Reduced corticospinal drive and inflexible temporal adaptation during visually guided walking in older adults.

Corticospinal drive during walking is reduced in older adults compared with young adults, but it is not clear how this decrease might compromise one's ability to adjust stepping, particularly during visuomotor adaptation. We hypothesize that age-related changes in corticospinal drive could predict differences in older adults' step length and step time adjustments in response to visual perturbations compared with younger adults. Healthy young (n = 21; age 18-33 yr) and older adults (n = 20; age 68-80 yr) were tested with a treadmill task, incorporating visual feedback of the foot position and stepping targets in real-time. During adaptation, the visuomotor gain was reduced on one side, causing the foot cursor and step targets to move slower on that side of the screen (i.e., split-visuomotor adaptation). Corticospinal drive was quantified by coherence between electromyographic signals in the beta-gamma frequency band (15-45 Hz). The results showed that 1) older adults adapted to visuomotor perturbations during walking, with a similar reduction in error asymmetry compared with younger adults; 2) however, older adults showed reduced adaptation in step time symmetry, despite demonstrating similar adaptation in step length asymmetry compared with younger adults; and 3) smaller overall changes in step time asymmetry was associated with reduced corticospinal drive to the tibialis anterior in the slow leg during split-visuomotor adaptation. These findings suggest that changes in corticospinal drive may affect older adults' control of step timing in response to visual challenges. This could be important for safe navigation when walking in different environments or dealing with unexpected circumstances.NEW & NOTEWORTHY Corticospinal input is essential for visually guided walking, especially when the walking pattern must be modified to accurately step on safe locations. Age-related changes in corticospinal drive are associated with inflexible step time, which necessitates different locomotor adaptation strategies in older adults.

Visuomotor errors drive step length and step time adaptation during 'virtual' split-belt walking: the effects of reinforcement feedback.

Precise foot placement is dependent on changes in spatial and temporal coordination between two legs in response to a perturbation during walking. Here, we used a 'virtual' split-belt adaptation task to examine the effects of reinforcement (reward and punishment) feedback about foot placement on the changes in error, step length and step time asymmetry. Twenty-seven healthy adults (20 ± 2.5 years) walked on a treadmill with continuous feedback of the foot position and stepping targets projected on a screen, defined by a visuomotor gain for each leg. The paradigm consisted of a baseline period (same gain on both legs), visuomotor adaptation period (split: one high = 'fast', one low = 'slow' gain) and post-adaptation period (same gain). Participants were divided into 3 groups: control group received no score, reward group received increasing score for each target hit, and punishment group received decreasing score for each target missed. Re-adaptation was assessed 24 ± 2 h later. During early adaptation, the slow foot undershot and fast foot overshot the stepping target. Foot placement errors were gradually reduced by late adaptation, accompanied by increasing step length asymmetry (fast < slow step length) and step time asymmetry (fast > slow step time). Only the punishment group showed greater error reduction and step length re-adaptation on the next day. The results show that (1) explicit feedback of foot placement alone drives adaptation of both step length and step time asymmetry during virtual split-belt walking, and (2) specifically, step length re-adaptation driven by visuomotor errors may be enhanced by punishment feedback.

Disentangling the energetic costs of step time asymmetry and step length asymmetry in human walking.

The metabolic cost of walking in healthy individuals increases with spatiotemporal gait asymmetries. Pathological gait, such as post-stroke, often has asymmetry in step length and step time which may contribute to an increased energy cost. But paradoxically, enforcing step length symmetry does not reduce metabolic cost of post-stroke walking. The isolated and interacting costs of asymmetry in step time and step length remain unclear, because previous studies did not simultaneously enforce spatial and temporal gait asymmetries. Here, we delineate the isolated costs of asymmetry in step time and step length in healthy human walking. We first show that the cost of step length asymmetry is predicted by the cost of taking two non-preferred step lengths (one short and one long), but that step time asymmetry adds an extra cost beyond the cost of non-preferred step times. The metabolic power of step time asymmetry is about 2.5 times greater than the cost of step length asymmetry. Furthermore, the costs are not additive when walking with asymmetric step time and asymmetric step length: the metabolic power of concurrent asymmetry in step length and step time is driven by the cost of step time asymmetry alone. The metabolic power of asymmetry is explained by positive mechanical power produced during single support phases to compensate for a net loss of center of mass power incurred during double support phases. These data may explain why metabolic cost remains invariant to step length asymmetry in post-stroke walking and suggest how effects of asymmetry on energy cost can be attenuated.

