Errant ensembles: dysfunctional neuronal network dynamics in schizophrenia

Abstract

Most complex psychiatric disorders cannot be explained by pathology of a single brain region, but arise as a consequence of dysfunctional interactions between brain regions. Schizophrenia, in particular, has been described as a ‘disconnection syndrome’, but similar principles are likely to apply to depression and ADHD (attention deficit hyperactivity disorder). All these diseases are associated with impaired co-ordination of neural population activity, which manifests as abnormal EEG (electroencephalogram) and LFP (local field potential) oscillations both within and across subcortical and cortical brain regions. Importantly, it is increasingly possible to link oscillations and interactions at distinct frequencies to the physiology and/or pathology of distinct classes of neurons and interneurons. Such analyses increasingly implicate abnormal levels, timing or modulation of GABA (γ-aminobutyric acid)-ergic inhibition in brain disease. The present review discusses the evidence suggesting that dysfunction of a particular class of interneurons, marked by their expression of the calcium-binding protein parvalbumin, could contribute to the broad range of neurophysiological and behavioural symptoms characteristic of schizophrenia.