Brain Noradrenergic Innervation Supports the Development of Parkinson's Tremor: A Study in a Reserpinized Rat Model.

The pathophysiology of tremor in Parkinson's disease (PD) is evolving towards a complex alteration to monoaminergic innervation, and increasing evidence suggests a key role of the locus coeruleus noradrenergic system (LC-NA). However, the difficulties in imaging LC-NA in patients challenge its direct investigation. To this end, we studied the development of tremor in a reserpinized rat model of PD, with or without a selective lesioning of LC-NA innervation with the neurotoxin DSP-4. Eight male rats (Sprague Dawley) received DSP-4 (50 mg/kg) two weeks prior to reserpine injection (10 mg/kg) (DR-group), while seven male animals received only reserpine treatment (R-group). Tremor, rigidity, hypokinesia, postural flexion and postural immobility were scored before and after 20, 40, 60, 80, 120 and 180 min of reserpine injection. Tremor was assessed visually and with accelerometers. The injection of DSP-4 induced a severe reduction in LC-NA terminal axons (DR-group: 0.024 ± 0.01 vs. R-group: 0.27 ± 0.04 axons/um2, p < 0.001) and was associated with significantly less tremor, as compared to the R-group (peak tremor score, DR-group: 0.5 ± 0.8 vs. R-group: 1.6 ± 0.5; p < 0.01). Kinematic measurement confirmed the clinical data (tremor consistency (% of tremor during 180 s recording), DR-group: 37.9 ± 35.8 vs. R-group: 69.3 ± 29.6; p < 0.05). Akinetic-rigid symptoms did not differ between the DR- and R-groups. Our results provide preliminary causal evidence for a critical role of LC-NA innervation in the development of PD tremor and foster the development of targeted therapies for PD patients.

Reliability of Shoulder Helical Axes During Intransitive and Transitive Upper Limb Tasks.

Shoulder complex stability can be estimated in vivo through the analysis of helical axes (HAs) dispersion during upper limb movements. The study aimed at investigating test-retest reliability of shoulder HAs dispersion parameters during upper limb tasks. Twenty healthy volunteers performed 2 intransitive (shoulder flexion and rotation) and one transitive (combing) tasks with the dominant and nondominant upper limbs during 2 recording sessions at 1-week distance. Kinematics was detected through an optoelectronic system. Mean distance and mean angle (MA) were adopted as HAs dispersion indexes. Reliability was excellent for mean distance (intraclass correlation coefficient [ICC]: .91) and MA (ICC: .92) during dominant flexion, and good for MA (ICC: .90) during nondominant flexion. Moderate reliability was found for HAs parameters during rotation (ICCs from .70 to .59), except for MA during dominant rotation where reliability was poor. Reliability was good for mean distance (ICC: .83) and moderate for MA (ICC: .67) during the dominant combing task, whereas no reliability was found during the nondominant combing task. HAs dispersion parameters revealed high reliability during simple intransitive tasks with the dominant limb. Reliability decreased with the increase in task complexity due to the increase in movement variability. HAs dispersion technique could be used to assess shoulder complex stability in patients after rehabilitation or surgery.

Action observation plus motor imagery and somatosensory discrimination training are effective non-motor approaches to improve manual dexterity.