Step time asymmetry but not step length asymmetry is adapted to optimize energy cost of split-belt treadmill walking.

KEY POINTS: The relationship between spatiotemporal gait asymmetry and walking energetics is currently under debate. The split-belt treadmill paradigm has been used to study adaptation of spatiotemporal gait parameters in relation to energetics, but it remains unclear why people reduce asymmetry in step lengths, but prefer asymmetry in step times. In this study we characterized the effects of step time asymmetry and step length asymmetry on energy cost during steady-state walking on a split-belt treadmill at increasing speed-differences. Both the optimal and preferred step time asymmetry increased with greater speed differences, while preferred step lengths remained constant and nearly symmetric. Preferred asymmetric step times were energetically optimal across all speed-difference conditions, while preferred step length asymmetry was not optimal. The findings show that humans will adopt an asymmetric gait that is associated with an energy reduction and suggest that step time asymmetry plays a dominant role in shaping the energetic cost of gait asymmetry. ABSTRACT: Healthy human walking is symmetric and economical; hemiparetic and amputee gait is often asymmetric and requires more energy. Consequently, asymmetry has been attributed to account for the added energy cost of pathological gait. But it is also possible that asymmetric gait may be adopted if it is energetically optimal under certain biomechanical and neurological constraints of the locomotor system. Here, we assessed how preferred asymmetry in step times and step lengths of healthy human gait is adapted during split-belt treadmill walking and tested the hypothesis that asymmetry is adapted to optimize metabolic energy cost. Ten healthy, young participants walked on a split-belt treadmill in three conditions in which the average belt speed was always 1.25 m s-1 and the speed difference between the belts was 0.5 m s-1 , 1.0 m s-1 and 1.5 m s-1 while a range of values of step time asymmetry and step length asymmetry were enforced. We found that preferred step time asymmetry increased with greater speed differences while preferred step length asymmetry remained constant and nearly symmetric. With increasing speed differences participants increased their preferred value of step time asymmetry to coincide with the lowest energy cost. However, our results show that preferred step length asymmetry was not optimal even with extensive experience of split-belt treadmill walking. Overall, our results indicate that humans will adopt an asymmetric gait that is associated with an energy reduction and suggest that step time asymmetry plays a dominant role in shaping the energetic cost of gait asymmetry.

Increased intramuscular coherence is associated with temporal gait symmetry during split-belt locomotor adaptation.

When walking on a split-belt treadmill where one belt moves faster than the other, the nervous system consistently attempts to maintain symmetry between legs, quantified as deviation from double support time or step length symmetry. It is known that the cerebellum plays a critical role in locomotor adaptation. Less is known about the role of corticospinal drive in maintaining this type of proprioceptive-driven locomotor adaptation. The objective of this study was to examine the functional role of oscillatory drive in relation to changes in spatiotemporal gait parameters during split-belt walking adaptation. Eighteen healthy participants adapted and deadapted on a split-belt treadmill; 13 out of 18 participants repeated the paradigm two more times to examine the effects of reexposure. Coherence analysis was used to quantify the coupling between electromyography (EMG) from the proximal (TAprox) and distal tibialis anterior (TAdist) muscle during the swing phase of walking. EMG-EMG coherence was examined within the alpha (8-15 Hz), beta (15-30 Hz), and gamma (30-45 Hz) frequencies. Our results showed that 1) beta- and gamma-band coherence (markers of corticospinal drive) increased during early split-belt walking compared with baseline walking in the slow leg, 2) beta-band coherence decreased from early to late split-belt adaptation in the fast leg, 3) alpha-, beta-, and gamma-band coherence decreased from first to third split-belt exposure in the fast leg, and 4) there was a relationship between higher beta coherence in the slow leg TA and smaller double support asymmetry. Our results suggest that corticospinal drive may play a functional role in the temporal control of split-belt walking adaptation.NEW & NOTEWORTHY This is the first study to examine the functional role of intramuscular coherence in relation to changes in spatiotemporal gait parameters during split-belt walking adaptation. We found that the corticospinal drive measured by intramuscular coherence in tibialis anterior changes with adaptation and that the corticospinal drive is related to temporal but not spatial parameters. This study may give insight as to the specific role of the motor cortex during gait.

