Person:

Spencer, Kevin

Several studies have reported deficits in (\gamma) oscillatory activity elicited by sensory stimulation or cognitive processes in schizophrenia patients (SZ) compared to healthy control subjects (HC). However, the evidence for cortical hyperexcitability and reduced function of N-methyl-D-aspartate receptors (NMDARs) on parvalbumin-expressing inhibitory interneurons in schizophrenia leads to the prediction that (\gamma) activity should rather be increased in SZ, but data supporting this hypothesis have been lacking. One possibility is that baseline induced (\gamma) power is increased, an effect that might have gone unnoticed in studies of stimulus-locked oscillations. Here we addressed this question by re-analyzing the data from a previously published study on the 40 Hz auditory steady-state response (ASSR) in schizophrenia in which dipole source localization was used to examine (\gamma) responses in the left and right auditory cortices. Subjects were 16 HC and 18 chronic SZ, who listened to trains of clicks presented at 40 Hz during electroencephalogram recording. Independent component analysis was used to remove ocular artifacts. Power spectra were computed for the pre-stimulus baseline period. We found that baseline power was higher in SZ than HC at 40 Hz in the left auditory cortex. Baseline 40 Hz power in the left auditory cortex was also correlated with ASSR evoked power in SZ. Thus, (\gamma) oscillation abnormalities in schizophrenia may include abnormal increases in baseline power as well as deficits in evoked oscillations. These baseline increases could be the sign of NMDAR hypofunction on parvalbumin-expressing inhibitory interneurons, which would be consistent with acute NMDAR antagonism and genetic ablation models of schizophrenia.

Background: Abnormalities in γ oscillations (30–100 Hz) in the scalp-recorded electroencephalogram (EEG) have been proposed to reflect neural circuitry abnormalities in schizophrenia. Oscillations in the γ band are thought to play an important role in visual perception, mediating the binding of visual features into coherent objects. However, there is relatively little evidence to date of deficits in γ-mediated processes associated with Gestalt perception in schizophrenia. Methods: Fourteen healthy control subjects (HC) and 17 chronic schizophrenia patients (SZ) discriminated between illusory Kanisza Squares and No-Square control stimuli, indicating their judgment with a manual button press. Time-frequency decomposition of the EEG was computed with the Morlet wavelet transform. Time-frequency maps of phase locking factor (PLF) values were calculated for stimulus- and response-locked oscillations. Results: HC and SZ did not differ in reaction time, error rate, an early ERP effect associated with Gestalt processing, nor an early visual-evoked γ oscillation. Two response-locked high γ effects had greater PLF for Square than No-Square stimuli in HC, and the reverse pattern in SZ. One of these effects was correlated with thought disorder symptom ratings in SZ. Conclusions: SZ demonstrated abnormalities in γ oscillations associated with the perception of Gestalt objects, while their early visual-evoked γ activity was mostly normal, contrary to previous results. This study supports the hypothesis that high-frequency oscillations are sensitive to aspects of psychosis.

Background: The early visual-evoked gamma oscillation (VGO) elicited by Gestalt stimuli is reduced in schizophrenia patients compared to healthy individuals, but it is unknown whether this effect is specific to these particular stimuli and task. In contrast, the early auditory-evoked gamma oscillation (AGO) was reported to be unaffected in a sample of unmedicated, mostly first-episode schizophrenics (Gallinat et al, 2004, Clin Neurophysiol), but it is unknown whether this oscillation is abnormal in chronic, medicated patients. We investigated these issues by examining the VGO and AGO in chronic schizophrenics (SZ) and matched healthy controls (HC). Methods: Subjects (21 HC, 23 SZ) performed visual and auditory oddball tasks. Visual stimuli were letters, and auditory stimuli were simple tones. Event-related spectral measures (phase locking factor and evoked power) were computed on Morlet wavelet-transformed single epochs from the standard trials. Results: VGO phase locking at occipital electrodes was reduced in SZ compared to HC. In contrast, AGO phase locking and evoked power did not differ between groups. Conclusions: The VGO deficit may be a general phenomenon in schizophrenia, while the AGO evoked by simple tone stimuli does not appear to be abnormal in chronic, medicated schizophrenics.

Background: In chronic schizophrenia and chronic bipolar disorder, gamma band (30–100 Hz) auditory steady-state EEG responses (ASSRs) are reduced in power and phase locking, likely reflecting neural circuit dysfunction. Here we examined whether gamma ASSR deficits are also present at first hospitalization for psychosis. Methods: Subjects were 16 first episode schizophrenia patients (SZ), 16 first episode affective disorder patients (AFF) (13 with bipolar disorder), and 33 healthy controls (HC). Stimuli were 20, 30, and 40 Hz binaural click trains. ASSR phase locking and evoked power were analyzed using the Morlet wavelet transform. Results: At 40 Hz stimulation, SZ and AFF had significantly reduced phase locking compared to HC. This deficit was more pronounced over the left hemisphere in SZ. Evoked power at 40 Hz was also reduced in the patients compared to HC. At 30 Hz stimulation phase locking and evoked power were reduced in both patient groups. The 20 Hz ASSR did not differ between groups, but phase locking and evoked power of the 40 Hz harmonic of the 20 Hz ASSR were reduced in both SZ and AFF. Phase locking of this 40 Hz harmonic was correlated with total positive symptoms in SZ. Conclusions: The gamma ASSR deficit is present at first hospitalization for both schizophrenia and affective disorder, but shows a left hemisphere bias in first hospitalized SZ. Some of the neural circuitry abnormalities underlying the gamma ASSR deficit may be common to psychoses in general, while others may be specific to particular disorders.

Attentional deficits are prominent among the cognitive disturbances found in schizophrenia. Given that schizophrenia is also characterized by abnormalities in high-frequency oscillations, we investigated whether attentional function in schizophrenia is related to abnormalities in high-frequency oscillations in a visual discrimination task in which attentional load was manipulated. Sixteen healthy control subjects (HC) and 23 chronic schizophrenia patients (SZ) discriminated between target discs (p = 0.2) and standard discs (p = 0.8). Attentional load was manipulated by varying the size difference between the target and standard discs across blocks: large (Easy condition), medium (Medium), and small (Difficult). The electroencephalogram was recorded and the oscillations evoked by the standard stimuli were analyzed using the Morlet wavelet transform. Subjects’ performance decreased as attentional load increased, but HC and SZ did not differ. Attentional load increased β phase-locking factor at frontal, parietal, and occipital electrode sites in HC but not SZ. In SZ, however, there was a correlation between the β attentional load effect and overall d′, indicating that high-performing SZ had relatively normal β attentional load effects. These results show that variations in attentional load are associated with β oscillations and provide a link between attentional dysfunction and β-generating neural circuitry in schizophrenia.