Initial development of skill with a reversed bicycle and a case series of experienced riders.

Riding a bicycle is considered a durable skill that cannot be forgotten. Here, novice participants practiced riding a reversed bicycle, in which a reversing gear inverted the handlebar's rotation. Although learning to ride the reversed bicycle was possible, it was slow, highly variable, implicit, and followed an S-shape pattern. In the initial learning phase, failed attempts to ride the normal bicycle indicated strong interference between the two bicycle skills. While additional practice decreased this interference effect, a subset of learners could not ride either bicycle after eight sessions of practice. Experienced riders who performed extensive practice could switch bicycles without failed attempts and exhibited similar performance (i.e., similar handlebar oscillations) on both bicycles. However, their performance on the normal bicycle was worse than that of the novice bicycle riders at baseline. In conclusion, "unlearning" of the normal bicycle skill precedes the initial learning of the reversed bicycle skill, and a signature of such unlearning is still present following extensive practice.

Global Estimate of Human Brucellosis Incidence.

Brucellosis is a major public health concern worldwide, especially for persons living in resource-limited settings. Historically, an evidence-based estimate of the global annual incidence of human cases has been elusive. We used international public health data to fill this information gap through application of risk metrics to worldwide and regional at-risk populations. We performed estimations using 3 statistical models (weighted average interpolation, bootstrap resampling, and Bayesian inference) and considered missing information. An evidence-based conservative estimate of the annual global incidence is 2.1 million, significantly higher than was previously assumed. Our models indicate Africa and Asia sustain most of the global risk and cases, although areas within the Americas and Europe remain of concern. This study reveals that disease risk and incidence are higher than previously suggested and lie mainly within resource-limited settings. Clarification of both misdiagnosis and underdiagnosis is required because those factors will amplify case estimates.

Task-dependent alteration of beta-band intermuscular coherence is associated with ipsilateral corticospinal tract excitability.

Beta-band (15-30 Hz) synchronization between the EMG signals of active limb muscles can serve as a non-invasive assay of corticospinal tract integrity. Tasks engaging a single limb often primarily utilize one corticospinal pathway, although bilateral neural circuits can participate in goal-directed actions involving multi-muscle coordination and utilization of feedback. Suboptimal utilization of such circuits after CNS injury can result in unintended mirror movements and activation of pathological synergies. Accordingly, it is important to understand how the actions of one limb (e.g., a less-affected limb after strokes) influence the opposite corticospinal pathway for the rehabilitation target. Certain unimanual actions decrease the excitability of the "unengaged" corticospinal tract, presumably to prevent mirror movement, but there is no direct way to predict the extent to which this will occur. In this study, we tested the hypothesis that task-dependent changes in beta-band drives to muscles of one hand will inversely correlate with changes in the opposite corticospinal tract excitability. Ten participants completed spring pinching tasks known to induce differential 15-30 Hz drive to muscles. During compressions, transcranial magnetic stimulation single pulses to the ipsilateral M1 were delivered to generate motor-evoked potentials in the unengaged hand. The task-induced changes in ipsilateral corticospinal excitability were inversely correlated with associated changes in EMG-EMG coherence of the task hand. These results demonstrate a novel connection between intermuscular coherence and the excitability of the "unengaged" corticospinal tract and provide a springboard for further mechanistic studies of unimanual tasks of varying difficulty and their effects on neural pathways relevant to rehabilitation.

A risk-based mutual insurance premium framework for establishing indices of vulnerability to the intentional introduction of transboundary animal diseases.

Biological agents as weapons of agro-crime or agro-terrorism pose threats to peace and economic stability. Such agents pre-exist worldwide as hazards, adversely affecting animal health, as well as imposing substantial burdens on many nations. Few studies have quantified the global risks and vulnerabilities of countries and regions to potential terrorist or criminal operations targeting animal health. We present here a risk-based mutual insurance premium framework for animal health outcomes built upon the World Organisation for Animal Health (WOAH) quantitative risk assessment paradigm. Our objective was to generate dimensionless and relative domain indices related to release and exposure for several biological factors, as well as to assess the preparedness and response ability of each country. We also considered disease-specific measures relating to pathogens, targeted animal populations, the ongoing disease situation, within- and among-country peace or conflict, disease-specific control measures, and the availability of technical tools and personnel for successful disease management. National economic, political, and research and development competencies were used to assess each WOAH Member's potential for resilience. We formulated indices of vulnerability for 25 WOAH Members selected from five worldwide regions; initially, against four transboundary infectious animal diseases that target diverse animal species. We developed these indices using variables obtained from public databases arising from multiple intergovernmental organizations. Subsequently, we compared the relative vulnerability indices among countries for each given disease using three different index building methods: arithmetic mean, distance matrix, and principal component analysis (PCA). The PCA-based approach provided the greatest ability to discriminate among the components and among countries and regions. Due to its transparency and reliance on publicly available datasets, the risk premium framework proposed herein may readily be adjusted by policymakers and agencies and utilized to improve risk management strategies against agro-crime or agro-terror events, as well as for unintentional disease introductions.

