The barriers and facilitators to satisfaction with botulinum neurotoxin treatment in people with cervical dystonia: a systematic review.

BACKGROUND: Cervical dystonia (CD) is an isolated, focal, idiopathic dystonia affecting the neck and upper back. CD is usually treated by botulinum neurotoxin (BoNT) injections into the dystonic muscles; however, about 20% of people will discontinue BoNT therapy. This systematic review aimed to determine the barriers to satisfaction and facilitators that could improve satisfaction with BoNT therapy for people with CD. METHODS: A database search for journal articles investigating satisfaction with BoNT treatment in CD identified seven qualitative studies and one randomised controlled trial. Results were grouped into "direct" and "indirect" barriers and facilitators. RESULTS: The most reported direct barrier to satisfaction with BoNT was treatment non-response, reported by up to 66% of participants. Other direct barriers included negative side effects, early wearing-off of treatment effect and inexperience of the treating physician. Indirect barriers included limited accessibility to treatment (including cost) and personal choice. Direct facilitators of satisfaction with BoNT included relief of symptoms and flexible re-treatment intervals. Indirect facilitators included easy accessibility to treatment. CONCLUSIONS: Despite BoNT having a discontinuation rate of only 20%, it appears a much greater proportion of people with CD are dissatisfied with this treatment. As BoNT is currently the main treatment offered to people with CD, efforts to improve treatment response rates, reduce side effects and make treatment more flexible and readily available should be adopted to improve the quality of life for people with CD.

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.

Neurorehabilitation in dystonia: a holistic perspective.

Rehabilitation for isolated forms of dystonia, such as cervical or focal hand dystonia, is usually targeted towards the affected body part and focuses on sensorimotor control and motor retraining of affected muscles. Recent evidence, has revealed people who live with dystonia experience a range of functional and non-motor deficits that reduce engagement in daily activities and health-related quality of life, which should be addressed with therapeutic interventions. These findings support the need for a holistic approach to the rehabilitation of dystonia, where assessment and treatments involve non-motor signs and symptoms, and not just the dystonic body part. Most studies have investigated Cervical Dystonia, and in this population, it is evident there is reduced postural control and walking speed, high fear of falling and actual falls, visual compensation for the impaired neck posture, and a myriad of non-motor symptoms including pain, fatigue, sleep disorders and anxiety and depression. In other populations of dystonia, there is also emerging evidence of falls and reduced vision-related quality of life, along with the inability to participate in physical activity due to worsening of dystonic symptoms during or after exercise. A holistic approach to dystonia would support the management of a wide range of symptoms and signs, that if properly addressed could meaningfully reduce disability and improve quality of life in people living with dystonia.

Neck rotation modulates motor-evoked potential duration of proximal muscle cortical representations in healthy adults.

Transcranial magnetic stimulation (TMS) produces motor-evoked potentials (MEP) used to infer changes in corticomotor excitability. In humans, neck rotation can probe reticulospinal input on corticomotor output. This study investigated the effect of neck rotation on MEP duration in a proximal and distal upper limb muscle and compared responses between rest and preactivation. Single-pulse TMS to motor cortex was used to evoke MEPs at two stimulus intensities in 18 healthy adults (20-40 years). Surface electromyography recorded MEPs from the non-dominant biceps brachii (BB) and first dorsal interosseous (FDI). Participants were seated with the target muscle at rest or 10% preactivated, and head rotated ipsilateral, contralateral, or in neutral position. The primary outcome was MEP tail, defined as the mean difference in MEP duration between active and rest trials. Secondary outcomes were MEP duration and amplitude. MEP tail was modulated by neck rotation in the proximal BB (P = 0.03) but not distal FDI (P > 0.19), with shorter duration during ipsilateral or contralateral rotation relative to neutral. In a neutral neck position, MEP duration was prolonged by muscle preactivation and higher TMS intensities in the FDI and BB (P < 0.03). Neck rotation attenuated the prolongation of MEP duration during preactivation in the BB, but not the FDI. Neck rotation had no effect on MEP amplitude for either muscle (P > 0.05). Modulation of the late portion of the MEP by rotation of the neck could indicate subcortical projections to alpha-motoneuron pools are stronger in proximal than distal upper limb muscles. These findings may have relevance for using MEP duration as a neural biomarker in neurological diseases.

Consensus Paper: Experimental Neurostimulation of the Cerebellum.