BACKGROUND: Action observation plus motor imagery (AOMI) and somatosensory discrimination training (SSDT) represent sensory input-based approaches to train the motor system without necessarily asking subjects to perform active movements. PURPOSE: To investigate AOMI and SSDT effects compared to no intervention on manual dexterity in healthy subjects. STUDY DESIGN: Randomized controlled study. METHODS: Sixty healthy right-handed participants were randomized into AOMI, SSDT or Control (CTRL) groups. AOMI observed video-clips including right-hand dexterity tasks and concurrently performed motor imagery, SSDT performed surfaces recognition and 2-point distance discrimination tasks with the right hand, whereas CTRL underwent no intervention. A blinded physiotherapist assessed participants for manual dexterity using the Purdue Pegboard Test (Right hand-R, Left hand-L, Both hands-B, R+L+B and assembly tasks) at baseline (T0) and training end (T1). A mixed-design Analysis of Variance with Time as within-subject factor and Group as between-subject factor was used to investigate between-group differences over time. RESULTS: A Time by Group interaction and Time effect were found for R task, which increased from T0 to T1 in all groups with very large effect sizes for SSDT (d = 1.8, CI95 2.4-1.0, P < .001) and AOMI (d = 1.7, CI95 2.5-1.0, P < .001) and medium effect size for CTRL (d = 0.6, CI95 1.2-0.2, P < .001). Between-group post-hoc comparison for deltas (T1-T0) showed large effect size (d = 1.0, CI95 1.6-0.3, P = .003) in favor of SSDT and medium effect size (d = 0.7, CI95 1.4-0.1, P = .026) in favor of AOMI compared to CTRL. Time effects were found for L, B, R + L + B and assembly tasks (P < .001). CONCLUSIONS: AOMI and SSDT induced greater manual dexterity improvements than no intervention. These findings supported the role of visual and somatosensory stimuli in building a motor plan and enhancing the accuracy of hand movements. These non-motor approaches may enhance motor performance in job or hobbies requiring marked manual dexterity.

Motor resonance to non-visible postural adaptation: A novel aspect of the mirror mechanism.

The activation of the Mirror Neuron System (MNS) has been described to reflect visible movements, but not postural, non-visible, adaptations that accompany the observed movements. Since any motor act is the result of a well-tailored dialogue between these two components, we decided to investigate whether a motor resonance to nonvisible postural adaptations could be detected. Possible changes in soleus corticospinal excitability were investigated by eliciting the H-reflex during the observation of three videos, corresponding to three distinct experimental conditions: 'Chest pass', 'Standing' and 'Sitting', and comparing its size with that measured during observation of a control videoclip (a landscape). In the observed experimental conditions, the Soleus muscle has different postural roles: a dynamic role in postural adaptations during the Chest pass; a static role while Standing still; no role while Sitting. The H-reflex amplitude was significantly enhanced in the 'Chest pass' condition compared to the 'Sitting' and 'Standing' conditions. No significant difference was found between 'Sitting' and 'Standing' conditions. The increased corticospinal excitability of the Soleus during the 'Chest pass' condition suggests that the mirror mechanisms produce a resonance to postural components of an observed action, although they may not be visible. This observation highlights the fact that mirror mechanisms echo non intentional movements as well and points to a novel possible role of mirror neurons in motor recovery.

A Novel Viewpoint on the Anticipatory Postural Adjustments During Gait Initiation.

Anticipatory postural adjustments (APAs) are the coordinated muscular activities that precede the voluntary movements to counteract the associated postural perturbations. Many studies about gait initiation call APAs those activities that precede the heel-off of the leading foot, thus taking heel-off as the onset of voluntary movement. In particular, leg muscles drive the center of pressure (CoP) both laterally, to shift the body weight over the trailing foot and backward, to create a disequilibrium torque pushing forward the center of mass (CoM). However, since subjects want to propel their body rather than lift their foot, the onset of gait should be the CoM displacement, which starts with the backward CoP shift. If so, the leg muscles driving such a shift are the prime movers. Moreover, since the disequilibrium torque is mechanically equivalent to a forward force acting at the pelvis level, APAs should be required to link the body segments to the pelvis: distributing such concentrated force throughout the body would make all segments move homogeneously. In the aim of testing this hypothesis, we analyzed gait initiation in 15 right-footed healthy subjects, searching for activities in trunk muscles that precede the onset of the backward CoP shift. Subjects stood on a force plate for about 10 s and then started walking at their natural speed. A minimum of 10 trials were collected. A force plate measured the CoP position while wireless probes recorded the electromyographic activities. Recordings ascertained that at gait onset APAs develop in trunk muscles. On the right side, Rectus Abdominis and Obliquus Abdominis were activated in 11 and 13 subjects, respectively, starting on average 33 and 54 ms before the CoP shift; Erector Spinae (ES) at L2 and T3 levels was instead inhibited (9 and 7 subjects, 104 and 120 ms). On the contralateral side, the same muscles showed excitatory APAs (abdominals in 11 and 12 subjects, 27 and 82 ms; ES in 10 and 7 subjects, 75 and 32 ms). The results of this study provide a novel framework for distinguishing postural from voluntary actions, which may be relevant for the diagnosis and rehabilitation of gait disorders.

