BACKGROUND: In Huntington disease (HD), speech alterations are common and may emerge before onset of chorea. Slow and irregular motion rates, i.e. altered oral diadochokinesis (oDDK), are a distinctive feature. This study investigated oDDK using alternating (AMR) and sequential motion rate (SMR) tasks in manifest HD and explored the impact of antidopaminergic medications (ADM). METHODS: Speech samples were acquired from 30 healthy controls (14 men; 27-78 years¸ age- and gender-matched to HD subjects) and 35 individuals with early-to-moderate HD (18 men; 22-76 years) phenotyped using standardized scales (UHDRS'99) and MR imaging to estimate disease severity. Acoustic analysis was used to quantify rate and regularity of oDDK. In an exploratory subgroup analysis, the impact of ADMs on oDKK was explored by comparing patients with and without ADMs (HD-ADM: n = 16; 8 men; 22-76 years; HD-nADM; n = 19; 10 men; 28-61 years). RESULTS: HD patients were slower and more irregular in AMR and SMR tasks (p < 0.001) compared to controls. Analyses using area under the receiver-operating characteristic curve (AUC) showed the best characteristics for AMR (AUC = 95.0%). oDDK parameters correlated with measures of motor, cognitive and functional impairment and striatal atrophy. Patients on ADMs showed slower motion rates in both tasks (AMR p = 0.021; SMR p = 0.026), but unchanged regularity. CONCLUSIONS: Decreased AMR performance alone captured early motor impairment accurately, reflects disease severity and is ADM-sensitive. Therefore, objective acoustic analysis of AMR performance is a simple measure which may serve as read-out to monitor disease progression, e.g. in clinical trials.

Department of Circuit Theory Faculty of Electrical Engineering Czech Technical University Prague Prague Czech Republic

Department of Neurology and Centre of Clinical Neuroscience 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Neurology Huntington Center Ulm Ulm University Oberer Eselsberg 45 89081 Ulm Germany

Huntington Center South Kbo Isar Amper Klinikum Taufkirchen Germany

Swiss Epilepsy Clinic Klinik Lengg Zürich Switzerland

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Walker FO (2007) Huntington’s disease. Lancet 369(9557):218–228 PubMed

MacDonald ME et al (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72(6):971–983 PubMed

Vonsattel JP, Keller C, Cortes Ramirez EP (2011) Huntington’s disease - neuropathology. Handb Clin Neurol 100:83–100 PubMed

Vonsattel JP, Myers RH, Stevens TJ (1985) Neuropathological classification of Huntington’s disease. J Neuropathol Exp Neurol 44(6):559–577 PubMed

Correia JM et al (2020) Phonatory and articulatory representations of speech production in cortical and subcortical fMRI responses. Sci Rep 10(1):4529 PubMed PMC

Tremblay P, Deschamps I, Gracco VL (2016) Chapter 59 - neurobiology of speech production: a motor control perspective. In: Hickok G, Small SL (eds) neurobiology of language. Academic Press, San Diego, pp 741–750

Rusz J et al (2014) Phonatory dysfunction as a preclinical symptom of Huntington disease. PLoS ONE 9(11):e113412 PubMed PMC

Vogel AP et al (2012) Speech acoustic markers of early stage and prodromal Huntington’s disease: a marker of disease onset? Neuropsychologia 50(14):3273–3278 PubMed

Kouba T et al (2023) Speech biomarkers in Huntington’s disease: a cross-sectional study in pre-symptomatic, prodromal and early manifest stages. Eur J Neurol 30(5):1262–1271 PubMed

Chan JCS, Stout JC, Vogel AP (2019) Speech in prodromal and symptomatic Huntington’s disease as a model of measuring onset and progression in dominantly inherited neurodegenerative diseases. Neurosci Biobehav Rev 107:450–460 PubMed

Duffy J (2019) Motor speech disorders: substrates, differential diagnosis, and management, 4th edn. Elsevier, Maryland Heights

HSG,

Müller T et al (2013) Diadochokinetic movements differ between patients with Huntington’s disease and controls. NeuroRehabilitation 33(4):649–655 PubMed

Ackermann H, Hertrich I, Hehr T (1995) Oral diadochokinesis in neurological dysarthrias. Folia Phoniatr Logop 47(1):15–23 PubMed

Rozenstoks K et al (2020) Automated assessment of oral diadochokinesis in multiple sclerosis using a neural network approach: effect of different syllable repetition paradigms. IEEE Trans Neural Syst Rehabil Eng 28(1):32–41 PubMed

Kaploun LR et al (2011) Acoustic analysis of voice and speech characteristics in presymptomatic gene carriers of Huntington’s disease: biomarkers for preclinical sign onset? J Med Speech-Lang Patho 19(2):49–63

Kent RD, Kent JF, Rosenbek JC (1987) Maximum performance tests of speech production. J Speech Hear Disord 52(4):367–387 PubMed

Lange KW et al (1995) Comparison of executive and visuospatial memory function in Huntington’s disease and dementia of Alzheimer type matched for degree of dementia. J Neurol Neurosurg Psychiatry 58(5):598–606 PubMed PMC

Skodda S et al (2016) Two different phenomena in basic motor speech performance in premanifest Huntington disease. Neurology 86:1329–1335 PubMed

Ludlow CL, Connor NP, Bassich CJ (1987) Speech timing in Parkinson’s and Huntington’s disease. Brain Lang 32(2):195–214 PubMed

