Hallucinations in schizophrenia, sensory impairment, and brain disease: A unifying model

Abstract

Based on recent insight into the thalamocortical system and its role in perception and conscious experience, a unified pathophysiological framework for hallucinations in neurological and psychiatric conditions is proposed, which integrates previously unrelated neurobiological and psychological findings. Gamma-frequency rhythms of discharge activity from thalamic and cortical neurons are facilitated by cholinergic arousal and resonate in networks of thalamocortical circuits, thereby transiently forming assemblies of coherent gamma oscillations under constraints of afferent sensory input and prefrontal attentional mechanisms. If perception is based on synchronisation of intrinsic gamma activity in the thalamocortical system, then sensory input to specific thalamic nuclei may merely play a constraining role. Hallucinations can be regarded as underconstrained perceptions that arise when the impact of sensory input on activation of thalamocortical circuits and synchronisation of thalamocortical gamma activity is reduced. In conditions that are accompanied by hallucinations, factors such as cortical hyperexcitability, cortical attentional mechanisms, hyperarousal, increased noise in specific thalamic nuclei, and random sensory input to specific thalamic nuclei may, to a varying degree, contribute to underconstrained activation of thalamocortical circuits. The reticular thalamic nucleus plays an important role in suppressing random activity of relay cells in specific thalamic nuclei, and its dysfunction may be implicated in the biological vulnerability to hallucinations in schizophrenia. Combined with general activation during cholinergic arousal, this leads to excessive disinhibition in specific thalamic nuclei, which may allow cortical attentional mechanisms to recruit thalamic relay cells into resonant assemblies of gamma oscillations, regardless of their actual sensory input, thereby producing an underconstrained perceptual experience.

What Is the Link Between Hallucinations, Dreams, and Hypnagogic–Hypnopompic Experiences?

“…• The thalamo-cortical circuit described in models of sleep regulation and dreams (involved in perceptual release mechanisms) is also implicated in complex hallucinations of neurodegenerative disease and psychosis 66,[75][76][77] ; • Increased cortical activation in primary and secondary sensory cortices is consistent with perceptual images in hallucinations and sleep-related perceptions (rows 1 and 3, table 1); • In both sleep-related phenomena and hallucinations, the thalamus is activated (potentiated by ACh in sleep), and the brain is focused inwards and selectively attentive to internal experiences 19 ; • Limbic activity is thought to contribute to affective salience and emotive contents of both sleep-related perceptions 78 and hallucinations in psychosis (row 4); • Finally, in both phenomena, a possibility exists of spontaneous "sensory discharges" arising from a process of deafferentiation. Cortical deafferentiation is produced by ascending brainstem cholinergic projections activated under conditions of reduced perceptual input, resulting in a failure of the brainstem to deactivate.…”

What links schizophrenia and dreaming? Common phenomenological and neurobiological features of schizophrenia and REM sleep.

“…Furthermore, the results obtained from the CT scans allowed formulating a hypothesis about the formation of hallucinations in schizophrenia. It is assumed that hallucinations could be under-constrained perceptions which occur when the impact of sensory input on activation of thalamacortical circuits and synchronization of thalamacortical gamma rhythm are reduced [37]. A similar phenomenon is observed during REM sleep [31], therefore it could at least partially explain the hallucinatory characteristic of dreaming.…”

Thalamocortical Pathfinding Defects Precede Degeneration of the Reticular Thalamic Nucleus in Polysialic Acid-Deficient Mice

“…On the one hand, incomplete polysialylation of NCAM during brain development has been proposed as a mechanism for a predisposition to schizophrenia because it causes defects of cortical connectivity, including internal capsule defects, resembling those seen in schizophrenic patients ). On the other hand, dysfunction of the Rt has been linked to schizophrenia (O'Donnell and Grace, 1998;Sharp et al, 2001;Krause et al, 2003;Behrendt and Young, 2004;Behrendt, 2006;Zikopoulos and Barbas, 2007). Since all connections between thalamus and cortex traverse the Rt, this nucleus is ideally positioned to play a role in feedback control of thalamocortical circuits and sensory gating.…”