Pontomedullary Reticular Formation Research Articles

Pallidal Activity Related to Posture and Movement during Reaching in the Cat.

We tested the hypothesis that the pallidum contributes to the control of both posture and movement. We recorded neuronal activity from the pallidum in a task in which male cats reached forward from a standing posture to depress a lever. In agreement with previous studies, we found that a majority of pallidal cells (91/116, 78%), including neurons in both the entopeduncular nucleus and the globus pallidus, showed significant modulation of their activity during reaching with the contralateral limb. Mostly different populations of cells were active during the transport (flexion) and lever press (extension) phase of the task. Most cells showed dynamic patterns of activity related to the movement. However, a modest proportion of modulated cells (18/91, 20%) showed properties consistent with a contribution to the control of anticipatory postural responses, whereas a further 10% showed activity consistent with a contribution to postural support during the movement. Although some cells that showed modified activity only during reaches with the contralateral forelimb, many cells (65/91, 71%) were also activated during reaches with the ipsilateral forelimb. This was particularly true for cells related to the lever press, many of which discharged similarly during reaches of either limb. This suggests a context-dependent control of movement and posture in which the same muscles are used for different functions during contralateral and ipsilateral reach. Comparison with the results from recordings made previously from the motor cortex and the pontomedullary reticular formation in the same task show more similarities with the former than the latter.SIGNIFICANCE STATEMENT Pathologic changes in basal ganglia function frequently lead to problems with postural stability and gait initiation. Here, we show that some neurons in one of the output regions of the basal ganglia, the pallidum, show discharge activity compatible with a contribution to postural control. At the same time, we note that such cells are a minority in this region with most cells being related to movement rather than posture. We also show that many neurons are active during movements of both the contralateral and ipsilateral limbs, sometimes with identical discharge patterns. We suggest that this indicates a context-dependent regulation of movement and posture in the pallidum.

Mapping the human corticoreticular pathway with multimodal delineation of the gigantocellular reticular nucleus and high-resolution diffusion tractography

The corticoreticular pathway (CRP) is a major motor tract that transmits cortical input to the reticular formation motor nuclei and may be an important mediator of motor recovery after central nervous system damage. However, its cortical origins, trajectory and laterality are incompletely understood in humans. This study aimed to map the human CRP and generate an average CRP template in standard MRI space. Following recently established guidelines, we manually delineated the primary reticular formation motor nucleus (gigantocellular reticular nucleus [GRN]) using several group-mean MRI contrasts from the Human Connectome Project (HCP). CRP tractography was then performed with HCP diffusion-weighted MRI data (N = 1065) by selecting diffusion streamlines that reached both the cortex and GRN. Corticospinal tract (CST) tractography was also performed for comparison. Results suggest that the human CRP has widespread origins, which overlap with the CST across most of the motor cortex and include additional exclusive inputs from the medial and anterior prefrontal cortices. The estimated CRP projected through the anterior and posterior limbs of the internal capsule before partially decussating in the midbrain tegmentum and converging bilaterally on the pontomedullary reticular formation. Thus, the CRP trajectory appears to partially overlap the CST, while being more distributed and anteromedial to the CST in the cerebrum before moving posterior to the CST in the brainstem. These findings have important implications for neurophysiologic testing, cortical stimulation and movement recovery after brain lesions. We expect that our GRN and tract maps will also facilitate future CRP research.

35 The Impact of Postural Hyperkyphosis on Postural Stability and Cognition

Abstract Background Postural Hyperkyphosis results from flexor dominant posture habits. Flexor dominance occurs due to dysfunction of the pontomedullary reticular formation (PMRF) of the brainstem and the vestibular system. The role of the PMRF is to inhibit anterior flexion above T6 spinal level, and the vestibular system stimulates upright postural extension and balance. When patients present with flexor dominance they have a Postural Hyperkyphosis postural distortion pattern and abnormal muscle activation patterns. To correct flexor dominance, practitioners should perform brain-based exercises, not just structural exercises. Brain based stimulation of the vestibular system and the brainstem stimulates upright extension of the Posture System and inhibition of anterior flexion to reduce Postural Hyperkyphosis. Postural Hyperkyphosis contributes to multiple health discrepancies. According to Cohen, Vasavada, and Wiest et al. (2016) in the Frontiers of Neuroscience, Postural Hyperkyphosis is associated with a lower state of cognition. According to Kado, Huang, and Nguyen et al. (2007) in the Journals of Gerontology hyperkyphosis is associated with poor balance and injurious falls in the elderly. Brainstem and vestibular activation reduces flexion and improves extension for better postural correction outcomes. Results Brain Based exercises reduce Postural Hyperkyphosis and improve postural stability and cognition of elderly patients. Brain Based exercises are safe for the elderly to perform and can be easily implemented into physical rehabilitation treatment plans for better postural correction results. Conclusion Correcting Postural Hyperkyphosis to improve Postural Stability and cognition requires a Brain Based treatment protocol.

