A Neural Biomarker for Hallucinations: Medial Prefrontal Aberrations in Neural Connectivity Predict Self-Agency Deficits and Hallucination Severity in Schizophrenia

Abstract

Prior studies have shown that the medial prefrontal cortex (mPFC) represents one neural substrate that mediates judgments of self-agency (i.e., the awareness that 'I am the originator of my actions'). Patients with schizophrenia (SZ) manifest cardinal self-agency deficits that contribute to debilitating psychotic symptoms (e.g. hallucinations) and distort reality monitoring. This is the first study in which we examine across 2 SZ samples, the mPFC site that underlies self-agency deficits during an explicit reality-monitoring task (i.e., while subjects distinguish self-generated information from externally-derived information) in one SZ sample, and link intrinsic functional connectivity (iFC) during rest within this a priori task-evoked self-agency seed with hallucination symptoms in a different SZ sample. In particular, we examined the iFC between the mPFC site that underlies self-agency deficits with all other brain regions in SZ using resting-state functional magnetic resonance imaging (fMRI). Resting-state fMRI data were collected from 32 SZ and 28 age, gender, and education-matched healthy control (HC) subjects. Functional connectivity maps were computed for each subject and compared between the HC and SZ groups. Within-group and between-group analyses revealed that aberrant iFC in this a priori-defined mPFC 'self-agency seed' predicted hallucination severity. The present findings reveal that the neural aberrations in this mPFC site represents one cardinal biomarker that underlies explicit self-agency deficits during a reality-monitoring task in one SZ sample that generalized to aberrant iFC differences in a different SZ sample and predicted worsening psychotic hallucinatory experiences. This region may represent a key neurobiological target for treatment avenues to improve hallucinatory symptoms.

Keywords: hallucinations; medial prefrontal cortex; reality monitoring; resting-state fMRI; schizophrenia; self-agency.

Figure 1.

A. Illustration of mPFC seed 5mm sphere defined from our previous reality-monitoring task in which SZ had revealed aberrant neural activation while making self-agency judgments. B & C. Illustrate within-group connectivity strengths between the mPFC seed (shown in A) and surrounding voxels that predicted worsening hallucination severity in SZ.

Figure 2.

A. Highly significant between-group connectivity differences between the mPFC seed and R. M/SFG. B & C. Illustrate mean connectivity strengths between the mPFC seed R.M/SFG that predicted worsening hallucination severity in SZ.