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@ARTICLE{Kukolja:7950,
      author       = {Kukolja, J. and Thiel, C.M. and Fink, G. R.},
      title        = {{C}holinergic stimulation enhances neural activity
                      associated with encoding but reduces neural activity
                      associated with retrieval in humans},
      journal      = {The journal of neuroscience},
      volume       = {29},
      issn         = {0270-6474},
      address      = {Washington, DC},
      publisher    = {Soc.},
      reportid     = {PreJuSER-7950},
      pages        = {8119 - 8128},
      year         = {2009},
      note         = {This work was supported by a grant of the Deutsche
                      Forschungsgemeinschaft (DFG-KFO 112, TP8) to G. R. F. and C.
                      M. T. We thank all our volunteers. We are grateful to our
                      colleagues of the MR and Cognitive Neurology groups for
                      valuable support. We thank Laura Amort and Birte Berger for
                      neuropsychological testing.},
      abstract     = {The cerebral cholinergic system is centrally involved in
                      memory formation. Studies in rodents suggest that
                      cholinergic stimulation may facilitate encoding of new
                      information but may interfere with retrieval. We
                      investigated the effect of cholinergic stimulation on
                      encoding and retrieval of episodic memory in humans. We also
                      tested whether the putative benefit of cholinergic
                      stimulation on memory function depends on individual
                      baseline performance. Since such effects were expected to be
                      greatest in an older population resulting from an
                      age-related degeneration of the cholinergic system, we
                      recruited 22 healthy older subjects (51-68 years) for an
                      event-related functional magnetic resonance imaging
                      experiment. In two separate scanning sessions, subjects
                      encoded and retrieved items and their spatial context under
                      cholinergic stimulation or placebo with the
                      acetylcholine-esterase inhibitor physostigmine or saline
                      being administered intravenously in a double-blind
                      cross-over design. Baseline performance was recorded at a
                      separate occasion without scanning. Cholinergic stimulation
                      enhanced neural activity for successful versus unsuccessful
                      spatial context encoding in the right hippocampus but
                      reduced activity for successful versus unsuccessful spatial
                      context retrieval in the right amygdala. These data may
                      bridge the gap between rodent and human studies by showing
                      that also in man cholinergic stimulation enhances encoding
                      but interferes with retrieval on a neural level.
                      Furthermore, baseline performance negatively correlated with
                      the effect of cholinergic stimulation. Thus, participants
                      who were worse at baseline benefited more from cholinergic
                      stimulation than those who had better baseline values,
                      indicating that a cholinergic deficit contributes to the
                      memory decline even in healthy older subjects.},
      keywords     = {Aged / Amygdala: drug effects / Amygdala: physiology /
                      Analysis of Variance / Cholinesterase Inhibitors:
                      administration $\&$ dosage / Cholinesterase Inhibitors:
                      pharmacology / Cross-Over Studies / Double-Blind Method /
                      Female / Functional Laterality: drug effects / Hippocampus:
                      drug effects / Hippocampus: physiology / Humans /
                      Injections, Intravenous / Magnetic Resonance Imaging / Male
                      / Memory: drug effects / Middle Aged / Neuropsychological
                      Tests / Physostigmine: administration $\&$ dosage /
                      Physostigmine: pharmacology / Psychomotor Performance: drug
                      effects / Reaction Time: drug effects / Space Perception:
                      drug effects / Spatial Behavior: drug effects /
                      Cholinesterase Inhibitors (NLM Chemicals) / Physostigmine
                      (NLM Chemicals) / J (WoSType)},
      cin          = {INM-3},
      ddc          = {590},
      cid          = {I:(DE-Juel1)INM-3-20090406},
      pnm          = {Funktion und Dysfunktion des Nervensystems},
      pid          = {G:(DE-Juel1)FUEK409},
      shelfmark    = {Neurosciences},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:19553452},
      UT           = {WOS:000267339000019},
      doi          = {10.1523/JNEUROSCI.0203-09.2009},
      url          = {https://juser.fz-juelich.de/record/7950},
}