Effects of deep brain stimulation of the subthalamic nucleus on patients with Parkinson's disease: a machine-learning voice analysis.

Introduction: Deep brain stimulation of the subthalamic nucleus (STN-DBS) can exert relevant effects on the voice of patients with Parkinson's disease (PD). In this study, we used artificial intelligence to objectively analyze the voices of PD patients with STN-DBS. Materials and methods: In a cross-sectional study, we enrolled 108 controls and 101 patients with PD. The cohort of PD was divided into two groups: the first group included 50 patients with STN-DBS, and the second group included 51 patients receiving the best medical treatment. The voices were clinically evaluated using the Unified Parkinson's Disease Rating Scale part-III subitem for voice (UPDRS-III-v). We recorded and then analyzed voices using specific machine-learning algorithms. The likelihood ratio (LR) was also calculated as an objective measure for clinical-instrumental correlations. Results: Clinically, voice impairment was greater in STN-DBS patients than in those who received oral treatment. Using machine learning, we objectively and accurately distinguished between the voices of STN-DBS patients and those under oral treatments. We also found significant clinical-instrumental correlations since the greater the LRs, the higher the UPDRS-III-v scores. Discussion: STN-DBS deteriorates speech in patients with PD, as objectively demonstrated by machine-learning voice analysis.

Acoustic analysis in stuttering: a machine-learning study.

Background: Stuttering is a childhood-onset neurodevelopmental disorder affecting speech fluency. The diagnosis and clinical management of stuttering is currently based on perceptual examination and clinical scales. Standardized techniques for acoustic analysis have prompted promising results for the objective assessment of dysfluency in people with stuttering (PWS). Objective: We assessed objectively and automatically voice in stuttering, through artificial intelligence (i.e., the support vector machine - SVM classifier). We also investigated the age-related changes affecting voice in stutterers, and verified the relevance of specific speech tasks for the objective and automatic assessment of stuttering. Methods: Fifty-three PWS (20 children, 33 younger adults) and 71 age-/gender-matched controls (31 children, 40 younger adults) were recruited. Clinical data were assessed through clinical scales. The voluntary and sustained emission of a vowel and two sentences were recorded through smartphones. Audio samples were analyzed using a dedicated machine-learning algorithm, the SVM to compare PWS and controls, both children and younger adults. The receiver operating characteristic (ROC) curves were calculated for a description of the accuracy, for all comparisons. The likelihood ratio (LR), was calculated for each PWS during all speech tasks, for clinical-instrumental correlations, by using an artificial neural network (ANN). Results: Acoustic analysis based on machine-learning algorithm objectively and automatically discriminated between the overall cohort of PWS and controls with high accuracy (88%). Also, physiologic ageing crucially influenced stuttering as demonstrated by the high accuracy (92%) of machine-learning analysis when classifying children and younger adults PWS. The diagnostic accuracies achieved by machine-learning analysis were comparable for each speech task. The significant clinical-instrumental correlations between LRs and clinical scales supported the biological plausibility of our findings. Conclusion: Acoustic analysis based on artificial intelligence (SVM) represents a reliable tool for the objective and automatic recognition of stuttering and its relationship with physiologic ageing. The accuracy of the automatic classification is high and independent of the speech task. Machine-learning analysis would help clinicians in the objective diagnosis and clinical management of stuttering. The digital collection of audio samples here achieved through smartphones would promote the future application of the technique in a telemedicine context (home environment).

Robust and language-independent acoustic features in Parkinson's disease.