The cerebellum is best known for its role in controlling motor behaviors. However, recent work supports the view that it also influences non-motor behaviors. The contribution of the cerebellum towards different brain functions is underscored by its involvement in a diverse and increasing number of neurological and neuropsychiatric conditions including ataxia, dystonia, essential tremor, Parkinson's disease (PD), epilepsy, stroke, multiple sclerosis, autism spectrum disorders, dyslexia, attention deficit hyperactivity disorder (ADHD), and schizophrenia. Although there are no cures for these conditions, cerebellar stimulation is quickly gaining attention for symptomatic alleviation, as cerebellar circuitry has arisen as a promising target for invasive and non-invasive neuromodulation. This consensus paper brings together experts from the fields of neurophysiology, neurology, and neurosurgery to discuss recent efforts in using the cerebellum as a therapeutic intervention. We report on the most advanced techniques for manipulating cerebellar circuits in humans and animal models and define key hurdles and questions for moving forward.

Anodal Direct Current Stimulation of the Cerebellum Reduces Cerebellar Brain Inhibition but Does Not Influence Afferent Input from the Hand or Face in Healthy Adults.

BACKGROUND: The cerebellum controls descending motor commands by outputs to primary motor cortex (M1) and the brainstem in response to sensory feedback. The cerebellum may also modulate afferent input en route to M1 and the brainstem. OBJECTIVE: The objective of this study is to determine if anodal transcranial direct current stimulation (tDCS) to the cerebellum influences cerebellar brain inhibition (CBI), short afferent inhibition (SAI) and trigeminal reflexes (TRs) in healthy adults. METHODS: Data from two studies evaluating effects of cerebellar anodal and sham tDCS are presented. The first study used a twin coil transcranial magnetic stimulation (TMS) protocol to investigate CBI and combined TMS and cutaneous stimulation of the digit to assess SAI. The second study evaluated effects on trigemino-cervical and trigemino-masseter reflexes using peripheral nerve stimulation of the face. RESULTS: Fourteen right-handed healthy adults participated in experiment 1. CBI was observed at baseline and was reduced by anodal cerebellar DCS only (P < 0.01). There was SAI at interstimulus intervals of 25 and 30 ms at baseline (both P < 0.0001), but cerebellar tDCS had no effect. Thirteen right-handed healthy adults participated in experiment 2. Inhibitory reflexes were evoked in the ipsilateral masseter and sternocleidomastoid muscles. There was no effect of cerebellar DCS on either reflex. CONCLUSIONS: Anodal DCS reduced CBI but did not change SAI or TRs in healthy adults. These results require confirmation in individuals with neurological impairment.

Ipsilateral corticomotor excitability is associated with increased gait variability in unilateral transtibial amputees.

Ipsilateral primary motor cortex (M1) reorganisation after unilateral lower-limb amputation may degrade function of the amputated limb. We hypothesised unilateral lower-limb amputees would have a bilateral increase in corticomotor excitability, and increased excitability of ipsilateral M1 would be associated with increased step-time variability during gait. Twenty transtibial amputees (16 male) aged 60.1 years (range 45-80 years), and 20 age- and gender-matched healthy adult controls were recruited. Single-pulse transcranial magnetic stimulation assessed corticomotor excitability. Two indices of corticomotor excitability were calculated. An index of corticospinal excitability (ICE) determined relative excitability of ipsilateral and contralateral corticomotor projections to alpha-motoneurons innervating the quadriceps muscle (QM) of the amputated limb. A laterality index (LI) assessed relative excitability of contralateral projections from each hemisphere. Spatial-temporal gait analysis was performed to calculate step-time variability. Amputees had lower ICE values, indicating relatively greater excitability of ipsilateral corticomotor projections than controls (P = 0.04). A lower ICE value was associated with increased step-time variability for amputated (P = 0.04) and non-amputated limbs (P = 0.02). This association suggests corticomotor projections from ipsilateral M1 to alpha-motoneurons innervating the amputated limb QM may interfere with gait. Cortical excitability in amputees was not increased bilaterally, contrary to our hypothesis. There was no difference in excitability of contralateral M1 between amputees and controls (P = 0.10), and no difference in LI (P = 0.71). It appears both hemispheres control one QM, with predominance of contralateral corticomotor excitability in healthy adults. Following lower-limb amputation, putative ipsilateral corticomotor excitability is relatively increased in some amputees and may negatively impact on function.

