Effect of bilateral stimulation of the subthalamic nucleus on different speech subsystems in patients with Parkinson's disease

Effect of bilateral stimulation of the subthalamic nucleus

on different speech subsystems in patients with

Parkinson’s disease

MANFRED PUTZER1, WILLIAM J. BARRY1, & JEAN RICHARD

MORINGLANE2

1Institute of Phonetics, University of the Saarland, Saarbrucken, Germany, and 2Department of

Neurosurgery, University of the Saarland, Homburg/Saar, Germany

(Received 23 April 2008; accepted 17 July 2008)

AbstractThe effect of deep brain stimulation on the two speech-production subsystems, articulation andphonation, of nine Parkinsonian patients is examined. Production parameters (stop closure voicing;stop closure, VOT, vowel) in fast syllable-repetitions were defined and measured and quantitative,objective metrics of vocal fold function were obtained during vowel production. Speech material wasrecorded for patients (with and without stimulation) and for a reference group of healthy controlspeakers. With stimulation, precision of the glottal and supraglottal articulation as well as thephonatory function is reduced for some individuals, whereas for other individuals an improvement isobserved. Importantly, the improvement or deterioration is determined not only on the basis of thedirection of parameter change but also on the individuals’ position relative to the healthy control data.This study also notes differences within an individual in the effects of stimulation on the two speechsubsystems. These findings qualify the value of global statements about the effect of neurostimulatoryoperations on Parkinsonian patients. They also underline the importance of careful consideration ofindividual differences in the effect of deep brain stimulation on different speech subsystems.

Keywords: Parkinson’s disease, deep brain stimulation with STN, speech subsystems, instrumental-phonetics analyses, glottal-supraglottal articulation, electroglottographic analyses of voice

Introduction

Speech disturbances in patients with Parkinson’s disease (PD) may include breathy or

rough phonation quality with reduced pitch and loudness variability (e.g. Darley, Aronson,

and Brown, 1969; Aronson, 1990; Brin, Fahn, Blitzer, Ramig, and Stewart, 1992) as well

as reduced articulatory precision (e.g. Wendler, Seidner, Kittel, and Eyshold, 1996;

Ziegler, Vogel, Grone, and Schroter-Morasch, 1998). These symptoms are also considered

undesirable after neurosurgical treatment for certain kinds of tremor (Hartelius and Lillvik,

2003).

Correspondence: Manfred Putzer, PhD, MD, Associate Professor, Institut fur Phonetik, Universitat des Saarlandes, Postfach 15

11 50, D-66041 Saarbrucken, Germany. Tel: +49 681/302-4695. Fax: +49 681/302-4684. E-mail: [email protected]

Clinical Linguistics & Phonetics, December 2008; 22(12): 957–973

ISSN 0269-9206 print/ISSN 1464-5076 online # 2008 Informa UK Ltd

DOI: 10.1080/02699200802394823

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Since 1993, stimulation of the Subthalamic Nucleus (STN) has been used to treat

patients with disabling PD and severe motor fluctuations. It is well known that stimulation

of the STN can improve motor ability in PD patients, but reports of the effect of this

neurosurgical treatment on phonation and articulation have varied in the literature. On the

one hand, an improvement in phonatory function and/or in the force of the articulatory

movements has been noted (e.g. Dromey, Kumar, Lang, and Lozano, 2000; Gentil,

Gracia-Ruiz, Pollak, and Benabid, 2000; Gentil, Chauvin, Pinto, Pollak, and Benabid,

2001; Sataloff, Heuer, Munz, Yoon, and Spiegel, 2002; Pinto, Gentil, Fraix, Benabid, and

Pollak, 2003; Rousseaux, Krystkowiak, Kozlowski, Ozsancak, Blond, and Destee, 2004).

On the other hand, greater disturbance under stimulation has been registered for most

patients (e.g. Putzer, Barry. Fuß, and Moringlane, 2003; Putzer, Barry, Moringlane, Fuß,

Spiegel, Dillmann, and Sittinger, 2003; Pinto, Ozsancak, Tripoliti, Thobios, Limousin-

Dowsey, and Auzou, 2004) or varying effects on speech have been reported (e.g. Wang,

Verhagen Metman, Bakay, Arzbaecher, and Bernard, 2003; Farell, Theodoros, and Ward,

2005; Pinto, Gentil, Krack, Sauleau, Fraix, Benabid, and Pollak, 2005; D’Alatri, Paludetti,

Contarino, Galla, Marchese, and Bentivoglio, 2008). Although the effect of deep brain

stimulation (DBS) of the STN for PD has been reported in many papers, it has rarely been

investigated on all the components of speech at the same time (but see Gentil, Pinto,

Pollak, and Benabid, 2003).

