Biology subjects

Ting, L. H.

Publications and source records attributed to Ting, L. H..

31 records · Page 2Linked to original sources

bioRxiv2022

Distinct features of the cortical N1 response to balance perturbation are associated with balance and cognitive impairments in Parkinson's disease

Mechanisms underlying associations between balance and cognitive impairments in older adults with and without Parkinsons disease are poorly understood. Balance disturbances evoke a cortical N1 response that is associated with both balance and cognitive abilities in unimpaired populations. We hypothesized that the N1 response reflects neural mechanisms that are shared between balance and cognitive function, and would therefore be associated with both balance and cognitive impairments in Parkinsons disease. Although N1 responses did not differ at the group level, they showed different associations with balance and cognitive function in the Parkinsons disease vs. control groups. In the control group, higher N1 amplitudes were correlated with lower cognitive set shifting ability and lower balance confidence. However, in Parkinsons disease, narrower N1 widths (i.e., shorter durations) were associated with greater parkinsonian motor symptom severity, lower balance ability and confidence, lower mobility, and lower overall cognitive function. Despite different relationships across populations, the present results suggest the N1 response reflects neural processes related to both balance and cognitive function. A better understanding of neural mechanisms linking balance and cognitive function could provide insight into associations between balance and cognitive decline in aging populations.

neuroscience↗

bioRxiv2021

An approximate stochastic optimal control framework to simulate nonlinear neuromusculoskeletal models in the presence of noise

Optimal control simulations have shown that both musculoskeletal dynamics and physiological noise are important determinants of movement. However, due to the limited efficiency of available computational tools, deterministic simulations of movement focus on accurately modelling the musculoskeletal system while neglecting physiological noise, and stochastic simulations account for noise while simplifying the dynamics. We took advantage of recent approaches where stochastic optimal control problems are approximated using deterministic optimal control problems, which can be solved efficiently using direct collocation. We were thus able to extend predictions of stochastic optimal control as a theory of motor coordination to include muscle coordination and movement patterns emerging from non-linear musculoskeletal dynamics. In stochastic optimal control simulations of human standing balance, we demonstrated that the inclusion of muscle dynamics can predict muscle co-contraction as minimal effort strategy that complements sensorimotor feedback control in the presence of sensory noise. In simulations of reaching, we demonstrated that nonlinear multi-segment musculoskeletal dynamics enables complex perturbed and unperturbed reach trajectories under a variety of task conditions to be predicted. In both behaviors, we demonstrated how interactions between task constraint, sensory noise, and the intrinsic properties of muscle influence optimal muscle coordination patterns, including muscle co-contraction, and the resulting movement trajectories. Our approach enables a true minimum effort solution to be identified as task constraints, such as movement accuracy, can be explicitly imposed, rather than being approximated using penalty terms in the cost function. Our approximate stochastic optimal control framework predicts complex features, not captured by previous simulation approaches, providing a generalizable and valuable tool to study how musculoskeletal dynamics and physiological noise may alter neural control of movement in both healthy and pathological movements.

neuroscience↗

bioRxiv2021

Lower cognitive set shifting ability is associated with stiffer balance recovery behavior and larger perturbation-evoked cortical responses in older adults

1.The mechanisms underlying associations between cognitive set shifting impairments and balance dysfunction are unclear. Cognitive set shifting refers to the ability to flexibly adjust behavior to changes in task rules or contexts, which could be involved in flexibly adjusting balance recovery behavior to different contexts, such as the direction the body is falling. Prior studies found associations between cognitive set shifting impairments and severe balance dysfunction in populations experiencing frequent falls. The objective of this study was to test whether cognitive set shifting ability is expressed in successful balance recovery behavior in older adults with high clinical balance ability (N=19, 71 {+/-} 7 years, 6 female). We measured cognitive set shifting ability using the Trail Making Test and clinical balance ability using the miniBESTest. For most participants, cognitive set shifting performance (Trail Making Test B-A = 37 {+/-} 20s) was faster than normative averages (46s for comparable age and education levels), and balance ability scores (miniBESTest = 25 {+/-} 2 / 28) were above the threshold for fall risk (23 for people between 70-80 years). Reactive balance recovery in response to support-surface translations in anterior and posterior directions was assessed in terms of body motion, muscle activity, and brain activity. Across participants, lower cognitive set shifting ability was associated with smaller peak center of mass displacement during balance recovery, lower directional specificity of late phase balance-correcting muscle activity (i.e., greater antagonist muscle activity 200-300ms after perturbation onset), and larger cortical N1 responses (100-200ms). None of these measures were associated with clinical balance ability. Our results suggest that cognitive set shifting ability is expressed in balance recovery behavior even in the absence of profound clinical balance disability. Specifically, our results suggest that lower flexibility in cognitive task performance is associated with lower ability to incorporate the directional context into the cortically-mediated later phase of the motor response. The resulting antagonist activity and stiffer balance behavior may help explain associations between cognitive set shifting impairments and frequent falls.

