The coupling between brain connectivity and heartbeat dynamics unveils the altered interoceptive mechanisms in Parkinson’s disease

Parkinson’s disease (PD) is often known for its classical motor symptoms, but non-motor symptoms are often reported including interoceptive and autonomic dysfunctions. Autonomic dysfunctions, such as cardiovascular, urinary, or thermoregulatory abnormalities, are more prone to be associated with motor and cognitive decline, as well as increase the risk of mortality. More recent evidence has shown that Parkinsonian patients may experience alterations in interoceptive processing, i.e., reduced sensitivity to accurately sensing and interpreting internal cues, leading to further impairment in self-awareness, cognitive and emotional processing. Noteworthy, the mechanisms behind these autonomic/interoceptive dysfunctions are not well understood. During the early stages of PD, disruptions in the connectivity of multiple brain regions occur, which has prompted the study of PD as a network-level phenomenon. Our hypothesis is that by examining the relationship between brain connectivity and heartbeat dynamics, we can gain insight into the large-scale network disruptions and the neurophysiology of the disrupted interoceptive mechanisms in PD. Our results show that the coupling of fluctuating alpha and gamma connectivity with heartbeat dynamics is reduced in PD patients, as compared to healthy participants. Furthermore, we show that PD patients under dopamine medication recover part of the brain-heart coupling, in proportion with the reduced motor symptoms. Our proposal offers a promising approach to unveil the physiopathology of PD and promoting the development of new diagnostic methods for the early stages of the disease. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Research supported by Agence Nationale de la Recherche (France), grant ANR-20-CE37-0012-03. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The data is part of a publicly available dataset UC San Diego Resting State EEG Data from Patients with Parkinson's Disease, gathered from OpenNeuro.org the 21st of November of 2022 I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data is part of a publicly available dataset UC San Diego Resting State EEG Data from Patients with Parkinson's Disease, gathered from OpenNeuro.org the 21st of November of 2022