Digital markers of motor speech impairments in spontaneous speech of patients with ALS-FTD spectrum disorders

Abstract

Objective

To evaluate automated digital speech measures, derived from spontaneous speech (picture descriptions), in assessing bulbar motor impairments in patients with ALS-FTD spectrum disorders (ALS-FTSD).

Methods

Automated vowel algorithms were employed to extract two vowel acoustic measures: vowel space area (VSA), and mean second formant slope (F2 slope). Vowel measures were compared between ALS with and without clinical bulbar symptoms (ALS + bulbar (n = 49, ALSFRS-r bulbar subscore: x¯ = 9.8 (SD = 1.7)) vs. ALS-nonbulbar (n = 23), behavioral variant frontotemporal dementia (bvFTD, n = 25) without a motor syndrome, and healthy controls (HC, n = 32). Correlations with bulbar motor clinical scales, perceived listener effort, and MRI cortical thickness of the orobuccal primary motor cortex (oral PMC) were examined. We compared vowel measures to speaking rate, a conventional metric for assessing bulbar dysfunction.

Results

ALS + bulbar had significantly reduced VSA and F2 slope than ALS-nonbulbar (|d|=0.94 and |d|=1.04, respectively), bvFTD (|d|=0.89 and |d|=1.47), and HC (|d|=0.73 and |d|=0.99). These reductions correlated with worse bulbar clinical scores (VSA: R = 0.33, p = 0.043; F2 slope: R = 0.38, p = 0.011), greater listener effort (VSA: R=-0.43, p = 0.041; F2 slope: p > 0.05), and cortical thinning in oral PMC (F2 slope: β = 0.0026, p = 0.017). Vowel measures demonstrated greater sensitivity and specificity for bulbar impairment than speaking rate, while showing independence from cognitive and respiratory impairments.

Conclusion

Automatic vowel measures are easily derived from a brief spontaneous speech sample, are sensitive to mild-moderate stage of bulbar disease in ALS-FTSD, and may present better sensitivity to bulbar impairment compared to traditional assessments such as speaking rate.

Keywords:

• motor speech
• biomarker
• digital speech
• dysarthria

Authors’ contributions

SS, SC, SA, SS, CTM, DJI, ML, MG and NN had major contributions to the conception of the research question and overall design of the study. CGR, LE, CQ, DA, MB, LM and MG were involved in data acquisition and measurement. CTM and CO was involved in the neuroimaging analysis. SS performed all statistical analyses and comparisons in this study. SS, SC, SA, CGR, CTM, LE, CQ, DA, MB, DJI, LM, CO, ML, MG and NN were all involved in the manuscript drafting and have approved the final draft.

Declaration of interest

No potential conflict of interest was reported by the author(s).

Data availability statement

Anonymized data will be shared by a reasonable request from any qualified investigator.

Additional information

Funding

This work is supported by funding from the American Academy of Neurology (2022-2784), the Alzheimer’s Association (AARF-21-851126), National Institute of Health (R01-NS109260, P01-AG066597, R01-AG054519, P30-AG072979, AG073510-01), and U.S. Department of Defense (W81XWH-20-1-0531). This work was also supported by National Institute on Aging; National Institutes of Health;Alzheimer’s Association Research Fellowship.