Regional structural hypo- and hyperconnectivity of frontal-striatal and frontal-thalamic pathways in behavioral variant frontotemporal dementia

Authors

David D. Jakabek, University of WollongongFollow
Brian D. Power, University of Notre Dame
Matthew D. Macfarlane, University of Wollongong, Illawarra Shoalhaven Local Health DistrictFollow
Mark Walterfang, University of Melbourne
Dennis Velakoulis, University of Melbourne
Danielle Van Westen, Skane University Hospital
Jimmy Latt, Lund University, Skane University Hospital
Markus Nilsson, Lund University
Jeffrey C. L Looi, Australian National University Medical School, University of Melbourne
Alexander Frizell Santillo, Lund University

RIS ID

130159

Publication Details

Jakabek, D., Power, B. D., Macfarlane, M. D., Walterfang, M., Velakoulis, D., Van Westen, D., Latt, J., Nilsson, M., Looi, J. C. L. & Santillo, A. F. (2018). Regional structural hypo- and hyperconnectivity of frontal-striatal and frontal-thalamic pathways in behavioral variant frontotemporal dementia. Human Brain Mapping, 39 (10), 4083-4093.

Abstract

Behavioral variant frontotemporal dementia (bvFTD) has been predominantly considered as a frontotemporal cortical disease, with limited direct investigation of frontal-subcortical connections. We aim to characterize the grey and white matter components of frontal-thalamic and frontal-striatal circuits in bvFTD. Twenty-four patients with bvFTD and 24 healthy controls underwent morphological and diffusion imaging. Subcortical structures were manually segmented according to published protocols. Probabilistic pathways were reconstructed separately from the dorsolateral, orbitofrontal and medial prefrontal cortex to the striatum and thalamus. Patients with bvFTD had smaller cortical and subcortical volumes, lower fractional anisotropy, and higher mean diffusivity metrics, which is consistent with disruptions in frontal-striatal-thalamic pathways. Unexpectedly, regional volumes of the striatum and thalamus connected to the medial prefrontal cortex were significantly larger in bvFTD (by 135% in the striatum, p =.032, and 217% in the thalamus, p =.004), despite smaller dorsolateral prefrontal cortex connected regional volumes (by 67% in the striatum, p =.002, and 65% in the thalamus, p =.020), and inconsistent changes in orbitofrontal cortex connected regions. These unanticipated findings may represent compensatory or maladaptive remodeling in bvFTD networks. Comparisons are made to other neuropsychiatric disorders suggesting a common mechanism of changes in frontal-subcortical networks; however, longitudinal studies are necessary to test this hypothesis.