J Neural Transm (2014) 121:1529–1539 DOI 10.1007/s00702-014-1229-8
NEUROLOGY AND PRECLINICAL NEUROLOGICAL STUDIES - ORIGINAL ARTICLE
Characteristics and occurrence of speech impairment in Huntington’s disease: possible influence of antipsychotic medication Jan Rusz • Jirˇ´ı Klempı´rˇ • Tereza Tykalova´ • ˇ mejla • Evzˇen Ru˚zˇicˇka Eva Baborova´ • Roman C Jan Roth
•
Received: 6 March 2014 / Accepted: 22 April 2014 / Published online: 9 May 2014 Ó Springer-Verlag Wien 2014
Abstract Although motor speech impairment is a common manifestation of Huntington’s disease (HD), its description remains limited. The aim of the current study was therefore to estimate the occurrence and characteristics of speech disorder in HD and to explore the influence of antipsychotic medication on speech performance. Speech samples, including reading passage and monologue, were acquired from 40 individuals diagnosed with HD and 40 age- and sex-matched healthy controls. Objective acoustic analyses were used to evaluate key aspects of speech including vowel articulation, intensity, pitch and timing. A predictive model was constructed to detect the occurrence and most prominent patterns of speech dysfunction in HD. We revealed that 93 % of HD patients manifest some degree of speech impairment. Decreased number of pauses, slower articulation rate, imprecise vowel articulation and excess intensity variations were found to be the most salient patterns of speech dysfunction in HD. We further demonstrated that antipsychotic medication may induce excessive loudness and pitch variations perceptually resembling excess patterns of word stress, and may also accentuate general problems with speech timing. Additionally, antipsychotics induced a slight improvement of vowel articulation. Specific speech alterations observed in HD patients indicate that speech production may reflect the
J. Rusz (&) T. Tykalova´ R. Cˇmejla Department of Circuit Theory, Faculty of Electrical Engineering, Czech Technical University in Prague, Technicka´ 2, 160 00 Prague 6, Czech Republic e-mail:
[email protected] J. Rusz J. Klempı´ˇr E. Baborova´ E. Ru˚zˇicˇka J. Roth Department of Neurology, Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague, Katerˇinska´ 30, 120 00 Prague 2, Czech Republic
pathophysiology of the disease as well as treatment effects, and may therefore be considered a valuable marker of functional disability in HD. Keywords Huntington’s disease Hyperkinetic dysarthria Speech disorder Acoustic analysis Neuroleptic medication
Introduction Huntington’s disease (HD) is an autosomal-dominant neurodegenerative disorder caused by an expansion in the number of CAG repeats in the IT15 gene (Kremer et al. 1994). HD is characterized by progressive, irrepressible motor dysfunction as well as behavioural changes and cognitive decline resulting in dementia. From a clinical perspective, HD is primarily manifested by involuntary movements termed as chorea, which may be accompanied by bradykinesia, motor impersistence, and deficits in movement planning, aiming, tracing, and termination (Berardelli et al. 1999; Paulsen 2011). Additionally, rigidity and dystonia may occur in some cases as HD progresses. The motor speech disorder characterized as hyperkinetic dysarthria represents another common sign of HD, occurring primarily as a consequence of chorea (Hartelius et al. 2003; Saldert et al. 2010). Based upon 30 speakers with various underlying choreatic movement disorders, Darley et al. (1969) perceptually defined the characteristic patterns of hyperkinetic dysarthria mainly by the presence of imprecise consonants, prolonged intervals, variable rate, monopitch, harsh voice, inappropriate silence, distorted vowels, and excess loudness variations. Subsequently, only a few studies have endeavoured to provide a more accurate
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description of hyperkinetic dysarthria in patients with genetically confirmed HD. These studies have primarily been restricted to the documentation of voice dysfunction (Ramig 1986; Zwirner et al. 1991; Velasco Garcia et al. 2011; Rusz et al. 2013a) or abnormalities in speech timing (Ludlow et al. 1987; Hertrich and Ackermann 1994; Ackermann et al. 1995; Liss et al. 2009; Vogel et al. 2012; Skodda et al. 2014). Little effort has been put into the investigation of complex speech impairment in HD; the fundamental aspects of hyperkinetic dysarthria such as vowel articulation, pitch, and intensity remain largely unexplored. Moreover, interpretation of most previous findings is limited due to small sample sizes, heterogeneity regarding gender, various speaking material, and the possible influence of medication and/or disease severity. Therefore, using objective acoustic analyses, we quantitatively analysed key dimensions of speech including subtests on vowel articulation, intensity, pitch, and timing in a representative sample of 40 HD subjects in different stages of disease with the following aims: 1.
2.
To estimate occurrence of speech impairment and find the most distinct features of hyperkinetic dysarthria in HD with respect to possible gender- and task-specific effects on speech; to explore the influence of antipsychotic medication and/or disease severity on speech performance in an effort to provide deeper insight into the pathophysiology of hyperkinetic dysarthria in HD.
