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Purpose: This study aimed to evaluate the reliability of different approaches for estimating the articulation rates in connected speech of Parkinsonian patients with different stages of neurodegeneration compared to healthy controls. Method: Monologues and reading passages were obtained from 25 patients with idiopathic rapid eye movement sleep behavior disorder (iRBD), 25 de novo patients with Parkinson's disease (PD), 20 patients with multiple system atrophy (MSA), and 20 healthy controls. The recordings were subsequently evaluated using eight syllable localization algorithms, and their performances were compared to a manual transcript used as a reference. Results: The Google & Pyphen method, based on automatic speech recognition followed by hyphenation, outperformed the other approaches (automated vs. hand transcription: r > 0.87 for monologues and r > 0.91 for reading passages, p < 0.001) in precise feature estimates and resilience to dysarthric speech. The Praat script algorithm achieved sufficient robustness (automated vs. hand transcription: r > 0.65 for monologues and r > 0.78 for reading passages, p < 0.001). Compared to the control group, we detected a slow rate in patients with MSA and a tendency toward a slower rate in patients with iRBD, whereas the articulation rate was unchanged in patients with early untreated PD. Conclusions: The state-of-the-art speech recognition tool provided the most precise articulation rate estimates. If speech recognizer is not accessible, the freely available Praat script based on simple intensity thresholding might still provide robust properties even in severe dysarthria. Automated articulation rate assessment may serve as a natural, inexpensive biomarker for monitoring disease severity and a differential diagnosis of Parkinsonism.

Background: Speech dysfunction represents one of the initial motor manifestations to develop in Parkinson's disease (PD) and is measurable through smartphone. Objective: The aim was to develop a fully automated and noise‐resistant smartphone‐based system that can unobtrusively screen for prodromal parkinsonian speech disorder in subjects with isolated rapid eye movement sleep behavior disorder (iRBD) in a real‐world scenario. Methods: This cross‐sectional study assessed regular, everyday voice call data from individuals with iRBD compared to early PD patients and healthy controls via a developed smartphone application. The participants also performed an active, regular reading of a short passage on their smartphone. Smartphone data were continuously collected for up to 3 months after the standard in‐person assessments at the clinic. Results: A total of 3525 calls that led to 5990 minutes of preprocessed speech were extracted from 72 participants, comprising 21 iRBD patients, 26 PD patients, and 25 controls. With a high area under the curve of 0.85 between iRBD patients and controls, the combination of passive and active smartphone data provided a comparable or even more sensitive evaluation than laboratory examination using a high‐quality microphone. The most sensitive features to induce prodromal neurodegeneration in iRBD included imprecise vowel articulation during phone calls (P = 0.03) and monopitch in reading (P = 0.05). Eighteen minutes of speech corresponding to approximately nine calls was sufficient to obtain the best sensitivity for the screening. Conclusion: We consider the developed tool widely applicable to deep longitudinal digital phenotyping data with future applications in neuroprotective trials, deep brain stimulation optimization, neuropsychiatry, speech therapy, population screening, and beyond. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Objective: This study assessed the relationship between speech and language impairment and outcome in a multicenter cohort of isolated/idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). Methods: Patients with iRBD from 7 centers speaking Czech, English, German, French, and Italian languages underwent a detailed speech assessment at baseline. Story‐tale narratives were transcribed and linguistically annotated using fully automated methods based on automatic speech recognition and natural language processing algorithms, leading to the 3 distinctive linguistic and 2 acoustic patterns of language deterioration and associated composite indexes of their overall severity. Patients were then prospectively followed and received assessments for parkinsonism or dementia during follow‐up. The Cox proportional hazard was performed to evaluate the predictive value of language patterns for phenoconversion over a follow‐up period of 5 years. Results: Of 180 patients free of parkinsonism or dementia, 156 provided follow‐up information. After a mean follow‐up of 2.7 years, 42 (26.9%) patients developed neurodegenerative disease. Patients with higher severity of linguistic abnormalities (hazard ratio [HR = 2.35]) and acoustic abnormalities (HR = 1.92) were more likely to develop a defined neurodegenerative disease, with converters having lower content richness (HR = 1.74), slower articulation rate (HR = 1.58), and prolonged pauses (HR = 1.46). Dementia‐first (n = 16) and parkinsonism‐first with mild cognitive impairment (n = 9) converters had higher severity of linguistic abnormalities than parkinsonism‐first with normal cognition converters (n = 17). Interpretation: Automated language analysis might provide a predictor of phenoconversion from iRBD into synucleinopathy subtypes with cognitive impairment, and thus can be used to stratify patients for neuroprotective trials. ANN NEUROL 2024;95:530–543 [ABSTRACT FROM AUTHOR]

