Utility of gut-brain electrophysiological coupling in predicting L-Dopa induced dyskinesia in Parkinson’s Disease

Abstract In this study, we focus on Levodopa induced dyskinesia (LID) condition in Parkinson’s Disease (PD) and investigate the mechanistic role of gut-brain coupling in explaining the dyskinesia severity. Earlier studies have provided evidences for abnormal dynamics in the cortico-basal ganglia loops and also in the gut functioning, for explaining LID. However to our knowledge, assessing gut-brain coupling isn’t a standard practice for development of the treatment strategy in LID patients for understanding the odds of dyskinesia onset and progression. In this study, we use scalable data acquisition technologies such as electroencephalography (EEG) and electrogastrography (EGG) for investigating the gut-brain coupling, and for the first time assess its utility to inform about dyskinesia severity in PD patients. We collected data from N=67 subjects (healthy = 26) in middle to old age adulthood and acquire their gut-brain coupling data during various cognitive engagement tasks, using simultaneous EEG and EGG recording setup. Some of our results include that gut-brain coupling can predict the severity of dyskinesia in PD during interoception, especially in hyperventilating and eyes closed resting state paradigms. Second, specific frequencies of gut coupling activity are more sensitive to explaining motor complications. Third, the gut activity differentially couples with different brain regions to explain the symptom severity. The most salient features of our model were the normogastric gut coupling with the temporo-occipital brain region, normogastric gut coupling with the frontal region, and the tachygastric gut coupling with the centro-parietal region. Furthermore of translational significance, the latter two features also significantly interacted with cardiac measures, and the model was able to predict sensitive heart rate variability levels for reducing the symptom severity. Altogether, our study paves way for utitlizing gut-brain coupling as a clinical measure for strategizing interventions in PD.