neuroscience↗

bioRxiv2021

Prefrontal-motor and somatosensory-motor cortical network interactions during reactive balance are associated with distinct aspects of balance behavior in older adults

Heightened reliance on the cerebral cortex for postural stability with aging is well-known, yet the cortical dynamics of balance control, particularly in relationship to balance function, is unclear. Here we aimed to investigate motor cortical activity in relationship to the level of balance challenge presented during reactive balance recovery, and identify circuit-specific interactions between motor cortex and prefrontal or somatosensory regions to metrics of balance function that predict fall risk. Using electroencephalography, we assessed motor cortical beta power, and beta coherence during balance reactions to perturbations in older adults. We found that individuals with greater somatosensory-motor beta coherence at baseline and lower beta power evoked over motor regions following perturbations demonstrated higher general clinical balance function. At the group-level, beta coherence between prefrontal-motor regions reduced during balance reactions. Older adults with the highest post-perturbation prefrontal-motor coherence showed greater cognitive dual-task interference and elicited stepping reactions at lower perturbation magnitudes. Our results support motor cortical beta activity as a potential biomarker for individual level of balance challenge and implicate prefrontal-and somatosensory-motor cortical networks in different aspects of balance control in older adults. Cortical network activity during balance may provide a neural target for precision-medicine efforts aimed at fall-prevention with aging.

neuroscience↗

bioRxiv2020

Cortical beta oscillatory activity evoked during reactive balance recovery scales with perturbation difficulty and individual balance ability

I.Cortical beta oscillations (13-30 Hz) reflect sensorimotor cortical activity, but have not been fully investigated in balance recovery behavior. We hypothesized that more challenging balance conditions would lead to greater recruitment of cortical sensorimotor brain regions for balance recovery. We predicted that beta power would be enhanced when balance recovery is more challenging, either due to more difficult perturbations or due to lower intrinsic balance ability. In 19 young adults, we measured beta power evoked over motor cortical areas (Cz electrode) during 3 magnitudes of backward support-surface translational perturbations using electroencephalography. Peak beta power was measured during early (50-150 ms), late (150-250 ms), and overall (0-400 ms) time bins, and wavelet-based analyses quantified the time course of evoked beta power and agonist and antagonist ankle muscle activity. We further assessed the relationship between individual balance ability measured in a challenging beam walking task and perturbation-evoked beta power within each time bin. In balance perturbations, cortical beta power increased [~]50 ms after perturbation onset, demonstrating greater increases with increasing perturbation magnitude. Balance ability was negatively associated with peak beta power in only the late (150-250 ms) time bin, with higher beta power in individuals who performed worse in the beam walking task. Additionally, the time course of cortical beta power followed a similar waveform as the evoked muscle activity, suggesting these evoked responses may be initially evoked by shared underlying mechanisms. These findings support the active role of sensorimotor cortex in balance recovery behavior, with greater recruitment of cortical resources under more challenging balance conditions. Cortical beta power may therefore provide a biomarker for engagement of sensorimotor cortical resources during reactive balance recovery and reflect the individual level of balance challenge.

neuroscience↗

bioRxiv2020

Abnormal center of mass control during balance is associated with falls in Parkinson's disease