Dual-Hemisphere Transcranial Direct Current Stimulation on Parietal Operculum Does Not Affect the Programming of Intra-limb Anticipatory Postural Adjustments.

Evidence shows that the postural and focal components within the voluntary motor command are functionally unique. In 2015, we reported that the supplementary motor area (SMA) processes Anticipatory Postural Adjustments (APAs) separately from the command to focal muscles, so we are still searching for a hierarchically higher area able to process both components. Among these, the parietal operculum (PO) seemed to be a good candidate, as it is a hub integrating both sensory and motor streams. However, in 2019, we reported that transcranial Direct Current Stimulation (tDCS), applied with an active electrode on the PO contralateral to the moving segment vs. a larger reference electrode on the opposite forehead, did not affect intra-limb APAs associated to brisk flexions of the index-finger. Nevertheless, literature reports that two active electrodes of opposite polarities, one on each PO (dual-hemisphere, dh-tDCS), elicit stronger effects than the "active vs. reference" arrangement. Thus, in the present study, the same intra-limb APAs were recorded before, during and after dh-tDCS on PO. Twenty right-handed subjects were tested, 10 for each polarity: anode on the left vs. cathode on the right, and vice versa. Again, dh-tDCS was ineffective on APA amplitude and timing, as well as on prime mover recruitment and index-finger kinematics. These results confirm the conclusion that PO does not take part in intra-limb APA control. Therefore, our search for an area in which the motor command to prime mover and postural muscles are still processed together will have to address other structures.

Transcranial Direct Current Stimulation on Parietal Operculum Contralateral to the Moving Limb Does Not Affect the Programming of Intra-Limb Anticipatory Postural Adjustments.

Recent data suggest that the parietal operculum acts as an integration center within a multimodal network, originating from different primary sensory and motor cortices and projecting to frontal, parietal and temporal cortical hubs, which in turn govern cognitive and motor functions. Thus, parietal operculum might also play a crucial role in the integrated control of voluntary movement and posture. As a first step to test this hypothesis, the Anticipatory Postural Adjustments (APAs) stabilizing the arm when the index-finger is briskly flexed were recorded, on the preferred side, in three groups of 10 healthy subjects, before, during and after CATHODAL or ANODAL transcranial Direct Current Stimulation (tDCS, 20 min at 2 mA) applied over the contralateral Parietal Operculum (coPO). Results were compared to those obtained in a SHAM group. In agreement with literature, in the SHAM group the activation of the prime mover Flexor Digitorum Superficialis was preceded by an inhibitory APA in Biceps Brachii and Anterior Deltoid, and almost simultaneous to an excitatory APA in Triceps Brachii. The same pattern was observed in both the CATHODAL and ANODAL groups, with no significant tDCS effects on APAs amplitude and timing. Index-finger kinematics were also unchanged. These negative results suggest that the coPO does not disturb the key network governing APAs in index-finger flexion. Since it has been well documented that such APAs share many features with those observed in trunk and limb muscles when performing several other movements, we suggest that coPO may not be crucial to the general APA control.

Ephaptic interactions between myelinated nerve fibres of rodent peripheral nerves.

