Non-Invasive Neuromodulation Therapies for Parkinson’s Disease

Noninvasive brain stimulation (NIBS) technologies have been applied to study brain physiology and, more recently, have been recognized for their therapeutic potential as an adjunctive treatment for various neurologic and psychiatric disorders. Transcranial magnetic stimulation (TMS) and transcranial electric stimulation (tES) are two of the most studied NIBS modalities in Parkinson’s disease. They are non-systemic and relatively safe. Most therapeutic trials have been conducted to ameliorate motor symptoms of Parkinson’s disease (PD) with overall positive results using various stimulation modalities and methods. Notwithstanding significant results, evidence has not yet been compelling mainly due to small-size studies, lack of standardization of methodologies and other study design limitations. NIBS hold promise for treatment of PD symptoms and PD related complications. Large, well designed clinical trials are needed to corroborate these positive findings and inform its durability and the overall clinical relevance for the treatment of PD

Art therapy for Parkinson's disease.

Abstract Objective To explore the potential rehabilitative effect of art therapy and its underlying mechanisms in Parkinson's disease (PD). Methods Observational study of eighteen patients with PD, followed in a prospective, open-label, exploratory trial. Before and after twenty sessions of art therapy, PD patients were assessed with the UPDRS, Pegboard Test, Timed Up and Go Test (TUG), Beck Depression Inventory (BDI), Modified Fatigue Impact Scale and PROMIS-Self-Efficacy, Montreal Cognitive Assessment, Rey-Osterrieth Complex Figure Test (RCFT), Benton Visual Recognition Test (BVRT), Navon Test, Visual Search, and Stop Signal Task. Eye movements were recorded during the BVRT. Resting-state functional MRI (rs-fMRI) was also performed to assess functional connectivity (FC) changes within the dorsal attention (DAN), executive control (ECN), fronto-occipital (FOC), salience (SAL), primary and secondary visual (V1, V2) brain networks. We also tested fourteen age-matched healthy controls at baseline. Results At baseline, PD patients showed abnormal visual-cognitive functions and eye movements. Analyses of rs-fMRI showed increased functional connectivity within DAN and ECN in patients compared to controls. Following art therapy, performance improved on Navon test, eye tracking, and UPDRS scores. Rs-fMRI analysis revealed significantly increased FC levels in brain regions within V1 and V2 networks. Interpretation Art therapy improves overall visual-cognitive skills and visual exploration strategies as well as general motor function in patients with PD. The changes in brain connectivity highlight a functional reorganization of visual networks

Using illusions to understand hallucinations: differences in perceptual performances on illusory figures may underscore specific visuoperceptual impairments in Parkinson’s disease

Visual hallucinations are prevalent, potentially disabling symptoms of Parkinson’s Disease. Multiple impairments in bottom-up sensory processing and top-down perceptual modulation are implicated in the pathophysiology of these phenomena. In healthy individuals, visual illusions are elicited by illusory figures through parametric manipulations of geometrical configurations, contrast, color, or spatial relationships between stimuli. These illusory percepts provide insight on the physiologic processes subserving conscious and unconscious perception. In this exploratory, cross-sectional, controlled study, perceptual performance on illusory figures was assessed on 11 PD patients with hallucinations, 10 non-hallucinating PD patients, and 10 age-matched healthy individuals. In order to characterize potential neural substrates of perceptual performances, patients’ brain metabolic patterns on FDG PET were also analyzed. Illusions relying on attentional modulation and global perception were attenuated in PD patients without hallucinations. This pattern was no longer recognizable in hallucinating patients. Conversely, illusory effects normally counteracted by figure to background segregation and overlapping figures recognition were enhanced in PD patients with hallucinations. FDG PET findings further suggest that perceptual differences between PD patients might be linked to abnormal top-down perceptual modulation

