Mapping brain synergy dysfunction in heart failure patients with reduced and mildly reduced ejection fraction using multimodal neuroimaging: Functional and molecular insights.

BACKGROUND

Heart failure (HF) is frequently accompanied by cognitive and affective impairments, yet the underlying neural mechanisms of altered brain information processing in HF remain poorly defined.

METHODS

We applied an integrated information decomposition framework to resting-state fMRI from 48 HF patients (including HFrEF and HFmrEF, with LVEF < 50 %) and 33 matched healthy controls, quantifying synergistic and redundant information across 246 brain regions. Group differences were assessed at global and regional levels and correlated with cardiac function, cognitive performance, and affective symptoms. Neuromaps, neurotransmitter and neuropeptide receptor maps and cognition-related meta-analytic data from NeuroSynth were used to contextualize findings.

RESULTS

HF patients exhibited significantly greater global brain synergy, with regional elevations in the thalamus, basal ganglia, and limbic-temporal areas. Altered synergistic interactions correlated with lower ejection fraction, poorer cognition, and greater depression. Spatial mapping showed negative associations between synergy and cerebral blood flow, glucose and oxygen metabolism, and microstructural integrity. Synergy patterns overlapped with the distribution of dopamine, histamine, and opioid receptors, and neuropeptides including somatostatin, vasopressin, and kinin/tensin. NeuroSynth decoding linked these patterns to memory, emotion, pain, and motor control domains.

CONCLUSIONS

HF is characterized by distinct alterations in synergistic brain information processing that relate to cognitive-emotional impairment and show exploratory spatial correspondence with normative molecular architecture. These findings provide multimodal evidence for altered heart-brain interactions in HF.