Human brucellosis: Widespread information deficiency hinders an understanding of global disease frequency.

BACKGROUND: For decades, human brucellosis has been recognized worldwide as a significant cause of morbidity, yet the annual incidence of this disease remains unknown. We analyzed this frequency, using international reports (2005-2019), identifying information gaps, and distinguishing a possible path forward. METHODOLOGY/PRINCIPAL FINDINGS: A novel approach to estimating the incidence of this disease was explored. We utilized annual health data extracted from the World Organization for Animal Health (OIE)-World Animal Health Information System (WAHIS) database, assessing the dataset completeness and representativeness of the data for the world population. Additionally, we assessed the reported country level human brucellosis case counts and the factors that influenced the observed changes over time. Our analysis revealed incomplete and unrepresentative information, preventing the estimation of annual human brucellosis case incidence at the global level. In the OIE-WAHIS database, only 48.4% of the required reports have been submitted as of 2019, with approximately 47.3% of the world population represented. Additionally, geographic regions were disproportionate in completeness, representativeness, and actual reported case counts. Africa and Asia constituted the majority of reported cases, while simultaneously submitting the lowest percentage of reports as well as covering the lowest percentage of their populations within those reports, when compared to the rest of the world. CONCLUSIONS/SIGNIFICANCE: The global annual frequency of human brucellosis cases remains elusive. Furthermore, there exists great heterogeneity in diagnostic, surveillance, and reporting systems worldwide, calling into question the validity of available information. This study reveals that the Neglected Zoonotic Disease priority status for brucellosis should be restored.

Temporal control of muscle synergies is linked with alpha-band neural drive.

KEY POINTS: It is theorized that the nervous system controls groups of muscles together as functional units, or 'synergies', resulting in correlated electromyographic (EMG) signals among muscles. However, such correlation does not necessarily imply group-level neural control. Oscillatory synchronization (coherence) among EMG signals implies neural coupling, but it is not clear how this relates to control of muscle synergies. EMG was recorded from seven arm muscles of 10 adult participants rotating an upper limb ergometer, and EMG-EMG coherence, EMG amplitude correlations and their relationship with each other were characterized. A novel method to derive multi-muscle synergies from EMG-EMG coherence is presented and these are compared with classically defined synergies. Coherent alpha-band (8-16 Hz) drive was strongest among muscles whose gross activity levels are well correlated within a given task. The cross-muscle distribution and temporal modulation of coherent alpha-band drive suggests a possible role in the neural coordination/monitoring of synergies. ABSTRACT: During movement, groups of muscles may be controlled together by the nervous system as an adaptable functional entity, or 'synergy'. The rules governing when (or if) this occurs during voluntary behaviour in humans are not well understood, at least in part because synergies are usually defined by correlated patterns of muscle activity without regard for the underlying structure of their neural control. In this study, we investigated the extent to which comodulation of muscle output (i.e. correlation of electromyographic (EMG) amplitudes) implies that muscles share intermuscular neural input (assessed via EMG-EMG coherence analysis). We first examined this relationship among pairs of upper limb muscles engaged in an arm cycling task. We then applied a novel multidimensional EMG-EMG coherence analysis allowing synergies to be characterized on the basis of shared neural drive. We found that alpha-band coherence (8-16 Hz) is related to the degree to which overall muscle activity levels correlate over time. The extension of this coherence analysis to describe the cross-muscle distribution and temporal modulation of alpha-band drive revealed a close match to the temporal and structural features of traditionally defined muscle synergies. Interestingly, the coherence-derived neural drive was inversely associated with, and preceded, changes in EMG amplitudes by ∼200 ms. Our novel characterization of how alpha-band neural drive is dynamically distributed among muscles is a fundamental step forward in understanding the neural origins and correlates of muscle synergies.

