Ten‐Year Reflections on the Neurophysiological Abnormalities of Focal Dystonias in Humans

Abstract

The physiological landscape of dystonia has changed considerably over the past 10 years. Initial ideas that dystonic motor symptoms could be explained by a combination of loss of inhibition and increased plasticity, together with subtle deficits in sensory processing, have been questioned, whereas the possible role of the cerebellum has risen in importance. In addition, it has been recognized that symptoms affect more than just the motor and sensory systems and encompass independent cognitive and psychological changes. Finally, it has become clear that, despite similarities in symptoms, there may be pathophysiological differences between idiopathic, inherited, and acquired forms of dystonia. In other words, progress in the pathophysiology of dystonia has followed the usual pattern from an initial phase in which core deficits are readily explained by highly simplified models to a realization that within a highly interconnected network, effects are more nuanced with widespread changes that might either compensate or contribute to the clinical symptoms to different degrees in different individuals. © 2019 International Parkinson and Movement Disorder Society

A microstructural neural network biomarker for dystonia diagnosis identified by a DystoniaNet deep learning platform

“…Recent advances in brain imaging methodologies and analytical techniques have allowed the identification of widespread alterations of brain structure and function in this disorder, involving not only the basal ganglia and cerebellum but also higher-order motor and associative cortical regions ( 18 ). Different forms of dystonia have been characterized by similarities in large-scale disorganization of gray and white matter architecture, including abnormal distribution of influential regions of information transfer (hubs) in prefrontal, parietal, occipital cortices and thalamus and reduced connectivity of the sensorimotor and frontoparietal regions ( 19 – 23 ). This knowledge critically shifted our understanding of dystonia pathophysiology from a basal ganglia disorder to a large-scale neural network disorder and thrust the field toward probing these alterations as potential candidate markers for its diagnosis and treatment ( 24 – 28 ).…”

The Dystonia Coalition: A Multicenter Network for Clinical and Translational Studies

“…Another common theme has involved abnormalities of neuronal excitability or neural plasticity among individuals with different types of dystonia (37). Glutamate receptors play a key role in neuronal excitability.…”

Mal de Debarquement Syndrome: A Matter of Loops?

“…The involvement of excessive synaptic plasticity has been reported for various disorders, e.g., diminished LTP and long term depression (LTD) in schizophrenia ( 60 ), dopamine-driven synaptic facilitation in drug addiction ( 61 ), or unbalanced excitatory and inhibitory stimuli on fusiform cells of the dorsal cochlear nuclei in tinnitus ( 62 ). Even closer to MdDS, maladaptive cortical plasticity is involved in the pathophysiology of focal dystonia, such as writer's cramp and spasmodic torticollis, where repetitive sensory input reaches cortical sensory areas that show excessive plastic adaptation characterized by increased motor output, excessive muscle contractions, abnormal postures, and involuntary movements ( 63 – 66 ). Similarly, we suggest that in MdDS abnormal plasticity occurs in vestibular and Purkinje neurons.…”