Speech abnormalities in Parkinson's disease (PD) are heterogeneous and often considered resistant to levodopa. However, human hearing may miss subtle treatment-related speech changes. Digital speech biomarkers offer a sensitive alternative to measure such changes objectively. Speech was recorded in 51 PD patients during ON and OFF medication states and compared to 43 healthy controls matched for language and gender. Acute levodopa effects were significant in prosodic (F0 standard deviation, p = 0.03, effect size = 0.47), respiratory (intensity slope, p = 0.02, effect size = 0.49), and spectral domains (LTAS mean, p = 0.01, effect size = 0.35). Stepwise backward regression identified 8 biomarkers reflecting hypokinetic symptoms, 6 for dyskinetic symptoms, and 7 for medication-state transitions. Hypokinetic compound score correlated strongly with MDS-UPDRS-III changes (r = 0.70; MAE = 6.06/92), and the dyskinetic compound score with dyskinesia ratings (r = 0.50; MAE = 1.81/12). Medication-state transitions were detected with AUC = 0.86. This study highlights the potential of digital speech biomarkers to objectively measure levodopa-induced changes in PD symptoms and medication states.

• Publication type
• Journal Article MeSH

BACKGROUND: Research on the possible influence of lateralised basal ganglia dysfunction on speech in Parkinson's disease is scarce. This study aimed to compare speech in de-novo, drug-naive patients with Parkinson's disease (PD) with asymmetric nigral dopaminergic dysfunction, predominantly in either the right or left hemisphere. METHODS: Acoustic analyses of reading passages were performed. Asymmetry of nigral dysfunction was defined using dopamine transporter-single-photon emission CT (DAT-SPECT). RESULTS: From a total of 135 de novo patients with PD assessed, 47 patients had a lower right and 36 lower left DAT availability in putamen based on DAT-SPECT. Patients with PD with lower left DAT availability had higher dysarthria severity via composite dysarthria index compared with patients with lower right DAT availability (p=0.01). CONCLUSION: Our data support the crucial role of DAT availability in the left putamen in speech. This finding might provide important clues for managing speech following deep brain stimulation.

• Keywords
• MOTOR CONTROL, MOVEMENT DISORDERS, PARKINSON'S DISEASE, SPEECH,
• MeSH
• Basal Ganglia * physiopathology   diagnostic imaging   MeSH
• Dysarthria physiopathology   diagnostic imaging   etiology   MeSH
• Functional Laterality * physiology   MeSH
• Tomography, Emission-Computed, Single-Photon MeSH
• Middle Aged MeSH
• Humans MeSH
• Parkinson Disease * physiopathology   diagnostic imaging   complications   MeSH
• Dopamine Plasma Membrane Transport Proteins metabolism   MeSH
• Putamen diagnostic imaging   metabolism   physiopathology   MeSH
• Speech * physiology   MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Dopamine Plasma Membrane Transport Proteins MeSH

BACKGROUND AND OBJECTIVES: Patients with synucleinopathies such as multiple system atrophy (MSA) and Parkinson's disease (PD) frequently display speech and language abnormalities. We explore the diagnostic potential of automated linguistic analysis of natural spontaneous speech to differentiate MSA and PD. METHODS: Spontaneous speech of 39 participants with MSA compared to 39 drug-naive PD and 39 healthy controls matched for age and sex was transcribed and linguistically annotated using automatic speech recognition and natural language processing. A quantitative analysis was performed using 6 lexical and syntactic and 2 acoustic features. Results were compared with human-controlled analysis to assess the robustness of the approach. Diagnostic accuracy was evaluated using sensitivity analysis. RESULTS: Despite similar disease duration, linguistic abnormalities were generally more severe in MSA than in PD, leading to high diagnostic accuracy with an area under the curve of 0.81. Compared to controls, MSA showed decreased grammatical component usage, more repetitive phrases, shorter sentences, reduced sentence development, slower articulation rate, and increased duration of pauses, whereas PD had only shorter sentences, reduced sentence development, and longer pauses. Only slower articulation rate was distinctive for MSA while unchanged for PD relative to controls. The highest correlation was found between bulbar/pseudobulbar clinical score and sentence length (r = -0.49, p = 0.002). Despite the relatively high severity of dysarthria in MSA, a strong agreement between manually and automatically computed results was achieved. DISCUSSION: Automated linguistic analysis may offer an objective, cost-effective, and widely applicable biomarker to differentiate synucleinopathies with similar clinical manifestations.