In general, differences between the ON and OFF conditions are not easy to distinguish

perceptually, so instrumental measurements are more suitable; they operate below the

perceptual threshold. Therefore, this study focuses, like other recent studies (e.g. Gentil

et al., 2000; 2001; 2003; Wang et al., 2003), on the instrumentally measurable changes in

phonation and/or articulation.

The study investigates the components of speech represented by the two speech

subsystems, the phonation system and the glottal-supraglottal articulation system.

Synchronous recording of the electroglottographic and the microphone signals allows

analysis of articulatory and phonatory behaviour together, thus throwing more light on the

effect of DBS on speech.

The patients in the study already benefit from DBS stimulation in that their limb motor

ability is improved (e.g. Deuschl, Schade-Brittinger, Krack, Volkmann, Schafer, Botzel,

Daniels, Deutschlander, Dillmann, Eisner, Gruber, Hamel, Herzog, Hilker, Klebe, Kloß,

Koy, Krause, Kupsch, Lorenz, Lorenzl, Mehdorn, Moringlane, Oertel, Pinsker,

Reichmann, Reuß, Schneider, Schnitzler, Steude, Sturm, Timmermann, Tronnier,

Trottenberg, Wojtecki, Wolf, Poewe, and Voges, 2006). It is therefore of interest to know

how their speech motor ability under stimulation can be characterized. The aim of this

study is to compare the performance of the speech subsystems with and without

stimulation.

Procedures

Participants

We studied nine German patients suffering from PD (five males and four females). Patients

underwent bilateral stereotaxic electrode implantation into the STN for chronic high

stimulation (Moringlane, Ceballos-Baumann, and Alesch, 1998). The age of the five male

patients ranged from 52–71 years at the time of speech registration. The four female

patients ranged in age from 42–74 years. Mean (SD) age for patients was 61 (9) years. The

958 M. Putzer et al.

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motor disability of the patients was pre-operative qualitatively assessed by the modified

Hoehn and Yahr scale (Hoehn and Yahr, 1967). This scale differentiates in steps from level

0 to level 5 (with 0 as normal and 5 as very severe).

Table I gives an overview of patient data (sex, age, Hoehn and Yahr levels).

The nine patients were selected consecutively. They were not selected because of any

conspicuous phonation and/or articulation impairment. Patients were being treated for

tremor, rigor, on/off fluctuation, and/or L-dopa induced dyskinesia. Before neurosurgical

treatment, symptoms of dysarthria in the form of supraglottal articulation disturbances had

sometimes been apparent. Perceptual judgements of voice quality using the ‘Roughness-

Breathiness-Hoarseness scores’ (RBH scores, e.g. Nawka and Anders, 1996; Putzer and

Barry, 2004) did not reveal pathological results. However, since limb control, not speech

quality, was the reason for undertaking DBS, there had been no pre-operative dysarthria

quality classification. No patient had been under voice therapy.

The patients underwent stereotactic surgery, performed with the Riechert/Mundinger

system for the implantation of quadripolar stimulation electrodes (model 3387 or 3389,

Medtronic GmbH, Dusseldorf, Germany) into the STN on both sides. Comprehensive details

of the surgical technique have been published elsewhere (Moringlane et al., 1998; Moringlane,

Fuß, and Becher, 2005; Pinto, Le Bas, Castana, Krack, Pollak, and Benabid, 2007).

The implant stimulation parameters were those providing the best control of the motor

disability symptoms with no side effects. The lowest possible dose of dopamine was

maintained. At the time of the recordings the patients had all received satisfactory to

optimal adjustment of their medication with regard to motor control. They were all in the

same experimental condition concerning their drug status, namely midway in their daily

drug-taking cycle.

To assure a stable baseline reference, 20 healthy subjects (10 males and 10 females) with

no known speaking or hearing problems served as control subjects. Healthy subjects ranged

in age from 42–74 years.

Speech material and recording procedure

Subjects were required to produce syllable-repetitions consisting of the plosive-vowel-

combination /pa/, /ta/, /ka/ as fast as possible on a single breath (at least 20 times). These

syllable-repetitions, well known as diadochokinesis, are a traditional component of motor

speech assessment for speakers with dysarthria (e.g. Ackermann, Hertrich, and Hehr, 1995;

Tjaden and Watling, 2003). Voice and speech recording were carried out in a soundproof

room at the Neurosurgery Clinic of the University of the Saarland in Homburg/Saar and at

Table I. Patients’ sex, age, and Hoehn and Yahr levels.

