Grantley W. Taylor

The Early Auditory Gamma-Band Response Is Heritable and a Putative Endophenotype of Schizophrenia

BACKGROUND Reduced power and phase locking of the early auditory gamma-band response (EAGBR) have been reported in schizophrenia, but findings are equivocal. Further, little is known about genetic (heritability) and environmental influences on the EAGBR or its potential as an endophenotype of schizophrenia. The present study used a twin design to examine whether EAGBR power and phase locking are heritable and reduced in schizophrenic patients and their unaffected co-twins and thus putative endophenotypes of schizophrenia. METHODS The study sample included a total of 194 individuals, consisting of 15 monozygotic [MZ] twin pairs concordant for schizophrenia, 9 MZ twin pairs discordant for schizophrenia, and 42 MZ and 31 dizygotic (DZ) control pairs. Evoked power and phase-locking factor of the EAGBR were computed on Morlet wavelet-transformed electroencephalogram responses to standard tones during an auditory oddball target detection task. Structural equation modeling was applied to estimate heritability and genetic and environmental correlations with schizophrenia for the EAGBR measures. RESULTS Both evoked power and phase-locking phenotypes were heritable traits (power: h(2) = 0.65; phase locking: h(2) = 0.63). Impaired EAGBR measures were significantly associated with schizophrenia. Patients with schizophrenia and their unaffected identical co-twins exhibited significantly reduced EAGBR power compared with control subjects. In each phenotype, shared genetic factors were likely the source of the observed associations with schizophrenia. CONCLUSIONS Our results support EAGBR measures as putative endophenotypes of schizophrenia, likely reflecting an ubiquitous local cortical circuit deficit.

Sensory Gating Event–Related Potentials and Oscillations in Schizophrenia Patients and Their Unaffected Relatives

BACKGROUND The P50 event-related potential sensory gating deficit, a failure to inhibit responses to repeated stimuli, is a leading endophenotype for schizophrenia (SZ). Both gamma and beta event-related oscillations (EROs) are major contributors to the auditory P50 response. However, the topographic distribution of gamma and beta ERO responses to initial (S1) and repeat (S2) stimuli and the association of these oscillations with P50 sensory gating are not clear. METHODS A total of 51 schizophrenic patients, 25 unaffected first-degree relatives, and 34 healthy comparison subjects were tested using a paired-click paradigm. Evoked power of gamma- and beta-band responses using wavelet analyses to S1 and S2 stimuli and gating of EROs and P50 were the main outcome measures. RESULTS A P50 gating deficit was found in patients (P < .001) and at a trend level in relatives (P = .087). Patients showed widely distributed reductions in gamma and beta EROs to S1 stimuli and S2 stimuli, respectively, and impaired gating in both frequencies. Reduced gamma and beta ERO activity in patients was associated primarily with age of onset. Relatives did not differ significantly from control subjects in either EROs power or gating. Gating of P50, gamma, and beta were not significantly correlated (r = .18-.19, P > .05). CONCLUSIONS These results suggest that ERO deficits in gamma to S1 and beta to S2 stimuli and impaired ERO gating are associated with SZ, but are not related to genetic liability for the illness. The components of information processing assessed by gamma- and beta gating appear to be independent from those mediated by P50 suppression.

Early auditory gamma band response abnormalities in first hospitalized schizophrenia.

BACKGROUND Abnormalities in coherent cortical circuit functioning, reflected in gamma band activity (to approximately 40 Hz), may be a core deficit in schizophrenia. The early auditory gamma band response (EAGBR) is a neurophysiologically simple probe of circuit functioning in primary auditory cortex. We examined the EAGBR in first hospitalized schizophrenia to assess whether it was reduced at first hospitalization. METHOD Wavelet evoked power and intertrial phase locking of the EAGBR at Fz to standard tones during an oddball target detection task were examined in 28 first hospitalized schizophrenia patients (10 female) and 44 control subjects (17 female). RESULTS At first hospitalization EAGBR trial-to-trial phase locking and evoked power were significantly reduced in patients. Although reduced overall in patients, greater total symptoms were significantly associated with greater gamma phase locking and power. Additionally, greater EAGBR power was marginally associated with greater positive factor scores, hallucinations, and thinking disturbance. CONCLUSIONS Abnormalities of gamma band functioning in local auditory sensory circuits are present in schizophrenia at first hospitalization further evidence that basic sensory processes are impaired in schizophrenia. It remains to be determined whether the EAGBR becomes permanently impaired with disease progression, and if its reduction is specific to schizophrenia.

Semantic priming increases left hemisphere theta power and intertrial phase synchrony.

Information is stored in distributed cortical networks, but it is unclear how distributed stores are synthesized into a unified percept. Activation of local circuits in the gamma range (30 < < 80 Hz), and distributed stores in the low theta range (3-5 Hz) may underlie perceptual binding. Words have a crucial role in semantic memory. Within memory, the activation of distributed semantic stores is facilitated by conceptually related previous items, termed semantic priming. We sought to detect event-related brain oscillations (EROs) sensitive to semantic activation and priming. Here, we show that low theta evoked power and intertrial phase locking (4-5 Hz) from 250-350 msec over left hemisphere language areas was greater to related than to unrelated words. Theta band event-related oscillations over left hemisphere language areas may provide a brain signature for semantic activation across distributed stores being facilitated by semantic priming.

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