We report evidence that ephaptic interactions may occur between intact mammalian myelinated nerve fibres and not only between demyelinated or damaged mammalian nerve fibres or nerve cells as analysed in previous studies. The ephaptic interactions were investigated between nerve fibres traversing the lumbar dorsal roots and between bundles of fibres in the sciatic nerve in anaesthetized rats in vivo. The interactions were estimated by comparing the excitability of nerve fibres originating from one of the hindlimb nerves (peroneal or sural) under control conditions and when the stimulation of these fibres was combined with stimulation of another nerve (tibial). An increase in nerve volleys recorded from group I muscle afferents in the peroneal nerve and of the fastest skin afferents in the sural nerve was used as a measure of the increase in the excitability. The excitability of these fibres was increased during a fraction of a millisecond, coinciding with the period of passage of nerve impulses evoked by the conditioning stimulation of the tibial nerve. The degree of the increase was comparable to the increases in the excitability evoked by 1-2 min lasting fibre polarization. Ephaptic interactions were found to be more potent and with longer lasting after-effects within the dorsal roots than within the sciatic nerve. We postulate that ephaptic interactions may result in the synchronization of information forwarded via neighbouring afferent nerve fibres prior to their entry into the spinal cord and thereby securing the propagation of nerve impulses across branching points within the spinal grey matter.

Interactions Between Baclofen and DC-induced Plasticity of Afferent Fibers within the Spinal Cord.

The aims of the study were to compare effects of baclofen, a GABAB receptor agonist commonly used as an antispastic drug, on direct current (DC) evoked long-lasting changes in the excitability of afferent fibers traversing the dorsal columns and their terminal branches in the spinal cord, and to examine whether baclofen interferes with the development and expression of these changes. The experiments were performed on deeply anesthetized rats by analyzing the effects of DC before, during and following baclofen administration. Muscle and skin afferent fibers within the dorsal columns were stimulated epidurally and changes in their excitability were investigated following epidural polarization by 1.0-1.1 µA subsequent to i.v. administration of baclofen. Epidural polarization increased the excitability of these fibers during post-polarization periods of at least 1 h. The facilitation was as potent as in preparations that were not pretreated with baclofen, indicating that the advantages of combining epidural polarization with epidural stimulation would not be endangered by pharmacological antispastic treatment with baclofen. In contrast, baclofen-reduced effects of intraspinal stimulation combined with intraspinal polarization (0.3 µA) of terminal axonal branches of the afferents within the dorsal horn or in motor nuclei, whether administered ionophoretically or intravenously. Effects of DC on monosynaptically evoked synaptic actions of these fibers (extracellular field potentials) were likewise reduced by baclofen. The study thus provides further evidence for differential effects of DC on afferent fibers in the dorsal columns and the preterminal branches of these fibers and their involvement in spinal plasticity.

Disrupt of Intra-Limb APA Pattern in Parkinsonian Patients Performing Index-Finger Flexion.

Voluntary movements induce postural perturbations which are counteracted by anticipatory postural adjustments (APAs). These actions are known to build up long fixation chains toward available support points (inter-limb APAs), so as to grant whole body equilibrium. Moreover, recent studies highlighted that APAs also build-up short fixation chains, within the same limb where a distal segment is moved (intra-limb APAs), aimed at stabilizing the proximal segments. The neural structures generating intra-limb APAs still need investigations; the present study aims to compare focal movement kinematics and intra-limb APA latencies and pattern between healthy subjects and parkinsonian patients, assuming the latter as a model of basal ganglia dysfunction. Intra-limb APAs that stabilize the arm when the index-finger is briskly flexed were recorded in 13 parkinsonian patients and in 10 age-matched healthy subjects. Index-finger movement was smaller in parkinsonian patients vs. healthy subjects (p = 0.01) and more delayed with respect to the onset of the prime mover flexor digitorum superficialis (FDS, p < 0.0001). In agreement with the literature, in all healthy subjects the FDS activation was preceded by an inhibitory intra-limb APA in biceps brachii (BB) and anterior deltoid (AD), and almost simultaneous to an excitatory intra-limb APA in triceps brachii (TB). In parkinsonian patients, no significant differences were found for TB and AD intra-limb APA timings, however only four patients showed an inhibitory intra-limb APA in BB, while other four did not show any BB intra-limb APAs and five actually developed a BB excitation. The frequency of occurrence of normal sign, lacking, and inverted BB APAs was different in healthy vs. parkinsonian participants (p = 0.0016). The observed alterations in index-finger kinematics and intra-limb APA pattern in parkinsonian patients suggest that basal ganglia, in addition to shaping the focal movement, may also contribute to intra-limb APA control.

