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When we perform a movement we generally have a clear distinction between which parts of the world constitute our body and which parts do not. However, how the sense of ownership over our body supports movement is not yet fully understood. We aimed to see whether a sense of ownership over the hand supports the performance of rapid hand movements. In three experiments (n = 48, n = 30, n = 24), we presented participants with congruent and incongruent visuotactile and visuoproprioceptive information regarding their own hand. In keeping with previous experiments, multisensory disintegration resulted in a reduction in the subjective sensation of ownership over the hand, as reflected in questionnaire responses. Following sensory stimulation, participants were required to rapidly abduct their index finger whilst the movement was tracked. We examined the hypothesis that, should a sense of ownership over the limb be necessary for generating rapid movements with that limb, reaction time would increase when hand ownership was reduced, whilst the acceleration and velocity of the movement would decrease. We observed that reductions in own hand ownership did not interfere with rapid index finger abduction, suggesting that the motor system may not be reliant on a subjective sense of ownership over the body in order to generate movement. [ABSTRACT FROM AUTHOR]

The amount of practice and time interval between practice sessions are important factors that influence motor learning efficiency. Here, we aimed to reveal the relationship between the retention and consolidation of a new internal model, and the amount of practice and time interval between practice sessions. We employed a visuomotor rotation tracking task to test the hypotheses that (1) a new internal model consolidates owing to extensive practice after reaching a task performance plateau and (2) a longer time interval between practice sessions makes it difficult to activate a new internal model. The participants were assigned to one of the four groups that differed in terms of the amount of practice and the time interval between practice sessions. They performed a tracking task in which they experienced 120° clockwise visuomotor rotation and were required to track a moving target on a computer display using a mouse cursor. To evaluate the retention and consolidation of a new internal model, we calculated the aftereffects and savings as measures of motor learning. To the best our knowledge, this is the first study to manipulate both the amount of practice and the time interval between practice sessions simultaneously in one experiment using a visuomotor tracking task. Our results support the previously reported idea that extensive practice is necessary for the consolidation of a new internal model. [ABSTRACT FROM AUTHOR]

The main aim of the present study was to explore the value of several measures of handwriting in the study of motor abnormalities in patients with bipolar or psychotic disorders. 54 adult participants with a schizophrenia spectrum disorder or bipolar disorder and 44 matched healthy controls, participated in the study. Participants were asked to copy a handwriting pattern consisting of four loops, with an inking pen on a digitizing tablet. We collected a number of classical, non-linear and geometrical measures of handwriting. The handwriting of patients was characterized by a significant decrease in velocity and acceleration and an increase in the length, disfluency and pressure with respect to controls. Concerning non-linear measures, we found significant differences between patients and controls in the Sample Entropy of velocity and pressure, Lempel-Ziv of velocity and pressure, and Higuchi Fractal Dimension of pressure. Finally, Lacunarity, a measure of geometrical heterogeneity, was significantly greater in handwriting patterns from patients than from controls. We did not find differences in any handwriting measure on function of the specific diagnosis or the antipsychotic dose. Results indicate that participants with a schizophrenia spectrum disorder or bipolar disorder exhibit significant motor impairments and that these impairments can be readily quantified using measures of handwriting movements. Besides, they suggest that motor abnormalities are a core feature of several mental disorders and they seem to be unrelated to the pharmacological treatment. [ABSTRACT FROM AUTHOR]

Utilization by humans of a precise and adaptable internal model of the dynamics of the body in generating movements is a well-supported concept. The prevailing opinion is that such an internal model ceaselessly develops through long-term repetition and accumulation in the central nervous system (CNS). However, a long-term learning process would not be absolutely necessary for the formation of internal models. It is possible to estimate the dynamics of the system by using a motor command and its resulting output, instead of constructing a model of the dynamics with precise parameters. In this study, a computational model is proposed that uses a motor command and its corresponding output to estimate the dynamics of the system and it is examined whether the proposed model is capable of describing a series of empirical movements. The proposed model was found to be capable of describing humans’ fast movements which require compensation for system dynamics as well as sensory delays. In addition, the proposed model shows equifinality under inertial perturbations as seen in several experimental studies. This satisfactory reproducibility of the proposed computation raises the possibility that humans make a movement by estimating the system dynamics with a copy of motor command and sensory output on a momentary basis, without the need to identify precise system parameters. [ABSTRACT FROM AUTHOR]

Movement time (MT) is one of the most important variables influencing the way we control our movements. A few previous studies have generally found that MT reduces with reaction time testing during exercise. However, limited evidence exists concerning change in MT following an acute bout of exercise. Our purpose was to investigate the effect of an acute bout of aerobic exercise on movement time as assessed by a Fitts’ Law task. We also sought to determine if exercise would further lower MT during the more difficult task conditions compared with rest. Nineteen (12 male, 7 female) volunteers (19–28 yrs) completed a computerized paired serial pointing task to measure movement time before and after rest (R) and an acute bout of moderate aerobic exercise (E) using a within subjects crossover design. Comparisons between exercise and rest conditions were made to determine if there were differences in movement time. Exercise significantly reduced MT compared with rest. Movement time was reduced by an average of 208 ms following exercise compared with 108 ms following rest. Exercise did not further lower MT during the more difficult task conditions. These results suggest that an acute bout of aerobic exercise reduces movement time which is an important component of motor control. Further studies are needed to determine the duration of the effect as well as the optimum duration and intensity of exercise. [ABSTRACT FROM AUTHOR]

Traditional pyramidotomy models have a high mortality rate from breathing difficulties and show early recovery from the induced motor deficits. This study establishes a novel pyramidotomy technique in Sprague Dawley rats that generates persistent motor deficits and has a reduced mortality rate. We used viral neural tracing to identify the course and relative distribution of forelimb and hindlimb motor fibers (n = 9). On basis of the neural tracing data, the medullary pyramid was targeted dorsally from the cerebellar cortex for photothrombotic infarct lesioning (n = 18). The photothrombotic technique selectively destroyed the corticospinal fibers in the medullary pyramid with relative preservation of neighboring grey-matter tissue. MicroPET imaging using 2-deoxy-2-[18F]-fluoro-D-glucose (FDG-microPET) showed a decrease in regional cerebral glucose metabolism (rCGM) in the bilateral pyramid and ipsilateral sensory cortex (p < 0.001, FDR q < 0.05). In addition, the trapezoid bodies and superior olivary nuclei showed a decrease in rCGM, compatible with damage caused during the introduction of the optical fiber. Connected structures such as the inferior colliculi and auditory cortices also showed decreases in rCGM in both hemispheres (p < 0.001, FDR q < 0.05). There was a significant and persistent decrease in motor and sensory function in the contralateral limb following pyramidotomy, as demonstrated by performance in the single pellet reaching task and the foot-fault test. There was no operative mortality or loss of respiratory function in this study. These results indicate that photothrombotic pyramidotomy with a dorsal transcortical approach is a safe and reliable technique for generating a pyramidotomy model with persistent motor deficits. [ABSTRACT FROM AUTHOR]