Although Parkinson disease (PD) causes profound balance impairments, we know very little about how PD impacts the sensorimotor networks we rely on for automatically maintaining balance control. In young healthy people and animals, muscles are activated in a precise temporal and spatial organization when the center of body mass (CoM) is unexpectedly moved that is largely automatic and determined by feedback of CoM motion. Here, we show that PD alters the sensitivity of the sensorimotor feedback transformation. Importantly, sensorimotor feedback transformations for balance in PD remain temporally precise, but become spatially diffuse by recruiting additional muscle activity in antagonist muscles during balance responses. The abnormal antagonist muscle activity remains precisely time-locked to sensorimotor feedback signals encoding undesirable motion of the body in space. Further, among people with PD, the sensitivity of abnormal antagonist muscle activity to CoM motion varies directly with the number of recent falls. Our work shows that in people with PD, sensorimotor feedback transformations for balance are intact but disinhibited in antagonist muscles, likely contributing to balance deficits and falls.

neuroscience↗

bioRxiv2019

Diverse muscle spindle firing properties emerge from multiscale muscle mechanics

AO_SCPLOWBSTRACTC_SCPLOWDespite decades of research, we lack a mechanistic framework capable of predicting how movement-related signals are transformed into the diversity of muscle spindle afferent firing patterns observed experimentally, particularly in naturalistic behaviors. Here, a biophysical model demonstrates that well-known firing characteristics of muscle spindle Ia afferents - including dependence on movement history, and nonlinear scaling with muscle stretch velocity - emerge from first principles of muscle contractile mechanics. Further, mechanical interactions of the muscle spindle with muscle-tendon dynamics reveal how motor commands to the muscle (alpha drive) versus muscle spindle (gamma drive) can cause highly variable and complex activity during active muscle contraction and muscle stretch that defy simple explanation. Depending on the neuromechanical conditions, the muscle spindle model output appears to "encode" aspects of muscle force, yank, length, stiffness, velocity, and/or acceleration, providing an extendable, multiscale, biophysical framework for understanding and predicting proprioceptive sensory signals in health and disease.

neuroscience↗

bioRxiv2019

Perception of whole-body motion during balance perturbations is impaired in Parkinson’s disease and is associated with balance impairment

BackgroundIn addition to motor deficits, Parkinsons disease (PD) may cause perceptual impairments. The role of perceptual impairments in sensorimotor function is unclear, and has typically been studied in single-joint motions. Research Question: We hypothesized that perception of whole-body motion is impaired in PD and contributes to balance impairments. We tested 1) whether directional acuity to whole body perturbations during standing was worse in people with PD compared to neurotypical older adults (NOA), and 2) whether balance ability, as assessed by the MiniBESTest, was associated with poor directional acuity in either group.\n\nMethodsParticipants were exposed to pairs of support-surface translation perturbations in a two-alternative forced choice testing paradigm developed previously in a young healthy population. The first perturbation of each pair was directly backward and the second deviated to the left or right (1{degrees}-44{degrees}). Participants judged and reported whether the perturbations in each pair were in the \"same\" or \"different\" direction. This information was used to calculate directional acuity thresholds corresponding to \"just-noticeable differences\" in perturbation direction. Linear mixed models determined associations between directional thresholds and clinical variables including MDS UPDRS-III score, age, and MiniBESTest score. Results: 20 PD (64{+/-}7 y, 12 male, [>=]12 hours since last intake of antiparkinsonian medications) and 12 NOA (64{+/-}8, 6 male) were assessed. Directional thresholds were higher (worse) among PD participants (17.6{+/-}5.9{degrees} vs. 12.8{+/-}3.3{degrees}, P<0.01). Linear mixed models further showed that higher thresholds were associated with MDS UPDRS-III score (P<0.01), and were associated with poorer balance ability among PD participants (P<0.01), but not among NOA participants (P=0.40). Significance: Perception of whole-body motion is impaired in PD and may contribute to impaired balance and falls.