Patients Sex Age Hoehn and Yahr levels

1 male 52 2 to 3

2 male 58 3 to 4

3 male 60 2 to 2.5

4 male 71 2

5 male 69 2

6 female 74 3

7 female 42 2

8 female 62 4

9 female 61 4

Bilateral stimulation in Parkinson’s disease 959

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the Institute of Phonetics of the University of the Saarland in Saarbrucken, respectively. All

recordings of the patients’ speech production were carried out with the stimulation ON and

OFF, observing a pause of at least 30 minutes before recording after switching to either of

the two conditions.

Electroglottogram (EGG) and microphone signals were recorded simultaneously. Both

signals were fed directly into a Computerised Speech Lab (CSL) station (model 4300B) at

a 50-kHz sampling rate, giving a temporal resolution of 0.02 ms with 16-bit amplitude

resolution. The microphone signal was recorded using a headset condenser microphone

(NEM 192.15, Beyerdynamic, Heilbronn, Germany) which fits comfortably over the ears

and behind the head and allows one to keep the distance to the lips constant during speech,

independent of head movements (Titze and Winholts, 1993). The EGG-signal was

acquired with a Portable Laryngograph from Laryngograph Ltd.

Experimental procedure and measures

Ten syllables were selected from the middle of the /pa/, /ta/, and /ka/ sequences to obtain

representative syllables avoiding any irregularities that may be associated with ‘phrasal’

onset and offset phenomena. The same criterion was applied for selecting the syllables in

the OFF and ON conditions. By using synchronously recorded glottal and microphone

signals, the study offers a basis for more stringent comparison than previous studies (e.g.

Gentil et al., 2001; 2003; Putzer, Barry, Fuß, et al., 2003; Putzer, Barry, Moringlane, et al.,

2003) where articulatory and/or phonatory behaviour were analysed using separately

Figure 1. Schematic diagram of phonation and articulation gestures in plosive-vowel production.


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produced speech material (e.g. sustained vowels for phonation analysis and nonsense words

for articulation analysis).

Figure 1 shows the schematic articulation pattern (glottal and oral gestures) of a typical

plosive-vowel production in relation to the microphone signal (oscillogram) as produced by a

healthy subject. This schematic articulation pattern doesn’t represent any aspect of the

phonatory quality. It simply illustrates the glottal and oral gestures during the productions of

plosive-vowel-combination which can be derived from examination of the acoustic signal.

Figure 2 shows the spectrographic display of the relevant production parts of the syllable

described below. The phonation and articulation gestures are identified in the time-

pressure waveform and the spectrogram. From this display, all the parameters used in the

study can be derived.

Figure 2 shows that the oral closure is synchronized with the glottal opening. There is no

voicing during the closure. After the release of the closure and the start of the glottal

adduction gesture a well defined aspiration phase (VOT) and a normal duration of the

following vowel appear.

To define the glottal–supraglottal articulation behaviour, the acoustic signal was

segmented with relation to the spectrogram and to the EGG signal.

In contrast to this normal pattern of synchronized oral and glottal articulation — glottal

abduction synchronized with the oral closure, and glottal adduction occurring 50–60 ms

after oral release to allow sufficient aspiration — the following articulatory disturbances are

hypothetically possible:

Figure 2. Plosive-vowel production components as reflected in the acoustic signal. Top section: time-pressure

waveform (microphone signal); Bottom section: time-frequency representation (spectrogram).


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(1) an oral gestures with (a) insufficient closure or (b) insufficient opening movement of

jaw, lips and tongue.

(2) a glottal gestures with (a) insufficient adduction or (b) insufficient abduction of the

vocal folds.

(3) desynchronization of the oral and glottal gestural cycles (interarticulatory

desynchronization) is also a theoretical possibility, but it was not observed.

In the case of (1), closure durations either become (a) shorter and incomplete (resulting in

friction and longer vowels) or (b) overlong (with shortened vowels). With (2), phonation is

either (a) shortened and breathy or (b) pressed with a tendency for voicing to continue

throughout the oral closure.

In this study, only disturbances of the oral gestures with insufficient closure (1a) and

insufficient abduction of the vocal folds (2b) are observed in patients.