Motor Overflow and Spasticity in Chronic Stroke Share a Common Pathophysiological Process: Analysis of Within-Limb and Between-Limb EMG-EMG Coherence

The phenomenon of exaggerated motor overflow is well documented in stroke survivors with spasticity. However, the mechanism underlying the abnormal motor overflow remains unclear. In this study, we aimed to investigate the possible mechanisms behind abnormal motor overflow and its possible relations with post-stroke spasticity. 11 stroke patients (63.6 ± 6.4 yrs; 4 women) and 11 healthy subjects (31.18 ± 6.18 yrs; 2 women) were recruited. All of them were asked to perform unilateral isometric elbow flexion at submaximal levels (10, 30, and 60% of maximum voluntary contraction). Electromyogram (EMG) was measured from the contracting biceps (iBiceps) muscle and resting contralateral biceps (cBiceps), ipsilateral flexor digitorum superficialis (iFDS), and contralateral FDS (cFDS) muscles. Motor overflow was quantified as the normalized EMG of the resting muscles. The severity of motor impairment was quantified through reflex torque (spasticity) and weakness. EMG-EMG coherence was calculated between the contracting muscle and each of the resting muscles. During elbow flexion on the impaired side, stroke subjects exhibited significant higher motor overflow to the iFDS muscle compared with healthy subjects (ipsilateral or intralimb motor overflow). Stroke subjects exhibited significantly higher motor overflow to the contralateral spastic muscles (cBiceps and cFDS) during elbow flexion on the non-impaired side (contralateral or interlimb motor overflow), compared with healthy subjects. Moreover, there was significantly high EMG-EMG coherence in the alpha band (6–12 Hz) between the contracting muscle and all other resting muscles during elbow flexion on the non-impaired side. Our results of diffuse ipsilateral and contralateral motor overflow with EMG-EMG coherence in the alpha band suggest subcortical origins of motor overflow. Furthermore, correlation between contralateral motor overflow to contralateral spastic elbow and finger flexors and their spasticity was consistently at moderate to high levels. A high correlation suggests that diffuse motor overflow to the impaired side and spasticity likely share a common pathophysiological process. Possible mechanisms are discussed.

Changes of motor corticobulbar projections following different lesion types affecting the central nervous system in adult macaque monkeys.

Functional recovery from central nervous system injury is likely to be partly due to a rearrangement of neural circuits. In this context, the corticobulbar (corticoreticular) motor projections onto different nuclei of the ponto‐medullary reticular formation (PMRF) were investigated in 13 adult macaque monkeys after either, primary motor cortex injury (MCI) in the hand area, or spinal cord injury (SCI) or Parkinson's disease‐like lesions of the nigro‐striatal dopaminergic system (PD). A subgroup of animals in both MCI and SCI groups was treated with neurite growth promoting anti‐Nogo‐A antibodies, whereas all PD animals were treated with autologous neural cell ecosystems (ANCE). The anterograde tracer BDA was injected either in the premotor cortex (PM) or in the primary motor cortex (M1) to label and quantify corticobulbar axonal boutons terminaux and en passant in PMRF. As compared to intact animals, after MCI the density of corticobulbar projections from PM was strongly reduced but maintained their laterality dominance (ipsilateral), both in the presence or absence of anti‐Nogo‐A antibody treatment. In contrast, the density of corticobulbar projections from M1 was increased following opposite hemi‐section of the cervical cord (at C7 level) and anti‐Nogo‐A antibody treatment, with maintenance of contralateral laterality bias. In PD monkeys, the density of corticobulbar projections from PM was strongly reduced, as well as that from M1, but to a lesser extent. In conclusion, the densities of corticobulbar projections from PM or M1 were affected in a variable manner, depending on the type of lesion/pathology and the treatment aimed to enhance functional recovery.

