title: Disrupted thalamocortical connectivity in PSP: a resting-state fMRI, DTI, and VBM study.
abstract: Progressive supranuclear palsy (PSP) is associated with pathological changes along the dentatorubrothalamic tract and in premotor cortex. We aimed to assess whether functional neural connectivity is disrupted along this pathway in PSP, and to determine how functional changes relate to changes in structure and diffusion. Eighteen probable PSP subjects and 18 controls had resting-state (task-free) fMRI, diffusion tensor imaging and structural MRI. Functional connectivity was assessed between thalamus and the rest of the brain, and within the basal ganglia, salience and default mode networks (DMN). Patterns of atrophy were assessed using voxel-based morphometry, and patterns of white matter tract degeneration were assessed using tract-based spatial statistics. Reduced in-phase functional connectivity was observed between the thalamus and premotor cortex including supplemental motor area (SMA), striatum, thalamus and cerebellum in PSP. Reduced connectivity in premotor cortex, striatum and thalamus were observed in the basal ganglia network and DMN, with subcortical salience network reductions. Tract degeneration was observed between cerebellum and thalamus and in superior longitudinal fasciculus, with grey matter loss in frontal lobe, premotor cortex, SMA and caudate nucleus. SMA functional connectivity correlated with SMA volume and measures of cognitive and motor dysfunction, while thalamic connectivity correlated with degeneration of superior cerebellar peduncles. PSP is therefore associated with disrupted thalamocortical connectivity that is associated with degeneration of the dentatorubrothalamic tract and the presence of cortical atrophy.
authors.affiliation: Department of Radiology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA. Whitwell.jennifer@mayo.edu
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Whitwell
authors.forename: Ramesh
authors.initials: R
authors.lastname: Avula
authors.forename: Ankit
authors.initials: A
authors.lastname: Master
authors.forename: Prashanthi
authors.initials: P
authors.lastname: Vemuri
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.forename: David T
authors.initials: DT
authors.lastname: Jones
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.forename: Keith A
authors.initials: KA
authors.lastname: Josephs
mesh_terms: D000368:Aged; D001284:Atrophy; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008875:Middle Aged; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011446:Prospective Studies; D013494:Supranuclear Palsy, Progressive / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology*; D013788:Thalamus / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*