Transdiagnostic circuits in neurodegerative disease

 
   Lead Investigator:    Michael Fox
   Institution      :    Beth Israel Deaconess Medical Center
   E-Mail           :    mfox3@bidmc.harvard.edu
   Proposal ID      :    1330



   Proposal Description:
   Neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) can all cause memory, mood, and motor symptoms. The severity of these symptoms varies across diseases, but also across individual patients with the same diagnosis. Identifying the brain circuits responsible for these symptoms could facilitate personalized prognosis and treatment based on routinely acquired anatomical MRI data. Here, we test the hypothesis that these symptoms map to specific brain circuits previously identified based on focal brain lesions.                                          To test this hypothesis, we leverage three recent advances. First, there are now large databases of symptoms and anatomical MRI data from patients with AD     (ADNI), PD (PPMI), and HD (PREDICT-HD). Second, advances in MRI processing allow us to detect patterns of brain atrophy at the single-subject level which can be related to individual differences in symptoms. Finally, we have recently used focal brain lesions to identify human brain circuits causally linked to memory, mood, and movement symptoms. Intersection of lesion locations with these circuits can predict the presence and severity of lesion-induced symptoms in independent datasets. Preliminary data suggests relevance of these same circuits for neurodegenerative disease. Here, we will test whether intersection of individual atrophy patterns with these circuits predicts symptoms across different neurodegenerative diseases.                                             Aim 1: To test whether movement symptoms in neurodegenerative disease are associated with atrophy in a priori movement circuits derived from focal brain lesions                                                                           I hypothesize that movement scores will be associated with atrophy in our a priori movement circuits (parkinsonism and chorea) across patients with the same diagnosis (1A), across patients independent of d