Patients and methods Subjects Between 2011 and 2013, a total of 40 consecutive patients [20 men, 20 women; age 23–69 years; mean 48.6 ± standard deviation (SD) 13.4] with genetically confirmed HD were recruited for this study. None of the HD patients suffered from chronic obstructive pulmonary disease, respiratory tract infection, allergy, asthma, facial paresis, or other malady unrelated to HD that could negatively influence patient speech performance. Neuropsychological testing revealed slight to moderate cognitive deficits (Mini Mental Scale Examination \ 25) in 12 of 40 patients. Nevertheless, all patients were able to fully cooperate and complete the examination and recording procedure, and no subjects were disoriented to time and place. At the time of examination, 22 of 40 patients were treated with antipsychotic medication (subgroup HD-AP), in monotherapy or in combination with antidepressants, benzodiazepines or amantadine, whereas 18 patients received no antipsychotic therapy (subgroup HD-NoAP).
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Prior to further analyses, antipsychotic doses were converted to chlorpromazine equivalent (Woods 2003). All HD patients were further assessed by a movement disorders specialist using the motor score of the Unified Huntington’s Disease Rating Scale (UHDRS) (Huntington Study Group 1996). In addition, the burden of disease score was calculated for each subject using a formula [age 9 (CAG repeat - 35.5)] (Penney et al. 1997). The healthy control (HC) group consisted of 40 sex- and age-matched subjects (20 men, 20 women; age 26–70 years; mean 49.2 ± SD 13.3), with no history of neurological or communication disorder. All recruited subjects were Czech native speakers. Each participant provided written, informed consent, and the study was approved by the Ethics Committee of the General University Hospital in Prague, Czech Republic. Speech recordings Speech recordings were performed in a quiet room with a low ambient noise level using a head-mounted condenser microphone (Beyerdynamic Opus 55, Heilbronn, Germany) situated approximately 5 cm from the participants’ mouth. The audio data were sampled at 48 kHz with 16-bit resolution. The recordings were obtained during a single session with a speech specialist. No time limits were imposed for the completion of the recording procedure. Each participant was asked to perform a standardized reading passage composed of four sentences and a monologue on a given topic for approximately 90 s. All participants read the given passage twice in order to become more familiar with the content of the text and to avoid potential difficulties in reading. The second repetition of the reading passage was considered for final analyses. Moreover, test–retest reliability was assessed across the first and second cycle of each reading passage and was found to be relatively high (r = 0.89–0.97, p \ 0.001). Acoustic analyses Quantitative acoustic measurements were performed to investigate different aspects of speech including subtests on pitch, loudness, vowel articulation, and speech timing. Acoustic analyses were preferred as they provide a noninvasive, objective, and relatively easy to administer method as precisely assess the degree of vocal impairment. Table 1 provides a detailed description of the specific measures used in this study. To examine vowel articulation, each corner vowel /a/, /i/, and /u/ was extracted ten times from various predefined words within entire utterances, using methodology designed by our group previously for application in parkinsonian articulation (Rusz et al. 2013b). The average values of the
Speech impairment in Huntington’s disease Table 1 Overview of measurement methods used Abbreviation
Description
Vowel articulation VSA
Vowel space area, defined as Euclidean distances between the first (F1) and second (F2) formant frequency coordinates of the corner vowels /a/, /i/, /u/ in the triangular F1–F2 vowel space. F1 and F2 for each vowel were averaged by extraction of ten defined corner vowels. VSA = 0.5 9 |F1i 9 (F2a - F2u) ? F1a 9 (F2u - F2i) ? F1u 9 (F2i - F2a)|
VAIHD
Vowel articulation index, sensitive for description of hyperkinetic dysarthria in HD. VAIHD is based on formant centralization and can be defined as VAIHD = (F1a ? F2a ? F2i)/ (F1i ? F1u ? F2u). F1 and F2 for each vowel were averaged by extraction of ten defined corner vowels
Pitch Pitch level
Mean fundamental frequency (F0), referring to natural level of the vibration rate of vocal folds
Intonation
Pitch variation, defined as standard deviation of F0 contour converted to semitone scale
Intensity Intensity level
Mean speech loudness, representing average squared amplitude within a predefined time-energy segment
Intensity variation
Speech loudness variation, defined as standard deviation of intensity contour after removing a period of silence exceeding 60 ms
Timing Pause ratio
Pause time percentage relative to total speech time
No. pauses
Number of pauses relative to total speech time after removing periods of silence lasting \60 ms
Articulation rate
Number of words per second after removing periods of silence exceeding 60 ms
first (F1) and second (F2) frequencies of each corner vowel were used for calculation of the vowel space area (VSA) and vowel articulation index (VAI). VSA is a traditional parameter that represents the area inside the vowel triangle and can be easily calculated by the formula 0.5 9 |F1i 9 (F2a - F2u) ? F1a 9 (F2u - F2i) ? F1u 9 (F2 - F2a)|. Further research on parkinsonian vowel articulation has revealed that dysarthria leads to increased F1i, F1u, F2a, and F2u and decreased F1a and F2i formant frequencies, which may be better reflected by VAI = (F1a ? F2i)/(F1i ? F1u ? F2a ? F2u) (Sapir et al. 2010; Skodda et al. 2012). As we observed different patterns of formant centralization due to hyperkinetic dysarthria where F2a tends to decrease, a modification of the VAI following the formula VAIHD = (F1a ? F2a ? F2i)/(F1i ? F1u ? F2u) was introduced. This modification should therefore better reflect alterations of vowel articulation in patients with HD as compared to parkinsonian subjects.
