Exploration of Various Fractional Order Derivatives in Parkinson's Disease Dysgraphia Analysis

Parkinson's disease (PD) is a common neurodegenerative disorder with a prevalence rate estimated to 2.0% for people aged over 65 years. Cardinal motor symptoms of PD such as rigidity and bradykinesia affect the muscles involved in the handwriting process resulting in handwriting abnormalities called PD dysgraphia. Nowadays, online handwritten signal (signal with temporal information) acquired by the digitizing tablets is the most advanced approach of graphomotor difficulties analysis. Although the basic kinematic features were proved to effectively quantify the symptoms of PD dysgraphia, a recent research identified that the theory of fractional calculus can be used to improve the graphomotor difficulties analysis. Therefore, in this study, we follow up on our previous research, and we aim to explore the utilization of various approaches of fractional order derivative (FD) in the analysis of PD dysgraphia. For this purpose, we used the repetitive loops task from the Parkinson's disease handwriting database (PaHaW). Handwritten signals were parametrized by the kinematic features employing three FD approximations: Gr\"unwald-Letnikov's, Riemann-Liouville's, and Caputo's. Results of the correlation analysis revealed a significant relationship between the clinical state and the handwriting features based on the velocity. The extracted features by Caputo's FD approximation outperformed the rest of the analyzed FD approaches. This was also confirmed by the results of the classification analysis, where the best model trained by Caputo's handwriting features resulted in a balanced accuracy of 79.73% with a sensitivity of 83.78% and a specificity of 75.68%.Comment: Print ISBN 978-3-031-19744-

Prodromal Diagnosis of Lewy Body Diseases Based on the Assessment of Graphomotor and Handwriting Difficulties

To this date, studies focusing on the prodromal diagnosis of Lewy body diseases (LBDs) based on quantitative analysis of graphomotor and handwriting difficulties are missing. In this work, we enrolled 18 subjects diagnosed with possible or probable mild cognitive impairment with Lewy bodies (MCI-LB), 7 subjects having more than 50% probability of developing Parkinson's disease (PD), 21 subjects with both possible/probable MCI-LB and probability of PD > 50%, and 37 age- and gender-matched healthy controls (HC). Each participant performed three tasks: Archimedean spiral drawing (to quantify graphomotor difficulties), sentence writing task (to quantify handwriting difficulties), and pentagon copying test (to quantify cognitive decline). Next, we parameterized the acquired data by various temporal, kinematic, dynamic, spatial, and task-specific features. And finally, we trained classification models for each task separately as well as a model for their combination to estimate the predictive power of the features for the identification of LBDs. Using this approach we were able to identify prodromal LBDs with 74% accuracy and showed the promising potential of computerized objective and non-invasive diagnosis of LBDs based on the assessment of graphomotor and handwriting difficulties.Comment: Print ISBN 978-3-031-19744-

Neuromechanical Modelling of Articulatory Movements from Surface Electromyography and Speech Formants

Speech articulation is produced by the movements of muscles in the larynx, pharynx, mouth and face. Therefore speech shows acoustic features as formants which are directly related with neuromotor actions of these muscles. The first two formants are strongly related with jaw and tongue muscular activity. Speech can be used as a simple and ubiquitous signal, easy to record and process, either locally or on e-Health platforms. This fact may open a wide set of applications in the study of functional grading and monitoring neurodegenerative diseases. A relevant question, in this sense, is how far speech correlates and neuromotor actions are related. This preliminary study is intended to find answers to this question by using surface electromyographic recordings on the masseter and the acoustic kinematics related with the first formant. It is shown in the study that relevant correlations can be found among the surface electromyographic activity (dynamic muscle behavior) and the positions and first derivatives of the first formant (kinematic variables related to vertical velocity and acceleration of the joint jaw and tongue biomechanical system). As an application example, it is shown that the probability density function associated to these kinematic variables is more sensitive than classical features as Vowel Space Area (VSA) or Formant Centralization Ratio (FCR) in characterizing neuromotor degeneration in Parkinson's Disease.This work is being funded by Grants TEC2016-77791-C4-4-R from the Ministry of Economic Affairs and Competitiveness of Spain, Teka-Park 55 02 CENIE-0348_CIE_6_E POCTEP (InterReg Programme) and 16-30805A, SIX Research Center (CZ.1.05/2.1.00/03.0072), and LO1401 from the Czech Republic Government

Diffusion kurtosis imaging detects the time-dependent progress of pathological changes in the oral rotenone mouse model of Parkinson's disease

Clinical diagnosis of Parkinson's disease (PD) occurs typically when a substantial proportion of dopaminergic neurons in the substantia nigra (SN) already died, and the first motor symptoms appear. Therefore, tools enabling the early diagnosis of PD are essential to identify early-stage PD patients in which neuroprotective treatments could have a significant impact. Here, we test the utility and sensitivity of the diffusion kurtosis imaging (DKI) in detecting progressive microstructural changes in several brain regions of mice exposed to chronic intragastric administration of rotenone, a mouse model that mimics the spatiotemporal progression of PD-like pathology from the ENS to the SN as described by Braak's staging. Our results show that DKI, especially kurtosis, can detect the progression of pathology-associated changes throughout the CNS. Increases in mean kurtosis were first observed in the dorsal motor nucleus of the vagus (DMV) after 2 months of exposure to rotenone and before the loss of dopaminergic neurons in the SN occurred. Remarkably, we also show that limited exposure to rotenone for 2 months is enough to trigger the progression of the disease in the absence of the environmental toxin, thus suggesting that once the first pathological changes in one region appear, they can self-perpetuate and progress within the CNS. Overall, our results show that DKI can be a useful radiological marker for the early detection and monitoring of PD pathology progression in patients with the potential to improve the clinical diagnosis and the development of neuroprotective treatments. (Figure presented.). © 2021 International Society for Neurochemistr

