Abstract
PurposeAlthough dysphonia has been shown to be a common sign of Huntington disease (HD), the extent of phonatory dysfunction in gene positive premanifest HD individuals remains unknown. The aim of the current study was to explore the possible occurrence of phonatory abnormalities in prodromal HD.MethodSustained vowel phonations were acquired from 28 premanifest HD individuals and 28 healthy controls of comparable age. Data were analysed acoustically for measures of several phonatory dimensions including airflow insufficiency, aperiodicity, irregular vibration of vocal folds, signal perturbations, increased noise, vocal tremor and articulation deficiency. A predictive model was built to find the best combination of acoustic features and estimate sensitivity/specificity for differentiation between premanifest HD subjects and controls. The extent of voice deficits according to a specific phonatory dimension was determined using statistical decision making theory. The results were correlated to global motor function, cognitive score, disease burden score and estimated years to disease onset.ResultsMeasures of aperiodicity and increased noise were able to significantly differentiate between premanifest HD individuals and controls (p<0.01). The combination of these aspects of dysphonia led to a sensitivity of 91.5% and specificity of 79.2% to correctly distinguish speakers with premanifest HD from healthy individuals. Some form of disrupted phonatory function was revealed in 68% of our premanifest HD subjects, where 18% had one affected phonatory dimension and 50% showed impairment of two or more dimensions. A relationship between pitch control and cognitive score was also observed (r = −0.50, p = 0.007).ConclusionsPhonatory abnormalities are detectable even the in premotor stages of HD. Speech investigation may have the potential to provide functional biomarkers of HD and could be included in future clinical trials and therapeutic interventions.
Highlights
Huntington disease (HD) is an autosomal-dominantly inherited neurodegenerative disorder caused by an expansion in the number of CAG repeats in the IT15 gene [1], leading to widespread neuronal atrophy of both white and grey matter
Some form of disrupted phonatory function was revealed in 68% of our premanifest HD subjects, where 18% had one affected phonatory dimension and 50% showed impairment of two or more dimensions
From all investigated phonatory dimensions, the voice of premanifest HD (PreHD) individuals was mainly affected by the presence of aperiodicity and increased noise
Summary
Huntington disease (HD) is an autosomal-dominantly inherited neurodegenerative disorder caused by an expansion in the number of CAG repeats in the IT15 gene [1], leading to widespread neuronal atrophy of both white and grey matter. HD is associated with the progressive decline of both motor and cognitive function, as well as psychiatric disturbances. There is a growing body of evidence that progressive functional (e.g., tapping), cognitive and structural changes in the brain precede the clinical onset of HD by many years [2,3,4,5,6,7]. Motor manifestations of HD are generally characterized by involuntary movements termed chorea, which predominate in the initial and middle stages of the disease and are frequently later supplanted by rigidity and dystonia [9]. Abnormalities of voluntary motor function such as problems with planning, initiation, tracing and termination of movements accompany chorea but may already be present in preclinical stages [10]
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