Gamma frequency-range abnormalities to auditory stimulation in schizophrenia.

BACKGROUND: Basic science studies at the neuronal systems level have indicated that gamma-range (30-50 Hz) neural synchronization may be a key mechanism of information processing in neural networks, reflecting integration of various features of an object. Furthermore, gamma-range synchronization is thought to depend on the glutamatergically mediated interplay between excitatory projection neurons and inhibitory neurons utilizing gamma-aminobutyric acid (GABA), which postmortem studies suggest may be abnormal in schizophrenia. We therefore tested whether auditory neural networks in patients with schizophrenia could support gamma-range synchronization. METHODS: Synchronization of the electroencephalogram (EEG) to different rates (20-40 Hz) of auditory stimulation was recorded from 15 patients with schizophrenia and 15 sex-, age-, and handedness-matched control subjects. The EEG power at each stimulation frequency was compared between groups. The time course of the phase relationship between each stimulus and EEG peak was also evaluated for gamma-range (40 Hz) stimulation. RESULTS: Schizophrenic patients showed reduced EEG power at 40 Hz, but not at lower frequencies of stimulation. In addition, schizophrenic patients showed delayed onset of phase synchronization and delayed desynchronization to the click train. CONCLUSIONS: These data provide new information on selective deficits in early-stage sensory processing in schizophrenia, a failure to support the entrainment of intrinsic gamma-frequency oscillators. The reduced EEG power at 40 Hz in schizophrenic patients may reflect a dysfunction of the recurrent inhibitory drive on auditory neural networks.

High-density recording and topographic analysis of the auditory oddball event-related potential in patients with schizophrenia.

BACKGROUND: Prior research has shown reductions of the N1, N2, and P300 auditory event-related potential (ERP) components in schizophrenic patients. Most studies have shown a greater P300 reduction in left versus right temporal leads in schizophrenic patients. These studies were done with sparse electrode arrays, covering restricted areas of the head, thus providing an incomplete representation of the topographic field distribution. METHODS: We used a 64-channel montage to acquire auditory oddball ERPs from 24 schizophrenic patients and 24 controls subjects. The N1, P2, N2, P300, and N2 difference (N2d) amplitudes and latencies were tested for group and laterality differences. Component topographies were mapped onto a three-dimensional head model to display the group differences. RESULTS: The schizophrenic group showed reduction of the N1 component, perhaps reflecting reduced arousal or vigilance, but no N1 topographic difference. An N2d was not apparent in the schizophrenic patients, perhaps reflecting severe disruption in neural systems of stimulus categorization. In the patients, the P300 was smaller over the left temporal lobe sites than the right. CONCLUSIONS: The increased ERP spatial sampling allowed a more complete representation of the dipolar nature of the P300, which showed field contours consistent with neural sources in the posterior superior temporal plane.

Auditory mismatch negativity in schizophrenia: topographic evaluation with a high-density recording montage.

OBJECTIVE: The mismatch negativity, a negative component in the auditory event-related potential, is thought to index automatic processes involved in sensory or echoic memory. The authors' goal in this study was to examine the topography of auditory mismatch negativity in schizophrenia with a high-density, 64-channel recording montage. METHOD: Mismatch negativity topography was evaluated in 23 right-handed male patients with schizophrenia who were receiving medication and in 23 nonschizophrenic comparison subjects who were matched in age, handedness, and parental socioeconomic status. The Positive and Negative Syndrome Scale was used to measure psychiatric symptoms. RESULTS: Mismatch negativity amplitude was reduced in the patients with schizophrenia. They showed a greater left-less-than-right asymmetry than comparison subjects at homotopic electrode pairs near the parietotemporal junction. There were correlations between mismatch negativity amplitude and hallucinations at left frontal electrodes and between mismatch negativity amplitude and passive-apathetic social withdrawal at left and right frontal electrodes. CONCLUSIONS: Mismatch negativity was reduced in schizophrenia, especially in the left hemisphere. This finding is consistent with abnormalities of primary or adjacent auditory cortex involved in auditory sensory or echoic memory.

Frontal evaluation and posterior representation in target detection.

