Journal of Parkinson’s Disease xx (20xx) x–xx 1

DOI 10.3233/JPD-191798
IOS Press

1 Research Report

2 Longitudinal Speech Change After

Subthalamic Nucleus Deep Brain

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4 Stimulation in Parkinson’s Disease Patients:
5 A 2-Year Prospective Study

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6 Yasuhiro Tanakaa,b , Takashi Tsuboia,c , Hirohisa Watanabeb,d , Daisuke Nakatsuboe ,
7 Satoshi Maesawab,e , Sachiko Katoe , Yasukazu Kajitaf , Maki Satoa , Reiko Oodakeb , Makoto Hattoria ,

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8 Masahiko Yamamotog , Toshihiko Wakabayashie , Masahisa Katsunoa and Gen Sobueb,h,∗
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a Department of Neurology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Aichi, Japan
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b Brainand Mind Research Center, Nagoya University, Showa-ku, Nagoya, Aichi, Japan
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c Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville,

FL, USA
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d Department of Neurology, Fujita Health University, School of Medicine, Kutsukake-cho, Toyoake, Aichi, Japan

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e Department of Neurosurgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Aichi, Japan

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f Department of Neurosurgery, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

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g Department of Health Science, Aichi Gakuin University, Iwasaki-cho, Nisshin-city, Aichi, Japan

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h Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of
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18 Medicine, Showa-ku, Nagoya, Aichi, Japan

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Accepted 25 November 2019

19 Abstract.
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20 Background: Speech disorders are among the most common adverse effects after subthalamic nucleus deep brain stimula-
21 tion (STN-DBS) in Parkinson’s disease (PD) patients. However, longitudinal speech changes after STN-DBS are not fully
22 understood.
23 Objective: We performed a two-year prospective study on PD patients who underwent STN-DBS and analyzed changes in
speech function to clarify factors predicting for speech deterioration.
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25 Methods: Twenty-five PD patients were assessed before and up to two years after STN implantation. Speech function
26 was evaluated in the on-stimulation condition and 30 min after stimulation cessation using auditory-perceptual assessment.
27 Patients who experienced overall worsening in speech intelligibility or naturalness ≥1 point during follow-up were classified
into a deteriorated group (n = 16), with the remaining subjects being classified into a stable group (n = 9). Cognitive and motor
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29 functions were also assessed.

30 Results: The stable group had significantly better values of low volume, monoloudness, and asthenic voice subscores of
31 the auditory-perceptual assessment in the on-stimulation condition compared with the off-stimulation condition. Imprecise
32 consonants, excess loudness variation, and strained voice subscores were improved via cessation of stimulation in both
33 groups. Before surgery, the deteriorated group had significantly lower scores in the Stroop Color-Word Test and Digit Span
34 compared to the stable group.

∗ Correspondence to: Gen Sobue, MD, PhD, Brain and Mind Nagoya, Aichi, Japan, 466-8560. Fax: +81 52 744 2943; E-mail:
Research Center, Nagoya University, 65 Tsurumai-cho, Showa-ku, sobueg@med.nagoya-u.ac.jp.

ISSN 1877-7171/19/$35.00 © 2019 – IOS Press and the authors. All rights reserved
 2 Y. Tanaka et al. / Speech Change After STN-DBS in PD

35 Conclusions: During follow-up, some subscores showed significant worsening in the on-stimulation condition in both
36 groups. However, beneficial effects of STN-DBS on speech appeared to counterbalance negative effects of STN-DBS on
37 speech function only in the stable group. Worse cognitive function may be a potential predictor for speech deterioration after
38 STN-DBS in PD patients.

39 Keywords: Parkinson’s disease, subthalamic nucleus deep brain stimulation, dysarthria, speech, voice, longitudinal change

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35 INTRODUCTION unknown how speech characteristics change longitu- 78

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dinally in postoperative cases. Therefore, a long-term 79

36 Subthalamic nucleus deep brain stimulation (STN- prospective evaluation of auditory-perceptual assess- 80

37 DBS) is a widely accepted surgical treatment for ment subscores in PD patients treated with DBS is 81

38 advanced Parkinson’s disease (PD) patients with needed. 82

39 motor complications. It effectively improves motor In the present study, we evaluated longitudinal 83

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40 function, motor complications, and quality of life, and change in speech characteristics by analyzing struc- 84