Motor overflow in spastic hemiplegia after stroke

The phenomenon of exaggerated motor overflow (involuntary movements accompanying a motor task) is well documented, particularly in stroke survivors with spasticity. In this study, we aimed to investigate the possible underlying mechanisms its possible relations with post-stroke spasticity. Eleven stroke patients (63.6 yrs ± 6.4 yrs; 4 women) and 11 healthy subjects (age: 31.18 yrs ± 6.18 yrs; 2 women) were recruited and performed unilateral isometric elbow flexion at submaximal levels (10%, 30%, and 60% of maximum voluntary contraction, MVC). Electromyograms (EMG) was measured from the contracting biceps muscle and resting contralateral biceps, ipsilateral flexor digitorum superficialis, and contralateral FDS muscles. Motor overflow was quantified as the normalized EMG of the resting muscles. EMG-EMG coherence was calculated between the contracting muscle and each of the resting muscle. Elbow flexor spasticity was quantified through reflex torque. Overall, our results demonstrated that unilateral elbow flexion caused diffuse motor overflow from proximal to distal muscles on the impaired side (ipsilateral motor overflow) and from the non-impaired side to the impaired side (contralateral motor overflow). Moreover, there were significantly high EMG-EMG coherence between 6–12 Hz between the contracting muscle and all other resting muscles during elbow flexion on the non-impaired side. Our results of diffuse ipsilateral and contralateral motor overflow with EMG-EMG coherence in the alpha band suggest subcortical origins of motor overflow. Post-stroke spasticity is attributed to reticulospinal hyperexcitability secondary to the unmasking of ponto-medullary reticular formation. A high correlation between spasticity and motor overflow supports a potential role of reticulospinal activation in motor overflow. Collectively, these results suggest that diffuse motor overflow to the impaired side is likely related to activation of hyperexcitable reticulospinal pathways after stroke.

Neuromodulatory Inputs to Motoneurons Contribute to the Loss of Independent Joint Control in Chronic Moderate to Severe Hemiparetic Stroke.

In chronic hemiparetic stroke, increased shoulder abductor activity causes involuntary increases in elbow, wrist, and finger flexor activation, an abnormal muscle coactivation pattern known as the flexion synergy. Recent evidence suggests that flexion synergy expression may reflect recruitment of contralesional cortico-reticulospinal motor pathways following damage to the ipsilesional corticospinal tract. However, because reticulospinal motor pathways produce relatively weak post-synaptic potentials in motoneurons, it is unknown how preferential use of these pathways could lead to robust muscle activation. Here, we hypothesize that the descending neuromodulatory component of the ponto-medullary reticular formation, which uses the monoaminergic neurotransmitters norepinephrine and serotonin, serves as a gain control mechanism to facilitate motoneuron responses to reticulospinal motor commands. Thus, inhibition of the neuromodulatory component would reduce flexion synergy expression by disfacilitating spinal motoneurons. To test this hypothesis, we conducted a pre-clinical study utilizing two targeted neuropharmacological probes and inert placebo in a cohort of 16 individuals with chronic hemiparetic stroke. Test compounds included Tizanidine (TIZ), a noradrenergic α2 agonist and imidazoline ligand selected for its ability to reduce descending noradrenergic drive, and Isradipine, a dihyropyridine calcium-channel antagonist selected for its ability to post-synaptically mitigate a portion of the excitatory effects of monoamines on motoneurons. We used a previously validated robotic measure to quantify flexion synergy expression. We found that Tizanidine significantly reduced expression of the flexion synergy. A predominantly spinal action for this effect is unlikely because Tizanidine is an agonist acting on a baseline of spinal noradrenergic drive that is likely to be pathologically enhanced post-stroke due to increased reliance on cortico-reticulospinal motor pathways. Although spinal actions of TIZ cannot be excluded, particularly from Group II pathways, our finding is consistent with a supraspinal action of Tizanidine to reduce descending noradrenergic drive and disfacilitate motoneurons. The effects of Isradipine were not different from placebo, likely related to poor central bioavailability. These results support the hypothesis that the descending monoaminergic component of the ponto-medullary reticular formation plays a key role in flexion synergy expression in chronic hemiparetic stroke. These results may provide the basis for new therapeutic strategies to complement physical rehabilitation.

