Age-related changes in muscle coordination patterns of stepping responses to recover from loss of balance.

INTRODUCTION: Reactive stepping capacity to recover from a loss of balance declines with aging, which increases the risk of falling. To gain insight into the underlying mechanisms, we investigated whether muscle coordination patterns of reactive stepping differed between healthy young and older individuals. METHODS: We performed a cross-sectional study between 15 healthy young and 14 healthy older adults. They recovered from 200 multidirectional platform translations that evoked reactive stepping responses. We determined spatiotemporal step variables and used muscle synergy analysis to characterize stance- and swing-leg muscle coordination patterns from the start of perturbation until foot landing. RESULTS: We observed delayed step onsets in older individuals, without further spatiotemporal differences. Muscle synergy structure was not different between young and older individuals, but age-related differences were observed in the time-varying synergy activation patterns. In anterior-posterior directions, the older individuals demonstrated significantly enhanced early swing-leg synergy activation consistent with non-stepping behavior. In addition, around step onset they demonstrated increased levels of synergy coactivation (mainly around the ankle) in lateral and anterior directions, which did not appear to hamper foot clearance. CONCLUSION: Although synergy structure was not affected by age, the delayed step onsets and the enhanced early synergy recruitment point at a relative bias towards non-stepping behavior in older adults. They may need more time for accumulating information on the direction of perturbation and making the corresponding sensorimotor transformations before initiating the step. Future work may investigate whether perturbation-based training improves these age-related deficits.

The influence of prosthetic suspension on gait and cortical modulations is persons with a transfemoral amputation: socket-suspended versus bone-anchored prosthesis.

BACKGROUND: Persons with a transfemoral amputation (TFA) often experience difficulties in daily-life ambulation, including an asymmetrical and less stable gait pattern and a greater cognitive demand of walking. However, it remains unclear whether this is effected by the prosthetic suspension, as eliminating the non-rigid prosthetic connection may influence stability and cortical activity during walking. Spatiotemporal and stability-related gait parameters, as well as cortical activity during walking, were evaluated between highly active individuals (MFC-level K3-4) with a TFA and able-bodied (AB) persons, and between persons with a bone-anchored prosthesis (BAP) and those with a socket-suspended prosthesis (SSP). METHODS: 18 AB persons and 20 persons with a unilateral TFA (10 BAP-users, 10 SSP-users) walked on a treadmill at their preferred speed. Spatiotemporal and margin of stability parameters were extracted from three-dimensional movement recordings. In addition, 126-channel electroencephalogram (EEG) was recorded. Brain-related activity from several cortical areas was isolated using independent component analysis. Source-level data were divided into gait cycles and subjected to time-frequency analysis to determine gait-cycle dependent modulations of cortical activity. RESULTS: Persons with TFA walked with smaller and wider steps and with greater variability in mediolateral foot placement than AB subjects; no significant differences were found between BAP- and SSP-users. The EEG analysis yielded four cortical clusters in frontal, central (both hemispheres), and parietal areas. No statistically significant between-group differences were found in the mean power over the entire gait cycle. The event-related spectral perturbation maps revealed differences in power modulations (theta, alpha, and beta bands) between TFA and AB groups, and between BAP- and SSP-users, with largest differences observed around heel strike of either leg. CONCLUSIONS: The anticipated differences in gait parameters in persons with TFA were confirmed, however no significant effect of the fixed suspension of a BAP was found. The preliminary EEG findings may indicate more active monitoring and control of stability in persons with TFA, which appeared to be timed differently in SSP than in BAP-users. Future studies may focus on walking tasks that challenge stability to further investigate differences related to prosthetic suspension.

Distinct cortico-muscular coupling between step and stance leg during reactive stepping responses.