41 reduces the levodopa equivalent daily dose (LEDD) tured auditory-perceptual analysis subscores to better 85

42 [1]. However, speech disorders are one of the most understand stimulation-induced speech deterioration. 86

43 common adverse effects following STN-DBS in PD Additionally, we aimed to identify factors predicting 87

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44 patients [2], and speech deterioration is a possible speech deterioration after STN-DBS. 88

45 obstacle to fully benefiting from STN-DBS therapy in

46 these patients [3]. Nevertheless, detailed prospective MATERIALS AND METHODS 89

47 studies on perceptual speech change after STN-DBS

48 remain scarce. Participants 90
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49 Recent prospective studies using auditory-
50 perceptual assessment have demonstrated significant The inclusion criteria were as follows: 1) diagno- 91

51 deterioration in speech intelligibility one year after sis of PD based on the United Kingdom Parkinson’s 92

52 STN-DBS [4–6], and an average deterioration Disease Society Brain Bank criteria [9]; 2) no further 93

53 rate of 12.3–16.9% in speech intelligibility was neurological diseases; 3) Japanese as native lan- 94

noted [4, 5]. They reported that the lower speech guage; 4) absence of severe cognitive impairment or
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54 95

55 intelligibility before bilateral STN implantation, psychiatric disorders that may hinder speech assess- 96
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56 longer disease duration, and medially-placed active ment; and 5) bilateral STN implantation at Nagoya 97

57 contacts in the left hemisphere were predictive University Hospital. We identified 30 consecutive 98

58 factors for deterioration in speech intelligibility patients who underwent bilateral STN implantation 99

59 following STN-DBS [4]. A retrospective study for in the period from 2013 to 2015. Of these, two 100

60 15 years reported that 52% of PD patients lost their patients refused on- and off-stimulation assessment, 101
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61 ability to speak over time after STN-DBS [7]. In a one refused to participate, and two died during the 102

62 previous study, we prospectively evaluated a change follow-up period of 24 months after STN implan- 103

63 in speech function with DBS in 32 PD patients tation. Therefore, 25 PD patients (10 males and 15 104

64 and reported not only significant deterioration in females) in total were enrolled in the study (Table 1). 105
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65 speech intelligibility one year after STN-DBS but All participants were taking antiparkinsonian medi- 106

66 also significant deterioration in speech naturalness cation. A board-certified neurologist (T.T.) evaluated 107

67 and subscores constituting speech intelligibil- all participants using the Unified Parkinson’s Disease 108

68 ity/naturalness [6]. Among these subscores, two Rating Scale (UPDRS) [10]. A skilled and certi- 109
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69 items, grade of dysphonia and strained voice, were fied speech-language-hearing therapist (SLHT; Y.T.) 110

70 significantly worsened during one-year follow-up performed speech recordings and cognitive function 111

71 in patients treated with STN-DBS, compared with examinations. 112

72 those treated with medical therapy. All the PD patients were assessed before bilat- 113

73 Speech disturbance due to STN stimulation is eral STN implantation (baseline) and at 3, 6, 12, 18, 114

74 multifaceted [8]; namely, the degree of speech dete- and 24 months after surgery. Baseline assessments 115

75 rioration after DBS differs among patients, although of motor, cognitive, and speech functions were done 116

76 the factors responsible for the variation in prognosis in inpatient settings. Following surgery, each patient 117

77 have not been fully understood. In addition, it remains was followed regularly for clinical assessments and 118
 Y. Tanaka et al. / Speech Change After STN-DBS in PD 3

Table 1 recorder (ICD-SX813; Sony, Tokyo, Japan) at a sam- 136

Patient characteristics pling rate of 44.1 kHz with 16-bit quantization. A 137

Number 25 microphone (ECM-MS907; Sony) was positioned to 138

Sex (female, %) 60.0
maintain a constant mouth-to-microphone distance of 139
Age (y) 65.0 ± 8.8
Disease duration (y) 11.8 ± 4.1 15 cm during recording. Recorded speech and voice 140

UPDRS III on 15.8 ± 6.6 samples were subsequently used in perceptual anal- 141
UPDRS IV 7.0 ± 3.4 yses, for which we used the Assessment of Motor 142
LEDD (mg) 971.1 ± 365.9
S & E on (%) 83.5 ± 11.5
Speech for Dysarthria (AMSD) [12] consisting of 143