• Keywords
• Automated linguistic analysis, Language, Multiple system atrophy, Natural language processing, Spontaneous discourse,
• MeSH
• Diagnosis, Differential MeSH
• Middle Aged MeSH
• Humans MeSH
• Multiple System Atrophy * diagnosis   complications   MeSH
• Parkinson Disease * diagnosis   complications   MeSH
• Aged MeSH
• Natural Language Processing * MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

INTRODUCTION: Dysarthria, a motor speech disorder caused by muscle weakness or paralysis, severely impacts speech intelligibility and quality of life. The condition is prevalent in motor speech disorders such as Parkinson's disease (PD), atypical parkinsonism such as progressive supranuclear palsy (PSP), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Improving intelligibility is not only an outcome that matters to patients but can also play a critical role as an endpoint in clinical research and drug development. This study validates a digital measure for speech intelligibility, the ki: SB-M intelligibility score, across various motor speech disorders and languages following the Digital Medicine Society (DiMe) V3 framework. METHODS: The study used four datasets: healthy controls (HCs) and patients with PD, HD, PSP, and ALS from Czech, Colombian, and German populations. Participants' speech intelligibility was assessed using the ki: SB-M intelligibility score, which is derived from automatic speech recognition (ASR) systems. Verification with inter-ASR reliability and temporal consistency, analytical validation with correlations to gold standard clinical dysarthria scores in each disease, and clinical validation with group comparisons between HCs and patients were performed. RESULTS: Verification showed good to excellent inter-rater reliability between ASR systems and fair to good consistency. Analytical validation revealed significant correlations between the SB-M intelligibility score and established clinical measures for speech impairments across all patient groups and languages. Clinical validation demonstrated significant differences in intelligibility scores between pathological groups and healthy controls, indicating the measure's discriminative capability. DISCUSSION: The ki: SB-M intelligibility score is a reliable, valid, and clinically relevant tool for assessing speech intelligibility in motor speech disorders. It holds promise for improving clinical trials through automated, objective, and scalable assessments. Future studies should explore its utility in monitoring disease progression and therapeutic efficacy as well as add data from further dysarthrias to the validation.

• Keywords
• Huntington's disease (HD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), digital biomarkers, intelligibility, progressive supranuclear palsy (PSP), speech analysis,
• Publication type
• Journal Article MeSH

Approximately 90% of Parkinson's patients (PD) suffer from dysarthria. However, there is currently a lack of research on acoustic measurements and speech impairment patterns among Mandarin-speaking individuals with PD. This study aims to assess the diagnosis and disease monitoring possibility in Mandarin-speaking PD patients through the recommended speech paradigm for non-tonal languages, and to explore the anatomical and functional substrates. We examined total of 160 native Mandarin-speaking Chinese participants consisting of 80 PD patients, 40 healthy controls (HC), and 40 MRI controls. We screened the optimal acoustic metric combination for PD diagnosis. Finally, we used the objective metrics to predict the patient's motor status using the Naïve Bayes model and analyzed the correlations between cortical thickness, subcortical volumes, functional connectivity, and network properties. Comprehensive acoustic screening based on prosodic, articulation, and phonation abnormalities allows differentiation between HC and PD with an area under the curve of 0.931. Patients with slowed reading exhibited atrophy of the fusiform gyrus (FDR p = 0.010, R = 0.391), reduced functional connectivity between the fusiform gyrus and motor cortex, and increased nodal local efficiency (NLE) and nodal efficiency (NE) in bilateral pallidum. Patients with prolonged pauses demonstrated atrophy in the left hippocampus, along with decreased NLE and NE. The acoustic assessment in Mandarin proves effective in diagnosis and disease monitoring for Mandarin-speaking PD patients, generalizing standardized acoustic guidelines beyond non-tonal languages. The speech impairment in Mandarin-speaking PD patients not only involves motor aspects of speech but also encompasses the cognitive processes underlying language generation.

• Publication type
• Journal Article MeSH
• Review MeSH

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.

• Keywords
• Parkinson's disease, dysarthria, gait, postural instability gait difficulty, speech disorder,
• MeSH
• Gait MeSH
• Walking MeSH
• Humans MeSH
• Gait Disorders, Neurologic * etiology   MeSH
• Parkinson Disease * complications   MeSH
• Postural Balance MeSH
• Speech MeSH
• Tremor MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

While speech disorder represents an early and prominent clinical feature of atypical parkinsonian syndromes such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), little is known about the sensitivity of speech assessment as a potential diagnostic tool. Speech samples were acquired from 215 subjects, including 25 MSA, 20 PSP, 20 Parkinson's disease participants, and 150 healthy controls. The accurate differential diagnosis of dysarthria subtypes was based on the quantitative acoustic analysis of 26 speech dimensions related to phonation, articulation, prosody, and timing. A semi-supervised weighting-based approach was then applied to find the best feature combinations for separation between PSP and MSA. Dysarthria was perceptible in all PSP and MSA patients and consisted of a combination of hypokinetic, spastic, and ataxic components. Speech features related to respiratory dysfunction, imprecise consonants, monopitch, slow speaking rate, and subharmonics contributed to worse performance in PSP than MSA, whereas phonatory instability, timing abnormalities, and articulatory decay were more distinctive for MSA compared to PSP. The combination of distinct speech patterns via objective acoustic evaluation was able to discriminate between PSP and MSA with very high accuracy of up to 89% as well as between PSP/MSA and PD with up to 87%. Dysarthria severity in MSA/PSP was related to overall disease severity. Speech disorders reflect the differing underlying pathophysiology of tauopathy in PSP and α-synucleinopathy in MSA. Vocal assessment may provide a low-cost alternative screening method to existing subjective clinical assessment and imaging diagnostic approaches.

