Neural Basis of Pain Empathy Dysregulations in Mental Disorders – A Pre-registered Neuroimaging Meta-Analysis

Abstract

Pain empathy represents a fundamental building block of several social functions, which have been demonstrated to be impaired across various mental disorders by accumulating evidence from case-control functional magnetic resonance imaging (fMRI) studies. However, it remains unclear whether the dysregulations are underpinned by robust neural alterations across mental disorders. This study utilized coordinate-based meta-analyses to quantitatively determine robust markers of altered pain empathy across mental disorders. To support the interpretation of the findings exploratory network-level and behavioral meta-analyses were conducted. Quantitative analysis of eleven case-control fMRI studies with data from 296 patients and 229 controls revealed patients with mental disorders exhibited increased pain empathic reactivity in the left anterior cingulate gyrus, adjacent medial prefrontal cortex, and right middle temporal gyrus, yet decreased activity in the left cerebellum IV/V and left middle occipital gyrus compared to controls. The hyperactive regions showed network-level interactions with the core default mode network (DMN) and were associated with affective and social cognitive domains. The findings suggest that pain-empathic alterations across mental disorders are underpinned by excessive empathic reactivity in brain systems involved in empathic distress and social processes, highlighting a shared therapeutic target to normalize basal social dysfunctions in mental disorders.