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To assess pitch characteristics, fundamental frequency (F0) contour was estimated using an autocorrelation-based procedure (Boersma and Weenink 2001). The pitch level was defined as the mean value of pitch contour. The evaluation of intonation was based on the standard deviation of pitch contour, which was further converted to a semitone scale in order to compensate for gender-related differences present in hertz-based scales (Rusz et al. 2011). To investigate loudness of speech, the mean value of intensity contour was designated as the intensity level. Additionally, intensity variation was defined as the standard deviation of intensity contour after the removal of silent periods exceeding 60 ms, which may be associated with stop closure (Rusz et al. 2011). To capture problems related to speech timing, the pause ratio was defined as the percentage of pause time relative to total speech time. The number of pauses was defined as the number of all pauses compared to total speech time after removing pauses shorter than 60 ms. Finally, the articulation rate was determined as the number of words per second after the removal of pauses longer than 60 ms (Rusz et al. 2011). Statistical analysis As the Kolmogorov–Smirnov test showed that acoustic parameters were normally distributed, a t test for independent samples was used for comparisons between groups. Considering that the acoustic parameters of VSA, VAIHD, pitch level, and number of pauses were found to be gender-dependent, group differences were calculated for male and female groups separately. The Pearson and Spearman correlations were applied to test for significant relationships between normally distributed data (speech metrics, disease severity scores) and non-normally distributed data (chlorpromazine equivalents), respectively. With respect to the explorative nature of the present study, the adjustment for multiple comparisons was not performed and the level of significance was maintained at p \ 0.05. To reveal the most salient signs of speech disorder in HD, we introduced a classification experiment to find best combination of acoustic features for precise differentiation between the HD and HC groups. To this extent, a support vector machine (SVM) was applied to search for all possible combinations across ten proposed acoustic features (Hastie et al. 2001; Rusz et al. 2013a). We employed a Gaussian radial basis kernel as the data for HD and HC groups do not need to be separable by a simple linear decision boundary. The optimal SVM parameters were determined by a grid search over a range of values (Hastie et al. 2001; Tsanas et al. 2012). Subsequently, a crossvalidation scheme was used to validate reproducibility of
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the SVM classifier where the original data were randomly separated into a training subset composed of 60 % of the data (speech recordings of 24 subjects) and a testing subset containing 40 % of the data (speech recordings of 16 subjects); this cross-validation process was repeated 20 times for each combination. The overall classification performance of the SVM-based model was computed as the average percentage of correctly classified subjects into appropriate HD or HC group through all 20 cycles.
significantly increased in HD males and decreased in HD females, while pitch variation and intensity level in HD speakers did not significantly differ from controls. HD speakers also showed significantly increased intensity variation. Concerning speech timing, HD patients demonstrated a significantly increased pause ratio, decreased number of pauses, and slower speech rate. Most of these specific patterns of HD speech dysfunction were similar with respect to gender and more pronounced during reading.
