Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/577148

Swallowing and chewing difficulties are associated with presynaptic dopaminergic dysfunction and greater non-motor symptom burden in early drug-naïve Parkinson’s patients

Polychronis, S.·Dervenoulas, G.·Yousaf, T.·Niccolini, F.·Pagano, G.·Politis, M.
View original source ↗Export metadata ↓

Abstract

BackgroundThe underlying pathophysiology of swallowing and chewing difficulties is multifactorial and evidence clarifying the precise mechanisms are scarce. Dysfunction in dopamine-related and non-dopamine-related pathways, changes in cortical networks related with swallowing and peripheral mechanisms have been implicated in the pathogenesis of swallowing difficulties. We aimed at investigating whether swallowing and chewing difficulties are associated with presynaptic dopaminergic deficits, faster motor symptom progression and cognitive decline in a population of early drug-naive patients with Parkinsons disease.\n\nMethodsBy exploring the database of Parkinsons Progression Markers Initiative we identified forty-nine early drug-naive Parkinsons disease patients with swallowing difficulties. Swallowing and chewing impairment was identified with SCOPA-AUT question 1 (answer regularly) and was assessed with MDS-UPDRS Part-II, Item 2.3 (Chewing and Swallowing). We compared Parkinsons disease patients with swallowing and chewing difficulties to Parkinsons disease patients without difficulties, and investigated differences in striatal [123I]FP-CIT single photon emission computed tomography levels. Using Cox proportional hazards analyses, we also evaluated whether swallowing impairment can predict motor deterioration and cognitive dysfunction.\n\nResultsPatients with Parkinsons disease, harbored a greater deterioration regarding motor and non-motor symptoms and decreased [123I]FP-CIT binding when compared with patients without swallowing and chewing impairment. Higher burden of swallowing and chewing dysfunction (MDS-UPDRS-II, item 2.3) was correlated with lower [123I]FP-CIT uptakes within the striatum (rs=-0.157; P=0.002) and the caudate (rs=-0.156; P=0.002). The presence of swallowing and chewing difficulties was not a predictor of motor progression (Hazard ratio [HR]: 1.143, 95% confidence interval [CI]: 0.848-1.541; P=0.379) or cognitive decline (HR: 1.294, 95% CI: 0.616-2.719; P=0.496).\n\nConclusionsSwallowing and chewing impairment is associated with decreased presynaptic dopaminergic integrity within caudate and greater motor and non-motor symptoms burden in early drug-naive PD.\n\nAuthor contributionsS.P. and M.P. conceived the study, conceptualized the experimental design. M.P., S.P., G.D. and G.P. gave input to experimental design. S.P. wrote the first draft and prepared the manuscript. G.P. and S.P. performed the statistical analysis. G.P., G.D., T.Y. and S.P. generated the figures. F.N., M.P., S.P., G.P., G.D. interpreted the data. All authors revised and gave input to the manuscript.\n\nFinancial Disclosure StatementData used in the preparation of this article were obtained from the Parkinsons Progression Markers Initiative (PPMI) database (www.ppmi-info.org/data). For up-to-date information on the study, visit www.ppmi-info.org. PPMI - a public-private partnership - is sponsored by the Michael J. Fox Foundation for Parkinsons Research (MJFF) and is co-funded by MJFF, Abbvie, Avid Radiopharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Covance, Eli Lilly & Co., F. Hoffman-La Roche, Ltd., GE Healthcare, Genentech, GlaxoSmithKline, Lundbeck, Merck, MesoScale, Piramal, Pfizer and UCB.PPMI. Industry partners are contributing to PPMI through financial and in-kind donations and are playing a lead role in providing feedback on study parameters through the Industry Scientific Advisory Board (ISAB). Through close interaction with the study, the ISAB is positioned to inform the selection and review of potential progression markers that could be used in clinical testing.\n\nMr. Polychronis, Dr. Dervenoulas, Ms Yousaf, Dr. Niccolini, Dr. Pagano and Prof. Politis report no disclosures.\n\nPotential Conflicts of InterestNo potential conflict of interest relevant to this article was reported.

