Elayne Borges Fernandes

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder marked by motor and non-motor symptoms, including cognitive decline, mood disturbances, and sensory deficits. While dopaminergic treatments remain the gold standard, they present long-term side effects and limited impact on non-motor symptoms. Transcranial Pulse Stimulation (TPS) has emerged as a promising adjunct therapy in neurological and psychiatric conditions, but its effects in PD remain underexplored. This open-label, single-arm trial protocol involves 14 PD participants and outlines a personalized 12-session treatment approach combined with a homogeneously distributed TPS intervention among patients with PD. The approach addresses the subject’s most prominent symptoms, as identified through validated clinical assessments, encompassing domains related to both motor and non-motor symptoms. Over 2.5 months, besides the intervention sessions, the 14 participants will undergo an MRI brain scan, a baseline assessment, a post-treatment assessment, and a 1-month follow-up assessment. The study aims to determine whether personalized TPS is a feasible and safe intervention and whether it improves PD symptoms across multiple functional domains. This study represents the first structured attempt to evaluate a multimodal, personalized TPS intervention in patients with PD. It addresses gaps in current treatment approaches and may support the development of future strategies for integrated, symptom-targeted neuromodulation.

Background: Asymmetrical brain oscillations may be characteristic of Parkinson’s disease (PD). We investigated differences in oscillation asymmetry between individuals with PD and healthy controls and explored associations between the asymmetry and clinical features. Methods: Clinical and resting-state EEG data from 37 patients and 24 controls were cross-sectionally analyzed. EEG asymmetry indices were calculated for the delta, theta, alpha, and beta frequencies in the frontal, central, and parietal regions. Independent t-tests and linear regression models were employed. Results: Patients exhibited lower alpha asymmetry than controls in the parietal region (t(59) = 2.12, p = 0.03). In the frontal alpha asymmetry models, there were associations with time since diagnosis (β = −0.042) and attention/orientation (β = 0.061), and with Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRSIII)-posture (β = 0.136) and MDS-UPDRSIII-rest-tremor persistence (β = −0.111). In the central alpha model, higher asymmetry was associated with the physical activity levels (International Physical Activity Questionnaire) IPAQ-active (β = 0.646) and IPAQ-very active (β = 0.689), (Timed Up and Go) TUG dual-task cost (β = 0.023), MDS-UPDRSII-freezing (β = 0.238), and being male (β = 0.535). In the parietal alpha asymmetry model, MDS-UPDRSII-gait/balance was inversely associated with alpha asymmetry (β = −0.156), while IPAQ-active (β = −0.247) and being male (β = −0.191) were associated with lower asymmetry. Conclusions: Our findings highlight the potential role of alpha asymmetry as a neurophysiological marker of PD’s motor symptoms, mainly rest tremor, gait/balance, freezing, and specific cognitive domains such as attention/orientation. The models stressed the relationship between disease progression and reduced alpha asymmetry. Brazilian Registry of Clinical Trials (RBR-7zjgnrx, 9 June 2022).

Parkinson’s disease (PD) is a progressive neurodegenerative disorder primarily characterized by motor impairments resulting from dopaminergic neuron degeneration in the substantia nigra. However, PD is increasingly recognized as a multisystem disorder, where non-motor symptoms such as cognitive impairment, mood disturbances, sleep disorders, and autonomic dysfunction significantly impact patients’ quality of life. These non-motor symptoms often exhibit poor responsiveness to traditional dopaminergic therapies, underscoring a critical gap in current treatment strategies. Our systematic review investigates established methods of PD induction in rodent models and evaluates the methodologies used to assess non-motor symptoms. The review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Cochrane handbook. Thirty-two studies from 832 articles were included. The studies were characterized by MPTP, 6-OHDA, and rotenone. Our results indicate that there was considerable heterogeneity in behavioral and motor tests, which poses challenges for data comparability and highlights the lack of consensus regarding the most appropriate modeling strategies for specific PD-related behavioral outcomes. All three models demonstrated behavioral changes consistent with dopaminergic impairment when compared to control groups. MPTP-induced models showed significant non-motor deficits across various tests, except in social recognition and novelty-suppressed feeding. The 6-OHDA model consistently produced non-motor impairments, supporting its utility in replicating PD-like neurotoxicity. Rotenone-treated animals exhibited reduced social interaction, decreased sucrose preference, and increased immobility in behavioral assays, further supporting its validity. Overall, our findings indicate that these neurotoxin-based models are effective in reproducing non-motor symptoms of PD, though methodological heterogeneity highlights the need for greater standardization in future preclinical research.