Development of a Low-Cost, Modular Muscle-Computer Interface for At-Home Telerehabilitation for Chronic Stroke.

Stroke is a leading cause of long-term disability in the United States. Recent studies have shown that high doses of repeated task-specific practice can be effective at improving upper-limb function at the chronic stage. Providing at-home telerehabilitation services with therapist supervision may allow higher dose interventions targeted to this population. Additionally, muscle biofeedback to train patients to avoid unwanted simultaneous activation of antagonist muscles (co-contractions) may be incorporated into telerehabilitation technologies to improve motor control. Here, we present the development and feasibility of a low-cost, portable, telerehabilitation biofeedback system called Tele-REINVENT. We describe our modular electromyography acquisition, processing, and feedback algorithms to train differentiated muscle control during at-home therapist-guided sessions. Additionally, we evaluated the performance of low-cost sensors for our training task with two healthy individuals. Finally, we present the results of a case study with a stroke survivor who used the system for 40 sessions over 10 weeks of training. In line with our previous research, our results suggest that using low-cost sensors provides similar results to those using research-grade sensors for low forces during an isometric task. Our preliminary case study data with one patient with stroke also suggest that our system is feasible, safe, and enjoyable to use during 10 weeks of biofeedback training, and that improvements in differentiated muscle activity during volitional movement attempt may be induced during a 10-week period. Our data provide support for using low-cost technology for individuated muscle training to reduce unintended coactivation during supervised and unsupervised home-based telerehabilitation for clinical populations, and suggest this approach is safe and feasible. Future work with larger study populations may expand on the development of meaningful and personalized chronic stroke rehabilitation.

Force variability is mostly not motor noise: Theoretical implications for motor control.

Variability in muscle force is a hallmark of healthy and pathological human behavior. Predominant theories of sensorimotor control assume 'motor noise' leads to force variability and its 'signal dependence' (variability in muscle force whose amplitude increases with intensity of neural drive). Here, we demonstrate that the two proposed mechanisms for motor noise (i.e. the stochastic nature of motor unit discharge and unfused tetanic contraction) cannot account for the majority of force variability nor for its signal dependence. We do so by considering three previously underappreciated but physiologically important features of a population of motor units: 1) fusion of motor unit twitches, 2) coupling among motoneuron discharge rate, cross-bridge dynamics, and muscle mechanics, and 3) a series-elastic element to account for the aponeurosis and tendon. These results argue strongly against the idea that force variability and the resulting kinematic variability are generated primarily by 'motor noise.' Rather, they underscore the importance of variability arising from properties of control strategies embodied through distributed sensorimotor systems. As such, our study provides a critical path toward developing theories and models of sensorimotor control that provide a physiologically valid and clinically useful understanding of healthy and pathologic force variability.

Scoping review of brucellosis in Cameroon: Where do we stand, and where are we going?

Brucellosis is a zoonotic disease known to be endemic to parts of western and sub-Saharan Africa. However, the epidemiology for humans and animals remains largely unknown in many of these countries with Cameroon being a typical example. Despite common knowledge that brucellosis affects livestock, the actual number of infected animals remains unknown. Through a scoping review, the current known status of the disease is described. The aim is to ascertain relevant and publicly accessible research and knowledge of human and animal brucellosis in the country, and to provide an overview of the factors associated with its known persistence. Seroprevalence has been estimated and published in 12 separate instances (1 human; 9 cattle; 1 human and cattle; and 1 that includes cattle, pigs, and small ruminants), between 1982 and 2020, in 9 of the country's 10 geopolitical regions. In 1983, Brucella abortus and B. melitensis were isolated in cattle, but no further bacterial isolation has been published since. The seroprevalence from 196 total humans has ranged between 5.6% and 28.1%, and between 3.0% and 30.8% for 14,044 total cattle. As there is no ongoing surveillance program, it is not currently possible to identify the specific Brucella spp. that are endemic to the country and its regions. There are sufficient agricultural systems of cattle, pigs, goats, and sheep to sustain the presence of multiple Brucella spp. Surveillance information is the cornerstone of epidemiologic decision making, and is needed to direct policy makers, public health authorities, and veterinary services to appropriate actions. A combination of serological and molecular based diagnostics for surveillance is necessary to identify, quantify, and direct the appropriate public health interventions. Cameroon has an opportunity to build public and animal health infrastructure, leading the way for central Africa in the management and future eradication of brucellosis.