Balance recovery often relies on successful stepping responses, which presumably require precise and rapid interactions between the cerebral cortex and the leg muscles. Yet, little is known about how cortico-muscular coupling (CMC) supports the execution of reactive stepping. We conducted an exploratory analysis investigating time-dependent CMC with specific leg muscles in a reactive stepping task. We analyzed high density EEG, EMG, and kinematics of 18 healthy young participants while exposing them to balance perturbations at different intensities, in the forward and backward directions. Participants were instructed to maintain their feet in place, unless stepping was unavoidable. Muscle-specific Granger causality analysis was conducted on single step- and stance-leg muscles over 13 EEG electrodes with a midfrontal scalp distribution. Time-frequency Granger causality analysis was used to identify CMC from cortex to muscles around perturbation onset, foot-off and foot strike events. We hypothesized that CMC would increase compared to baseline. In addition, we expected to observe different CMC between step and stance leg because of their functional role during the step response. In particular, we expected that CMC would be most evident for the agonist muscles while stepping, and that CMC would precede upregulation in EMG activity in these muscles. We observed distinct Granger gain dynamics over theta, alpha, beta, and low/high-gamma frequencies during the reactive balance response for all leg muscles in each step direction. Interestingly, between-leg differences in Granger gain were almost exclusively observed following the divergence of EMG activity. Our results demonstrate cortical involvement in the reactive balance response and provide insights into its temporal and spectral characteristics. Overall, our findings suggest that higher levels of CMC do not facilitate leg-specific EMG activity. Our work is relevant for clinical populations with impaired balance control, where CMC analysis may elucidate the underlying pathophysiological mechanisms.

Midfrontal theta dynamics index the monitoring of postural stability.

Stepping is a common strategy to recover postural stability and maintain upright balance. Postural perturbations have been linked to neuroelectrical markers such as the N1 potential and theta frequency dynamics. Here, we investigated the role of cortical midfrontal theta dynamics of balance monitoring, driven by balance perturbations at different initial standing postures. We recorded electroencephalography, electromyography, and motion tracking of human participants while they stood on a platform that delivered a range of forward and backward whole-body balance perturbations. The participants' postural threat was manipulated prior to the balance perturbation by instructing them to lean forward or backward while keeping their feet-in-place in response to the perturbation. We hypothesized that midfrontal theta dynamics index the engagement of a behavioral monitoring system and, therefore, that perturbation-induced theta power would be modulated by the initial leaning posture and perturbation intensity. Targeted spatial filtering in combination with mixed-effects modeling confirmed our hypothesis and revealed distinct modulations of theta power according to postural threat. Our results provide novel evidence that midfrontal theta dynamics subserve action monitoring of human postural balance. Understanding of cortical mechanisms of balance control is crucial for studying balance impairments related to aging and neurological conditions (e.g. stroke).

Cortical midfrontal theta dynamics following foot strike may index response adaptation during reactive stepping.

Reactive balance recovery often requires stepping responses to regain postural stability following a sudden change in posture. The monitoring of postural stability has been linked to neuroelectrical markers such as the N1 potential and midfrontal theta frequency dynamics. Here, we investigated the role of cortical midfrontal theta dynamics during balance monitoring following foot landing of a reactive stepping response to recover from whole-body balance perturbations. We hypothesized that midfrontal theta dynamics reflect the engagement of a behavioral monitoring system, and therefore that theta would increase time-locked to the moment of foot strike after a stepping response, coinciding with a re-assessment of postural balance to determine if an additional step is necessary. We recorded high-density EEG and kinematic data of 15 healthy young participants while they stood on a platform that delivered multi-directional balance perturbations. Participants were instructed to recover balance with a single step utilizing either their left or right leg (in separate blocks). We used targeted spatial filtering (generalized eigen decomposition) in combination with time-frequency analysis of the EEG data to investigate whether theta dynamics increase following foot strike event. In line with our hypothesis, the results indicate that the foot strike event elicits a midfrontal theta power increase, though only for backward stepping. Counter to our expectations, however, this theta power increase was positively correlated with the margin of stability at foot strike, suggesting a different role of foot strike related theta from monitoring stability. Post-hoc analysis suggests that midfrontal theta dynamics following foot landing may instead facilitate adaptation of stability margins at subsequent stepping responses. We speculate that increase of theta power following foot strikes was not related to stability monitoring but instead may indicate cortical dynamics related to performance monitoring of the balance response.

