Compensatory hallucinogenesis across three neuropsychiatric disorders: A Bayesian account
Authors: Vin Raina , Galbraith Jordan , Seabury Rashina , Yi Hae Young , Hernández-Busot Gabriela , Oland Lucas , Epie Boris , Trainer Anne , Fredericks Carolyn , powers albert 
Published: February 2025

Visual hallucinations have haunted humanity for millennia. While our explanations for these phenomena are now more soundly based in neuroscience, our understanding of their provenance remains superficial. In particular, the role of specific visual system disruptions in the generation of visual hallucinations remains unclear. We and others have recently demonstrated that hallucinations in psychosis-spectrum illness can be engendered by over-weighting expectations during perception. Emerging evidence suggests this state of affairs is also true for hallucinations in other neuropsychiatric illnesses. This includes alpha synucleinopathies like Parkinson’s Disease and Dementia with Lewy Bodies, in which hallucinations are a core diagnostic feature of illness. It also includes Charles Bonnet Syndrome, which produces vivid hallucinations in the context of a lesion, such as macular degeneration or occipital infarct, in the primary visual pathway. However, each of these disorders is also characterized by disruption in incoming sensory information at levels of the visual processing hierarchy ranging from the retina to primary visual cortex, the dorsal and ventral visual streams, and thalamo-cortico-striatal circuits. In this piece, we ask whether an over-weighting of expectations may be conceived of as a compensatory response to incoming sensory noise. We make the case that visual hallucinogenesis across a wide array of neuropsychiatric disorders can be captured within a common Bayesian computational framework, as a compensatory response to sensory signal disruptions at different levels of the visual processing hierarchy. We highlight three specific disorders (Charles Bonnet Syndrome, Dementia with Lewy Bodies, and Schizophrenia) that are known for visual hallucinations. We also appeal to the fact that these disorders describe a spectrum of visual impairment where the overtness and localization of the visual processing disruption is reflected in the characteristics of the emerging visual hallucinations. We examine how known sensory disruptions in Charles Bonnet Syndrome translate to hallucinations via known circuits, and then how different disruptions in Dementia with Lewy Bodies and Schizophrenia may lead to hallucinations with distinct phenomenology, comorbidities, and circuit involvement. Finally, we appeal to emerging computational theories to unite these observations under a common umbrella that drives hypothesis generation around important clinical factors like the existence of pathophysiologically distinct patient subgroups and the efficacy of pharmacological and circuit-based interventions.Taken together, the synthesis we present provides evidence for the emergence of a broad and computationally-informed framework for understanding how sensory disruptions could interact with other aspects of cognitive and neural architecture to produce hallucinations across neuropsychiatric disease.