The following duration-related variables were measured: (1) stop-closure voicing (closv_,

measured from vowel formant (F1) offset to the cessation of periodicity). (2) the stop

closure (clos_, defined as the period from vowel formant (F1) offset to the stop burst). (3)

the VOT (Voice Onset Time; VOT_, defined as the time from the stop burst to the start of

vocal fold vibrations). (4) the following vowel (vowel_, defined as the time from the start of

vocal fold vibrations to the vowel formant (F1) offset). These variables are one group of

production parameters (see Figure 2).

Two further articulation parameters were also determined: (1) the duration of all the

voiced segments in the syllable-cycle (voicing-syll_, defined as combined values of closv_

and vowel_ in the syllable-cycle) (see Figure 2). (2) the duration of the whole syllable-cycle

(syll-cycl_, defined as the time from the start of one plosive closure (i.e. the formant (F1)

offset of the vowel /a/) to the start of the next) (see Figure 2). Syll-cycl_ indicates the overall

speed of ‘fast’ syllable repetition. Voicing-syll_ reflects the absolute time spent phonating

during the syllable cycle. The vowel_ and closv_ variables give the separate voicing

components of voicing-syll_, namely during the vowel and during the stop closure (voice

perseveration). VOT_ and the part of clos_ without voicing reflect the duration of the

voiceless phase. From the total number of syllables produced by each speaker for each place

of articulation, 10 syllable-cycles of the /pa/, ta/, and /ka/ syllables are used for the statistical

analysis. To investigate the articulatory control, three aspects are considered: (1) the

voicing parts in the syllable-cycle reflecting the glottal adduction and abduction gestures;

(2) the oral closing and opening gestures for the consonant and vowel production; and (3)

the timing of the glottal adduction and abduction gestures relative to the oral gestures.

Figure 3. Phases and signal parts of the EGG-waveform.


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For objective metrics of vocal fold function, the EGG signal of the vowel segments from

10 syllable-repetitions (taken from each of the /pa/-, /ta/-, and ka/-syllable sequences) were

used. The data were averaged over the 10 repetitions.

The phonation behaviour was determined by using the analysis of the EGG-signal. This

signal was analysed using the EGG program developed by Marasek (1997). Figure 3 shows

the model of the EGG-waveform with annotated phases of the vocal fold cycle.

The seven most important parameters of the programme used in this study quantify the

following aspects of the EGG-curve: (1) Open quotient (parameter OQ); (2) Start of the

closing phase (parameter SCV); (3) Skewness of start of the closing phase (parameter

SCA); (4) End of the closing phase (parameter ECV); (5) Contact phase (parameter CV);

(6) Skewness of the whole closing phase (parameter CLA); and (7) Skewness of the whole

opening phase (parameter OPA). Their importance in the differentiation of voice

production patterns has been documented in a number of recent studies (Putzer and

Marasek, 2000; Putzer, Erriquez, Barry, and Just, 2001; Putzer, Barry, Moringlane, et al.,

2003; Moringlane, Putzer, and Barry, 2004; Moringlane, Spiegel, Fuß, Dillmann, Putzer,

and Sittinger, 2004; Putzer, Barry, and Moringlane, 2007). Table II gives an overview of

the analysis approach, the above mentioned parameters and their calculation which can be

derived from the annotated phases in of the vocal fold cycle (see Figure 3).

More details of the EGG analysis and of further parameters not used in this study have

been published elsewhere (Marasek, 1997; Putzer and Marasek, 2000).

The measurements of the acoustic and electroglottographic signal were used to evaluate

the effect of deep brain stimulation on two subsystems of speech production in patients

with Parkinson’s disease, i.e. glottal–supraglottal articulation on the one hand and

phonation on the other.

The phonatory and articulatory behaviour of the patients was analysed at group and at

individual level with and without stimulation. The patients’ group and individual behaviour

was also compared with healthy speakers’ articulation and phonation behaviour (10 male

and 10 female speakers).

Statistical procedures

Data analysis was performed using SPSS version 15 for all tests.

First, to normalize for the gender differences, the parameter-values of all measurements

from the individual patients and from the appropriate controls were expressed as z-scores.

In this way, the experimental subjects could be pooled across gender for the statistical

analyses. The z-scores serve as the data base of all statistical procedures.

Table II. Analysis of the EGG-signal (analysis approach, parameters, and parameter-calculation).

Analysis-approach Parameters Parameter–calculation

Open quotient OQ tf 2 tc/T06100 (stretches d + e + f)

Phases of closure SCV te to tf’ (stretch f)

SCA te to tf’ (stretch f)

ECV t0 to ta (stretch a)

CV ta to tb (stretch b)

CLA te to ta (stretches f + a)

Phase of opening OPA tb to td (stretches c + d)


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Secondly, for each of the parameters as a dependent variable, an analysis of variance

ANOVA (with repeated measures) was carried out for the effects of condition with and

without stimulation.

