Vibro-tactile stimulation of the neck reduces pain in people with cervical dystonia: a proof-of-concept study.

BACKGROUND: Pain is a common non-motor symptom in patients with cervical dystonia (CD), severely impacting their quality of life. The pathophysiology of CD is incompletely understood but it involves altered processing of proprioceptive and pain signals. OBJECTIVES: The purpose of this proof-of-concept study was to determine if vibro-tactile stimulation (VTS)-a non-invasive form of neuromodulation targeting the somatosensory system-can modulate neck pain in people with CD. METHODS: In a multi-center study, 44 CD patients received VTS to sternocleidomastoid and/or trapezius muscles for up to 45 min under 9 different stimulation conditions that either targeted a single or a pair of muscles. The primary outcome measure was a perceived pain score (PPS) rated by participants on a 100-point analogue scale. RESULTS: During VTS, 29/44 (66%) of participants experienced a reduction in PPS of at least 10% with 17/44 (39%) reporting a reduction in pain of 50% or higher. After VTS cessation, 57% of participants still reported a 10% or higher reduction in PPS. Effects were significant at the group level and persisted for up to 20 min post-treatment. No distinct optimal stimulation profiles were identified for specific CD phenotypes. Clinical markers of disease severity or duration did not predict the degree of VTS-induced pain reduction. CONCLUSION: This proof-of-concept study demonstrates the potential of VTS as a new non-invasive therapeutic option for treating neck pain associated with CD. Further research needs to delineate optimal dosage and long-term effects.

Robot-aided assessment and associated brain lesions of impaired ankle proprioception in chronic stroke.

BACKGROUND: Impaired ankle proprioception strongly predicts balance dysfunction in chronic stroke. However, only sparse data on ankle position sense and no systematic data on ankle motion sense dysfunction in stroke are available. Moreover, the lesion sites underlying impaired ankle proprioception have not been comprehensively delineated. Using robotic technology, this study quantified ankle proprioceptive deficits post-stroke and determined the associated brain lesions. METHODS: Twelve adults with chronic stroke and 13 neurotypical adults participated. A robot passively plantarflexed a participant's ankle to two distinct positions or at two distinct velocities. Participants subsequently indicated which of the two movements was further/faster. Based on the stimulus-response data, psychometric just-noticeable-difference (JND) thresholds and intervals of uncertainty (IU) were derived as measures on proprioceptive bias and precision. To determine group differences, Welch's t-test and the Wilcoxon-Mann-Whitney test were performed for the JND threshold and IU, respectively. Voxel-based lesion subtraction analysis identified the brain lesions associated with observed proprioceptive deficits in adults with stroke. RESULTS: 83% of adults with stroke exhibited abnormalities in either position or motion sense, or both. JND and IU measures were significantly elevated compared to the control group (Position sense: + 77% in JND, + 148% in IU; Motion sense: +153% in JND, + 78% in IU). Adults with stroke with both impaired ankle position and motion sense had lesions in the parietal, frontal, and temporoparietal regions. CONCLUSIONS: This is the first study to document the magnitude and frequency of ankle position and motion sense impairment in adults with chronic stroke. Proprioceptive dysfunction was characterized by elevated JND thresholds and increased uncertainty in perceiving ankle position/motion. Furthermore, the associated cortical lesions for impairment in both proprioceptive senses were largely overlapping.

A robot-aided visuomotor wrist training induces motor and proprioceptive learning that transfers to the untrained ipsilateral elbow.