Source connections

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Polychronis, S., Dervenoulas, G., Yousaf, T., Niccolini, F., Pagano, G., Politis, M.. 2019-03-14. Swallowing and chewing difficulties are associated with presynaptic dopaminergic dysfunction and greater non-motor symptom burden in early drug-naïve Parkinson’s patients. https://doi.org/10.1101/577148

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Novel Tau Interaction Partners as Potential Biomarkers and Therapeutic Targets in Neurodegenerative Diseases

Alzheimers disease is a progressive neurodegenerative disorder leading to cognitive decline and ultimately death. One of the main hallmarks of this disease is the accumulation of pathological tau protein into neurofibrillary tangles. To better understand these pathological mechanisms, it is essential to characterize the tau protein interactome in health and disease. In this study, we performed a yeast two-hybrid screening using a human brain cDNA library, from which we identified 15 novel tau-interacting proteins that bind to full-length human tau, or its fragments: the N-terminus, microtubule-binding domain, or C-terminus. We subsequently validated these novel interactions using in vitro co-immunoprecipitation and colocalization assays with both physiological and pathological tau isoforms. Furthermore, their interactions with the human tau protein were analyzed using surface plasmon resonance. Finally, an in silico interactome analysis of these newly discovered tau-binding partners revealed several additional interactors that can link them to downstream processes critical to neurodegenerative pathways Our findings offer fresh insights into tau biology and highlight novel targets for therapeutic intervention and biomarker development.

neuroscience↗
bioRxiv2026

Early visual cortex is not functionally necessary for temporal attention: A TMS study

Temporal attention enhances the selective processing of information at a specific point in time and improves perception. Previous neuroimaging studies investigating its neural mechanisms have either conflated temporal attention with temporal expectation or provided correlational evidence. Thus, whether early visual cortex is functionally necessary for temporal attention remains unknown. Here, we combined psychophysics with transcranial magnetic stimulation (TMS) to examine whether V1/V2 are functionally necessary and play a causal role in temporal attention. Observers performed an orientation-discrimination task in which two consecutive stimuli, T1 and T2, were presented in the periphery, preceded by a precue providing either valid or neutral temporal information. Double-pulse TMS was delivered under four conditions: at T1 (T1-TMS), at T2 (T2-TMS), at both T1 and T2 (both-TMS), or not at all (none-TMS), to assess its effects on temporal attention and the efficacy of the stimulation was verified by pupil size analysis. Behavioral results revealed robust temporal attention benefits on d', reaction time, and the Balanced Integration Score (BIS) across all four TMS conditions, indicating that the benefits of temporal attention were unaffected by occipital TMS. Furthermore, pupil dilation was largest in the both-TMS condition, followed by the T1-TMS and T2-TMS conditions, and smallest in the none-TMS condition, providing physiological verification of the stimulation protocol. Together, these findings reveal the first causal evidence that the early visual cortex is not functionally necessary for endogenous temporal attention.

neuroscience↗
bioRxiv2026

Disentanglement of persistent and dynamic neural substrates of working memory

Competing theories of working memory have alternatively emphasized the importance of persistent and dynamic substrates of this cognitive function. Here, we directly tested these theories by computationally isolating the contributions of persistent and dynamic activity to working memory. We analyzed neuronal population activity recordings in macaques doing match/non-match working memory tasks. We first extracted signatures of persistent and dynamic activity through cue-specific temporal means, temporal principal components, and correlations of activity patterns across task epochs. We then generated synthetic data constrained by these signatures, and decoded cue stimuli from these data, separately from persistent and non-persistent neurons. We found that high decoding performance arose from a nuanced interplay of persistent and dynamic activity. Specifically, we could decode stimuli at empirical or above-chance levels across all tasks only from persistent neurons, but only after constraining correlations of activity patterns across epochs. In this way, we showed distinct roles for persistent and dynamic neuronal activity that help to unify two competing theories of working memory. More broadly, we also advanced computational controlled experiments as a principled framework for adjudicating between competing models of neuronal population activity.

neuroscience↗