Community dwelling stroke survivors most often fall while walking. Understanding how post-stroke individuals control mediolateral footpath during walking may help elucidate the mechanisms that contribute to walking instability. By applying the Uncontrolled Manifold (UCM) approach, we investigated (1) how post-stroke individuals coordinate lower-extremity joint motions to stabilize mediolateral footpath of the swing leg, and (2) how the inter-joint coordination in footpath stabilization correlates to their walking stability. Nine stroke subjects and nine healthy controls walked on a treadmill at four different speeds. UCM analysis partitions the variance of kinematic configurations across gait cycles into “good variance” (i.e., the variance component leading to a consistent footpath) or “bad variance” (i.e., the variance component leading to an inconsistent footpath). We found that both groups had a significantly greater “good” than “bad” variance (p<0.05) for most of the swing phase, suggesting that mediolateral footpath is an important variable stabilized by the central nervous system during walking. Stroke subjects had significantly greater relative variance difference (ΔV) (i.e. normalized difference between “good” and “bad” variance) (p<0.05), indicating a stronger kinematic synergy in footpath stabilization, than the controls. In addition, the kinematic synergy in mediolateral footpath stabilization is strongest during mid-swing but weakest during late swing in healthy gait. However, this phase-dependent strategy is preserved for mid-swing but not for late swing in stroke gait. Moreover, stroke and healthy subjects demonstrated different relationships between UCM and walking stability measures. A stronger kinematic synergy in healthy gait is associated with better walking stability whereas having more “good variance” or stronger kinematic synergy in stroke gait is associated with less walking stability. The current findings suggest that walking with too much “good variance” in people following stroke, despite no effect on the footpath, may adversely affect their walking stability to some extent. [ABSTRACT FROM AUTHOR]

Several neuroimaging studies have shown that listening to music activates brain regions that reside in the motor system, even when there is no overt movement. However, many of these studies report the activation of varying motor system areas that include the primary motor cortex, supplementary motor area, dorsal and ventral pre-motor areas and parietal regions. In order to examine what specific roles are played by various motor regions during music perception, we used activation likelihood estimation (ALE) to conduct a meta-analysis of neuroimaging literature on passive music listening. After extensive search of the literature, 42 studies were analyzed resulting in a total of 386 unique subjects contributing 694 activation foci in total. As suspected, auditory activations were found in the bilateral superior temporal gyrus, transverse temporal gyrus, insula, pyramis, bilateral precentral gyrus, and bilateral medial frontal gyrus. We also saw the widespread activation of motor networks including left and right lateral premotor cortex, right primary motor cortex, and the left cerebellum. These results suggest a central role of the motor system in music and rhythm perception. We discuss these findings in the context of the Action Simulation for Auditory Prediction (ASAP) model and other predictive coding accounts of brain function. [ABSTRACT FROM AUTHOR]

In sports, success and failure are believed to be contagious. Yet it is unclear what might cause contagion. This study investigated whether motor contagion is associated with the active observation of the kinematic actions of others. In Experiment 1, six skilled hammer throwers threw a hammer after watching a video of a model throwing toward the left, center, or right. The video included two types of action kinematics which resulted in throw directions that were either easy or difficult to predict based on the model’s kinematics. In Experiment 2, the athletes threw hammers after watching the same stimuli as Experiment 1, but while engaging in one of two types of focus (self-focus or non-self-focus) to determine whether motor contagion could be diminished. Results demonstrated that the direction of each participant’s throw was more influenced by the videos that contained easy action kinematics, supporting a critical role for the meaningfulness of the link between an action and its outcome in producing motor contagion. Motion analysis revealed that motor contagion was not likely to be a result of the observer imitating the model’s action kinematics. The contagion observed in Experiment 1 disappeared when participants engaged in self-focus. These results suggest that motor contagion is influenced by the predictability of an action outcome when observing an action, and that motor contagion can be inhibited through self-focus when observing. [ABSTRACT FROM AUTHOR]

Human central nervous system (CNS) undergoes neurological changes during the aging process, leading to declines in hand and finger functions. Previous studies have shown that the CNS can independently process multi-finger force control and moment of force control. However, if both force and moment control are simultaneously imposed by motor task constraints, the CNS needs to resolve competing interests of generating negative and positive covariances between fingers, respectively, which causes “conflict of interest or COI”. Here, we investigated how aging affects the CNS’s abilities to solve COI through a new experimental paradigm. Both elderly and young subjects performed a constant force production task using index and middle fingers under two conditions, multi-finger pressing with no COI and with COI. We found that the elderly increased variance of a virtual finger (VF: an imagined finger producing the same mechanical effect as both fingers together) in time-to-time basis (i.e. online control), while increasing covariance between individual fingers (IF) forces in trial-to-trial basis (i.e. offline control) with COI than no COI. Aging affects the CNS’s abilities to solve COI by deteriorating VF actions in online control and IF actions in offline control. [ABSTRACT FROM AUTHOR]

Depression and schizophrenia are defined only by their clinical features, and diagnostic separation between them can be difficult. Disturbances in motor activity pattern are central features of both types of disorders. We introduce a new method to analyze time series, called the similarity graph algorithm. Time series of motor activity, obtained from actigraph registrations over 12 days in depressed and schizophrenic patients, were mapped into a graph and we then applied techniques from graph theory to characterize these time series, primarily looking for changes in complexity. The most marked finding was that depressed patients were found to be significantly different from both controls and schizophrenic patients, with evidence of less regularity of the time series, when analyzing the recordings with one hour intervals. These findings support the contention that there are important differences in control systems regulating motor behavior in patients with depression and schizophrenia. The similarity graph algorithm we have described can easily be applied to the study of other types of time series. [ABSTRACT FROM AUTHOR]

Activity-dependent changes in the properties of the motor system underlie the necessary adjustments in its responsiveness on the basis of the environmental and developmental demands of the organism. Although plastic changes in the properties of the spinal cord have historically been neglected because of the archaic belief that the spinal cord is constituted by a hardwired network that simply relays information to muscles, plenty of evidence has been accumulated showing that synapses impinging on spinal motoneurons undergo short- and long-term plasticity. In the brain, brief changes in the activity level of the network have been shown to be paralleled by changes in the intrinsic excitability of the neurons and are suggested to either reinforce or stabilize the changes at the synaptic level. However, rapid activity-dependent changes in the intrinsic properties of spinal motoneurons have never been reported. In this study, we show that in neonatal mice the intrinsic excitability of spinal motoneurons is depressed after relatively brief but sustained changes in the spinal cord network activity. Using electrophysiological techniques together with specific pharmacological blockers of KCNQ/Kv7 channels, we demonstrate their involvement in the reduction of the intrinsic excitability of spinal motoneurons. This action results from an increased M-current, the product of the activation of KCNQ/Kv7 channels, which leads to a hyperpolarization of the resting membrane potential and a decrease in the input resistance of spinal motoneurons. Computer simulations showed that specific up-regulations in KCNQ/Kv7 channels functions lead to a modulation of the intrinsic excitability of spinal motoneurons as observed experimentally. These results indicate that KCNQ/Kv7 channels play a fundamental role in the activity-dependent modulation of the excitability of spinal motoneurons. [ABSTRACT FROM AUTHOR]

Is the neural control of movements towards moving targets independent to that of static targets? In the following experiments, we used a visuomotor rotation adaptation paradigm to examine the extent to which adapting arm movements to static targets generalize to that of moving targets (i.e. pursuit or tracking). In the first and second experiments, we showed that adaptation to perturbed tracking movements generalizes to reaching movements; reach aftereffects following perturbed tracking were about half the size (≈9°) of those produced following reach training (≈ 19°). Given these findings, in the final experiment we associated opposing perturbations (-30° and +30°) with either reaching or tracking movements and presented them within the same experimental block to determine whether these contexts allow for dual adaptation. We found that the group that experienced opposing perturbations was able to reduce both reaching and tracking errors, as well as produce reach aftereffects following dual training of ≈7°, which were substantially smaller than those produced when reach training was not concurrent with tracking training. This reduction in reach aftereffects is consistent with the extent of the interference from tracking training as measured by the reach aftereffects produced when only that condition was performed. These results suggest partial, but not complete, overlap in the learning processes involved in the acquisition of tracking and reaching movements. [ABSTRACT FROM AUTHOR]

