Phase-Amplitude Coupling of the Electroencephalogram in the Auditory Cortex in Schizophrenia.

BACKGROUND: Cross-frequency interactions may coordinate neural circuits operating at different frequencies. While neural oscillations associated with particular circuits in schizophrenia (SZ) are impaired, few studies have examined cross-frequency interactions. Here we examined phase-amplitude coupling (PAC) in the electroencephalograms of individuals with SZ and healthy control subjects (HCs). We computed PAC during the baseline period of 40-Hz auditory steady-state stimulation and rest. We hypothesized that subjects with SZ would show abnormal theta/gamma coupling during stimulation, especially in the left auditory cortex, and coupling with high frequencies would be higher during stimulation than during rest. METHODS: We reanalyzed data from 18 subjects with SZ and 18 HCs. Auditory cortex electroencephalogram activity was estimated using dipole source localization. PAC was computed using the debiased PAC measure, calculated with the generalized Morse wavelet transform. PAC clusters were identified using cluster-corrected permutation testing and interrogated in analyses of variance with correction for multiple tests. RESULTS: Overall, coupling of high beta and gamma amplitude was higher during the auditory steady-state response, while alpha/beta PAC was higher during rest. Theta/alpha PAC was higher in subjects with SZ than in HCs. Theta/gamma PAC was lateralized to the left hemisphere in HCs but was not lateralized in subjects with SZ. CONCLUSIONS: PAC involving high frequencies was state dependent and not abnormal in SZ. Increased theta/alpha PAC in subjects with SZ was consistent with other evidence of increased low-frequency activity. Hemispheric lateralization of theta/gamma PAC was reduced in subjects with SZ, consistent with evidence for left hemisphere auditory cortex abnormalities in subjects with SZ. PAC may reveal new insights into neural circuitry abnormalities in SZ and other neuropsychiatric disorders.

Preattentive dysfunction in patients with bipolar disorder as revealed by the pitch-mismatch negativity: a magnetoencephalography (MEG) study.

OBJECTIVES: Mismatch negativity (MMN) and its magnetic counterpart (MMNm) are thought to reflect an automatic process that detects a difference between an incoming stimulus and the sensory memory trace of preceding stimuli. In patients with schizophrenia, an attenuation of the MMN/MMNm amplitude has been repeatedly reported. Heschl's gyrus (HG) is one of the major generators of MMN and the functional alteration of HG has been reported in patients with bipolar disorder. The present study investigated the pitch-MMNm in patients with bipolar disorder using whole-head 306-ch magnetoencephalography (MEG). METHODS: Twenty-two patients and 22 healthy controls participated in this study. Subjects were presented with two types of auditory stimulus sequences. One consisted of 1,000 Hz standards (probability = 90%) and 1,200 Hz deviants (probability = 10%), and the other consisted of 1,000 Hz standards (90%) and 1,200 Hz deviants (10%). These two tasks were each performed twice. Event-related brain responses to standard tones were subtracted from responses to deviant tones. RESULTS: Patients with bipolar disorder showed a significant bilateral reduction in magnetic global field power (mGFP) amplitudes (p = 0.02) and dipole moments of the MMNm (p = 0.04) compared with healthy controls. Patients with admission experience showed significantly reduced mGFP amplitudes of MMNm compared with patients without admission experience (p = 0.004). Additionally, patients with more severe manic symptoms had smaller mGFP amplitudes of MMNm (ρ = -0.50, p = 0.05). CONCLUSIONS: The results of this study suggest that patients with bipolar disorder may exhibit preattentive auditory dysfunction indexed by reduced pitch-MMNm responses. Pitch-MMNm could be a potential trait marker reflecting the global severity of bipolar disorder.

Reduced high and low frequency gamma synchronization in patients with chronic schizophrenia.

Schizophrenia has been conceptualized by dysfunctional cognition and behavior related to abnormalities in neural circuitry. The functioning of the neural circuitry can be assessed using the auditory steady state response (ASSR). Moreover, in recent years, research on high (>60 Hz) gamma band oscillations has become of increasing interest. The current study used whole-head, 306-channel magnetoencephalography (MEG) and investigated low and high gamma band oscillations with the ASSR. The subjects comprised 17 patients with schizophrenia and 22 controls. The current study investigated the MEG-ASSR elicited by click trains of 20-, 30-, 40- and 80-Hz frequencies, and symptom-ASSR associations in patients with schizophrenia. The mean power, phase-locking factor, dipole moments and source locations of the ASSR were estimated. The main findings were: (1) patients with schizophrenia showed bilaterally reduced ASSR power and dipole moments specific to the 40-Hz and 80-Hz frequencies; (2) patients with schizophrenia showed less right-greater-than-left 40-Hz ASSR power and phase-locking factor compared with healthy subjects, indicating that schizophrenics may be characterized by an abnormal asymmetry of the 40-Hz ASSR; (3) increased severity of global hallucinatory experiences was significantly associated with smaller left 80-Hz MEG-ASSR in patients with schizophrenia. The current study highlights the high and low frequency gamma abnormalities and provides clear evidence that schizophrenia is characterized by abnormalities in neural circuitry.