BACKGROUND: Learning of a visuomotor task not only leads to changes in motor performance but also improves proprioceptive function of the trained joint/limb system. Such sensorimotor learning may show intra-joint transfer that is observable at a previously untrained degrees of freedom of the trained joint. OBJECTIVE: Here, we examined if and to what extent such learning transfers to neighboring joints of the same limb and whether such transfer is observable in the motor as well as in the proprioceptive domain. Documenting such intra-limb transfer of sensorimotor learning holds promise for the neurorehabilitation of an impaired joint by training the neighboring joints. METHODS: Using a robotic exoskeleton, 15 healthy young adults (18-35 years) underwent a visuomotor training that required them to make continuous, increasingly precise, small amplitude wrist movements. Wrist and elbow position sense just-noticeable-difference (JND) thresholds and spatial movement accuracy error (MAE) at wrist and elbow in an untrained pointing task were assessed before and immediately after, as well as 24 h after training. RESULTS: First, all participants showed evidence of proprioceptive and motor learning in both trained and untrained joints. The mean JND threshold decreased significantly by 30% in trained wrist (M: 1.26° to 0.88°) and by 35% in untrained elbow (M: 1.96° to 1.28°). Second, mean MAE in untrained pointing task reduced by 20% in trained wrist and the untrained elbow. Third, after 24 h the gains in proprioceptive learning persisted at both joints, while transferred motor learning gains had decayed to such extent that they were no longer significant at the group level. CONCLUSION: Our findings document that a one-time sensorimotor training induces rapid learning gains in proprioceptive acuity and untrained sensorimotor performance at the practiced joint. Importantly, these gains transfer almost fully to the neighboring, proximal joint/limb system.

Motor training-related brain reorganization in patients with cerebellar degeneration.

Cerebellar degeneration progressively impairs motor function. Recent research showed that cerebellar patients can improve motor performance with practice, but the optimal feedback type (visual, proprioceptive, verbal) for such learning and the underlying neuroplastic changes are unknown. Here, patients with cerebellar degeneration (N = 40) and age- and sex-matched healthy controls (N = 40) practiced single-joint, goal-directed forearm movements for 5 days. Cerebellar patients improved performance during visuomotor practice, but a training focusing on either proprioceptive feedback, or explicit verbal feedback and instruction did not show additional benefits. Voxel-based morphometry revealed that after training gray matter volume (GMV) was increased prominently in the visual association cortices of controls, whereas cerebellar patients exhibited GMV increase predominantly in premotor cortex. The premotor cortex as a recipient of cerebellar efferents appears to be an important hub in compensatory remodeling following damage of the cerebro-cerebellar motor system.

Neurostructural changes and declining sensorimotor function due to cerebellar cortical degeneration.

Neurodegeneration of the cerebellum progresses over years and primarily affects cerebellar cortex. It leads to a progressive loss of control and coordination of gait, posture, speech, fine motor, and oculomotor function. Yet, little is known how the cerebro-cerebellar network compensates for the loss in cerebellar cortical neurons. To address this knowledge gap, we examined 30 people with cerebellar cortical degeneration and a group of 30 healthy controls. We assessed visuomotor performance during a forearm-pointing task to 10°, 25°, and 50° targets. In addition, using MRI imaging, we determined neurodegenerative-induced changes in gray matter volume (GMV) in the cerebro-cerebellar network and correlated them to markers of motor performance. The main results are as follows: first, the relative joint position error (RJPE) during pointing was significantly greater in the ataxia group for all targets confirming the expected motor control deficit. Second, in the ataxia group, GMV was significantly reduced in cerebellar cortex but increased in the deep cerebellar nuclei. Motor error (RJPE) correlated negatively with decreased cerebellar GMV but positively with increased GMV in supplementary motor area (SMA) and premotor cortex. GMV of the deep cerebellar nuclei did not correlate significantly with markers of motor performance. We discuss whether the GMV changes in the cerebellar output nuclei and the extracerebellar efferent targets in secondary motor cortex can be understood as a central compensatory response to the neurodegeneration of the cerebellar cortex.NEW & NOTEWORTHY Neurodegeneration of the cerebellum progresses over years and primarily affects cerebellar cortex. It leads to a progressive loss of control and coordination of movement. We here show that the neurodegenerative process not only leads to cells loss in cerebellar cortex but also induces neurostructural changes in the form of increased gray matter in the efferent targets of the cerebellar cortex, namely, the cerebellar output nuclei, the SMA, and premotor cortex.

