C02 Jun Miyata

C02 Localization of prediction error/salience in midbrain-striatal pathway and their association with delusion/hallucination　

Salience refers to the automatic attention allocation to “salient” stimuli and the perception of their importance. One computational definition of salience involves the absolute value of the prediction error, i.e., the error between prediction and actual input. In animals, there are reports of a gradient or localization within the midbrain-striatum dopamine neurons, where the ventromedial part encodes prediction error and the dorsolateral part encodes salience (Matsumoto & Hikosaka, 2009; Menegas et al., 2017). Whether such localization exists in humans is not yet known.

It is postulated that delusions and hallucinations are formed due to excessive attribution of salience to normal stimuli because of dopamine excess in the midbrain-striatum (aberrant salience hypothesis: Kapur, 2003). We have, for the first time, revealed that the functional connectivity (synchronization of activity) of the striatum correlates with the formation and severity of delusions (Miyata et al, 2024. DOI:10.1111/pcn.13652). However, there is no consensus on whether the ventromedial or dorsolateral part of the midbrain-striatum is involved in the formation of delusions and hallucinations.

In this research project, we will elucidate the localization of prediction error and salience in humans and clarify whether they are related to delusions and hallucinations, using functional MRI (fMRI) during rest, which can estimate functional connectivity between brain regions, diffusion MRI, which can estimate structural connectivity of white matter fibers, and fMRI to estimate neural activity using tasks related to prediction error and salience.