Bridging the Gap? Altered Thalamocortical Connectivity in Psychotic and Psychedelic States

Psychiatry has a well-established tradition of comparing drug-induced experiences to psychotic symptoms, based on shared phenomena such as altered perceptions. The present review focuses on experiences induced by classic psychedelics, which are substances capable of eliciting powerful psychoactive effects, characterized by distortions/alterations of several neurocognitive processes (e.g., hallucinations). Herein we refer to such experiences as psychedelic states. Psychosis is a clinical syndrome defined by impaired reality testing, also characterized by impaired neurocognitive processes (e.g., hallucinations and delusions). In this review we refer to acute phases of psychotic disorders as psychotic states. Neuropharmacological investigations have begun to characterize the neurobiological mechanisms underpinning the shared and distinct neurophysiological changes observed in psychedelic and psychotic states. Mounting evidence indicates changes in thalamic filtering, along with disturbances in cortico-striato-pallido-thalamo-cortical (CSPTC)-circuitry, in both altered states. Notably, alterations in thalamocortical functional connectivity were reported by functional magnetic resonance imaging (fMRI) studies. Thalamocortical dysconnectivity and its clinical relevance are well-characterized in psychotic states, particularly in schizophrenia research. Specifically, studies report hyperconnectivity between the thalamus and sensorimotor cortices and hypoconnectivity between the thalamus and prefrontal cortices, associated with patients' psychotic symptoms and cognitive disturbances, respectively. Intriguingly, studies also report hyperconnectivity between the thalamus and sensorimotor cortices in psychedelic states, correlating with altered visual and auditory perceptions. Taken together, the two altered states appear to share clinically and functionally relevant dysconnectivity patterns. In this review we discuss recent findings of thalamocortical dysconnectivity, its putative extension to CSPTC circuitry, along with its clinical implications and future directions.