Effects of a robot-aided somatosensory training on proprioception and motor function in stroke survivors.

BACKGROUND: Proprioceptive deficits after stroke are associated with poor upper limb function, slower motor recovery, and decreased self-care ability. Improving proprioception should enhance motor control in stroke survivors, but current evidence is inconclusive. Thus, this study examined whether a robot-aided somatosensory-based training requiring increasingly accurate active wrist movements improves proprioceptive acuity as well as motor performance in chronic stroke. METHODS: Twelve adults with chronic stroke completed a 2-day training (age range: 42-74 years; median time-after-stroke: 12 months; median Fugl-Meyer UE: 65). Retention was assessed at Day 5. Grasping the handle of a wrist-robotic exoskeleton, participants trained to roll a virtual ball to a target through continuous wrist adduction/abduction movements. During training vision was occluded, but participants received real-time, vibro-tactile feedback on their forearm about ball position and speed. Primary outcome was the just-noticeable-difference (JND) wrist position sense threshold as a measure of proprioceptive acuity. Secondary outcomes were spatial error in an untrained wrist tracing task and somatosensory-evoked potentials (SEP) as a neural correlate of proprioceptive function. Ten neurologically-intact adults were recruited to serve as non-stroke controls for matched age, gender and hand dominance (age range: 44 to 79 years; 6 women, 4 men). RESULTS: Participants significantly reduced JND thresholds at posttest and retention (Stroke group: pretest: mean: 1.77° [SD: 0.54°] to posttest mean: 1.38° [0.34°]; Control group: 1.50° [0.46°] to posttest mean: 1.45° [SD: 0.54°]; F[2,37] = 4.54, p = 0.017, ηp2 = 0.20) in both groups. A higher pretest JND threshold was associated with a higher threshold reduction at posttest and retention (r = - 0.86, - 0.90, p ≤ 0.001) among the stroke participants. Error in the untrained tracing task was reduced by 22 % at posttest, yielding an effect size of w = 0.13. Stroke participants exhibited significantly reduced P27-N30 peak-to-peak SEP amplitude at pretest (U = 11, p = 0.03) compared to the non-stroke group. SEP measures did not change systematically with training. CONCLUSIONS: This study provides proof-of-concept that non-visual, proprioceptive training can induce fast, measurable improvements in proprioceptive function in chronic stroke survivors. There is encouraging but inconclusive evidence that such somatosensory learning transfers to untrained motor tasks. Trial registration Clinicaltrials.gov; Registration ID: NCT02565407; Date of registration: 01/10/2015; URL: https://clinicaltrials.gov/ct2/show/NCT02565407 .

Robot-aided developmental assessment of wrist proprioception in children.

BACKGROUND: Several neurodevelopmental disorders and brain injuries in children have been associated with proprioceptive dysfunction that will negatively affect their movement. Unfortunately, there is lack of reliable and objective clinical examination protocols and our current knowledge of how proprioception evolves in typically developing children is still sparse. METHODS: Using a robotic exoskeleton, we investigated proprioceptive acuity of the wrist in a group of 49 typically developing healthy children (8-15 years), and a group of 40 young adults. Without vision participants performed an ipsilateral wrist joint position matching task that required them to reproduce (match) a previously experienced target position. All three joint degrees-of-freedom of the wrist/hand complex were assessed. Accuracy and precision were evaluated as a measure of proprioceptive acuity. The cross-sectional data indicating the time course of development of acuity were then fitted by four models in order to determine which function best describes developmental changes in proprioception across age. RESULTS: First, the robot-aided assessment proved to be an easy to administer method for objectively measuring proprioceptive acuity in both children and adult populations. Second, proprioceptive acuity continued to develop throughout middle childhood and early adolescence, improving by more than 50% with respect to the youngest group. Adult levels of performance were reached approximately by the age of 12 years. An inverse-root function best described the development of proprioceptive acuity across the age groups. Third, wrist/forearm proprioception is anisotropic across the three DoFs with the Abduction/Adduction exhibiting a higher level of acuity than those of Flexion/extension and Pronation/Supination. This anisotropy did not change across development. CONCLUSIONS: Proprioceptive development for the wrist continues well into early adolescence. Our normative data obtained trough this novel robot-aided assessment method provide a basis against which proprioceptive function of pediatric population can be compared. This may aid the design of more effective sensorimotor intervention programs.

