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1.
Nature ; 632(8023): 55-62, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39085539

RESUMO

Advancements in optical coherence control1-5 have unlocked many cutting-edge applications, including long-haul communication, light detection and ranging (LiDAR) and optical coherence tomography6-8. Prevailing wisdom suggests that using more coherent light sources leads to enhanced system performance and device functionalities9-11. Our study introduces a photonic convolutional processing system that takes advantage of partially coherent light to boost computing parallelism without substantially sacrificing accuracy, potentially enabling larger-size photonic tensor cores. The reduction of the degree of coherence optimizes bandwidth use in the photonic convolutional processing system. This breakthrough challenges the traditional belief that coherence is essential or even advantageous in integrated photonic accelerators, thereby enabling the use of light sources with less rigorous feedback control and thermal-management requirements for high-throughput photonic computing. Here we demonstrate such a system in two photonic platforms for computing applications: a photonic tensor core using phase-change-material photonic memories that delivers parallel convolution operations to classify the gaits of ten patients with Parkinson's disease with 92.2% accuracy (92.7% theoretically) and a silicon photonic tensor core with embedded electro-absorption modulators (EAMs) to facilitate 0.108 tera operations per second (TOPS) convolutional processing for classifying the Modified National Institute of Standards and Technology (MNIST) handwritten digits dataset with 92.4% accuracy (95.0% theoretically).


Assuntos
Redes Neurais de Computação , Óptica e Fotônica , Fótons , Tomografia de Coerência Óptica , Humanos , Óptica e Fotônica/instrumentação , Óptica e Fotônica/métodos , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Silício/química , Tomografia de Coerência Óptica/instrumentação , Tomografia de Coerência Óptica/métodos , Marcha/fisiologia , Conjuntos de Dados como Assunto , Sensibilidade e Especificidade
2.
Nature ; 600(7889): 468-471, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34853470

RESUMO

Bipedal trackways discovered in 1978 at Laetoli site G, Tanzania and dated to 3.66 million years ago are widely accepted as the oldest unequivocal evidence of obligate bipedalism in the human lineage1-3. Another trackway discovered two years earlier at nearby site A was partially excavated and attributed to a hominin, but curious affinities with bears (ursids) marginalized its importance to the paleoanthropological community, and the location of these footprints fell into obscurity3-5. In 2019, we located, excavated and cleaned the site A trackway, producing a digital archive using 3D photogrammetry and laser scanning. Here we compare the footprints at this site with those of American black bears, chimpanzees and humans, and we show that they resemble those of hominins more than ursids. In fact, the narrow step width corroborates the original interpretation of a small, cross-stepping bipedal hominin. However, the inferred foot proportions, gait parameters and 3D morphologies of footprints at site A are readily distinguished from those at site G, indicating that a minimum of two hominin taxa with different feet and gaits coexisted at Laetoli.


Assuntos
Pé/anatomia & histologia , Pé/fisiologia , Fósseis , Marcha/fisiologia , Hominidae/classificação , Hominidae/fisiologia , Animais , Arquivos , Feminino , Hominidae/anatomia & histologia , Humanos , Imageamento Tridimensional , Lasers , Masculino , Modelos Biológicos , Pan troglodytes/anatomia & histologia , Pan troglodytes/fisiologia , Fotogrametria , Filogenia , Tanzânia , Ursidae/anatomia & histologia , Ursidae/fisiologia
3.
Nat Methods ; 19(5): 620-627, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35545713

RESUMO

Animal behavior emerges from an interaction between neural network dynamics, musculoskeletal properties and the physical environment. Accessing and understanding the interplay between these elements requires the development of integrative and morphologically realistic neuromechanical simulations. Here we present NeuroMechFly, a data-driven model of the widely studied organism, Drosophila melanogaster. NeuroMechFly combines four independent computational modules: a physics-based simulation environment, a biomechanical exoskeleton, muscle models and neural network controllers. To enable use cases, we first define the minimum degrees of freedom of the leg from real three-dimensional kinematic measurements during walking and grooming. Then, we show how, by replaying these behaviors in the simulator, one can predict otherwise unmeasured torques and contact forces. Finally, we leverage NeuroMechFly's full neuromechanical capacity to discover neural networks and muscle parameters that drive locomotor gaits optimized for speed and stability. Thus, NeuroMechFly can increase our understanding of how behaviors emerge from interactions between complex neuromechanical systems and their physical surroundings.


Assuntos
Drosophila melanogaster , Marcha , Animais , Fenômenos Biomecânicos , Simulação por Computador , Marcha/fisiologia , Modelos Biológicos , Caminhada/fisiologia
4.
PLoS Comput Biol ; 20(1): e1011771, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38241215

