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000137781 1001_ $$0P:(DE-HGF)0$$aStoppel, Christian Michael$$b0$$eCorresponding author
000137781 245__ $$aStructural and functional hallmarks of amyotrophic lateral sclerosis progression in motor- and memory-related brain regions.
000137781 260__ $$a[Amsterdam u.a.]$$bElsevier$$c2014
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000137781 520__ $$aPrevious 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.
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000137781 650_2 $$2MeSH$$aAdult
000137781 650_2 $$2MeSH$$aAged
000137781 650_2 $$2MeSH$$aAged, 80 and over
000137781 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: physiopathology
000137781 650_2 $$2MeSH$$aBrain: physiopathology
000137781 650_2 $$2MeSH$$aBrain Mapping
000137781 650_2 $$2MeSH$$aDisease Progression
000137781 650_2 $$2MeSH$$aFemale
000137781 650_2 $$2MeSH$$aHumans
000137781 650_2 $$2MeSH$$aImage Interpretation, Computer-Assisted
000137781 650_2 $$2MeSH$$aLongitudinal Studies
000137781 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000137781 650_2 $$2MeSH$$aMale
000137781 650_2 $$2MeSH$$aMiddle Aged
000137781 7001_ $$0P:(DE-2719)2000035$$aVielhaber, Stefan$$b1$$udzne
000137781 7001_ $$0P:(DE-HGF)0$$aEckart, Cindy$$b2
000137781 7001_ $$0P:(DE-HGF)0$$aMachts, Judith$$b3
000137781 7001_ $$0P:(DE-HGF)0$$aKaufmann, Jörn$$b4
000137781 7001_ $$0P:(DE-HGF)0$$aHeinze, Hans-Jochen$$b5
000137781 7001_ $$0P:(DE-HGF)0$$aKollewe, Katja$$b6
000137781 7001_ $$0P:(DE-HGF)0$$aPetri, Susanne$$b7
000137781 7001_ $$0P:(DE-HGF)0$$aDengler, Reinhard$$b8
000137781 7001_ $$0P:(DE-HGF)0$$aHopf, Jens-Max$$b9
000137781 7001_ $$0P:(DE-HGF)0$$aSchoenfeld, Mircea Ariel$$b10
000137781 77318 $$2Crossref$$3journal-article$$a10.1016/j.nicl.2014.07.007$$b : Elsevier BV, 2014-01-01$$p277-290$$tNeuroImage: Clinical$$v5$$x2213-1582$$y2014
000137781 773__ $$0PERI:(DE-600)2701571-3$$a10.1016/j.nicl.2014.07.007$$gVol. 5, p. 277 - 290$$p277-290$$q5<277 - 290$$tNeuroImage: Clinical$$v5$$x2213-1582$$y2014
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