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S & E off (%) 53.5 ± 21.2 analogous variables developed by Darley et al. [13] 144

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Speech intelligibility 1.5 ± 0.5 and GRBAS scale [14]. The overall severity of speech 145
Speech naturalness 2.3 ± 0.7 disorders, speech intelligibility and naturalness, are 146
VHI 35.0 ± 22.2
MMSE total 27.6 ± 2.2
scored from 1 to 5 with a 0.5 increment; a score of 147

MoCA-J total 23.7 ± 3.8 1 indicates normal, a score of 5 indicates severe, 148

Verbal fluency and a score of 2 to 4 indicate cases with speech 149

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Letter (number/min.) 10.3 ± 3.9 disorders between these two points. Subscores of 150
Semantic (number/min.) 15.5 ± 5.8
SCWT AMSD and GRBAS scale were scored from 0 to 151

Part 1 (sec.) 15.4 ± 4.1 3; 0 = normal, 1 = mild, 2 = moderate, and 3 = severe. 152

Part 2 (sec.) 31.2 ± 13.2 Definitions and interpretations of the variables are 153
Total errors (number) 2.5 ± 1.8

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summarized in Supplementary Table 1. The speech 154
Digit span forward 10.2 ± 2.0
Digit span backward 6.8 ± 2.6 and voice samples included reading a standard pas- 155

RCPM total 29.9 ± 5.1 sage (Japanese version of “The North Wind and the 156

Line-orientation 16.1 ± 3.6 Sun”), short conversations, and sustained vowels. All 157

Values are mean ± SD; Motor and cognitive assessments before patients were asked to speak in their habitual and 158
DBS implantation were performed in the On-medication con-
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comfortable pitch, loudness, and rate. Three certified 159
dition. UPDRS-III, Unified Parkinson’s Disease Rating Scale
SLHTs (M.S., R.O., and Y.T.) blindly evaluated the 160
motor examination; UPDRS-IV, Unified Parkinson’s Disease Rat-
ing Scale motor complications; LEDD, levodopa equivalent daily speech samples and a mean value of the three raters 161

dose; S & E, Schwab and England Independence Scale; VHI, Voice was derived for each score. The inter-evaluator relia- 162

Handicap Index; MMSE, Mini-Mental State Examination; MoCA- bility kappa coefficient (R, http://www.r-project.org/) 163
J, Montreal Cognitive Assessment Japanese version; SCWT, The was 0.641, representing substantial agreement [15].
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Stroop Color and Word Test; Part 1, naming task of different
For detailed understanding of postoperative speech 165
color patches; Part 2, task of named color-word condition; RCPM:
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Raven’s Colored Progressive Matrices. symptoms, we divided the 25 PD patients into two 166

groups per the following criteria. All patients expe- 167

riencing worsening in overall speech intelligibility 168

119 adjustment of stimulation settings and medication. or speech naturalness in the on-stimulation condi- 169
120 They were assessed in the on-state under continued tion by ≥1 point during the follow-up period were 170
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121 medication. The LEDD [11] and DBS parameters classified as the “deteriorated group”. The remain- 171
122 in the PD patients are shown in Tables 2 and 3. ing subjects were classified as the “stable group”. 172
123 For auditory-perceptual analyses, speech was first The cut-off value for worsening was consistent with 173
124 recorded in the on-stimulation condition and then the guidelines for perceptual analysis and a level that 174
30 min after stimulation cessation.
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125 clearly shows a meaningful difference [12]. 175

126 The study adhered to the Ethical Guidelines for
127 Medical and Health Research Involving Human Sub-
128 jects endorsed by the Japanese government and Motor function examination 176
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129 was approved by the Ethical Review Committee of

130 Nagoya University Graduate School of Medicine. The motor symptoms were assessed using UPDRS 177
131 Written informed consent was obtained from all par- motor examination (UPDRS III). To reveal the factors 178
132 ticipants. predicting deterioration in speech after STN-DBS, 179

we subdivided UPDRS III score into four subscores 180

133 Speech and voice analyses [16] and compared them between the deteriorated and 181

stable groups: axial (items 18–19 and 27–30), tremor 182

134 Speech and voice samples were recorded in a (items 20–21), rigidity (items 22), and bradykinesia 183

135 sound-treated room and digitized using a voice score (items 23–26, 31).
 4 Y. Tanaka et al. / Speech Change After STN-DBS in PD

