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@ARTICLE{Stoppel:137781,
      author       = {Stoppel, Christian Michael and Vielhaber, Stefan and
                      Eckart, Cindy and Machts, Judith and Kaufmann, Jörn and
                      Heinze, Hans-Jochen and Kollewe, Katja and Petri, Susanne
                      and Dengler, Reinhard and Hopf, Jens-Max and Schoenfeld,
                      Mircea Ariel},
      title        = {{S}tructural and functional hallmarks of amyotrophic
                      lateral sclerosis progression in motor- and memory-related
                      brain regions.},
      journal      = {NeuroImage: Clinical},
      volume       = {5},
      issn         = {2213-1582},
      address      = {[Amsterdam u.a.]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2020-04103},
      pages        = {277-290},
      year         = {2014},
      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.},
      keywords     = {Adult / Aged / Aged, 80 and over / Amyotrophic Lateral
                      Sclerosis: physiopathology / Brain: physiopathology / Brain
                      Mapping / Disease Progression / Female / Humans / Image
                      Interpretation, Computer-Assisted / Longitudinal Studies /
                      Magnetic Resonance Imaging / Male / Middle Aged},
      cin          = {AG Düzel},
      ddc          = {610},
      cid          = {I:(DE-2719)5000006},
      pnm          = {344 - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25161894},
      pmc          = {pmc:PMC4141983},
      doi          = {10.1016/j.nicl.2014.07.007},
      url          = {https://pub.dzne.de/record/137781},
}