Gamma oscillation deficits and the onset and early progression of schizophrenia

Abstract

A fascinating convergence of evidence in recent years has implicated the disturbances of neural synchrony in the gamma frequency band (30-100 Hz) as a major pathophysiologic feature of schizophrenia. Evidence suggests that reduced glutamatergic neurotransmission via the N-methyl-D-aspartate (NMDA) receptors that are localized to inhibitory interneurons, perhaps especially the fast-spiking cells that contain the calcium-binding protein parvalbumin (PV), may contribute to gamma band synchrony deficits. These deficits may underlie the brain's failure to integrate information and hence the manifestations of many symptoms and deficits of schizophrenia. Furthermore, because gamma oscillations are thought to provide the temporal structure that is necessary for synaptic plasticity, gamma oscillation deficits may disturb the developmental synaptic reorganization process that is occurring during the period of late adolescence and early adulthood. This disturbance may contribute to the onset of schizophrenia and the functional deterioration that is characteristic of the early stage of the illness. Finally, reduced NMDA neurotransmission on inhibitory interneurons, including the PV-containing cells, may inflict excitotoxic or oxidative injury to downstream pyramidal neurons, leading to further loss of synapses and dendritic branchings. Hence, a key element in the conceptualization of rational early-intervention and prevention strategies for schizophrenia may involve correcting the abnormal NMDA neurotransmission on inhibitory interneurons-possibly that on the PV-containing neurons, in particular-thereby normalizing gamma oscillation deficits and attenuating downstream neuronal pathology.

Conflict of interest statement

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Figures

Fig. 1

Types of time/frequency domain measures derived from single-trial epochs of EEG. The data were recorded at a parieto-occipital electrode (PO6) from a healthy subject performing a visual discrimination task (44). Stimulus onset is at 0 ms. A) Raw single trial ERPs. B) The average ERP is computed by averaging together the single trials (N=90 here). The P1 N1 components are clearly visible. C) Time frequency maps of spectral power for the corresponding single trials. Time-frequency decomposition was performed using the M orlet wavelet transform. D) Average of the single trial time-frequency power maps. This measure of “total power” represents both “background” (induced, or non-stimulus-locked) and stimulus-locked oscillations. E) Evoked power is the power of stimulus-locked oscillations (i.e., the average ERP). The P1 N1 components occupy the low-frequency rang (<20 Hz). The early evoked visual gamma oscillation (g) is apparent in the time-frequency map. F) phase-locked represents the phase variability across trials and is insensitive to oscillatory power. Low phase locking values (PLV) indicate high phase variability (top circle plot) and high PLV indicate low phase variability (bottom circle plot). (Figure adapted with permission form Javitt et al., 2008, Nat Rev Drug Discovery).