Continuous theta burst stimulation over left supplementary motor area facilitates auditory-vocal integration in individuals with Parkinson's disease.

Accumulating evidence suggests that impairment in auditory-vocal integration characterized by abnormally enhanced vocal compensations for auditory feedback perturbations contributes to hypokinetic dysarthria in Parkinson's disease (PD). However, treatment of this abnormality remains a challenge. The present study examined whether abnormalities in auditory-motor integration for vocal pitch regulation in PD can be modulated by neuronavigated continuous theta burst stimulation (c-TBS) over the left supplementary motor area (SMA). After receiving active or sham c-TBS over left SMA, 16 individuals with PD vocalized vowel sounds while hearing their own voice unexpectedly pitch-shifted two semitones upward or downward. A group of pairwise-matched healthy participants was recruited as controls. Their vocal responses and event-related potentials (ERPs) were measured and compared across the conditions. The results showed that applying c-TBS over left SMA led to smaller vocal responses paralleled by smaller P1 and P2 responses and larger N1 responses in individuals with PD. Major neural generators of reduced P2 responses were located in the right inferior and medial frontal gyrus, pre- and post-central gyrus, and insula. Moreover, suppressed vocal compensations were predicted by reduced P2 amplitudes and enhanced N1 amplitudes. Notably, abnormally enhanced vocal and P2 responses in individuals with PD were normalized by c-TBS over left SMA when compared to healthy controls. Our results provide the first causal evidence that abnormalities in auditory-motor control of vocal pitch production in PD can be modulated by c-TBS over left SMA, suggesting that it may be a promising non-invasive treatment for speech motor disorders in PD.

Neurobehavioral Effects of LSVT® LOUD on Auditory-Vocal Integration in Parkinson's Disease: A Preliminary Study.

Individuals with Parkinson's disease (PD) are impaired in auditory-vocal integration, characterized by abnormal compensatory responses to auditory feedback errors during self-monitoring of vocal production. The present study examined whether auditory feedback control of vocal pitch production in PD can benefit from Lee Silverman voice treatment (LSVT® LOUD), a high effort, intensive speech treatment for hypokinetic dysarthria in PD. Before and immediately after LSVT LOUD, 12 individuals with PD were instructed to produce sustained vowel sounds while hearing their voice unexpectedly pitch-shifted by -200 cents. Their vocal responses and event-related potentials (ERPs) to pitch perturbations were measured to assess the treatment outcomes. A group of 12 healthy controls were one-to-one pair matched by age, sex, and language. Individuals with PD exhibited abnormally enhanced vocal and ERP P2 responses to pitch perturbations relative to healthy controls. Successful treatment with LSVT LOUD, however, led to significantly smaller and faster vocal compensations that were accompanied by significantly larger P2 responses. Moreover, improved vocal loudness during passage reading was significantly correlated with reduced vocal compensations for pitch perturbations. These preliminary findings provide the first neurobehavioral evidence for beneficial effects of LSVT LOUD on impaired auditory-vocal integration associated with PD, which may be related to improved laryngeal motor functions and a top-down modulation of the speech motor network by LSVT LOUD.

External cueing facilitates auditory-motor integration for speech control in individuals with Parkinson's disease.

Instructing individuals with Parkinson's disease (PD) to speak loudly and clearly with external cues leads to improvements of their speech in loudness, pitch, and articulatory movement, but the underlying neural mechanisms are largely unknown. The present event-related potential study investigated whether and how external cueing can facilitate auditory-motor control of speech production in PD. Individuals with PD and healthy controls produced sustained vowels with internal and external auditory cues while hearing their voice pitch-shifted -200 cents. Individuals with PD produced significantly larger vocal compensations than healthy controls in the internally cued condition and exhibited a significant decrease in the magnitudes of vocal compensations with external cueing. Moreover, individuals with PD produced significantly smaller N1 responses and larger P2 responses in the externally versus internally cued condition and exhibited a significant correlation between decreased vocal compensations and increased P2 amplitudes after external cueing. These findings provide the first neurobehavioral evidence that external auditory cueing can compensate for impaired auditory-motor processing of vocal feedback errors associated with PD in a top-down manner.

