Cortical neurophysiology of primary isolated dystonia and non-dystonic adults: A meta-analysis.

Transcranial magnetic stimulation (TMS) is a non-invasive method to assess neurophysiology of the primary motor cortex in humans. Dystonia is a poorly understood neurological movement disorder, often presenting in an idiopathic, isolated form across different parts of the body. The neurophysiological profile of isolated dystonia compared to healthy adults remains unclear. We conducted a systematic review with meta-analysis of neurophysiologic TMS measures in people with isolated dystonia to provide a synthesized understanding of cortical neurophysiology associated with isolated dystonia. We performed a systematic database search and data were extracted independently by the two authors. Separate meta-analyses were performed for TMS measures of: motor threshold, corticomotor excitability, short interval intracortical inhibition, cortical silent period, intracortical facilitation and afferent-induced inhibition. Standardized mean differences were calculated using a random effects model to determine overall effect sizes and confidence intervals. Heterogeneity was explored using dystonia type subgroup analysis. The search resulted in 78 studies meeting inclusion criteria, of these 57 studies reported data in participants with focal hand dystonia, cervical dystonia, blepharospasm or spasmodic dysphonia, and were included in at least one meta-analysis. The cortical silent period, short-interval intracortical inhibition and afferent-induced inhibition was found to be reduced in isolated dystonia compared to controls. Reduced GABAergic-mediated inhibition in the primary motor cortex in idiopathic isolated dystonia's suggest interventions targeted to aberrant cortical disinhibition could provide a novel treatment. Future meta-analyses require neurophysiology studies to use homogeneous cohorts of isolated dystonia participants, publish raw data values, and record electromyographic responses from dystonic musculature where possible

Physical activity, sedentary behavior, and barriers to exercise in people living with dystonia

© 2019 McCambridge, Meiring and Bradnam. Background: Dystonia is a neurological movement disorder that presents as sustained or intermittent involuntary muscle contractions causing abnormal postures and movements. Knowledge of dystonia is mostly at the impairment level with minimal understanding of activity and participation limitations. Physical activity (PA) is an important aspect of neurological disease management, with wide-ranging benefits for overall health and quality of life. No studies have quantified PA and sedentary behavior (SB), nor explored barriers to being physically active in people with dystonia. Methods: Participants diagnosed with any form of dystonia completed a mixed-methods anonymous online survey on activity behaviors. The International Physical Activity Questionnaire (IPAQ) and Adult Sedentary Behavior Questionnaire (SBQ) assessed self-reported PA and SB. Barriers to exercise engagement were investigated according to the five-factor social-ecological framework and dystonia-specific questions regarding the impact of exercise on symptoms were included. Results: Two-hundred and sixty-three participants consented to the study (mean (SD) age = 55 (13) years, 76% Female). A large proportion of respondents (40%) reported living with cervical dystonia (CD). Overall, the median (IQR) time spent in walking, moderate, and vigorous activity was 60 (0–120), 120 (15–300), and 0 (0–13) min/day, respectively. SB time during weekdays was 285.0 (157.5–465.0) min/day and 345.0 (195.0–502.5) min/day on weekends. Fifty-five percent of participants were dissatisfied with their current level of PA and 75% reported dystonia had decreased their level of PA. Fifty-seven percent found their symptoms were worsened during exercise though the after-effects on symptoms varied. Fatigue, motor symptoms, pain, and poor balance were commonly cited limiting factors. Qualitative and quantitative data indicated difficulties with more vigorous intensity activity. The common barriers to engagement were personal and governmental factors, such as physical impairments, lack of funding and lack of trained exercise professionals. Conclusion: While more than half of respondents indicated they were not satisfied with their current level of PA, and exercise primarily worsened their dystonia symptoms, most participants were meeting the minimum guidelines. Future studies should incorporate robust objective methods of PA and SB measurement and explore the causal mechanisms underpinning exercise-induced aggravation of dystonic symptoms to further enhance life participation of people living with dystonia