Introduction: The analysis of vocal samples from patients with Parkinson's disease (PDP) can be relevant in supporting early diagnosis and disease monitoring. Intriguingly, speech analysis embeds several complexities influenced by speaker characteristics (e.g., gender and language) and recording conditions (e.g., professional microphones or smartphones, supervised, or non-supervised data collection). Moreover, the set of vocal tasks performed, such as sustained phonation, reading text, or monologue, strongly affects the speech dimension investigated, the feature extracted, and, as a consequence, the performance of the overall algorithm. Methods: We employed six datasets, including a cohort of 176 Healthy Control (HC) participants and 178 PDP from different nationalities (i.e., Italian, Spanish, Czech), recorded in variable scenarios through various devices (i.e., professional microphones and smartphones), and performing several speech exercises (i.e., vowel phonation, sentence repetition). Aiming to identify the effectiveness of different vocal tasks and the trustworthiness of features independent of external co-factors such as language, gender, and data collection modality, we performed several intra- and inter-corpora statistical analyses. In addition, we compared the performance of different feature selection and classification models to evaluate the most robust and performing pipeline. Results: According to our results, the combined use of sustained phonation and sentence repetition should be preferred over a single exercise. As for the set of features, the Mel Frequency Cepstral Coefficients demonstrated to be among the most effective parameters in discriminating between HC and PDP, also in the presence of heterogeneous languages and acquisition techniques. Conclusion: Even though preliminary, the results of this work can be exploited to define a speech protocol that can effectively capture vocal alterations while minimizing the effort required to the patient. Moreover, the statistical analysis identified a set of features minimally dependent on gender, language, and recording modalities. This discloses the feasibility of extensive cross-corpora tests to develop robust and reliable tools for disease monitoring and staging and PDP follow-up.

Artificial Intelligence-Based Voice Assessment of Patients with Parkinson's Disease Off and On Treatment: Machine vs. Deep-Learning Comparison.

Parkinson's Disease (PD) is one of the most common non-curable neurodegenerative diseases. Diagnosis is achieved clinically on the basis of different symptoms with considerable delays from the onset of neurodegenerative processes in the central nervous system. In this study, we investigated early and full-blown PD patients based on the analysis of their voice characteristics with the aid of the most commonly employed machine learning (ML) techniques. A custom dataset was made with hi-fi quality recordings of vocal tasks gathered from Italian healthy control subjects and PD patients, divided into early diagnosed, off-medication patients on the one hand, and mid-advanced patients treated with L-Dopa on the other. Following the current state-of-the-art, several ML pipelines were compared usingdifferent feature selection and classification algorithms, and deep learning was also explored with a custom CNN architecture. Results show how feature-based ML and deep learning achieve comparable results in terms of classification, with KNN, SVM and naïve Bayes classifiers performing similarly, with a slight edge for KNN. Much more evident is the predominance of CFS as the best feature selector. The selected features act as relevant vocal biomarkers capable of differentiating healthy subjects, early untreated PD patients and mid-advanced L-Dopa treated patients.

Deep learning and machine learning-based voice analysis for the detection of COVID-19: A proposal and comparison of architectures.

Alongside the currently used nasal swab testing, the COVID-19 pandemic situation would gain noticeable advantages from low-cost tests that are available at any-time, anywhere, at a large-scale, and with real time answers. A novel approach for COVID-19 assessment is adopted here, discriminating negative subjects versus positive or recovered subjects. The scope is to identify potential discriminating features, highlight mid and short-term effects of COVID on the voice and compare two custom algorithms. A pool of 310 subjects took part in the study; recordings were collected in a low-noise, controlled setting employing three different vocal tasks. Binary classifications followed, using two different custom algorithms. The first was based on the coupling of boosting and bagging, with an AdaBoost classifier using Random Forest learners. A feature selection process was employed for the training, identifying a subset of features acting as clinically relevant biomarkers. The other approach was centered on two custom CNN architectures applied to mel-Spectrograms, with a custom knowledge-based data augmentation. Performances, evaluated on an independent test set, were comparable: Adaboost and CNN differentiated COVID-19 positive from negative with accuracies of 100% and 95% respectively, and recovered from negative individuals with accuracies of 86.1% and 75% respectively. This study highlights the possibility to identify COVID-19 positive subjects, foreseeing a tool for on-site screening, while also considering recovered subjects and the effects of COVID-19 on the voice. The two proposed novel architectures allow for the identification of biomarkers and demonstrate the ongoing relevance of traditional ML versus deep learning in speech analysis.

Voice in Parkinson's Disease: A Machine Learning Study.