Table 2
Patient characteristics at baseline and during follow-up period after surgery
BL 3M 6M 12M 18M 24M p value
UPDRS-III 15.8 ± 6.6 15.1 ± 8.2 14.0 ± 8.8 14.9 ± 7.9 15.1 ± 9.2 15.3 ± 8.7 n.s.
UPDRS-IV 7.0 ± 3.4 n.d. n.d. 2.9 ± 3.2∗ n.d. 2.3 ± 2.5∗∗ <0.001
LEDD (mg) 971.1 ± 365.9 612.0 ± 254.0∗∗ 618.3 ± 249.6∗∗ 642.1 ± 283.8∗∗ 726.0 ± 385.1∗∗ 693.6 ± 265.6∗∗ <0.001
S & E on (%) 83.5 ± 11.5 n.d. n.d. 84.1 ± 15.9 n.d. 83.0 ± 14.9 n.s.
S & E off (%) 53.5 ± 21.2 n.d. n.d. 73.6 ± 21.1∗∗ n.d. 74.8 ± 19.0∗∗ <0.001
Speech intelligibility

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Stim on-condition n/a 1.7 ± 0.5∗,† 1.7 ± 0.4∗,† 2.0 ± 0.6∗∗,† 2.0 ± 0.4∗∗,†† 2.2 ± 0.6∗∗,†† <0.001
1.5 ± 0.5 1.6 ± 0.4 1.6 ± 0.4 1.8 ± 0.4∗ 1.8 ± 0.4∗∗ 2.0 ± 0.6∗∗

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Stim off-condition <0.001
Speech naturalness
Stim on-condition n/a 2.4 ± 0.7 2.5 ± 0.7† 2.8 ± 0.9∗,† 3.1 ± 0.9∗∗,†† 3.2 ± 0.8∗∗,†† <0.001
Stim off-condition 2.3 ± 0.7 2.3 ± 0.6 2.3 ± 0.7 2.5 ± 0.7 2.6 ± 0.8 2.8 ± 0.7 <0.001
VHI 35.0 ± 22.2 n.d. n.d. 33.5 ± 24.2 n.d. 43.0 ± 31.5 n.s.
MMSE 27.6 ± 2.2 n.d. n.d. 27.5 ± 2.2 n.d. 27.8 ± 2.3 n.s.
MoCA-J 23.7 ± 3.8 n.d. n.d. 23.7 ± 4.4 n.d. 24.2 ± 3.7 n.s.

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Verbal fluency
Letter (number/min.) 10.3 ± 3.9 n.d. n.d. 7.6 ± 4.3∗∗∗ n.d. 8.9 ± 4.0 0.007
Semantic (number/min.) 15.5 ± 5.8 n.d. n.d. 12.6 ± 7.0 n.d. 13.5 ± 4.5 0.037
∗ p < 0.05, ∗∗ p < 0.01: significant longitudinal changes within group by Holm post-hoc test. † p < 0.05, †† p < 0.01: significant difference between

the on- and off-stimulation conditions by Wilcoxon signed-rank tests. Values are mean ± SD; BL, before bilateral STN implantation; M,