Thirdly, to compare the patients’ data (with and without stimulation) with the healthy

control data, an ANOVA between ON and controls and OFF and controls was carried out.

Fourthly, in order to look at the individual articulation and phonation behaviour of the

nine patients, an ANOVA (with repeated measurers) for the effects of condition with and

without stimulation as well as an ANOVA between ON and controls and OFF and controls

was carried out using their individual data.

Results

Motor disability

The tremor, rigor, on/off fluctuation, and/or L-dopa-induced dyskinasia of all the patients

improved as a result of the STN nucleus stimulation. This improvement is shown,

comparing pre-operative (without stimulation) with post-operative (with stimulation)

UPDRS-scores. These scores are given in Table III.

The articulatory and phonatory behaviour with and without stimulation will be described

in detail and then related to the healthy subjects’ behaviour in the following sections.

Group behaviour for patients and healthy controls

Articulation. All z-scores (means and standard deviation) of the statistically relevant

articulatory parameters are given in Table IV. Scores for each of the three plosives (for the

patients in the two conditions and for the control group) are shown.

For five parameters, statistically significant differences between the two conditions are

apparent (see parameters in bold in Table IV). These differences indicate the potentially

negative effect of the neurostimulation on articulation. The effect can be summarized as

follows: First, voicing increases in the /ka/-syllable-cycles (longer vowel duration and

voicing perseveration in the oral closure phase). The greater duration of voicing in the stop

closure in the /k/-syllable-cycles together with a considerably shorter VOT in comparison to

the VOT without stimulation supports the assumption of insufficient vocal fold abduction

(rather then a temporal shift of an otherwise normal abduction-adduction cycle). This shift

Table III. Patients’ sex, age, and UPDRS-scores.

Patients Sex

UPDRS-scores

pre-operative post-operative

1 male 46 14

2 male 61 20

3 male 40 14

4 male 29 17

5 male 35 23

6 female 50 24

7 female 37 27

8 female 68 20

9 female 66 25


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for the two parameters in the different production conditions is illustrated in Figure 4. The

net result is an overall increase in the amount of voicing under stimulation.

Second, at the supra-glottal level, a significantly shorter closure duration is found for /t/

under stimulation. In some cases there is no complete closure, and the result is a fricative

rather than a stop. This production behaviour also co-occurs with an extremely short or

without any measurable VOT. An example of this behaviour is illustrated in Figure 5.

By comparing the patients’ data with the healthy control data, we note that for 13

parameters shown in Table IV the values for both the ON and OFF condition are

Table IV. Z-scores (mean and standard deviation) for the production parameters for patients with and without

stimulation and for the control group.

Production

aspects Parameters (1) With stimulation (2) Without stimulation (3) Contol group

Glottal gesture voicing-syll_p (1,2/3) 1.40 (SD 2.25) 1.05 (SD 1.31) 0.25 (SD 1.00)

voicing-syll_t (1,2/3) 3.07 (SD 2.43) 2.77 (SD 2.07) 20.31 (SD 2.28)

voicing-syll_k (1/2/3) 4.73 (SD 4.20) 2.96 (SD 1.89) 20.11 (SD 0.98)

Oral gesture syll-cycl_p (1,2/3) 1.12 (SD 2.28) 1.39 (SD 1.72) 0.06 (SD 0.94)

syll-cycl_t (1/2/3) 1.03 (SD 1.85) 2.17 (SD 2.23) 20.02 (SD 1.02)

syll-cycl_k (1,2/3) 2.34 (SD 3.82) 2.52 (SD 2.26) 20.04 (SD 1.02)

clos_p (1/2/3) 1.11 (SD 1.54) 1.64 (SD 0.96) 20.71 (SD 0.89)

clos_t (1/2/3) 20.14 (SD 1.72) 1.26 (SD 1.56) 0.37 (SD 0.68)

vowel_t (1,2/3) 1.99 (SD 2.13) 1.97 (SD 1.66) 20.24 (SD 0.88)

vowel_k (1,2/3) 3.19 (SD 3.39) 2.36 (SD 1.74) 20.10 (SD 1.02)

Oral-glottal

relationship

clos-v_p (1,2/3) 2.48 (SD 2.90) 2.24 (SD 2.00) 20.29 (SD 0.86)

clos-v_t (1,2/3) 3.31 (SD 3.75) 2.70 (SD 2.87) 0.31 (SD 1.07)

clos-v_k (1/2/3) 4.07 (SD 7.31) 2.11 (SD 1.81) 20.02 (SD 0.95)

VOT_t (1,2/3) 20.59 (SD 0.98) 20.41 (SD 1.28) 0.76 (SD 0.54)

Parameters in bold 5 Significant differences between the two conditions and in comparison to the control group;

p,.001. 1,2/3, or 2/3 5 Significant differences in comparison to the control group; p,.001.

