TY  - JOUR
AU  - Stoppel, Christian Michael
AU  - Vielhaber, Stefan
AU  - Eckart, Cindy
AU  - Machts, Judith
AU  - Kaufmann, Jörn
AU  - Heinze, Hans-Jochen
AU  - Kollewe, Katja
AU  - Petri, Susanne
AU  - Dengler, Reinhard
AU  - Hopf, Jens-Max
AU  - Schoenfeld, Mircea Ariel
TI  - Structural and functional hallmarks of amyotrophic lateral sclerosis progression in motor- and memory-related brain regions.
JO  - NeuroImage: Clinical
VL  - 5
SN  - 2213-1582
CY  - [Amsterdam u.a.]
PB  - Elsevier
M1  - DZNE-2020-04103
SP  - 277-290
PY  - 2014
AB  - 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.
KW  - Adult
KW  - Aged
KW  - Aged, 80 and over
KW  - Amyotrophic Lateral Sclerosis: physiopathology
KW  - Brain: physiopathology
KW  - Brain Mapping
KW  - Disease Progression
KW  - Female
KW  - Humans
KW  - Image Interpretation, Computer-Assisted
KW  - Longitudinal Studies
KW  - Magnetic Resonance Imaging
KW  - Male
KW  - Middle Aged
LB  - PUB:(DE-HGF)16
C6  - pmid:25161894
C2  - pmc:PMC4141983
DO  - DOI:10.1016/j.nicl.2014.07.007
UR  - https://pub.dzne.de/record/137781
ER  -