The impact of parkinson's disease on the cortical mechanisms that support auditory-motor integration for voice control.

Several studies have shown sensorimotor deficits in speech processing in individuals with idiopathic Parkinson's disease (PD). The underlying neural mechanisms, however, remain poorly understood. In the present event-related potential (ERP) study, 18 individuals with PD and 18 healthy controls were exposed to frequency-altered feedback (FAF) while producing a sustained vowel and listening to the playback of their own voice. Behavioral results revealed that individuals with PD produced significantly larger vocal compensation for pitch feedback errors than healthy controls, and exhibited a significant positive correlation between the magnitude of their vocal responses and the variability of their unaltered vocal pitch. At the cortical level, larger P2 responses were observed for individuals with PD compared with healthy controls during active vocalization due to left-lateralized enhanced activity in the superior and inferior frontal gyrus, premotor cortex, inferior parietal lobule, and superior temporal gyrus. These two groups did not differ, however, when they passively listened to the playback of their own voice. Individuals with PD also exhibited larger P2 responses during active vocalization when compared with passive listening due to enhanced activity in the inferior frontal gyrus, precental gyrus, postcentral gyrus, and middle temporal gyrus. This enhancement effect, however, was not observed for healthy controls. These findings provide neural evidence for the abnormal auditory-vocal integration for voice control in individuals with PD, which may be caused by their deficits in the detection and correction of errors in voice auditory feedback. Hum Brain Mapp 37:4248-4261, 2016. © 2016 Wiley Periodicals, Inc.

Sensorimotor control of vocal pitch production in Parkinson's disease.

The present study was designed to investigate the sensorimotor control of voice fundamental frequency (F0) in individuals with Parkinson's diseases (PD). Fifteen Cantonese individuals with PD, and fifteen age- and sex-matched healthy Cantonese individuals participated in the experiment. Participants were asked to vocalize a vowel sound while hearing their voice auditory feedback unexpectedly pitch-shifted upwards or downwards through headphones. The size of pitch shifts varied from 50, 100, to 200 cents. One novel averaging method was used to categorize the individual trials such that only those trials that opposed the perturbation direction were averaged to generate an overall response. The results showed that Cantonese individuals with PD produced significantly larger magnitudes of vocal compensation for pitch perturbations than healthy participants. Both groups showed systematic changes in compensation magnitude as a function of perturbation size and direction: larger perturbation size or upward direction elicited greater compensation magnitude. Moreover, pitch variability indexed by the standard deviations of the baseline F0 was significantly correlated with the magnitude of vocal compensation in individuals with PD, whereas this correlation failed to reach significance for healthy participants. This study presents the first data demonstrating the abnormal processing of auditory feedback in the sensorimotor control of voice F0 for Cantonese individuals with PD. It is suggested that the abnormal sensorimotor integration of voice F0 control in PD may be caused by the increased weighting of auditory feedback control resulting from dysfunction of feedforward control and somatosensory feedback caused by the impairment of the basal ganglia.

Developmental sex-specific change in auditory-vocal integration: ERP evidence in children.

OBJECTIVE: The present event-related potential (ERP) study examined the developmental mechanisms of auditory-vocal integration in normally developing children. Neurophysiological responses to altered auditory feedback were recorded to determine whether they are affected by age and sex. METHOD: Forty-two children were pairwise matched for sex and were divided into a group of younger (10-12years) and a group of older (13-15years) children. Twenty healthy young adults (20-25years) also participated in the experiment. ERPs were recorded from the participants who heard their voice pitch feedback unexpectedly shifted -50, -100, or -200 cents during sustained vocalization. RESULTS: P1 amplitudes became smaller as subjects increased in age from childhood to adulthood, and males produced larger N1 amplitudes than females. An age-related decrease in the P1-N1 latencies was also found: latencies were shorter in young adults than in school children. A complex age-by-sex interaction was found for the P2 component, where an age-related increase in P2 amplitudes existed only in girls, and boys produced longer P2 latencies than girls but only in the older children. CONCLUSIONS: These findings demonstrate that neurophysiological responses to pitch errors in voice auditory feedback depend on age and sex in normally developing children. SIGNIFICANCE: The present study provides evidence that there is a sex-specific development of the neural mechanisms involved in auditory-vocal integration.

