The Crossed Flexor Plantar Response in Patients with Klippel-Feil Syndrome.

The plantar reflex is one of most important and widely tested components of the neurological examination. We describe 3 subjects with Klippel-Feil syndrome and mirror movements where unilateral cutaneous stimulation of the foot leads to flexor plantar responses in both feet. We discuss the evidence which suggests that this "crossed flexor" plantar response reveals a transcortical pathway for the flexor plantar response

The Expanding Horizon of Neural Stimulation for Hyperkinetic Movement Disorders

Novel methods of neural stimulation are transforming the management of hyperkinetic movement disorders. In this review the diversity of approach available is showcased. We first describe the most commonly used features that can be extracted from oscillatory activity of the central nervous system, and how these can be combined with an expanding range of non-invasive and invasive brain stimulation techniques. We then shift our focus to the periphery using tremor and Tourette's syndrome to illustrate the utility of peripheral biomarkers and interventions. Finally, we discuss current innovations which are changing the landscape of stimulation strategy by integrating technological advances and the use of machine learning to drive optimization

Editorial: Advances in Invasive and Non-invasive Brain Stimulation for Dystonia and Other Hyperkinetic Movement Disorders

No abstract availabl

The role of the cerebellum in the pathophysiology of dystonia

Research over the last decade has refined our understanding of the neuroanatomical substrates of dystonia. In addition to basal ganglia dysfunction a much wider sensorimotor network has been implicated and within this network the cerebellum is heralded as a core node. Much of the literature linking the cerebellum to dystonia consists of cases in which lesions of the cerebellum are linked to abnormal posture or indirect experimental associations (reviewed in chapter 1). Better defining the functional role of the cerebellum in the pathophysiology of dystonia could provide a scientific rational for future therapeutic advances, adding further weight to an early neurosurgical literature which advocates targeting the cerebellum and its outflow tracts. Within this thesis I applied experimental techniques from which direct inferences about cerebellar function could be made, trying to better define how the cerebellum is functionally involved in the pathogenesis of isolated dystonia. Methodology can be divided into major themes (i) two studies exploring cerebellar modulation of dystonic neurophysiological hallmarks; impaired motor surround inhibition (chapter 2) and excessive plasticity (chapter 3) (ii) evaluation of eye-blink conditioning a form of cerebellar associative learning (chapter 4, chapter 8) (iii) exploring whether millisecond timing, a cerebellar encoded process, is at the root of abnormal temporal discrimination thresholds (chapter 5) and finally (iv) testing adaptation a kinematic cerebellar paradigm in cervical dystonia (chapter 6) and DYT1 dystonia (chapter 7). Overall, my application of the ‘purest’ cerebellar paradigms did not provide a robust functional correlate to implicate specific cerebellar functions as a driver of dystonic pathophysiology. I present good evidence that fundamental computations such as adaptation and associative learning are intact in various groups of isolated dystonia. Thus isolated dystonia does not seem to selectively impair cerebellar functions (as currently defined). It is only with future research that we will be able to determine whether dystonia corrupts function(s) inherent to the dystonic network which includes the cerebellum or whether the cerebellar abnormalities observed experimentally are compensatory in nature

Plasticity and dystonia: a hypothesis shrouded in variability.

Studying plasticity mechanisms with Professor John Rothwell was a shared highlight of our careers. In this article, we discuss non-invasive brain stimulation techniques which aim to induce and quantify plasticity, the mechanisms and nature of their inherent variability and use such observations to review the idea that excessive and abnormal plasticity is a pathophysiological substrate of dystonia. We have tried to define the tone of our review by a couple of Professor John Rothwell's many inspiring characteristics; his endless curiosity to refine knowledge and disease models by scientific exploration and his wise yet humble readiness to revise scientific doctrines when the evidence is supportive. We conclude that high variability of response to non-invasive brain stimulation plasticity protocols significantly clouds the interpretation of historical findings in dystonia research. There is an opportunity to wipe the slate clean of assumptions and armed with an informative literature in health, re-evaluate whether excessive plasticity has a causal role in the pathophysiology of dystonia

Neural Competitive Queuing of Ordinal Structure Underlies Skilled Sequential Action.

Fluent retrieval and execution of movement sequences is essential for daily activities, but the neural mechanisms underlying sequence planning remain elusive. Here participants learned finger press sequences with different orders and timings and reproduced them in a magneto-encephalography (MEG) scanner. We classified the MEG patterns for each press in the sequence and examined pattern dynamics during preparation and production. Our results demonstrate the "competitive queuing" (CQ) of upcoming action representations, extending previous computational and non-human primate recording studies to non-invasive measures in humans. In addition, we show that CQ reflects an ordinal template that generalizes across specific motor actions at each position. Finally, we demonstrate that CQ predicts participants' production accuracy and originates from parahippocampal and cerebellar sources. These results suggest that the brain learns and controls multiple sequences by flexibly combining representations of specific actions and interval timing with high-level, parallel representations of sequence position

The Expanding Horizon of Neural Stimulation for Hyperkinetic Movement Disorders.

Novel methods of neural stimulation are transforming the management of hyperkinetic movement disorders. In this review the diversity of approach available is showcased. We first describe the most commonly used features that can be extracted from oscillatory activity of the central nervous system, and how these can be combined with an expanding range of non-invasive and invasive brain stimulation techniques. We then shift our focus to the periphery using tremor and Tourette's syndrome to illustrate the utility of peripheral biomarkers and interventions. Finally, we discuss current innovations which are changing the landscape of stimulation strategy by integrating technological advances and the use of machine learning to drive optimization