Brain changes associated with postural training in patients with cerebellar degeneration: a voxel-based morphometry study.

Recent research indicates that physiotherapy can improve motor performance of patients with cerebellar degeneration. Given the known contributions of the cerebellum to motor learning, it remains unclear whether such observable changes in performance are mediated by the cerebellum or cerebral brain areas involved in motor control and learning. The current study addressed this question by assessing the increase in gray matter volume due to sensorimotor training in cerebellar patients using voxel-based morphometry. Nineteen human subjects with pure cerebellar degeneration and matched healthy controls were trained for 2 weeks on a balance task. Postural and clinical assessments along with structural magnetic resonance imaging were performed pretraining and post-training. The main findings were as follows. First, training enhanced balance performance in cerebellar patients. Second, in contrast to controls patients revealed significantly more post-training gray matter volume in the dorsal premotor cortex. Third, training-related increase in gray matter volume was observed within the cerebellum and was more pronounced in controls than in patients. However, statistically cerebellar changes were at the trend level and thus require additional, independent confirmation. We conclude that sensorimotor training of patients with cerebellar neurodegeneration induces gray matter changes primarily within nonaffected neocortical regions of the cerebellar-cortical loop. Residual function of the cerebellum appears to be exploited suggesting either a recovery from degeneration or intact processes of cerebellar plasticity in the remaining healthy tissue.

Subthalamic nucleus deep brain stimulation improves somatosensory function in Parkinson's disease.

An established treatment for the motor symptoms of Parkinson's disease (PD) is deep brain stimulation (DBS) of the subthalamic nucleus (STN). Mounting evidence suggests that PD is also associated with somatosensory deficits, yet the effect of STN-DBS on somatosensory processing is largely unknown. This study investigated whether STN-DBS affects somatosensory processing, specifically the processing of tactile and proprioceptive cues, by systematically examining the accuracy of haptic perception of object size. (Haptic perception refers to one's ability to extract object features such as shape and size by active touch.) Without vision, 13 PD patients with implanted STN-DBS and 13 healthy controls haptically explored the heights of 2 successively presented 3-dimensional (3D) blocks using a precision grip. Participants verbally indicated which block was taller and then used their nonprobing hand to motorically match the perceived size of the comparison block. Patients were tested during ON and OFF stimulation, following a 12-hour medication washout period. First, when compared to controls, the PD group's haptic discrimination threshold during OFF stimulation was elevated by 192% and mean hand aperture error was increased by 105%. Second, DBS lowered the haptic discrimination threshold by 26% and aperture error decreased by 20%. Third, during DBS ON, probing with the motorically more affected hand decreased haptic precision compared to probing with the less affected hand. This study offers the first evidence that STN-DBS improves haptic precision, further indicating that somatosensory function is improved by STN-DBS. We conclude that DBS-related improvements are not explained by improvements in motor function alone, but rather by enhanced somatosensory processing.

A Physically Active Lifestyle Can Protect against Age-Related Decline in Ankle Proprioception.