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months after surgery; n/a, not applicable; n.d., not determined; n.s., not significant; UPDRS-III, Unified Parkinson’s Disease Rating Scale
motor examination; UPDRS-IV, Unified Parkinson’s Disease Rating Scale motor complications; LEDD, levodopa equivalent daily dose; S
& E, Schwab and England Independence Scale; Stim on-condition, Period of STN electrical stimulation on-condition; Stim off-condition,
Period of STN electrical stimulation off-condition; VHI, Voice Handicap Index; MMSE, Mini-Mental State Examination; MoCA-J, Montreal
Cognitive Assessment Japanese version.
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Table 3
DBS settings
3M 6M 12M 18M 24M p value
Left Amplitude (V) Total 1.8 ± 0.5 1.9 ± 0.5 2.0 ± 0.5 2.1 ± 0.5 2.1 ± 0.5 0.004
Deteriorated group 1.8 ± 0.7 1.9 ± 0.6 1.9 ± 0.5 1.9 ± 0.6 2.1 ± 0.5 n.s.
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Stable group 1.8 ± 0.3 2.0 ± 0.3 2.1 ± 0.4 2.3 ± 0.4 2.2 ± 0.4 n.s.
Frequency (Hz) Total 133.5 ± 11.9 132.0 ± 10.0 135.2 ± 10.8 135.0 ± 18.2 131.5 ± 14.1 n.s.
Deteriorated group 135.7 ± 15.0 133.1 ± 12.5 136.3 ± 11.5 127.0 ± 10.3 127.0 ± 10.3 n.s.
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Stable group 130.0 ± 0.0 130.0 ± 0.0 133.3 ± 10.0 140.0 ± 17.3 140.0 ± 15.8 n.s.
Pulse width (␮s) Total 62.6 ± 8.6 64.8 ± 11.2 69.6 ± 14.3 73.6 ± 15.3 73.8 ± 17.6 0.004
Deteriorated group 64.3 ± 10.9 63.8 ± 10.2 67.5 ± 13.4 72.0 ± 15.2 74.0 ± 19.2 n.s.
Stable group 60.0 ± 0.0 66.7 ± 13.2 73.3 ± 15.8 77.1 ± 16.0 73.3 ± 15.8 0.012
Right Amplitude (V) Total 1.8 ± 0.5 1.9 ± 0.4 2.1 ± 0.4 2.1 ± 0.5 2.2 ± 0.4 0.001
Deteriorated group 1.8 ± 0.6 1.9 ± 0.5 2.0 ± 0.5 2.0 ± 0.5 2.1 ± 0.4 0.010
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Stable group 1.8 ± 0.3 2.0 ± 0.43 2.1 ± 0.4 2.3 ± 0.4 2.3 ± 0.4 n.s.
Frequency (Hz) Total 133.5 ± 11.9 132.0 ± 10.0 135.2 ± 10.8 135.0 ± 18.2 131.9 ± 13.9 n.s.
Deteriorated group 135.7 ± 15.0 133.1 ± 12.5 136.3 ± 11.5 132.7 ± 18.7 127.0 ± 10.3 n.s.
Stable group 130.0 ± 0.0 130.0 ± 0.0 133.3 ± 10.0 140.0 ± 17.3 138.9 ± 16.9 n.s.
Pulse width (␮s) Total 62.6 ± 8.6 64.8 ± 11.2 69.6 ± 14.3 73.6 ± 15.3 73.8 ± 17.6 0.004
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Deteriorated group 64.3 ± 10.9 63.8 ± 10.2 67.5 ± 13.4 72.0 ± 15.2 74.0 ± 19.2 n.s.
Stable group 60.0 ± 0.0 66.7 ± 13.2 73.3 ± 15.8 77.1 ± 16.0 73.3 ± 15.8 0.012
Values are mean ± SD; M, months after surgery; p value by Friedman’s nonparametric Two-Way ANOVA.
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184 Cognitive function examinations ment of Line-orientation in the Repeatable Battery 192

for the Assessment of Neuropsychological Status 193

185 All patients underwent cognitive assessments (RBANS) [18] before operation (baseline). To assess 194

186 using the Mini-Mental State Examination (MMSE), general cognitive function of the patients, we fur- 195

187 the Montreal Cognitive Assessment (MoCA), ver- ther conducted MMSE, MoCA, and verbal fluency 196

188 bal fluency (letter: ka, semantic: animal), the Stroop assessments in the on-stimulation condition at 12 and 197

189 Color-Word Test (SCWT), Digit Span in the Wechsler 24 months after surgery (Table 2). We chose these 198

190 Adult Intelligence Scale-3rd edition (WAIS–III) [17], three cognitive examinations to minimize the effect 199

191 Raven’s Colored Progressive Matrices, and judg- of fatigue on the patients. 200
 Y. Tanaka et al. / Speech Change After STN-DBS in PD 5

201 Radiological evaluations To identify stimulation-induced speech distur- 247

bances, we also evaluated speech intelligibility and 248

202 Anatomical locations of DBS electrodes were plot- naturalness 30 minutes after stimulation cessation. 249

203 ted on the standard human brain atlas at the level The deteriorated group showed significantly worse 250

204 of 3.5 mm below the anterior commissure–posterior scores in the on-stimulation condition than in the off- 251

205 commissure line using the same technique we stimulation condition at every interval after Month 252