Background: Impairment of higher language functions associated with natural spontaneous speech in multiple sclerosis (MS) remains underexplored. Objectives: We presented a fully automated method for discriminating MS patients from healthy controls based on lexical and syntactic linguistic features. Methods: We enrolled 120 MS individuals with Expanded Disability Status Scale ranging from 1 to 6.5 and 120 age-, sex-, and education-matched healthy controls. Linguistic analysis was performed with fully automated methods based on automatic speech recognition and natural language processing techniques using eight lexical and syntactic features acquired from the spontaneous discourse. Fully automated annotations were compared with human annotations. Results: Compared with healthy controls, lexical impairment in MS consisted of an increase in content words (p = 0.037), a decrease in function words (p = 0.007), and overuse of verbs at the expense of noun (p = 0.047), while syntactic impairment manifested as shorter utterance length (p = 0.002), and low number of coordinate clause (p < 0.001). A fully automated language analysis approach enabled discrimination between MS and controls with an area under the curve of 0.70. A significant relationship was detected between shorter utterance length and lower symbol digit modalities test score (r = 0.25, p = 0.008). Strong associations between a majority of automatically and manually computed features were observed (r > 0.88, p < 0.001). Conclusion: Automated discourse analysis has the potential to provide an easy-to-implement and low-cost language-based biomarker of cognitive decline in MS for future clinical trials. [ABSTRACT FROM AUTHOR]