Ultraconformable Temporary Tattoo Electrodes for Electrophysiology.

Electrically interfacing the skin for monitoring personal health condition is the basis of skin-contact electrophysiology. In the clinical practice the use of stiff and bulky pregelled or dry electrodes, in contrast to the soft body tissues, imposes severe restrictions to user comfort and mobility while limiting clinical applications. Here, in this work dry, unperceivable temporary tattoo electrodes are presented. Customized single or multielectrode arrays are readily fabricated by inkjet printing of conducting polymer onto commercial decal transfer paper, which allows for easy transfer on the user's skin. Conformal adhesion to the skin is provided thanks to their ultralow thickness (<1 µm). Tattoo electrode-skin contact impedance is characterized on short- (1 h) and long-term (48 h) and compared with standard pregelled and dry electrodes. The viability in electrophysiology is validated by surface electromyography and electrocardiography recordings on various locations on limbs and face. A novel concept of tattoo as perforable skin-contact electrode, through which hairs can grow, is demonstrated, thus permitting to envision very long-term recordings on areas with high hair density. The proposed materials and patterning strategy make this technology amenable for large-scale production of low-cost sensing devices.

Effects of age and sex on epigenetic modification induced by an acute physical exercise.

It has been observed that, after 2 hours of aerobic exercise, plasma interleukin-6 (IL-6) increases whereas nuclear concentrations of enzyme DNA methyltransferase (DNMT) 3B significantly decreased in peripheral blood mononuclear cells (PBMCs), with no change observed in DNMT3A. The aim of the present study was to detect differences in these changes induced by exercise in plasma IL-6 levels as well as in PBMC nuclear concentrations of DNMT3A and DNMT3B, in relation to age and sex. Four groups were studied: 12 young men (24.8 ±â€Š1.77 years old), 12 young women (23.8 ±â€Š1.81 years old), 12 adult men (45.8 ±â€Š1.82 years old), 12 adult women (mean 44.5 ±â€Š2.07 years old). Participants had to run at 60% of maximal oxygen consumption (VO2max) for 120 minutes, interspersed with sprints at 90% of VO2max for the last 30 seconds of every 10 minutes. About 250 µL of PBMCs (1 × 10 cells) were treated with 100 µL of either pre-exercise plasma or post-exercise plasma and nuclear DNMT3A and DNMT3B concentrations were quantified. No change in nuclear concentration of DNMT3A following the exercise was observed. Conversely, nuclear concentrations of DNMT3B significantly decreased, with a reduction of about 78% in young men, 72% in young women, 61% in adult men, and 53% in adult women. Moreover, a strong positive correlation between the nuclear concentration of DNMT3B in PBMC following stimulation with post-exercise plasma and post-exercise plasma concentrations of IL-6 was observed in all the 4 studied groups. This study confirms that a single bout of endurance exercise is sufficient to decrease nuclear concentrations of DNMT3B and thus protein upregulation. Moreover, the epigenetic mechanisms induced by exercise apparently cause more intense changes in men than in women and that, in both of them, this effect seems to decrease with age.

Cough-Anal Reflex May Be the Expression of a Pre-Programmed Postural Action.