206 employed in our previous report [6, 8]. 6, while the stable group showed no significant dif- 253

ference at any timepoints (Fig. 1). The stimulation 254

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207 Statistical analysis conditions (amplitude, frequency, and pulse width) 255

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showed no significant differences between the dete- 256

208 We used the software SPSS statistics–24 (IBM, riorated and stable groups (Table 3). 257

209 Chicago, IL, USA) for statistical analysis. Longitudi-

210 nal changes in motor, cognitive, and speech functions The effects of STN stimulation on speech 258
211 were assessed by comparing the data at baseline with subscores 259

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212 those at each timepoint after surgery using Fried-
213 man’s non-parametric Two-Way ANOVA with Holm The differences in subscores of auditory- 260

214 post-hoc test with R (http://www.r-project.org/). The perceptual assessment between the on- and 261

215 differences in speech functions between the on- off-condition are summarized in Fig. 2. In the stable 262

and off-stimulation conditions were assessed using

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216 group, three subscores were significantly better in the 263

217 Wilcoxon signed-rank tests. Comparison of variables on-stimulation condition than in the off-stimulation 264

218 between the deteriorated and the stable group was condition (p < 0.05); low volume at Months 18 265

219 performed using Mann–Whitney U tests. A p value and 24, monoloudness at Months 18 and 24, and 266

220 <0.05 was considered statistically significant. asthenic voice at Months 12 and 24. In contrast, in 267
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the deteriorated group, no subscores were improved 268

221 RESULTS due to the stimulation. 269

Imprecise consonants, excess loudness variation, 270

222 The effects of STN stimulation on motor and and strained voice subscores were significantly 271

223 speech functions improved after cessation of stimulation in both 272

groups. Furthermore, in the deteriorated group,

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224 Compared with baseline, UPDRS IV, Schwab and abnormal pitch level and variable pitch level were 274
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225 England scale off-state significantly improved at 12 worse in the on-stimulation condition than in the off- 275

226 and 24 months after DBS implantation along with stimulation condition. Albeit not significant, a similar 276

227 significantly decreased LEDD (all p < 0.05; Table 2, trend was found in the stable group. 277

228 and Supplementary Table 2). Among the 25 patients

229 who underwent STN-DBS, 16 patients had dete- Clinical backgrounds before STN implantation 278
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230 rioration in overall speech intelligibility or speech

231 naturalness in the on-stimulation condition by ≥1 The clinical backgrounds of the patients in the 279

232 point during the follow-up period (the deterioration deteriorated and stable groups were compared to 280

233 group). The other nine patients with PD had no identify factors predicting speech deterioration after 281
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234 such deterioration (the stable group). Although both STN-DBS. At baseline, the deteriorated group had 282

235 groups showed worsening speech intelligibility (dete- significantly lower SCWT and Digit Span scores 283

236 riorated group, p < 0.001; stable group, p < 0.01) and compared with the stable group (p < 0.05), although 284

237 speech naturalness (deteriorated group, p < 0.001; there were no significant differences in speech and 285
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238 stable group, p < 0.01), the degree was more severe motor function, other cognitive tests, LEDD, age, or 286

239 in the deterioration group (Fig. 1). The deteriorated disease duration between the two groups (Table 4). 287

240 group showed significant worsening from baseline

241 in speech intelligibility at Month 12 or later and in Electrode positions 288

242 speech naturalness at Months 18 and 24. Neither the

243 deteriorated nor the stable group showed significant The electrode positions were available for 24 of 25 289

244 longitudinal changes in motor function during the PD patients. The overall positions of the deteriorated 290

245 follow-up period (UPDRS III; deteriorated group, group tended to locate laterally to STN compared 291

246 p = 0.679; stable group, p = 0.818). with the stable group (Supplementary Figure 1).
 6 Y. Tanaka et al. / Speech Change After STN-DBS in PD

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Fig. 1. Changes in overall severity of auditory perceptual assessment in the on- and off-stimulation conditions. The deteriorated group showed
more severe deterioration in speech intelligibility (A) and naturalness (B) compared with the stable group (C, D). BL, at baseline; M, months
after surgery. *p < 0.05; Significant longitudinal changes within a group in on-stimulation conditions. † p < 0.05; Significant longitudinal
changes within a group in off-stimulation conditions. ‡ p < 0.05, ‡‡ p < 0.01; Significant difference between the on- and off-stimulation
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conditions.