RESUMO

Humans can generate and sustain a wide range of walking velocities while optimizing their energy efficiency. Understanding the intricate mechanisms governing human walking will contribute to the engineering applications such as energy-efficient biped robots and walking assistive devices. Reflex-based control mechanisms, which generate motor patterns in response to sensory feedback, have shown promise in generating human-like walking in musculoskeletal models. However, the precise regulation of velocity remains a major challenge. This limitation makes it difficult to identify the essential reflex circuits for energy-efficient walking. To explore the reflex control mechanism and gain a better understanding of its energy-efficient maintenance mechanism, we extend the reflex-based control system to enable controlled walking velocities based on target speeds. We developed a novel performance-weighted least squares (PWLS) method to design a parameter modulator that optimizes walking efficiency while maintaining target velocity for the reflex-based bipedal system. We have successfully generated walking gaits from 0.7 to 1.6 m/s in a two-dimensional musculoskeletal model based on an input target velocity in the simulation environment. Our detailed analysis of the parameter modulator in a reflex-based system revealed two key reflex circuits that have a significant impact on energy efficiency. Furthermore, this finding was confirmed to be not influenced by setting parameters, i.e., leg length, sensory time delay, and weight coefficients in the objective cost function. These findings provide a powerful tool for exploring the neural bases of locomotion control while shedding light on the intricate mechanisms underlying human walking and hold significant potential for practical engineering applications.


Assuntos
Sistema Musculoesquelético , Caminhada , Humanos , Caminhada/fisiologia , Marcha/fisiologia , Locomoção , Reflexo/fisiologia , Fenômenos Biomecânicos
5.
PLoS Comput Biol ; 20(3): e1011906, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38437243

RESUMO

Adult animals display robust locomotion, yet the timeline and mechanisms of how juvenile animals acquire coordinated movements and how these movements evolve during development are not well understood. Recent advances in quantitative behavioral analyses have paved the way for investigating complex natural behaviors like locomotion. In this study, we tracked the swimming and crawling behaviors of the nematode Caenorhabditis elegans from postembryonic development through to adulthood. Our principal component analyses revealed that adult C. elegans swimming is low dimensional, suggesting that a small number of distinct postures, or eigenworms, account for most of the variance in the body shapes that constitute swimming behavior. Additionally, we found that crawling behavior in adult C. elegans is similarly low dimensional, corroborating previous studies. Further, our analysis revealed that swimming and crawling are distinguishable within the eigenworm space. Remarkably, young L1 larvae are capable of producing the postural shapes for swimming and crawling seen in adults, despite frequent instances of uncoordinated body movements. In contrast, late L1 larvae exhibit robust coordination of locomotion, while many neurons crucial for adult locomotion are still under development. In conclusion, this study establishes a comprehensive quantitative behavioral framework for understanding the neural basis of locomotor development, including distinct gaits such as swimming and crawling in C. elegans.


Assuntos
Comportamento Animal , Caenorhabditis elegans , Animais , Caenorhabditis elegans/fisiologia , Comportamento Animal/fisiologia , Locomoção/fisiologia , Natação/fisiologia , Marcha/fisiologia
6.
PLoS Comput Biol ; 20(6): e1012219, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38900787

RESUMO

The unique structure of the human foot is seen as a crucial adaptation for bipedalism. The foot's arched shape enables stiffening the foot to withstand high loads when pushing off, without compromising foot flexibility. Experimental studies demonstrated that manipulating foot stiffness has considerable effects on gait. In clinical practice, altered foot structure is associated with pathological gait. Yet, experimentally manipulating individual foot properties (e.g. arch height or tendon and ligament stiffness) is hard and therefore our understanding of how foot structure influences gait mechanics is still limited. Predictive simulations are a powerful tool to explore causal relationships between musculoskeletal properties and whole-body gait. However, musculoskeletal models used in three-dimensional predictive simulations assume a rigid foot arch, limiting their use for studying how foot structure influences three-dimensional gait mechanics. Here, we developed a four-segment foot model with a longitudinal arch for use in predictive simulations. We identified three properties of the ankle-foot complex that are important to capture ankle and knee kinematics, soleus activation, and ankle power of healthy adults: (1) compliant Achilles tendon, (2) stiff heel pad, (3) the ability to stiffen the foot. The latter requires sufficient arch height and contributions of plantar fascia, and intrinsic and extrinsic foot muscles. A reduced ability to stiffen the foot results in walking patterns with reduced push-off power. Simulations based on our model also captured the effects of walking with anaesthetised intrinsic foot muscles or an insole limiting arch compression. The ability to reproduce these different experiments indicates that our foot model captures the main mechanical properties of the foot. The presented four-segment foot model is a potentially powerful tool to study the relationship between foot properties and gait mechanics and energetics in health and disease.


Assuntos
, Marcha , Humanos , Pé/fisiologia , Pé/anatomia & histologia , Marcha/fisiologia , Fenômenos Biomecânicos , Adulto , Masculino , Simulação por Computador , Modelos Biológicos , Músculo Esquelético/fisiologia , Feminino , Biologia Computacional , Caminhada/fisiologia , Tornozelo/fisiologia , Tornozelo/anatomia & histologia
7.
J Physiol ; 602(3): 507-525, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38252405

