title: Structural hallmarks of amyotrophic lateral sclerosis progression revealed by probabilistic fiber tractography.
abstract: 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.
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Str. 44, 39120, Magdeburg, Germany. robert.steinbach@st.ovgu.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Steinbach
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Str. 44, 39120, Magdeburg, Germany.|Department of Knowledge and Language Processing, Otto-von-Guericke-University, Universitätsplatz 2, 39106, Magdeburg, Germany.
authors.forename: Kristian
authors.initials: K
authors.lastname: Loewe
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Joern
authors.initials: J
authors.lastname: Kaufmann
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Machts
authors.affiliation: Department of Neurology, Medical School Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Kollewe
authors.affiliation: Department of Neurology, Medical School Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Petri
authors.affiliation: Department of Neurology, Medical School Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dengler
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Str. 44, 39120, Magdeburg, Germany.|Leibniz-Institute for Neurobiology, Brennecke Str. 6, 39118, Magdeburg, Germany.
authors.forename: Hans-Jochen
authors.initials: HJ
authors.lastname: Heinze
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Vielhaber
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Str. 44, 39120, Magdeburg, Germany.|Leibniz-Institute for Neurobiology, Brennecke Str. 6, 39118, Magdeburg, Germany.|Kliniken Schmieder, Zum Tafelholz 8, 78476, Allensbach, Germany.
authors.forename: Mircea Ariel
authors.initials: MA
authors.lastname: Schoenfeld
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Str. 44, 39120, Magdeburg, Germany. christian.stoppel@charite.de.|Leibniz-Institute for Neurobiology, Brennecke Str. 6, 39118, Magdeburg, Germany. christian.stoppel@charite.de.|Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. christian.stoppel@charite.de.
authors.forename: Christian Michael
authors.initials: CM
authors.lastname: Stoppel
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology* / Q000503:physiopathology*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D011712:Pyramidal Tracts / Q000473:pathology*
keywords: Amyotrophic lateral sclerosis; Corticospinal tract; Longitudinal DTI; Medial temporal lobe; Probabilistic fiber tractography