Reticulospinal Systems for Tuning Motor Commands.

The pontomedullary reticular formation (RF) is a key site responsible for integrating descending instructions to execute particular movements. The indiscrete nature of this region has led not only to some inconsistencies in nomenclature, but also to difficulties in understanding its role in the control of movement. In this review article, we first discuss nomenclature of the RF, and then examine the reticulospinal motor command system through evolution. These command neurons have direct monosynaptic connections with spinal interneurons and motoneurons. We next review their roles in postural adjustments, walking and sleep atonia, discussing their roles in movement activation or inhibition. We propose that knowledge of the internal organization of the RF is necessary to understand how the nervous system tunes motor commands, and that this knowledge will underlie strategies for motor functional recovery following neurological injuries or diseases.

Gait initiation and attention

Step initiation combines motor and cognitive processes involved in movement preparation and execution. Intracerebral recordings in the cat have shown that the pontomedullary reticular formation has a central role in: – postural preparation prior to movement execution; – the coupling between preparation and execution. Furthermore, cortical control of the pontomedullary reticular structures modulates the release of postural adjustments. Imaging studies in humans have also shown that the prefrontal cortex has a particular role in postural adjustments. Accordingly, it has been hypothesized that attentional processes [which involve cortical structures] can also modulate the step initiation program. Investigation of this motor modulation provides a better understanding of the interaction between attention on the one hand and motor preparation and execution on the other. Postural modulation can be investigated by recording anticipated postural adjustments (APAs). An APA is essential for step initiation because it unloads the swing leg and thus creates the conditions required for progression. Indeed, the amplitude and duration of APAs are predictive of the subsequent peak step velocity. Recent literature showed that this APA can be modulated by general attentional alert processes, orientation processes or even executive control processes. When the subject is conditioned for gait initiation, an attentional stimulus provokes an involuntary release of the gait initiation program (referred to as “early APAs” or “pre-APAs”). This elevated involuntary release of a motor program might reflect failure to inhibit distracter stimuli and are more frequent during pathological gait initiation (as seen in Parkinson's disease patients, who are known to have attention deficits). The occurrence of APA errors also perturbs the gait initiation program. This corresponds to the correction of a step initiation APA when the initial direction of postural adjustment is not appropriate. The APA error then indicates a motor program error, which is efficiently corrected and prevents incorrect step initiation from taking place. It is known that APA errors are modulated by attention suggesting a link with delayed stimulus integration. Further research investigates cortical mechanisms implied in this interaction between motor programming and attention using event related potentials and time frequency analysis. Step initiation's biomechanical processes are useful for precisely studying how well-known attentional cortical process can modulate the different steps of automatized motor program. They are of clinical significance to understand gait initiation failure in elderly and patients with various neurological diseases including Parkinson's disease.

Corticobulbar projections from distinct motor cortical areas to the reticular formation in macaque monkeys.

Corticospinal and corticobulbar descending pathways act in parallel with brainstem systems, such as the reticulospinal tract, to ensure the control of voluntary movements via direct or indirect influences onto spinal motoneurons. The aim of this study was to investigate the corticobulbar projections from distinct motor cortical areas onto different nuclei of the reticular formation. Seven adult macaque monkeys were analysed for the location of corticobulbar axonal boutons, and one monkey for reticulospinal neurons' location. The anterograde tracer BDA was injected in the premotor cortex (PM), in the primary motor cortex (M1) or in the supplementary motor area (SMA), in 3, 3 and 1 monkeys respectively. BDA anterograde labelling of corticobulbar axons were analysed on brainstem histological sections and overlapped with adjacent Nissl-stained sections for cytoarchitecture. One adult monkey was analysed for retrograde CB tracer injected in C5-C8 hemispinal cord to visualise reticulospinal neurons. The corticobulbar axons formed bilateral terminal fields with boutons terminaux and en passant, which were quantified in various nuclei belonging to the Ponto-Medullary Reticular Formation (PMRF). The corticobulbar projections from both PM and SMA tended to end mainly ipsilaterally in PMRF, but contralaterally when originating from M1. Furthermore, the corticobulbar projection was less dense when originating from M1 than from non-primary motor areas (PM, SMA). The main nuclei of bouton terminals corresponded to the regions where reticulospinal neurons were located with CB retrograde tracing. In conclusion, the corticobulbar projection differs according to the motor cortical area of origin in density and laterality.

