{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:18:57Z","timestamp":1768562337055,"version":"3.49.0"},"posted":{"date-parts":[[2023,5,1]]},"group-title":"Neurology","reference-count":50,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background and objectives<\/jats:title>\n                  <jats:p>Patients with ALS-FTD spectrum disorders (ALS-FTSD) have mixed motor and cognitive impairments and require valid and quantitative assessment tools to support diagnosis and tracking of bulbar motor disease. This study aimed to validate a novel automated digital speech tool that analyzes vowel acoustics from natural, connected speech as a marker for impaired articulation due to bulbar motor disease in ALS-FTSD.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We used an automatic algorithm called Forced Alignment Vowel Extraction (FAVE) to detect spoken vowels and extract vowel acoustics from 1 minute audio-recorded picture descriptions. Using automated acoustic analysis scripts, we derived two articulatory-acoustic measures: vowel space area (VSA, in Bark\n                    <jats:sup>2<\/jats:sup>\n                    ) which represents tongue range-of-motion (size), and average second formant slope of vowel trajectories (F2 slope) which represents tongue movement speed. We compared vowel measures between ALS with and without clinically-evident bulbar motor disease (ALS+bulbar vs. ALS-bulbar), behavioral variant frontotemporal dementia (bvFTD) without a motor syndrome, and healthy controls (HC). We correlated impaired vowel measures with bulbar disease severity, estimated by clinical bulbar scores and perceived listener effort, and with MRI cortical thickness of the orobuccal part of the primary motor cortex innervating the tongue (oralPMC). We also tested correlations with respiratory capacity and cognitive impairment.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Participants were 45 ALS+bulbar (30 males, mean age=61\u00b111), 22 ALS-nonbulbar (11 males, age=62\u00b110), 22 bvFTD (13 males, age=63\u00b17), and 34 HC (14 males, age=69\u00b18). ALS+bulbar had smaller VSA and shallower average F2 slopes than ALS-bulbar (VSA: |\n                    <jats:italic>d<\/jats:italic>\n                    |=0.86,\n                    <jats:italic>p<\/jats:italic>\n                    =0.0088; F2 slope: |\n                    <jats:italic>d<\/jats:italic>\n                    |=0.98,\n                    <jats:italic>p<\/jats:italic>\n                    =0.0054), bvFTD (VSA: |\n                    <jats:italic>d<\/jats:italic>\n                    |=0.67,\n                    <jats:italic>p<\/jats:italic>\n                    =0.043; F2 slope: |\n                    <jats:italic>d<\/jats:italic>\n                    |=1.4,\n                    <jats:italic>p<\/jats:italic>\n                    &lt;0.001), and HC (VSA: |\n                    <jats:italic>d<\/jats:italic>\n                    |=0.73,\n                    <jats:italic>p<\/jats:italic>\n                    =0.024; F2 slope: |\n                    <jats:italic>d<\/jats:italic>\n                    |=1.0,\n                    <jats:italic>p<\/jats:italic>\n                    &lt;0.001). Vowel measures declined with worsening bulbar clinical scores (VSA: R=0.33,\n                    <jats:italic>p<\/jats:italic>\n                    =0.033; F2 slope: R=0.25,\n                    <jats:italic>p<\/jats:italic>\n                    =0.048), and smaller VSA was associated with greater listener effort (R=-0.43,\n                    <jats:italic>p<\/jats:italic>\n                    =0.041). Shallower F2 slopes were related to cortical thinning in oralPMC (R=0.50,\n                    <jats:italic>p<\/jats:italic>\n                    =0.03). Neither vowel measure was associated with respiratory nor cognitive test scores.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Vowel measures extracted with automatic processing from natural speech are sensitive to bulbar motor disease in ALS-FTD and are robust to cognitive impairment.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.04.29.23289308","type":"posted-content","created":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T01:25:11Z","timestamp":1682990711000},"source":"Crossref","is-referenced-by-count":0,"title":["Digital markers of motor speech impairments in natural speech of patients with ALS-FTD spectrum 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