Results
Frequency of occurrence and most salient patterns of speech disorder in HD
Clinical data The clinical characteristics of HD patients are presented in Table 2. In particular, the UHDRS dysarthria item indicated that 8 patients manifested normal speech (score of 0), 29 patients had reduced intelligibility (score of 1, no need to repeat speech performance to be understood), and only 1 patient showed severely affected speech (score of 2, must repeat speech performance to be understood). UHDRS motor evaluation was not performed in two patients. Comparison between HD patients and controls Tables 3 and 4 provide numerical data and comparison between the HD and HC groups for male and female speakers, respectively. In comparison to controls, deficits in the speech of HD subjects were observed in all speech dimensions investigated. With respect to vowel articulation, HD speakers manifested significantly restricted VSA and reduced VAIHD. Figure 1 illustrates changes in vowel formants including mainly decreased F1a, F2a, F2i and increased F2u frequency, overall leading to compressed VSA in HD speakers. Subsequently, pitch level was
Articulation rate, number of pauses, and VAIHD can be considered as the most salient patterns of speech dysfunction in male HD speakers, as the combination of these three aspects was able to best predict male HD group membership with a classification accuracy of 99.0 ± 2.5 % (sensitivity 99.8 ± 1.6 %; specificity 98.5 ± 4.1 %). Interestingly, all of these features were based upon the reading passage. The combination of intensity variation, number of pauses, and VAIHD led to the best classification performance of 92.2 ± 6.5 % (sensitivity 98.6 ± 5.3 %; specificity 88.6 ± 8.7 %) in the separation of female HD and HC groups. In this case, the number of pauses and VAIHD were based on the reading passage, whereas intensity variation was extracted from monologue. Figure 2 shows selected pairs of acoustic features representing the most prominent signs of HD speech disorder across both genders with a classification boundary allowing the separation of HD and HC speakers. Taking results for best classification combination across individual speakers, only three female HD subjects manifested speech performance comparable to those of controls and were repeatedly misclassified as healthy, whereas no control speakers were
Table 2 Clinical characteristics of HD patients HD n = 40 (20 men)
HD-AP n = 22 (14 men)
HD-NoAP n = 18 (6 men)
HD-AP vs. HD-NoAP
Mean ± SD
Mean ± SD
Mean ± SD
(t test)
Range
Range
Range
Age (years)
48.6 ± 13.4
23–69
50.5 ± 13.0
30–69
46.3 ± 13.8
23–67
n.s.
Age of HD onset (years)
42.5 ± 13.3
14–62
43.6 ± 12.5
26–61
41.1 ± 14.4
14–62
n.s.
Disease duration (years)
6.1 ± 3.4
1–16
6.8 ± 3.6
2–16
5.2 ± 3.1
1–13
n.s.
44.9 ± 3.6
40–54
45.1 ± 3.5
41–53
44.8 ± 3.9
40–54
n.s.
Disease burden score
427 ± 79
302–638
451 ± 78
345–638
397 ± 71
302–592
p = 0.037
MMSE
25.2 ± 2.6
20–29
24.4 ± 2.6
20–29
26.2 ± 2.4
21–29
n.s.
CAG triplet repeats
UHDRS motor score
26.9 ± 11.6
3–54
32.7 ± 8.6
12–54
19.8 ± 11.0
3–51
p = 0.0002
UHDRS dysarthria score Chlorpromazine equivalent (mg)
0.82 ± 0.46 69.6 ± 86.3
0–2 0–300
0.95 ± 0.38 126.6 ± 79.3
0–2 25–300
0.65 ± 0.49 0
0–1 0
p = 0.039 p \ 0.0001
HD-AP HD subgroup treated with antipsychotics, HD-NoAP HD subgroup received no antipsychotic treatment, n.s. not significant, UHDRS Unified Huntington’s Disease Rating Scale, MMSE Mini Mental Scale Examination
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Speech impairment in Huntington’s disease Table 3 Results of speech analyses in male HD subjects and controls
Speech parameter
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HD male (n = 20)
Effect sizea
HC male (n = 20)
Mean ± SD
Range
Mean ± SD
Range
HD vs. HC
Reading
118.2 ± 34.6
71.7–179.8
125.3 ± 28.4
60.9–175.0
-0.22
Monologue
106.1 ± 34.2
44.5–182.9
128.6 ± 25.6
71.7–164.7
-0.72*
Reading
2.48 ± 0.16
2.11–2.75
2.65 ± 0.15
2.34–3.06
-1.07**
Monologue
2.27 ± 0.19
1.85–2.57
2.42 ± 0.17
2.09–2.81
-0.81*
129.0 ± 19.6
96.2–165.4
119.8 ± 17.8
94.5–169.1
0.49
127.9 ± 18.4
86.3–151.3
110.6 ± 17.1
88.0–148.2
0.97**
Reading
2.27 ± 0.74
1.41–4.38
2.63 ± 0.60
1.50–3.54
-0.54
Monologue
2.41 ± 0.66
1.49–4.31
2.20 ± 0.45
1.27–2.89
0.38
Reading
63.8 ± 3.1
57.0–69.4
64.4 ± 2.9
60.3–71.9
-0.20
Monologue
62.9 ± 2.9
56.9–68.0
61.7 ± 3.4
54.9–66.8
0.40
Reading
8.21 ± 1.67
4.58–11.31
7.09 ± 0.71
6.07–8.84
0.87**
Monologue
8.55 ± 1.98
4.63–12.23
7.70 ± 0.99
6.02–9.75