• Publication type
• Journal Article MeSH

INTRODUCTION: Early identification of Parkinson's disease (PD) in its prodromal stage has fundamental implications for the future development of neuroprotective therapies. However, no sufficiently accurate biomarkers of prodromal PD are currently available to facilitate early identification. The vocal assessment of patients with isolated rapid eye movement sleep behaviour disorder (iRBD) and PD appears to have intriguing potential as a diagnostic and progressive biomarker of PD and related synucleinopathies. METHODS AND ANALYSIS: Speech patterns in the spontaneous speech of iRBD, early PD and control participants' voice calls will be collected from data acquired via a developed smartphone application over a period of 2 years. A significant increase in several aspects of PD-related speech disorders is expected, and is anticipated to reflect the underlying neurodegeneration processes. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of the General University Hospital in Prague, Czech Republic and all the participants will provide written, informed consent prior to their inclusion in the research. The application satisfies the General Data Protection Regulation law requirements of the European Union. The study findings will be published in peer-reviewed journals and presented at international scientific conferences.

• Keywords
• Audiology, Parkinson-s disease, Speech pathology,
• MeSH
• Biomarkers MeSH
• Smartphone MeSH
• Humans MeSH
• Parkinson Disease * complications   diagnosis   MeSH
• Speech MeSH
• Synucleinopathies * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers MeSH

The effect of dopaminergic medication on speech has rarely been examined in early-stage Parkinson's disease (PD) and the respective literature is inconclusive and limited by inappropriate design with lack of PD control group. The study aims to examine the short-term effect of dopaminergic medication on speech in PD using patients with good motor responsiveness to levodopa challenge compared to a control group of PD patients with poor motor responsiveness. A total of 60 early-stage PD patients were investigated before (OFF) and after (ON) acute levodopa challenge and compared to 30 age-matched healthy controls. PD patients were categorised into two clinical subgroups (PD responders vs. PD nonresponders) according to the comparison of their motor performance based on movement disorder society-unified Parkinson's disease rating scale, part III. Seven distinctive parameters of hypokinetic dysarthria were examined using quantitative acoustic analysis. We observed increased monopitch (p > 0.01), aggravated monoloudness (p > 0.05) and longer duration of stop consonants (p > 0.05) in PD compared to healthy controls, confirming the presence of hypokinetic dysarthria in early PD. No speech alterations from OFF to ON state were revealed in any of the two PD groups and speech dimensions investigated including monopitch, monoloudness, imprecise consonants, harsh voice, slow sequential motion rates, articulation rate, or inappropriate silences, although a subgroup of PD responders manifested obvious improvement in motor function after levodopa intake (p > 0.001). Since the short-term usage of levodopa does not easily affect voice and speech performance in PD, speech assessment may provide a medication state-independent motor biomarker of PD.

• Publication type
• Journal Article MeSH

Substantial variability and severity of dysarthric patterns across Parkinson's disease (PD) patients may reflect distinct phenotypic differences. We aimed to compare patterns of speech disorder in early-onset PD (EOPD) and late-onset PD (LOPD) in drug-naive patients at early stages of disease. Speech samples were acquired from a total of 96 participants, including two subgroups of 24 de-novo PD patients and two subgroups of 24 age- and sex-matched young and old healthy controls. The EOPD group included patients with age at onset below 51 (mean 42.6, standard deviation 6.1) years and LOPD group patients with age at onset above 69 (mean 73.9, standard deviation 3.0) years. Quantitative acoustic vocal assessment of 10 unique speech dimensions related to respiration, phonation, articulation, prosody, and speech timing was performed. Despite similar perceptual dysarthria severity in both PD subgroups, EOPD showed weaker inspirations (p = 0.03), while LOPD was characterized by decreased voice quality (p = 0.02) and imprecise consonant articulation (p = 0.03). In addition, age-independent occurrence of monopitch (p < 0.001), monoloudness (p = 0.008), and articulatory decay (p = 0.04) was observed in both PD subgroups. The worsening of consonant articulation was correlated with the severity of axial gait symptoms (r = 0.38, p = 0.008). Speech abnormalities in EOPD and LOPD share common features but also show phenotype-specific characteristics, likely reflecting the influence of aging on the process of neurodegeneration. The distinct pattern of imprecise consonant articulation can be interpreted as an axial motor symptom of PD.

• Publication type
• Journal Article MeSH