title: A mechanistic model of mismatch negativity in the ageing brain.
abstract: OBJECTIVE
  We investigated the neurophysiological mechanisms underpinning the generation of the mismatch negativity (MMN) in the ageing brain.
  
  
  METHODS
  We used dynamic causal modelling (DCM) to study connectivity models for healthy young and old subjects. MMN was elicited with an auditory odd-ball paradigm in two groups of healthy subjects with mean age 74 (n=30) and 26 (n=26). DCM was implemented using up to five cortical nodes. We tested models with different hierarchical complexities.
  
  
  RESULTS
  We showed that the network generating MMN consisted of 5 nodes that could modulate all intra- and inter-nodal connections. The inversion of this model showed that old subjects had increased input from rSTG to the rIFG (p<0.01) together with increased inhibition of pyramidal cells (p<0.05). Furthermore, there was reduced modulation of activity within rIFG (p<0.02) on stimulus change.
  
  
  CONCLUSIONS
  The age related change in MMN is due to a decline in frontal-based control mechanisms, with alterations in connectivity between temporal and frontal regions together with a dysregulation of the excitatory-inhibitory balance in the rIFG.
  
  
  CONCLUSIONS
  This study provides for the first time a neurobiological explanation for the age related changes of the MMN in the ageing brain.
authors.affiliation: Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address: gerald.cooray@ki.se.
authors.forename: Gerald
authors.initials: G
authors.lastname: Cooray
authors.affiliation: Wellcome Trust Centre for Neuroimaging, University College London, London, UK; Queensland Brain Institute, The University of Queensland, Brisbane, Australia; Australian Research Council Centre of Excellence for Integrative Brain Function, The University of Queensland, St Lucia, 4072 Brisbane, Australia.
authors.forename: Marta I
authors.initials: MI
authors.lastname: Garrido
authors.affiliation: Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Hyllienmark
authors.affiliation: Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tom
authors.initials: T
authors.lastname: Brismar
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D001921:Brain / Q000254:growth & development* / Q000502:physiology*; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008959:Models, Neurological; D009415:Nerve Net / Q000254:growth & development / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology
keywords: Ageing; Dynamic causal modelling; EEG; ERP; Mismatch negativity