Contralesional hemisphere control of the proximal paretic upper limb following stroke.

Cathodal transcranial direct current stimulation (c-tDCS) can reduce excitability of neurons in primary motor cortex (M1) and may facilitate motor recovery after stroke. However, little is known about the neurophysiological effects of tDCS on proximal upper limb function. We hypothesized that suppression of contralesional M1 (cM1) excitability would produce neurophysiological effects that depended on the severity of upper limb impairment. Twelve patients with varying upper limb impairment after subcortical stroke were assessed on clinical scales of upper limb spasticity, impairment, and function. Magnetic resonance imaging was used to determine lesion size and fractional anisotropy (FA) within the posterior limbs of the internal capsules indicative of corticospinal tract integrity. Excitability within paretic M1 biceps brachii representation was determined from motor-evoked potentials during selective isometric tasks, after cM1 sham stimulation and after c-tDCS. These neurophysiological data indicate that c-tDCS improved selective proximal upper limb control for mildly impaired patients and worsened it for moderate to severely impaired patients. The direction of the neurophysiological after effects of c-tDCS was strongly related to upper limb spasticity, impairment, function, and FA asymmetry between the posterior limbs of the internal capsules. These results indicate systematic variation of cM1 for proximal upper limb control after stroke and that suppression of cM1 excitability is not a "one size fits all" approach.

Cathodal transcranial direct current stimulation suppresses ipsilateral projections to presumed propriospinal neurons of the proximal upper limb.

This study investigated whether cathodal transcranial direct current stimulation (c-tDCS) of left primary motor cortex (M1) modulates excitability of ipsilateral propriospinal premotoneurons (PNs) in healthy humans. Transcranial magnetic stimulation (TMS) of the right motor cortex was used to obtain motor evoked potentials (MEPs) from the left biceps brachii (BB) while participants maintained contraction of the left BB. To examine presumed PN excitability, left BB MEPs were compared with those conditioned by median nerve stimulation (MNS) at the left elbow. Interstimulus intervals between TMS and MNS were set to produce summation at the C3-C4 level of the spinal cord. MNS facilitated BB MEPs elicited at TMS intensities near active motor threshold but inhibited BB MEPs at slightly higher intensities, indicative of putative PN modulation. c-tDCS suppressed the facilitatory and inhibitory effects of MNS. Sham tDCS did not alter either component. There was no effect of c-tDCS and sham tDCS on nonconditioned left BB MEPs or on the ipsilateral silent period of left BB. Right first dorsal interosseous MEPs were suppressed by c-tDCS. These results indicate that M1 c-tDCS can be used to modulate excitability of ipsilateral projections to presumed PNs controlling the proximal arm muscle BB. This technique may hold promise for promoting motor recovery of proximal upper limb function after stroke.

Cathodal transcranial direct current stimulation of the primary motor cortex improves selective muscle activation in the ipsilateral arm.

Proximal upper limb muscles are represented bilaterally in primary motor cortex. Goal-directed upper limb movement requires precise control of proximal and distal agonist and antagonist muscles. Failure to suppress antagonist muscles can lead to abnormal movement patterns, such as those commonly experienced in the proximal upper limb after stroke. We examined whether noninvasive brain stimulation of primary motor cortex could be used to improve selective control of the ipsilateral proximal upper limb. Thirteen healthy participants performed isometric left elbow flexion by contracting biceps brachii (BB; agonist) and left forearm pronation (BB antagonist) before and after 20 min of cathodal transcranial direct current stimulation (c-tDCS) or sham tDCS of left M1. During the tasks, motor evoked potentials (MEPs) in left BB were acquired using single-pulse transcranial magnetic stimulation of right M1 150-270 ms before muscle contraction. As expected, left BB MEPs were facilitated before flexion and suppressed before pronation. After c-tDCS, left BB MEP amplitudes were reduced compared with sham stimulation, before pronation but not flexion, indicating that c-tDCS enhanced selective muscle activation of the ipsilateral BB in a task-specific manner. The potential for c-tDCS to improve BB antagonist control correlated with BB MEP amplitude for pronation relative to flexion, expressed as a selectivity ratio. This is the first demonstration that selective muscle activation in the proximal upper limb can be improved after c-tDCS of ipsilateral M1 and that the benefits of c-tDCS for selective muscle activation may be most effective in cases where activation strategies are already suboptimal. These findings may have relevance for the use of tDCS in rehabilitation after stroke.