This study examined whether physically active middle-aged (50-64 years) and older adults (65-80 years) demonstrate age-related ankle proprioceptive decline relative to younger counterparts. Empirical data indicate that ankle proprioception declines with aging and such sensory decline negatively affects balance. Using a passive motion apparatus, we employed a psychophysical forced-choice paradigm in which the ankle was passively plantarflexed to a reference position (15° or 25°) and a comparison position that was always smaller than the reference. Subsequently, participants indicated which position was more plantarflexed. As outcome measures of ankle position sense acuity, a just-noticeable-difference (JND) threshold and the uncertainty area (UA) were derived from the psychometric stimulus-response difference function for each participant. The JND threshold is a measure of proprioceptive bias and UA constitutes a measure of precision. The main results are: First, at the 15° reference, most middle-aged (74%) and older adults (71%) had thresholds within the range of the young adults. The respective median JND threshold of young adults was statistically lower when compared to both older groups. Second, no differences between age groups were observed at the 25° reference. Third, no age-related differences were found for UA at either reference. These data indicate that physically active aging adults may be spared from age-related decline in ankle position sense and that age-related differences emerge for small ankle displacements. The findings underscore the importance of remaining active during aging.

Dyad motor learning in a wrist-robotic environment: Learning together is better than learning alone.

OBJECTIVE: Dyad motor practice is characterized by two learners alternating between physical and observational practice, which can lead to better motor outcomes and reduce practice time compared to physical practice alone. Robot-assisted therapy has become an established neurorehabilitation tool but is limited by high therapy cost and access. Implementing dyad practice in robot-assisted rehabilitation has the potential to improve therapeutic outcomes and/or to achieve them faster. This study aims to determine the effects of dyad practice on motor performance in a wrist-robotic environment to evaluate its potential use in robotic rehabilitation settings. METHODS: Forty-two healthy participants (18-35 years) were randomized into three groups (n = 14): Dyad practice, physical practice with rest and physical practice without rest. Participants practiced a 2 degree-of-freedom gamified wrist movement task for 20 trials using a custom-made wrist robotic device. A motor performance score (MPS) that captured temporal and spatial time-series kinematics was computed at baseline, the end of training and 24 h later to assess retention. RESULTS: MPS did not differ between groups at baseline. All groups revealed significant performance gains by the end of training. However, dyads outperformed the other groups at the end of training (p < 0.001) and showed higher retention after 24-h (p = 0.02). Median MPS improved by 46.5% in dyads, 25.3% in physical practice-rest, and 33.6% in physical practice-no rest at the end of training compared to baseline. CONCLUSION: Compared to physical practice alone, dyad practice leads to superior motor outcomes in a robot-assisted motor learning task. Dyads still outperformed their counterparts 24-h after practice. IMPACT STATEMENT: Improving motor function in complex motor tasks without increasing required practice time, dyad practice can optimize therapeutic resources. This is particularly impactful in robot-assisted rehabilitation regimens as it would help to improve patients' outcomes and increase care efficiency.

Ankle proprioception in children with cerebral palsy.

PURPOSE: There is no established clinical standard to evaluate ankle proprioception in children with cerebral palsy (CP). This study compared ankle position sense of children with CP to age-matched children who are typically developing (TD). METHODS: Children aged 6-17 years participated (15 CP, 58 TD). Using a custom-built device, the ankle was passively rotated to two positions for 25 trials. Using a psychophysical forced-choice paradigm, participants indicated which position was more plantarflexed. A psychometric function was fitted to the response data to determine the just noticeable difference (JND) threshold and the associated uncertainty (random error) for ankle position sense. RESULTS: Median JND thresholds for the CP group were elevated (CP: 4.3°, TD: 3.0°). Three children with CP exceeded the 95th percentile of TD. No differences in random error were found. CONCLUSION: This method assessed ankle proprioception relative to norm data and identified position sense impairments in children with CP. Using this method can provide data on proprioceptive status in CP, augmenting the assessment of motor impairment.

Effects of an 11-week vibro-tactile stimulation treatment on voice symptoms in laryngeal dystonia.