When coughing, an involuntary contraction of the external anal sphincter occurs, in order to prevent unwanted leakages or sagging of the pelvis muscular wall. Literature originally described such cough-anal response as a reflex elicited by cough, therefore identifying a precise cause-effect relationship. However, recent studies report that the anal contraction actually precedes the rise in abdominal pressure during cough expiratory effort, so that the sphincter activity should be pre-programmed. In recent years, an important family of pre-programmed muscle activities has been well documented to precede voluntary movements: these anticipatory actions play a fundamental role in whole body and segmental postural control, hence they are referred to as anticipatory postural adjustments (APAs). On these basis, we searched in literature for similarities between APAs and the cough-anal response, observing that both follow the same predictive homeostatic principle, namely that anticipatory collateral actions are needed to prevent the unwanted mechanical consequences induced by the primary movement. We thus propose that the cough-anal response also belongs to the family of pre-programmed actions, as it may be interpreted as an APA acting on the abdominal-thoracic compartment; in other words, the cough-anal response may actually be an Anticipatory Sphincter Adjustment, the visceral counterpart of APAs.

Direct current stimulation modulates the excitability of the sensory and motor fibres in the human posterior tibial nerve, with a long-lasting effect on the H-reflex.

Several studies demonstrated that transcutaneous direct current stimulation (DCS) may modulate central nervous system excitability. However, much less is known about how DC affects peripheral nerve fibres. We investigated the action of DCS on motor and sensory fibres of the human posterior tibial nerve, with supplementary analysis in acute experiments on rats. In forty human subjects, electric pulses at the popliteal fossa were used to elicit either M-waves or H-reflexes in the Soleus, before (15 min), during (10 min) and after (30 min) DCS. Cathodal or anodal current (2 mA) was applied to the same nerve. Cathodal DCS significantly increased the H-reflex amplitude; the post-polarization effect lasted up to ~ 25 min after the termination of DCS. Anodal DCS instead significantly decreased the reflex amplitude for up to ~ 5 min after DCS end. DCS effects on M-wave showed the same polarity dependence but with considerably shorter after-effects, which never exceeded 5 min. DCS changed the excitability of both motor and sensory fibres. These effects and especially the long-lasting modulation of the H-reflex suggest a possible rehabilitative application of DCS that could be applied either to compensate an altered peripheral excitability or to modulate the afferent transmission to spinal and supraspinal structures. In animal experiments, DCS was applied, under anaesthesia, to either the exposed peroneus nerve or its Dorsal Root, and its effects closely resembled those found in human subjects. They validate therefore the use of the animal models for future investigations on the DCS mechanisms.

Long-lasting increase in axonal excitability after epidurally applied DC.

Effects of direct current (DC) on nerve fibers have primarily been investigated during or just after DC application. However, locally applied cathodal DC was recently demonstrated to increase the excitability of intraspinal preterminal axonal branches for >1 h. The aim of this study was therefore to investigate whether DC evokes a similarly long-lasting increase in the excitability of myelinated axons within the dorsal columns. The excitability of dorsal column fibers stimulated epidurally was monitored by recording compound action potentials in peripheral nerves in acute experiments in deeply anesthetized rats. The results show that 1) cathodal polarization (0.8-1.0 µA) results in a severalfold increase in the number of epidurally activated fibers and 2) the increase in the excitability appears within seconds, 3) lasts for >1 h, and 4) is activity independent, as it does not require fiber stimulation during the polarization. These features demonstrate an unexplored form of plasticity of myelinated fibers and indicate the conditions under which it develops. They also suggest that therapeutic effects of epidural stimulation may be significantly enhanced if it is combined with DC polarization. In particular, by using DC to increase the number of fibers activated by low-intensity epidural stimuli, the low clinical tolerance to higher stimulus intensities might be overcome. The activity independence of long-lasting DC effects would also allow the use of only brief periods of DC polarization preceding epidural stimulation to increase the effect.NEW & NOTEWORTHY The study indicates a new form of plasticity of myelinated fibers. The differences in time course of DC-evoked increases in the excitability of myelinated nerve fibers in the dorsal columns and in preterminal axonal branches suggest that distinct mechanisms are involved in them. The results show that combining epidural stimulation and transspinal DC polarization may dramatically improve their outcome and result in more effective pain control and the return of impaired motor functions.