Can Transcranial Direct Current Stimulation Enhance Poststroke Motor Recovery? Development of a Theoretical Patient-Tailored Model.

New treatments that can facilitate neural repair and reduce persistent impairments have significant value in promoting recovery following stroke. One technique that has gained interest is transcranial direct current stimulation (tDCS) as early research suggested it could enhance plasticity and enable greater behavioral recovery. However, several studies have now identified substantial intersubject variability in response to tDCS and clinical trials revealed insufficient evidence of treatment effectiveness. A possible explanation for the varied and negative findings is that the physiologic model of stroke recovery that researchers have used to guide the application of tDCS-based treatments in stroke is overly simplistic and does not account for stroke heterogeneity or known determinants that affect the tDCS response. Here, we propose that tDCS could have a more clearly beneficial role in enhancing stroke recovery if greater consideration is given to individualizing treatment. By critically reviewing the proposed mechanisms of tDCS, stroke physiology across the recovery continuum, and known determinants of tDCS response, we propose a new, theoretical, patient-tailored approach to delivering tDCS after stroke. The proposed model includes a step-by-step principled selection strategy for identifying optimal neuromodulation targets and outlines key areas for further investigation. Tailoring tDCS treatment to individual neuroanatomy and physiology is likely our best chance at producing robust and meaningful clinical benefit for people with stroke and would therefore accelerate opportunities for clinical translation.

Theta burst stimulation of human primary motor cortex degrades selective muscle activation in the ipsilateral arm.

This study investigated whether repetitive transcranial magnetic stimulation (TMS) delivered as continuous theta burst stimulation (cTBS) to left M1 degraded selective muscle activation in the contralateral and ipsilateral upper limb in healthy participants. Contralateral motor-evoked potentials (cMEPs) were elicited in left and right biceps brachii (BB) before either elbow flexion or forearm pronation. A neurophysiological index, the excitability ratio (ER), was computed from the relative size of BB cMEPs before each type of movement. Short interval intracortical inhibition (SICI) was assessed in cMEPs of right BB with paired-pulse TMS of left M1. Ipsilateral MEPs (iMEPs) and silent periods (iSPs) were measured in left BB with single-pulse TMS of left M1. Low-intensity cTBS was expected to suppress corticospinal output from left M1. A sham condition was also included. Real but not sham cTBS caused increases in BB ER bilaterally. In the right arm, ER increased because BB cMEPs before flexion were less facilitated, whereas cMEPs in the pronation task were unaffected. This was accompanied by an increase in left M1 SICI. In the left arm, ER increased because BB cMEPs before pronation were facilitated but were unaffected in the flexion task. There was also facilitation of left BB iMEPs. These changes in the left arm are consistent with inappropriate facilitation of left BB α-motoneurons (αMNs) before pronation. This is the first demonstration that cTBS of M1 can alter excitability of neurons controlling ipsilateral proximal musculature and degrade ipsilateral upper limb motor control, providing evidence that ipsilateral and contralateral M1 shape the spatial and temporal characteristics of proximal muscle activation appropriate for the task at hand.

Task-dependent modulation of inputs to proximal upper limb following transcranial direct current stimulation of primary motor cortex.

Cathodal transcranial DC stimulation (c-tDCS) suppresses excitability of primary motor cortex (M1) controlling contralateral hand muscles. This study assessed whether c-tDCS would have similar effects on ipsi- and contralateral M1 projections to a proximal upper limb muscle. Transcranial magnetic stimulation (TMS) of left M1 was used to elicit motor evoked potentials (MEPs) in the left and right infraspinatus (INF) muscle immediately before and after c-tDCS of left M1, and at 20 and 40 min, post-c-tDCS. TMS was delivered as participants preactivated each INF in isolation (left, right) or both INF together (bilateral). After c-tDCS, ipsilateral MEPs in left INF and contralateral MEPs in right INF were suppressed in the left task but not in the bilateral or right tasks, indicative of task-dependent modulation. Ipsilateral silent period duration in the left INF was reduced after c-tDCS, indicative of altered transcallosal inhibition. These findings may have implications for the use of tDCS as an adjunct to therapy for the proximal upper limb after stroke.

Physical Activity, Sedentary Behavior, and Barriers to Exercise in People Living With Dystonia.

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.

Investigating the mechanisms of acupuncture on neural excitability in healthy adults.