Background: It is important to understand the motor deficits of children with Cerebral Palsy (CP). Our understanding of this motor disorder can be enriched by computational models of motor control. One crucial stage in generating movement involves combining uncertain information from different sources, and deficits in this process could contribute to reduced motor function in children with CP. Healthy adults can integrate previously-learned information (prior) with incoming sensory information (likelihood) in a close-to-optimal way when estimating object location, consistent with the use of Bayesian statistics. However, there are few studies investigating how children with CP perform sensorimotor integration. We compare sensorimotor estimation in children with CP and age-matched controls using a model-based analysis to understand the process. Methods and findings: We examined Bayesian sensorimotor integration in children with CP, aged between 5 and 12 years old, with Gross Motor Function Classification System (GMFCS) levels 1–3 and compared their estimation behavior with age-matched typically-developing (TD) children. We used a simple sensorimotor estimation task which requires participants to combine probabilistic information from different sources: a likelihood distribution (current sensory information) with a prior distribution (learned target information). In order to examine sensorimotor integration, we quantified how participants weighed statistical information from the two sources (prior and likelihood) and compared this to the statistical optimal weighting. We found that the weighing of statistical information in children with CP was as statistically efficient as that of TD children. Conclusions: We conclude that Bayesian sensorimotor integration is not impaired in children with CP and therefore, does not contribute to their motor deficits. Future research has the potential to enrich our understanding of motor disorders by investigating the stages of motor processing set out by computational models. Therapeutic interventions should exploit the ability of children with CP to use statistical information. [ABSTRACT FROM AUTHOR]

Background: Body representation disturbances in body schema (i.e. unconscious sensorimotor body representations for action) have been frequently reported in eating disorders. Recently, it has been proposed that body schema relies on adequate functioning of the motor system, which is strongly implicated in discriminating between one’s own and someone else’s body. The present study aimed to investigate the motor-based bodily self in eating disorders and controls, in order to examine the role of the motor system in body representation disturbances at the body schema level. Method: Female outpatients diagnosed with eating disorders (N = 15), and healthy controls (N = 18) underwent a hand laterality task, in which their own (self-stimuli) and someone else’s hands (other-stimuli) were displayed at different orientations. Participants had to mentally rotate their own hand in order to provide a laterality judgement. Group differences in motor-based bodily self-recognition—i.e. whether a general advantage occurred when implicitly processing self- vs. other-stimuli − were evaluated, by analyzing response times and accuracy by means of mixed ANOVAs. Results: Patients with eating disorders did not show a temporal advantage when mentally rotating self-stimuli compared to other-stimuli, as opposed to controls (F(1, 31) = 5.6, p = 0.02; eating disorders-other = 1092 ±256 msec, eating disorders-self = 1097±254 msec; healthy controls-other = 1239±233 msec, healthy controls -self = 1192±232 msec). Conclusion: This study provides initial indication that high-level motor functions might be compromised as part of body schema disturbances in eating disorders. Further larger investigations are required to test motor system abnormalities in the context of body schema disturbance in eating disorders. [ABSTRACT FROM AUTHOR]

Essential tremor (ET) is the most common age-related disease leading to abnormal tremulous behaviors in the upper and lower extremities. Non-invasive brain stimulation (NIBS) may be an effective ET therapy by modulating the oscillating network of the brain. The current systematic review and meta-analysis examined the effects of NIBS interventions on tremor symptoms in ET patients. Our comprehensive search identified eight studies that used 1 Hz of rTMS, cTBS, or ctDCS protocols. Twenty total comparisons from the eight qualified studies were statistically synthesized, and the meta-analytic findings revealed that NIBS techniques reduced tremulous behaviors in individuals with ET. Moreover, the four moderator variable analyses demonstrated that the positive therapeutic effects of NIBS appeared across the following subgroups: (a) tremor assessment (clinical test vs. quantitative tremor assessment), (b) stimulation site (cerebellum vs. motor cortex), (c) session number (single session vs. multiple sessions), and (d) sustained positive treatment effect (posttest vs. retention test). This comprehensive systematic review and meta-analysis provided evidence that support positive treatment effects of NIBS techniques on ET motor therapy. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) can excite both cortico-cortical and cortico-spinal axons resulting in TMS-evoked potentials (TEPs) and motor-evoked potentials (MEPs), respectively. Despite this remarkable difference with other cortical areas, the influence of motor output and its amplitude on TEPs is largely unknown. Here we studied TEPs resulting from M1 stimulation and assessed whether their waveform and spectral features depend on the MEP amplitude. To this aim, we performed two separate experiments. In experiment 1, single-pulse TMS was applied at the same supra-threshold intensity on primary motor, prefrontal, premotor and parietal cortices and the corresponding TEPs were compared by means of local mean field power and time-frequency spectral analysis. In experiment 2 we stimulated M1 at resting motor threshold in order to elicit MEPs characterized by a wide range of amplitudes. TEPs computed from high-MEP and low-MEP trials were then compared using the same methods applied in experiment 1. In line with previous studies, TMS of M1 produced larger TEPs compared to other cortical stimulations. Notably, we found that only TEPs produced by M1 stimulation were accompanied by a late event-related desynchronization (ERD—peaking at ~300 ms after TMS), whose magnitude was strongly dependent on the amplitude of MEPs. Overall, these results suggest that M1 produces peculiar responses to TMS possibly reflecting specific anatomo-functional properties, such as the re-entry of proprioceptive feedback associated with target muscle activation. [ABSTRACT FROM AUTHOR]

Repetition suppression (RS) is evident as a weakened response to repeated stimuli after the initial response. RS has been demonstrated in motor-evoked potentials (MEPs) induced with transcranial magnetic stimulation (TMS). Here, we investigated the effect of inter-train interval (ITI) on the induction of RS of MEPs with the attempt to optimize the investigative protocols. Trains of TMS pulses, targeted to the primary motor cortex by neuronavigation, were applied at a stimulation intensity of 120% of the resting motor threshold. The stimulus trains included either four or twenty pulses with an inter-stimulus interval (ISI) of 1 s. The ITI was here defined as the interval between the last pulse in a train and the first pulse in the next train; the ITIs used here were 1, 3, 4, 6, 7, 12, and 17 s. RS was observed with all ITIs except with the ITI of 1 s, in which the ITI was equal to ISI. RS was more pronounced with longer ITIs. Shorter ITIs may not allow sufficient time for a return to baseline. RS may reflect a startle-like response to the first pulse of a train followed by habituation. Longer ITIs may allow more recovery time and in turn demonstrate greater RS. Our results indicate that RS can be studied with confidence at relatively short ITIs of 6 s and above. [ABSTRACT FROM AUTHOR]

Reaching movements are comprised of the coordinated action across multiple joints. The human skeleton is redundant for this task because different joint configurations can lead to the same endpoint in space. How do people learn to use combinations of joints that maximize success in goal-directed motor tasks? To answer this question, we used a 3-degree-of-freedom manipulandum to measure shoulder, elbow and wrist joint movements during reaching in a plane. We tested whether a shift in the relative contribution of the wrist and elbow joints to a reaching movement could be learned by an implicit reinforcement regime. Unknown to the participants, we decreased the task success for certain joint configurations (wrist flexion or extension, respectively) by adding random variability to the endpoint feedback. In return, the opposite wrist postures were rewarded in the two experimental groups (flexion and extension group). We found that the joint configuration slowly shifted towards movements that provided more control over the endpoint and hence higher task success. While the overall learning was significant, only the group that was guided to extend the wrist joint more during the movement showed substantial learning. Importantly, all changes in movement pattern occurred independent of conscious awareness of the experimental manipulation. These findings suggest that the motor system is generally sensitive to its output variability and can optimize joint-space solutions that minimize task-relevant output variability. We discuss biomechanical biases (e.g. joint’s range of movement) that could impose hurdles to the learning process. [ABSTRACT FROM AUTHOR]

Spontaneous motor recovery after stroke appears to be associated with structural and functional changes in the motor network. The aim of the current study was to explore time-dependent changes in resting-state (rs) functional connectivity in motor-impaired stroke patients, using rs-functional MRI at 5 weeks and 26 weeks post-stroke onset. For this aim, 13 stroke patients from the EXPLICIT-stroke Trial and age and gender-matched healthy control subjects were included. Patients’ synergistic motor control of the paretic upper-limb was assessed with the upper extremity section of the Fugl-Meyer Assessment (FMA-UE) within 2 weeks, and at 5 and 26 weeks post-stroke onset. Results showed that the ipsilesional rs-functional connectivity between motor areas was lower compared to the contralesional rs-functional connectivity, but this difference did not change significantly over time. No relations were observed between changes in rs-functional connectivity and upper-limb motor recovery, despite changes in upper-limb function as measured with the FMA-UE. Last, overall rs-functional connectivity was comparable for patients and healthy control subjects. To conclude, the current findings did not provide evidence that in moderately impaired stroke patients the lower rs-functional connectivity of the ipsilesional hemisphere changed over time. [ABSTRACT FROM AUTHOR]

Transgenic mice that express channelrhodopsin-2 or its variants provide a powerful tool for optogenetic study of the nervous system. Previous studies have established that introducing such exogenous genes usually does not alter anatomical, electrophysiological, and behavioral properties of neurons in these mice. However, in a line of Thy1-ChR2-YFP transgenic mice (line 9, Jackson lab), we found that short-latency motor evoked potentials (MEPs) induced by transcranial magnetic stimulation had a longer latency and much lower amplitude than that of wild type mice. MEPs evoked by transcranial electrical stimulation also had a much higher threshold in ChR2 mice, although similar amplitudes could be evoked in both wild and ChR2 mice at maximal stimulation. In contrast, long-latency MEPs evoked by electrically stimulating the motor cortex were similar in amplitude and latency between wild type and ChR2 mice. Whole-cell patch clamp recordings from layer V pyramidal neurons of the motor cortex in ChR2 mice revealed no significant differences in intrinsic membrane properties and action potential firing in response to current injection. These data suggest that corticospinal tract is not accountable for the observed abnormality. Motor behavioral assessments including BMS score, rotarod, and grid-walking test showed no significant differences between the two groups. Because short-latency MEPs are known to involve brainstem reticulospinal tract, while long-latency MEPs mainly involve primary motor cortex and dorsal corticospinal tract, we conclude that this line of ChR2 transgenic mice has normal function of motor cortex and dorsal corticospinal tract, but reduced excitability and responsiveness of reticulospinal tracts. This abnormality needs to be taken into account when using these mice for related optogenetic study. [ABSTRACT FROM AUTHOR]

Observation of others' actions evokes in primary motor cortex and spinal circuits of observers a subliminal motor resonance response, which reflects the motor program encoding observed actions. We investigated the role of attention in human motor resonance with four experimental conditions, explored in different subject groups: in the first explicit condition, subjects were asked to observe a rhythmic hand flexion-extension movement performed live in front of them. In two other conditions subjects had to monitor the activity of a LED light mounted on the oscillating hand. The hand was clearly visible but it was not the focus of subjects’ attention: in the semi-implicit condition hand movement was relevant to task completion, while in the implicit condition it was irrelevant. In a fourth, baseline, condition subjects observed the rhythmic oscillation of a metal platform. Motor resonance was measured with the H-reflex technique as the excitability modulation of cortico-spinal motorneurons driving a hand flexor muscle. As expected, a normal resonant response developed in the explicit condition, and no resonant response in the baseline condition. Resonant responses also developed in both semi-implicit and implicit conditions and, surprisingly, were not different from each other, indicating that viewing an action is, per se, a powerful stimulus for the action observation network, even when it is not the primary focus of subjects’ attention and even when irrelevant to the task. However, the amplitude of these responses was much reduced compared to the explicit condition, and the phase-lock between the time courses of observed movement and resonant motor program was lost. In conclusion, different parameters of the response were differently affected by subtraction of attentional resources with respect to the explicit condition: time course and muscle selection were preserved while the activation of motor circuits resulted in much reduced amplitude and lost its kinematic specificity. [ABSTRACT FROM AUTHOR]

It is unclear how descending inputs from the vestibular system affect the excitability of cervical interneurons in humans. To elucidate this, we investigated the effects of galvanic vestibular stimulation (GVS) on the spatial facilitation of motor-evoked potentials (MEPs) induced by combined pyramidal tract and peripheral nerve stimulation. To assess the spatial facilitation, electromyograms were recorded from the biceps brachii muscles (BB) of healthy subjects. Transcranial magnetic stimulation (TMS) over the contralateral primary motor cortex and electrical stimulation of the ipsilateral ulnar nerve at the wrist were delivered either separately or together, with interstimulus intervals of 10 ms (TMS behind). Anodal/cathodal GVS was randomly delivered with TMS and/or ulnar nerve stimulation. The combination of TMS and ulnar nerve stimulation facilitated BB MEPs significantly more than the algebraic summation of responses induced separately by TMS and ulnar nerve stimulation (i.e., spatial facilitation). MEP facilitation significantly increased when combined stimulation was delivered with GVS (p < 0.01). No significant differences were found between anodal and cathodal GVS. Furthermore, single motor unit recordings showed that the short-latency excitatory peak in peri-stimulus time histograms during combined stimulation increased significantly with GVS. The spatial facilitatory effects of combined stimulation with short interstimulus intervals (i.e., 10 ms) indicate that facilitation occurred at the premotoneuronal level in the cervical cord. The present findings therefore suggest that GVS facilitates the cervical interneuron system that integrates inputs from the pyramidal tract and peripheral nerves and excites motoneurons innervating the arm muscles. [ABSTRACT FROM AUTHOR]

Measuring phosphene thresholds (PTs) is often used to investigate changes in the excitability of the human visual cortex through different brain stimulation methods like repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS). In several studies, PT increase or decrease has been shown after rTMS or tDCS application. Recently, using PT measurements we showed that the state of the neurons in the visual cortex after rTMS might have an influence on the modulatory effects of stimulation. In the present study we aimed to investigate whether visual cortex activity following stimulation influences the modulatory effects of tDCS as well. In a between-group design, anodal or cathodal tDCS was applied to the visual cortex twice per subject, with either high or low visual demand following stimulation. We observed no modulation of PT neither directly following both anodal and cathodal tDCS nor following the visual demand periods. We rather found high inter-individual variability in the response to tDCS, and intra-individual reliability in the direction of modulation was observed for cathodal tDCS only. Thus, our results do not confirm the modulatory effects of tDCS on visual cortex excitability published previously. Moreover, they support the confirmation that tDCS effects have little reliability on varied TMS outcome measurements. [ABSTRACT FROM AUTHOR]

Musical rhythms encompass temporal patterns that often yield regular metrical accents (e.g., a beat). There have been mixed results regarding perception as a function of metrical saliency, namely, whether sensitivity to a deviant was greater in metrically stronger or weaker positions. Besides, effects of metrical position have not been examined in non-isochronous rhythms, or with respect to multisensory influences. This study was concerned with two main issues: (1) In non-isochronous auditory rhythms with clear metrical accents, how would sensitivity to a deviant be modulated by metrical positions? (2) Would the effects be enhanced by multisensory information? Participants listened to strongly metrical rhythms with or without watching a point-light figure dance to the rhythm in the same meter, and detected a slight loudness increment. Both conditions were presented with or without an auditory interference that served to impair auditory metrical perception. Sensitivity to a deviant was found greater in weak beat than in strong beat positions, consistent with the Predictive Coding hypothesis and the idea of metrically induced illusory phenomenal accents. The visual rhythm of dance hindered auditory detection, but more so when the latter was itself less impaired. This pattern suggested that the visual and auditory rhythms were perceptually integrated to reinforce metrical accentuation, yielding more illusory phenomenal accents and thus lower sensitivity to deviants, in a manner consistent with the principle of inverse effectiveness. Results were discussed in the predictive framework for multisensory rhythms involving observed movements and possible mediation of the motor system. [ABSTRACT FROM AUTHOR]