0.54
Vowel articulation VSA (kHz2)
VAIHD (-)
Pitch Pitch level (Hz) Reading Monologue Pitch variation (st)
Intensity Intensity level (dB)
Intensity variation (dB)
Timing Pause ratio (%)
VSA vowel space area, VAI vowel articulation index t test: * p \ 0.05; ** p \ 0.01; *** p \ 0.001 a Cohen’s d: effect size 0.8 is considered large, 0.5 is considered medium, and 0.2 is considered small
Reading
35.0 ± 4.2
25.3–41.8
32.5 ± 2.3
29.4–37.3
0.73*
Monologue
35.6 ± 3.8
29.8–41.2
33.7 ± 2.9
28.5–38.9
0.58
3.39 ± 0.35 3.40 ± 0.36
2.52–4.02 2.93–4.22
4.45 ± 0.60 3.6 7 ± 0.55
3.53–5.53 3.02–5.05
-2.15*** -0.58
No. pauses (pauses/s) Reading Monologue
Articulation rate (word/s) Reading
2.29 ± 0.56
1.15–3.34
3.43 ± 0.25
3.08–3.96
-2.66***
Monologue
2.52 ± 0.60
1.64–3.50
2.75 ± 0.50
1.94–3.57
-0.41
misclassified as HD. In summary, some form of speech impairment was objectively detected in 93 % of our HD speakers. Comparison between HD-AP and HD-NoAP patients Tables 5 and 6 provide numerical data for male and female speakers of the HD-AP and HD-NoAP subgroups, respectively, and their comparison with controls. Although we detected statistically significant differences between HD-AP and HD-NoAP subgroups only for the number of pauses in men and for intensity variation in women (p \ 0.01), the performances of the HD-AP subgroup were poorer in pause ratio, number of pauses, articulation rate, intensity variation and pitch variation,
which were well reflected by large effect sizes (d [ 0.8). However, no differences were detected between the HDAP and HD-NoAP subgroups for VSA, VAIHD, pitch level, and intensity level. In comparison to controls, both HD-AP and HD-NoAP patients demonstrated a significantly slower articulation rate, decreased number of pauses and increased pause ratio, although these speech timing deficits were more pronounced in the HD-AP subgroup. In addition, the HDNoAP subgroup showed significantly decreased pitch variation while intensity variation was significantly increased only in the HD-AP subgroup. VSA and VAIHD were significantly reduced in both the HD-AP and HD-NoAP subgroups, whereas vowel articulation problems were generally less pronounced in the HD-AP subgroup.
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1534 Table 4 Results of speech analyses in female HD subjects and controls
J. Rusz et al.
Speech parameter
HD female n = 20 Mean ± SD
Effect sizea
HC female n = 20 Range
Mean ± SD
Range
HD vs. HC
Vowel articulation VSA (kHz2) Reading
177.4 ± 76.4
74.1–352.1
230.4 ± 61.1
89.8–338.6
Monologue
177.2 ± 58.2
86.6–306.4
257.0 ± 77.7
120.4–371.4
-0.77* -1.16***
VAIHD (-) Reading
2.68 ± 0.26
2.33–3.15
2.91 ± 0.19
2.54–3.32
-1.01**
Monologue
2.47 ± 0.22
2.13–2.88
2.69 ± 0.24
2.26–3.10
-0.97**
Pitch Pitch level (Hz) Reading
181.0 ± 30.6
116.8–228.4
203.5 ± 23.2
153.9–240
-0.83*
Monologue
179.4 ± 31.7
119.4–239.6
191.2 ± 21.8
142.8–223.9
-0.44 -0.51
Pitch variation (st) Reading
2.14 ± 0.68
1.27–3.39
2.49 ± 0.70
1.13–4.0
Monologue
2.28 ± 0.58
1.37–3.89
2.20 ± 0.60
1.43–3.55
0.13
Intensity Intensity level (dB) Reading
63.6 ± 4.6
54.9–69.4
63.6 ± 2.7
59.0–71.6
-0.01
Monologue
61.7 ± 3.8
52.5–68.3
62.2 ± 3.3
56.5–68.8
-0.13
Intensity variation (dB) Reading
7.45 ± 1.62
4.15–12.01
6.91 ± 0.50
5.76–8.19
0.45
Monologue
7.85 ± 1.26
5.77–10.90
7.04 ± 0.63
5.98–8.47
0.81*
Timing Pause ratio (%)
VSA vowel space area, VAI vowel articulation index t test: * p \ 0.05, ** p \ 0.01, *** p \ 0.001 a
Cohen’s d: effect size 0.8 is considered large, 0.5 is considered medium, and 0.2 is considered small
Reading
34.2 ± 3.1
30.3–40.2
32.4 ± 2.1
29.3–36.2
0.68*
Monologue
35.7 ± 2.6
31.8–42.3
33.7 ± 2.8
28.6–38.8
0.74*
Reading
3.79 ± 0.60
2.91–5.28
4.82 ± 0.58
3.70–5.94
-1.74***
Monologue
3.67 ± 0.56
2.74–4.64
4.29 ± 0.52
3.18–5.23
-1.15***
No. pauses (pauses/s)
Articulation rate (word/s) Reading
2.38 ± 0.52
1.17–3.22
3.45 ± 0.45
2.74–4.15
-2.19***
Monologue
2.55 ± 0.56
1.46–3.68
2.83 ± 0.39
1.93–3.54
-0.58
Correlation between speech and clinical data Antipsychotic medication dose correlated with articulation rate in reading (r = -0.41, p = 0.009) and intensity variation in monologue (r = 0.43, p = 0.006). The UHDRS motor score showed weak but significant correlations with parameters of speech timing (|r| = 0.33–0.40, p \ 0.05). Admittedly, the UHDRS motor score positively correlated with antipsychotic medication dose (r = 0.45, p = 0.004). No other significant correlations between speech and clinical data were observed.