Acupuncture is gaining interest as a potential treatment modality for various neurological conditions. Yet, the underlying mechanisms and efficacy on brain function are not well understood. Therefore, this study investigated the previously proposed hypothesis that acupuncture suppresses motor cortex excitability using transcranial magnetic stimulation (TMS) in healthy adults. The study was randomised, sham-controlled, and double-blinded. Single and paired-pulse TMS was delivered before, during, immediately after, and 30 min after removal of the needle. Acupuncture to the right Hegu acupoint (LI-4) of the hand was delivered by an experienced acupuncturist using standardised manipulations. A disposable (0.22×30 mm, Hwato) needle was used for verum stimulation (penetrating) and a Park retractable needle for sham (nonpenetrating). The peak-to-peak amplitude of TMS-induced motor-evoked potentials was recorded from two intrinsic hand muscles. Needling sensations were quantified using the Massachusett's acupuncture sensation scale. Participant needling sensations were not different between verum or sham acupuncture (P>0.54). Corticomotor excitability, intracortical inhibition, and intracortical facilitation were not modulated by verum or sham acupuncture during, immediately after, or 30 min after, recorded from a local or distant hand muscle to the needling site (all P>0.075). Contrary to previous studies, manual acupuncture did not affect motor cortex excitability in healthy adults. Because of the increasing popularity of acupuncture therapy, further research using patient populations should be considered.

Reorganization of the primary motor cortex following lower-limb amputation for vascular disease: a pre-post-amputation comparison.

PURPOSE: This study compared bilateral corticomotor and intracortical excitability of the primary motor cortex (M1), pre- and post-unilateral transtibial amputation. METHOD: Three males aged 45, 55, and 48 years respectively who were scheduled for elective amputation and thirteen (10 male, 3 female) healthy control participants aged 58.9 (SD 9.8) were recruited. Transcranial magnetic stimulation assessed corticomotor and intracortical excitability of M1 bilaterally. Neurophysiological assessments were performed 10 (SD 7) days prior to surgery and again at 10 (SD 3) days following surgery. Data were analyzed descriptively and objectively compared to 95% confidence intervals from control data. RESULTS: Prior to amputation, all three patients demonstrated stronger short-latency intracortical inhibition evoked from M1 ipsilateral to the affected limb and reduced long-latency intracortical inhibition evoked from M1 contralateral to the affected limb compared to control subjects. Following amputation, short-latency intracortical inhibition was reduced in both M1s and long-latency intracortical inhibition was reduced for the ipsilateral M1. Single-pulse motor evoked potential amplitude and motor thresholds were similar pre-to-post amputation. CONCLUSIONS: Modulation of intracortical excitability shortly following amputation indicates that the cortical environment may be optimized for reorganization in the acute post-amputation period which might be significant for learning to support prosthetic mobility. Implications for Rehabilitation Amputation of a lower-limb is associated with extensive reorganization at the level of the cortex. Reorganization occurs in the acute post-amputation period implying a favorable cortical environment for recovery. Rehabilitation or brain interventions may target the acute pre-prosthetic post-amputation period to optimize recovery.

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

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.

Cerebellar Intermittent Theta-Burst Stimulation and Motor Control Training in Individuals with Cervical Dystonia.

BACKGROUND: There is emerging evidence that cervical dystonia is a neural network disorder with the cerebellum as a key node. The cerebellum may provide a target for neuromodulation as a therapeutic intervention in cervical dystonia. OBJECTIVE: This study aimed to assess effects of intermittent theta-burst stimulation of the cerebellum on dystonia symptoms, quality of life, hand motor dexterity and cortical neurophysiology using transcranial magnetic stimulation. METHODS: Sixteen participants with cervical dystonia were randomised into real or sham stimulation groups. Cerebellar neuromodulation was combined with motor training for the neck and an implicit learning task. The intervention was delivered over 10 working days. Outcome measures included dystonia severity and pain, quality of life, hand dexterity, and motor-evoked potentials and cortical silent periods recorded from upper trapezius muscles. Assessments were taken at baseline and after 5 and 10 days, with quality of life also measured 4 and 12 weeks later. RESULTS: Intermittent theta-burst stimulation improved dystonia severity (Day 5, -5.44 points; p = 0.012; Day 10, -4.6 points; p = 0.025), however, effect sizes were small. Quality of life also improved (Day 5, -10.6 points, p = 0.012; Day 10, -8.6 points, p = 0.036; Week 4, -12.5 points, p = 0.036; Week 12, -12.4 points, p = 0.025), with medium or large effect sizes. There was a reduction in time to complete the pegboard task pre to post intervention (both p < 0.008). Cortical neurophysiology was unchanged by cerebellar neuromodulation. CONCLUSION: Intermittent theta-burst stimulation of the cerebellum may improve cervical dystonia symptoms, upper limb motor control and quality of life. The mechanism likely involves promoting neuroplasticity in the cerebellum although the neurophysiology remains to be elucidated. Cerebellar neuromodulation may have potential as a novel treatment intervention for cervical dystonia, although larger confirmatory studies are required.

