Structural hallmarks of amyotrophic lateral sclerosis progression revealed by probabilistic fiber tractography

Robert Steinbach, Kristian Loewe, Joern Kaufmann, Judith Machts, Katja Kollewe, Susanne Petri, Reinhard Dengler, Hans-Jochen Heinze, Stefan Vielhaber, Mircea Ariel Schoenfeld, Christian Michael Stoppel

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive limb and/or bulbar muscular weakness and atrophy. Although ALS-related alterations of motor and extra-motor neuronal networks have repeatedly been reported, their temporal dynamics during disease progression are not well understood. Recently, we reported a decline of motor system activity and a concurrent increase of hippocampal novelty-evoked modulations across 3 months of ALS progression. To address whether these functional changes are associated with structural ones, the current study employed probabilistic fiber tractography on diffusion tensor imaging (DTI) data using a longitudinal design. Therein, motor network integrity was assessed by DTI-based tracking of the intracranial corticospinal tract, while connectivity estimates of occipito-temporal tracts (between visual and entorhinal, perirhinal or parahippocampal cortices) served to assess structural changes that could be related to the increased novelty-evoked hippocampal activity across time described previously. Complementing these previous functional observations, the current data revealed an ALS-related decrease in corticospinal tract structural connectivity compared to controls, while in contrast, visuo-perirhinal connectivity was relatively increased in the patient group. Importantly, beyond these between-group differences, a rise in the patients' occipito-temporal tract strengths occurred across a 3-month interval, while at the same time no changes in corticospinal tract connectivity were observed. In line with previously identified functional alterations, the dynamics of these structural changes suggest that the affection of motor- and memory-related networks in ALS emerges at distinct disease stages: while motor network degeneration starts primarily during early (supposedly pre-symptomatic) phases, the hippocampal/medial temporal lobe dysfunctions arise at later stages of the disease.