Individuals show significant variations in performing a motor act. Previous studies in the action observation literature have largely ignored this ubiquitous, if often unwanted, characteristic of motor performance, assuming movement patterns to be highly similar across repetitions and individuals. In the present study, we examined the possibility that individual variations in motor style directly influence the ability to understand and predict others’ actions. To this end, we first recorded grasping movements performed with different intents and used a two-step cluster analysis to identify quantitatively ‘clusters’ of movements performed with similar movement styles (). Next, using videos of the same movements, we proceeded to examine the influence of these styles on the ability to judge intention from action observation (Experiments and ). We found that motor styles directly influenced observers’ ability to ‘read’ others’ intention, with some styles always being less ‘readable’ than others. These results provide experimental support for the significance of motor variability for action prediction, suggesting that the ability to predict what another person is likely to do next directly depends on her individual movement style. [ABSTRACT FROM AUTHOR]

Motor balance in developmental stuttering (DS) was investigated with Transcranial Magnetic Stimulation (TMS), with the aim to define novel neural markers of persistent DS in adulthood. Eleven DS adult males were evaluated with TMS on tongue primary motor cortex, compared to 15 matched fluent speakers, in a “state” condition (i.e. stutterers vs. fluent speakers, no overt stuttering). Motor and silent period thresholds (SPT), recruitment curves, and silent period durations were acquired by recording tongue motor evoked potentials. Tongue silent period duration was increased in DS, especially in the left hemisphere (P<0.05; Hedge’s g or Cohen’s dunbiased = 1.054, i.e. large effect size), suggesting a “state” condition of higher intracortical inhibition in left motor cortex networks. Differences in motor thresholds (different excitatory/inhibitory ratios in DS) were evident, as well as significant differences in SPT. In fluent speakers, the left hemisphere may be marginally more excitable than the right one in motor thresholds at lower muscular activation, while active motor thresholds and SPT were higher in the left hemisphere of DS with respect to the right one, resulting also in a positive correlation with stuttering severity. Pre-TMS electromyography data gave overlapping evidence. Findings suggest the existence of a complex intracortical balance in DS tongue primary motor cortex, with a particular interplay between excitatory and inhibitory mechanisms, also in neural substrates related to silent periods. Findings are discussed with respect to functional and structural impairments in stuttering, and are also proposed as novel neural markers of a stuttering “state” in persistent DS, helping to define more focused treatments (e.g. neuro-modulation). [ABSTRACT FROM AUTHOR]

Interactions between the auditory and the motor systems are critical in music as well as in other domains, such as speech. The premotor cortex, specifically the dorsal premotor cortex (dPMC), seems to play a key role in auditory-motor integration, and in mapping the association between a sound and the movement used to produce it. In the present studies we tested the causal role of the dPMC in learning and applying auditory-motor associations using 1 Hz repetitive Transcranical Magnetic Stimulation (rTMS). In this paradigm, non-musicians learn a set of auditory-motor associations through melody training in two contexts: first when the sound to key-press mapping was in a conventional sequential order (low to high tones mapped onto keys from left to right), and then when it was in a novel scrambled order. Participant’s ability to match the four pitches to four computer keys was tested before and after the training. In both experiments, the group that received 1 Hz rTMS over the dPMC showed no significant improvement on the pitch-matching task following training, whereas the control group (who received rTMS to visual cortex) did. Moreover, in Experiment 2 where the pitch-key mapping was novel, rTMS over the dPMC also interfered with learning. These findings suggest that rTMS over dPMC disturbs the formation of auditory-motor associations, especially when the association is novel and must be learned rather explicitly. The present results contribute to a better understanding of the role of dPMC in auditory-motor integration, suggesting a critical role of dPMC in learning the link between an action and its associated sound. [ABSTRACT FROM AUTHOR]

There is considerable interest in the therapeutic benefits of long-term sensory stimulation for improving cognitive abilities and motor performance of stroke patients. The rationale is that such stimulation would activate mechanisms of neural plasticity to promote enhanced coordination and associated circuit functions. Experimental approaches to characterize such mechanisms are needed. Drosophila melanogaster is one of the most attractive model organisms to investigate neural mechanisms responsible for stimulation-induced behaviors with its powerful accessibility to genetic analysis. In this study, the effect of chronic sensory stimulation (pulsed light stimulation) on motor activity in w1118 flies was investigated. Flies were exposed to a chronic pulsed light stimulation protocol prior to testing their performance in a standard locomotion assay. Flies responded to pulsed light stimulation with increased boundary preference and travel distance in a circular arena. In addition, pulsed light stimulation increased the power of extracellular electrical activity, leading to the enhancement of periodic electrical activity which was associated with a centrally-generated motor pattern (struggling behavior). In contrast, such periodic events were largely missing in w1118 flies without pulsed light treatment. These data suggest that the sensory stimulation induced a response in motor activity associated with the modifications of electrical activity in the central nervous system (CNS). Finally, without pulsed light treatment, the wild-type genetic background was associated with the occurrence of the periodic activity in wild-type Canton S (CS) flies, and w+ modulated the consistency of periodicity. We conclude that pulsed light stimulation modifies behavioral and electrophysiological activities in w1118 flies. These data provide a foundation for future research on the genetic mechanisms of neural plasticity underlying such behavioral modification. [ABSTRACT FROM AUTHOR]

Subthreshold continuous theta burst stimulation of the visual cortex has been reported to cause inhibitory effects on phosphene threshold. In contrast, we observed no inhibition in a former study applying higher stimulation intensities. The main discrepancies between our experiments and the former studies were stimulation intensity and coil type. We aimed at investigating the role of these factors on the modulatory effects of continuous theta burst stimulation applied to the visual cortex. In a between-group-design, we used either a figure-of-eight-coil or a round coil, respectively. We measured phosphene thresholds prior and after continuous theta burst stimulation applied at 80% of individual phosphene threshold. With the figure-of-eight-coil, phosphene thresholds significantly decreased following stimulation. This is in line with the results of our former study but contrary to the increase observed in the other two studies. Using a round coil, no significant effect was observed. A correlation analysis revealed an inhibitory effect in subjects with higher phosphene thresholds only. Furthermore, the slope of the baseline phosphene threshold seems to predict the direction of modulation, independent from coil type. Thus, modulatory effects of continuous theta burst stimulation seem to depend on coil type and psychophysics parameters, probably due to different cortex volumes stimulated. Stochastic resonance phenomena might account for the differences observed. [ABSTRACT FROM AUTHOR]

Grounded cognition proposes that memory shares processing resources with sensorimotor systems. The aim of the present study was to show that motor simulation participates in the conceptual representation of manipulable objects in long-term memory. In two experiments, lists of manipulable and nonmanipulable objects were presented. Participants were instructed to memorize the items while adopting different postures. In the control condition, they had to keep their hands at rest in front of them. In the interference condition, participants had to keep their hands crossed behind their back to make their hands less free for action. After each list, participants had to perform first a distractive task, and then an oral free recall. The results showed that the interfering posture produced a specific decrease in the recall of manipulable objects, but not of nonmanipulable ones. This decrease was similar when the items were presented as pictures (Experiment 1) or as words (Experiment 2), thus excluding a purely visual effect. These results provide strong evidence that the motor simulation plays a role in the memory trace of the object. [ABSTRACT FROM AUTHOR]