Cortical Correlates of Gait Compensation Strategies in Parkinson Disease.

OBJECTIVE: Gait impairment in persons with Parkinson disease is common and debilitating. Compensation strategies (eg, external cues) are an essential part of rehabilitation, but their underlying mechanisms remain unclear. Using electroencephalography (EEG), we explored the cortical correlates of 3 categories of strategies: external cueing, internal cueing, and action observation. METHODS: Eighteen participants with Parkinson disease and gait impairment were included. We recorded 126-channel EEG during both stance and gait on a treadmill under 4 conditions: (1) uncued, (2) external cueing (listening to a metronome), (3) internal cueing (silent rhythmic counting), and (4) action observation (observing another person walking). To control for the effects of sensory processing of the cues, we computed relative power changes as the difference in power spectral density between walking and standing for each condition. RESULTS: Relative to uncued gait, the use of all 3 compensation strategies induced a decrease of beta band activity in sensorimotor areas, indicative of increased cortical activation. Parieto-occipital alpha band activity decreased with external and internal cueing, and increased with action observation. Only internal cueing induced a change in frontal cortical activation, showing a decrease of beta band activity compared to uncued gait. INTERPRETATION: The application of compensation strategies resulted in changed cortical activity compared to uncued gait, which could not be solely attributed to sensory processing of the cueing modality. Our findings suggest there are multiple routes to control gait, and different compensation strategies seem to rely on different cortical mechanisms to achieve enhanced central motor activation in persons with Parkinson disease. ANN NEUROL 2022;91:329-341.

Time to move: Brain dynamics underlying natural action and cognition.

Advances in Mobile Brain/Body Imaging (MoBI) technology allows for real-time measurements of human brain dynamics during every day, natural, real-life situations. This special issue Time to Move brings together a collection of experimental papers, targeted reviews and opinion articles that lay out the latest MoBI findings. A wide range of topics across different fields are covered including art, athletics, virtual reality, and mobility. What unites these diverse topics is the common goal to enhance and restore human abilities by reaching a better understanding on how cognition is implemented by the brain-body relationship. The breadth and novelty of paradigms and findings reported here positions MoBI as a new frontier in the field of human cognitive neuroscience.

The Cortical Response Evoked by Robotic Wrist Perturbations Reflects Level of Proprioceptive Impairment After Stroke.

Background: Proprioception is important for regaining motor function in the paretic upper extremity after stroke. However, clinical assessments of proprioception are subjective and require verbal responses from the patient to applied proprioceptive stimuli. Cortical responses evoked by robotic wrist perturbations and measured by electroencephalography (EEG) may be an objective method to support current clinical assessments of proprioception. Objective: To establish whether evoked cortical responses reflect proprioceptive deficits as assessed by clinical scales and whether they predict upper extremity motor function at 26 weeks after stroke. Methods: Thirty-one patients with stroke were included. In week 1, 3, 5, 12, and 26 after stroke, the upper extremity sections of the Erasmus modified Nottingham Sensory Assessment (EmNSA-UE) and the Fugl-Meyer Motor Assessment (FM-UE) and the EEG responses (64 channels) to robotic wrist perturbations were measured. The extent to which proprioceptive input was conveyed to the affected hemisphere was estimated by the signal-to-noise ratio (SNR) of the evoked response. The relationships between SNR and EmNSA-UE as well as SNR and time after stroke were investigated using linear regression. Receiver-operating-characteristic curves were used to compare the predictive values of SNR and EmNSA-UE for predicting whether patients regained some selective motor control (FM-UE > 22) or whether they could only move their paretic upper extremity within basic limb synergies (FM-UE ≤ 22) at 26 weeks after stroke. Results: Patients (N = 7) with impaired proprioception (EmNSA-UE proprioception score < 8) had significantly smaller SNR than patients with unimpaired proprioception (N = 24) [EmNSA-UE proprioception score = 8, t(29) = 2.36, p = 0.03]. No significant effect of time after stroke on SNR was observed. Furthermore, there was no significant difference in the predictive value between EmNSA-UE and SNR for predicting motor function at 26 weeks after stroke. Conclusion: The SNR of the evoked cortical response does not significantly change as a function of time after stroke and differs between patients with clinically assessed impaired and unimpaired proprioception, suggesting that SNR reflects persistent damage to proprioceptive pathways. A similar predictive value with respect to EmNSA-UE suggests that SNR may be used as an objective predictor next to clinical sensory assessments for predicting motor function at 26 weeks after stroke.