Anodal Cerebellar Direct Current Stimulation Reduces Facilitation of Propriospinal Neurons in Healthy Humans.

BACKGROUND: Coordinated muscle synergies in the human upper limb are controlled, in part, by a neural distribution network located in the cervical spinal cord, known as the cervical propriospinal system. Studies in the cat and non-human primate indicate the cerebellum is indirectly connected to this system via output pathways to the brainstem. Therefore, the cerebellum may indirectly modulate excitability of putative propriospinal neurons (PNs) in humans during upper limb coordination tasks. OBJECTIVE/HYPOTHESIS: This study aimed to test whether anodal direct current stimulation (DCS) of the cerebellum modulates PNs and upper limb coordination in healthy adults. The hypothesis was that cerebellar anodal DCS would reduce descending facilitation of PNs and improve upper limb coordination. METHODS: Transcranial magnetic stimulation (TMS), paired with peripheral nerve stimulation, probed activity in facilitatory and inhibitory descending projections to PNs following an established protocol. Coordination was tested using a pursuit rotor task performed by the non-dominant (ipsilateral) hand. Anodal and sham DCS were delivered over the cerebellum ipsilateral to the non-dominant hand in separate experimental sessions. Anodal DCS was applied to a control site lateral to the vertex in a third session. Twelve right-handed healthy adults participated. RESULTS: Pairing TMS with sub-threshold peripheral nerve stimulation facilitated motor evoked potentials at intensities just above threshold in accordance with the protocol. Anodal cerebellar DCS reduced facilitation without influencing inhibition, but the reduction in facilitation was not associated with performance of the pursuit rotor task. CONCLUSIONS: The results of this study indicate dissociated indirect control over cervical PNs by the cerebellum in humans. Anodal DCS of the cerebellum reduced excitability in the facilitatory descending pathway with no effect on the inhibitory pathway to cervical PNs. The reduction in PN excitability is likely secondary to modulation of primary motor cortex or brainstem nuclei, and identifies a neuroanatomical pathway for the cerebellum to assist in coordination of upper limb muscle synergies in humans.

Transcranial non-invasive brain stimulation in swallowing rehabilitation following stroke--a review of the literature.

BACKGROUND: This descriptive review of the literature outlines the current evidence-base underpinning the potential of transcranial brain stimulation techniques to modulate swallowing function in healthy individuals and in treating post-stroke dysphagia. METHODS: Published research was identified by review of scientific databases (Scopus, Medline Ovid, Science Direct, AMED and Google Scholar) using relevant keywords. In addition, the reference lists of identified articles were scrutinized to identify further potentially relevant papers. Studies employing variants of transcranial magnetic or direct current stimulation for the purpose of modulating swallowing motor cortical excitability in healthy participants or dysphagia following stroke were included. Due to a significant heterogeneity in stimulation paradigms, all included studies were summarised and descriptively analysed in relation to the participants tested, cortical representations targeted by brain stimulation and outcome measures used. RESULTS: Seventeen studies met inclusion criteria (seven evaluating healthy participants, 10 evaluating participants presenting with post-stroke dysphagia). Cortical stimulation most commonly targeted pharyngeal motor representations (13/17 studies). In the 10 clinical studies, stimulation was applied contralesionally (5/10 studies), ipsilesionally (3/10 studies) or bilaterally (2/10 studies). A range of behavioural and neurophysiological outcome measures demonstrated positive effects on swallowing function across studies. CONCLUSION: There is promising proof of concept that non-invasive brain stimulation may provide a useful adjunct to post-stroke swallowing rehabilitation practice. Eventual transition of optimal paradigms into routine clinical practice will be accompanied by practical considerations in relation to local and national frameworks, e.g. the prescription and provision of treatment.