RESUMO

Evoking muscle responses by electrical vestibular stimulation (EVS) may help to understand the contribution of the vestibular system to postural control. Although paraspinal muscles play a role in postural stability, the vestibulo-muscular coupling of these muscles during walking has rarely been studied. This study aimed to investigate how vestibular signals affect paraspinal muscle activity at different vertebral levels during walking with preferred and narrow step width. Sixteen healthy participants were recruited. Participants walked on a treadmill for 8 min at 78 steps/min and 2.8 km/h, at two different step width, either with or without EVS. Bipolar electromyography was recorded bilaterally from the paraspinal muscles at eight vertebral levels from cervical to lumbar. Coherence, gain, and delay of EVS and EMG responses were determined. Significant EVS-EMG coupling (P < 0.01) was found at ipsilateral and/or contralateral heel strikes. This coupling was mirrored between left and right relative to the midline of the trunk and between the higher and lower vertebral levels, i.e. a peak occurred at ipsilateral heel strike at lower levels, whereas it occurred at contralateral heel strike at higher levels. EVS-EMG coupling only partially coincided with peak muscle activity. EVS-EMG coherence slightly, but not significantly, increased when walking with narrow steps. No significant differences were found in gain and phase between the vertebral levels or step width conditions. In summary, vertebral level specific modulation of paraspinal muscle activity based on vestibular signals might allow a fast, synchronized, and spatially co-ordinated response along the trunk during walking. KEY POINTS: Mediolateral stabilization of gait requires an estimate of the state of the body, which is affected by vestibular afference. During gait, the heavy trunk segment is controlled by phasic paraspinal muscle activity and in rodents the medial and lateral vestibulospinal tracts activate these muscles. To gain insight in vestibulospinal connections in humans and their role in gait, we recorded paraspinal surface EMG of cervical to lumbar paraspinal muscles, and characterized coherence, gain and delay between EMG and electrical vestibular stimulation, during slow walking. Vestibular stimulation caused phasic, vertebral level specific modulation of paraspinal muscle activity at delays of around 40 ms, which was mirrored between left, lower and right, upper vertebral levels. Our results indicate that vestibular afference causes fast, synchronized, and spatially co-ordinated responses of the paraspinal muscles along the trunk, that simultaneously contribute to stabilizing the centre of mass trajectory and to keeping the head upright.


Assuntos
Músculo Esquelético , Músculos Paraespinais , Humanos , Músculo Esquelético/fisiologia , Caminhada/fisiologia , Eletromiografia , Marcha/fisiologia , Coluna Vertebral/fisiologia
8.
J Physiol ; 602(14): 3489-3504, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39008710

RESUMO

Cerebral palsy (CP) describes some upper motoneuron disorders due to non-progressive disturbances occurring in the developing brain that cause progressive changes to muscle. While longer sarcomeres increase muscle stiffness in patients with CP compared to typically developing (TD) patients, changes in extracellular matrix (ECM) architecture can increase stiffness. Our goal was to investigate how changes in muscle and ECM architecture impact muscle stiffness, gait and joint function in CP. Gracilis and adductor longus biopsies were collected from children with CP undergoing tendon lengthening surgery for hamstring and hip adduction contractures, respectively. Gracilis biopsies were collected from TD patients undergoing anterior cruciate ligament reconstruction surgery with hamstring autograft. Muscle mechanical testing, two-photon imaging and hydroxyproline assay were performed on biopsies. Corresponding data were compared to radiographic hip displacement in CP adductors (CPA), gait kinematics in CP hamstrings (CPH), and joint range of motion in CPA and CPH. We found at matched sarcomere lengths muscle stiffness and collagen architecture were similar between TD and CP hamstrings. However, CPH stiffness (R2 = 0.1973), collagen content (R2 = 0.5099) and cross-linking (R2 = 0.3233) were correlated to decreased knee range of motion. Additionally, we observed collagen fibres within the muscle ECM increase alignment during muscular stretching. These data demonstrate that while ECM architecture is similar between TD and CP hamstrings, collagen fibres biomechanics are sensitive to muscle strain and may be altered at longer in vivo sarcomere lengths in CP muscle. Future studies could evaluate the impact of ECM architecture on TD and CP muscle stiffness across in vivo operating ranges. KEY POINTS: At matched sarcomere lengths, gracilis muscle mechanics and collagen architecture are similar in TD patients and patients with CP. In both TD and CP muscles, collagen fibres dynamically increase their alignment during muscle stretching. Aspects of muscle mechanics and collagen architecture are predictive of in vivo knee joint motion and radiographic hip displacement in patients with CP. Longer sarcomere lengths in CP muscle in vivo may alter collagen architecture and biomechanics to drive deficits in joint mobility and gait function.


Assuntos
Paralisia Cerebral , Colágeno , Humanos , Paralisia Cerebral/fisiopatologia , Paralisia Cerebral/patologia , Criança , Masculino , Feminino , Colágeno/metabolismo , Fenômenos Biomecânicos , Adolescente , Músculo Grácil , Amplitude de Movimento Articular , Músculo Esquelético/fisiologia , Músculo Esquelético/fisiopatologia , Marcha/fisiologia , Músculos Isquiossurais/fisiologia , Músculos Isquiossurais/fisiopatologia , Matriz Extracelular/fisiologia
9.
Stroke ; 55(7): 1748-1757, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38860389