Vocal responses to perturbations in voice auditory feedback in individuals with Parkinson's disease.

BACKGROUND: One of the most common symptoms of speech deficits in individuals with Parkinson's disease (PD) is significantly reduced vocal loudness and pitch range. The present study investigated whether abnormal vocalizations in individuals with PD are related to sensory processing of voice auditory feedback. Perturbations in loudness or pitch of voice auditory feedback are known to elicit short latency, compensatory responses in voice amplitude or fundamental frequency. METHODOLOGY/PRINCIPAL FINDINGS: Twelve individuals with Parkinson's disease and 13 age- and sex-matched healthy control subjects sustained a vowel sound (/α/) and received unexpected, brief (200 ms) perturbations in voice loudness (±3 or 6 dB) or pitch (±100 cents) auditory feedback. Results showed that, while all subjects produced compensatory responses in their voice amplitude or fundamental frequency, individuals with PD exhibited larger response magnitudes than the control subjects. Furthermore, for loudness-shifted feedback, upward stimuli resulted in shorter response latencies than downward stimuli in the control subjects but not in individuals with PD. CONCLUSIONS/SIGNIFICANCE: The larger response magnitudes in individuals with PD compared with the control subjects suggest that processing of voice auditory feedback is abnormal in PD. Although the precise mechanisms of the voice feedback processing are unknown, results of this study suggest that abnormal voice control in individuals with PD may be related to dysfunctional mechanisms of error detection or correction in sensory feedback processing.

ERP correlates of language-specific processing of auditory pitch feedback during self-vocalization.

The present study investigated whether the neural correlates for auditory feedback control of vocal pitch can be shaped by tone language experience. Event-related potentials (P2/N1) were recorded from adult native speakers of Mandarin and Cantonese who heard their voice auditory feedback shifted in pitch by -50, -100, -200, or -500 cents when they sustained the vowel sound /u/. Cantonese speakers produced larger P2 amplitudes to -200 or -500 cents stimuli than Mandarin speakers, but this language effect failed to reach significance in the case of -50 or -100 cents. Moreover, Mandarin speakers produced shorter N1 latencies over the left hemisphere than the right hemisphere, whereas Cantonese speakers did not. These findings demonstrate that neural processing of auditory pitch feedback in vocal motor control is subject to language-dependent neural plasticity, suggesting that cortical mechanisms of auditory-vocal integration can be shaped by tone language experience.

Effect of tonal native language on voice fundamental frequency responses to pitch feedback perturbations during sustained vocalizations.

The purpose of this cross-language study was to examine whether the online control of voice fundamental frequency (F(0)) during vowel phonation is influenced by language experience. Native speakers of Cantonese and Mandarin, both tonal languages spoken in China, participated in the experiments. Subjects were asked to vocalize a vowel sound /u/at their comfortable habitual F(0), during which their voice pitch was unexpectedly shifted (± 50, ± 100, ± 200, or ± 500 cents, 200 ms duration) and fed back instantaneously to them over headphones. The results showed that Cantonese speakers produced significantly smaller responses than Mandarin speakers when the stimulus magnitude varied from 200 to 500 cents. Further, response magnitudes decreased along with the increase in stimulus magnitude in Cantonese speakers, which was not observed in Mandarin speakers. These findings suggest that online control of voice F(0) during vocalization is sensitive to language experience. Further, systematic modulations of vocal responses across stimulus magnitude were observed in Cantonese speakers but not in Mandarin speakers, which indicates that this highly automatic feedback mechanism is sensitive to the specific tonal system of each language.

Evaluation of the effects of deep brain stimulation of the subthalamic nucleus and levodopa treatment on parkinsonian voice using perturbation, nonlinear dynamic, and perceptual analysis.