B12 deficiency leading to marked poikilocytosis versus true schistocytosis, a pernicious problem.

Severe vitamin B12 deficiency is caused most commonly by autoimmune atrophic gastritis leading to loss of intrinsic factor. Vitamin B12 deficiency leading to megaloblastic anemia and demyelinating central nervous system disease is well known; however, a rare presentation of B12 deficiency described as pseudothrombotic microangiopathy is not well known. This complication presents with signs of mechanical hemolysis, elevated lactate dehydrogenase (LDH), thrombocytopenia, and a low reticulocyte count, which can be incorrectly diagnosed as thrombotic thrombocytopenic purpura and managed incorrectly. Decreased reticulocyte count and an LDH >2500IU/L is more commonly seen in B12 deficiency. However, recognizing the differences in marked poikilocytosis can be challenging, as seen with megaloblastic changes and true schistocytosis. To illustrate the challenge in differentiating between megaloblastic changes and true schistocytosis, we present the case of a 27-year-old woman who presented to her physician for symptomatic anemia and complaints of nausea, vomiting, and loose stool. She had a hemoglobin of 5.1g/dL, platelet count of 39×109/L, LDH of 9915IU/L, haptoglobin below assay limit, and a reticulocyte count of 2.5%. Peripheral smear showed macrocytic anemia, rare hypersegmented neutrophils, and schistocytes. Vitamin B12 level was less than 50pg/mL, methylmalonic acid was 0.33µmol/L, anti-parietal cell antibody was >1:640, and intrinsic factor blocking antibody was positive-confirming the diagnosis of pernicious anemia. While hospitalized, she was treated with vitamin B12 1000µg intramuscular injections daily and thereafter continued with monthly injections, which ultimately resolved her severe macrocytic anemia.

Error signals driving locomotor adaptation: cutaneous feedback from the foot is used to adapt movement during perturbed walking.

KEY POINTS: Sensory input from peripheral receptors are important for the regulation of walking patterns. Cutaneous input mediates muscle responses to deal with immediate external perturbations. In this study we focused on the role of cutaneous feedback in locomotor adaptation that takes place over minutes of training. We show that interfering with cutaneous feedback reduced adaptation to ankle perturbations during walking. These results help us understand the neural mechanisms underlying walking adaptation, and have clinical implications for treating walking impairments after neurological injuries. ABSTRACT: Locomotor patterns must be adapted to external forces encountered during daily activities. The contribution of different sensory inputs to detecting perturbations and adapting movements during walking is unclear. In the present study, we examined the role of cutaneous feedback in adapting walking patterns to force perturbations. Forces were applied to the ankle joint during the early swing phase using an electrohydraulic ankle-foot orthosis. Repetitive 80 Hz electrical stimulation was applied to disrupt cutaneous feedback from the superficial peroneal nerve (foot dorsum) and medial plantar nerve (foot sole) during walking (Choi et al. 2013). Sensory tests were performed to measure the cutaneous touch threshold and perceptual threshold of force perturbations. Ankle movement were measured when the subjects walked on the treadmill over three periods: baseline (1 min), adaptation (1 min) and post-adaptation (3 min). Subjects (n = 10) showed increased touch thresholds measured with Von Frey monofilaments and increased force perception thresholds with stimulation. Stimulation reduced the magnitude of walking adaptation to force perturbation. In addition, we compared the effects of interrupting cutaneous feedback using anaesthesia (n = 5) instead of repetitive nerve stimulation. Foot anaesthesia reduced ankle adaptation to external force perturbations during walking. The results of the present study suggest that cutaneous input plays a role in force perception, and may contribute to the 'error' signal involved in driving walking adaptation when there is a mismatch between expected and actual force.

Locomotor sequence learning in visually guided walking.

Voluntary limb modifications must be integrated with basic walking patterns during visually guided walking. In this study we tested whether voluntary gait modifications can become more automatic with practice. We challenged walking control by presenting visual stepping targets that instructed subjects to modify step length from one trial to the next. Our sequence learning paradigm is derived from the serial reaction-time (SRT) task that has been used in upper limb studies. Both random and ordered sequences of step lengths were used to measure sequence-specific and sequence-nonspecific learning during walking. In addition, we determined how age (i.e., healthy young adults vs. children) and biomechanical factors (i.e., walking speed) affected the rate and magnitude of locomotor sequence learning. The results showed that healthy young adults (age 24 ± 5 yr,n= 20) could learn a specific sequence of step lengths over 300 training steps. Younger children (age 6-10 yr,n= 8) had lower baseline performance, but their magnitude and rate of sequence learning were the same compared with those of older children (11-16 yr,n= 10) and healthy adults. In addition, learning capacity may be more limited at faster walking speeds. To our knowledge, this is the first study to demonstrate that spatial sequence learning can be integrated with a highly automatic task such as walking. These findings suggest that adults and children use implicit knowledge about the sequence to plan and execute leg movement during visually guided walking.

Neuromuscular effort predicts walk-run transition speed in normal and adapted human gaits.

Often, humans and other animals move in a manner that minimizes energy costs. It is more economical to walk at slow speeds, and to run at fast speeds. Here, we asked whether humans select a gait that minimizes neuromuscular effort under novel and unfamiliar conditions, by imposing interlimb asymmetry during split-belt treadmill locomotion. The walk-run transition speed changed markedly across different gait conditions: forward, backward, hybrid (one leg forward, one leg backward) and forward with speed differences (one leg faster than the other). Most importantly, we showed that the human walk-run transition speed across conditions was predicted by changes in neuromuscular effort (i.e. summed leg muscle activations). Our results for forward gait and forward gait with speed differences suggest that human locomotor patterns are optimized under both familiar and novel gait conditions by minimizing the motor command for leg muscle activation.

Disruption of Locomotor Adaptation with Repetitive Transcranial Magnetic Stimulation Over the Motor Cortex.

Locomotor patterns are adapted on a trial-and-error basis to account for predictable dynamics. Once a walking pattern is adapted, the new calibration is stored and must be actively de-adapted. Here, we tested the hypothesis that storage of newly acquired ankle adaptation in walking is dependent on corticospinal mechanisms. Subjects were exposed to an elastic force that resisted ankle dorsiflexion during treadmill walking. Ankle movement was adapted in <30 strides, leading to after-effects on removal of the force. We used a crossover design to study the effects of repetitive transcranial magnetic stimulation (TMS) over the primary motor cortex (M1), compared with normal adaptation without TMS. In addition, we tested the effects of TMS over the primary sensory cortex (S1) and premotor cortex (PMC) during adaptation. We found that M1 TMS, but not S1 TMS and PMC TMS, reduced the size of ankle dorsiflexion after-effects. The results suggest that suprathreshold M1 TMS disrupted the initial processes underlying locomotor adaptation. These results are consistent with the hypothesis that corticospinal mechanisms underlie storage of ankle adaptation in walking.

Syphilitic hepatitis treated with doxycycline in an HIV-infected patient and review of the literature.

An HIV-infected male patient who had sex with men and with a penicillin allergy presented with liver dysfunction due to secondary syphilis and was successfully treated with doxycycline. This case highlights that syphilitic hepatitis may be overlooked in this particular population, and health care providers should be attuned to this diagnosis. Doxycycline may be an acceptable alternative to penicillin for treatment of this clinical syndrome.

Sleep benefits perceptual but not movement-based learning of locomotor sequences.

