information can influence the motor programs of the contralateral hand. [ABSTRACT FROM AUTHOR]

Motor imagery (MI) is the mental simulation of an action without any overt motor execution. Interestingly, a temporal coupling between durations of real and imagined movements, i.e., the so-called isochrony principle, has been demonstrated in healthy adults. On the contrary, anisochrony has frequently been reported in elderly subjects or those with neurological disease such as Parkinson disease or multiple sclerosis (MS). Here, we tested whether people with MS (PwMS) may have impaired MI when they imagined themselves walking on paths with different widths. When required to mentally simulate a walking movement along a constrained pathway, PwMS tended to overestimate mental movement duration with respect to actual movement duration. Interestingly, in line with previous evidence, cognitive fatigue was found to play a role in the MI of PwMS. These results suggest that investigating the relationship between cognitive fatigue and MI performances could be key to shedding new light on the motor representation of PwMS and providing critical insights into effective and tailored rehabilitative treatments. [ABSTRACT FROM AUTHOR]

Cognitive impairment and related abnormal brain activity are common in people with multiple sclerosis (PwMS). Adaptive training based on working memory (WM) has been shown to ameliorate cognitive symptoms, although the effects at a neural level are unclear. The aim of this study was to expand the existing research on the effects of an adaptive WM rehabilitative intervention on brain functional activity in PwMS. A sample of eighteen PwMS performed an 8-week home-based cognitive rehabilitation treatment based on adaptive WM training. PwMS were assessed before and after treatment using a validated neuropsychological battery and undergoing an fMRI session while carrying out a cognitive task (i.e., Paced Visual Serial Addition Test - PVSAT). fMRI activations were compared to the activation pattern elicited by eighteen matched healthy subjects performing the same task. At baseline, we found abnormal brain activity during PVSAT in PwMS when compared to healthy subjects, with a pattern including several bilateral activation clusters. Following rehabilitation, PwMS improved cognitive performance, as evaluated by the neuropsychological battery, and showed a different activation map with clusters mainly located in the right cerebellum and in the left hemisphere. The only significant cluster in the right hemisphere was located in the inferior parietal lobule, and the BOLD signal extracted in this area significantly correlated with cognitive performance both before and after the treatment. We suggest that WM training can improve the cognitive performance and reduce the abnormal activation of PwMS by partially maintaining or even restoring brain cognitive function. [ABSTRACT FROM AUTHOR]

Tendon vibration of a limb elicits illusory movements in the direction that the vibrated muscle would be stretched, followed by a transient perception of movement in the opposite direction, that was demonstrated to correspond to a "cortical" aftereffect (Goodwin et al. Science 175:1382-1384, 1972). Primary motor cortex (M1) excitability of the non-vibrated antagonist muscle of the vibrated muscle increased during vibration and decreased thereafter. The cortical aftereffect is of interest when considering the possibility to use tendon vibration in rehabilitation for restoring unbalance activity between antagonistic muscles but, due to its short-lasting duration, has not been explored so far. We investigated the possibility to consolidate the cortical aftereffect by combining tendon vibration with a concomitant high-frequency 5-Hz repetitive transcranial magnetic stimulation (rTMS) protocol. The distal tendon of the flexor carpi radialis muscle (FCR) was vibrated and concomitantly a 2-min 5-Hz rTMS protocol was administered on the left hemi-scalp hot spot of the vibrated FCR or its antagonist muscle (extensor carpi radialis (ECR)). We found that this protocol induced a pattern of unbalanced M1 excitability between vibrated muscle and its antagonist with increased excitability of the FCR and decreased excitability of ECR cortical areas, which persisted up to 30 min. [ABSTRACT FROM AUTHOR]

Motor imagery is a mental process during which subjects internally simulate a movement without any motor output. Mental and actual movement durations are similar in healthy adults (isochrony) while temporal discrepancies (anisochrony) could be an expression of neurological deficits on action representation. It is unclear whether patients with multiple sclerosis (PwMS) preserve the capacity to simulate their own movements. This study investigates the ability of PwMS to predict their own actions by comparing temporal features of dominant and non-dominant actual and mental actions. Fourteen PwMS and nineteen healthy subjects (HS) were asked to execute and to imagine pointing arm movements among four pairs of targets of different sizes. Task duration was calculated for both actual and mental movements by an optoelectronic device. Results showed temporal consistency and target-by-target size modulation in actual movements through the four cycles for both groups with significantly longer actual and mental movement durations in PwMS with respect to HS. An index of performance (IP) was used to examine actual/mental isochrony properties in the two groups. Statistical analysis on IP showed in PwMS significantly longer actual movement durations with respect to mental movement durations (anisochrony), more relevant for the non-dominant than dominant arm. Mental prediction of motor actions is not well preserved in MS where motor and cognitive functional changes are present. Differences in performing imagined task with dominant and non-dominant arm could be related to increased cognitive effort required for performing non-dominant movements. [ABSTRACT FROM AUTHOR]

