MODIFI: protocol for randomised feasibility study of eye-movement desensitisation and reprocessing therapy (EMDR) for functional neurological disorder (FND).

INTRODUCTION: Functional neurological disorder (FND) refers to an involuntary loss of control over and/or aberrant perception of the body. Common presenting symptoms are functional (non-epileptic) seizures, and functional motor disorder, for example, walking difficulties, weakness or tremor. Greater access to effective treatments would lead to reduced distress and disability; and reduce unnecessary healthcare costs.This study will examine eye-movement desensitisation and reprocessing therapy (EMDR) as a treatment for FND. EMDR is an evidence-based treatment for post-traumatic stress disorder (PTSD), but its use for other conditions is growing. An FND-specific EMDR protocol will be tested, and if the intervention proves feasible with promising clinical outcomes, progression to a substantive study could take place. METHODS AND ANALYSIS: Fifty adult patients diagnosed with FND will be recruited. It will be a single-blind randomised controlled trial with two arms: EMDR (plus standard neuropsychiatric care; NPC) and standard NPC. The two groups will be compared at baseline (T0), 3 months (T1), 6 months (T2) and 9 months (T3). Measures of feasibility include safety, recruitment, retention, treatment adherence and acceptability. Clinical outcome measures will assess health-related functioning/quality of life, ratings of FND symptoms and severity, depression, anxiety, PTSD, dissociation, service utilisation and other costs. Improvement and satisfaction ratings will also be assessed. Feasibility outcomes will be summarised using descriptive statistics. Exploratory analyses using (linear/logistic) mixed-effect models will examine the rate of change in the groups' clinical outcome measures across the four time-points.After the intervention period, a sample of participants, and clinicians, will be invited to attend semistructured interviews. The interviews will be analysed using reflexive thematic analysis. ETHICS AND DISSEMINATION: This study has been approved by the NHS West Midlands-Edgbaston Research Ethics Committee. Study findings will be published in open access peer-reviewed journals, presented at conferences, and communicated to participants and other relevant stakeholders. TRIAL REGISTRATION: NCT05455450 (www. CLINICALTRIALS: gov).

Cervical dystonia: Normal auditory mismatch negativity and abnormal somatosensory mismatch negativity.

OBJECTIVE: Previous electrophysiological and psychophysical tests have suggested that somatosensory integration is abnormal in dystonia. Here, we hypothesised that this abnormality could relate to a more general deficit in pre-attentive error/deviant detection in patients with dystonia. We therefore tested patients with dystonia and healthy subjects using a mismatch negativity paradigm (MMN), where evoked potentials generated in response to a standard repeated stimulus are subtracted from the responses to a rare "odd ball" stimulus. METHODS: We assessed MMN for somatosensory and auditory stimuli in patients with cervical dystonia and healthy age matched controls. RESULTS: We found a significant group ∗ oddball type interaction effect (F (1, 34) = 4.5, p = 0.04, ρI = 0.63). A follow up independent t-test for sMMN data, showed a smaller sMMN amplitude in dystonic patients compared to controls (mean difference control-dystonia: -1.0 µV ± 0.3, p < 0.00, t = -3.1). However the amplitude of aMMN did not differ between groups (mean difference control-dystonia: -0.2 µV ± 0.2, p = 0.24, t = -1.2). We found a positive correlation between somatosensory MMN and somatosensory temporal discrimination threshold. CONCLUSION: These results suggest that pre-attentive error/deviant detection, specifically in the somatosensory domain, is abnormal in dystonia. This could underlie some previously reported electrophysiological and psychophysical abnormalities of somatosensory integration in dystonia. SIGNIFICANCE: One could hypothesize a deficit in pre-conscious orientation towards potentially salient signals might lead to a more conservative threshold for decision-making in dystonia.

Normal eyeblink classical conditioning in patients with fixed dystonia.

Fixed dystonia without evidence of basal ganglia lesions or neurodegeneration typically affects young women following minor peripheral trauma. We use eyeblink classical conditioning (EBCC) to study whether cerebellar functioning is abnormal in patients with fixed dystonia, since this is part of the pathophysiology of primary dystonia. An auditory tone (conditioning stimulus) was paired with a supraorbital nerve stimulus (unconditioned stimulus) with a delay of 400 ms in order to yield conditioned responses. We recruited 11 fixed dystonia patients of whom six used medication and seven age-matched healthy controls. Non-medicated patients with fixed dystonia performed as well as healthy controls, while medicated patients showed fewer conditioned responses. We found an influence of medication and possibly extent of dystonic features and/or co-occurrence of complex regional pain syndrome (CRPS) on EBCC performance. Our study argues against abnormal cerebellar function in non-medicated, fixed dystonia patients without CRPS or spread of symptoms.

The brighter side of music in dystonia.

OBJECTIVE: To report a patient with genetically proven DYT1 dystonia who shows dramatic improvement in symptoms while playing the piano. DESIGN: Case study. SETTING: Sobell Department for Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, England. PATIENT: A 49-year-old right-handed male civil servant. MAIN OUTCOME MEASURES: The patient was videotaped, and electromyographic activity was recorded from the splenius capitis, sternocleidomastoid, and orbicularis oculi muscles, while he was (1) at rest, (2) playing an electric piano with auditory feedback, and (3) playing an electric piano without auditory feedback (ie, when the sound of the piano is turned off). RESULTS: At baseline, the patient had generalized dystonia with prominent upper limb, neck, and facial involvement. While he was playing the piano, there was an instant and almost complete improvement in dystonia symptoms. The improvement was also noticeable when he played the piano without auditory feedback. There was a significant reduction in electromyographic activity for all recorded muscles when he played the piano, compared with his baseline electromyographic activity. CONCLUSION: This is a unique case of "paradoxical" improvement in dystonia symptoms with activity (ie, playing a piano), in contrast to the typical worsening of dystonia symptoms with activity. We discuss the possible mechanisms underlying this phenomenon. One of the most intriguing features of primary dystonia is the variability of abnormal muscle activity relative to the context in which movement is attempted (eg, the exquisite task specificity of focal hand dystonia or the phenomenon of the geste antagoniste). We present a unique case of an amateur pianist with genetically proven DYT1 dystonia who shows dramatic improvement in generalized dystonia symptoms while playing piano.

Theta burst stimulation of the human motor cortex.

It has been 30 years since the discovery that repeated electrical stimulation of neural pathways can lead to long-term potentiation in hippocampal slices. With its relevance to processes such as learning and memory, the technique has produced a vast literature on mechanisms of synaptic plasticity in animal models. To date, the most promising method for transferring these methods to humans is repetitive transcranial magnetic stimulation (rTMS), a noninvasive method of stimulating neural pathways in the brain of conscious subjects through the intact scalp. However, effects on synaptic plasticity reported are often weak, highly variable between individuals, and rarely last longer than 30 min. Here we describe a very rapid method of conditioning the human motor cortex using rTMS that produces a controllable, consistent, long-lasting, and powerful effect on motor cortex physiology and behavior after an application period of only 20-190 s.