Thalamocortical interactions reflecting the intensity of flicker light-induced visual hallucinatory phenomena

Abstract

The thalamus has a critical role in the orchestration of cortical activity. Aberrant thalamocortical connectivity occurs together with visual hallucinations in various pathologies and drug-induced states, highlighting the need to better understand how thalamocortical interactions may contribute to hallucinatory phenomena. However, concurring symptoms and physiological changes that occur during psychopathologies and pharmacological interventions make it difficult to distil the specific neural correlates of hallucinatory experiences. Flicker light stimulation (FLS) at 10 Hz reliably and selectively induces transient visual hallucinations in healthy participants. Arrhythmic flicker elicits fewer hallucinatory effects while delivering equal amounts of visual stimulation, together facilitating a well-controlled experimental setup to investigate the neural correlates of visual hallucinations driven by flicker rhythmicity. In this study, we implemented rhythmic and arrhythmic FLS during fMRI scanning to test the elicited changes in cortical activation and thalamocortical functional connectivity. We found that rhythmic FLS elicited stronger activation in higher-order visual cortices compared to arrhythmic control. Consistently, we found that rhythmic flicker selectively increased connectivity between ventroanterior thalamic nuclei and higher-order visual cortices compared to arrhythmic control, which was also found be positively associated with the subjective intensity of visual hallucinatory effects. As these thalamic and cortical areas do not receive primary visual inputs, it suggests that the thalamocortical connectivity changes relate to a higher-order function of the thalamus, such as in the coordination of cortical activity. In sum, we present novel evidence for the role of specific thalamocortical interactions with ventroanterior nuclei within visual hallucinatory experiences. Importantly, this can inform future clinical research into the mechanistic underpinnings of pathologic hallucinations.