Figure 4. Stop-closure voicing and VOT (Voice Onset Time) under the two experimental conditions expressed as

z-scores (/k/-syllables; p,.001).


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significantly different from the control data. These differences are indicated in Table IV by

the following symbols: (1,2/3). Many of these differences are the direct consequence of

overall slower articulation rate (cf. syll-cycle_values).

The following tendencies are also observed: First, the overall voicing duration (voicing-

syll_) in the syllable cycles (/p/-, /t/-, and /k/-syllables) is greater under stimulation.

Secondly, the whole syllable cycles (syll-cycl_), indicating the overall speed of syllable

repetition, are shorter under stimulation.

All observations clearly show intra-articulatory timing deficits in the glottal abduction

and adductions pattern. In addition, a reduction of the supraglottal closure is found.

Phonation. For patients the ON and OFF condition cannot be statistically differentiated.

However, it is shown that the change in phonation behaviour between the two conditions

varies across patients. The parameter values show on the one hand a reduced adduction

gesture (increased open phase values for OQ and OPA) and on the other hand an increased

adduction gesture (decreased closure phase values for SCV, ECV, and CV) under

stimulation in comparison to the values without stimulation. This points to improvement as

well as impairment under stimulation so that a uniform tendency of phonatory behaviour

cannot be formulated for this condition (see Table V).

However, when the phonation behaviour of the patients is compared to the control

group, it is easier to interpret. Table V shows significant differences both under stimulation

and without stimulation in relation to the control group data.

The negative difference for the EGG-parameters SCV (start of the closing phase), ECV

(end of the closing phase), and CV (contact phase) and the positive difference for of the

Figure 5. /t/ production with friction in the closure phase.


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EGG-parameter OQ (open quotien) and OPA (skewness of the whole opening phase)

under the two conditions reflect a laxer course of the whole closing–opening cycle for

patients in comparison to the healthy controls.

To sum up the results of the group analysis, it is shown that in comparison to the control

group a reduced precision of articulation exists under both conditions with some signs of

increased impairment under stimulation. Phonation behaviour is not reflected by uniform

tendencies for the two conditions. Therefore, it is not possible to give a global statement

about the effect of deep brain stimulation on this speech subsystem. The necessity for

individually orientated evaluation is apparent.

Results for individual patients

Articulation. In five of nine patients the closure phase, above all of the plosive /t/, is replaced

by friction under stimulation, indicating a very weak closing gesture in these patients

(patients M1, 4, 5; F6, 7). It co-occurs with an extremely short VOT or without any

measurable VOT (see Figure 5). When friction replaces closure for all repetitions of /ta/ (or

/ka/) in the sequence, VOT becomes 0. However, a weak apical (or dorsal) closing gesture

Table V. Z-scores (mean and standard deviation) for the voice parameters relative to the appropriate control

group (f, m) for patients with and without stimulation.

Analysis-

methods Analysis-approach Parameters (1) With stimulation

(2 ) Without

stimulation (3) Controlgroup

EGG-

analysis

Open quotient OQ (1,2/3)** 0.39 (SD 1.02) 0.25 (SD 0.85) 0.00 (SD 1.00)

Phases of closure SCV (1,2/3)*** 20.37 (SD 1.44) 20.49 (SD 0.92) 0.00 (SD 1.00)

ECV (1,2/3)** 20.23 (SD 1.22) 20.42 (SD 1.11) 0.00 (SD 1.00)

CV (1,2/3)*** 20.36 (SD 1.40) 20.51 (SD 1.23) 0.00 (SD 1.00)

Phase of opening OPA (1,2/3)** 0.84 (SD 2.73) 0.68 (SD 0.97) 0.00 (SD 1.00)

1,2/3 5 Significant differences in comparison to the control group; *** p,.001; ** p,.01.

Figure 6. Stop-closure and VOT (Voice Onset Time) for one patient under the two conditions expressed as z-

scores (/t/-syllables; p,.001).


