Objective: We study the role of spontaneous brain activity in the cross-talk between gut microbiota and cognition in PD.

Background: Gut dysbiosis is a prevalent and prodromal non-motor symptom of PD. Intestinal bacteria are involved in regulatory and immune functions, and in the synthesis of neurotransmitters [1]. Ecosystem stability can be described by summary metrics, as evenness and diversity. Additionally, PD can be aggravated by cognitive decline and dementia. rs-fMRI is a noninvasive tool to assess brain activity, and it has been used to study alterations in PD. Regional Homogeneity (ReHo) measures the similarity among time series of neighbouring voxels, can differentiate PD from controls and correlates with clinical features [2].

Method: 68 PD patients were recruited at Padova University Hospital. 15 minutes of 3 Tesla rs-fMRI data, were pre-processed to compute ReHo in 200 cortical ROIs [3]. Cognitive assessment included MoCA, and a II-level evaluation of six domains (attention, visuospatial, memory, executive function, social cognition, language). Stool samples were analysed using 16S rRNA sequencing, and processed to compute evenness and diversity. ReHo was related to microbial and cognitive measures through multiple linear regression, accounting for nuisance variables. Significant results were further explored using mediation analysis, testing ReHo as a mediator between microbial statistics and cognitive performance.

Results: ReHo was positively related to microbial evenness and diversity within central and peripheral visual ROIs. ReHo was positively related to MoCA and to attention and visuospatial abilities in ROIs distributed across all brain networks in occipital, temporal and parietal areas [figure1]. ReHo mediates between microbial scores and both global and domain-specific cognitive scores in striatal and extra-striatal visual cortex ROIs (see [table1] and [figure2]).

Conclusion: Evenly distributed and diverse gut microbiota, and higher cognitive outcome in PD are positively related to higher occipital spontaneous brain activity. Occipital regions may be affected by cholinergic degeneration, which can be a risk factor for dementia [4]. Moreover, in PD, those regions are subject to hypoperfusion, associated with visual impairments [5]. As ReHo is a measure of functional activity coupled with perfusion, further studies will focus on disentangling the neural and haemodynamic contributions.

Figure1

Table1

Figure2

References: [1] Zhang X, Tang B, Guo J. Parkinson’s disease and gut microbiota: from clinical to mechanistic and therapeutic studies. Transl Neurodegener. 2023;12(1):59. Published 2023 Dec 15. doi:10.1186/s40035-023-00392-8
[2] Su M, Wang S, Cheng O, et al. Constipation is associated with emotional and cognitive impairment in patients with Parkinson’s disease: A clinical and brain functional study. Neuroscience. 2024;559:17-25. doi:10.1016/j.neuroscience.2024.08.027
[3] Yan X, Kong R, Xue A, et al. Homotopic local-global parcellation of the human cerebral cortex from resting-state functional connectivity. Neuroimage. 2023;273:120010. doi:10.1016/j.neuroimage.2023.120010
[4] Biundo R, Weis L, Antonini A. Cognitive decline in Parkinson’s disease: the complex picture. NPJ Parkinsons Dis. 2016;2:16018. Published 2016 Sep 1. doi:10.1038/npjparkd.2016.18
[5] Abe Y, Kachi T, Kato T, et al. Occipital hypoperfusion in Parkinson’s disease without dementia: correlation to impaired cortical visual processing. J Neurol Neurosurg Psychiatry. 2003;74(4):419-422. doi:10.1136/jnnp.74.4.419

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MDS Abstracts - https://www.mdsabstracts.org/abstract/regional-homogeneity-in-the-visual-network-mediates-between-microbiota-and-cognition-in-parkinsons-disease/