Variation in left posterior parietal-motor cortex interhemispheric facilitation following right parietal continuous theta-burst stimulation in healthy adults

© 2016 IBRO. Spatial neglect is modeled on an imbalance of interhemispheric inhibition (IHI); however evidence is emerging that it may not explain neglect in all cases. The aim of this study was to investigate the IHI imbalance model of visual neglect in healthy adults, using paired pulse transcranial magnetic stimulation to probe excitability of projections from posterior parietal cortex (PPC) to contralateral primary motor cortex (M1) bilaterally. Motor-evoked potentials (MEPs) were recorded from the first dorsal interossei and facilitation was determined as ratio of conditioned to non-conditioned MEP amplitude. A laterality index reflecting the balance of excitability between the two hemispheres was calculated. A temporal order judgment task (TOJ) assessed visual attention. Continuous theta-burst stimulation was used to transiently suppress right parietal cortex activity and the effect on laterality and judgment task measured, along with associations between baseline and post stimulation measures. Stimulation had conflicting results on laterality, with most participants demonstrating an effect in the negative direction with no decrement in the TOJ task. Correlation analysis suggests a strong association between laterality direction and degree of facilitation of left PPC-to right M1 following stimulation (r = .902), with larger MEP facilitation at baseline demonstrating greater reduction (r = -.908). Findings indicate there was relative balance between the cortices at baseline but right PPC suppression did not evoke left PPC facilitation in most participants, contrary to the IHI imbalance model. Left M1 facilitation prior to stimulation may predict an individual's response to continuous theta-burst stimulation of right PPC

Intracortical inhibition is modulated by phase of prosthetic rehabilitation in transtibial amputees

© 2015 Hordacre, Bradnam, Barr, Patritti and Crotty. Reorganization of primary motor cortex (M1) is well-described in long-term lower limb amputees. In contrast cortical reorganization during the rehabilitation period after amputation is poorly understood. Thirteen transtibial amputees and 13 gender matched control participants of similar age were recruited. Transcranial magnetic stimulation was used to assess corticomotor and intracortical excitability of M1 bilaterally. Neurophysiological assessments were conducted at admission, prosthetic casting, first walk and discharge. Gait variability at discharge was assessed as a functional measure. Compared to controls, amputees had reduced short-latency intracortical inhibition (SICI) for the ipsilateral M1 at admission (p = 0.01). Analysis across rehabilitation revealed SICI was reduced for the contralateral M1 at first walk compared to discharge (p = 0.003). For the ipsilateral M1 both short and long-latency intracortical inhibition were reduced at admission (p < 0.05) and prosthetic casting (p < 0.02). Analysis of the neurophysiology and gait function revealed several interesting relationships. For the contralateral M1, reduced inhibition at admission (p = 0.04) and first walk (p = 0.05) was associated with better gait function. For the ipsilateral M1, reduced inhibition at discharge (p = 0.05) was associated with poor gait function. This study characterized intracortical excitability in rehabilitating amputees. A dichotomous relationship between reduced intracortical inhibition for each M1 and gait function was observed at different times. Intracortical inhibition may be an appropriate cortical biomarker of gait function in lower limb amputees during rehabilitation, but requires further investigation. Understanding M1 intracortical excitability of amputees undertaking prosthetic rehabilitation provides insight into brain reorganization in the sub-acute post-amputation period and may guide future studies seeking to improve rehabilitation outcomes

Short-term effects of unilateral lesion of the primary motor cortex (M1) on ipsilesional hand dexterity in adult macaque monkeys