A Virtual Reality Muscle-Computer Interface for Neurorehabilitation in Chronic Stroke: A Pilot Study.

Severe impairment of limb movement after stroke can be challenging to address in the chronic stage of stroke (e.g., greater than 6 months post stroke). Recent evidence suggests that physical therapy can still promote meaningful recovery after this stage, but the required high amount of therapy is difficult to deliver within the scope of standard clinical practice. Digital gaming technologies are now being combined with brain-computer interfaces to motivate engaging and frequent exercise and promote neural recovery. However, the complexity and expense of acquiring brain signals has held back widespread utilization of these rehabilitation systems. Furthermore, for people that have residual muscle activity, electromyography (EMG) might be a simpler and equally effective alternative. In this pilot study, we evaluate the feasibility and efficacy of an EMG-based variant of our REINVENT virtual reality (VR) neurofeedback rehabilitation system to increase volitional muscle activity while reducing unintended co-contractions. We recruited four participants in the chronic stage of stroke recovery, all with severely restricted active wrist movement. They completed seven 1-hour training sessions during which our head-mounted VR system reinforced activation of the wrist extensor muscles without flexor activation. Before and after training, participants underwent a battery of clinical and neuromuscular assessments. We found that training improved scores on standardized clinical assessments, equivalent to those previously reported for brain-computer interfaces. Additionally, training may have induced changes in corticospinal communication, as indexed by an increase in 12-30 Hz corticomuscular coherence and by an improved ability to maintain a constant level of wrist muscle activity. Our data support the feasibility of using muscle-computer interfaces in severe chronic stroke, as well as their potential to promote functional recovery and trigger neural plasticity.

Parkinson's Disease Exhibits Amplified Intermuscular Coherence During Dynamic Voluntary Action.

Parkinson's disease (PD) is typically diagnosed and evaluated on the basis of overt motor dysfunction, however, subtle changes in the frequency spectrum of neural drive to muscles have been reported as well. During dynamic actions, coactive muscles of healthy adults often share a common source of 6-15 Hz (alpha-band) neural drive, creating synchronous alpha-band activity in their EMG signals. Individuals with PD commonly exhibit kinetic action tremor at similar frequencies, but the potential relationship between the intermuscular alpha-band neural drive seen in healthy adults and the action tremor associated with PD is not well-understood. A close relationship is most tenable during voluntary dynamic tasks where alpha-band neural drive is strongest in healthy adults, and where neural circuits affected by PD are most engaged. In this study, we characterized the frequency spectrum of EMG synchronization (intermuscular coherence) in 16 participants with PD and 15 age-matched controls during two dynamic motor tasks: (1) rotation of a dial between the thumb and index finger, and (2) dynamic scaling of isometric precision pinch force. These tasks produce different profiles of coherence between the first dorsal interosseous and abductor pollicis brevis muscles. We sought to determine if alpha-band intermuscular coherence would be amplified in participants with PD relative to controls, if such differences would be task-specific, and if they would correlate with symptom severity. We found that relative to controls, the PD group displayed amplified, but similarly task-dependent, coherence in the alpha-band. The magnitude of coherence during the rotation task correlated with overall symptom severity as per the UPDRS rating scale. Finally, we explored the potential for our coherence measures, with no additional information, to discriminate individuals with PD from controls. The area under the Receiver Operating Characteristic curve (AUC) indicated a clear separation between groups (AUC = 0.96), even though participants with PD were on their typical medication and displayed only mild-moderate symptoms. We conclude that a task-dependent, intermuscular neural drive within the alpha-band is amplified in PD. Its quantification via intermuscular coherence analysis may provide a useful tool for detecting the presence of PD, or assessing its progression.

Periodontal mechanoreceptors and bruxism at low bite forces.