INTRODUCTION: Parkinson's disease (PD) is characterized by specific voice disorders collectively termed hypokinetic dysarthria. We here investigated voice changes by using machine learning algorithms, in a large cohort of patients with PD in different stages of the disease, OFF and ON therapy. METHODS: We investigated 115 patients affected by PD (mean age: 68.2 ± 9.2 years) and 108 age-matched healthy subjects (mean age: 60.2 ± 11.0 years). The PD cohort included 57 early-stage patients (Hoehn &Yahr ≤ 2) who never took L-Dopa for their disease at the time of the study, and 58 mid-advanced-stage patients (Hoehn &Yahr >2) who were chronically-treated with L-Dopa. We clinically evaluated voices using specific subitems of the Unified Parkinson's Disease Rating Scale and the Voice Handicap Index. Voice samples recorded through a high-definition audio recorder underwent machine learning analysis based on the support vector machine classifier. We also calculated the receiver operating characteristic curves to examine the diagnostic accuracy of the analysis and assessed possible clinical-instrumental correlations. RESULTS: Voice is abnormal in early-stage PD and as the disease progresses, voice increasingly degradres as demonstrated by high accuracy in the discrimination between healthy subjects and PD patients in the early-stage and mid-advanced-stage. Also, L-dopa therapy improves but not restore voice in PD as shown by high accuracy in the comparison between patients OFF and ON therapy. Finally, for the first time we achieved significant clinical-instrumental correlations by using a new score (LR value) calculated by machine learning. CONCLUSION: Voice is abnormal in early-stage PD, progressively degrades in mid-advanced-stage and can be improved but not restored by L-Dopa. Lastly, machine learning allows tracking disease severity and quantifying the symptomatic effect of L-Dopa on voice parameters with previously unreported high accuracy, thus representing a potential new biomarker of PD.

The Impact of Wearable Electronics in Assessing the Effectiveness of Levodopa Treatment in Parkinson's Disease.

OBJECTIVE: In order to evaluate Parkinson disease patients' response to therapeutic interventions, sources of information are mainly patient reports and clinicians' assessment of motor functions. However, these sources can suffer from patient's subjectivity and from inter/intra rater's score variability. Our work aimed at determining the impact of wearable electronics and data analysis in objectifying the effectiveness of levodopa treatment. METHODS: Seven motor tasks performed by thirty-six patients were measured by wearable electronics and related data were analyzed. This was at the time of therapy initiation (T0), and repeated after six (T1) and 12 months (T2). Wearable electronics consisted of inertial measurement units each equipped with 3-axis accelerometer and 3-axis gyroscope, while data analysis of ANOVA and Pearson correlation algorithms, in addition to a support vector machine (SVM) classification. RESULTS: According to our findings, levodopa-based therapy alters the patient's conditions in general, ameliorating something (e.g., bradykinesia), leaving unchanged others (e.g., tremor), but with poor correlation to the levodopa dose. CONCLUSION: A technology-based approach can objectively assess levodopa-based therapy effectiveness. SIGNIFICANCE: Novel devices can improve the accuracy of the assessment of motor function, by integrating the clinical evaluation and patient reports.

Worldwide Healthy Adult Voice Baseline Parameters: A Comprehensive Review.

The voice results in acoustic signals analyzed and synthetized at first for telecommunication matters, and more recently investigated for medical purposes. In particular, voice signal characteristics can evidence individual health conditions useful for screening, diagnostic and remote monitoring aims. Within this frame, the knowledge of baseline features of healthy voice is mandatory, in order to balance a comparison with their unhealthy counterpart. However, the baseline features of the human voice depend on gender, age-range and ethnicity and, as far as we know, no work reports as those features spread worldwide. This paper intends to cover this lack. Our database research yielded 179 relevant published studies, retrieved using digital libraries of IEEE Xplore, Scopus, Web of Science, Iop Science, Taylor and Francis Online, and Scitepress. These relevant studies report different features, among which here we consider the most investigated ones, within the most investigated age-range. In particular, the features are the fundamental frequency, the jitter, the shimmer, the harmonic-to-noise ratio, and the cepstral peak prominence, the most investigated age-range is within 20-40 years and, related to the ethnicity, 20 countries are considered.

Machine Learning-based Voice Assessment for the Detection of Positive and Recovered COVID-19 Patients.