Converging evidence suggest that motor training is associated with early and late changes of the cortical motor system. Transcranial magnetic stimulation (TMS) offers the possibility to study plastic rearrangements of the motor system in physiological and pathological conditions. We used TMS to characterize long-term changes in upper limb motor cortical representation and interhemispheric inhibition associated with bimanual skill training in pianists who started playing in an early age. Ipsilateral silent period (iSP) and cortical TMS mapping of hand muscles were obtained from 30 strictly right-handed subjects (16 pianists, 14 naïve controls), together with electromyographic recording of mirror movements (MMs) to voluntary hand movements. In controls, motor cortical representation of hand muscles was larger on the dominant (DH) than on the non-dominant hemisphere (NDH). On the contrary, pianists showed symmetric cortical output maps, being their DH less represented than in controls. In naïve subjects, the iSP was smaller on the right vs left abductor pollicis brevis (APB) indicating a weaker inhibition from the NDH to the DH. In pianists, interhemispheric inhibition was more symmetric as their DH was better inhibited than in controls. Electromyographic MMs were observed only in naïve subjects (7/14) and only to voluntary movement of the non-dominant hand. Subjects with MM had a lower iSP area on the right APB compared with all the others. Our findings suggest a more symmetrical motor cortex organization in pianists, both in terms of muscle cortical representation and interhemispheric inhibition. Although we cannot disentangle training-related from preexisting conditions, it is possible that long-term bimanual practice may reshape motor cortical representation and rebalance interhemispheric interactions, which in naïve right-handed subjects would both tend to favour the dominant hemisphere. [ABSTRACT FROM AUTHOR]

Objective: Megalencephalic leukoencephalopathy with subcortical cysts (MLC, OMIM 604004) is a rare neurological deterioration disease. We aimed to clarify clinical and genetic features of Chinese MLC patients. Methods: Clinical information and peripheral venous blood of 20 patients and their families were collected, Sanger-sequencing and Multiple Ligation-dependent Probe Amplification were performed to make genetic analysis. Splicing-site mutation was confirmed with RT-PCR. UPD was detected by haplotype analysis. Follow-up study was performed through telephone for 27 patients. Results: Out of 20 patients, macrocephaly, classic MRI features, motor development delay and cognitive impairment were detected in 20(100%), 20(100%), 17(85%) and 4(20%) patients, respectively. 20(100%) were clinically diagnosed with MLC. 19(95%) were genetically diagnosed with 10 novel mutations in MLC1, MLC1 and GlialCAM mutations were identified in 15 and 4 patients, respectively. Deletion mutation from exon4 to exon9 and a homozygous point mutation due to maternal UPD of chromosome22 in MLC1 were found firstly. c.598-2A>C in MLC1 leads to the skip of exon8. c.772-1G>C in MLC1 accounting for 15.5%(9/58) alleles in Chinese patients might be a founder or a hot-spot mutation. Out of 27 patients in the follow-up study, head circumference was ranged from 56cm to 61cm in patients older than 5yeas old, with a median of 57cm. Motor development delay and cognitive impairment were detected in 22(81.5%) and 5(18.5%) patients, respectively. Motor and cognitive deterioration was found in 5 (18.5%) and 2 patients (7.4%), respectively. Improvements and MRI recovery were first found in Chinese patients. Rate of seizures (45.5%), transient motor retrogress (45.5%) and unconsciousness (13.6%) after head trauma was much higher than that after fever (18.2%, 9.1%, 0%, respectively). Significance: It’s a clinical and genetic analysis and a follow-up study for largest sample of Chinese MLC patients, identifying 10 novel mutations, expanding mutation spectrums and discovering clinical features of Chinese MLC patients. [ABSTRACT FROM AUTHOR]

Neuroplasticity and reorganization of brain motor networks are thought to enable recovery of motor function after ischemic stroke. Especially in the cortex surrounding the ischemic scar (i.e., peri-infarct cortex), evidence for lasting reorganization has been found at the level of neurons and networks. This reorganization depends on expression of specific genes and subsequent protein synthesis. To test the functional relevance of the peri-infarct cortex for recovery we assessed the effect of protein synthesis inhibition within this region after experimental stroke. Long-Evans rats were trained to perform a skilled-reaching task (SRT) until they reached plateau performance. A photothrombotic stroke was induced in the forelimb representation of the primary motor cortex (M1) contralateral to the trained paw. The SRT was re-trained after stroke while the protein synthesis inhibitor anisomycin (ANI) or saline were injected into the peri-infarct cortex through implanted cannulas. ANI injections reduced protein synthesis within the peri-infarct cortex by 69% and significantly impaired recovery of reaching performance through re-training. Improvement of motor performance within a single training session remained intact, while improvement between training sessions was impaired. ANI injections did not affect infarct size. Thus, protein synthesis inhibition within the peri-infarct cortex impairs recovery of motor deficits after ischemic stroke by interfering with consolidation of motor memory between training sessions but not short-term improvements within one session. [ABSTRACT FROM AUTHOR]

Neuronal oscillatory activity in the beta band (15–30 Hz) is a prominent signal within the human sensorimotor cortex. Computational modeling and pharmacological modulation studies suggest an influence of GABAergic interneurons on the generation of beta band oscillations. Accordingly, studies in humans have demonstrated a correlation between GABA concentrations and power of beta band oscillations. It remains unclear, however, if GABA concentrations also influence beta peak frequencies and whether this influence is present in the sensorimotor cortex at rest and without pharmacological modulation. In the present study, we investigated the relation between endogenous GABA concentration (measured by magnetic resonance spectroscopy) and beta oscillations (measured by magnetoencephalography) at rest in humans. GABA concentrations and beta band oscillations were measured for left and right sensorimotor and occipital cortex areas. A significant positive linear correlation between GABA concentration and beta peak frequency was found for the left sensorimotor cortex, whereas no significant correlations were found for the right sensorimotor and the occipital cortex. The results show a novel connection between endogenous GABA concentration and beta peak frequency at rest. This finding supports previous results that demonstrated a connection between oscillatory beta activity and pharmacologically modulated GABA concentration in the sensorimotor cortex. Furthermore, the results demonstrate that for a predominantly right-handed sample, the correlation between beta band oscillations and endogenous GABA concentrations is evident only in the left sensorimotor cortex. [ABSTRACT FROM AUTHOR]

Background: Hereditary spastic paraplegias (HSP) are a composite and genetically heterogeneous group of conditions mainly expressed by the impairment of the central motor system (“pure” forms). The involvement of other components of the central nervous system or of other systems is described in the “complicate” forms. The definition of an investigation protocol capable, by assembling clinical and paraclinical indicators to fully represent the extent of the motor system impairment, would help both the clinical handling of these conditions and contribute to our understanding of their pathogenesis. Methods: We applied a clinical and paraclinical protocol which included tools exploring motor and non motor functioning, neurophysiology and MRI to a composite cohort of 70 molecularly defined HSP patients aged 3 to 65, to define for each indicator its significance in detailing the presence and the severity of the pathology. Results: Clinically increased deep tendon reflexes and lower limb (LL) weakness are constant findings in all patients. The “complicated” forms are characterized by peripheral motor impairment, cognitive and cerebellar involvement. The Spastic Paraplegia Rating Scale efficiently reflects the severity of functional problems and correlates with disease duration. Neurophysiology consistently documents the impairment of the central motor pathway to the LLs. Nevertheless, the upper extremities and sensory system involvement is a frequent finding. MRI diffusion tensor imaging (DTI) highlighted a significant alteration of FA and MD. Combining the sampling of the various portion of the cortico-spinal tract (CST) DTI consistently discriminated patients from controls. Conclusion: We propose a graded clinical and paraclinical protocol for HSP phenotype definition, indicating for each tool the discriminative and descriptive capacity. Our protocol applied to 9 different forms of HSP showed that the functional impairment often extends beyond the CST. The novel DTI approach may add significant elements in disease recognition, staging and mapping. [ABSTRACT FROM AUTHOR]