Background: Laryngeal dystonia is a task-specific focal dystonia of laryngeal muscles that impairs speech and voice production. At present, there is no cure for LD. The most common therapeutic option for patients with LD involves Botulinum neurotoxin injections. Objective: Provide empirical evidence that non-invasive vibro-tactile stimulation (VTS) of the skin over the voice box can provide symptom relief to those affected by LD. Methods: Single-group 11-week randomized controlled trial with a crossover between two dosages (20 min of VTS once or 3 times per week) self-administered in-home in two 4-week blocks. Acute effects of VTS on voice and speech were assessed in-lab at weeks 1, 6 and 11. Participants were randomized to receive either 40 Hz or 100 Hz VTS. Main outcome measures: Primary: smoothed cepstral peak prominence (CPPS) of the voice signal to quantify voice and speech abnormalities, and perceived speech effort (PSE) ranked by participants as a measure of voice effort (scale 1-10). Secondary: number of voice breaks during continuous speech, the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) inventory as a measure of overall disease severity and the Voice Handicap Index 30-item self report. Results: Thirty-nine people with a confirmed diagnosis of adductor-type LD (mean [SD] age, 60.3 [11.3] years; 18 women and 21 men) completed the study. A single application of VTS improved voice quality (median CPPS increase: 0.41 dB, 95% CI [0.20, 0.61]) and/or reduced voice effort (PSE) by at least 30% in up to 57% of participants across the three study visits. Effects lasted from less than 30 min to several days. There was no effect of dosage and no evidence that the acute therapeutic effects of VTS increased or decreased longitudinally over the 11-week study period. Both 100 and 40 Hz VTS induced measurable improvements in voice quality and speech effort. VTS induced an additional benefit to those receiving Botulinum toxin. Participants, not receiving Botulinum treatment also responded to VTS. Conclusion: This study provides the first systematic empirical evidence that the prolonged use of laryngeal VTS can induce repeatable acute improvements in voice quality and reductions of voice effort in LD. Clinical trial registration: ClinicalTrials.gov ID: NCT03746509.

Parkinson's disease accelerates age-related decline in haptic perception by altering somatosensory integration.

This study investigated how Parkinson's disease alters haptic perception and the underlying mechanisms of somatosensory and sensorimotor integration. Changes in haptic sensitivity and acuity (the abilities to detect and to discriminate between haptic stimuli) due to Parkinson's disease were systematically quantified and contrasted to the performance of healthy older and young adults. Using a robotic force environment, virtual contours of various curvatures were presented. Participants explored these contours with their hands and indicated verbally whether they could detect or discriminate between two contours. To understand what aspects of sensory or sensorimotor integration are altered by ageing and disease, we manipulated the sensorimotor aspect of the task: the robot either guided the hand along the contour or the participant actively moved the hand. Active exploration relies on multimodal sensory and sensorimotor integration, while passive guidance only requires sensory integration of proprioceptive and tactile information. The main findings of the study are as follows: first, a decline in haptic precision can already be observed in adults before the age of 70 years. Parkinson's disease may lead to an additional decrease in haptic sensitivity well beyond the levels typically seen in middle-aged and older adults. Second, the haptic deficit in Parkinson's disease is general in nature. It becomes manifest as a decrease in sensitivity and acuity (i.e. a smaller perceivable range and a diminished ability to discriminate between two perceivable haptic stimuli). Third, thresholds during both active and passive exploration are elevated, but not significantly different from each other. That is, active exploration did not enhance the haptic deficit when compared to passive hand motion. This implies that Parkinson's disease affects early stages of somatosensory integration that ultimately have an impact on processes of sensorimotor integration. Our results suggest that the known motor problems in Parkinson's disease that are generally characterized as a failure of sensorimotor integration may, in fact, have a sensory origin.

Typical Development of Finger Position Sense From Late Childhood to Adolescence.