Modulation of the sensorimotor system by sustained manual pressure stimulation

In Vojta physiotherapy, also known as reflex locomotion therapy, prolonged peripheral pressure stimulation induces complex generalized involuntary motor responses and modifies subsequent behavior, but its neurobiological basis remains unknown. We hypothesized that the stimulation would induce sensorimotor activation changes in functional magnetic resonance imaging (fMRI) during sequential finger opposition. Thirty healthy volunteers (mean age 24.2) underwent two randomized fMRI sessions involving manual pressure stimulation applied either at the right lateral heel according to Vojta, or at the right lateral ankle (control site). Participants were scanned before and after the stimulation when performing auditory-paced sequential finger opposition with their right hand. Despite an extensive activation decrease following both stimulation paradigms, the stimulation of the heel specifically led to an increase in task-related activation in the predominantly contralateral pontomedullary reticular formation and bilateral posterior cerebellar hemisphere and vermis. Our findings suggest that sustained pressure stimulation of the foot is associated with differential short-term changes in hand motor task-related activation depending on the stimulation. This is the first evidence for brainstem modulation after peripheral pressure stimulation, suggesting that the after-effects of reflex locomotion physiotherapy involve a modulation of the pontomedullary reticular formation.

Neurons in the pontomedullary reticular formation receive converging inputs from the hindlimb and labyrinth.

The integration of inputs from vestibular and proprioceptive sensors within the central nervous system is critical to postural regulation. We recently demonstrated in both decerebrate and conscious cats that labyrinthine and hindlimb inputs converge onto vestibular nucleus neurons. The pontomedullary reticular formation (pmRF) also plays a key role in postural control, and additionally participates in regulating locomotion. Thus, we hypothesized that like vestibular nucleus neurons, pmRF neurons integrate inputs from the limb and labyrinth. To test this hypothesis, we recorded the responses of pmRF neurons to passive ramp-and-hold movements of the hindlimb and to whole-body tilts, in both decerebrate and conscious felines. We found that pmRF neuronal activity was modulated by hindlimb movement in the rostral-caudal plane. Most neurons in both decerebrate (83% of units) and conscious (61% of units) animals encoded both flexion and extension movements of the hindlimb. In addition, hindlimb somatosensory inputs converged with vestibular inputs onto pmRF neurons in both preparations. Pontomedullary reticular formation neurons receiving convergent vestibular and limb inputs likely participate in balance control by governing reticulospinal outflow.

Brainstem control of locomotion and muscle tone with special reference to the role of the mesopontine tegmentum and medullary reticulospinal systems.

The lateral part of the mesopontine tegmentum contains functionally important structures involved in the control of posture and gait. Specifically, the mesencephalic locomotor region, which may consist of the cuneiform nucleus and pedunculopontine tegmental nucleus (PPN), occupies the interest with respect to the pathophysiology of posture-gait disorders. The purpose of this article is to review the mechanisms involved in the control of postural muscle tone and locomotion by the mesopontine tegmentum and the pontomedullary reticulospinal system. To make interpretation and discussion more robust, the above issue is considered largely based on our findings in the experiments using decerebrate cat preparations in addition to the results in animal experimentations and clinical investigations in other laboratories. Our investigations revealed the presence of functional topographical organizations with respect to the regulation of postural muscle tone and locomotion in both the mesopontine tegmentum and the pontomedullary reticulospinal system. These organizations were modified by neurotransmitter systems, particularly the cholinergic PPN projection to the pontine reticular formation. Because efferents from the forebrain structures as well as the cerebellum converge to the mesencephalic and pontomedullary reticular formation, changes in these organizations may be involved in the appropriate regulation of posture-gait synergy depending on the behavioral context. On the other hand, abnormal signals from the higher motor centers may produce dysfunction of the mesencephalic-reticulospinal system. Here we highlight the significance of elucidating the mechanisms of the mesencephalic-reticulospinal control of posture and locomotion so that thorough understanding of the pathophysiological mechanisms of posture-gait disorders can be made.

