Gamma band oscillations: a key to understanding schizophrenia symptoms and neural circuit abnormalities

Abstract

Purpose of review: We review our current understanding of abnormal γ band oscillations in schizophrenia, their association with symptoms and the underlying cortical circuit abnormality, with a particular focus on the role of fast-spiking parvalbumin gamma-aminobutyric acid (GABA) neurons in the disease state.

Recent findings: Clinical electrophysiological studies of schizophrenia patients and pharmacological models of the disorder show an increase in spontaneous γ band activity (not stimulus-evoked) measures. These findings provide a crucial link between preclinical and clinical work examining the role of γ band activity in schizophrenia. MRI-based experiments measuring cortical GABA provides evidence supporting impaired GABAergic neurotransmission in schizophrenia patients, which is correlated with γ band activity level. Several studies suggest that stimulation of the cortical circuitry, directly or via subcortical structures, has the potential to modulate cortical γ activity, and improve cognitive function.

Summary: Abnormal γ band activity is observed in patients with schizophrenia and disease models in animals, and is suggested to underlie the psychosis and cognitive/perceptual deficits. Convergent evidence from both clinical and preclinical studies suggest the central factor in γ band abnormalities is impaired GABAergic neurotransmission, particularly in a subclass of neurons which express parvalbumin. Rescue of γ band abnormalities presents an intriguing option for therapeutic intervention.

FIGURE 1

Auditory steady-state response is impaired in the γ band oscillation frequency range in schizophrenia patients. Figures show mean power spectra for EEGs recorded during trains of clicks at the following three stimulus rates: 40 Hz (upper), 30 Hz (middle), and 20 Hz (lower). Schizophrenia patients show decreased power at 40-Hz stimulation (arrow) compared with control study participants, while there was no difference between groups at 30 Hz stimulation. Note: controls show a prominent 40 Hz harmonic to 20 Hz stimulation, whereas schizophrenia patients do not, further evidence of a 40 Hz impairment. (Adapted from Kwon et al. [10].)

FIGURE 2

Oversimplified model of the cortical circuitry responsible for generating of γ oscillations. The cortical circuitry consists principally of excitatory pyramidal neurons and inhibitory GABAergic interneurons. The behavior of these circuits is defined by the interaction of these two neuronal subtypes. Of particular interest are interneurons containing the calcium-binding protein parvalbumin (PV), which appear to be essential for the generation of rhythmic activity because of their fast-action firing as well as the perisomatic location of their synapses. Postmortem studies have found altered parvalbumin, GAD67, and NMDA receptor subunit levels in these neurons in individuals with schizophrenia.