title: Oscillatory underpinnings of mismatch negativity and their relationship with cognitive function in patients with schizophrenia.
abstract: BACKGROUND
  Impairments in mismatch negativity (MMN) generation have been consistently reported in patients with schizophrenia. However, underlying oscillatory activity of MMN deficits in schizophrenia and the relationship with cognitive impairments have not been investigated in detail. Time-frequency power and phase analyses can provide more detailed measures of brain dynamics of MMN deficits in schizophrenia.
  
  
  METHODS
  21 patients with schizophrenia and 21 healthy controls were tested with a roving frequency paradigm to generate MMN. Time-frequency domain power and phase-locking (PL) analysis was performed on all trials using short-time Fourier transforms with Hanning window tapering. A comprehensive battery (CANTAB) was used to assess neurocognitive functioning.
  
  
  RESULTS
  Mean MMN amplitude was significantly lower in patients with schizophrenia (95% CI 0.18 - 0.77). Patients showed significantly lower EEG power (95% CI -1.02 - -0.014) in the ~4-7 Hz frequency range (theta band) between 170 and 210 ms. Patients with schizophrenia showed cognitive impairment in multiple domains of CANTAB. However, MMN impairments in amplitude and power were not correlated with clinical measures, medication dose, social functioning or neurocognitive performance.
  
  
  CONCLUSIONS
  The findings from this study suggested that while MMN may be a useful marker to probe NMDA receptor mediated mechanisms and associated impairments in gain control and perceptual changes, it may not be a useful marker in association with clinical or cognitive changes. Trial-by-trial EEG power analysis can be used as a measure of brain dynamics underlying MMN deficits which also can have implications for the use of MMN as a biomarker for drug discovery.
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom ; Bahcesehir University, Istanbul, Turkey ; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Muzaffer
authors.initials: M
authors.lastname: Kaser
authors.affiliation: GlaxoSmithKline, Clinical Unit Cambridge, Medicines Discovery and Development, Cambridge, United Kingdom.
authors.forename: Fruzsina
authors.initials: F
authors.lastname: Soltesz
authors.affiliation: GlaxoSmithKline, Clinical Unit Cambridge, Medicines Discovery and Development, Cambridge, United Kingdom.
authors.forename: Phil
authors.initials: P
authors.lastname: Lawrence
authors.affiliation: GlaxoSmithKline, Clinical Unit Cambridge, Medicines Discovery and Development, Cambridge, United Kingdom.
authors.forename: Sam
authors.initials: S
authors.lastname: Miller
authors.affiliation: GlaxoSmithKline, Clinical Unit Cambridge, Medicines Discovery and Development, Cambridge, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Dodds
authors.affiliation: Department of Psychology, University of Wollongong, Wollongong, Australia.
authors.forename: Rodney
authors.initials: R
authors.lastname: Croft
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom ; Cambridge and Peterborough NHS Foundation Trust, United Kingdom.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Dudas
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom ; South Essex Partnership NHS Foundation Trust, United Kingdom.
authors.forename: Rashid
authors.initials: R
authors.lastname: Zaman
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom ; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom ; Cambridge and Peterborough NHS Foundation Trust, United Kingdom.
authors.forename: Emilio
authors.initials: E
authors.lastname: Fernandez-Egea
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom ; Cambridge and Peterborough NHS Foundation Trust, United Kingdom.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Müller
authors.affiliation: Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Dean
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom ; GlaxoSmithKline, Clinical Unit Cambridge, Medicines Discovery and Development, Cambridge, United Kingdom ; Cambridge and Peterborough NHS Foundation Trust, United Kingdom ; Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Bullmore
authors.affiliation: Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom ; School of Psychology and Psychiatry, Monash University, Melbourne, Australia ; Neuroscience Discovery Medicine, UCB Pharma, Brussels, Belgium.
authors.forename: Pradeep J
authors.initials: PJ
authors.lastname: Nathan
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000503:physiopathology*; D003071:Cognition / Q000502:physiology*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009341:Negativism; D009483:Neuropsychological Tests; D012559:Schizophrenia / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D055815:Young Adult