Motorized treadmills have been widely used in locomotion studies, although a debate remains concerning the extrapolation of results obtained from treadmill experiments to overground locomotion. Slight differences between treadmill (TRD) and overground running (OVG) kinematics and muscle activity have previously been reported. However, little is known about differences in the modular control of muscle activation in these two conditions. Therefore, we aimed at investigating differences between motor modules extracted from TRD and OVG by factorization of multi-muscle electromyographic (EMG) signals. Twelve healthy men ran on a treadmill and overground at their preferred speed while we recorded tibial acceleration and surface EMG from 11 ipsilateral lower limb muscles. We extracted motor modules representing relative weightings of synergistic muscle activations by non-negative matrix factorization from 20 consecutive gait cycles. Four motor modules were sufficient to accurately reconstruct the EMG signals in both TRD and OVG (average reconstruction quality = 92±3%). Furthermore, a good reconstruction quality (80±7%) was obtained also when muscle weightings of one condition (either OVG or TRD) were used to reconstruct the EMG data from the other condition. The peak amplitudes of activation signals showed a similar timing (pattern) across conditions. The magnitude of peak activation for the module related to initial contact was significantly greater for OVG, whereas peak activation for modules related to leg swing and preparation to landing were greater for TRD. We conclude that TRD and OVG share similar muscle weightings throughout motion. In addition, modular control for TRD and OVG is achieved with minimal temporal adjustments, which were dependent on the phase of the running cycle. [ABSTRACT FROM AUTHOR]

Motor control is a challenging task for the central nervous system, since it involves redundant degrees of freedom, nonlinear dynamics of actuators and limbs, as well as noise. When an action is carried out, which factors does your nervous system consider to determine the appropriate set of muscle forces between redundant degrees-of-freedom? Important factors determining motor output likely encompass effort and the resulting motor noise. However, the tasks used in many previous motor control studies could not identify these two factors uniquely, as signal-dependent noise monotonically increases as a function of the effort. To address this, a recent paper introduced a force control paradigm involving one finger in each hand that can disambiguate these two factors. It showed that the central nervous system considers both force noise and amplitude, with a larger weight on the absolute force and lower weights on both noise and normalized force. While these results are valid for the relatively low force range considered in that paper, the magnitude of the force shared between the fingers for large forces is not known. This paper investigates this question experimentally, and develops an appropriate Markov chain Monte Carlo method in order to estimate the weightings given to these factors. Our results demonstrate that the force sharing strongly depends on the force level required, so that for higher force levels the normalized force is considered as much as the absolute force, whereas the role of noise minimization becomes negligible. [ABSTRACT FROM AUTHOR]

Background: The available clinical outcome measures of disability in multiple sclerosis are not adequately responsive or sensitive. Objective: To investigate the feasibility of inertial sensor-based gait analysis in multiple sclerosis. Methods: A cross-sectional study of 80 multiple sclerosis patients and 50 healthy controls was performed. Lower-limb kinematics was evaluated by using a commercially available magnetic inertial measurement unit system. Mean and standard deviation of range of motion (mROM, sROM) for each joint of lower limbs were calculated in one minute walking test. A motor performance index (E) defined as the sum of sROMs was proposed. Results: We established two novel observer-independent measures of disability. Hip mROM was extremely sensitive in measuring lower limb motor impairment, being correlated with muscle strength and also altered in patients without clinically detectable disability. On the other hand, E index discriminated patients according to disability, being altered only in patients with moderate and severe disability, regardless of walking speed. It was strongly correlated with fatigue and patient-perceived health status. Conclusions: Inertial sensor-based gait analysis is feasible and can detect clinical and subclinical disability in multiple sclerosis. [ABSTRACT FROM AUTHOR]

Unilateral strength training can cause cross-transfer strength effects to the homologous contralateral muscles. However, the impact of the cross-over effects on the muscle tissue is unclear. To test the hypothesis that unilateral muscle overuse causes bilateral alterations in muscle fiber composition and vascular supply, we have used an experimental rabbit model with unilateral unloaded overstrain exercise via electrical muscle stimulation (E/EMS). The soleus (SOL) and gastrocnemius (GA) muscles of both exercised (E) and contralateral non-exercised (NE) legs (n = 24) were morphologically analyzed after 1w, 3w and 6w of EMS. Non-exercised rabbits served as controls (n = 6). After unilateral intervention the muscles of both E and NE legs showed myositis and structural and molecular tissue changes that to various degrees mirrored each other. The fiber area was bilaterally smaller than in controls after 3w of E/EMS in both SOL (E 4420 and NE 4333 µm2 vs. 5183 µm2, p<0.05) and GA (E 3572 and NE 2983 µm2 vs. 4697 µm2, p<0.02) muscles. After 6w of E/EMS, the percentage of slow MyHCI fibers was lower than in controls in the NE legs of SOL (88.1% vs. 98.1%, p<0.009), while the percentage of fast MyHCIIa fibers was higher in the NE legs of GA (25.7% vs. 15.8%, p = 0.02). The number of capillaries around fibers in the E and NE legs was lower (SOL 13% and 15%, respectively, GA 25% and 23%, respectively, p<0.05) than in controls. The overall alterations were more marked in the fast GA muscle than in the slow SOL muscle, which on the other hand showed more histopathological muscle changes. We conclude that unilateral repetitive unloaded overuse exercise via EMS causes myositis and muscle changes in fiber type proportions, fiber area and fiber capillarization not only in the exercised leg, but also in the homologous muscles in the non-exercised leg. [ABSTRACT FROM AUTHOR]

Previous studies have shown that saccades may deviate towards or away from task irrelevant visual distractors. This observation has been attributed to active suppression (inhibition) of the distractor location unfolding over time: early in time inhibition at the distractor location is incomplete causing deviation towards the distractor, while later in time when inhibition is complete the eyes deviate away from the distractor. In a recent computational study, Wang, Kruijne and Theeuwes proposed an alternative theory that the lateral interactions in the superior colliculus (SC), which are characterized by short-distance excitation and long-distance inhibition, are sufficient for generating both deviations towards and away from distractors. In the present study, we performed a meta-analysis of the literature, ran model simulations and conducted two behavioral experiments to further explore this unconventional theory. Confirming predictions generated by the model simulations, the behavioral experiments show that a) saccades deviate towards close distractors and away from remote distractors, and b) the amount of deviation depends on the strength of fixation activity in the SC, which can be manipulated by turning off the fixation stimulus before or after target onset (Experiment 1), or by varying the eccentricity of the target and distractor (Experiment 2). [ABSTRACT FROM AUTHOR]

Use of illicit stimulant drugs such as methamphetamine, cocaine, and ecstasy are a significant worldwide problem. However, little is known about the effect of these drugs on movement. The aim of the current study was to investigate hand function in adults with a history of illicit stimulant use. We hypothesized that prior use of illicit stimulant drugs is associated with abnormal manipulation of objects. The study involved 22 subjects with a history of illicit stimulant use (aged 29±8 yrs; time since last use: 1.8±4.0 yrs) and two control groups comprising 27 non-drug users (aged 25±8 yrs) and 17 cannabis users with no history of stimulant use (aged 22±5 yrs). Each subject completed screening tests (neuropsychological assessment, medical history questionnaire, lifetime drug history questionnaire, and urine drug screen) prior to gripping and lifting a light-weight object with the dominant right hand. Horizontal grip force, vertical lift force, acceleration, and first dorsal interosseus electromyographic (EMG) activity were recorded during three trials. In trial one, peak grip force was significantly greater in the stimulant group (12.8±3.9 N) than in the control groups (non-drug: 10.3±4.6 N; cannabis: 9.4±2.9 N, P<0.022). However, peak grip force did not differ between groups in trials two and three. The results suggest that individuals with a history of stimulant use overestimate the grip force required to manipulate a novel object but, are able to adapt grip force in subsequent lifts. The results suggest that movement dysfunction may be an unrecognized consequence of illicit stimulant use. [ABSTRACT FROM AUTHOR]