Discussion In our previous study, we objectively determined the main indicators of voice dysfunction in HD (Rusz et al. 2013a),
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whereas in the present study we have attempted to broaden our understanding concerning speech disorder in HD. In a large sample of 40 HD patients, we were able to objectively capture speech impairment in 93 % of subjects. Although HD speakers demonstrated impairment in all investigated aspects of speech, imprecise vowel articulation, decreased number of pauses, slower articulation rate and increased intensity variation were found to be the most distinctive patterns of hyperkinetic dysarthria. In addition, speech discrepancies in HD seem to be more prominent during reading when compared to monologue. Our findings further indicate that treatment by antipsychotic medication may induce excessive loudness and pitch variations perceptually resembling excess patterns of word stress, and may accentuate general problems with speech timing. Conversely, treatment with antipsychotics induced a slight improvement of vowel articulation in HD speakers.
Speech impairment in Huntington’s disease
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Fig. 1 Mean F1 and F2 values and vowel space areas for male and female HD subjects as compared to controls
Fig. 2 Selected pairs of acoustic features representing most prominent aspects of speech disorder in HD. All presented acoustic metrics are based on reading passage with the exception of intensity variation extracted from monologue
According to the present results, deficits in timing appear to be one of the cardinal manifestations of HD speech dysfunction. In particular, our HD patients showed a markedly reduced speech rate and decreased number of
pauses. In addition, HD speech was accompanied by prolonged intervals that resulted in an increased pause ratio. These abnormal speech patterns appear to be associated with general problems in timing, however, the effect of
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Table 5 Results of speech analyses in male HD subgroups Speech parameter
HD-AP male n = 14 Mean ± SD
Effect sizea
HD-NoAP male n=6 Range
Mean ± SD
Range
104.1 ± 30.8 101.9 ± 44.2
72.1–155.3 54.5–182.9
HD-AP vs. HD-NoAP
HD-AP vs. HC
HD-NoAP vs. HC
-0.03 -0.69
-0.71 -0.74
Vowel articulation VSA (kHz2) Reading Monologue
124.2 ± 35.4 107.9 ± 33.9
71.7–179.8 44.5–153.9
0.61 0.15
VAIHD (-) Reading
2.50 ± 0.18
2.11–2.75
2.44 ± 0.12
2.28–2.56
0.36
-0.92*
-1.50**
Monologue
2.29 ± 0.20
1.85–2.57
2.22 ± 0.17
1.95–2.50
0.36
-0.68
-1.13*
Reading
131.0 ± 17.1
100.6–157.9
124.4 ± 25.6
96.2–165.4
0.30
0.64
0.21
Monologue
130.0 ± 15.1
102.1–151.3
123.0 ± 24.5
86.3–150.7
0.33
1.20**
0.57
VAIPD (-) Pitch Pitch level (Hz)
Pitch variation (st) Reading
2.39 ± 0.80
1.45–4.38
1.98 ± 0.52
1.41–2.60
0.61
-0.34
Monologue
2.57 ± 0.68
1.72–4.31
2.04 ± 0.46
1.49–2.51
0.92
0.65
-0.34
-1.16*
63.4 ± 3.2 62.9 ± 2.4
57.0–67.8 57.9–66.5
65.1 ± 3.0 63.0 ± 4.6
62.5–69.4 56.9–68.0
-0.56 -0.01
-0.33 0.42
0.25 0.31
Intensity Intensity level (dB) Reading Monologue
Intensity variation (dB) Reading
8.46 ± 1.88
4.58–11.31
7.60 ± 0.89
6.45–8.68
0.58
0.97**
Monologue
8.91 ± 2.16
4.63–12.23
7.69 ± 1.20
6.52–9.31
0.70
0.72*
0.63 -0.01
Timing Pause ratio (%) Reading
36.0 ± 3.7
29.0–41.8
32.5 ± 4.5
25.3–38.0
0.86
1.13*
-0.01
Monologue
36.5 ± 3.2
31.6–40.7
33.6 ± 4.5
29.8–41.2
0.73
0.91*
-0.01
No. pauses (pauses/s) Reading
3.41 ± 0.34
2.52–4.02
3.34 ± 0.41
2.81–3.89
0.18
Monologue
3.27 ± 0.21
2.93–3.60
3.71 ± 0.46
3.18–4.22
-1.24**
-2.12*** -0.97*
-2.15*** 0.07
Articulation rate (word/s) Reading
2.14 ± 0.51
1.15–3.10
2.65 ± 0.53
2.03–3.34
-0.98
-3.22***
Monologue
2.42 ± 0.62
1.64–3.50
2.76 ± 0.52
2.11–3.24
-0.60
-0.59
-1.91*** 0.02
HD-AP HD subgroup treated with antipsychotics, HD-NoAP HD subgroup received no antipsychotic treatment, VSA vowel space area, VAI vowel articulation index t test: * p \ 0.05, ** p \ 0.01, *** p \ 0.001 a
Cohen’s d: effect size 0.8 is considered large, 0.5 is considered medium, and 0.2 is considered small