Many virological tests have been implemented during the Coronavirus Disease 2019 (COVID-19) pandemic for diagnostic purposes, but they appear unsuitable for screening purposes. Furthermore, current screening strategies are not accurate enough to effectively curb the spread of the disease. Therefore, the present study was conducted within a controlled clinical environment to determine eventual detectable variations in the voice of COVID-19 patients, recovered and healthy subjects, and also to determine whether machine learning-based voice assessment (MLVA) can accurately discriminate between them, thus potentially serving as a more effective mass-screening tool. Three different subpopulations were consecutively recruited: positive COVID-19 patients, recovered COVID-19 patients and healthy individuals as controls. Positive patients were recruited within 10 days from nasal swab positivity. Recovery from COVID-19 was established clinically, virologically and radiologically. Healthy individuals reported no COVID-19 symptoms and yielded negative results at serological testing. All study participants provided three trials for multiple vocal tasks (sustained vowel phonation, speech, cough). All recordings were initially divided into three different binary classifications with a feature selection, ranking and cross-validated RBF-SVM pipeline. This brough a mean accuracy of 90.24%, a mean sensitivity of 91.15%, a mean specificity of 89.13% and a mean AUC of 0.94 across all tasks and all comparisons, and outlined the sustained vowel as the most effective vocal task for COVID discrimination. Moreover, a three-way classification was carried out on an external test set comprised of 30 subjects, 10 per class, with a mean accuracy of 80% and an accuracy of 100% for the detection of positive subjects. Within this assessment, recovered individuals proved to be the most difficult class to identify, and all the misclassified subjects were declared positive; this might be related to mid and short-term vocal traces of COVID-19, even after the clinical resolution of the infection. In conclusion, MLVA may accurately discriminate between positive COVID-19 patients, recovered COVID-19 patients and healthy individuals. Further studies should test MLVA among larger populations and asymptomatic positive COVID-19 patients to validate this novel screening technology and test its potential application as a potentially more effective surveillance strategy for COVID-19.

Technology-based therapy-response and prognostic biomarkers in a prospective study of a de novo Parkinson's disease cohort.

Early noninvasive reliable biomarkers are among the major unmet needs in Parkinson's disease (PD) to monitor therapy response and disease progression. Objective measures of motor performances could allow phenotyping of subtle, undetectable, early stage motor impairments of PD patients. This work aims at identifying prognostic biomarkers in newly diagnosed PD patients and quantifying therapy-response. Forty de novo PD patients underwent clinical and technology-based kinematic assessments performing motor tasks (MDS-UPDRS part III) to assess tremor, bradykinesia, gait, and postural stability (T0). A visit after 6 months (T1) and a clinical and kinematic assessment after 12 months (T2) where scheduled. A clinical follow-up was provided between 30 and 36 months after the diagnosis (T3). We performed an ANOVA for repeated measures to compare patients' kinematic features at baseline and at T2 to assess therapy response. Pearson correlation test was run between baseline kinematic features and UPDRS III score variation between T0 and T3, to select candidate kinematic prognostic biomarkers. A multiple linear regression model was created to predict the long-term motor outcome using T0 kinematic measures. All motor tasks significantly improved after the dopamine replacement therapy. A significant correlation was found between UPDRS scores variation and some baseline bradykinesia (toe tapping amplitude decrement, p = 0.009) and gait features (velocity of arms and legs, sit-to-stand time, p = 0.007; p = 0.009; p = 0.01, respectively). A linear regression model including four baseline kinematic features could significantly predict the motor outcome (p = 0.000214). Technology-based objective measures represent possible early and reproducible therapy-response and prognostic biomarkers.

Generalized Finite-Length Fibonacci Sequences in Healthy and Pathological Human Walking: Comprehensively Assessing Recursivity, Asymmetry, Consistency, Self-Similarity, and Variability of Gaits.

Healthy and pathological human walking are here interpreted, from a temporal point of view, by means of dynamics-on-graph concepts and generalized finite-length Fibonacci sequences. Such sequences, in their most general definition, concern two sets of eight specific time intervals for the newly defined composite gait cycle, which involves two specific couples of overlapping (left and right) gait cycles. The role of the golden ratio, whose occurrence has been experimentally found in the recent literature, is accordingly characterized, without resorting to complex tools from linear algebra. Gait recursivity, self-similarity, and asymmetry (including double support sub-phase consistency) are comprehensively captured. A new gait index, named Φ-bonacci gait number, and a new related experimental conjecture-concerning the position of the foot relative to the tibia-are concurrently proposed. Experimental results on healthy or pathological gaits support the theoretical derivations.