Anticipatory Postural Adjustments associated with reaching movements are programmed according to the availability of visual information.

During goal-directed arm movements, the eyes, head, and arm are coordinated to look at and reach the target. We examined whether the expectancy of visual information about the target modifies Anticipatory Postural Adjustments (APAs). Ten standing subjects had to (1) move the eyes, head and arm, so as to reach, with both gaze and index-finger, a target of known position placed outside their visual field (Gaze-Reach); (2) look at the target while reaching it (Reach in Full Vision); (3) keep the gaze away until having touched it (Reach then Gaze) and (4) just Gaze without Reach the target. We recorded eye, head, right arm, and acromion kinematics, EMGs from upper- and lower-limb muscles, and forces exerted on the ground. In Gaze-Reach, two coordination strategies were found: when gaze preceded arm muscle recruitment (Gaze-first) and when the opposite occurred (Reach-first). APAs in acromion kinematics, leg muscles, and ground forces started significantly earlier in Gaze-first vs. Reach-first (mean time advance: 44.3 ± 8.9 ms), as it was in Reach in Full Vision vs. Reach then Gaze (39.5 ± 7.9 ms). The Gaze-first to Reach-first time-shift was similar to that between Reach in Full Vision and Reach then Gaze (p = 0.58). Moreover, Gaze without Reach data witnessed that the head-induced postural actions did not affect the APA onset in Gaze-first and Reach-first. In conclusion, in Gaze-first, the central control of posture considers visual information while planning the movement, like in Reach in Full Vision; while Reach-first is more similar to Reach then Gaze, where vision is not required.

The Organization and Control of Intra-Limb Anticipatory Postural Adjustments and Their Role in Movement Performance.

Anticipatory Postural Adjustments (APAs) are commonly described as unconscious muscular activities aimed to counterbalance the perturbation caused by the primary movement, so as to ensure the whole-body balance, as well as contributing to initiate the displacement of the body center of mass when starting gait or whole-body reaching movements. These activities usually create one or more fixation chains which spread over several muscles of different limbs, and may be thus called inter-limb APAs. However, it has been reported that APAs also precede voluntary movements involving tiny masses, like a flexion/extension of the wrist or even a brisk flexion of the index-finger. In particular, such movements are preceded by an intra-limb APA chain, that involves muscles acting on the proximal joints. Considering the small mass of the moving segments, it is unlikely that the ensuing perturbation could threaten the whole-body balance, so that it is interesting to enquire the physiological role of intra-limb APAs and their organization and control compared to inter-limb APAs. This review is focused on intra-limb APAs and highlights a strict correspondence in their behavior and temporal/spatial organization with respect to inter-limb APAs. Hence it is suggested that both are manifestations of the same phenomenon. Particular emphasis is given to intra-limb APAs preceding index-finger flexion, because their relatively simple biomechanics and the fact that muscular actions were limited to a single arm allowed peculiar investigations, leading to important conclusions. Indeed, such paradigm provided evidence that by granting a proper fixation of those body segments proximal to the moving one APAs are involved in refining movement precision, and also that APAs and prime mover activation are driven by a shared motor command.

Higher Precision in Pointing Movements of the Preferred vs. Non-Preferred Hand Is Associated with an Earlier Occurrence of Anticipatory Postural Adjustments.