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does not necessarily result in lack of closure for all repetitions. An occasional brief closure

leads to a short VOT phase on release, giving a very short average VOT over the 10

repetitions. An example for this production behaviour is given in Figure 6.

Also, longer vowel duration in the /ta/- and/or in the /ka/-syllables is found as an

accompanying property of the short or fricativized stop closure for three of these five

patients (patients M1; F6, 7) under stimulation. The comparison with the healthy control

data underlines these findings (see Table IV).

In contrast to these results, an improvement in articulatory function under stimulation is

found for the other four patients (patients M2, 3; F8, 9). An example of this improvement

produced by one of the speakers is the reduction in vowel duration, a shift towards values

for the healthy control data under stimulation. This is shown in Figure 7.

In summary, reduced precision of the tongue movements and a longer vowel duration is

found for five patients, whereas for four patients an improvement of articulation behaviour

under stimulation can be attested.

Phonation. Phonation behaviour with and without stimulation is not uniform across

individuals for either male or female patients. The z-scores of the appropriate control group

give a reference baseline for the interpretation of the individually different development

under the two conditions.

On the one hand, an improvement under stimulation is found for one male patient and two

female patients (patients M2; F6, 9). In Figure 8 an example is given for this improvement.

The value of the EGG-parameter OQ (open quotient) is lower. This reflects regular

adduction behaviour of the vocal folds.

Figure 7. Differences in vowel duration for one patient with and without stimulation in comparison to the control

groups’ vowel duration expressed as z-scores (/ka/-syllables; p,.001).


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On the other hand, an impairment is observed for two male patients (3, 5) and one

female patient (8). Now, a higher value of the EGG-parameter OQ (open quotient) reflects

less adduction of the vocal folds (see Figure 9).

For three patients (M1; M5, and F7) no clear tendencies are observed under the two

conditions.

In comparison to the healthy control data, different patterns of individual development

under the two conditions are observed. Therefore, a global statement about the effect of

deep brain stimulation on phonatory functions cannot be given.

Figure 8. Parameter values for one patient with and without stimulation expressed as z-scores (Parameter OQ 5

open quotient; p,.001).

Figure 9. Parameter values for one patient with and without stimulation expressed as z-scores (Parameter OQ 5

open quotient; p,.001).


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Discussion

Measurements of the acoustic and electroglottographic signal were used to evaluate the

effect of deep brain stimulation on two subsystems of speech production in patients with

Parkinson’s disease. The subsystems are the glottal–supraglottal articulation-system on the

one hand and the phonation-system on the other.

A comparison of the group and individual patients’ data with data from healthy controls

provides a better basis to judge deviations of articulation and phonation performance under

the given circumstances of speech production.

First of all, the group behaviour on articulation for patients with and without stimulation

can be characterized by five parameters showing statistically significant differences between

the two conditions (see parameters in bold in Table IV). These differences indicate the

potentially negative effect of the neurostimulation on articulation. It can be shown that the

duration of all the voiced segments in the three syllable cycles (significantly different in the /k/-

syllable-cycle) is greater under stimulation for all patients. This comprises both a longer vowel

duration and the tendency for voicing to continue in the oral closure phase (see Table IV)

together with a considerably shorter VOT in comparison to the VOT without stimulation.

The former suggests altered relations of oral closure and opening in the syllabic cycle while the

latter supports the assumption of insufficient vocal fold abduction (rather then a temporal shift

of an otherwise normal abduction-adduction cycle).

The whole syllable cycles, indicating the overall speed of syllable repetition, are shorter

under stimulation (significantly different in the /t/-syllable-cycle). Therefore, we cannot

attribute the longer voiced segments in the syllable to a slower articulation rate. Finally, the

duration of stop closures is significantly shorter for the /p/- and /t/-syllables. Thus, the

manner of oral closing and opening for the plosive contributes to the shorter duration of the

whole syllable cycle under stimulation.

There was no obvious connection found between impairment or improvement in

articulatory or phonatory functions and pre-operative Hoehn and Yahr levels. Comparing

the pre- and post-operative UPDRS-scales levels with this impairment or improvement in

speech functions, a confirmation of the hypothesis is given that speech motor behaviour is

not necessarily improved in the same way as limb motor behaviour (Ziegler et al., 1998; see

Table III). In addition, these findings underline the approach of the study, which is to look

at the effect of DBS under the two conditions without reference to the pre-operative status.

This approach is geared towards the patients’ interests. Patients are not so interested in

knowing how their speech would be without surgical treatment. They were mainly being

treated for tremor, rigor, on/off fluctuation, and/or L-dopa induced hyperkinesias. An

improvement in these problems helps them to carry on their daily lives. Therefore, they are

more interested in the current status of their speech capacity as an additional effect of DBS.

