Emily Wang

Pre-clinical properties of the α4β2 nicotinic acetylcholine receptor partial agonists varenicline, cytisine and dianicline translate to clinical efficacy for nicotine dependence

Background and purpose:  Smoking cessation trials with three high‐affinity partial agonists of α4β2 neuronal nicotinic acetylcholine receptors (nAChRs) have demonstrated differences in their clinical efficacy. This work examines the origin of the differences by taking into account brain exposure and pharmacological effects at human α4β2 nAChRs.

deFOG — A real time system for detection and unfreezing of gait of Parkinson’s patients

Freezing of gait (FOG) is a common complication in movement disorders, typically associated with the advanced stages of Parkinson’s disease. Auditory cues might be used to facilitate unfreezing of gait and prevent fall related injuries. We present a wearable, unobtrusive system for real-time gait monitoring, which consists of an inertial wearable sensor and wireless headset for the delivery of acoustic cues. The system recognizes FOG episodes with minimum latency and delivers acoustic cues to unfreeze the gait. We present design of a system for the detection and unfreezing of gait (deFOG), and preliminary results of the feasibility study. In a limited test run of 4 test cases the system was able to detect freezing of gait with average latency of 332 ms, and maximum latency of 580 ms.

The effect of unilateral electrostimulation of the subthalamic nucleus on respiratory/ phonatory subsystems of speech production in Parkinson's disease: a preliminary report

This paper reports findings on the respiratory/phonatory subsystems from an on‐going study investigating the effect of unilateral electrostimulation of the subthalamic nucleus (STN) on different speech subsystems in people with Parkinsons disease (PD). Speech recordings were made in the medication‐off state at baseline, three months post surgery with stimulation‐on, and with stimulation‐off, in six right‐handed PD patients. Subjects completed several speech tasks. Acoustic analyses of the maximally sustained vowel phonation were reported. The results were compared to the scores of the motor section of the Unified Parkinsons Disease Rating Scale (UPDRS‐III) obtained under the same conditions. Results showed that stimulation‐on improved UPDRS‐III scores in all six subjects. While mild improvement was observed for all subjects in the Stimulation‐on condition, three subjects received left‐STN stimulation showed a significant decline in vocal intensity and vowel duration from their baseline indicating the speech function was very susceptible to micro lesions due to the surgical procedure itself when the surgical site was in the dominant hemisphere.

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.

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 Parkinsons 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 Parkinsons 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.

Perception of Dynamic Acoustic Patterns by an Individual with Unilateral Verbal Auditory Agnosia

Previous studies have found that subjects diagnosed with verbal auditory agnosia (VAA) from bilateral brain lesions may experience difficulties at the prephonemic level of acoustic processing. In this case study, we administered a series of speech and nonspeech discrimination tests to an individual with unilateral VAA as a result of left-temporal-lobe damage. The results indicated that the subjects ability to perceive steady-state acoustic stimuli was relatively intact but his ability to perceive dynamic stimuli was drastically reduced. We conclude that this particular aspect of acoustic processing may be a major contributing factor that disables speech perception in subjects with unilateral VAA.

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 Parkinsons 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.

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.

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 Parkinsons 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.

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.