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Brain Networks in Dystonia

肌张力障碍的大脑网络

基本信息

批准号：
9492159
负责人：
Kristina Simonyan
金额：
$ 48.77万
依托单位：
MASSACHUSETTS EYE AND EAR INFIRMARY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-06-01 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9492159
关键词：
Affect Autopsy Basal Ganglia Basal Ganglia Diseases Behavioral Biological Markers Biological Neural Networks Brain Brain Pathology Brain imaging Brain region Cerebellum Clinical Clinical Management Curiosities Data Deep Brain Stimulation Detection Development Diagnosis Differential Diagnosis Disease Dystonia Etiology Evaluation Exhibits Focal Dystonias Foundations Functional disorder Goals Hand Human Investigation Knowledge Larynx Lead Link Mission Motor Movement Muscle Muscle Contraction Music Normalcy Operative Surgical Procedures Outcome Pathway Analysis Patients Pattern Performance Pharmacologic Substance Pharmacology Play Positioning Attribute Posture Production Public Health Research Series Spastic Dysphonias Specificity Structure Structure-Activity Relationship Syndrome Task Performances Time United States National Institutes of Health Validation Work Writer&apos s cramp neurosis Writing base behavior test brain abnormalities brain tissue design diagnosis evaluation diagnostic biomarker disability endophenotype expectation improved innovation instrument motor control motor impairment multimodality musician neural correlate neuroimaging neuromechanism neuropathology novel novel diagnostics novel strategies novel therapeutics phenomenological models programs public health relevance relating to nervous system specific biomarkers

项目摘要

DESCRIPTION (provided by applicant): Task-specific primary focal dystonias (tsPFDs) are characterized by selective activation of dystonic movements during performance of highly learned motor tasks, such as writing, playing a musical instrument, speaking, or singing. Despite the recent advances in describing the clinical features of dystonia, there is a fundamental gap in understanding the neural abnormalities underlying the development of tsPFDs, which affect the same muscles but result in different clinical manifestations as in writer's cramp vs. pianist's dystonia or spasmodic dysphonia vs. singer's dystonia. Continued existence of this gap is an important problem because it renders us unable to differentiate between primary and secondary brain changes contributing to the tsPFD pathophysiology and to develop novel treatment options targeting disorder-specific brain alterations. Our long-term goal is to determine the causes and pathophysiology of primary focal dystonia for its improved clinical management. The objective of this application is to identify the brain mechanisms underlying the phenomenon of task specificity in two representative groups of patients with writer's cramp vs. musician's hand dystonia and spasmodic dysphonia vs. singer's laryngeal dystonia using a novel approach of combined clinico-behavioral examination, brain network analysis and quantitative neuropathology of postmortem brain tissue. Our central hypothesis is that each tsPFD is characterized by distinct brain abnormalities, which selectively affect the focal segments of brain networks responsible for the performance of the respective motor task. The rationale for the proposed research is that identification of tsPFD-specific brain changes and associated neuropathology will clarify the neural mechanisms (primary vs. secondary) contributing to the clinical manifestation of these disorders and thus explain the phenomenon of task-specificity in PFDs. The obtained results are expected to provide strong scientific bases for the next series of studies directed towards identification and validation of novel pharmacological and/or surgical therapies for these patients. We will pursue the following two specific aims: (1) determine distinct features of brain functional network abnormalities underlying task-specificity in differen tsPFDs, and (2) establish structural correlates of functional neuroimaging abnormalities in tsPFDs. This research is innovative because it will be among the first detailed investigations designed specifically to focus on defining tsPFD neu- ral markers. The proposed research is significant because it is expected to establish scientific evidence that tsPFD is a network disorder with abnormalities following distinct patterns in different tsPFDs and certain ab- normalities showing structure-function correlations are associated with underlying neuropathology. By converging the results from multimodal cross-disciplinary studies to a coherent and pathophysiologically meaningful picture, we will be well positioned to identify primary vs. secondary changes in tsPFDs and establish a scientific framework for the development of diagnostic biomarkers and novel treatment options for these disorders.