Subjective fatigue is a typical symptom in Multiple Sclerosis (MS) even in the earliest stages of the disease. The relationship between persistent fatigue and motor task performance is still unclear. Aim of this study was to better investigate this relationship at both the motor behavioral and neuroanatomical levels. Towards this goal, we combined a quantitative evaluation of an undemanding finger motor task with concurrent brain functional magnetic resonance imaging (fMRI) in a group of MS patients with minimal disability but reporting persistent subjective fatigue. We found an unexpected significant positive correlation between persistent subjective fatigue and task-related temporal accuracy, revealing a "fatigue-motor performance paradox". fMRI analysis indicated that this association is potentially mediated by cerebellar and orbitofrontal cortex activity, suggesting a role of these regions in developing subjective fatigue. Our data point to a possible adaptive role for fatigue as the subjective correlate of increased resource demand for motor activities. [ABSTRACT FROM AUTHOR]

Gait disturbances are frequent in Parkinson's disease (PD) and are associated with increased energy expenditure during walking. This study evaluated whether the effects of treadmill training are associated with an improvement of walking economy. Ten patients with idiopathic PD underwent treadmill training (30 min, three times a week for 4 weeks). Walking performance (Tauimed Up and Go, 6-min and 10-m walking tests) and metabolic function (oxygen uptake, heart and respiratory rate) were evaluated before training, at the end of treatment and after 30 days with two different graded exercises (treadmill and cycloergometer). Training significantly improved walking performance. Oxygen uptake, and heart and respiratory rates were significantly decreased only during graded exercise on the treadmill, but not on the cycloergometer. Treadmill training reduces energy expenditure during walking in PD, but the improvements of metabolic walking economy are associated with the specifically trained motor activity. [ABSTRACT FROM AUTHOR]

With a series of novel arm-reaching tasks, we have shown that visuomotor sequence learning encompasses the acquisition of the order of sequence elements, and the ability to combine them in a single, skilled behavior. The first component, which is mostly declarative, is reflected by changes in movement onset time (OT); the second, which occurs without subject’s awareness, is measured by changes in kinematic variables, including movement time (MT). Key-press-based serial reaction time tasks (SRTT) have been used to investigate sequence learning and results interpreted as indicative of the implicit acquisition of the sequence order. One limitation to SRT studies, however, is that only one measure is used, the response time, the sum of OT and MT: this makes interpretation of which component is learnt difficult and disambiguation of implicit and explicit processes problematic. Here, we used an arm-reaching version of SRTT to propose a novel interpretation of such results. The pattern of response time changes we obtained was similar to the key-press-based tasks. However, there were significant differences between OT and MT, suggesting that both partial learning of the sequence order and skill improvement took place. Further analyses indicated that the learning of the sequence order might not occur without subjects’ awareness. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that transcranial magnetic stimulation (TMS), in addition to its inhibitory action on the corticospinal output, can also exert some inhibitory effect on the transcallosal system connecting the two motor cortices. In seven normal subjects, instructed to keep their right opponens pollicis (OP) muscle fully relaxed and their left OP muscle voluntarily contracted, we used a paired-pulse TMS protocol, to stimulate the left motor cortex. We evaluated the effect of low-intensity conditioning stimulation on the ipsilateral silent period (iSP) elicited by the subsequent test stimulus. Compelling evidence exists to support that this iSP is mediated by the activation of transcallosal motor fibres. Simultaneously, the inhibition of the motor evoked potential (MEP) in the right OP muscle was also investigated. At the interstimulus interval (ISI) of 3 ms, the iSP was significantly (P<0.0001, repeated-measures ANOVA) suppressed by conditioning intensities ranging from 1.2 to 0.6 of MEP threshold. The assessment of the time-course showed that iSP inhibition was present in all the tested subjects only at ISIs of 2 and 3 ms (for each subject P<0.05, repeated-measures ANOVA). Several findings suggest that the suppression of iSP is brought about by the activation of inhibitory mechanisms operating in the stimulated (left) motor cortex. We propose that the assessment of iSP suppression could be a method to study the excitability of intracortical inhibitory circuits in the affected hemisphere of patients with unilateral damage of the corticospinal tract. [ABSTRACT FROM AUTHOR]