This study examined the topography of the event-related potential in visual-spatial compared to visual-object target detection. The initial index of target detection in the ERP was an inferior anterior P2a accompanied by a posterior N2b. Single unit studies in the monkey indicate that the detection of task-relevant stimuli requires interaction between prefrontal cortex and perceptual representation areas in the posterior brain. The posterior brain processes the physical features of stimuli while frontal cortex performs higher-order operations, such as evaluating the task-relevance of a stimulus. Target detection requires an interaction between feature representations and relevance representations. We hypothesize that the P2a and N2b ERP indices of target detection reflect this frontal/posterior interaction. Visual-spatial feature information is processed in the dorsal posterior brain (posterior parietal cortex) and visual-object information is processed in the ventral posterior brain (inferior occipito-temporal cortex). We observed that at the peak of the P2a the N2b was located over posterior dorsal leads in visual-spatial target detection and over posterior ventral leads in visual-object target detection. The P2a was largest over inferior prefrontal leads in both tasks. We suggest that this distribution is consistent with interaction between orbitofrontal cortical areas of salience representation and posterior cortical areas of stimulus feature representation.

Visual hemifield mapping using transcranial magnetic stimulation coregistered with cortical surfaces derived from magnetic resonance images.

The perception of a visual stimulus can be inhibited by occipital transcranial magnetic stimulation. This visual suppression effect has been attributed to disruption in the cortical gray matter of primary visual cortex or in the fiber tracts leading to V1 from the thalamus. However, others have suggested that the visual suppression effect is caused by disruption in secondary visual cortex. Here the authors used a figure-eight coil, which produces a focal magnetic field, and a Quadropulse stimulator to produce visual suppression contralateral to the stimulated hemisphere in five normal volunteer subjects. The authors coregistered the stimulation sites with magnetic resonance images in these same subjects using optical digitization. The stimulation sites were mapped onto the surface of the occipital lobes in three-dimensional reconstructions of the cortical surface to show the distribution of the visual suppression effect. The results were consistent with disruption of secondary visual cortical areas.

Emotional expectancy: brain electrical activity associated with an emotional bias in interpreting life events.

University students in either an optimistic or pessimistic mood state read brief stories of daily life events as event-related brain potentials were collected during the final word of each story. For subjects in a pessimistic mood, a bias to expect negative outcomes was seen as an N400/P300 effect over posterior scalp regions. For subjects in an optimistic mood, a differentiation between good and bad outcomes was also observed, but it was specific to medial frontal areas. Analysis of single-trial P300 latencies suggested that semantically incongruent and mood-incongruent outcome words resulted in increased median latency of the late positive complex (LPC) and resulted in increased variability of LPC latency across trials.

Dense sensor array topography of the event-related potential to task-relevant auditory stimuli.

High spatial density recording and better topographic mapping algorithms have improved the spatial resolving power of the event-related potential (ERP), adding to its already excellent temporal resolution. This study used a 64 channel recording array and spherical spline interpolation to create topographic descriptions of the voltage and current density scalp distributions of the ERP in an auditory oddball paradigm. Frequent (standard) and infrequent (target) tones were presented at a rate of one every approximately 2500 ms to a group of 20 college undergraduates in passive listening and active (count the infrequent tones) task blocks. ANOVAs and topographic analyses were performed on the primary deflections in the 'late' portion of the ERP: the P1, N1, P2, N2 and P3. A target minus standard difference wave was also created for each task. The difference wave contained a mismatch negativity (MMN), an N2b and a P3d. The MMN did not differ between the passive and active tasks and had a topography similar to the N1; also the difference wave P3d was topographically similar to the target P3. The N2b, which occurred only to targets in the active condition, and was the first index of target detection, had a scalp distribution consistent with generation in frontal and superior temporal cortex, suggesting activity in cortical areas of selective attention and auditory stimulus representation.

Identification of neural circuits underlying P300 abnormalities in schizophrenia.

Event-related potentials (ERPs) provide a noninvasive method to evaluate neural activation and cognitive processes in schizophrenia. The pathophysiological significance of these findings would be greatly enhanced if scalp-recorded ERP abnormalities could be related to specific neural circuits and/or regions of the brain. Using quantitative approaches in which scalp-recorded ERP components are correlated with underlying neuroanatomy in schizophrenia, we focused on biophysical and statistical procedures (partial least squares) to relate the auditory P300 component to anatomic measures obtained from quantitative magnetic resonance imaging. These findings are consistent with other evidence that temporal lobe structures contribute to the generation of the scalp-recorded P300 component and that P300 amplitude asymmetry over temporal recording sites on the scalp may reflect anatomic asymmetries in the volume of the superior temporal gyrus in schizophrenia.