Background: Patients with synucleinopathies frequently display language abnormalities. However, whether patients with isolated rapid eye movement sleep behavior disorder (iRBD) have prodromal language impairment remains unknown.Objective: We examined whether the linguistic abnormalities in iRBD can serve as potential biomarkers for conversion to synucleinopathy, including the possible effect of mild cognitive impairment (MCI), speaking task, and automation of analysis procedure.Methods: We enrolled 139 Czech native participants, including 40 iRBD without MCI and 14 iRBD with MCI, compared with 40 PD without MCI, 15 PD with MCI, and 30 healthy control subjects. Spontaneous discourse and story-tale narrative were transcribed and linguistically annotated. A quantitative analysis was performed computing three linguistic features. Human annotations were compared with fully automated annotations.Results: Compared with control subjects, patients with iRBD showed poorer content density, reflecting the reduction of content words and modifiers. Both PD and iRBD subgroups with MCI manifested less occurrence of unique words and a higher number of n-grams repetitions, indicating poorer lexical richness. The spontaneous discourse task demonstrated language impairment in iRBD without MCI with an area under the curve of 0.72, while the story-tale narrative task better reflected the presence of MCI, discriminating both PD and iRBD subgroups with MCI from control subjects with an area under the curve of up to 0.81. A strong correlation between manually and automatically computed results was achieved.Conclusions: Linguistic features might provide a reliable automated method for detecting cognitive decline caused by prodromal neurodegeneration in subjects with iRBD, providing critical outcomes for future therapeutic trials. © 2022 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Impairments of olfactory and speech function are likely early prodromal symptoms of α‐synucleinopathy. Objective: The aim of this study is to assess whether dysprosody is present in isolated rapid eye movement sleep behavior disorder (iRBD) with hyposmia/anosmia and a normal nigrostriatal system. Methods: Pitch variability during speech was investigated in 17 iRBD subjects with normal olfactory function (iRBD‐NOF), 30 iRBD subjects with abnormal olfactory function (iRBD‐AOF), and 50 healthy controls. iRBD subjects were evaluated using the University of Pennsylvania Smell Identification Test and [123I]‐2ß‐carbomethoxy‐3ß‐(4‐iodophenyl)‐N‐(3‐fluoropropyl)‐nortropane dopamine transporter single‐photon emission computed tomography (DAT‐SPECT). All iRBD subjects completed the 24‐month follow‐up with DAT‐SPECT, speech, and olfactory testing. Results: At baseline, only iRBD‐AOF showed monopitch when compared to iRBD‐NOF (P = 0.04) and controls (P = 0.03), with no difference between iRBD‐NOF and controls (P = 1). At follow‐up, dysprosody progressed only in iRBD‐AOF with abnormal DAT‐SPECT (P = 0.03). Conclusion: Prosody is impaired in hyposmic but not in normosmic iRBD subjects before the nigrostriatal dopaminergic transmission is affected (Braak stage 2). © 2021 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background: The mechanisms underlying speech abnormalities in Parkinson's disease (PD) remain poorly understood, with most of the available evidence based on male patients. This study aimed to estimate the occurrence and characteristics of speech disorder in early, drug‐naive PD patients with relation to gender and dopamine transporter imaging. Methods: Speech samples from 60 male and 40 female de novo PD patients as well as 60 male and 40 female age‐matched healthy controls were analyzed. Quantitative acoustic vocal assessment of 10 distinct speech dimensions related to phonation, articulation, prosody, and speech timing was performed. All patients were evaluated using [123]I‐2b‐carbomethoxy‐3b‐(4‐iodophenyl)‐N‐(3‐fluoropropyl) nortropane single‐photon emission computed tomography and Montreal Cognitive Assessment. Results: The prevalence of speech abnormalities in the de novo PD cohort was 56% for male and 65% for female patients, mainly manifested with monopitch, monoloudness, and articulatory decay. Automated speech analysis enabled discrimination between PD and controls with an area under the curve of 0.86 in men and 0.93 in women. No gender‐specific speech dysfunction in de novo PD was found. Regardless of disease status, females generally showed better performance in voice quality, consonant articulation, and pauses production than males, who were better only in loudness variability. The extent of monopitch was correlated to nigro‐putaminal dopaminergic loss in men (r = 0.39, p = 0.003) and the severity of imprecise consonants was related to cognitive deficits in women (r = −0.44, p = 0.005). Conclusions: Speech abnormalities represent a frequent and early marker of motor abnormalities in PD. Despite some gender differences, our findings demonstrate that speech difficulties are associated with nigro‐putaminal dopaminergic deficits. [ABSTRACT FROM AUTHOR]

Objective: This multilanguage study used simple speech recording and high‐end pattern analysis to provide sensitive and reliable noninvasive biomarkers of prodromal versus manifest α‐synucleinopathy in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) and early‐stage Parkinson disease (PD). Methods: We performed a multicenter study across the Czech, English, German, French, and Italian languages at 7 centers in Europe and North America. A total of 448 participants (337 males), including 150 with iRBD (mean duration of iRBD across language groups 0.5–3.4 years), 149 with PD (mean duration of disease across language groups 1.7–2.5 years), and 149 healthy controls were recorded; 350 of the participants completed the 12‐month follow‐up. We developed a fully automated acoustic quantitative assessment approach for the 7 distinctive patterns of hypokinetic dysarthria. Results: No differences in language that impacted clinical parkinsonian phenotypes were found. Compared with the controls, we found significant abnormalities of an overall acoustic speech severity measure via composite dysarthria index for both iRBD (p = 0.002) and PD (p < 0.001). However, only PD (p < 0.001) was perceptually distinct in a blinded subjective analysis. We found significant group differences between PD and controls for monopitch (p < 0.001), prolonged pauses (p < 0.001), and imprecise consonants (p = 0.03); only monopitch was able to differentiate iRBD patients from controls (p = 0.004). At the 12‐month follow‐up, a slight progression of overall acoustic speech impairment was noted for the iRBD (p = 0.04) and PD (p = 0.03) groups. Interpretation: Automated speech analysis might provide a useful additional biomarker of parkinsonism for the assessment of disease progression and therapeutic interventions. ANN NEUROL 2021;90:62–75 [ABSTRACT FROM AUTHOR]