Activity-dependent slow biochemical regulation processes, affecting intrinsic properties of a neuron, might play an important role in determining information processing strategies in the nervous system. We introduce second-order biochemical phenomena into a linear leaky integrate-and-fire model neuron together with a detailed kinetic description for synaptic signal transduction. In this framework, we investigate the membrane intrinsic electrical properties differentiation, showing the appearance of activity-dependent shifts between integration and temporal coincidence detection operating mode, for the single unit of a network. [ABSTRACT FROM AUTHOR]

Abstract. Experimental investigation of the dynamics of biological networks is a fundamental step towards understanding how the nervous system works. Spontaneous activity in cultured networks of cortical neurons has been investigated by using a multisite recording technique with planar electrode arrays. In these networks, the spatiotemporal firing patterns were studied in the presence of different extracellular solutions. Transitions from asynchronous firing dynamics to synchronous firing dynamics were observed when the extracellular Ca[sup 2+] concentration was increased from 0.1 mM to I mM. Addition of extracellular Mg[sup 2+] reduced the spontaneous activity at any Ca[sup 2+] concentration, and an increase in the extracellular K[sup +] concentration enhanced the frequency of periodical synchronous bursts. N-methyl-Daspartate (NM DA) and non-NMDA glutamate receptor antagonists inhibited synchronous activity. A spatio-temporal analysis of the data has been performed, and the properties of the network such as the synchronization and the periodicity have been quantified in order to clarify how variations of intrinsic parameters of the network can induce structural transitions in the neural dynamics. This experimental study is a possible approach to investigate the computational properties of a neuronal network. [ABSTRACT FROM AUTHOR]

The hand-blink reflex (HBR) is a subcortical response, elicited by the electrical stimulation of the median nerve, whose magnitude is specifically modulated according to the spatial properties of the defensive peripersonal space (DPPS) of the face. For these reasons, the HBR is commonly used as a model to assess the DPPS of the face. Little is known on the effects induced by the activation of cutaneous afferents from the face on the DPPS of the face. Therefore, we tested the effect of non-painful transcutaneous trigeminal nerve stimulation (TNS) on the amplitude of the HBR. Fifteen healthy participants underwent HBR recording before and after 20 min of sham- and real-TNS delivered bilaterally to the infraorbital nerve in two separate sessions. The HBR was recorded bilaterally from the orbicularis oculi muscles, following non-painful median nerve stimulation at the wrist. The HBR amplitude was assessed in the "hand‐far" and "hand‐near" conditions, relative to the hand position in respect to the face. The amplitudes of the hand-far and hand-near HBR were measured bilaterally before and after sham- and real-TNS. Real-TNS significantly reduced the magnitude of the HBR, while sham-TNS had no significant effect. The inhibitory effect of TNS was of similar extent on both the hand-far and hand-near components of the HBR, which suggests an action exerted mainly at brainstem level. [ABSTRACT FROM AUTHOR]

The Hand Blink Reflex (HBR) is a subcortical defensive response, elicited by the electrical stimulation of the median nerve. HBR increases when the stimulated hand is inside the defensive peripersonalspace (DPPS) of the face. However, the presence of a screen protecting the face could reduce the amplitude of this response. This work aimed to investigate whether the learning of a posture intended to protect the head could modulate the HBR responses. Boxing athletes learn a defensive posture consisting of blocking with arms opponent's blow towards the face. Two groups were recruited: 13 boxers and 13 people naïve to boxing. HBR response was recorded and elicited in three hand positions depending on the distance from the face. A suppression of HBR enhancement in the static position close to the face was observed in boxer group, contrary to the control group. Also, the higher years of practice in boxing, the higher suppression occurred. However, this suppression was not observed when boxers were asked to move the hand up-to/down-from the face. These findings might suggest that the sensorimotor experience related to a previously learnt protective posture can modify the HBR and thus shape the dimension of the DPPS. [ABSTRACT FROM AUTHOR]

During action observation (AO), the activity of the 'mirror system' is influenced by the viewer's expertise in the observed action. A question that remains open is whether the temporal aspects of the subjective motor repertoire can influence the 'mirror system' activation. [ABSTRACT FROM AUTHOR]