Skodda S et al (2014) Impaired motor speech performance in Huntington’s disease. J Neural Transm 121:399–407 PubMed

Saft C et al (2024) Speech biomarkers in Huntington’s disease: a longitudinal follow-up study in premanifest mutation carriers. J Huntingtons Dis 13(3):369–373 PubMed

Tabrizi SJ, Ghosh R, Leavitt BR (2019) Huntingtin lowering strategies for disease modification in Huntington’s disease. Neuron 101(5):801–819 PubMed

Bachoud-Levi AC et al (2019) International guidelines for the treatment of Huntington’s disease. Front Neurol 10:710 PubMed PMC

Harris KL et al (2020) Antidopaminergic treatment is associated with reduced chorea and irritability but impaired cognition in Huntington’s disease (Enroll-HD). J Neurol Neurosurg Psychiatry 91(6):622–630 PubMed PMC

van Vugt JP, van Hilten BJ, Roos RA (1996) Hypokinesia in Huntington’s disease. Mov Disord 11(4):384–388 PubMed

van Vugt JP et al (2003) Impaired antagonist inhibition may contribute to akinesia and bradykinesia in Huntington’s disease. Clin Neurophysiol 114(2):295–305 PubMed

Faheem AD, Brightwell DR, Burton GC, Struss A (1982) Respiratory dyskinesia and dysarthria from prolonged neuroleptic use: tardive dyskinesia? American Journal of Psychiatry 139(4) 517-518 10.1176/ajp.139.4.517

Rusz J et al (2014) Characteristics and occurrence of speech impairment in Huntington’s disease: possible influence of antipsychotic medication. J Neural Transm 121:1529–1539 PubMed

Tabrizi SJ, Schobel S, Gantman EC et al (2022) A biological classification of Huntington’s disease: the Integrated staging system. Lancet Neurol. 21(7):632–44 PubMed

Shoulson I, Fahn S (1979) Huntington disease: clinical care and evaluation. Neurology 29(1):1–3 PubMed

Warner JH et al (2022) Standardizing the CAP score in Huntington’s disease by predicting age-at-onset. J Huntingtons Dis 11(2):153–171 PubMed

Rusz J et al (2021) Guidelines for speech recording and acoustic analyses in dysarthrias of movement disorders. Mov Disord 36(4):803–814 PubMed

Lena, Hartelius Malin, Lillvik (2003) Lip and Tongue Function Differently Affected in Individuals with Multiple Sclerosis Folia Phoniatrica et Logopaedica 55(1) 1-9 10.1159/000068057

Novotny M et al (2020) Comparison of automated acoustic methods for oral diadochokinesis assessment in amyotrophic lateral sclerosis. J Speech Lang Hear Res 63(10):3453–3460 PubMed

Patel MX et al (2013) How to compare doses of different antipsychotics: a systematic review of methods. Schizophr Res 149(1–3):141–148 PubMed

Leucht S et al (2016) Dose equivalents for antipsychotic drugs: the DDD method. Schizophr Bull 42:S90-94 PubMed PMC

Huppertz HJ et al (2010) Intra- and interscanner variability of automated voxel-based volumetry based on a 3D probabilistic atlas of human cerebral structures. Neuroimage 49(3):2216–2224 PubMed

Huppertz HJ et al (2016) Differentiation of neurodegenerative parkinsonian syndromes by volumetric magnetic resonance imaging analysis and support vector machine classification. Mov Disord 31(10):1506–1517 PubMed

Desikan RS et al (2006) An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 31(3):968–980 PubMed

Cohen J (1998) Statistical power analysis for the behavioral sciences 2. Lawrence Erlbaum Associates, Hillsdale, NJ

Youden WJ (1950) Index for rating diagnostic tests. Cancer 3(1):32–35 PubMed

R Core Team (2019) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria

Team, J.,

Muhlback A et al (2023) Establishing normative data for the evaluation of cognitive performance in Huntington’s disease considering the impact of gender, age, language, and education. J Neurol 270(10):4903–4913 PubMed PMC

Schobel SA et al (2017) Motor, cognitive, and functional declines contribute to a single progressive factor in early HD. Neurology 89(24):2495–2502 PubMed PMC

Thompson JC et al (2010) Automaticity and attention in Huntington’s disease: when two hands are not better than one. Neuropsychologia. 10.1016/j.neuropsychologia.2009.09.002 PubMed DOI PMC

Bohland JW, Guenther FH (2006) An fMRI investigation of syllable sequence production. Neuroimage 32(2):821–841 PubMed

Wildgruber D, Ackermann H, Grodd W (2001) Differential contributions of motor cortex, basal ganglia, and cerebellum to speech motor control: effects of syllable repetition rate evaluated by fMRI. Neuroimage 13(1):101–109 PubMed

Graybiel AM et al (1994) The basal ganglia and adaptive motor control. Science 265(5180):1826–1831 PubMed

Argyropoulos GP, Tremblay P, Small SL (2013) The neostriatum and response selection in overt sentence production: an fMRI study. Neuroimage 82:53–60 PubMed PMC

Van der Merwe A (2009) A theoretical framework for the characterization of pathological speech sensorimotor control. In: McNeil MR (ed) Clinical management of sensorimotor speech disorders. Thieme, New York, NY, pp 3–18

Volkmann J et al (1992) Impairment of temporal organization of speech in basal ganglia diseases. Brain Lang 43(3):386–399 PubMed