Although the arrangement of the corticospinal projection in primates is consistent with a more prominent role of the ipsilateral motor cortex on proximal muscles, rather than on distal muscles involved in manual dexterity, the role played by the primary motor cortex on the control of manual dexterity for the ipsilateral hand remains a matter a debate, either in the normal function or after a lesion. We, therefore, tested the impact of permanent unilateral motor cortex lesion on the manual dexterity of the ipsilateral hand in 11 macaque monkeys, within a time window of 60 days post-lesion. For comparison, unilateral reversible pharmacological inactivation of the motor cortex was produced in an additional monkey. Manual dexterity was assessed quantitatively based on three motor parameters derived from two reach and grasp manual tasks. In contrast to the expected dramatic, complete deficit of manual dexterity of the contralesional hand that persists for several weeks, the impact on the manual dexterity of the ipsilesional hand was generally moderate (but statistically significant) and, when present, lasted less than 20 days. Out of the 11 monkeys, only 3 showed a deficit of the ipsilesional hand for 2 of the 3 motor parameters, and 4 animals had a deficit for only one motor parameter. Four monkeys did not show any deficit. The reversible inactivation experiment yielded results consistent with the permanent lesion data. In conclusion, the primary motor cortex exerts a modest role on ipsilateral manual dexterity, most likely in the form of indirect hand postural control

A biopsychosocial clinical reasoning model for Western acupuncture

© 2011, © W. S. Maney & Son Ltd 2011. Background: The ‘layering method’, a clinical reasoning model for Western acupuncture, is a theoretical framework based on pain and tissue mechanisms. This focus on the mechanics of disability is a limitation of the original model. From a holistic viewpoint, the psychological status of an individual should be considered in clinical reasoning models. Objectives: The first objective was to summarize the original layering model. The second was to determine mechanisms underlying integration of sensations and emotions in the human brain and their effect on the body via output transfer systems of the autonomic, immune, and endocrine systems. The third objective was to determine whether acupuncture can modulate similar regions in the brain and to formulate appropriate clinical reasoning questions. Major findings: Interoceptive sensory stimuli and emotions are integrated in limbic and frontal brain regions to allow emotional responses to feedback from the body and provide the individual with a ‘sense of self’. A strong connection with brainstem nuclei modulating output transfer systems allows emotions to regulate homeostatic balance. Acupuncture may be interpreted as an interoceptive stimulus by the brain. Neuroscience research has shown that acupuncture can modulate neural activity in similar brain regions to those processing emotional responses to sensory inputs. Conclusions: Acupuncture may influence emotional responses and their impact on the neurobiology of the human body. A biopsychosocial clinical reasoning model based on the modulation of emotional processing in the brain is proposed. This suggests that acupuncture may be used as an adjuvant to other therapies in disorders with a biopsychosocial component

The potential for non-invasive brain stimulation to improve function after amputation

© 2015 Taylor & Francis. Purpose: Lower limb amputee rehabilitation has traditionally focussed on restoration of gait and balance through use of prosthetic limbs and mobility aids. Despite these efforts, some amputees continue to experience difficulties with mastering prosthetic mobility. Emerging techniques in rehabilitation, such as non-invasive brain stimulation (NIBS), may be an appropriate tool to enhance prosthetic rehabilitation outcomes by promoting "normal" brain reorganisation and function. The purpose of this review is to highlight the potential of NIBS to improve functional outcomes for lower limb amputees. Methods: To demonstrate the rationale for applying NIBS to amputees, this study will first review literature regarding human motor control of gait, followed by neurophysiological reorganisation of the motor system after amputation and the relationship between brain reorganisation and gait function. We will conclude by reviewing literature demonstrating application of NIBS to lower limb muscle representations and evidence supportive of subsequent functional improvements. Results: Imaging, brain stimulation and behavioural evidence indicate that the cortex contributes to locomotion in humans. Following amputation both hemispheres reorganise with evidence suggesting brain reorganisation is related to functional outcomes in amputees. Previous studies indicate that brain stimulation techniques can be used to selectively promote neuroplasticity of lower limb cortical representations with improvements in function.Conclusions: We suggest NIBS has the potential to transform lower limb amputee rehabilitation and should be further investigated.Implications for RehabilitationDespite extensive rehabilitation some amputees continue to experience difficulty with prosthetic mobilityBrain reorganisation following amputation has been related to functional outcomes and may be an appropriate target for novel interventionsNon-invasive brain stimulation is a promising tool which has potential to improve functional outcomes for lower limb amputees