Practicing complex locomotor skills, such as those involving a step sequence engages distinct perceptual and motor mechanisms that support the recall of learning under new conditions (i.e., skill transfer). While sleep has been shown to enhance learning of sequences of fine movements (i.e., sleep-dependent consolidation), here we examined whether this benefit extends to learning of a locomotor pattern. Specifically, we tested the perceptual and motor learning of a locomotor sequence following sleep compared to wake. We hypothesized that post-practice sleep would increase locomotor sequence learning in the perceptual, but not in the motor domain. In this study, healthy young adult participants (n = 48; 18-33 years) practiced a step length sequence on a treadmill cued by visual stimuli displayed on a screen during training. Participants were then tested in a perceptual condition (backward walking with the same visual stimuli), or a motor condition (forward walking but with an inverted screen). Skill was assessed immediately, and again after a 12-h delay following overnight sleep or daytime wake (n = 12 for each interval/condition). Off-line learning improved following sleep compared to wake, but only for the perceptual condition. Our results suggest that perceptual and motor sequence learning are processed separately after locomotor training, and further points to a benefit of sleep that is rooted in the perceptual as opposed to the motor aspects of motor learning.

Thematic analysis to explore patients' experiences with long COVID-19: a conceptual model of symptoms and impacts on daily lives.

OBJECTIVES: There is limited qualitative research on patients' experiences with long COVID-19, and how specific symptoms impact their daily lives. The study aimed to understand patients' lived experiences of long COVID-19 and to develop a conceptual model representing the symptoms and their impact on overall quality of life. SETTING: Qualitative study consisting of a comprehensive literature review, and in-depth clinician and patient semistructured interviews. PARTICIPANTS: Forty-one adult patients with long COVID-19, of whom 18 (44%) were recruited through Regeneron Pharmaceuticals's clinical trials and 23 (56%) through recruitment agencies; 85.4% were female and 73.2% were White. Five independent clinicians treating patients with long COVID-19 were interviewed. Concept saturation was also assessed. PRIMARY AND SECONDARY OUTCOMES: Interview transcripts were analysed thematically to identify concepts of interest spontaneously mentioned by patients, including symptoms and their impacts on daily life, to guide the development of the conceptual model. RESULTS: Findings from the literature review and clinician and patient interviews resulted in the development of a conceptual model comprising two overarching domains: symptoms (upper respiratory tract, lower respiratory tract, smell and taste, systemic, gastrointestinal, neurocognitive and other) and impacts (activities of daily living, instrumental activities of daily living, physical impacts, emotional, social/leisure activities and professional impacts). Saturation was achieved for the reported impacts. The symptoms reported were heterogenic; neurocognitive symptoms, such as numbness, ringing in ears, haziness, confusion, forgetfulness/memory problems, brain fog, concentration, difficulties finding the right word and challenges with fine motor skills, were particularly pertinent for several months. CONCLUSION: The conceptual model, developed based on patient experience data of long COVID-19, highlighted numerous symptoms that impact patients' physical and mental well-being, and suggests humanistic unmet needs. Prospective real-world studies are warranted to understand the pattern of long COVID-19 experienced in larger samples over longer periods of time.

Visuospatial cognition predicts performance on an obstructed vision obstacle walking task in older adults.

Walking performance and cognitive function demonstrate strong associations in older adults, with both declining with advancing age. Walking requires the use of cognitive resources, particularly in complex environments like stepping over obstacles. A commonly implemented approach for measuring the cognitive control of walking is a dual-task walking assessment, in which walking is combined with a second task. However, dual-task assessments have shortcomings, including issues with scaling the task difficulty and controlling for task prioritization. Here we present a new assessment designed to be less susceptible to these shortcomings while still challenging cognitive control of walking: the Obstructed Vision Obstacle (OBVIO) task. During the task, participants hold a lightweight tray at waist level obstructing their view of upcoming foam blocks, which are intermittently spaced along a 10 m walkway. This forces the participants to use cognitive resources (e.g., attention and working memory) to remember the exact placement of upcoming obstacles to facilitate successful crossing. The results demonstrate that adding the obstructed vision board significantly slowed walking speed by an average of 0.26 m/s and increased the number of obstacle strikes by 8-fold in healthy older adults (n = 74). Additionally, OBVIO walking performance (a score based on both speed and number of obstacle strikes) significantly correlated with computer-based assessments of visuospatial working memory, attention, and verbal working memory. These results provide initial support that the OBVIO task is a feasible walking test that demands cognitive resources. This study lays the groundwork for using the OBVIO task in future assessment and intervention studies.

