Neuroplasticity in Parkinson's disease.

Parkinson's disease (PD) is the second most frequent neurodegenerative disorder, affecting millions of people and rapidly increasing over the last decades. Even though there is no intervention yet to stop the neurodegenerative pathology, many efficient treatment methods are available, including for patients with advanced PD. Neuroplasticity is a fundamental property of the human brain to adapt both to external changes and internal insults and pathological processes. In this paper we examine the current knowledge and concepts concerning changes at network level, cellular level and molecular level as parts of the neuroplastic response to protein aggregation pathology, synapse loss and neuronal loss in PD. We analyse the beneficial, compensatory effects, such as augmentation of nigral neurons efficacy, as well as negative, maladaptive effects, such as levodopa-induced dyskinesia. Effects of physical activity and different treatments on neuroplasticity are considered and the opportunity of biomarkers identification and use is discussed.

Cortical Generators and Connections Underlying Phoneme Perception: A Mismatch Negativity and P300 Investigation.

The cortical generators of the pure tone MMN and P300 have been thoroughly studied. Their nature and interaction with respect to phoneme perception, however, is poorly understood. Accordingly, the cortical sources and functional connections that underlie the MMN and P300 in relation to passive and active speech sound perception were identified. An inattentive and attentive phonemic oddball paradigm, eliciting a MMN and P300 respectively, were administered in 60 healthy adults during simultaneous high-density EEG recording. For both the MMN and P300, eLORETA source reconstruction was performed. The maximal cross-correlation was calculated between ROI-pairs to investigate inter-regional functional connectivity specific to passive and active deviant processing. MMN activation clusters were identified in the temporal (insula, superior temporal gyrus and temporal pole), frontal (rostral middle frontal and pars opercularis) and parietal (postcentral and supramarginal gyrus) cortex. Passive discrimination of deviant phonemes was aided by a network connecting right temporoparietal cortices to left frontal areas. For the P300, clusters with significantly higher activity were found in the frontal (caudal middle frontal and precentral), parietal (precuneus) and cingulate (posterior and isthmus) cortex. Significant intra- and interhemispheric connections between parietal, cingulate and occipital regions constituted the network governing active phonemic target detection. A predominantly bilateral network was found to underly both the MMN and P300. While passive phoneme discrimination is aided by a fronto-temporo-parietal network, active categorization calls on a network entailing fronto-parieto-cingulate cortices. Neural processing of phonemic contrasts, as reflected by the MMN and P300, does not appear to show pronounced lateralization to the language-dominant hemisphere.

Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson's disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial.

Background: Dysregulation of the gut microbiome has been implicated in Parkinson's disease (PD). This study aimed to evaluate the clinical effects and safety of a single faecal microbiota transplantation (FMT) in patients with early-stage PD. Methods: The GUT-PARFECT trial, a single-centre randomised, double-blind, placebo-controlled trial was conducted at Ghent University Hospital between December 01, 2020 and December 12, 2022. Participants (aged 50-65 years, Hoehn and Yahr stage 2) were randomly assigned to receive nasojejunal FMT with either healthy donor stool or their own stool. Computer-generated randomisation was done in a 1:1 ratio through permutated-block scheduling. Treatment allocation was concealed for participants and investigators. The primary outcome measure at 12 months was the change in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score obtained during off-medication evaluations. Intention-to-treat analysis was performed using a mixed model for repeated measures analysis. This completed trial is registered on ClinicalTrials.gov (NCT03808389). Findings: Between December 2020 and December 2021, FMT procedures were conducted on 46 patients with PD: 22 in the healthy donor group and 24 in the placebo group. Clinical evaluations were performed at baseline, 3, 6, and 12 months post-FMT. Full data analysis was possible for 21 participants in the healthy donor group and 22 in the placebo group. After 12 months, the MDS-UPDRS motor score significantly improved by a mean of 5.8 points (95% CI -11.4 to -0.2) in the healthy donor group and by 2.7 points (-8.3 to 2.9) in the placebo group (p = 0.0235). Adverse events were limited to temporary abdominal discomfort. Interpretation: Our findings suggested a single FMT induced mild, but long-lasting beneficial effects on motor symptoms in patients with early-stage PD. These findings highlight the potential of modulating the gut microbiome as a therapeutic approach and warrant a further exploration of FMT in larger cohorts of patients with PD in various disease stages. Funding: Flemish PD patient organizations (VPL and Parkili), Research Foundation Flanders (FWO), Biocodex Microbiota Foundation.