Dystonias are a group of devastating neurological movement disorders characterized by involuntary muscle contractions that can affect any body region. There is no cure or effective treatment as the pathophysiology of the disorder remains largely unknown. In focal dystonia, symptoms are restricted to one specific body part. Dystonia affecting the hand is called focal hand dystonia (FHD), whereas when the vocal chords are affected it is termed adductor spasmodic dysphonia (AdSD). Despite different clinical manifestations (impaired voice or use of hand), both are thought to share a common underlying mechanism. But commonalities in pathophysiology of focal dystonias have not been well explored. Our central hypothesis is that focal dystonia is a brain network disorder with desynchronized connectivity (?dysconnectivity?), or ineffective collaboration between brain areas within the network associated with the dystonic task during either resting state, active state or both. This hypothesis can be tested with functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) seeds that represent different but related parts of the voluntary motor network. Therefore, using each seed for a functional connectivity (fc) assessment elucidates more precisely the nature of the dysconnectivity. We will determine the fc during resting state (resting state fc) and active state (task fc) between the loci and through the whole brain.
Aim 1 will determine the individual fc of fMRI and TMS loci for the vocalization and hand motor networks in CTL and dystonia.
Sub Aim 1. 1 will determine if the individual fc between fMRI and TMS loci differs between CTL and dystonia and if this difference is state dependent, meaning the fc differs between resting (resting state fc) and active (task fc);
Sub Aim 1. 2 will determine if the individual whole brain fc map differs between CTL and dystonia and if this difference is related to a certain loci or state;
Sub Aim 1. 3 will determine if fc analyzed in standard space reveal differences between CTL and dystonia and if this difference is state dependent.
Aim 2 will determine the relationship between disease severity and brain behavioral findings. Relevance: The pathophysiology of focal dystonia is unknown. Recent advances in neuroimaging and brain stimulation made by this team will allow multimodal assessments of anatomical and voluntary brain networks that will provide a novel window into the pathophysiology of both FHD and AdSD individually, as well as determine unifying features in both disorders. These findings will leave us well positioned to develop common treatment strategies in all focal dystonias based upon specific physiologic underpinnings. Further, the unique nature of this focal brain-based disease also has implications for our understanding of general brain function. Understanding how brain networks interact and form faulty associations could have wide reaching implications for many other disorders.
Focal dystonia is a devastating neurological movement disorder that can affect any body part. This proposal will address potential underlying causes of two types of focal dystonia (dystonia of the vocal cords and of the hand) using new measurements of brain networks. This will provide a novel window into the mechanisms of these disorders individually, as well as determine common features between them. Understanding which connections in the brain are faulty is important to assist development of interventions. Furthermore, understanding how disruptions of brain networks work together to affect movement behavior could have wide reaching implications for understanding many other disorders as well as normal brain function.