RESUMO

BACKGROUND: Studies in individuals with chronic stroke indicate high-intensity training (HIT) focused on walking improves locomotor function, which may be due to repeated activation of locomotor circuits and serotonin-dependent modulation of motor output. Separate studies in animals and individuals with spinal cord injury suggest acute intermittent hypoxia (AIH) can augment the effects of locomotor interventions through similar serotonin-dependent mechanisms, although no studies have coupled AIH with HIT in individuals poststroke. The goal of this study was to evaluate the safety and efficacy of AIH+HIT versus HIT alone in individuals with chronic stroke. METHODS: This phase II double-blind randomized, crossover trial recruited individuals between 18 and 85 years old, >6 months poststroke, and self-selected speeds <1.0 m/s. Participants received up to 15 sessions of AIH for 30 minutes using 15 cycles of hypoxia (60-90 seconds; 8%-9% O2) and normoxia (30-60 seconds; 21% O2), followed by 1 hour of HIT targeting >75% heart rate reserve. The control condition received normoxia for 30 minutes before HIT. Following the first training phase, participants performed the second phase >1 month later. The primary outcomes were self-selected speed and fastest speed, a 6-minute walk test, and peak treadmill speed. A 3-way mixed-model ANOVA assessed the effects of time, training, and order of interventions. RESULTS: Of 55 individuals screened, 35 were randomized to AIH+HIT or normoxia+HIT first, and 28 individuals completed both interventions, revealing greater gains in self-selected speeds (0.14 [0.08-0.18] versus 0.05 [0.01-0.10] m/s), fastest speed (0.16 [0.10-0.21] versus 0.06 [0.02-0.10] m/s), and peak treadmill speed (0.21 [0.14-0.29] versus 0.11 [0.06-0.16] m/s) following AIH+HIT versus normoxia+HIT (P<0.01) with no order effects. Greater gains in spatiotemporal symmetry were observed with AIH+HIT, with worse outcomes for those prescribed serotonin-mediated antidepressant medications. CONCLUSIONS: AIH+HIT resulted in greater gains in locomotor function than normoxia+HIT. Subsequent phase III trials should further evaluate the efficacy of this intervention. REGISTRATION: URL: https://clinicaltrials.gov/; Unique identifier: NCT04472442.


Assuntos
Estudos Cross-Over , Hipóxia , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Reabilitação do Acidente Vascular Cerebral/métodos , Método Duplo-Cego , Hipóxia/fisiopatologia , Hipóxia/terapia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Adulto , Marcha/fisiologia , Doença Crônica , Idoso de 80 Anos ou mais , Resultado do Tratamento , Terapia por Exercício/métodos , Treinamento Intervalado de Alta Intensidade/métodos
10.
Neuroimage ; 288: 120531, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38331333

RESUMO

Gait is an excellent indicator of physical, emotional, and mental health. Previous studies have shown that gait impairments in ageing are common, but the neural basis of these impairments are unclear. Existing methodologies are suboptimal and novel paradigms capable of capturing neural activation related to real walking are needed. In this study, we used a hybrid PET/MR system and measured glucose metabolism related to both walking and standing with a dual-injection paradigm in a single study session. For this study, 15 healthy older adults (10 females, age range: 60.5-70.7 years) with normal cognition were recruited from the community. Each participant received an intravenous injection of [18F]-2-fluoro-2-deoxyglucose (FDG) before engaging in two distinct tasks, a static postural control task (standing) and a walking task. After each task, participants were imaged. To discern independent neural functions related to walking compared to standing, we applied a bespoke dose correction to remove the residual 18F signal of the first scan (PETSTAND) from the second scan (PETWALK) and proportional scaling to the global mean, cerebellum, or white matter (WM). Whole-brain differences in walking-elicited neural activity measured with FDG-PET were assessed using a one-sample t-test. In this study, we show that a dual-injection paradigm in healthy older adults is feasible with biologically valid findings. Our results with a dose correction and scaling to the global mean showed that walking, compared to standing, increased glucose consumption in the cuneus (Z = 7.03), the temporal gyrus (Z = 6.91) and the orbital frontal cortex (Z = 6.71). Subcortically, we observed increased glucose metabolism in the supraspinal locomotor network including the thalamus (Z = 6.55), cerebellar vermis and the brainstem (pedunculopontine/mesencephalic locomotor region). Exploratory analyses using proportional scaling to the cerebellum and WM returned similar findings. Here, we have established the feasibility and tolerability of a novel method capable of capturing neural activations related to actual walking and extended previous knowledge including the recruitment of brain regions involved in sensory processing. Our paradigm could be used to explore pathological alterations in various gait disorders.


Assuntos
Fluordesoxiglucose F18 , Neuroanatomia , Feminino , Humanos , Idoso , Pessoa de Meia-Idade , Marcha/fisiologia , Caminhada/fisiologia , Tomografia por Emissão de Pósitrons/métodos , Glucose/metabolismo
11.
J Neurophysiol ; 131(6): 1260-1270, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38748413