Finger position sense is a proprioceptive modality highly important for fine motor control. Its developmental time course is largely unknown. This cross-sectional study examined its typical development in 138 children (8-17 years) and a group of 14 healthy young adults using a fast and novel psychophysical test that yielded objective measures of position sense acuity. Participants placed their hands underneath a computer tablet and judged the perceived position of their unseen index finger relative to two visible areas displayed on a tablet following a two-forced-choice paradigm. Responses were fitted to a psychometric acuity function from which the difference between the point-of-subjective-equality and the veridical finger position (ΔPSE) was derived as a measure of position sense bias, and the uncertainty area (UA) as a measure of precision. The main results are: First, children under 12 exhibited a significantly greater UA than adults while adolescent children (13-17 years) exhibited no significant differences when compared to adults. Second, no significant age-related differences in ΔPSE were found across the age range of 8-17 years. This implies that the typical development of finger position sense from late childhood to adulthood is characterized as an age-dependent increase in proprioceptive precision and not as a decrease in bias.

A Robotic Device for Measuring Human Ankle Motion Sense.

Proprioceptive signals about ankle motion are essential for the control of balance and gait. However, objective, accurate methods for testing ankle motion sense in clinical settings are not established. This study presents a fast and accurate method to assess human ankle motion sense acuity. A one degree-of-freedom (DOF) robotic device was used to passively rotate the ankle under controlled conditions and applied a psychophysical forced-choice paradigm. Twenty healthy participants were recruited for study participation. Within a trial, participants experienced one of three reference velocities (10°/s, 15°/s, and 20°/s), and a smaller comparison velocity. Subsequently, they verbally indicated which of the two movements was faster. As outcome measures, a just-noticeable-difference (JND) threshold and interval of uncertainty (IU) were derived from the psychometric stimulus-response difference function for each participant. Our data show that mean JND threshold increased almost linearly from 0.53°/s at the 10°/s reference to 1.6°/s at 20°/s ( ). Perceptual uncertainty increased similarly (median IU = 0.33°/s at 10°/s and 0.97°/s at 20°/s; ). Both measures were strongly correlated ( r s = 0.70). This implies that the bias of the human ankle motion sense is approximately 5 - 8% of the experienced movement velocity. We demonstrate that this robot-aided test produces quantitative data on human ankle motion sense acuity. It provides a useful addition to the current measures of ankle proprioceptive function.

Atypical Activation of Laryngeal Somatosensory-Motor Cortex During Vocalization in People With Unexplained Chronic Cough.

Importance: Unexplained chronic cough is common and has substantial negative quality-of-life implications, yet its causes are not well understood. A better understanding of how peripheral and central neural processes contribute to chronic cough is essential for treatment design. Objective: To determine if people with chronic cough exhibit signs of abnormal neural processing over laryngeal sensorimotor cortex during voluntary laryngeal motor activity such as vocalization. Design, Setting, and Participants: This was a cross-sectional study of a convenience sample of participants with chronic cough and healthy participants. Testing was performed in an acoustically and electromagnetically shielded chamber. In a single visit, electroencephalographic (EEG) signals were recorded from participants with chronic cough and healthy participants during voice production. The chronic cough group participants presented with unexplained cough of 8 weeks or longer duration with prior medical evaluation including negative results of chest imaging. None of the participants had a history of any neurologic disease known to impair vocalization or swallowing. Data collection for the healthy control group occurred from February 2 to June 28, 2018, and for the chronic cough group, from November 22, 2021, to June 21, 2022. Data analysis was performed from May 1 to October 30, 2022. Exposure: Participants with or without chronic cough. Main Outcome Measures: Event-related spectral perturbation over the laryngeal area of somatosensory-motor cortex from 0 to 30 Hz (ie, θ, α, and ß bands) and event-related coherence as a measure of synchronous activity between somatosensory and motor cortical regions. Results: The chronic cough group comprised 13 participants with chronic cough (mean [SD] age, 63.5 [7.8] years; 9 women and 4 men) and the control group, 10 healthy age-matched individuals (mean [SD] age, 60.3 [13.9] years; 6 women and 4 men). In the chronic cough group, the typical movement-related desynchronization over somatosensory-motor cortex during vocalization was significantly reduced across θ, α, and ß frequency bands when compared with the control group. Conclusions and Relevance: This cross-sectional study found that the typical movement-related suppression of brain oscillatory activity during vocalization is weak or absent in people with chronic cough. Thus, chronic cough affects sensorimotor cortical activity during the asymptomatic voluntary activation of laryngeal muscles.

