Abnormal beta and gamma frequency neural oscillations mediate auditory sensory gating deficit in schizophrenia.

BACKGROUND: Sensory gating is a process in which the brain's response to irrelevant and repetitive stimuli is inhibited. The sensory gating deficit in schizophrenia (SZ) is typically measured by the ratio or difference score of the P50 event-related potential (ERP) amplitudes in response to a paired click paradigm. While the P50 gating effect has usually been measured in relation to the peak amplitude of the S1 and S2 P50 ERPs, there is increasing evidence that inhibitory processes may be reflected by evoked or induced oscillatory activity during the inter-click interval in the beta (20-30 Hz) and gamma (30-50 Hz) frequency bands. We therefore examined the relationship between frequency specific activity in the inter-click interval with gating effects in the time and frequency domains. METHOD: Paired-auditory stimuli were presented to 131 participants with schizophrenia and 196 healthy controls (HC). P50 ERP amplitudes to S1 and S2as well as averaged- and single-trial beta (20-30 Hz) and gamma (30-50 Hz) frequency power during the inter-click interval were measured from the CZ electrode site. RESULTS: In the time domain, P50 gating deficits were apparent in both ratio and difference scores. This effect was mainly due to smaller S1 amplitudes in the patient group. SZ patients exhibited less evoked beta and gamma power, particularly at the 0-100 ms time point, in response to S1. Early (0-100 ms) evoked beta and gamma responses were critical in determining the S1 amplitude and extent of P50 gating across the delay interval for both HC and SZ. CONCLUSION: Our findings support a disruption in initial sensory registration in those with SZ, and do not support an active mechanism throughout the delay interval. The degree of response to S1 and early beta and gamma frequency oscillations in the delay interval provides information about the mechanisms supporting auditory sensory gating, and may provide a framework for studying the mechanisms that support sensory inhibition.

Auditory steady state response in the schizophrenia, first-degree relatives, and schizotypal personality disorder.

The power and phase synchronization of the auditory steady state response (ASSR) at 40 Hz stimulation is usually reduced in schizophrenia (SZ). The sensitivity of the 40 Hz ASSR to schizophrenia spectrum phenotypes, such as schizotypal personality disorder (SPD), or to familial risk has been less well characterized. We compared the ASSR of patients with SZ, persons with schizotypal personality disorder, first degree relatives of patients with SZ, and healthy control participants. ASSRs were obtained to 20, 30, 40 and 50 Hz click trains, and assessed using measures of power (mean trial power or MTP) and phase consistency (phase locking factor or PLF). The MTP to 40 Hz stimulation was reduced in relatives, and there was a trend for MTP reduction in SZ. The 40 Hz ASSR was not reduced in SPD participants. PLF did not differ among groups. These data suggest the 40 Hz ASSR is sensitive to familial risk factors associated with schizophrenia.

Auditory steady state response in bipolar disorder: relation to clinical state, cognitive performance, medication status, and substance disorders.

OBJECTIVES: Abnormalities in auditory steady state response (ASSR) at gamma range frequencies have been found in bipolar disorder, but the relationship of these neurophysiological disturbances to clinical factors has not been well characterized. We therefore evaluated the ASSR in bipolar disorder and examined its sensitivity to clinical symptoms, cognitive function, and pharmacological treatment. METHODS: A total of 68 patients with bipolar disorder and 77 control participants were evaluated. Click trains presented at 20, 30, 40, and 50 Hz evoked ASSRs. Mean trial power (MTP) and phase locking factor (PLF) measured response magnitude and phase synchronization of the ASSR at each stimulation frequency. Clinical state, pharmacological treatment, and neuropsychological performance were assessed, and their respective relationships with ASSR measures were evaluated. RESULTS: Patients with bipolar disorder showed reduced MTP and PLF compared to control participants. Bipolar disorder patients taking psychotropic medications had decreased PLF relative to patients withdrawn from medications. Control participants performed better on neuropsychological tests than bipolar disorder patients; however, test scores did not correlate with ASSR measures. CONCLUSIONS: Deficits in the generation and maintenance of ASSR are present in bipolar disorder, implicating disturbances in auditory pathways. ASSR may be sensitive to medication status. Other clinical features, including mood state, psychotic features, cognitive performance, smoking, or history of substance use disorder, were unrelated to MTP or PLF.

Increased temporal variability of auditory event-related potentials in schizophrenia and Schizotypal Personality Disorder.

Previous studies suggest that deficits in neural synchronization and temporal integration are characteristic of schizophrenia. These phenomena have been rarely studied in SPD, which shares phenomenological and genetic similarities with schizophrenia. Event-related potentials (ERPs) were obtained using an auditory oddball task from 21 patients with schizophrenia, 19 subjects with SPD and 19 healthy control subjects. Inter-trial coherence (ITC) and event-related spectral perturbation (ERSP) were measured across trials to target tones using time-frequency analysis. ITC measures phase locking or consistency, while ERSP measures changes in power relative to baseline activity. P300 latency and amplitude were also measured from the averaged ERP to target tones. In the time-frequency analysis, subjects with SPD showed intact power but a deficit in the ITC in delta and theta frequencies compared to control subjects. Patients with schizophrenia showed deficits for both ERSP and ITC in the delta and theta frequencies. While patients with schizophrenia showed reduced P300 amplitude and delayed latency for averaged ERPs, subjects with SPD did not differ from either group. Synchronization or timing abnormalities may represent a biomarker for schizophrenia spectrum disorders, and contribute to aberrant perceptual and cognitive integration.