Voice Analysis with Machine Learning: One Step Closer to an Objective Diagnosis of Essential Tremor.

BACKGROUND: Patients with essential tremor have upper limb postural and action tremor often associated with voice tremor. The objective of this study was to objectively examine voice tremor and its response to symptomatic pharmacological treatment in patients with essential tremor using voice analysis consisting of power spectral analysis and machine learning. METHODS: We investigated 58 patients (24 men; mean age ± SD, 71.7 ± 9.2 years; range, 38-85 years) and 74 age- and sex-matched healthy subjects (20 men; mean age ± SD, 71.0 ± 12.4 years; range, 43-95 years). We recorded voice samples during sustained vowel emission using a high-definition audio recorder. Voice samples underwent sound signal analysis, including power spectral analysis and support vector machine classification. We compared voice recordings in patients with essential tremor who did and did not manifest clinically overt voice tremor and in patients who were and were not under the symptomatic effect of the best medical treatment. RESULTS: Power spectral analysis demonstrated a prominent oscillatory activity peak at 2-6 Hz in patients who manifested a clinically overt voice tremor. Voice analysis with support vector machine classifier objectively discriminated with high accuracy between controls and patients who did and did not manifest clinically overt voice tremor and between patients who were and were not under the symptomatic effect of the best medical treatment. CONCLUSIONS: In patients with essential tremor, voice tremor is characterized by abnormal oscillatory activity at 2-6 Hz. Voice analysis, including power spectral analysis and support vector machine classification, objectively detected voice tremor and its response to symptomatic pharmacological treatment in patients with essential tremor. © 2021 International Parkinson and Movement Disorder Society.

Bending Sensors Based on Thin Films of Semitransparent Bithiophene-Fulleropyrrolidine Bisadducts.

A novel bithiophene-fulleropyrrolidine bisadducts system (bis-Th2PC60 ) was synthesized and electropolymerized by chronoamperometry onto flexible ITO/PET substrates. The resulting semitransparent thin film was characterized by XPS, FT-IR, cyclic voltammetry and optical techniques, confirming the good outcome of the electropolymerization process. AFM investigations permitted to highlight an inherent disordered granular morphology, in which the grain-to-grain separation depends upon the application of bending. The electrical resistance of the thin film was characterized as a function of bending (in the range 0°-90°), showing promising responsivity to low bending angles (10°-30°). The ΔR/R0 variations turn out to be 8 %,16 % and 20 % for bending angles equal to 10°, 20° and 30°, respectively. This study represents a first step towards the understanding of piezoresistive properties in electropolymerized fullerenes-based thin films, opening up applications as bending sensor.

Machine-Learning Analysis of Voice Samples Recorded through Smartphones: The Combined Effect of Ageing and Gender.

BACKGROUND: Experimental studies using qualitative or quantitative analysis have demonstrated that the human voice progressively worsens with ageing. These studies, however, have mostly focused on specific voice features without examining their dynamic interaction. To examine the complexity of age-related changes in voice, more advanced techniques based on machine learning have been recently applied to voice recordings but only in a laboratory setting. We here recorded voice samples in a large sample of healthy subjects. To improve the ecological value of our analysis, we collected voice samples directly at home using smartphones. METHODS: 138 younger adults (65 males and 73 females, age range: 15-30) and 123 older adults (47 males and 76 females, age range: 40-85) produced a sustained emission of a vowel and a sentence. The recorded voice samples underwent a machine learning analysis through a support vector machine algorithm. RESULTS: The machine learning analysis of voice samples from both speech tasks discriminated between younger and older adults, and between males and females, with high statistical accuracy. CONCLUSIONS: By recording voice samples through smartphones in an ecological setting, we demonstrated the combined effect of age and gender on voice. Our machine learning analysis demonstrates the effect of ageing on voice.

Sign Language Recognition Using Wearable Electronics: Implementing k-Nearest Neighbors with Dynamic Time Warping and Convolutional Neural Network Algorithms.