Evidence for a role of the reticulospinal system in recovery of skilled reaching after cortical stroke: initial results from a model of ischemic cortical injury

The purposes of this pilot study were to create a model of focal cortical ischemia in Macaca fascicularis and to explore contributions of the reticulospinal system in recovery of reaching. Endothelin-1 was used to create a focal lesion in the shoulder/elbow representation of left primary motor cortex (M1) of two adult female macaques. Repetitive microstimulation was used to map upper limb motor outputs from right and left cortical motor areas and from the pontomedullary reticular formation (PMRF). In subject 1 with a small lesion and spontaneous recovery, reaching was mildly impaired. Changes were evident in the shoulder/elbow representations of both the lesioned and contralesional M1, and there appeared to be fewer than expected upper limb responses from the left (ipsilesional) PMRF. In subject 2 with a substantial lesion, reaching was severely impaired immediately after the lesion. After 12 weeks of intensive rehabilitative training, reach performance recovered to near-baseline levels, but movement times remained about 50% slower. Surprisingly, the shoulder/elbow representation in the lesioned M1 remained completely absent after recovery, and there was a little change in the contralesional M1. There was a definite difference in motor output patterns for left versus right PMRF for this subject, with an increase in right arm responses from right PMRF and a paucity of left arm responses from left PMRF. The results are consistent with increased reliance on PMRF motor outputs for recovery of voluntary upper limb motor control after significant cortical ischemic injury.

Cerebellar control of saccade dynamics: contribution of the fastigial oculomotor region.

The fastigial oculomotor region is the output by which the medioposterior cerebellum influences the generation of saccades. Recent inactivation studies reported observations suggesting an involvement in their dynamics (velocity and duration). In this work, we tested this hypothesis in the head-restrained monkey with the electrical microstimulation technique. More specifically, we studied the influence of duration, frequency, and current on the saccades elicited by fastigial stimulation and starting from a central (straight ahead) position. The results show ipsilateral or contralateral saccades whose amplitude and dynamics depend on the stimulation parameters. The duration and amplitude of their horizontal component increase with the duration of stimulation up to a maximum amplitude. Varying the stimulation frequency mostly changes their latency and the peak velocity (for contralateral saccades). Current also influences the metrics and dynamics of saccades: the horizontal amplitude and peak velocity increase with the intensity, whereas the latency decreases. The changes in peak velocity and in latency observed in contralateral saccades are not correlated. Finally, we discovered that contralateral saccades can be evoked at sites eliciting ipsilateral saccades when the stimulation frequency is reduced. However, their onset is timed not with the onset but with the offset of stimulation. These results corroborate the hypothesis that the fastigial projections toward the pontomedullary reticular formation (PMRF) participate in steering the saccade, whereas the fastigiocollicular projections contribute to the bilateral control of visual fixation. We propose that the cerebellar influence on saccade generation involves recruiting neurons and controlling the size of the active population in the PMRF.

Arm and hand movement: current knowledge and future perspective.