Cortical responses to whole-body balance perturbations index perturbation magnitude and predict reactive stepping behavior.

The goal of this study was to determine whether the cortical responses elicited by whole-body balance perturbations were similar to established cortical markers of action monitoring. Postural changes imposed by balance perturbations elicit a robust negative potential (N1) and a brisk increase of theta activity in the electroencephalogram recorded over midfrontal scalp areas. Because action monitoring is a cognitive function proposed to detect errors and initiate corrective adjustments, we hypothesized that the possible cortical markers of action monitoring during balance control (N1 potential and theta rhythm) scale with perturbation intensity and the eventual execution of reactive stepping responses (as opposed to feet-in-place responses). We recorded high-density electroencephalogram from eleven young individuals, who participated in an experimental balance assessment. The participants were asked to recover balance following anteroposterior translations of the support surface at various intensities, while attempting to maintain both feet in place. We estimated source-resolved cortical activity using independent component analysis. Combining time-frequency decomposition and group-level general linear modeling of single-trial responses, we found a significant relation of the interaction between perturbation intensity and stepping responses with multiple cortical features from the midfrontal cortex, including the N1 potential, and theta, alpha, and beta rhythms. Our findings suggest that the cortical responses to balance perturbations index the magnitude of a deviation from a stable postural state to predict the need for reactive stepping responses. We propose that the cortical control of balance may involve cognitive control mechanisms (i.e., action monitoring) that facilitate postural adjustments to maintain postural stability.

Rhythmic neural activity is comodulated with short-term gait modifications during first-time use of a dummy prosthesis: a pilot study.

BACKGROUND: After transfemoral amputation, many hours of practice are needed to re-learn walking with a prosthesis. The long adaptation process that consolidates a novel gait pattern seems to depend on cerebellar function for reinforcement of specific gait modifications, but the precise, step-by-step gait modifications (e.g., foot placement) most likely rely on top-down commands from the brainstem and cerebral cortex. The aim of this study was to identify, in able-bodied individuals, the specific modulations of cortical rhythms that accompany short-term gait modifications during first-time use of a dummy prosthesis. METHODS: Fourteen naïve participants walked on a treadmill without (one block, 4 min) and with a dummy prosthesis (three blocks, 3 × 4 min), while ground reaction forces and 32-channel EEG were recorded. Gait cycle duration, stance phase duration, step width, maximal ground reaction force and, ground reaction force trace over time were measured to identify gait modifications. Independent component analysis of EEG data isolated brain-related activity from distinct anatomical sources. The source-level data were segmented into gait cycles and analyzed in the time-frequency domain to reveal relative enhancement or suppression of intrinsic cortical oscillations. Differences between walking conditions were evaluated with one-way ANOVA and post-hoc testing (α = 0.05). RESULTS: Immediate modifications occurred in the gait parameters when participants were introduced to the dummy prosthesis. Except for gait cycle duration, these modifications remained throughout the duration of the experimental session. Power modulations of the theta, mu, beta, and gamma rhythms, of sources presumably from the fronto-central and the parietal cortices, were found across the experimental session. Significant power modulations of the theta, beta, and gamma rhythms within the gait cycle were predominately found around the heel strike of both feet and the swing phase of the right (prosthetic) leg. CONCLUSIONS: The modulations of cortical activity could be related to whole-body coordination, including the swing phase and placing of the prosthesis, and the bodyweight transfer between legs and arms. Reduced power modulation of the gamma rhythm within the experimental session may indicate initial motor memories being formed. Better understanding of the sensorimotor processes behind gait modifications may inform the development of neurofeedback strategies to assist gait rehabilitation.