Relationships between auditory event-related potentials and mood state, medication, and comorbid psychiatric illness in patients with bipolar disorder.

BACKGROUND: Patients with bipolar disorder (BD) exhibit aberrations in auditory event-related potentials (ERPs), although the relationships between these measures and mood state at testing, comorbid psychiatric illness, presence of psychotic features, and medication usage are unclear. The purpose of this study was to investigate the relationships between these factors and auditory ERP measures in BD patients. METHODS: An auditory 'oddball' discrimination task was used to elicit ERPs from 69 patients with type I BD and 52 healthy controls. Patients were placed into subgroups based upon their mood state at testing (euthymic or symptomatic), and ANOVA was used to compare amplitude and peak latency measures from the N100, P200, N200, and P300 ERP components across subgroups. Multiple regression was used to investigate relationships between ERP measures and comorbid psychiatric diagnosis, history of psychotic features, and medication status. RESULTS: Relative to healthy control participants, euthymic and symptomatic BD patients exhibited reduced P300 and P200 amplitude, but ERP measures did not differ among BD patients on the basis of mood status. A history of a comorbid anxiety disorder was associated with reduced N200 peak latency, but prolonged P300 peak latency among BD patients. No other relationships between clinical variables and ERP measures were significant. CONCLUSIONS: The results suggest that disrupted auditory attention may be observed in BD patients regardless of their mood state at testing, medication status, or history of psychosis. These results extend previous findings, and provide further evidence for aberrations in the P300 ERP as an endophenotype for BD.

Event-related potential abnormalities in schizophrenia: a failure to "gate in" salient information?

Sensory gating refers to the central nervous system's ability to filter sensory inputs, and can be measured by comparing the suppression of event-related brain potential (ERP) amplitudes in a paired auditory stimulus procedure. Poor gating scores in schizophrenia may be caused by abnormal responses to the first (S1), the second (S2) or both of the paired stimuli. However, since S1 and S2 responses may index separate psychological phenomenon, corresponding to the ability to "gate in" and "gate out" sensory stimuli respectively, the precise mechanism affected in schizophrenia remains unclear. To examine the extent to which saliency processing abnormalities may contribute to S1 response deficits, standard and rare (15% probability) paired stimuli were presented to 21 participants with schizophrenia and 22 healthy controls. P50 and N100 ERP amplitude as well as low, beta and gamma frequency power were measured to examine the time course and relative contributions of oscillatory activity affecting auditory processing in schizophrenia. In this study, schizophrenia patients exhibited less evoked beta 1 power (12-20 Hz) in response to salient stimuli at S1, and lower N100 amplitude in response to all S1 stimuli. No group differences were found in the low, beta 2 (20-30 Hz), or gamma frequency ranges. These findings suggest aberrant sensory processing during stages of stimulus evaluation and saliency detection in schizophrenia.

P50 and acoustic startle gating are not related in healthy participants.

Although P50 event-related potential (ERP) suppression and acoustic startle prepulse inhibition are conceptualized as measures of sensory and sensorimotor gating, respectively, the relationship between these measures is unclear. In the present study, P50 and prepulse inhibition trials were interleaved in a single testing session to determine their relationship. Thirty-one healthy participants were presented with startle- and P50-eliciting stimuli across six trial blocks. Lead stimuli (i.e., the prepulse to the acoustic startle and the first click in the dual click ERP paradigm) resulted in significant gating, or amplitude attenuation, of responses to the startle probe and second paired click. There were no meaningful correlations between the P50 and prepulse inhibition variables, indicating that P50 suppression and acoustic startle prepulse inhibition measure distinct neural mechanisms. The implications of these findings for operationally defining the psychological construct of gating with these psychophysiological measures are discussed.

EEG synchronization to modulated auditory tones in schizophrenia, schizoaffective disorder, and schizotypal personality disorder.

OBJECTIVE: The authors tested whether neural synchronization deficits were present in subjects with schizophrenia and schizotypal personality disorder. METHOD: Amplitude-modulated tones were used to evaluate auditory steady-state evoked potential entrainment in a combined group of 21 subjects with schizophrenia or schizoaffective disorder, 11 subjects with schizotypal personality disorder, and 22 nonpsychiatric comparison subjects. RESULTS: The schizophrenia or schizoaffective disorder group exhibited decreased power compared to the schizotypal personality disorder and nonpsychiatric comparison groups. There were no differences between groups in N100 amplitude. CONCLUSIONS: Subjects with schizophrenia but not subjects with schizotypal personality disorder have deficits in steady-state responses to periodic stimuli, despite an intact response to sensory-evoked potentials (N100). These deficits reflect aberrant neural synchronization or resolution and may contribute to disturbed perceptual and cognitive integration in schizophrenia.