RESUMO

Visual information is essential to navigate the environment and maintain postural stability during gait. Visual field rotations alter the perceived heading direction, resulting in gait trajectory deviations, known as visual coupling. It is unclear how center of mass (CoM) control relative to a continuously changing base of support (BoS) is adapted to facilitate visual coupling. This study aimed to characterize mediolateral (ML) balance control during visual coupling in steady-state gait. Sixteen healthy participants walked on an instrumented treadmill, naive to sinusoidal low-frequency (0.1 Hz) rotations of the virtual environment around the vertical axis. Rotations were continuous with 1) high or 2) low amplitude or were 3) periodic with 10-s intervals. Visual coupling was characterized with cross-correlations between CoM trajectory and visual rotations. Balance control was characterized with the ML margin of stability (MoSML) and by quantifying foot placement control as the relation between CoM dynamics and lateral foot placement. Visual coupling was strong on a group level (continuous low: 0.88, continuous high: 0.91, periodic: 0.95) and moderate to strong on an individual level. Higher rotation amplitudes induced stronger gait trajectory deviations. The MoSML decreased toward the deviation direction and increased at the opposite side. Foot placement control was similar compared with regular gait. Furthermore, pelvis and foot reorientation toward the rotation direction was observed. We concluded that visual coupling was facilitated by reorientating the body and shifting the extrapolated CoMML closer to the lateral BoS boundary toward the adjusted heading direction while preserving CoM excursion and foot placement control.NEW & NOTEWORTHY Healthy, naive participants were unaware of subtle, low-frequency rotations of the visual field but still coupled their gait trajectory to a rotating virtual environment. In response, participants decreased their margin of stability toward the new heading direction, without changing the center of mass excursion magnitude and foot placement strategy.


Assuntos
Marcha , Equilíbrio Postural , Percepção Visual , Humanos , Masculino , Feminino , Marcha/fisiologia , Equilíbrio Postural/fisiologia , Adulto , Rotação , Percepção Visual/fisiologia , Adulto Jovem , Fenômenos Biomecânicos/fisiologia
12.
J Neurophysiol ; 131(3): 562-575, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38324891

RESUMO

The ability to adapt our locomotion in a feedforward (i.e., "predictive") manner is crucial for safe and efficient walking behavior. Equally important is the ability to quickly deadapt and update behavior that is no longer appropriate for the given context. It has been suggested that anxiety induced via postural threat may play a fundamental role in disrupting such deadaptation. We tested this hypothesis, using the "broken escalator" phenomenon: Fifty-six healthy young adults walked onto a stationary walkway ("BEFORE" condition, 5 trials), then onto a moving walkway akin to an airport travelator ("MOVING" condition, 10 trials), and then again onto the stationary walkway ("AFTER" condition, 5 trials). Participants completed all trials while wearing a virtual reality headset, which was used to induce postural threat-related anxiety (raised clifflike drop at the end of the walkway) during different phases of the paradigm. We found that performing the locomotor adaptation phase in a state of increased threat disrupted subsequent deadaptation during AFTER trials: These participants displayed anticipatory muscular activity as if expecting the platform to move and exhibited inappropriate anticipatory forward trunk movement that persisted during multiple AFTER trials. In contrast, postural threat induced during AFTER trials did not affect behavioral or neurophysiological outcomes. These findings highlight that actions learned in the presence of postural threat-induced anxiety are strengthened, leading to difficulties in deadapting these behaviors when no longer appropriate. Given the associations between anxiety and persistent maladaptive gait behaviors (e.g., "overly cautious" gait, functional gait disorders), the findings have implications for the understanding of such conditions.NEW & NOTEWORTHY Safe and efficient locomotion frequently requires movements to be adapted in a feedforward (i.e., "predictive") manner. These adaptations are not always correct, and thus inappropriate behavior must be quickly updated. Here we showed that increased threat disrupts this process. We found that locomotor actions learned in the presence of postural threat-induced anxiety are strengthened, subsequently impairing one's ability to update (or "deadapt") these actions when they are no longer appropriate for the current context.


Assuntos
Aprendizagem , Caminhada , Adulto Jovem , Humanos , Caminhada/fisiologia , Aprendizagem/fisiologia , Marcha/fisiologia , Locomoção/fisiologia , Ansiedade , Equilíbrio Postural/fisiologia
13.
N Engl J Med ; 384(6): 521-532, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33567192

RESUMO

BACKGROUND: Bilateral vestibular hypofunction is associated with chronic disequilibrium, postural instability, and unsteady gait owing to failure of vestibular reflexes that stabilize the eyes, head, and body. A vestibular implant may be effective in alleviating symptoms. METHODS: Persons who had had ototoxic (7 participants) or idiopathic (1 participant) bilateral vestibular hypofunction for 2 to 23 years underwent unilateral implantation of a prosthesis that electrically stimulates the three semicircular canal branches of the vestibular nerve. Clinical outcomes included the score on the Bruininks-Oseretsky Test of Motor Proficiency balance subtest (range, 0 to 36, with higher scores indicating better balance), time to failure on the modified Romberg test (range, 0 to 30 seconds), score on the Dynamic Gait Index (range, 0 to 24, with higher scores indicating better gait performance), time needed to complete the Timed Up and Go test, gait speed, pure-tone auditory detection thresholds, speech discrimination scores, and quality of life. We compared participants' results at baseline (before implantation) with those at 6 months (8 participants) and at 1 year (6 participants) with the device set in its usual treatment mode (varying stimulus pulse rate and amplitude to represent rotational head motion) and in a placebo mode (holding pulse rate and amplitude constant). RESULTS: The median scores at baseline and at 6 months on the Bruininks-Oseretsky test were 17.5 and 21.0, respectively (median within-participant difference, 5.5 points; 95% confidence interval [CI], 0 to 10.0); the median times on the modified Romberg test were 3.6 seconds and 8.3 seconds (difference, 5.1; 95% CI, 1.5 to 27.6); the median scores on the Dynamic Gait Index were 12.5 and 22.5 (difference, 10.5 points; 95% CI, 1.5 to 12.0); the median times on the Timed Up and Go test were 11.0 seconds and 8.7 seconds (difference, 2.3; 95% CI, -1.7 to 5.0); and the median speeds on the gait-speed test were 1.03 m per second and 1.10 m per second (difference, 0.13; 95% CI, -0.25 to 0.30). Placebo-mode testing confirmed that improvements were due to treatment-mode stimulation. Among the 6 participants who were also assessed at 1 year, the median within-participant changes from baseline to 1 year were generally consistent with results at 6 months. Implantation caused ipsilateral hearing loss, with the air-conducted pure-tone average detection threshold at 6 months increasing by 3 to 16 dB in 5 participants and by 74 to 104 dB in 3 participants. Changes in participant-reported disability and quality of life paralleled changes in posture and gait. CONCLUSIONS: Six months and 1 year after unilateral implantation of a vestibular prosthesis for bilateral vestibular hypofunction, measures of posture, gait, and quality of life were generally in the direction of improvement from baseline, but hearing was reduced in the ear with the implant in all but 1 participant. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT02725463.).