neuroscience↗

bioRxiv2019

Lower-limb rigidity is associated with frequent falls in Parkinson disease

BACKGROUND AND OBJECTIVEThe role of muscle rigidity as an etiological factor of falls in Parkinson disease (PD) is poorly understood. Our objective was to determine whether lower leg rigidity was differentially associated with frequent falls in PD compared to upper limb, neck, and total rigidity measures. METHODS: We examined associations between UPDRS-III (motor) rigidity subscores and history of monthly or more frequent falls in N=216 individuals with PD (age, 66{+/-}10 y; 36% female, disease duration, 7{+/-}5 y) with logistic regression. RESULTS: N=35 individuals were frequent fallers. Significant associations were identified between lower limb rigidity and frequent falls (P=0.01) after controlling for age, sex, PD duration, total UPDRS-III score, and presence of FOG. No significant associations (P[≥]0.14) were identified for total, arm, or neck rigidity. CONCLUSION: Lower limb rigidity is related to frequent falls in people with PD. Further investigation may be warranted into how parkinsonian rigidity could cause falls.\n\nFinancial Disclosures/Conflict of Interest concerning the research related to the manuscript: None\n\nFundingNIH K25HD086276, R01HD046922, R21HD075612, UL1TR002378, UL1TR000454; Department of Veterans Affairs R&D Service Career Development Awards E7108M and N0870W, Consolidated Anti-Aging Foundation, and the Sartain Lanier Family Foundation.

neuroscience↗

bioRxiv2018

Noncontractile tissue forces mask muscle fiber forces underlying muscle spindle Ia afferent firing rates in stretch of relaxed rat muscle

Stretches of relaxed cat and rat muscle elicit similar history-dependent muscle spindle Ia firing rates that resemble history-dependent forces seen in single activated muscle fibers (Nichols and Cope, 2004). During stretch of relaxed cat muscle, whole musculotendon forces exhibit history-dependence that mirror history-dependent muscle spindle firing rates, where both muscle force and muscle spindle firing rates are elevated in the first stretch in a series of stretch-shorten cycles (Blum et al., 2017). By contrast, rat musculotendon are only mildly history-dependent and do not mirror history-dependent muscle spindle firing rates in the same way (Haftel et al., 2004). We hypothesized that history-dependent muscle spindle firing rates elicited in stretch of relaxed rat muscle would mirror history-dependent muscle fiber forces, which are masked by noncontractile tissue at the level of whole musculotendon force. We removed noncontractile tissue force contributions from the recorded musculotendon force using an exponentially-elastic tissue model. We then show that the remaining estimated muscle fiber force resembles history-dependent muscle spindle firing rates recorded simultaneously. These forces also resemble history-dependent forces recorded in stretch of single activated fibers and attributed to muscle cross-bridge mechanisms (Campbell and Moss, 2000). Our results suggest that history-dependent muscle spindle firing in both rats and cats arise from stretch of cross-bridges in muscle fibers.

neuroscience↗

bioRxiv2018

Motor module generalization across balance and walking is reduced after stroke

Here, we examined features of muscle coordination associated with reduced walking performance in chronic stroke survivors. Using motor module (a.k.a. muscle synergy) analysis, we identified differences in the modular control of overground walking and standing reactive balance in stroke survivors compared to age-similar neurotypical controls. In contrast to previous studies that demonstrated reduced motor module number post-stroke, our cohort of stroke survivors did not exhibit a reduction in motor module number compared to controls during either walking or reactive balance. Instead, the pool of motor modules common to walking and reactive balance was smaller, suggesting a reduction in generalizability of motor module function across behaviors. The motor modules common to walking and reactive balance tended to be less variable and more distinct, suggesting more reliable output compared to motor modules specific to one behavior. Indeed, higher levels of motor module generalization was associated with faster walking speeds in stroke survivors. Further, recruitment of a common independent plantarflexor module across both behaviors was associated with faster walking speeds. Our work is the first to show that motor module generalization across walking and balance may help to distinguish important and clinically-relevant differences in walking performance across stroke survivors that would have been overlooked by examining only a single behavior. Finally, as similar relationships between motor module generalization and walking performance have been demonstrated in healthy young adults and individuals with Parkinsons disease, our work suggests that motor module generalization across walking and balance may be important for well-coordinated walking.\n\nNew and NoteworthyOur study is the first to simultaneously examine neuromuscular control of walking and standing reactive balance in stroke survivors. We show that motor module generalization across these behaviors (i.e., recruiting common motor modules) is reduced compared to neurotypical controls, which is associated with slower walking speeds. This is true despite no difference in motor module number between groups within each behavior, suggesting that motor module generalization across walking and balance is important for well-coordinated walking.

