title: Structural and functional hallmarks of amyotrophic lateral sclerosis progression in motor- and memory-related brain regions.
abstract: Previous studies have shown that in amyotrophic lateral sclerosis (ALS) multiple motor and extra-motor regions display structural and functional alterations. However, their temporal dynamics during disease-progression are unknown. To address this question we employed a longitudinal design assessing motor- and novelty-related brain activity in two fMRI sessions separated by a 3-month interval. In each session, patients and controls executed a Go/NoGo-task, in which additional presentation of novel stimuli served to elicit hippocampal activity. We observed a decline in the patients' movement-related activity during the 3-month interval. Importantly, in comparison to controls, the patients' motor activations were higher during the initial measurement. Thus, the relative decrease seems to reflect a breakdown of compensatory mechanisms due to progressive neural loss within the motor-system. In contrast, the patients' novelty-evoked hippocampal activity increased across 3 months, most likely reflecting the build-up of compensatory processes typically observed at the beginning of lesions. Consistent with a stage-dependent emergence of hippocampal and motor-system lesions, we observed a positive correlation between the ALSFRS-R or MRC-Megascores and the decline in motor activity, but a negative one with the hippocampal activation-increase. Finally, to determine whether the observed functional changes co-occur with structural alterations, we performed voxel-based volumetric analyses on magnetization transfer images in a separate patient cohort studied cross-sectionally at another scanning site. Therein, we observed a close overlap between the structural changes in this cohort, and the functional alterations in the other. Thus, our results provide important insights into the temporal dynamics of functional alterations during disease-progression, and provide support for an anatomical relationship between functional and structural cerebral changes in ALS.
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Str. 44, Magdeburg 39120, Germany.
authors.forename: Christian Michael
authors.initials: CM
authors.lastname: Stoppel
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Str. 44, Magdeburg 39120, Germany ; DZNE - German Centre for Neurodegenerative Diseases, Leipziger Str. 44, Magdeburg 39120, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Vielhaber
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Str. 44, Magdeburg 39120, Germany ; Institute for Systemic Neurosciences, University Clinic, Martinistr. 52, Hamburg 20246, Germany.
authors.forename: Cindy
authors.initials: C
authors.lastname: Eckart
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Str. 44, Magdeburg 39120, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Machts
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Str. 44, Magdeburg 39120, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Kaufmann
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Str. 44, Magdeburg 39120, Germany ; Leibniz-Institute for Neurobiology, Brennecke Str. 6, Magdeburg 39118, Germany.
authors.forename: Hans-Jochen
authors.initials: HJ
authors.lastname: Heinze
authors.affiliation: Department of Neurology, Medical School Hannover, Carl-Neuberg-str. 1, Hannover 30625, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Kollewe
authors.affiliation: Department of Neurology, Medical School Hannover, Carl-Neuberg-str. 1, Hannover 30625, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Petri
authors.affiliation: Department of Neurology, Medical School Hannover, Carl-Neuberg-str. 1, Hannover 30625, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dengler
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Str. 44, Magdeburg 39120, Germany ; Leibniz-Institute for Neurobiology, Brennecke Str. 6, Magdeburg 39118, Germany.
authors.forename: Jens-Max
authors.initials: JM
authors.lastname: Hopf
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Leipziger Str. 44, Magdeburg 39120, Germany ; Leibniz-Institute for Neurobiology, Brennecke Str. 6, Magdeburg 39118, Germany ; Kliniken Schmieder, Zum Tafelholz 8, Allensbach 78476, Germany.
authors.forename: Mircea Ariel
authors.initials: MA
authors.lastname: Schoenfeld
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D018450:Disease Progression; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
keywords: Amyotrophic lateral sclerosis; Hippocampus; Longitudinal fMRI; Novelty processing