Cutaneous mechanisms of isometric ankle force control.

The sense of force is critical in the control of movement and posture. Multiple factors influence our perception of exerted force, including inputs from cutaneous afferents, muscle afferents and central commands. Here, we studied the influence of cutaneous feedback on the control of ankle force output. We used repetitive electrical stimulation of the superficial peroneal (foot dorsum) and medial plantar nerves (foot sole) to disrupt cutaneous afferent input in 8 healthy subjects. We measured the effects of repetitive nerve stimulation on (1) tactile thresholds, (2) performance in an ankle force-matching and (3) an ankle position-matching task. Additional force-matching experiments were done to compare the effects of transient versus continuous stimulation in 6 subjects and to determine the effects of foot anesthesia using lidocaine in another 6 subjects. The results showed that stimulation decreased cutaneous sensory function as evidenced by increased touch threshold. Absolute dorsiflexion force error increased without visual feedback during peroneal nerve stimulation. This was not a general effect of stimulation because force error did not increase during plantar nerve stimulation. The effects of transient stimulation on force error were greater when compared to continuous stimulation and lidocaine injection. Position-matching performance was unaffected by peroneal nerve or plantar nerve stimulation. Our results show that cutaneous feedback plays a role in the control of force output at the ankle joint. Understanding how the nervous system normally uses cutaneous feedback in motor control will help us identify which functional aspects are impaired in aging and neurological diseases.

Hummingbird ingestion of low-concentration ethanol within artificial nectar.

Both frugivores and nectarivores are potentially exposed to dietary ethanol produced by fermentative yeasts which metabolize sugars. Some nectarivorous mammals exhibit a preference for low-concentration ethanol solutions compared to controls of comparable caloric content, but behavioural responses to ethanol by nectar-feeding birds are unknown. We investigated dietary preference by Anna's Hummingbirds (Calypte anna) for ethanol-enhanced sucrose solutions. Via repeated binary-choice experiments, three adult male hummingbirds were exposed to sucrose solutions containing 0%, 1% or 2% ethanol; rates of volitional nectar consumption were measured over a 3 h interval. Hummingbirds did not discriminate between 0% and 1% ethanol solutions, but exhibited significantly reduced rates of consumption of a 2% ethanol solution. Opportunistic measurements of ethanol concentrations within hummingbird feeders registered values peaking at about 0.05%. Ethanol at low concentrations (i.e. up to 1%) is not aversive to Anna's Hummingbirds and may be characteristic of both natural and anthropogenic nectars upon which they feed. Given high daily amounts of nectar consumption by hummingbirds, chronic physiological exposure to ethanol can thus be substantial, although naturally occurring concentrations within floral nectar are unknown.

Neural Control of Human Locomotor Adaptation: Lessons about Changes with Aging.

Walking patterns are adaptable in response to different environmental demands, which requires neural input from spinal and supraspinal structures. With an increase in age, there are changes in walking adaptation and in the neural control of locomotion, but the age-related changes in the neural control of locomotor adaptation is unclear. The purpose of this narrative review is to establish a framework where the age-related changes of neural control of human locomotor adaptation can be understood in terms of reactive feedback and predictive feedforward control driven by sensory feedback during locomotion. We parse out the effects of aging on (a) reactive adaptation to split-belt walking, (b) predictive adaptation to split-belt walking, (c) reactive visuomotor adaptation, and (d) predictive visuomotor adaptation, and hypothesize that specific neural circuits are influenced differentially with age, which influence locomotor adaptation. The differences observed in the age-related changes in walking adaptation across different locomotor adaptation paradigms will be discussed in light of the age-related changes in the neural mechanisms underlying locomotion.