The current study investigated the rhythmic coordination between vocalization and whole-body movement. Previous studies have reported that spatiotemporal stability in rhythmic movement increases when coordinated with a rhythmic auditory stimulus or other effector in a stable coordination pattern. Therefore, the present study conducted two experiments to investigate (1) whether there is a stable coordination pattern between vocalization and whole-body movement and (2) whether a stable coordination pattern reduces variability in whole-body movement and vocalization. In , two coordination patterns between vocalizations and whole-body movement (hip, knee, and ankle joint flexion-on-the-voice vs. joint extension-on-the-voice) in a standing posture were explored at movement frequencies of 80, 130, and 180 beats per minute. At higher movement frequencies, the phase angle in the extension-on-the-voice condition deviated from the intended phase angle. However, the angle of the flexion-on-the-voice was maintained even when movement frequency increased. These results suggest that there was a stable coordination pattern in the flexion-on-the-voice condition. In , variability in whole-body movement and voice-onset intervals was compared between two conditions: one related to tasks performed in the flexion-on-the-voice coordination (coordination condition) that was a stable coordination pattern, and the other related to tasks performed independently (control condition). The results showed that variability in whole-body movement and voice-onset intervals was smaller in the coordination condition than in the control condition. Overall, the present study revealed mutual stabilization between rhythmic vocalization and whole-body movement via coordination within a stable pattern, suggesting that coupled action systems can act as a single functional unit or coordinative structure. [ABSTRACT FROM AUTHOR]

Speech impairment is one of the most intriguing and least understood effects of alcohol on cognitive function, largely due to the lack of data on alcohol effects on vocalizations in the context of an appropriate experimental model organism. Zebra finches, a representative songbird and a premier model for understanding the neurobiology of vocal production and learning, learn song in a manner analogous to how humans learn speech. Here we show that when allowed access, finches readily drink alcohol, increase their blood ethanol concentrations (BEC) significantly, and sing a song with altered acoustic structure. The most pronounced effects were decreased amplitude and increased entropy, the latter likely reflecting a disruption in the birds’ ability to maintain the spectral structure of song under alcohol. Furthermore, specific syllables, which have distinct acoustic structures, were differentially influenced by alcohol, likely reflecting a diversity in the neural mechanisms required for their production. Remarkably, these effects on vocalizations occurred without overt effects on general behavioral measures, and importantly, they occurred within a range of BEC that can be considered risky for humans. Our results suggest that the variable effects of alcohol on finch song reflect differential alcohol sensitivity of the brain circuitry elements that control different aspects of song production. They also point to finches as an informative model for understanding how alcohol affects the neuronal circuits that control the production of learned motor behaviors. [ABSTRACT FROM AUTHOR]

Motoneurons are furnished with a vast repertoire of ionotropic and metabotropic receptors as well as ion channels responsible for maintaining the resting membrane potential and involved in the regulation of the mechanisms underlying its membrane excitability and firing properties. Among them, the GABAA receptors, which respond to GABA binding by allowing the flow of Cl− ions across the membrane, mediate two distinct forms of inhibition in the mature nervous system, phasic and tonic, upon activation of synaptic or extrasynaptic receptors, respectively. In a previous work we showed that furosemide facilitates the monosynaptic reflex without affecting the dorsal root potential. Our data also revealed a tonic inhibition mediated by GABAA receptors activated in motoneurons by ambient GABA. These data suggested that the high affinity GABAA extrasynaptic receptors may have an important role in motor control, though the molecular nature of these receptors was not determined. By combining electrophysiological, immunofluorescence and molecular biology techniques with pharmacological tools here we show that GABAA receptors containing the α6 subunit are expressed in adult turtle spinal motoneurons and can function as extrasynaptic receptors responsible for tonic inhibition. These results expand our understanding of the role of GABAA receptors in motoneuron tonic inhibition. [ABSTRACT FROM AUTHOR]

Human observers are able to perceive the motion direction of actions (either forward or backward) on the basis of the articulatory, relative motion of the limbs, even when the actions are shown under point-light conditions. However, most studies have focused on the action of walking. The primary purpose of the present study is to further investigate the perception of articulatory motion in different point-light actions (walking, crawling, hand walking, and rowing). On each trial, participants were presented with a forward or backward moving person and they had to decide on the direction of articulatory motion of the person. We analyzed sensitivity (d') as well as response bias (c). In addition to the type of action, the diagnosticity of the available information was manipulated by varying the visibility of the body parts (full body, only upper limbs, or only lower limbs) and the viewpoint from which the action was seen (from frontal view to sagittal view). We observe that, depending on the specific action, perception of direction of motion is driven by different body parts. Implications for the possible existence of a life detector, i.e., an evolutionarily old and innate visual filter that is tuned to quickly and automatically detect the presence of a moving living organism and direct attention to it, are discussed. [ABSTRACT FROM AUTHOR]

Forming the proper number of synapses is crucial for normal neuronal development. We found that loss of function of the phosphoinositide phosphatase mtm-6 results in a reduction in the number of synaptic puncta. The reduction in synapses is partially the result of MTM-6 regulation of the secretion of the Wnt ligand EGL-20 from cells in the tail and partially the result of neuronal action. MTM-6 shows relative specificity for EGL-20 over the other Wnt ligands. We suggest that the ability of MTM-6 to regulate EGL-20 secretion is a function of its expression pattern. We conclude that regulation of secretion of different Wnt ligands can use different components. Additionally, we present a novel neuronal function for MTM-6. [ABSTRACT FROM AUTHOR]

Background: Second-generation antihistamines (AHs) have, in general, fewer sedative effects than the first-generation. However, important inter-drug differences remain in the degree of cognitive and/or psychomotor impairment. The extent to which a particular compound causes disruption can be conveniently compared, to all other AHs, using the Proportional Impairment Ratio (PIR). Although the PIR can differentiate the relative impairment caused by individual drugs, there is no indication of the reliability of the ratios obtained. Objective: To calculate the PIRs –together with 95% confidence intervals (CIs), as an index of reliability– and compare AHs currently, or soon to be, available in Japan, with respect to their intrinsic capacity to cause impairment. Methods: Results from studies of cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, mequitazine, and olopatadine were included in the PIR calculations. All data utilised came from crossover studies in healthy volunteers which were randomised and placebo and positive-internal controlled. Existing databases from studies reporting the sedative effects of AHs on objective (speed, accuracy, memory) and subjective (feeling) psychometrics were augmented, via results from suitable studies published after the previous reviews. The null value for a PIR was one. Results: A total of 45 studies were finally included for this review. Of the AHs assessed, fexofenadine, ebastine, and levocetirizine showed a PIR for objective tests of 0. However, only fexofenadine (PIR = 0.49) had an upper limit of the 95% CI of less than 1. Fexofenadine, levocetirizine, desloratadine, olopatadine, loratadine, and mequitazine all had a PIR for subjective ratings of 0, but the upper limits of the 95% CIs were all in excess of 1, although fexofenadine (PIR = 2.57) was the lowest. Conclusions: The results show that there are differences between second-generation AHs in the extent of sedation produced. However, subjective ratings indicate that patients may not necessarily be aware of this. [ABSTRACT FROM AUTHOR]