Speech analysis for the differential diagnosis between Parkinson's disease, progressive supranuclear palsy and multiple system atrophy

International audienceAcoustic speech analysis has been shown to have a good potential in differentiation between Parkinson's disease andatypical Parkinsonian syndromes (APS) such as progressive supranuclear palsy (PSP) and multiple system atrophy (MSA).Objective speech features were able to discriminate between PD and APS with 95% accuracy and between PSP and MSAwith 75% accuracy in [7]. However, accuracy between PSP and MSA still has a large space to be improved and the moreimportant aim is to provide more explicit information for differential diagnosis. In [7], 75% accuracy was achieved usingsupport vector machine classifier based on radial basis function kernel. This means it's dffcult to interpret the relationbetween selected features and decision hyperplane. In this internship, for discrimination between PSP and MSA, 9%higher accuracy (i.e, 84% accuracy) was attained by using support vector machine classifier based on radial basis functionkernel and 80% accuracy was attained using linear dimension reduction methods and linear classifier. More importantly,with this strategy, we obtain a better understanding of feature discriminative power. This can be indeed very useful inclinical application

Behavioural disinhibition in the syndromes associated with frontotemporal lobar degeneration

The different clinical syndromes caused by frontotemporal lobar degeneration (FTLD) have highly heterogenous and overlapping features which complicate clinical and research practice. Behavioural impairments are associated with all FTLD syndromes, cause high morbidity and lack proven symptomatic treatments. Treatments for cognitive and behavioural impairment in other neurodegenerative diseases include restoration of neurotransmitter deficits. Deficits in the neurotransmitters glutamate and GABA occur in FTLD syndromes and are associated with behavioural disinhibition in other diseases. I propose that these neurotransmitter deficits contribute to behavioural change in FTLD syndromes. This thesis has two main aims. First, to develop a transdiagnostic approach to FTLD syndromes to facilitate a better understanding of aetiology, pathophysiology and in due course their symptomatic treatment. Second, to use this approach to test the hypothesis that glutamate and GABA deficits are associated with behavioural disinhibition in FTLD syndromes. In a cross-sectional epidemiological study, I examined 310 of 365 regional patients with a FTLD-associated syndrome, including behavioural variant frontotemporal dementia, the nonfluent and semantic variants of primary progressive aphasia, progressive supranuclear palsy and corticobasal syndrome. Multivariate analyses of clinical features and brain morphometry identified components that showed considerable overlap across the diagnostic groups. The transdiagnostic components of clinical features predicted neuropathology better than the current FTLD diagnostic labels. Behavioural disturbance, including disinhibition, was associated with reduced functionally independent survival, irrespective of diagnosis. Next, I investigated the role of glutamate and GABA in behavioural disinhibition. Ultrahigh-field magnetic resonance spectroscopy was used to measure glutamate and GABA in the frontal cortex of 44 patients with a FTLD syndrome and 20 healthy controls. Bayesian modelling of a response inhibition task was used to quantify behavioural disinhibition. Both neurotransmitters were reduced in the frontal cortex, but not occipital cortex, of patients compared to controls. Glutamate and GABA concentrations in the frontal cortex were inversely associated with behavioural disinhibition. In summary, the transdiagnostic approach provided new insights into the phenotypic heterogeneity in FTLD syndromes. Behavioural disinhibition, which can occur to a variable degree in all FTLD syndromes, was associated with reduced functionally independent survival. GABA and glutamate deficits in the frontal cortex are associated with behavioural disinhibition and are a potential target for future treatments.Holt Fellowshi

Deep Brain Stimulation (DBS) Applications

The issue is dedicated to applications of Deep Brain Stimulation and, in this issue, we would like to highlight the new developments that are taking place in the field. These include the application of new technology to existing indications, as well as ‘new’ indications. We would also like to highlight the most recent clinical evidence from international multicentre trials. The issue will include articles relating to movement disorders, pain, psychiatric indications, as well as emerging indications that are not yet accompanied by clinical evidence. We look forward to your expert contribution to this exciting issue

Exercise as Disease-Modifying Strategy for Parkinson's: a Multidimensional Assessment of Acute and Long-Term Interventions

Parkinson's Disease (PD) is a complex and variable neurodegenerative condition. Due to its progressive nature and lack of effective treatments, a range of motor and non-motor symptoms develop and, usually, lead to disability and disengagement with active lifestyles. Exercise interventions have the potential of improving and sustaining physical and cognitive function in PD, as well as stimulating functional and structural neuroplasticity. Published research suggests that multi-modal (MM) exercise, that also includes cognitive tasks, may be more beneficial than single modalities in improving physical and/or cognitive function. However, there have been contrasting results between studies, owing to differences in study design (mode, timing, amount, and intensity of the exercise) and analytical methods used to measure biomarkers, which makes it difficult to generate conclusions and definitive exercise guidelines for people with PD (PwP). As a result of this, the overall objectives of this thesis were to propose acute and long-term interventions that are beneficial for PwP and can be implemented in real-world settings (at home or in the community), investigate associated functional and cognitive outcomes concurrently, and assess potential mechanisms underlying the neuroprotective effects of exercise interventions (MM, aerobic and combined exercise with cognitive tasks) completed in real-world or clinical environments. The first study (presented in Chapter 3) evaluates neurotrophins levels (i.e., BDNF and pro-BDNF) as candidate biomarkers for PwP in several sample types (plasma, serum, and saliva) with the aim of improving current inconsistent methodologies that compromise the reliability and validity of these measurements. Optimisation trials of ELISA assays were completed and revealed that the use of an appropriate combination of reagent diluent for each sample type and analyte is key to improve assay performance and measurement accuracy. The samples collected for the studies presented in Chapters 4 and 6 were subsequently analysed following the methodological steps reported in this study. Future work should include these methodological considerations and previous studies not reporting these details must be interpreted with caution. The second study (Chapter 4) presents the long-term implementation of a weekly community-based MM exercise programme for PwP and shows that exercise attendees improve and maintain function for up to 1, 2 or 3 years. Compared to non-active PwP, PD exercisers improve their mobility, lower extremity strength, cognition and BDNF levels, slowing down PD progression. Subsequently, focus groups were conducted in the studies presented in chapters 5 and 7 to gain in- depth understanding of participants' views about the MM exercise class and its change towards an online delivery due to the coronavirus 2019 (COVID-19) pandemic. Participant's discussions about the feasibility, practicality, and perceptions of the online class for PD, were gathered to develop guidelines for the online delivery of exercise for PwP. Finally, using an experimental laboratory setting, chapter 6 further explores the neuroprotective effects of acute bouts of aerobic exercise (alone or combined with cognitively challenging tasks) on cognitive function. This pilot study provides preliminary evidence of the beneficial effects that, both, a second bout of cycling 24h after the first session and cycling combined with cognitive tasks have on cognitive function. Taken together, both the optimisation and lab-based experimental studies provide directions for future research, such as methodological steps to ensure accurate BDNF and pro-BDNF measurements and exercise interventions that are suggested to elicit cognitive benefits. Furthermore, this thesis provides evidence that a community-based MM exercise programme is able to improve and maintain physical and cognitive functions in PwP. This intervention offered an evidence-based exercise class that had been running for over 4 years and, following COVID-19 pandemic, transitioned from the community towards an online-based setting where it has been successfully running for the last 2 years and is ongoing. Accordingly, this thesis also provides novel insights into the online delivery of MM exercise for PwP and presents guidelines for an appropriate setting-up and delivery of online exercise programmes for health-care professionals and researchers working with PwP