Neurobiological Correlates of Normal and Altered Consciousness

Horáček J., Höschl C.

Abstract:

Information theory is the conceptual framework for understanding the psychopathology and mechanisms of psychiatric treatment. On the other hand, the analysis of neurobiological correlates of altered mental states and psychopathology could help us to understand the integration of neuronal networks under the normal conditions.

Information processing depends on a) connectivity of pyramidal neurons or neurotransmission, b) neuromodulation influencing excitability of neuronal cells and optimizing the signal/noise ratio in neuronal network. We investigated the role of neuronal disconnection in patophysiology of schizophrenia exploring the role of neuromodulators (serotonin and dopamine) in processing.

We used an animal model of disconnection induced in rats by the acute administration of MK-801, the non-competitive NMDA antagonist, which leads to measurable behavioral changes. The MK-801 model of schizophrenia could be interpreted as an acute disconnection of pyramidal neurons. Normalization of behavior in our sample of MK-801 treated rats can be regarded as a possible consequence of monoaminergic modulation compensating the neuronal disconnection. This idea is supported by our human study of fronto-temporal qEEG coherences. In order to determine the role of disconnection on the brain metabolism and information processing in schizophrenia, we evaluated resting brain metabolism by the 18F-deoxyglucose (18FDG) positron emission tomography (PET) in subjects with schizophrenia. For the statistical treatment of the neuroimaging data we used the standard voxel-to-voxel analysis (SPM99) with the F3-T5 and F4-T6 coherences as the covariates. The decreased fronto-temporal EEG coherences predict the higher metabolism in mediotemporal lobe, one of the treatment target structures related to altered consciousness schizophrenia.

The experiments demonstrate a) the role of neuronal disconnection in altered consciousness and b) the compensatory effect of neuromodulation in disconnected brain and the involvement of frontotemporal circuits in these processes. Our data suggest the role of fronto-temporal circuits (connectivity) and their neuromodulation in non-altered consciousness and in processing of data from external world.