Identifying body awareness-related brain network changes after Spring Forest Qigong™ practice or P.Volve low-intensity exercise in adults with chronic low back pain: a feasibility Phase I Randomized Clinical Trial.

Background: Chronic low back pain (cLBP) affects the quality of life of 52 million Americans and leads to an enormous personal and economic burden. A multidisciplinary approach to cLBP management is recommended. Since medication has limited efficacy and there are mounting concerns about opioid addiction, the American College of Physicians and American Pain Society recommend non-pharmacological interventions, such as mind and body approaches (e.g., Qigong, yoga, Tai Chi) before prescribing medications. Of those, Qigong practice might be most accessible given its gentle movements and because it can be performed standing, sitting, or lying down. The three available Qigong studies in adults with cLBP showed that Qigong reduced pain more than waitlist and equally well than exercise. Yet, the duration and/or frequency of Qigong practice were low (<12 weeks or less than 3x/week). The objectives of this study were to investigate the feasibility of practicing Spring Forest Qigong™ or performing P.Volve low intensity exercises 3x/week for 12 weeks, feasibility of recruitment, data collection, delivery of the intervention as intended, as well as identify estimates of efficacy on brain function and behavioral outcomes after Qigong practice or exercise. To our knowledge, this is the first study investigating the feasibility of the potential effect of Qigong on brain function in adults with cLBP. Methods: We conducted a feasibility Phase I Randomized Clinical Trial. Of the 36 adults with cLBP recruited between January 2020 and June 2021, 32 were enrolled and randomized to either 12 weeks of remote Spring Forest Qigong™ practice or remote P.Volve low-intensity exercises. Participants practiced at least 3x/week for 41min/session with online videos. Our main outcome measures were the Numeric Pain Rating Scale (highest, average, and lowest cLBP pain intensity levels in the prior week), assessed weekly and fMRI data (resting-state and task-based fMRI tasks: pain imagery, kinesthetic imagery of a Qigong movement, and robot-guided shape discrimination). We compared baseline resting-state connectivity and brain activation during fMRI tasks in adults with cLBP with data from a healthy control group (n=28) acquired in a prior study. Secondary outcomes included measures of function, disability, body awareness, kinesiophobia, balance, self-efficacy, core muscle strength, and ankle proprioceptive acuity with a custom-build device. Results: Feasibility of the study design and methods was demonstrated with 30 participants completing the study (94% retention) and reporting high satisfaction with the programs; 96% adherence to P.Volve low-intensity exercises, and 128% of the required practice intensity for Spring Forest Qigong™ practice. Both groups saw promising reductions in low back pain (effect sizes Cohen's d =1.01-2.22) and in most other outcomes ( d =0.90-2.33). Markers of ankle proprioception were not significantly elevated in the cLBP group after the interventions. Brain imaging analysis showed weaker parietal operculum and insula network connectivity in adults with cLBP (n=26), compared to data from a healthy control group (n=28). The pain imagery task elicited lower brain activation of insula, parietal operculum, angular gyrus and supramarginal gyrus at baseline in adults with cLBP than in healthy adults. Adults with cLBP had lower precentral gyrus activation than healthy adults for the Qigong movement and robot task at baseline. Pre-post brain function changes showed individual variability: Six (out of 13) participants in the Qigong group showed increased activation in the parietal operculum, angular gyrus, supramarginal gyrus, and precentral gyrus during the Qigong fMRI task. Interpretation: Our data indicate the feasibility and acceptability of using Spring Forest Qigong™ practice or P.Volve low-intensity exercises for cLBP relief showing promising results in terms of pain relief and associated symptoms. Our brain imaging results indicated brain function improvements after 12 weeks of Qigong practice in some participants, pointing to the need for further investigation in larger studies. Trial registration number: ClinicalTrials.gov: NCT04164225 .