It is a common experience to exhibit a greater dexterity when performing a pointing movement with the preferred limb (PREF) vs. the non-preferred (NON-PREF) one. Here we provide evidence that the higher precision in pointing movements of the PREF vs. NON-PREF hand is associated with an earlier occurrence of the anticipatory postural adjustments (APAs). In this aim, we compared the APAs which stabilize the left or the right arm when performing a pen-pointing movement (prime mover flexor carpi radialis (FCR)). Moreover, we analyzed the elbow and wrist kinematics as well as the precision of the pointing movement. The mean kinematics of wrist movement and its latency, with respect to prime mover recruitment, were similar in the two sides, while APAs in triceps brachii (TB), biceps brachii (BB) and anterior deltoid (AD) were more anticipated when movements were performed with the PREF than with the NON-PREF hand (60-70 vs. 20-30 ms). APAs amplitudes were comparable in the muscles of the two sides. Earlier APAs in the preferred limb were associated with a better fixation of the elbow, which showed a lower excursion, and with a less scattered pointing error (PREF: 10.1 ± 0.8 mm; NON-PREF: 16.3 ± 1.7). Present results suggest that, by securing the more proximal joints dynamics, an appropriate timing of the intra-limb APAs is necessary for refining the voluntary movement precision, which is known to be scarce on the NON-PREF side.

Evidence that some long-lasting effects of direct current in the rat spinal cord are activity-independent.

The effects of trans-spinal direct current (DC) stimulation (tsDCS) on specific neuronal populations are difficult to elucidate, as it affects a variety of neuronal networks. However, facilitatory and depressive effects on neurons processing information from the skin and from muscles can be evaluated separately when weak (0.2-0.3 µA) DC is applied within restricted areas of the rat spinal cord. The effects of such local DC application were recently demonstrated to persist for at least 1 h, and to include changes in the excitability of afferent fibres and their synaptic actions. However, whether these effects require activation of afferent fibres in spinal neuronal pathways during DC application, i.e. whether they are activity-dependent or activity-independent, remained an open question. The aim of the present study was to address this question by analysing the effects of local DC application on monosynaptic actions of muscle and skin afferents (extracellular field potentials) and afferent fibre excitability. The results revealed that long-lasting post-polarization changes evoked without concomitant activation of afferent fibres replicate changes evoked by stimuli applied during, before and after polarization. The study leads to the conclusion that the reported effects are activity-independent. As this conclusion applies to the local effects of DC application in at least two spinal pathways and to the effects of both cathodal and anodal polarization, it indicates that some of the more widespread effects of trans-spinal and trans-cranial stimulation (both tsDCS and transcranial DC stimulation) may be activity-independent. The results may therefore contribute to the design of more specific DC applications in clinical practice.

Transcranial direct current stimulation of SMA modulates anticipatory postural adjustments without affecting the primary movement.

Recent works provide evidences that anticipatory postural adjustments (APAs) are programmed with the prime mover recruitment as a shared posturo-focal command. However the ability of the CNS to adjust APAs to changes in the postural context implies that the postural and voluntary components should take different pathways before reaching the representation of single muscles in the primary motor cortex. Here we test if such bifurcation takes place at the level of the supplementary motor area (SMA). TDCS was applied over the SMA in 14 subjects, who produced a brisk index-finger flexion. This activity is preceded by inhibitory APAs, carved in the tonic activity of Biceps Brachii and Anterior Deltoid, and by an excitatory APA in Triceps Brachii. Subjects performed a series of 30 flexions before, during and after 20 min of tDCS in CATHODAL, ANODAL or SHAM configuration. The inhibitory APA in Biceps and the excitatory APA in Triceps were both greater in ANODAL than in SHAM and CATHODAL configurations, while no difference was found among the latter two (ANODAL vs. SHAM: biceps +26.5%, triceps +66%; ANODAL vs. CATHODAL: biceps +20.5%, triceps: +63.4%; for both muscles, ANOVA p<0.02, Tukey p<0.05). Instead, the APA in anterior deltoid was unchanged in all configurations. No changes were observed in prime mover recruitment and index-finger kinematics. Results show that the SMA is involved in modulating APAs amplitude. Moreover, the differential effect of tDCS observed on postural and voluntary commands suggests that these two components of the motor program are already separated before entering SMA.