We propose a sign language recognition system based on wearable electronics and two different classification algorithms. The wearable electronics were made of a sensory glove and inertial measurement units to gather fingers, wrist, and arm/forearm movements. The classifiers were k-Nearest Neighbors with Dynamic Time Warping (that is a non-parametric method) and Convolutional Neural Networks (that is a parametric method). Ten sign-words were considered from the Italian Sign Language: cose, grazie, maestra, together with words with international meaning such as google, internet, jogging, pizza, television, twitter, and ciao. The signs were repeated one-hundred times each by seven people, five male and two females, aged 29-54 y ± 10.34 (SD). The adopted classifiers performed with an accuracy of 96.6% ± 3.4 (SD) for the k-Nearest Neighbors plus the Dynamic Time Warping and of 98.0% ± 2.0 (SD) for the Convolutional Neural Networks. Our system was made of wearable electronics among the most complete ones, and the classifiers top performed in comparison with other relevant works reported in the literature.

Voice analysis in adductor spasmodic dysphonia: Objective diagnosis and response to botulinum toxin.

INTRODUCTION: Adductor-type spasmodic dysphonia is a task-specific focal dystonia characterized by involuntary laryngeal muscle spasms. Due to the lack of quantitative instrumental tools, voice assessment in patients with adductor-type spasmodic dysphonia is mainly based on qualitative neurologic examination. We evaluated patients with cepstral analysis and specific machine-learning algorithms and compared the results with those collected in healthy subjects. In patients, we also used cepstral analysis and machine-learning algorithms to investigate the effect of botulinum neurotoxin type A. METHODS: We investigated 60 patients affected by adductor-type spasmodic dysphonia before botulinum neurotoxin type A therapy and 60 age and gender-matched healthy subjects. A subgroup of 35 patients was also evaluated after botulinum neurotoxin type A therapy. We recorded the sustained emission of a vowel and a sentence by means of a high-definition audio recorder. Voice samples underwent cepstral analysis as well as machine-learning algorithm classification techniques. RESULTS: Cepstral analysis was able to differentiate between healthy subjects and patients, but receiver operating characteristic curve analysis demonstrated that machine-learning algorithms achieved better results than cepstral analysis in differentiating healthy subjects and patients affected by adductor-type spasmodic dysphonia. Similar results were obtained when differentiating patients before and after botulinum neurotoxin type A therapy. Cepstral analysis and machine-learning measures correlated with the severity of voice impairment in patients before and after botulinum neurotoxin type A therapy. CONCLUSIONS: Cepstral analysis and machine-learning algorithms are new tools that offer meaningful support to clinicians in the diagnosis and treatment of adductor-type spasmodic dysphonia.

Assessment of Motor Impairments in Early Untreated Parkinson's Disease Patients: The Wearable Electronics Impact.

OBJECTIVE: The complex nature of Parkinson's disease (PD) makes difficult to rate its severity, mainly based on the visual inspection of motor impairments. Wearable sensors have been demonstrated to help overcoming such a difficulty, by providing objective measures of motor abnormalities. However, up to now, those sensors have been used on advanced PD patients with evident motor impairment. As a novelty, here we report the impact of wearable sensors in the evaluation of motor abnormalities in newly diagnosed, untreated, namely de novo, patients. METHODS: A network of wearable sensors was used to measure motor capabilities, in 30 de novo PD patients and 30 healthy subjects, while performing five motor tasks. Measurement data were used to determine motor features useful to highlight impairments and were compared with the corresponding clinical scores. Three classifiers were used to differentiate PD from healthy subjects. RESULTS: Motor features gathered from wearable sensors showed a high degree of significance in discriminating the early untreated de novo PD patients from the healthy subjects, with 95% accuracy. The rates of severity obtained from the measured features are partially in agreement with the clinical scores, with some highlighted, though justified, exceptions. CONCLUSION: Our findings support the feasibility of adopting wearable sensors in the detection of motor anomalies in early, untreated, PD patients. SIGNIFICANCE: This work demonstrates that subtle motor impairments, occurring in de novo patients, can be evidenced by means of wearable sensors, providing clinicians with instrumental tools as suitable supports for early diagnosis, and subsequent management.