292 DISCUSSION addition, speech intelligibility and naturalness in the 301

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deteriorated group were significantly worse in the 302

293 The present study classified 25 PD patients into on-stimulation condition than in the off-stimulation 303

294 two groups (the deteriorated and stable groups) based condition at Month 6 or later, suggesting that electri- 304

295 on change in overall severity of speech intelligibil- cal stimulation negatively affected speech functions 305

296 ity and naturalness during the two-year follow-up as early as six months after the surgery. Tripoliti et 306

297 after STN-DBS. In the deteriorated group, over- al. [4] reported that significant speech deterioration in 307

298 all speech function significantly worsened at Month PD patients treated with STN-DBS emerged between 308

299 12 or later, whereas motor function remained sta- six months and one year, consistent with our find- 309

300 ble throughout the two-year follow-up period. In ings. Therefore, regular and detailed assessments of 310
 Y. Tanaka et al. / Speech Change After STN-DBS in PD 7

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Fig. 2. The longitudinal change of subscores of auditory-perceptual analysis. The difference in subscores of auditory-perceptual analysis
between the on- and off-conditions during 3 to 24 months after the surgery. M, months after surgery. *p < 0.05 or **p < 0.01, significant
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difference between the on- and off-stimulation conditions in the deteriorated group; † p < 0.05: significant difference between the on- and
off-stimulation conditions in the stable group.

311 speech function are recommended along with careful mouth/jaw and tongue by improving their symp- 337

312 DBS adjustments to maintain the good communica- toms using an acoustic analysis [26]. In addition, 338

tion abilities of PD patients. we also reported that a minority of PD patients

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313 339

314 In the stable group, there were no significant differ- treated with STN-DBS became almost speechless 340

ences in overall speech intelligibility or naturalness due to severe rigidity and akinesia after stimula-
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315 341

316 between the on- and off-stimulation conditions at any tion cessation [8]. Therefore, improvements in speech 342

317 follow-up timepoint. However, the speech function symptoms observed in the present study appear to 343

318 tended to deteriorate with time even when electri- stem from the beneficial effects of the stimulations 344

319 cal stimulation was stopped. This may be related on improving rigidity and akinesia of speech-related 345
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320 to disease progression [19] and/or residual stimula- muscles. Speech functions other than low volume, 346

321 tion effects. In terms of auditory-perceptual analysis, monoloudness, and asthenic voice showed similar 347

322 low volume, monoloudness, and asthenic voice sub- changes between the deteriorated and stable groups. 348

323 scores, the stable group showed better scores in the In particular, imprecise consonants, excess loud- 349
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324 on-stimulation condition than in the off-stimulation ness variation, and strained voice were significantly 350

325 condition, suggesting that STN stimulation had ben- improved due to cessation of stimulation in both 351

326 eficial effects on these items in certain populations. groups, as we previously documented [27, 28]. Taken 352

327 In support of our findings, a previous report also together, these findings suggest that negative effects 353
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328 documented that loudness of PD patients signifi- of STN-DBS on speech function commonly appear 354

329 cantly improved after STN-DBS [4]. These speech in PD patients, but significant beneficial effects of 355

330 aspects are thought to be mainly due to parkin- DBS may be obtained only in a subset of population, 356

331 sonian symptoms, i.e., rigidity and akinesia [13, leading to better prognosis of speech function after 357

332 16]. STN electrical stimulations are well known DBS. 358

333 for their effectiveness in improving rigidity and To clarify factors predicting deterioration in speech 359

334 akinesia symptoms of PD [19–23]. Our previous after STN-DBS, we compared preoperative clini- 360

335 study demonstrated that STN stimulation improves cal backgrounds of patients between the deteriorated 361

336 movement of articulation structures including the and stable groups. We found that SCWT and Digit 362
 8 Y. Tanaka et al. / Speech Change After STN-DBS in PD