Assuntos
Vestibulopatia Bilateral/cirurgia , Marcha/fisiologia , Perda Auditiva/etiologia , Neuroestimuladores Implantáveis , Equilíbrio Postural/fisiologia , Qualidade de Vida , Vestíbulo do Labirinto/cirurgia , Idoso , Vestibulopatia Bilateral/induzido quimicamente , Vestibulopatia Bilateral/complicações , Tontura/etiologia , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Neuroestimuladores Implantáveis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Canais Semicirculares/inervação , Nervo Vestibular/efeitos dos fármacos
14.
Osteoarthritis Cartilage ; 32(2): 138-147, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38043858

RESUMO

Biomechanics plays a significant yet complex role in osteoarthritis (OA) onset and progression. Identifying alterations in biomechanical factors and their complex interactions is critical for gaining new insights into OA pathophysiology and identification of clearly defined and modifiable mechanical treatment targets. This review synthesized biomechanics studies from March 2022 to April 2023, from which three themes relating to human gait emerged: (1) new insights into the pathogenesis of OA using computational modeling and machine learning, (2) technology-enhanced biomechanical interventions for OA, and (3) out-of-lab biomechanical assessments of OA. We further highlighted future-focused areas which may continue to advance the field of biomechanics in OA, with a particular emphasis on exploiting technology to understand and treat biomechanical mechanisms of OA outside the laboratory. The breadth of studies included in this review highlights the complex role of biomechanics in OA and showcase numerous innovative and outstanding contributions to the field. Exciting cross-disciplinary efforts integrating computational modeling, mobile sensors, and machine learning methods show great promise for streamlining in vivo multi-scale biomechanics workflows and are expected to underpin future breakthroughs in the understanding and treatment of biomechanics in OA.


Assuntos
Osteoartrite do Joelho , Osteoartrite , Humanos , Fenômenos Biomecânicos , Osteoartrite/etiologia , Marcha/fisiologia , Aprendizado de Máquina
15.
Osteoarthritis Cartilage ; 32(7): 912-921, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38642879

RESUMO

OBJECTIVE: Exercise remains a hallmark treatment for post-traumatic osteoarthritis (PTOA) and may maintain joint homeostasis in part by clearing inflammatory cytokines, cells, and particles. It remains largely unknown whether exercise-induced joint clearance can provide therapeutic relief of PTOA. In this study, we hypothesized that exercise could slow the progression of preclinical PTOA in part by enhancing knee joint clearance. DESIGN: Surgical medial meniscal transection was used to induce PTOA in 3-month-old male Lewis rats. A sham surgery was used as a control. Mild treadmill walking was introduced 3 weeks post-surgery and maintained to 6 weeks post-surgery. Gait and isometric muscle torque were measured at the study endpoint. Near-infrared imaging tracked how exercise altered lymphatic and venous knee joint clearance during discrete time points of PTOA progression. RESULTS: Exercise mitigated joint degradation associated with PTOA by preserving glycosaminoglycan content and reducing osteophyte volume (effect size (95% Confidence Interval (CI)); 1.74 (0.71-2.26)). PTOA increased hind step widths (0.57 (0.18-0.95) cm), but exercise corrected this gait dysfunction (0.54 (0.16-0.93) cm), potentially indicating pain relief. Venous, but not lymphatic, clearance was quicker 1-, 3-, and 6-weeks post-surgery compared to baseline. The mild treadmill walking protocol expedited lymphatic clearance rate in moderate PTOA (3.39 (0.20-6.59) hrs), suggesting exercise may play a critical role in restoring joint homeostasis. CONCLUSIONS: We conclude that mild exercise has the potential to slow disease progression in part by expediting joint clearance in moderate PTOA.


