Oscillatory Underpinnings of Mismatch Negativity and Their Relationship with Cognitive Function in Patients with Schizophrenia

Abstract

BackgroundImpairments 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.Method21 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.ResultsMean 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.ConclusionThe 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.

Paying attention to MMN in schizophrenia

“…However, the remaining two studies (Hermens et al, 2010;Toyomaki et al, 2008) report that MMN amplitude is correlated (rr0.62) with performance on trail making tasks, such that a decrease in amplitude was associated with slower processing. Inconsistency across published reports is also observed with other neuropsychological measures of controlled attention: the Intra and Extra Dimensional Set Shift tasks have shown no correlation with MMN amplitude (Kaser et al, 2013) whereas the Mental Control subtest of the Wechsler Memory Scale III was correlated (r¼0.50) with MMN (Hermens et al, 2010) such that a decrease in MMN was associated with a decrease in performance on this subtest.…”

Theta response in schizophrenia is indifferent to perceptual illusion

“…The highest consensus is that slow wave activity, including theta, in patients is enhanced during rest (Boutros et al, 2008). Task-related theta activity of patients may be reduced (A. T. Bates, Kiehl, Laurens, & Liddle, 2009;Doege, Jansen, Mallikarjun, Liddle, & Liddle, 2010;Doege et al, 2010;Haenschel et al, 2009;Kaser et al, 2013;Ramos-Loyo, Gonzalez-Garrido, Sanchez-Loyo, Medina, & Basar-Eroglu, 2009;Schmiedt, Brand, Hildebrandt, & Basar-Eroglu, 2005) or enhanced (Fehr et al, 2003;L.E. Hong, Moran, Du, O'Donnell, & Summerfelt, 2012;L.…”

Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia part I: Neurophysiology

“…Classical MMN paradigms may not be a useful marker in such association. Defi cits in complex paradigms are also most specifi c for schizophrenia (Pakarinen et al 2010;Baldeweg and Hirsch 2015;Kaser at al. 2013).…”