Secondly, we show the importance of careful consideration of individual differences in the

effect of deep brain stimulation on different speech subsystems rather than generalizing

from the evaluation at group level. There is clear evidence of different articulation

behaviour for patients under stimulation, related to different parts of the syllable-

production process.

In five of the nine patients the closure phases of the plosives (above all of the plosive /t/) are

replaced by friction under stimulation, documenting the lack of a true closure phase. The

replacement by friction, in particular in /t/-syllables, can be explained as follows: For apical

closure movements, a more differentiated and finer co-ordination of the tongue muscles is

needed to combine the coronal closure with the dorsal adjustments for the accompanying

vowel. For /k/ syllables the dorsum alone is needed, and the dorsal /k/-closure adjusts to


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whatever vowel accompanies it (only /a/ in the present study). For articulation of the /p/-

syllables the labial closure gesture is independent of the movements of the tongue. The tongue

remains in the vowel position during the fast articulation gestures. Furthermore, the motor

activity of the lips and jaw of patients suffering from dysarthria seems not to be disturbed to the

same extent as the activity of the tongue (e.g. Hartelius and Lillvik, 2003).

Additionally, in many cases voicing perseveration in the stop closure of the /ta/- and /ka/-

syllable-cycles is found without intervocalic friction. It occurs together with a shorter VOT

duration. Together, these indicate the impairment of the abduction gesture under

stimulation, whether or not there is an accompanying weakness in the supra-glottal closing

gesture.

By comparing the phonation data of the patients with the control groups’ data, different

effects of stimulation are apparent. Therefore, a global statement of the effect of

neurostimulatory operations on phonation cannot be given. Rather as with articulation,

variation in phonatory behaviour across patients must be expected. Finally, improvement

or deterioration in one subsystem does not imply the same direction of change in the other

subsystem. The need for, but also the possibility of an individually orientated evaluation of

this aspect of speech production is apparent.

In conclusion, high-frequency electrical impulses to the STN in patients with

Parkinson’s disease influence speech subsystems differently. Therefore, a global statement

of the effect of neurosurgical treatment cannot be given (Pinto et al., 2005). The potential

underlying neural mechanism of DBS is still not fully understood (e.g. Breit, Schulz, and

Benabid, 2004; Volkmann and Kupsch, 2004; Benabid, Wallance, Mitrofanis, Xia, Piallat,

Fraix, Batir, Krack, Pollak, and Berger, 2005). However, the main hypotheses on high-

frequency stimulation according to Breit et al. (2004) are: (1) depolarization blocking of

neural transmission through inactivation of voltage dependent ion-channels, (2) jamming

of information by imposing an efferent stimulation-driven high-frequency pattern, (3)

synaptic inhibition by stimulation of inhibitory afferents to the target nucleus, and (4)

synaptic failure by stimulation-induced neurotransmitter depletion. On the basis of these

hypotheses, it is not possible at the moment to provide well-funded physiological reasons

for the described differences in articulatory and phonatory behaviour with and without

stimulation.

The findings reported in the study have also been noted in two previous studies (Putzer,

Barry, Fuß, et al., 2003; Putzer, Barry, Moringlane, et al., 2003), but the two subsystems of

speech (phonation system and glottal–supraglottal articulation system) were investigated

separately and in a smaller number of patients.

The present study confirms the findings in a larger number of patients on the basis of

synchronically registered speech material which is analysed by using different methods of

instrumental-phonetic evaluation. However, further investigations, based on a much larger

sample of patients suffering from Parkinson’s disease with more and less severe dysarthria

are necessary to further clarify the effect of deep brain stimulation on speech performance.

Acknowledgements

This research was supported by the Deutsche Forschungsgemeinschaft, Bonn, BA 737/9-4.

Members of the Neuromodulation Study Group, Homburg/Saar, Germany involved: PD

Dr U. Dillmann, Dr G. Fuß, Dr S. Merkelbach, Dr J. Spiegel, J. Wilhelm, Department of

Neurology, University of the Saarland, Homburg/Saar; Dr Helmut Sittinger, Department

of Psychiatry, University of the Saarland, Homburg/Saar.


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Declaration of interest: The authors report no conflicts of interest. The authors alone are

responsible for the content and writing of the paper.

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Documents

Effect of bilateral stimulation of the subthalamic nucleus on different speech subsystems in patients with Parkinson's disease