Elevated striatal dopamine attenuates nigrothalamic inputs and impairs transthalamic cortico-cortical communication in schizophrenia: A hypothesis

Abstract

Schizophrenia has been found to involve source-monitoring deficits, whereby perceptions that result from self-initiated motor output become attributed to outside sources. One example of this phenomenon are the so called passivity experiences, such as delusions of control, during which the individual feels that own actions are controlled remotely by someone else. To explain these phenomena, it has been proposed that this illness involves efference copy failure. In other words, brain mechanism that prepare perceptual processes for the sensory consequences of self-initiated actions are impaired leading to their misattribution and to psychosis. In earlier work, it was argued that efference copy failure in schizophrenia is related to thalamic abnormalities. Namely, the thalamus can be thought of as a hub for cortico-cortical interactions, and these transthalamic cortico-cortical interactions were found to play a part in internal motor monitoring. Cortico-cortical communication via the thalamus can be impaired in a number of ways. For example, one way to impair these interactions is by interfering with the ability of the thalamus to display bursts of firing. As the burst firing mode in the thalamus requires a preceding period of prolonged hyperpolarization (100ms), one way to reduce the burst propensity of thalamic neurons is to interfere with the ability to display prolonged hyperpolarizations. In this paper, we argue that elevated striatal dopaminergic activity in schizophrenia attenuates nigrothalamic GABAergic inputs, and thereby reduces burst propensity of the mediodorsal (MD) thalamic nucleus in schizophrenia, with the ultimate result of reduced transthalamic cortico-cortical communication, relative disconnection between functionally associated cortical areas and to psychosis. Conversely, dopamine D2 receptor blockers (antipsychotics) may help restore nigrothalamic GABAergic inputs, thereby increasing the burst propensity in the thalamus.