bioengineering↗

bioRxiv2018

Identifying Gait Phases from Joint Kinematics during Walking with Switched Linear Dynamical Systems

Human-robot interaction (HRI) for gait rehabilitation could benefit from data-driven, subject-specific gait models that account for gait phases and gait dynamics. Here we address the current limitation in gait models driven by averaged kinematic data, which do not model interlimb gait dynamics and have not been shown to precisely identify gait events. We used Switched Linear Dynamical Systems (SLDS) to model joint angle kinematic data from healthy individuals walking on a treadmill during normal gait and during gait perturbed by electrical muscle stimulation. We compared model-inferred gait phases to gait phases measured independently via a force plate. We found that SLDS models accounted for over 88% of the variation in each joint angle and labeled the joint kinematics with the correct gait phase with 84% precision on average. The transitions between hidden states matched measured gait events, with a median absolute difference of 25ms. To our knowledge, this is the first time that SLDS inferred gait phases have been validated by an external measure of gait, instead of against pre-defined gait phase durations. SLDS provide individual-specific representations of gait that incorporate both gait phases and gait dynamics. SLDS may be useful for developing control policies for HRI aimed at improving gait by allowing for changes in control to be precisely timed to different gait phases.

bioengineering↗

bioRxiv2018

Antagonist muscle activity during reactive balance responses is elevated in Parkinson’s disease and in balance impairment

BACKGROUND: Abnormal antagonist leg muscle activity could indicate increased muscle co-contraction and clarify mechanisms of balance impairments in Parkinsons disease (PD). Prior studies in carefully selected patients showed PD patients demonstrate earlier, longer, and larger antagonist muscle activation during reactive balance responses to perturbations. RESEARCH QUESTION: Here, we tested whether antagonist leg muscle activity was abnormal in a group of PD patients who were not selected for phenotype, and most of whom had volunteered for exercise-based rehabilitation. METHODS: We compared antagonist activation during reactive balance responses to multidirectional support-surface translation perturbations in 31 patients with mild-moderate PD (age 68{+/-}9; H&Y 1-3; UPDRS -III 32{+/-}10) and 13 matched individuals (age 65{+/-}9). We quantified modulation of muscle activity (i.e., the ability to activate and inhibit muscles appropriately according to the perturbation direction) using modulation indices (MI) derived from minimum and maximum EMG activation levels observed across perturbation directions. RESULTS: Antagonist leg muscle activity was abnormal in unselected PD patients compared to controls. Linear mixed models identified significant associations between impaired modulation and PD (P<0.05), PD severity (P<0.01), and balance ability (P<0.05), but not age (P=0.10). SIGNIFICANCE: Antagonist activity is increased during reactive balance responses in PD patients of varying phenotypes who are candidates for rehabilitation. Abnormal antagonist activity may contribute to balance impairments in PD and be a potential rehabilitation target or outcome measure.\n\nFunding SourcesThis work was supported by the National Institutes of Health (NIH) KL2 TR000455, K25 HD086276, R01 HD46922, R21 HD075612, TL1TR000456, and UL1 TR000424. The study sponsors had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.\n\nDeclaration of InterestConflicts of interest: None.\n\nAuthor ContributionsResearch project: Conception, JLM, LHT, MEH; Organization, JLM, KCL, LHT, MEH; Execution, JLM, KCL, LHT, MEH.\n\nStatistical Analysis: Design and Execution, JLM, KCL; Review and Critique, LHT, MEH. Manuscript Preparation: Writing of the first draft, KCL; Review and Critique: JLM, LHT, MEH.\n\nHighlights O_LIWe quantified abnormal antagonist muscle activation during balance in PD.\nC_LIO_LIAbnormalities were related to PD severity as well as to overall balance ability.\nC_LIO_LIAbnormalities were similar across PD phenotypes with and without tremor.\nC_LIO_LIBalance antagonist activation may be a useful rehabilitative outcome measure.\nC_LI

neuroscience↗