Reaching with the arm and grasping with the hand and fingers is a complex behavior that appears in utero, is elaborated over the first few years of life, and serves useful everyday functions throughout the course of human life. Several neurological conditions can impair the ability to produce arm and hand movements and so greatly impact on the quality of life and well-being of the affected individuals. Given the fundamental role that arm and hand movements play in everyday life, deficits related to arm and hand function are one of the most debilitating motor conditions. Neurological conditions that can affect arm and hand movements include autism spectrum disorder, Parkinson’s and Huntington’s diseases, amyotrophic lateral sclerosis, cerebral palsy, and stroke-related motor cortex damage as well as spinal cord injury at cervical levels. While arm and hand movement has received considerable attention from both clinicians and researchers from diverse scientific backgrounds, there are a number of broad research questions that still need to be addressed in this research field. The present Research Topic is entirely devoted to arm and hand movement in health as well as in disease. It is a compilation of original research papers and reviews, clinical case studies, hypothesis and theory articles, opinions, commentaries, and methods articles that cover important aspects of the topic from different perspectives. In this volume, de Bruin et al. (1) present data that describe how healthy adults use space while performing a visually guided grasping task. A model for understanding hand functioning in children with cerebral palsy is proposed by Arnould et al. (2) while Johansson et al. (3) explore the effect of timing training on upper limb movement in three children with diplegic cerebral palsy. Parma et al. (4) compare the kinematics of the reach-to grasp movement in patients with vascular and idiopathic Parkinson’s disease whereas Aluru et al. (5) evaluate the effect of auditory constraints on motor performance at different stages after a stroke. Lawrence et al. (6) measure dexterous manipulation in a cross-sectional study comparing gender, age, and absence and presence of disease. Kirsh et al. (7) provide evidence to support the view that neurons outside the primary motor cortex – such as those populating the pontomedullary reticular formation and the spinal cord-drive movement and muscle synergies that primary motor cortex neurons then break up to create individual wrist and finger movements. Sacrey et al. (8) summarize current knowledge related to reaching and grasping in autism spectrum disorder. On the other hand, Whitwell et al. (9) reinstate patient DF’s amazing ability to use information regarding form and orientation of objects to guide skilled reaching actions despite her visual agnosia. In an opinion article, Moore (10) argues that nerve transfer is increasingly popular and is becoming the best treatment strategy for most brachial plexus damage as well as for patients with spinal cord injury at cervical levels. Vicario (11) provides a personal commentary on a paper from Hayashi et al. (12) and, in a review article, Karl and Whishaw (13) summarize the evidence that show that reaching and grasping are from distinct neural and evolutionary origins. Irvine et al. (14) contribute a methods article that assesses the reliability of the Irvine, Beatties, and Bresnahan (IBB) forelimb recovery scale. Fouad et al. (15) demonstrate that continuous viral-mediated brain-derived neurotrophic factor (BDNF) over-expression promotes spasticity in rats with spinal cord hemisections at cervical levels. Alstermark and Pettersson (16) bring evidence to show that lesions to the corticospinal tract that spare the cortico-reticulospinal pathway in the rat have no deleterious effects on skilled reaching and grasping. Finally, Tosolini et al. (17) describe how targeting the full length of the motor endplate region in the mouse forelimb with Fluoro-Gold increases the uptake of this neuroanatomical retrograde tracer in corresponding motor neurons. We are delighted to present “Arm and Hand Movement: Current Knowledge and Future Perspective” as a Research Topic in Frontiers in Neurology. We feel that this wide-ranging compilation of articles by leading experts in upperlimb/forelimb movement and working either in clinical or basic research settings has offered fresh perspectives on the topic. We are thankful for the support of all the scientists who have contributed to this Research Topic and have shared with us their expertise and point of views. Their contributions have deepened our appreciation of the challenge that restoring arm and hand function in different pathologies represents. We invite the readers to experience the diversity in methodological approaches and experimental designs that together have led to broaden our understanding of this particularly wide field of research.

Bilateral force transients in the upper limbs evoked by single-pulse microstimulation in the pontomedullary reticular formation.

Neurons in the pontomedullary reticular formation (PMRF) give rise to the reticulospinal tract. The motor output of the PMRF was investigated using stimulus-triggered averaging of electromyography (EMG) and force recordings in two monkeys (M. fascicularis). EMG was recorded from 12 pairs of upper limb muscles, and forces were detected using two isometric force-sensitive handles. Of 150 stimulation sites, 105 (70.0%) produced significant force responses, and 139 (92.5%) produced significant EMG responses. Based on the average flexor EMG onset latency of 8.3 ms and average force onset latency of 15.9 ms poststimulation, an electromechanical delay of ∼7.6 ms was calculated. The magnitude of force responses (∼10 mN) was correlated with the average change in EMG activity (P < 0.001). A multivariate linear regression analysis was used to estimate the contribution of each muscle to force generation, with flexors and extensors exhibiting antagonistic effects. A predominant force output pattern of ipsilateral flexion and contralateral extension was observed in response to PMRF stimulation, with 65.3% of significant ipsilateral force responses directed medially and posteriorly (P < 0.001) and 78.6% of contralateral responses directed laterally and anteriorly (P < 0.001). This novel approach permits direct measurement of force outputs evoked by central nervous system microstimulation. Despite the small magnitude of poststimulus EMG effects, low-intensity single-pulse microstimulation of the PMRF evoked detectable forces. The forces, showing the combined effect of all muscle activity in the arms, are consistent with reciprocal pattern of force outputs from the PMRF detectable with stimulus-triggered averaging of EMG.

Primary Motor Cortex Neurons during Individuated Finger and Wrist Movements: Correlation of Spike Firing Rates with the Motion of Individual Digits versus Their Principal Components.