OBJECTIVE: In this study, we examined if 6-9 Hz jaw tremor, an indirect indicator of Periodontal Mechanoreceptor (PMR) activity, is different in bruxists compared to healthy participants during production of a low-level constant bite force. METHODS: Bite force and surface EMG from the masseter muscle were recorded simultaneously as participants (13 patients, 15 controls) held a force transducer between the upper and lower incisors very gently. RESULTS: Tremor in 6-9 Hz band for bruxists was greater on average compared to controls, but the difference was not significant, both for force recordings and EMG activity. CONCLUSIONS: The low effect sizes measured with the current protocol contrast highly with those of our previous study, where larger, dynamic bite forces were used, and where jaw tremor was markedly different in bruxists compared with controls. SIGNIFICANCE: We have now gained important insight into the conditions under which abnormal jaw tremor can be elicited in bruxism. From a scientific standpoint, this is critical for understanding the 'abnormality' of PMR feedback in bruxism. From a clinical perspective, our results represent progress towards the development of an optimal protocol in which jaw tremor can serve as a biological marker of bruxism.

Cardinal features of involuntary force variability can arise from the closed-loop control of viscoelastic afferented muscles.

Involuntary force variability below 15 Hz arises from, and is influenced by, many factors including descending neural drive, proprioceptive feedback, and mechanical properties of muscles and tendons. However, their potential interactions that give rise to the well-structured spectrum of involuntary force variability are not well understood due to a lack of experimental techniques. Here, we investigated the generation, modulation, and interactions among different sources of force variability using a physiologically-grounded closed-loop simulation of an afferented muscle model. The closed-loop simulation included a musculotendon model, muscle spindle, Golgi tendon organ (GTO), and a tracking controller which enabled target-guided force tracking. We demonstrate that closed-loop control of an afferented musculotendon suffices to replicate and explain surprisingly many cardinal features of involuntary force variability. Specifically, we present 1) a potential origin of low-frequency force variability associated with co-modulation of motor unit firing rates (i.e.,'common drive'), 2) an in-depth characterization of how proprioceptive feedback pathways suffice to generate 5-12 Hz physiological tremor, and 3) evidence that modulation of those feedback pathways (i.e., presynaptic inhibition of Ia and Ib afferents, and spindle sensitivity via fusimotor drive) influence the full spectrum of force variability. These results highlight the previously underestimated importance of closed-loop neuromechanical interactions in explaining involuntary force variability during voluntary 'isometric' force control. Furthermore, these results provide the basis for a unifying theory that relates spinal circuitry to various manifestations of altered involuntary force variability in fatigue, aging and neurological disease.

Physiological tremor increases when skeletal muscle is shortened: implications for fusimotor control.

KEY POINTS: In tonic, isometric, plantarflexion contractions, physiological tremor increases as the ankle joint becomes plantarflexed. Modulation of physiological tremor as a function of muscle stretch differs from that of the stretch reflex amplitude. Amplitude of physiological tremor may be altered as a function of reflex pathway gains. Healthy humans likely increase their γ-static fusimotor drive when muscles shorten. Quantification of physiological tremor by manipulation of joint angle may be a useful experimental probe of afferent gains and/or the integrity of automatic fusimotor control. ABSTRACT: The involuntary force fluctuations associated with physiological (as distinct from pathological) tremor are an unavoidable component of human motor control. While the origins of physiological tremor are known to depend on muscle afferentation, it is possible that the mechanical properties of muscle-tendon systems also affect its generation, amplification and maintenance. In this paper, we investigated the dependence of physiological tremor on muscle length in healthy individuals. We measured physiological tremor during tonic, isometric plantarflexion torque at 30% of maximum at three ankle angles. The amplitude of physiological tremor increased as calf muscles shortened in contrast to the stretch reflex whose amplitude decreases as muscle shortens. We used a published closed-loop simulation model of afferented muscle to explore the mechanisms responsible for this behaviour. We demonstrate that changing muscle lengths does not suffice to explain our experimental findings. Rather, the model consistently required the modulation of  Î³-static fusimotor drive to produce increases in physiological tremor with muscle shortening - while successfully replicating the concomitant reduction in stretch reflex amplitude. This need to control γ-static fusimotor drive explicitly as a function of muscle length has important implications. First, it permits the amplitudes of physiological tremor and stretch reflex to be decoupled. Second, it postulates neuromechanical interactions that require length-dependent γ drive modulation to be independent from α drive to the parent muscle. Lastly, it suggests that physiological tremor can be used as a simple, non-invasive measure of the afferent mechanisms underlying healthy motor function, and their disruption in neurological conditions.

Intermuscular coherence reflects functional coordination.