Little is known about the minimum sample length required for the stable acoustic assessment of speech in Parkinson's disease (PD). This study aimed to investigate the effect of the duration of the reading passage on the determination of reliable acoustic patterns in individuals with PD treated with subthalamic nucleus deep brain stimulation. A phonetically balanced reading text of 313 words was collected from 32 Czech persons with PD, and 32 age- and sex-matched healthy controls. The reading passage was segmented to produce ten sub-texts of increasing length ranging from a one- to a ten-segment-long sub-text. An error rate analysis was used to estimate the required stabilization value by evaluating the differences between the sub-texts and the entire text across seven hypokinetic dysarthria features. The minimum length of a reading passage equal to 128 words was found to be necessary for acoustic assessment, with similar lengths being required for the controls (120 words) and the two PD subgroups, including Parkinsonian individuals with a mild (126 words) and moderate (128 words) dysarthria severity. The current study provides important guidelines for the necessary sample length for future expert instrumental dysarthria assessments and assists in decreasing the time required for clinical speech evaluations. [ABSTRACT FROM AUTHOR]

Pallidal deep-brain stimulation of the internal globus pallidus (GPi-DBS) is an effective treatment for dystonia. However, GPi-DBS may cause important stimulation-induced side effects such as hypokinetic dysarthria, which is particularly manifested by articulation rate abnormalities. However, little data regarding the effect of the location of the electrode and stimulation parameters for pallidal stimulation on articulation rate in dystonia is available. Speech data were acquired from 18 dystonic patients with GPi-DBS and 18 matched healthy controls. Each of dystonic patients was tested twice within 1 day in both the GPi-DBS ON and GPi-DBS OFF stimulation conditions. Compared to healthy controls, the decreased diadochokinetic rate and slower articulation rate in dystonic patients were observed in both stimulation conditions. No significant differences in speech rate measures between stimulation conditions were detected with no relation to contact localization and stimulation intensity. Our findings do not support the use articulation rate as a surrogate marker of stimulation-induced changes to the speech apparatus in dystonia. [ABSTRACT FROM AUTHOR]