Corticospinal drive is associated with temporal walking adaptation in both healthy young and older adults.

Healthy aging is associated with reduced corticospinal drive to leg muscles during walking. Older adults also exhibit slower or reduced gait adaptation compared to young adults. The objective of this study was to determine age-related changes in the contribution of corticospinal drive to ankle muscles during walking adaptation. Electromyography (EMG) from the tibialis anterior (TA), soleus (SOL), medial, and lateral gastrocnemius (MGAS, LGAS) were recorded from 20 healthy young adults and 19 healthy older adults while they adapted walking on a split-belt treadmill. We quantified EMG-EMG coherence in the beta-gamma (15-45 Hz) and alpha-band (8-15 Hz) frequencies. Young adults demonstrated higher coherence in both the beta-gamma band coherence and alpha band coherence, although effect sizes were greater in the beta-gamma frequency. The results showed that slow leg TA-TA coherence in the beta-gamma band was the strongest predictor of early adaptation in double support time. In contrast, early adaptation in step length symmetry was predicted by age group alone. These findings suggest an important role of corticospinal drive in adapting interlimb timing during walking in both young and older adults.

Cortico-Subthalamic Field Potentials Support Classification of the Natural Gait Cycle in Parkinson's Disease and Reveal Individualized Spectral Signatures.

The ability of humans to coordinate stereotyped, alternating movements between the two legs during bipedal walking is a complex motor behavior that requires precisely timed activities across multiple nodes of the supraspinal network. Understanding of the neural network dynamics that underlie natural walking in humans is limited. We investigated cortical and subthalamic neural activities during overground walking and evaluated spectral biomarkers to decode the gait cycle in three patients with Parkinson's disease without gait disturbances. Patients were implanted with chronic bilateral deep brain stimulation (DBS) leads in the subthalamic nucleus (STN) and electrocorticography paddles overlaying the primary motor and somatosensory cortices. Local field potentials were recorded from these areas while the participants performed overground walking and synchronized to external gait kinematic sensors. We found that the STN displays increased low-frequency (4-12 Hz) spectral power during the period before contralateral leg swing. Furthermore, STN shows increased theta frequency (4-8 Hz) coherence with the primary motor through the initiation and early phase of contralateral leg swing. Additional analysis revealed that each patient had specific frequency bands that could detect a significant difference between left and right initial leg swing. Our findings indicate that there are alternating spectral changes between the two hemispheres in accordance with the gait cycle. In addition, we identified patient-specific, gait-related biomarkers in both the STN and cortical areas at discrete frequency bands that may be used to drive adaptive DBS to improve gait dysfunction in patients with Parkinson's disease.

Stability in a frontal plane model of balance requires coupled changes to postural configuration and neural feedback control.

Postural stability depends on interactions between the musculoskeletal system and neural control mechanisms. We present a frontal plane model stabilized by delayed feedback to analyze the effects of altered stance width on postural responses to perturbations. We hypothesized that changing stance width alters the mechanical dynamics of the body and limits the range of delayed feedback gains that produce stable postural behaviors. Surprisingly, mechanical stability was found to decrease as stance width increased due to decreased effective inertia. Furthermore, due to sensorimotor delays and increased leverage of hip joint torque on center-of-mass motion, the magnitudes of the stabilizing delayed feedback gains decreased as stance width increased. Moreover, the ranges of the stable feedback gains were nonoverlapping across different stance widths such that using a single neural feedback control strategy at both narrow and wide stances could lead to instability. The set of stable feedback gains was further reduced by constraints on foot lift-off and perturbation magnitude. Simulations were fit to experimentally measured kinematics, and the identified feedback gains corroborated model predictions. In addition, analytical gain margin of the linearized system was found to predict step transitions without the need for simulation. In conclusion, this model offers a method to dissociate the complex interactions between postural configuration, delayed sensorimotor feedback, and nonlinear foot lift-off constraints. The model demonstrates that stability at wide stances can only be achieved if delayed neural feedback gains decrease. This model may be useful in explaining both expected and paradoxical changes in stance width in healthy and neurologically impaired individuals.