Coherence analysis has the ability to identify the presence of common descending drive shared by motor unit pools and reveals its spectral properties. However, the link between spectral properties of shared neural drive and functional interactions among muscles remains unclear. We assessed shared neural drive between muscles of the thumb and index finger while participants executed two mechanically distinct precision pinch tasks, each requiring distinct functional coordination among muscles. We found that shared neural drive was systematically reduced or enhanced at specific frequencies of interest (~10 and ~40 Hz). While amplitude correlations between surface EMG signals also exhibited changes across tasks, only their coherence has strong physiological underpinnings indicative of neural binding. Our results support the use of intermuscular coherence as a tool to detect when coactivated muscles are members of a functional group or synergy of neural origin. Furthermore, our results demonstrate the advantages of considering neural binding at 10, ~20, and >30 Hz, as indicators of task-dependent neural coordination strategies.NEW & NOTEWORTHY It is often unclear whether correlated activity among muscles reflects their neural binding or simply reflects the constraints defining the task. Using the fact that high-frequency coherence between EMG signals (>6 Hz) is thought to reflect shared neural drive, we demonstrate that coherence analysis can reveal the neural origin of distinct muscle coordination patterns required by different tasks.

Electrical Stimulation of Afferent Pathways for the Suppression of Pathological Tremor.

Pathological tremors are involuntary oscillatory movements which cannot be fully attenuated using conventional treatments. For this reason, several studies have investigated the use of neuromuscular electrical stimulation for tremor suppression. In a recent study, however, we found that electrical stimulation below the motor threshold also suppressed tremor, indicating involvement of afferent pathways. In this study, we further explored this possibility by systematically investigating how tremor suppression by afferent stimulation depends on the stimulation settings. In this way, we aimed at identifying the optimal stimulation strategy, as well as to elucidate the underlying physiological mechanisms of tremor suppression. Stimulation strategies varying the stimulation intensity and pulse timing were tested in nine tremor patients using either intramuscular or surface stimulation. Significant tremor suppression was observed in six patients (tremor suppression > 75% was observed in three patients) and the average optimal suppression level observed across all subjects was 52%. The efficiency for each stimulation setting, however, varied substantially across patients and it was not possible to identify a single set of stimulation parameters that yielded positive results in all patients. For example, tremor suppression was achieved both with stimulation delivered in an out-of-phase pattern with respect to the tremor, and with random timing of the stimulation. Overall, these results indicate that low-current stimulation of afferent fibers is a promising approach for tremor suppression, but that further research is required to identify how the effect can be maximized in the individual patient.

Beta Band Corticomuscular Drive Reflects Muscle Coordination Strategies.

During force production, hand muscle activity is known to be coherent with activity in primary motor cortex, specifically in the beta-band (15-30 Hz) frequency range. It is not clear, however, if this coherence reflects the control strategy selected by the nervous system for a given task, or if it instead reflects an intrinsic property of cortico-spinal communication. Here, we measured corticomuscular and intermuscular coherence between muscles of index finger and thumb while a two-finger pinch grip of identical net force was applied to objects which were either stable (allowing synergistic activation of finger muscles) or unstable (requiring individuated finger control). We found that beta-band corticomuscular coherence with the first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles, as well as their beta-band coherence with each other, was significantly reduced when individuated control of the thumb and index finger was required. We interpret these findings to show that beta-band coherence is reflective of a synergistic control strategy in which the cortex binds task-related motor neurons into functional units.

The Dynamics of Voluntary Force Production in Afferented Muscle Influence Involuntary Tremor.

Voluntary control of force is always marked by some degree of error and unsteadiness. Both neural and mechanical factors contribute to these fluctuations, but how they interact to produce them is poorly understood. In this study, we identify and characterize a previously undescribed neuromechanical interaction where the dynamics of voluntary force production suffice to generate involuntary tremor. Specifically, participants were asked to produce isometric force with the index finger and use visual feedback to track a sinusoidal target spanning 5-9% of each individual's maximal voluntary force level. Force fluctuations and EMG activity over the flexor digitorum superficialis (FDS) muscle were recorded and their frequency content was analyzed as a function of target phase. Force variability in either the 1-5 or 6-15 Hz frequency ranges tended to be largest at the peaks and valleys of the target sinusoid. In those same periods, FDS EMG activity was synchronized with force fluctuations. We then constructed a physiologically-realistic computer simulation in which a muscle-tendon complex was set inside of a feedback-driven control loop. Surprisingly, the model sufficed to produce phase-dependent modulation of tremor similar to that observed in humans. Further, the gain of afferent feedback from muscle spindles was critical for appropriately amplifying and shaping this tremor. We suggest that the experimentally-induced tremor may represent the response of a viscoelastic muscle-tendon system to dynamic drive, and therefore does not fall into known categories of tremor generation, such as tremorogenic descending drive, stretch-reflex loop oscillations, motor unit behavior, or mechanical resonance. Our findings motivate future efforts to understand tremor from a perspective that considers neuromechanical coupling within the context of closed-loop control. The strategy of combining experimental recordings with physiologically-sound simulations will enable thorough exploration of neural and mechanical contributions to force control in health and disease.