slurred speech, respiratory problems and poor articulation of stop consonants cannot be excluded. Nevertheless, our findings on speech timing are well in agreement with previous studies reporting the occurrence of variable and slow rate, prolonged intervals, and inappropriate silences in the speech of HD subjects (Ludlow et al. 1987; Hertrich and Ackermann 1994; Ackermann et al. 1995; Hartelius et al. 2003; Vogel et al. 2012; Skodda et al. 2014). Alterations in speech timing due to HD are not surprising, as
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there is clear evidence that widespread neuronal atrophy is related to decline in both cognitive and motor functions (Jech et al. 2007; Bohanna et al. 2011), which are the key elements for motor speech timing. In addition, we identified deficits in vowel articulation, pitch, and intensity that, to the best of our knowledge, have not been objectively documented in HD patients thus far. Imprecise vowel articulation was primarily characterized by decreased F1a, F2a and F2i and increased F2u
Speech impairment in Huntington’s disease
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Table 6 Results of speech analyses in female HD subgroups Speech parameter
HD-AP female n=8
HD-NoAP female n = 12
Effect sizea HD-AP vs. HD-NoAP
Mean ± SD
Range
Mean ± SD
189.8 ± 91.8 198.7 ± 55.6
80.4–352.1 144.6–306.4
169.1 ± 67.3 162.8 ± 57.6
Range
HD-AP vs. HC
HD-NoAP vs. HC
-0.52 -0.86*
-0.95* -1.38*
Vowel articulation VSA (kHz2) Reading Monologue
74.1–303.3 86.6–262.8
0.26 0.63
VAIHD (-) Reading
2.65 ± 0.23
2.33–2.98
2.69 ± 0.29
2.34–3.15
-0.16
Monologue
2.54 ± 0.18
2.30–2.81
2.43 ± 0.24
2.13–2.88
0.52
-1.22**
-0.87*
-0.74
-1.12**
Reading
176.1 ± 38.3
116.8–228.4
184.3 ± 25.5
136.8–221.0
-0.25
-0.86*
-0.78*
Monologue
178.0 ± 42.1
119.4–239.6
180.3 ± 24.6
138.7–211.2
-0.07
-0.40
-0.47
VAIPD (-) Pitch Pitch level (Hz)
Pitch variation (st) Reading
2.22 ± 0.87
1.27–3.39
2.09 ± 0.56
1.33–3.11
0.18
-0.35
-0.64
Monologue
2.51 ± 0.70
1.71–3.89
2.12 ± 0.44
1.37–2.97
0.67
0.48
-0.16
64.4 ± 5.0 61.4 ± 5.0
56.8–69.4 52.5–68.3
62.9 ± 4.3 62.0 ± 2.5
54.9–67.9 58.9–65.8
0.31 -0.17
0.19 -0.19
-0.20 -0.05
Intensity Intensity level (dB) Reading Monologue
Intensity variation (dB) Reading
8.29 ± 1.60
6.90–12.01
6.89 ± 1.43
4.15–8.69
0.93
1.17**
Monologue
8.82 ± 1.20
7.14–10.90
7.21 ± 0.83
5.77–8.52
1.56**
1.85***
-0.02 0.22
Timing Pause ratio (%) Reading
34.1 ± 3.7
30.3–40.2
34.2 ± 2.7
30.4–39.0
-0.02
0.57
0.75*
Monologue
35.6 ± 2.3
32.1–38.6
35.7 ± 2.8
31.8–42.3
-0.07
0.73
0.74
No. pauses (pauses/s) Reading
3.56 ± 0.54
2.91–4.52
3.95 ± 0.62
3.44–5.28
-0.66
-2.25***
-1.46***
Monologue
3.59 ± 0.44
3.15–4.53
3.72 ± 0.64
2.74–4.64
-0.23
-1.44**
-0.98**
Articulation rate (word/s) Reading
2.16 ± 0.58
1.17–2.88
2.52 ± 0.45
1.88–3.22
-0.69
-2.47***
-2.05***
Monologue
2.42 ± 0.60
1.46–3.31
2.64 ± 0.54
2.07–3.68
-0.39
-0.82*
-0.41
HD-AP HD subgroup treated with antipsychotics, HD-NoAP HD subgroup received no antipsychotic treatment, VSA vowel space area, VAI vowel articulation index t test: * p \ 0.05, ** p \ 0.01, *** p \ 0.001 a
Cohen’s d: effect size 0.8 is considered large, 0.5 is considered medium, and 0.2 is considered small
frequency, which led to reduced vowel space and formant centralization. The shifts in F1a, F2i and F2u frequencies in HD subjects are similar to those observed in hypokinetic-rigid syndromes (Sapir et al. 2010; Skodda et al. 2012; Rusz et al. 2013b), whereas decreases in F2a frequency may be related to reduced articulatory velocity (Tjaden and Wilding 2004). Concerning loudness of speech, HD speakers showed excessive intensity variation but their mean intensity level was essentially the same as in controls. Monotonous speech was observed in some of
our HD patients and was rather evident during reading. In particular, our healthy speakers generally reached better speech performance during reading when compared to monologue, while HD speech performance tended to be similar for both tasks, allowing reading-based metrics to more precisely separate HD subjects from controls. We further revealed increased pitch level in male HD speakers and decreased pitch level in female HD speakers. This observation is consistent with the general process of age-related speech degradation, where pitch