Classification of Rhythmic Cortical Activity Elicited by Whole-Body Balance Perturbations Suggests the Cortical Representation of Direction-Specific Changes in Postural Stability.

Postural responses that effectively recover balance following unexpected postural changes need to be tailored to the characteristics of the postural change. We hypothesized that cortical dynamics involved in top-down regulation of postural responses carry information about directional postural changes (i.e., sway) imposed by sudden perturbations to standing balance (i.e., support surface translations). To test our hypothesis, we evaluated the single-trial classification of perturbation-induced directional changes in postural stability from high-density EEG. We analyzed EEG recordings from six young able-bodied individuals and three older individuals with chronic hemiparetic stroke, which were acquired while individuals reacted to low-intensity balance perturbations. Using common spatial patterns for feature extraction and linear discriminant analysis or support vector machines for classification, we achieved classification accuracies above random level (p < 0.05; cross-validated) for the classification of four different sway directions (one vs. the rest scheme). Screening of spectral features (3-50 Hz) revealed that the highest classification performance occurred when low-frequency (3-10 Hz) spectral features were used. Strikingly, the participant-specific classification results were qualitatively similar between young able-bodied individuals and older individuals with chronic hemiparetic stroke. Our findings demonstrate that low-frequency spectral components, corresponding to the cortical theta rhythm, carry direction-specific information about changes in postural stability. Our work presents a new perspective on the cortical representation of postural stability and the possible role of the theta rhythm in the modulation of (directional) reactive balance responses. Importantly, our work provides preliminary evidence that the cortical encoding of direction-specific changes in postural stability is present in chronic hemiparetic stroke.

Understanding the dual-task costs of walking: a StartReact study.

The need to perform multiple tasks more or less simultaneously is a common occurrence during walking in daily life. Performing tasks simultaneously typically impacts task performance negatively. Hypothetically, such dual-task costs may be explained by a lowered state of preparation due to competition for attentional resources, or alternatively, by a 'bottleneck' in response initiation. Here, we investigated both hypotheses by comparing 'StartReact' effects during a manual squeezing task under single-task (when seated) and dual-task (when walking) conditions. StartReact is the acceleration of reaction times by a startling stimulation (a startling acoustic stimulus was applied in 25% of trials), attributed to the startling stimulus directly releasing a pre-prepared movement. If dual-task costs are due to a lowered state of preparation, we expected trials both with and without an accompanying startling stimulus to be delayed compared to the single-task condition, whereas we expected only trials without a startling stimulus to be delayed if a bottleneck in response initiation would underlie dual-task costs. Reaction times of the manual squeezing task in the flexor digitorum superficialis and extensor carpi radialis muscle were significantly delayed (approx. 20 ms) when walking compared to the seated position. A startling acoustic stimulus significantly decreased reaction times of the squeezing task (approx. 60 ms) both when walking and sitting. Dual-task costs during walking are, therefore, likely the result of lowered task preparation because of competition for attentional resources.

High-density EEG mobile brain/body imaging data recorded during a challenging auditory gait pacing task.