BACKGROUND/AIMS: To quantify aperiodic phonation, nonlinear dynamic methods of acoustic voice analysis, such as correlation dimension, have been shown to be useful. The purpose of this study is to evaluate the validity of nonlinear dynamic analysis as a voice analysis tool for the effects of deep brain stimulation (DBS) and levodopa on patients with Parkinson's disease (PD). METHODS: In this study, the effects of DBS and levodopa treatment on patients with PD were measured using perturbation, nonlinear dynamic, and perceptual analysis. Nineteen PD patients that received bilateral (n = 9), left (n = 7), or right (n = 3) DBS performed sustained vowel phonations, which were recorded before and after medication with the stimulator off and on. Recordings were also taken of 10 PD patients who did not receive DBS surgery before and after medication to provide a baseline. RESULTS: A mixed two-way ANOVA (surgery, medication) generated significant positive treatment effects of DBS only in mean log-transformed D2, which was supported by mean log-transformed shimmer, vF0 (variability in fundamental frequency), and vAm (peak-to-peak amplitude variation). CONCLUSION: These findings may indicate the validity of nonlinear dynamic analysis as a complement to perceptual analysis in clinical PD voice studies.

Perturbation and nonlinear dynamic analysis of acoustic phonatory signal in Parkinsonian patients receiving deep brain stimulation.

UNLABELLED: Nineteen PD patients who received deep brain stimulation (DBS), 10 non-surgical (control) PD patients, and 11 non-pathologic age- and gender-matched subjects performed sustained vowel phonations. The following acoustic measures were obtained on the sustained vowel phonations: correlation dimension (D2), percent jitter, percent shimmer, SNR, F0, vF0, and vAm. The results indicated the following: The mean D2 of control PD patients was significantly higher than the mean D2 of non-pathologic subjects and patients who received deep brain stimulation. These results suggest an improvement in PD voice in treated patients. Many PD vocal samples in this study have type 2 signals containing subharmonics that may not be suitable for perturbation analysis but are suitable for nonlinear dynamic analysis, making the D2 results more reliable. These findings show that DBS may provide measurable improvement in patients with severe vocal impairment. LEARNING OUTCOMES: Readers will be able to: (1) identify the advantages of nonlinear dynamic analysis as a clinical tool to evaluate the aperiodic voice commonly found in patients with Parkinson's disease, (2) describe in general the method of obtaining a correlation dimension measure from a voice sample and the significance of this measure in terms of specific voice signal properties, (3) consider the preliminary implications from nonlinear dynamic analysis of a positive DBS effect on Parkinsonian voice and the potential for further investigations using nonlinear dynamic analysis on the influence of gender, severity of disease, and combined treatments on Parkinsonian voice improvement.

Hemisphere-Specific Effects of Subthalamic Nucleus Deep Brain Stimulation on Speaking Rate and Articulatory Accuracy of Syllable Repetitions in Parkinson's Disease.

This study tested the hypothesis that left versus right deep brain stimulation (DBS) of the subthalamic nucleus (STN) would have differential effects on speech. Twenty right-handed individuals with advanced Parkinson's disease (PD) underwent unilateral STN DBS. Ten were operated on the right and 10 on the left hemisphere as indicated by severity of nonspeech motor function. Speech was evaluated before surgery and 3 to 6 months after surgery with stimulator-off and with stimulator-on, with all participants off anti-parkinsonian medication for 12 hours before evaluation. Evaluators and patient speakers were blinded to the stimulator status at the postsurgery evaluations. Motor performance was assessed with UPDRS-III. Each participant produced three samples of diadochokinetic syllables. Syllable rate, syllable and vowel duration, VOT, and F0 were obtained. The diadochokinetic syllables were rated for articulatory accuracy and speaking rate. Twenty graduate clinicians served as judges. The samples were randomly presented via headphones. A mixed ANOVA with repeated measures was used to assess the significance of the changes in UPRS-III scores and speech measures. The results indicated that unilateral STN DBS produced improvement in nonspeech motor function regardless of the side of stimulation. In contrast, the changes in articulatory accuracy and syllable rate associated with the STN DBS were hemisphere specific.