Table 4
Clinical backgrounds in deteriorated group and stable group before surgery
Deteriorated group Stable group p value
Number 16 9 –
Sex (female, %) 56.3 66.7 –
Age (y) 66.4 ± 8.8 62.4 ± 8.7 0.152
Disease duration (y) 12.6 ± 4.6 10.3 ± 2.7 0.136
UPDRS III
Total 16.6 ± 6.5 14.3 ± 7.1 0.419

f
Axial score 3.9 ± 2.4 4.1 ± 2.4 0.846
0.9 ± 1.4 1.0 ± 1.0

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Tremor score 0.522
Rigidity score 3.3 ± 1.5 3.3 ± 1.7 0.890
Bradykinesia score 7.7 ± 4.0 5.2 ± 4.3 0.121
UPDRS IV 6.8 ± 2.9 7.2 ± 4.2 0.926
LEDD (mg) 890.2 ± 362.6 951.1 ± 309.4 0.559
S & E on (%) 80.7 ± 12.1 87.8 ± 9.7 0.201
S & E off (%) 68.5 ± 23.4 81.1 ± 15.4 0.403

rP
Speech intelligibility 1.5 ± 0.4 2.2 ± 0.7 0.677
Speech naturalness 1.5 ± 0.6 2.4 ± 0.8 0.637
VHI 38.7 ± 23.9 30.1 ± 20.0 0.382
MMSE total 27.1 ± 2.2 28.4 ± 2.1 0.152
MoCA-J total 22.9 ± 3.9 25.0 ± 3.4 0.229

tho
Verbal fluency
Letter (number/min.) 9.7 ± 4.0 11.3 ± 3.8 0.301
Semantic (number/min.) 14.6 ± 6.5 17.1 ± 4.3 0.229
SCWT
Part1 (sec.) 16.3 ± 4.2 13.7 ± 3.6 0.070
Part2 (sec.) 35.1 ± 14.1 23.4 ± 6.1 0.045
Total errors 3.1 ± 1.9 1.1 ± 1.0 0.016
Au
Digit span forward 9.5 ± 1.6 11.6 ± 2.2 0.019
Digit span backward 5.9 ± 2.1 8.8 ± 2.6 0.019
RCPM total 28.9 ± 5.9 31.5 ± 3.0 0.267
Line orientation 15.7 ± 3.1 16.8 ± 4.3 0.238
Values are mean ± SD; UPDRS-III, Unified Parkinson’s Disease Rating Scale motor examination;
Axial score, items 18-19 and 27–30 of UPDRS III; Tremor score, items 20-21 of UPDRS III; Rigidity
d

score, items 22 of UPDRS III; Bradykinesia score, items 23–26 and 31 of UPDRS III; UPDRS-IV,
Unified Parkinson’s Disease Rating Scale motor complications; LEDD, levodopa equivalent daily
cte

dose; S & E, Schwab and England Independence Scale; VHI, Voice Handicap Index; MMSE, Mini-
Mental State Examination; MoCA-J, Montreal Cognitive Assessment Japanese version; SCWT, The
Stroop Color and Word Test; Part 1, naming task of different color patches; Part 2, task of named
color-word condition; RCPM, Raven’s Colored Progressive Matrices; p value by Mann–Whitney
U tests.
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363 Span Test scores in the deteriorated group were sig- after STN implantation in patients with PD [29, 30]. 379

364 nificantly worse in comparison with those in the Considering the above-mentioned results, we specu- 380

365 stable group. Moreover, the patients in the deterio- late that patients with worse cognitive function might 381
co

366 rated group tended to be older and to have longer be vulnerable to detrimental effects of the stimu- 382

367 disease duration and poorer UPDRS III total and lation on speech function because of less effective 383

368 bradykinesia scores and speech functions compared compensatory mechanisms in the brain with more 384

369 with the stable group. A recent prospective study advanced disease. Furthermore, we found that the 385
Un

370 reported that in 54 PD patients, lower speech intel- electrode positions of the deteriorated group tended 386

371 ligibility before bilateral STN implantation, longer to be laterally to STN compared with the stable 387

372 disease duration, and medially-placed active contacts group, suggesting the current spread to the surround- 388

373 in the left hemisphere were predictive factors for ing structures, such as the corticobulbar fibers [8]. 389

374 deterioration in speech intelligibility following STN- However, we were unable to assess the correlations 390

375 DBS although cognitive function were not analyzed between the electrode positions and speech outcomes 391

376 [5]. Other previous studies have documented these with our method. Future imaging-driven analyses of 392

377 cognitive functions before bilateral STN implanta- brain connectivity or diffusion tensor imaging should 393

378 tion may be predictive factors for motor function allow us to reveal the contributions of the current 394
 Y. Tanaka et al. / Speech Change After STN-DBS in PD 9

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