Hallucinations in psychosis may arise when the brain's default-mode network (DMN) disengages abnormally, similar to its response to real external stimuli. In 20 drug-free adolescents with brief psychotic disorder, multimodal MRI showed that during auditory, visual, and multisensory hallucinations, cortical thickness was reduced and blood oxygen level-dependent signal increased in modality-dependent association sensory cortices, while primary sensory cortex recruitment was not systematic and linked to greater vividness. DMN disengagement coincided with hallucinations, and spatial and temporal instabilities of the DMN correlated with hallucination severity and persisted even without symptoms. This suggests hallucinations emerge from spontaneous DMN withdrawal, offering a model beyond the auditory modality.
Hallucinations arise from at least three distinct pharmacological pathways: activation of dopamine D2 receptors by psychostimulants, activation of serotonin 5HT2A receptors by psychedelics, and blockage of glutamate NMDA receptors by dissociative anesthetics. In schizophrenia, the relative roles of NMDA and dopamine receptors remain debated, and slight clinical differences appear depending on the cause. This narrative review synthesizes how leading researchers have approached whether the concept of hallucination is clinically and neurobiologically homogeneous. Some favor a single mechanism, while others propose integrated theories based on pharmacological psychosis models. The authors suggest that although common neurobiological pathways may exist, each system likely has unique properties that explain observed clinical differences.