Purpose: Although speech motor changes are reported as a common sign of Huntington’s disease (HD), the most prominent signs of voice dysfunction remain unknown. The aim of the current study was to explore specific changes in phonatory function in subjects with HD. Method: 34 subjects with HD and 34 age- and sex-matched healthy controls were examined. Participants performed sustained vowel phonation for subsequent analyses of airflow insufficiency, aperiodicity, irregular vibrations of vocal folds, signal perturbations, increased noise, and articulation deficiency. In total, 272 phonations were collected and 12 voice parameters were extracted. Subsequently, a predictive model was built to find the most salient patterns of voice disorders in HD. The results were also correlated with disease severity according to the Unified HD Rating Scale (UHDRS) motor score. Results: Subjects with HD showed deterioration in all investigated phonatory functions. Irregular pitch fluctuations, sudden phonation interruption, increased noise, and misplacement of articulators were found to be most significant patterns of phonatory dysfunction in HD (p<0.001). The combination of these four dysphonia aspects contributed to the best classification performance of 94.1% (sensitivity: 95.1%; specificity: 93.2%) in the separation of HD patients from healthy participants. Our results further indicated stronger associations between sudden phonation interruption and voluntary components of the UHDRS (r = −0.48, p<0.01) and between misplacement of articulators and involuntary components of the UHDRS (r = 0.52, p<0.01). Conclusions: Our configuration of phonatory features can detect subtle voice abnormalities in subjects with HD. As impairment of phonatory function in HD was found to parallel increasing motor involvement, a qualitative description of voice dysfunction may be helpful to gain better insight into the pathophysiology of the vocal mechanism. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate associations of motor and non-motor symptoms with dopamine transporter binding in prodromal stage of synucleinopathies. We examined 74 patients with idiopathic REM sleep behavior disorder (RBD), which is a prodromal synucleinopathy, and 39 controls using Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment, University of Pennsylvania Smell Identification Test (UPSIT), Farnsworth-Munsell 100 hue test, orthostatic test, Scales for Outcomes in PD-Autonomic, Beck depression inventory-II, State-Trait Anxiety Inventory, and video-polysomnography. Electromyographic muscle activity during REM sleep was quantified according to Sleep Innsbruck-Barcelona criteria. In 65 patients, dopamine transporter single-photon emission computed tomography (DAT-SPECT) imaging was performed, putaminal binding ratio was calculated and scans were classified as normal, borderline, or abnormal. Compared to controls, RBD patients had significantly more severe scores in all examined tests. Patients with abnormal DAT-SPECT had higher MDS-UPDRS motor score (p = 0.006) and higher prevalence of orthostatic hypotension (p = 0.008). Putaminal binding ratio was positively associated with UPSIT score (p = 0.03) and negatively associated with tonic (p = 0.003) and phasic (p = 0.01) muscle activity during REM sleep. These associations likely reflect simultaneous advancement of underlying pathology in substantia nigra and susceptible brainstem and olfactory nuclei in prodromal synucleinopathy. [ABSTRACT FROM AUTHOR]

Aim: To investigate the presence and relationship of temporal speech and gait parameters in patients with postural instability/gait disorder (PIGD) and tremor-dominant (TD) motor subtypes of Parkinson's disease (PD)., Methods: Speech samples and instrumented walkway system assessments were acquired from a total of 60 de-novo PD patients (40 in TD and 20 in PIGD subtype) and 40 matched healthy controls. Objective acoustic vocal assessment of seven distinct speech timing dimensions was related to instrumental gait measures including velocity, cadence, and stride length., Results: Compared to controls, PIGD subtype showed greater consonant timing abnormalities by prolonged voice onset time (VOT) while also shorter stride length during both normal walking and dual task, while decreased velocity and cadence only during dual task. Speaking rate was faster in PIGD than TD subtype. In PIGD subtype, prolonged VOT correlated with slower gait velocity (r = -0.56, p = 0.01) and shorter stride length (r = -0.59, p = 0.008) during normal walking, whereas relationships were also found between decreased cadence in dual task and irregular alternating motion rates (r = -0.48, p = 0.04) and prolonged pauses (r = -0.50, p = 0.03). No correlation between speech and gait was detected in TD subtype., Conclusion: Our findings suggest that speech and gait rhythm disorder share similar underlying pathomechanisms specific for PIGD subtype., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

For generations, the evaluation of speech abnormalities in neurodegenerative disorders such as Parkinson's disease (PD) has been limited to perceptual tests or user-controlled laboratory analysis based upon rather small samples of human vocalizations. Our study introduces a fully automated method that yields significant features related to respiratory deficits, dysphonia, imprecise articulation and dysrhythmia from acoustic microphone data of natural connected speech for predicting early and distinctive patterns of neurodegeneration. We compared speech recordings of 50 subjects with rapid eye movement sleep behaviour disorder (RBD), 30 newly diagnosed, untreated PD patients and 50 healthy controls, and showed that subliminal parkinsonian speech deficits can be reliably captured even in RBD patients, which are at high risk of developing PD or other synucleinopathies. Thus, automated vocal analysis should soon be able to contribute to screening and diagnostic procedures for prodromal parkinsonian neurodegeneration in natural environments.