Degree of Parkinson's Disease Severity Estimation Based on Speech Signal Processing

International audienceThis paper deals with Parkinson's disease (PD) severity estimation according to the Unified Parkinson's Disease Rating Scale: motor subscale (UPDRS III), which quantifies the hallmark symptoms of PD, using an acoustic analysis of speech signals. Experimental dataset comprised 42 speech tasks acquired from 50 PD patients (UPDRS III ranged from 6 to 92). It was divided into subsets: words, sentences, reading text, monologue and diadochokinetic tasks. We performed a parametrization of the whole corpus and these groups separately using a wide range of conventional and novel speech features. We used guided regu-larized random forest algorithm to select features with maximum clinical information and performed random forests regression to estimate PD severity. According to significant correlations between true UPDRS III scores and scores predicted by the proposed methodology it was shown that information extracted through variety of speech tasks can be used to estimate the degree of PD severity

Comparison of CNN-Learned vs. Handcrafted Features for Detection of Parkinson's Disease Dysgraphia in a Multilingual Dataset

Parkinson's disease dysgraphia (PDYS), one of the earliest signs of Parkinson's disease (PD), has been researched as a promising biomarker of PD and as the target of a noninvasive and inexpensive approach to monitoring the progress of the disease. However, although several approaches to supportive PDYS diagnosis have been proposed (mainly based on handcrafted features (HF) extracted from online handwriting or the utilization of deep neural networks), it remains unclear which approach provides the highest discrimination power and how these approaches can be transferred between different datasets and languages. This study aims to compare classification performance based on two types of features: features automatically extracted by a pretrained convolutional neural network (CNN) and HF designed by human experts. Both approaches are evaluated on a multilingual dataset collected from 143 PD patients and 151 healthy controls in the Czech Republic, United States, Colombia, and Hungary. The subjects performed the spiral drawing task (SDT; a language-independent task) and the sentence writing task (SWT; a language-dependent task). Models based on logistic regression and gradient boosting were trained in several scenarios, specifically single language (SL), leave one language out (LOLO), and all languages combined (ALC). We found that the HF slightly outperformed the CNN-extracted features in all considered evaluation scenarios for the SWT. In detail, the following balanced accuracy (BACC) scores were achieved: SL—0.65 (HF), 0.58 (CNN); LOLO—0.65 (HF), 0.57 (CNN); and ALC—0.69 (HF), 0.66 (CNN). However, in the case of the SDT, features extracted by a CNN provided competitive results: SL—0.66 (HF), 0.62 (CNN); LOLO—0.56 (HF), 0.54 (CNN); and ALC—0.60 (HF), 0.60 (CNN). In summary, regarding the SWT, the HF outperformed the CNN-extracted features over 6% (mean BACC of 0.66 for HF, and 0.60 for CNN). In the case of the SDT, both feature sets provided almost identical classification performance (mean BACC of 0.60 for HF, and 0.58 for CNN). Copyright © 2022 Galaz, Drotar, Mekyska, Gazda, Mucha, Zvoncak, Smekal, Faundez-Zanuy, Castrillon, Orozco-Arroyave, Rapcsak, Kincses, Brabenec and Rektorova

The role of high-field magnetic resonance imaging in parkinsonian disorders:Pushing the boundaries forward

Historically, magnetic resonance imaging (MRI) has contributed little to the study of Parkinson's disease (PD), but modern MRI approaches have unveiled several complementary markers that are useful for research and clinical applications. Iron- and neuromelanin-sensitive MRI detect qualitative changes in the substantia nigra. Quantitative MRI markers can be derived from diffusion weighted and iron-sensitive imaging or volumetry. Functional brain alterations at rest or during task performance have been captured with functional and arterial spin labeling perfusion MRI. These markers are useful for the diagnosis of PD and atypical parkinsonism, to track disease progression from the premotor stages of these diseases and to better understand the neurobiological basis of clinical deficits. A current research goal using MRI is to generate time-dependent models of the evolution of PD biomarkers that can help understand neurodegeneration and provide reliable markers for therapeutic trials. This article reviews recent advances in MRI biomarker research at high-field (3T) and ultra high field-imaging (7T) in PD and atypical parkinsonism. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Gray Matter Changes in Parkinson's and Alzheimer's Disease and Relation to Cognition

Purpose of Review We summarize structural (s)MRI findings of gray matter (GM) atrophy related to cognitive impairment in Alzheimer's disease (AD) and Parkinson's disease (PD) in light of new analytical approaches and recent longitudinal studies results. Recent Findings The hippocampus-to-cortex ratio seems to be the best sMRI biomarker to discriminate between various AD subtypes, following the spatial distribution of tau pathology, and predict rate of cognitive decline. PD is clinically far more variable than AD, with heterogeneous underlying brain pathology. Novel multivariate approaches have been used to describe patterns of early subcortical and cortical changes that relate to more malignant courses of PD. New emerging analytical approaches that combine structural MRI data with clinical and other biomarker outcomes hold promise for detecting specific GM changes in the early stages of PD and preclinical AD that may predict mild cognitive impairment and dementia conversion

Sex differences in brain atrophy in dementia with Lewy bodies

Publisher Copyright: © 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.INTRODUCTION: Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). METHODS: We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n = 165; 69 ± 9 years, 72% males). RESULTS: We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. DISCUSSION: We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. Highlights: Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.Peer reviewe