The joints of the hand provide 24 mechanical degrees of freedom. Yet 2–7 principal components (PCs) account for 80–95% of the variance in hand joint motion during tasks that vary from grasping to finger spelling. Such findings have led to the hypothesis that the brain may simplify operation of the hand by preferentially controlling PCs. We tested this hypothesis using data recorded from the primary motor cortex (M1) during individuated finger and wrist movements. Principal component analysis (PCA) of the simultaneous position of the five digits and the wrist showed relatively consistent kinematic synergies across recording sessions in two monkeys. The first three PCs typically accounted for 85% of the variance. Cross-correlations then were calculated between the firing rate of single neurons and the simultaneous flexion/extension motion of each of the five digits and the wrist, as well as with each of their six PCs. For each neuron, we then compared the maximal absolute value of the cross-correlations (MAXC) achieved with the motion of any digit or the wrist to the MAXC achieved with motion along any PC axis. The MAXC with a digit and the MAXC with a PC were themselves highly correlated across neurons. A minority of neurons correlated more strongly with a PC than with any digit. But for the populations of neurons sampled from each of two subjects, MAXCs with digits were slightly but significantly higher than those with PCs. We therefore reject the hypothesis that M1 neurons preferentially control PCs of hand motion. We cannot exclude the possibility that M1 neurons might control kinematic synergies identified using linear or non-linear methods other than PCA. We consider it more likely, however, that neurons in other centers of the motor system – such as the pontomedullary reticular formation and the spinal gray matter – drive synergies of movement and/or muscles, which M1 neurons act to fractionate in producing individuated finger and wrist movements.

Reduced StartReact effect and freezing of gait in Parkinson’s disease: two of a kind?

Freezing of gait (FOG) is a disabling feature of Parkinson's disease. Emerging evidence suggests that dysfunction of the pedunculopontine nucleus (PPN) and pontomedullary reticular formation (pmRF) plays a role in the causation of FOG. These brainstem structures can be examined by the StartReact paradigm, which utilizes a startling stimulus to accelerate reaction times (StartReact). Here, we examined gait initiation in PD patients with and without FOG using this paradigm. Twenty-six patients with Parkinson's disease (12 freezers and 14 non-freezers) and 15 controls performed two tasks: rapid gait initiation in response to an imperative 'go' signal; and a control condition, involving a simple reaction-time task involving ankle dorsiflexion. During both tasks, a startling acoustic stimulus was combined with the imperative signal in 25 % of trials. In controls, the startle accelerated gait initiation and shortened the onset latency of tibialis anterior responses during ankle dorsiflexion. This acceleration was intact in non-freezers, but was significantly attenuated in the freezers. Independent of the occurrence of a startle, freezers showed a reduced length of the first step compared to non-freezers and controls. The diminished StartReact effect in freezers probably reflects deficient representation or release of motor programs at the brainstem reticular level due to dysfunction of the PPN, the pmRF, or both. These brainstem structures are presumably involved in integrating anticipatory postural adjustments with subsequent stepping movements. We suggest that with time-varying demands, these structures may no longer be able to coordinate the integration of anticipatory postural adjustments with steps, leading to FOG episodes.

Cells in the monkey ponto-medullary reticular formation modulate their activity with slow finger movements.

Recent work has shown that the primate reticulospinal tract can influence spinal interneurons and motoneurons involved in control of the hand. However, demonstrating connectivity does not reveal whether reticular outputs are modulated during the control of different types of hand movement. Here, we investigated how single unit discharge in the pontomedullary reticular formation (PMRF) modulated during performance of a slow finger movement task in macaque monkeys. Two animals performed an index finger flexion–extension task to track a target presented on a computer screen; single units were recorded both from ipsilateral PMRF (115 cells) and contralateral primary motor cortex (M1, 210 cells). Cells in both areas modulated their activity with the task (M1: 87%, PMRF: 86%). Some cells (18/115 in PMRF; 96/210 in M1) received sensory input from the hand, showing a short-latency modulation in their discharge following a rapid passive extension movement of the index finger. Effects in ipsilateral electromyogram to trains of stimuli were recorded at 45 sites in the PMRF. These responses involved muscles controlling the digits in 13/45 sites (including intrinsic hand muscles, 5/45 sites). We conclude that PMRF may contribute to the control of fine finger movements, in addition to its established role in control of more proximal limb and trunk movements. This finding may be especially important in understanding functional recovery after brain lesions such as stroke.