Altered spatiotemporal brain dynamics of interoception in behavioural-variant frontotemporal dementia

Hazelton J, Della Bella G, Barttfeld P, Dottori M, Gonzalez-Gomez R, Migeot J, Moguilner S, Legaz A, Hernandez H, Prado P, Cuadros J, Maito M, Fraile-Vazques M, González Gadea M, Çatal Y, Miller B , Piguet O, Northoff G, Ibanez A 2025. eBioMedicine

Summary

Background
Dysfunctional allostatic-interoception, altered processing of bodily signals in response to environmental demands, occurs behavioural-variant frontotemporal dementia (bvFTD) patients. Previous research has not investigated the dynamic nature of interoception using methods like intrinsic neural timescales. We hypothesised that longer intrinsic neural timescales of interoception would occur in bvFTD patients, evidencing dysfunctional allostatic-interoception.

Methods
One-hundred and twelve participants (31 bvFTD patients , 35 Alzheimer’s disease patients, AD and 46 healthy controls) completed a well-validated task measuring cardiac-interoception and exteroception. Simultaneous EEG and ECG were recorded. Intrinsic neural timescales were measured via the autocorrelation window (ACW) of broadband EEG signals from each heartbeat and a time-lagged version of itself. Spatiotemporal clustering analyses identified clusters with significant between-group differences in each condition. Voxel-based morphometry was used to target the allostatic-interoceptive network. Neuropsychological tests of cognition and social cognition were assessed.

Findings
In bvFTD patients, longer interoceptive-ACWs than controls were observed in the bilateral fronto-temporal and parietal regions. In AD patients, longer interoceptive-ACWs than controls were observed in central and occipitoparietal brain regions. No differences were observed during exteroception. In bvFTD patients only, longer interoceptive-ACW was linked to worse sociocognitive performance. Structural neural correlates of interoceptive-ACW in bvFTD involved the anterior cingulate, insula, orbitofrontal cortex, hippocampus, and angular gyrus.

Interpretation
Our findings suggest a core allostatic-interoceptive deficit occurs in people with bvFTD. Further, altered interoceptive intrinsic neural timescales may provide a neurobiological mechanism underpinning the complex behaviours observed in bvFTD patients. Our findings support synergistic models of brain disease and can inform clinical practice.