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increases in men with age while remaining constant or decreasing in women (Hollien and Shipp 1972; Russel et al. 1995). The speech abnormalities observed in HD subjects may additionally be influenced by antidopaminergic medication, as about half of our HD patients were treated with antipsychotics. Interestingly, previous research has shown that antipsychotic medication alone can induce hyperkinetic dysarthria (Faheem et al. 1982; Cohen et al. 1996). However, the effect of antipsychotics on motor speech performance in HD has remained unexplored. As the subgroup of HD patients that did not undergo antipsychotic therapy manifested speech deficits including imprecise vowel articulation, alterations in pitch level, monopitch, and problems with speech timing, we may assume that the impairment of speech in HD is, at least to some degree, induced by HD itself and not by antipsychotic medication alone. The worse inferior speech performances regarding articulation rate, number of pauses and pause ratio observed in our HD patients treated with antipsychotics is in accordance with previous work that reported pronounced abnormalities in speech timing in HD patients treated with antidopaminergic medication (Skodda et al. 2014). Notably, in the previous study (Skodda et al. 2014) as well as the present study, the HD subgroup treated with antipsychotics manifested more severe motor involvement as well as speech dysfunction. In particular, we observed correlation between articulation rate, antipsychotic medication dose, and the motor UHDRS score. Blockade of the dopamine receptors in the striatum by antipsychotics can lead to slowing of voluntary movements, together with suppressing primary dyskinesias. Therefore, the role of antipsychotic medication must be considered cautiously, as HD patients with more severe chorea usually receive higher doses of antipsychotic drugs, which in consequence may aggravate bradykinesia and rigidity (van Vugt et al. 1996), thus increasing motor disability as reflected by UHDRS scores. Our findings also indicate that antipsychotic medication may evoke excessive pitch and loudness variations. This observation is further supported by the correlation detected between intensity variation and antipsychotic dose. During spontaneous speech, the prosodic aspects of excessive pitch and loudness can together form the perceptual impression of excessive-inefficient-variable patterns of word stress, which has been documented previously in hyperkinetic dysarthria of chorea (Duffy 2013). One possible explanation is that the extent of intensity variation is partially influenced by speech rate, i.e. non-fluent discontinuous speech with frequent pauses between words inevitably results in excess intensity variations. Finally, antipsychotic medication appeared to slightly improve vowel articulation performance in our
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HD patients. Yet, antipsychotic medication may have a beneficial effect on involuntary choreatic movements, which can result in an improvement of articulation accuracy. In summary, the present study shows the potential of acoustic analyses in describing the patterns of speech disorder in HD. Based upon a large sample of patients, our results demonstrate that speech disorder is a prominent manifestation of HD in nearly all patients. Although HD subjects showed deficits in all examined aspects of speech, abnormalities in timing, intensity, and articulation were found to be the most salient patterns of speech dysfunction in HD speakers. Furthermore, dysarthric patterns of imprecise vowel articulation, alterations in pitch level, monopitch, slower articulation rate, decreased number of pauses, and prolonged pause ratio are induced by the underlying disease itself, whereas excessive pitch and loudness variations seem to be induced by antipsychotic medication alone. These specific speech differences, thus far observed only in our HD patients, suggest that speech production may reflect the underlying pathophysiology of the disease as well as treatment effects and may therefore be considered a valuable marker of functional disability in HD. Future longitudinal studies are necessary to confirm and further elaborate our results. Acknowledgments This study was supported by the Czech Science Foundation (GACR 102/12/2230), Czech Ministry of Health (NT 12288-5) and Charles University in Prague (PRVOUK-P26/LF1/4). Conflict of interest of interest.
The authors declare that they have no conflict
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