Mismatch negativity and low frequency oscillations in schizophrenia families

Abstract

Objective Theta-alpha range oscillations have been associated with MMN in healthy controls. Our previous studies showed that theta-alpha activities are highly heritable in schizophrenia patients’ families. We aimed to test the hypothesis that theta-alpha activities may contribute to MMN in schizophrenia patients and their family members. Methods We compared MMN and single trial oscillations during MMN in 95 patients, 75 first-degree relatives, 87 controls, and 34 community subjects with schizophrenia spectrum personality (SSP) traits. Results We found that 1) MMN was reduced in patients (p<.001) and SSP subjects (p=.047) but not in relatives (p=.42); 2) there were augmented 1–20 Hz oscillations in patients (p=.02 to <.001) during standard and deviant stimuli; 3) theta-alpha (5–12 Hz) oscillations had the strongest correlation to MMN in controls and relatives (ΔR2=21.4% – 23.9%, all p<.001), while delta (<5 Hz) showed the strongest correlation to MMN in schizophrenia and SSP trait subjects; and, 4) MMN (h2=.56, p=0.002) and theta-alpha (h2=.55, p=0.004) were heritable traits. Conclusions Low frequency oscillations have a robust relationship with MMN and the relationship appears altered by schizophrenia; and schizophrenia patients showed augmented low frequency activities during the MMN paradigm. Significance The results encourage investigation of low frequency oscillations to elucidate the neurophysiological pathology underlying MMN abnormalities in schizophrenia.

Frontal Glutamate and γ-Aminobutyric Acid Levels and Their Associations With Mismatch Negativity and Digit Sequencing Task Performance in Schizophrenia

“…The event-related potential and MRS methods have been described previously, 33,36,52 and details are given in the eMethods in the Supplement. Briefly, the event-related potential was recorded using a 64-channel system 2 (SynAmps; Compumedics Neuroscan) at a 1-kHz sampling rate with bandpass at 0.1 to 200 Hz.…”

“…The paradigm was a passive duration-deviant odd-ball task. 52 Standard and deviant trials were averaged separately, followed by subtraction of the 2 mean waveforms. Mismatch negativity was scored by peak detection within a poststimulus window of 100 to 225 milliseconds by an automatic algorithm, followed by visual inspection to verify correct placement of each marker for peak detection.…”

Stimulus-specific adaptation in the inferior colliculus: The role of excitatory, inhibitory and modulatory inputs

“…MMN has been positioned as a potentially promising biomarker candidate for the diagnosis of pathologies such as schizophrenia (Harms et al, 2014;Nagai et al, 2013) or autism spectrum disorders, including Asperger's syndrome (e.g., O'Connor, 2012). Patients with schizophrenia exhibited a reduced ability to detect acoustic changes reflected in reduced MMN (Fisher, Grant, Smith, Borracci, Labelle, & Knott, 2012;Hong, Moran, Du, O'Donnell, & Summerfelt, 2012;Michie, 2001). Schizophrenia has been associated with alterations in neurotransmission as the one mediated by the NMDA (N-methyl-d-aspartate) receptor (Matsuno et al, 2015).…”

Neural mechanisms of mismatch negativity (MMN) dysfunction in schizophrenia

“…64 ). By contrast, we 34 and others 35,36,65 have linked MMN deficits to impaired theta-frequency response, and underlying NMDAR dysfunction in rodent 66,67 and primate 28 models. At the local circuit level, theta rhythms are tied to interactions involving non-PV cells, especially somatostatintype inhibitory interneurons 6,29,68 .…”

“…We 34 and others 35,36 have previously linked MMN dysfunction in schizophrenia primarily to impaired theta frequency response. In the present study we investigate alpha-frequency activation to standard stimuli as well.…”