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Research paper
Increased functional connectivity common to symptomatic amyotrophic lateral sclerosis and those at genetic risk
  1. Ricarda A L Menke1,2,
  2. Malcolm Proudfoot1,
  3. Joanne Wuu3,
  4. Peter M Andersen4,
  5. Kevin Talbot1,
  6. Michael Benatar3,
  7. Martin R Turner1,2
  1. 1Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  2. 2FMRIB Centre, John Radcliffe Hospital, University of Oxford, Oxford, UK
  3. 3Miller School of Medicine, University of Miami, Miami, Florida, USA
  4. 4Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden
  1. Correspondence to Professor Martin Turner, Clinical Neurosciences, West Wing Level 6, John Radcliffe Hospital, Oxford OX3 9DU, UK; martin.turner{at}ndcn.ox.ac.uk Professor Michael Benatar, Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA; MBenatar{at}med.miami.edu

Abstract

Objective To discern presymptomatic changes in brain structure or function using advanced MRI in carriers of mutations predisposing to amyotrophic lateral sclerosis (ALS).

Methods T1-weighted, diffusion weighted and resting state functional MRI data were acquired at 3 T for 12 asymptomatic mutation carriers (psALS), 12 age-matched controls and affected patients with ALS. Cortical thickness analysis, voxel-based morphometry, volumetric and shape analyses of subcortical structures, tract-based spatial statistics of metrics derived from the diffusion tensor, and resting state functional connectivity (FC) analyses were performed.

Results Grey matter cortical thickness and shape analysis revealed significant atrophy in patients with ALS (but not psALS) compared with controls in the right primary motor cortex and right caudate. Comparison of diffusion tensor metrics showed widespread fractional anisotropy and radial diffusivity differences in patients with ALS compared to controls and the psALS group, encompassing parts of the corpus callosum, corticospinal tracts and superior longitudinal fasciculus. While FC in the resting-state sensorimotor network was similar in psALS and controls, FC between the cerebellum and a network comprising the precuneus, cingulate & middle frontal lobe was significantly higher in psALS and affected ALS compared to controls.

Conclusions Rather than structural brain changes, increased FC may be among the earliest detectable brain abnormalities in asymptomatic carriers of ALS-causing gene mutations. With replication and significant refinement, this technique has potential in the future assessment of neuroprotective strategies.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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