In this report we present a mobile brain/body imaging (MoBI) dataset that allows study of source-resolved cortical dynamics supporting coordinated gait movements in a rhythmic auditory cueing paradigm. Use of an auditory pacing stimulus stream has been recommended to identify deficits and treat gait impairments in neurologic populations. Here, the rhythmic cueing paradigm required healthy young participants to walk on a treadmill (constant speed) while attempting to maintain step synchrony with an auditory pacing stream and to adapt their step length and rate to unanticipated shifts in tempo of the pacing stimuli (e.g., sudden shifts to a faster or slower tempo). High-density electroencephalography (EEG, 108 channels), surface electromyography (EMG, bilateral tibialis anterior), pressure sensors on the heel (to register timing of heel strikes), and goniometers (knee, hip, and ankle joint angles) were concurrently recorded in 20 participants. The data is provided in the Brain Imaging Data Structure (BIDS) format to promote data sharing and reuse, and allow the inclusion of the data into fully automated data analysis workflows.

Cortical dynamics during preparation and execution of reactive balance responses with distinct postural demands.

The contributions of the cerebral cortex to human balance control are clearly demonstrated by the profound impact of cortical lesions on the ability to maintain standing balance. The cerebral cortex is thought to regulate subcortical postural centers to maintain upright balance and posture under varying environmental conditions and task demands. However, the cortical mechanisms that support standing balance remain elusive. Here, we present an EEG-based analysis of cortical oscillatory dynamics during the preparation and execution of balance responses with distinct postural demands. In our experiment, participants responded to backward movements of the support surface either with one forward step or by keeping their feet in place. To challenge the postural control system, we applied participant-specific high accelerations of the support surface such that the postural demand was low for stepping responses and high for feet-in-place responses. We expected that postural demand modulated the power of intrinsic cortical oscillations. Independent component analysis and time-frequency domain statistics revealed stronger suppression of alpha (9-13 Hz) and low-gamma (31-34 Hz) rhythms in the supplementary motor area (SMA) when preparing for feet-in-place responses (i.e., high postural demand). Irrespective of the response condition, support-surface movements elicited broadband (3-17 Hz) power increase in the SMA and enhancement of the theta (3-7 Hz) rhythm in the anterior prefrontal cortex (PFC), anterior cingulate cortex (ACC), and bilateral sensorimotor cortices (M1/S1). Although the execution of reactive responses resulted in largely similar cortical dynamics, comparison between the bilateral M1/S1 showed that stepping responses corresponded with stronger suppression of the beta (13-17 Hz) rhythm in the M1/S1 contralateral to the support leg. Comparison between response conditions showed that feet-in-place responses corresponded with stronger enhancement of the theta (3-7 Hz) rhythm in the PFC. Our results provide novel insights into the cortical dynamics of SMA, PFC, and M1/S1 during the control of human balance.

Quantification of task-dependent cortical activation evoked by robotic continuous wrist joint manipulation in chronic hemiparetic stroke.

BACKGROUND: Cortical damage after stroke can drastically impair sensory and motor function of the upper limb, affecting the execution of activities of daily living and quality of life. Motor impairment after stroke has been thoroughly studied, however sensory impairment and its relation to movement control has received less attention. Integrity of the somatosensory system is essential for feedback control of human movement, and compromised integrity due to stroke has been linked to sensory impairment. METHODS: The goal of this study is to assess the integrity of the somatosensory system in individuals with chronic hemiparetic stroke with different levels of sensory impairment, through a combination of robotic joint manipulation and high-density electroencephalogram (EEG). A robotic wrist manipulator applied continuous periodic disturbances to the affected limb, providing somatosensory (proprioceptive and tactile) stimulation while challenging task execution. The integrity of the somatosensory system was evaluated during passive and active tasks, defined as 'relaxed wrist' and 'maintaining 20% maximum wrist flexion', respectively. The evoked cortical responses in the EEG were quantified using the power in the averaged responses and their signal-to-noise ratio. RESULTS: Thirty individuals with chronic hemiparetic stroke and ten unimpaired individuals without stroke participated in this study. Participants with stroke were classified as having severe, mild, or no sensory impairment, based on the Erasmus modification of the Nottingham Sensory Assessment. Under passive conditions, wrist manipulation resulted in contralateral cortical responses in unimpaired and chronic stroke participants with mild and no sensory impairment. In participants with severe sensory impairment the cortical responses were strongly reduced in amplitude, which related to anatomical damage. Under active conditions, participants with mild sensory impairment showed reduced responses compared to the passive condition, whereas unimpaired and chronic stroke participants without sensory impairment did not show this reduction. CONCLUSIONS: Robotic continuous joint manipulation allows studying somatosensory cortical evoked responses during the execution of meaningful upper limb control tasks. Using such an approach it is possible to quantitatively assess the integrity of sensory pathways; in the context of movement control this provides additional information required to develop more effective neurorehabilitation therapies.