Art Therapy as a Comprehensive Complementary Treatment for Parkinson’s Disease

Introduction: Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease. Complementary and alternative therapies are increasingly utilized to address its complex multisystem symptomatology. Art therapy involves motoric action and visuospatial processing while promoting broad biopsychosocial wellness. The process involves hedonic absorption, which provides an escape from otherwise persistent and cumulative PD symptoms, refreshing internal resources. It involves the expression in nonverbal form of multilayered psychological and somatic phenomena; once these are externalized in a symbolic arts medium, they can be explored, understood, integrated, and reorganized through verbal dialogue, effecting relief and positive change. Methods: 42 participants with mild to moderate PD were treated with 20 sessions of group art therapy. They were assessed before and after therapy with a novel arts-based instrument developed to match the treatment modality for maximum sensitivity. The House-Tree-Person PD Scale (HTP-PDS) assesses motoric and visuospatial processing–core PD symptoms–as well as cognition (thought and logic), affect/mood, motivation, self (including body-image, self-image, and self- efficacy), interpersonal functioning, creativity, and overall level of functioning. It was hypothesized that art therapy will ameliorate core PD symptoms and that this will correlate with improvements in all other variables. Results: HTP-PDS scores across all symptoms and variables improved significantly, though causality among variables was indeterminate. Discussion: Art therapy is a clinically efficacious complementary treatment for PD. Further research is warranted to disentangle causal pathways among the aforementioned variables, and additionally, to isolate and examine the multiple, discrete healing mechanisms believed to operate simultaneously in art therapy

Blood transcriptomics of drug-na\uefve sporadic Parkinson's disease patients

BACKGROUND: Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. METHODS: Changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls ("Discovery set") were analyzed by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. Data analysis was performed by applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays. Functional annotations were assigned using GO, DAVID, GSEA to unveil significant enriched biological processes in the differentially expressed genes. The expressions of selected genes were validated using RT-qPCR and samples from an independent cohort of 12 patients and controls ("Validation set"). RESULTS: Gene expression profiling of blood samples discriminates PD patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts as CBX5, TCF3, MAN1C1 and DOCK10 were validated by RT-qPCR. CONCLUSIONS: Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

Ten millennia of hepatitis B virus evolution

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for ~4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic

Decalcifying capability of irrigating solutions on root canal dentin mineral content

Background: Chelating agents are believed to aid root canal irrigation and to be able to remove the inorganic smear layer. Aims: The purpose of the present study was to evaluate and to compare the decalcifying capability of different irrigating solutions (Tubuliclean, Largal Ultra, ethylenediaminetetraacetic acid 17%, Tetraclean, Tetraclean NA). Materials and Methods: Sixty maxillary central incisors were used. Root canals were instrumented and irrigated. From each root, four comparable slices of cervical dentin were obtained. At three successive 5-min interval immersion times, the concentration of calcium extracted from root canal dentin was assessed with an inductively coupled plasma-atomic emission spectrometer. Statistical Analysis Used: Data were analyzed by means of Kruskal Wallis and Mann–Whitney tests. Significance was predetermined at P < 0.05. Results and Conclusions: For all irrigating solutions, the maximum amount of Ca2+ extracted from root canal dentin samples was reached after 10 min contact time except for citric acid-based agents (Tetraclean and Tetraclean NA) which induced a higher and still increasing calcium release even after 10 min contact time. In order to obtain an efficient decalcifying action on dentin and to facilitate the biomechanical procedures, citric acid-based irrigants can be applied

Tele-monitored tDCS rehabilitation: feasibility, challenges and future perspectives in Parkinson’s disease

Abstract Transcranial direct current stimulation (tDCS) is a modality of non-invasive brain stimulation involving the application of low amplitude direct current via surface electrodes on the scalp. tDCS has been studied in healthy populations and in multiple brain disorders and has the potential to be a treatment for several neuropsychiatric conditions by virtue of its capability of influencing cognitive, motor and behavioral processes. tDCS is a generally safe technique when performed within standardized protocols in research or clinical settings. Furthermore, tDCS portability, high acceptability and user-friendly interface makes it highly appealing for telemedicine practices. The term “telemedicine” refers to the procedures, educational strategies, and care services that are remotely administered by means of different communication technologies, with the final goal of increasing access to care for individuals and for improving public health. The use of telemedicine combined with tDCS protocols is increasing, although the safety of this approach in different clinical settings awaits further assessment. While “do-it-yourself” tDCS should be discouraged due to the unknown risk of adverse events, the implementation of tele-monitored tDCS (tele-tDCS) within standardized frameworks ensuring safety, tolerability, and reproducibility may allow this technology to reach larger clinical populations and bypass some of the common barriers preventing access to health services and clinical trials. This review will discuss the current evidence supporting the feasibility of tele-tDCS paradigms and their therapeutic potential, with particular emphasis on the implications for patients with Parkinson’s disease