Force Variability during Dexterous Manipulation in Individuals with Mild to Moderate Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease affecting about 1-2% of the population over the age of 65. Individuals with PD experience gradual deterioration of dexterous manipulation for activities of daily living; however, current clinical evaluations are mostly subjective and do not quantify changes in dynamic control of fingertip force that is critical for manual dexterity. Thus, there is a need to develop clinical measures to quantify those changes with aging and disease progression. We investigated the dynamic control of fingertip forces in both hands of 20 individuals with PD (69.0 ± 7.4 years) using the Strength-Dexterity test. The test requires low forces (<3 N) to compress a compliant and slender spring prone to buckling. A maximal level of sustained compression is informative of the greatest instability the person can control, and thus is indicative of the integrity of the neuromuscular system for dexterous manipulation. Miniature sensors recorded fingertip force (F) during maximal sustained compressions. The force variability during sustained compression was quantified in two frequency bands: low (<4 Hz, F_LF) and high (4-12 Hz, F_HF). F_LF characterizes variability in voluntary fluctuations, while F_HF characterizes variability in involuntary fluctuations including tremor. The more-affected hand exhibited significantly lower F and lower F_LF than those in the less-affected hand. The more-affected hand showed significant negative correlations between F_LF and the Unified Parkinson's Disease Rating Scale motor scores for both total and hand-only, suggesting that greater force variability in the voluntary range was associated with less clinical motor impairment. We conclude the nature of force variability in the voluntary range during this dynamic and dexterous task may be a biomarker of greater motor capability/flexibility/adaptability in PD. This approach may provide a more quantitative clinical assessment of changes of sensorimotor control in individuals with PD.

Motor Neuron Pools of Synergistic Thigh Muscles Share Most of Their Synaptic Input.

Neural control of synergist muscles is not well understood. Presumably, each muscle in a synergistic group receives some unique neural drive and some drive that is also shared in common with other muscles in the group. In this investigation, we sought to characterize the strength, frequency spectrum, and force dependence of the neural drive to the human vastus lateralis and vastus medialis muscles during the production of isometric knee extension forces at 10 and 30% of maximum voluntary effort. High-density surface electromyography recordings were decomposed into motor unit action potentials to examine the neural drive to each muscle. Motor unit coherence analysis was used to characterize the total neural drive to each muscle and the drive shared between muscles. Using a novel approach based on partial coherence analysis, we were also able to study specifically the neural drive unique to each muscle (not shared). The results showed that the majority of neural drive to the vasti muscles was a cross-muscle drive characterized by a force-dependent strength and bandwidth. Muscle-specific neural drive was at low frequencies (<5 Hz) and relatively weak. Frequencies of neural drive associated with afferent feedback (6-12 Hz) and with descending cortical input (∼20 Hz) were almost entirely shared by the two muscles, whereas low-frequency (<5 Hz) drive comprised shared (primary) and muscle-specific (secondary) components. This study is the first to directly investigate the extent of shared versus independent control of synergist muscles at the motor neuron level. SIGNIFICANCE STATEMENT: Precisely how the nervous system coordinates the activity of synergist muscles is not well understood. One possibility is that muscles of a synergy share a common neural drive. In this study, we directly compared the relative strength of shared versus independent neural drive to synergistically activated thigh muscles in humans. The results of this analysis support the notion that synergistically activated muscles share most of their neural drive. Scientifically, this study addressed an important gap in our current understanding of how neural drive is delivered to synergist muscles. We have also demonstrated the feasibility of a novel approach to the study of muscle synergies based on partial coherence analysis of motor unit activity.