Quantifying Nonlinear Contributions to Cortical Responses Evoked by Continuous Wrist Manipulation.

Cortical responses to continuous stimuli as recorded using either magneto- or electroencephalography (EEG) have shown power at harmonics of the stimulated frequency, indicating nonlinear behavior. Even though the selection of analysis techniques depends on the linearity of the system under study, the importance of nonlinear contributions to cortical responses has not been formally addressed. The goal of this paper is to quantify the nonlinear contributions to the cortical response obtained from continuous sensory stimulation. EEG was used to record the cortical response evoked by continuous movement of the wrist joint of healthy subjects applied with a robotic manipulator. Multisine stimulus signals (i.e., the sum of several sinusoids) elicit a periodic cortical response and allow to assess the nonlinear contributions to the response. Wrist dynamics (relation between joint angle and torque) were successfully linearized, explaining 99% of the response. In contrast, the cortical response revealed a highly nonlinear relation; where most power (  âˆ¼ 80 %) occurred at non-stimulated frequencies. Moreover, only 10% of the response could be explained using a nonparametric linear model. These results indicate that the recorded evoked cortical responses are governed by nonlinearities and that linear methods do not suffice when describing the relation between mechanical stimulus and cortical response.

Nonlinear Coupling between Cortical Oscillations and Muscle Activity during Isotonic Wrist Flexion.

Coupling between cortical oscillations and muscle activity facilitates neuronal communication during motor control. The linear part of this coupling, known as corticomuscular coherence, has received substantial attention, even though neuronal communication underlying motor control has been demonstrated to be highly nonlinear. A full assessment of corticomuscular coupling, including the nonlinear part, is essential to understand the neuronal communication within the sensorimotor system. In this study, we applied the recently developed n:m coherence method to assess nonlinear corticomuscular coupling during isotonic wrist flexion. The n:m coherence is a generalized metric for quantifying nonlinear cross-frequency coupling as well as linear iso-frequency coupling. By using independent component analysis (ICA) and equivalent current dipole source localization, we identify four sensorimotor related brain areas based on the locations of the dipoles, i.e., the contralateral primary sensorimotor areas, supplementary motor area (SMA), prefrontal area (PFA) and posterior parietal cortex (PPC). For all these areas, linear coupling between electroencephalogram (EEG) and electromyogram (EMG) is present with peaks in the beta band (15-35 Hz), while nonlinear coupling is detected with both integer (1:2, 1:3, 1:4) and non-integer (2:3) harmonics. Significant differences between brain areas is shown in linear coupling with stronger coherence for the primary sensorimotor areas and motor association cortices (SMA, PFA) compared to the sensory association area (PPC); but not for the nonlinear coupling. Moreover, the detected nonlinear coupling is similar to previously reported nonlinear coupling of cortical activity to somatosensory stimuli. We suggest that the descending motor pathways mainly contribute to linear corticomuscular coupling, while nonlinear coupling likely originates from sensory feedback.

Nonlinear Connectivity in the Human Stretch Reflex Assessed by Cross-Frequency Phase Coupling.

