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Disruption of the thalamocortical signal-to-noise ratio in the pathogenesis of psychoses: Thalamocortical information processing

Abstract : Sensory and cognitive deficits are common in many neurobiological disorders. Mental illnesses, which worsen with senescence, are thought to result from dysfunctional cortex- and thalamus-related networks. So, understanding their pathogenesis and dysfunction with a reliable neurophysiological hallmark would certainly provide a new breath for the discovery of innovative therapies. In schizophrenia, sensory deficits are thought to originate from a reduced signal-to-noise ratio within sensory information processing circuits and to be due to NMDA receptors (NMDAr) hypofunction. The NMDAr antagonist ketamine is a psychotomimetic substance that induces sensory deficits and increases the amount of spontaneous gamma (30-80 Hz) brain network oscillations, suggesting that such deficits can be due to the increase of gamman noise. Here we show for the first time a reduction of the NMDAr-related sensory signal-to-gamma noise ratio during the pathogenesis of psychosis. We found that, in the rodent somatosensory system, ketamine (or MK-801) reduces both the sensory evoked thalamocortical response, including sensory-evoked gamma oscillations, and the signal-to-gamma noise ratio, and it weakens the long-term potentiation of the thalamocortical synapses. Ketamine or MK-801 increases gamma noise coherence only between interconnected structures, supporting the hypothesis of the existence of multiple independent cortical and subcortical generators of gamma oscillations during the resting state. Local cortical application of ketamine or MK-801 creates a focus of gamma hyperactivity, proving that such generators can be modulated independently. Furthermore, we found that thalamic deep brain stimulation increases the signal-to-noise ratio within thalamocortical somatosensory circuits. Therefore, we predict that any therapeutic-goal procedure enhancing the signal-to-noise ratio may have important implications for treating perceptual and cognitive abnormalities in mental illnesses.
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Contributor : Didier Pinault Connect in order to contact the contributor
Submitted on : Sunday, November 6, 2011 - 8:09:11 PM
Last modification on : Thursday, April 23, 2020 - 2:26:29 PM


  • HAL Id : inserm-00638656, version 1



Sofya Kulikova, Julien Gaudias, Elena Tolmacheva, Brendan Adams, Thomas Zheng, et al.. Disruption of the thalamocortical signal-to-noise ratio in the pathogenesis of psychoses: Thalamocortical information processing. Conference Abstract: BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011, Oct 2011, Freiburg, Germany. ⟨inserm-00638656⟩



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