Multimodal neuroimaging investigations of allostatic-interoception and social cognition in neurodegenerative diseases.

Allostatic-interoception, the anticipation and sensing of bodily signals, is linked to sociocognitive function and cardiovascular health. Impairments in this process may arise in behavioral-variant frontotemporal dementia (bvFTD) and Alzheimer’s disease (AD) due to structural and functional disruptions in the allostatic-interoception network (AIN). Here, we integrate three complementary studies to investigate the AIN's role in sociocognitive processes and cardiovascular risk in neurodegeneration. In Study 1, we conducted PRISMA Activated Likelihood Estimate (ALE) meta-analyses on 170 studies (N=7,032), including structural and functional neuroimaging data. We identified key AIN regions (e.g., insula, amygdala, orbitofrontal cortex, anterior cingulate cortex, thalamus, hippocampus) across interoception, emotion, and social cognition domains in all neurodegenerative diseases combined, with more pronounced involvement in bvFTD in patient specific analyses. Study 2 examined multimodal neuroimaging in 1,501 participants (bvFTD: N=304; AD: N=512; controls: N=685) and found that higher cardiovascular risk (e.g., BMI, hypertension, diabetes, smoking) correlated with reduced structural integrity and functional connectivity within the AIN. Functional disruptions were widespread in bvFTD (bilateral insula, cingulate, orbitofrontal cortex, thalamus, hippocampus) and localized in AD (hippocampus, parahippocampus). In Study 3, we analyzed intrinsic neural timescales of interoception using EEG (N=112; bvFTD: N=31; AD: N=35; controls: N=46). Longer autocorrelation windows (ACW) during interoception were observed in bvFTD (frontotemporal/parietal clusters) and AD (central/occipital-parietal clusters). Longer ACW correlated with poorer sociocognitive performance and AIN structural changes in bvFTD. Our findings reveal consistent AIN involvement in bvFTD and partial involvement in AD, supporting predictive coding theories of allostatic-interoception. Increased cardiovascular risk exacerbates AIN impairments, highlighting the need to address systemic health factors in dementia care. This work underscores the potential benefits of interventions targeting allostatic-interoception to mitigate behavioral impairments in neurodegenerative diseases, particularly in bvFTD.