Communication between neuronal populations is facilitated by synchronization of their oscillatory activity. Although nonlinearity has been observed in the sensorimotor system, its nonlinear connectivity has not been widely investigated yet. This study investigates nonlinear connectivity during the human stretch reflex based on neuronal synchronization. Healthy participants generated isotonic wrist flexion while receiving a periodic mechanical perturbation to the wrist. Using a novel cross-frequency phase coupling metric, we estimate directional nonlinear connectivity, including time delay, from the perturbation to brain and to muscle, as well as from brain to muscle. Nonlinear phase coupling is significantly stronger from the perturbation to the muscle than to the brain, with a shorter time delay. The time delay from the perturbation to the muscle is 33 ms, similar to the reported latency of the spinal stretch reflex at the wrist. Source localization of nonlinear phase coupling from the brain to the muscle suggests activity originating from the motor cortex, although its effect on the stretch reflex is weak. As such nonlinear phase coupling between the perturbation and muscle activity is dominated by the spinal reflex loop. This study provides new evidence of nonlinear neuronal synchronization in the stretch reflex at the wrist joint with respect to spinal and transcortical loops.

A Generalized Coherence Framework for Detecting and Characterizing Nonlinear Interactions in the Nervous System.

OBJECTIVE: This paper introduces a generalized coherence framework for detecting and characterizing nonlinear interactions in the nervous system, namely cross-spectral coherence (CSC). CSC can detect different types of nonlinear interactions including harmonic and intermodulation coupling as present in static nonlinearities and also subharmonic coupling, which only occurs with dynamic nonlinearities. METHODS: We verified the performance of CSC in model simulations with both static and dynamic nonlinear systems. We applied CSC to investigate nonlinear stimulus-response interactions in the human proprioceptive system. A periodic movement perturbation was imposed to the wrist when the subjects performed an isotonic wrist flexion. CSC analysis was performed between the perturbation and brain responses (electroencephalogram, EEG). RESULTS: Both the simulation and the application demonstrated that CSC successfully detected different types of nonlinear interactions. High-order nonlinearities were revealed in the proprioceptive system, shown in harmonic and intermodulation coupling between the perturbation and EEG for all subjects. Subharmonic coupling was found in some subjects but not all. CONCLUSION: This paper provides a general tool to detect and characterize nonlinear nature and dynamics of the nervous system. The application of CSC on the experimental dataset indicates a complex nonlinear dynamics in the proprioceptive system. SIGNIFICANCE: This novel framework 1) unveils the nonlinear neural dynamics in a more complete way than the existing coherence measures, and 2) is more suitable for estimating the input-output relation regarding both phase and amplitude compared to phase synchrony measures (which only consider phase coupling). Subharmonic coupling is reported in human proprioceptive system for the first time.

A General Approach for Quantifying Nonlinear Connectivity in the Nervous System Based on Phase Coupling.

Interaction between distant neuronal populations is essential for communication within the nervous system and can occur as a highly nonlinear process. To better understand the functional role of neural interactions, it is important to quantify the nonlinear connectivity in the nervous system. We introduce a general approach to measure nonlinear connectivity through phase coupling: the multi-spectral phase coherence (MSPC). Using simulated data, we compare MSPC with existing phase coupling measures, namely n : m synchronization index and bi-phase locking value. MSPC provides a system description, including (i) the order of the nonlinearity, (ii) the direction of interaction, (iii) the time delay in the system, and both (iv) harmonic and (v) intermodulation coupling beyond the second order; which are only partly revealed by other methods. We apply MSPC to analyze data from a motor control experiment, where subjects performed isotonic wrist flexions while receiving movement perturbations. MSPC between the perturbation, EEG and EMG was calculated. Our results reveal directional nonlinear connectivity in the afferent and efferent pathways, as well as the time delay (43 ± 8 ms) between the perturbation and the brain response. In conclusion, MSPC is a novel approach capable to assess high-order nonlinear interaction and timing in the nervous system.