Assuntos
Instabilidade Articular , Osteoartrite do Joelho , Condicionamento Físico Animal , Ratos Endogâmicos Lew , Animais , Masculino , Ratos , Condicionamento Físico Animal/fisiologia , Instabilidade Articular/fisiopatologia , Osteoartrite do Joelho/fisiopatologia , Modelos Animais de Doenças , Marcha/fisiologia , Articulação do Joelho/fisiopatologia , Glicosaminoglicanos/metabolismo , Osteoartrite/fisiopatologia , Osteoartrite/metabolismo , Osteófito , Progressão da Doença
16.
Osteoarthritis Cartilage ; 32(6): 730-739, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38442767

RESUMO

OBJECTIVE: To develop and validate a neural network to estimate hip contact forces (HCF), and lower body kinematics and kinetics during walking in individuals with hip osteoarthritis (OA) using synthesised anatomical key points and electromyography. To assess the capability of the neural network to detect directional changes in HCF resulting from prescribed gait modifications. DESIGN: A calibrated electromyography-informed neuromusculoskeletal model was used to compute lower body joint angles, moments, and HCF for 17 participants with mild-to-moderate hip OA. Anatomical key points (e.g., joint centres) were synthesised from marker trajectories and augmented with bias and noise expected from computer vision-based pose estimation systems. Temporal convolutional and long short-term memory neural networks (NN) were trained using leave-one-subject-out validation to predict neuromusculoskeletal modelling outputs from the synthesised key points and measured electromyography data from 5 hip-spanning muscles. RESULTS: HCF was predicted with an average error of 13.4 ± 7.1% of peak force. Joint angles and moments were predicted with an average root-mean-square-error of 5.3 degrees and 0.10 Nm/kg, respectively. The NN could detect changes in peak HCF that occur due to gait modifications with good agreement with neuromusculoskeletal modelling (r2 = 0.72) and a minimum detectable change of 9.5%. CONCLUSION: The developed neural network predicted HCF and lower body joint angles and moments in individuals with hip OA using noisy synthesised key point locations with acceptable errors. Changes in HCF magnitude due to gait modifications were predicted with high accuracy. These findings have important implications for implementation of load-modification based gait retraining interventions for people with hip OA in a natural environment (i.e., home, clinic).


Assuntos
Eletromiografia , Marcha , Articulação do Quadril , Redes Neurais de Computação , Osteoartrite do Quadril , Humanos , Osteoartrite do Quadril/fisiopatologia , Eletromiografia/métodos , Feminino , Masculino , Fenômenos Biomecânicos , Pessoa de Meia-Idade , Articulação do Quadril/fisiopatologia , Idoso , Marcha/fisiologia , Caminhada/fisiologia , Músculo Esquelético/fisiopatologia , Suporte de Carga/fisiologia
17.
Mov Disord ; 39(1): 85-93, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37860957

RESUMO

BACKGROUND: Preserved cycling capabilities in patients with Parkinson's disease, especially in those with freezing of gait are still poorly understood. Previous research with invasive local field potential recordings in the subthalamic nucleus has shown that cycling causes a stronger suppression of ß oscillations compared to walking, which facilitates motor continuation. METHODS: We recorded local field potentials from 12 patients with Parkinson's disease (six without freezing of gait, six with freezing of gait) who were bilaterally implanted with deep brain stimulation electrodes in the subthalamic nucleus. We investigated ß (13-30 Hz) and high γ (60-100 Hz) power during both active and passive cycling with different cadences and compared patients with and without freezing of gait. The passive cycling experiment, where a motor provided a fixed cadence, allowed us to study the effect of isolated sensory inputs without physical exercise. RESULTS: We found similarly strong suppression of pathological ß activity for both active and passive cycling. In contrast, there was stronger high γ band activity for active cycling. Notably, the effects of active and passive cycling were all independent of cadence. Finally, ß suppression was stronger for patients with freezing of gait, especially during passive cycling. CONCLUSIONS: Our results provide evidence for a link between proprioceptive input during cycling and ß suppression. These findings support the role of continuous external sensory input and proprioceptive feedback during rhythmic passive cycling movements and suggest that systematic passive mobilization might hold therapeutic potential. © 2023 International Parkinson and Movement Disorder Society.


Assuntos
Estimulação Encefálica Profunda , Transtornos Neurológicos da Marcha , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Doença de Parkinson/terapia , Doença de Parkinson/complicações , Transtornos Neurológicos da Marcha/etiologia , Caminhada , Marcha/fisiologia , Estimulação Encefálica Profunda/métodos , Ritmo beta/fisiologia
18.
Mov Disord ; 39(6): 1048-1053, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38477413

RESUMO

BACKGROUND: Gait disorders in patients with Parkinson's disease (PD) can become disabling with disease progression without effective treatment. OBJECTIVES: To investigate the efficacy of intermittent θ burst trans-spinal magnetic stimulation (TsMS) in PD patients with gait and balance disorders. METHODS: This was a randomized, parallel, double-blind, controlled trial. Active or sham TsMS was applied at third thoracic vertebra with 100% of the trans-spinal motor threshold, during 5 consecutive days. Participants were evaluated at baseline, immediately after last session, 1 and 4 weeks after last session. Primary outcome was Total Timed Up and Go (TUG) values comparing active versus sham phases 1 week after intervention. The secondary outcome measurements consisted of motor, gait and balance scales, and questionnaires for quality of life and cognition. RESULTS: Thirty-three patients were included, average age 68.5 (6.4) years in active group and 70.3 (6.3) years in sham group. In active group, Total TUG mean baseline was 107.18 (95% CI, 52.1-116.1), and 1 week after stimulation was 93.0 (95% CI, 50.7-135.3); sham group, Total TUG mean baseline was 101.2 (95% CI, 47.1-155.3) and 1 week after stimulation 75.2 (95% CI 34.0-116.4), P = 0.54. Similarly, intervention had no significant effects on secondary outcome measurements. During stimulation period, five patients presented with mild side effects (three in active group and two in sham group). DISCUSSION: TsMS did not significantly improve gait or balance analysis in patients with PD and gait disorders. The protocol was safe and well tolerated. © 2024 International Parkinson and Movement Disorder Society.


Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Doença de Parkinson/fisiopatologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/terapia , Transtornos Neurológicos da Marcha/fisiopatologia , Método Duplo-Cego , Equilíbrio Postural/fisiologia , Resultado do Tratamento , Qualidade de Vida , Estimulação da Medula Espinal/métodos , Estimulação Magnética Transcraniana/métodos , Marcha/fisiologia , Magnetoterapia/métodos
19.
Mov Disord ; 39(5): 788-797, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38419144

RESUMO

BACKGROUND: With disease-modifying drugs in reach for cerebellar ataxias, fine-grained digital health measures are highly warranted to complement clinical and patient-reported outcome measures in upcoming treatment trials and treatment monitoring. These measures need to demonstrate sensitivity to capture change, in particular in the early stages of the disease. OBJECTIVE: Our aim is to unravel gait measures sensitive to longitudinal change in the-particularly trial-relevant-early stage of spinocerebellar ataxia type 2 (SCA2). METHODS: We performed a multicenter longitudinal study with combined cross-sectional and 1-year interval longitudinal analysis in early-stage SCA2 participants (n = 23, including nine pre-ataxic expansion carriers; median, ATXN2 CAG repeat expansion 38 ± 2; median, Scale for the Assessment and Rating of Ataxia [SARA] score 4.8 ± 4.3). Gait was assessed using three wearable motion sensors during a 2-minute walk, with analyses focused on gait measures of spatio-temporal variability that have shown sensitivity to ataxia severity (eg, lateral step deviation). RESULTS: We found significant changes for gait measures between baseline and 1-year follow-up with large effect sizes (lateral step deviation P = 0.0001, effect size rprb = 0.78), whereas the SARA score showed no change (P = 0.67). Sample size estimation indicates a required cohort size of n = 43 to detect a 50% reduction in natural progression. Test-retest reliability and minimal detectable change analysis confirm the accuracy of detecting 50% of the identified 1-year change. CONCLUSIONS: Gait measures assessed by wearable sensors can capture natural progression in early-stage SCA2 within just 1 year-in contrast to a clinical ataxia outcome. Lateral step deviation represents a promising outcome measure for upcoming multicenter interventional trials, particularly in the early stages of cerebellar ataxia. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Progressão da Doença , Ataxias Espinocerebelares , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Ataxias Espinocerebelares/fisiopatologia , Ataxias Espinocerebelares/genética , Estudos Longitudinais , Estudos Transversais , Marcha/fisiologia , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Transtornos Neurológicos da Marcha/diagnóstico , Ataxina-2/genética
20.
Cerebellum ; 23(4): 1478-1489, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38279000

RESUMO

This study aimed to assess the responsiveness to the rehabilitation of three trunk acceleration-derived gait indexes, namely the harmonic ratio (HR), the short-term longest Lyapunov's exponent (sLLE), and the step-to-step coefficient of variation (CV), in a sample of subjects with primary degenerative cerebellar ataxia (swCA), and investigate the correlations between their improvements (∆), clinical characteristics, and spatio-temporal and kinematic gait features. The trunk acceleration patterns in the antero-posterior (AP), medio-lateral (ML), and vertical (V) directions during gait of 21 swCA were recorded using a magneto-inertial measurement unit placed at the lower back before (T0) and after (T1) a period of inpatient rehabilitation. For comparison, a sample of 21 age- and gait speed-matched healthy subjects (HSmatched) was also included. At T1, sLLE in the AP (sLLEAP) and ML (sLLEML) directions significantly improved with moderate to large effect sizes, as well as SARA scores, stride length, and pelvic rotation. sLLEML and pelvic rotation also approached the HSmatched values at T1, suggesting a normalization of the parameter. HRs and CV did not significantly modify after rehabilitation. ∆sLLEML correlated with ∆ of the gait subscore of the SARA scale (SARAGAIT) and ∆stride length and ∆sLLEAP correlated with ∆pelvic rotation and ∆SARAGAIT. The minimal clinically important differences for sLLEML and sLLEAP were ≥ 36.16% and ≥ 28.19%, respectively, as the minimal score reflects a clinical improvement in SARA scores. When using inertial measurement units, sLLEAP and sLLEML can be considered responsive outcome measures for assessing the effectiveness of rehabilitation on trunk stability during walking in swCA.


Assuntos
Ataxia Cerebelar , Marcha , Tronco , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Tronco/fisiopatologia , Fenômenos Biomecânicos/fisiologia , Idoso , Marcha/fisiologia , Ataxia Cerebelar/reabilitação , Ataxia Cerebelar/fisiopatologia , Adulto , Equilíbrio Postural/fisiologia , Transtornos Neurológicos da Marcha/reabilitação , Transtornos Neurológicos da Marcha/fisiopatologia , Resultado do Tratamento
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