Unraveling Shared Pathways: A Comprehensive Systematic Review of Common Fiber Tracts in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia using Diffusion Tensor Imaging

1 Abstract: This systematic review evaluated MRI studies of fibre tract abnormalities in patients with amyotrophic lateral sclerosis (ALS) and/or fronto-temporal dementia (FTD). After searching 5 databases, 63 papers met inclusion criteria reporting 1674 patients and 1411 healthy controls. The papers studied a range of fibre tracts. Techniques used included overall comparisons and regions of interest. All papers reported results of fractional anisotropy (FA) and some also reported other DTI metrics. In ALS, the hallmark feature of cortico-spinal tracts (CST) involvement is consistently found, while in FTD the only part of the motor tracts that was found to show changes is the corona radiata (CR). The review also highlighted overlapping abnormalities between ALS and FTD, suggesting that these conditions exist on a spectrum. Both ALS and FTD exhibited CST abnormalities, with extra-motor involvement in the cingulum and the CC. Many tracts including the corpus callosum (CC) and cingulum (Cg), the superior longitudinal fasciculus (SLF) and inferior fronto-occiptal fasciculus (IFOF), were abnormal in both ALS and FTD. The integrity of specific white matter tracts, such as the uncinated fasciculus (uncF), forceps minor, and callosal radiation, appeared critical for cognitive functions related to Theory of Mind, cognitive control, and emotion recognition.There was, however, extramotor involvement in ALS. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors