Functional connectivity changes resemble patterns of pTDP-43 pathology in amyotrophic lateral sclerosis

Sci Rep. 2016 Dec 8:6:38391. doi: 10.1038/srep38391.

Abstract

'Resting-state' fMRI allows investigation of alterations in functional brain organization that are associated with an underlying pathological process. We determine whether abnormal connectivity in amyotrophic lateral sclerosis (ALS) in a priori-defined intrinsic functional connectivity networks, according to a neuropathological staging scheme and its DTI-based tract correlates, permits recognition of a sequential involvement of functional networks. 'Resting-state' fMRI data from 135 ALS patients and 56 matched healthy controls were investigated for the motor network (corresponding to neuropathological stage 1), brainstem (stage 2), ventral attention (stage 3), default mode/hippocampal network (stage 4), and primary visual network (as the control network) in a cross-sectional analysis and longitudinally in a subgroup of 27 patients after 6 months. Group comparison from cross-sectional and longitudinal data revealed significantly increased functional connectivity (p < 0.05, corrected) in all four investigated networks (but not in the control network), presenting as a network expansion that was correlated with physical disability. Increased connectivity of functional networks, as investigated in a hypothesis-driven approach, is characterized by network expansions and resembled the pattern of pTDP-43 pathology in ALS. However, our data did not allow for the recognition of a sequential involvement of functional connectivity networks at the individual level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / diagnostic imaging
  • Amyotrophic Lateral Sclerosis / metabolism
  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Attention / physiology
  • Brain / physiopathology*
  • Brain Stem / diagnostic imaging
  • Brain Stem / physiopathology*
  • Connectome
  • DNA-Binding Proteins / metabolism
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Motor Neurons / metabolism
  • Motor Neurons / pathology*
  • Neural Pathways / pathology
  • Neural Pathways / physiology

Substances

  • DNA-Binding Proteins
  • TARDBP protein, human