Effect of duration of pitch-shifted feedback on vocal responses in patients with Parkinson's disease.

Study of the pitch-shift reflex is useful for the investigation of how auditory feedback is used in the control of voice fundamental frequency. The present study was an attempt to learn if the basal ganglia are involved in central mechanisms of the pitch-shift reflex by comparing measures of the reflex in a group of Parkinson's disease patients with those measures in a group of control participants. The effect of varying duration of the pitch-shift stimulus (PSS) on the voice fundamental frequency (F0) response in 10 Parkinson's disease (PD) patients and 10 age-matched unaffected participants was investigated. Participants were instructed to vocalize into a microphone while their voice was fed back to them over headphones. This feedback of the vocal signal was shifed in pitch either up or down, with the duration of this shift systematically manipulated at 100 ms, 500 ms, and 1000 ms. Although the participants were on medication, making interpretation of the results problematic with regard to basal ganglia function, it was reasoned that positive effects could nevertheless suggest basal ganglia involvement in this reflex and motivate further research. Results indicated that both groups responded to increased stimulus duration of the pitch-shift stimulus with increases in reflex peak time, magnitude, and end times. However, PD patients had significantly longer peak times and end times than control participants for stimulus durations of 100 ms. These results suggest that basal ganglia dysfunction may affect mechanisms relating to the execution and termination of the pitch-shift reflex for brief stimulus durations. The results also support hypotheses of impaired sensory integration of auditory feedback in PD patients.

Effects of delayed auditory feedback (DAF) on the pitch-shift reflex.

Changes in voice pitch auditory feedback to vocalizing subjects elicit compensatory changes in voice fundamental frequency (F0). The neural mechanisms responsible for this behavior involve the auditory and vocal-motor systems, collectively known as the audio-vocal system. Previous work [Burnett et al., J. Acoust. Soc. Am. 103, 3153-3161 (1998); Hain et al., Exp. Brain Res. 130, 133-141 (2000); Larson et al., J. Acoust. Soc. Am. 107, 559-564 (2000)] indicated that this system operates using negative feedback to cancel out low-level errors in voice F0 output. By introducing delays in the auditory feedback pathway, we hoped to transiently "open" the feedback loop and learn which components of the response are most closely related to the timing of the auditory feedback signal. Subjects were presented with pitch-shift stimuli that were paired with a delay of 0, 50, 100, 200, 300, or 500 ms. Delayed auditory feedback did not affect voice F0 response latency or magnitude, but it delayed the timing of later parts of the response. As a further test of the audio-vocal control system, a second experiment was conducted in which delays of 100, 200, or 300 ms were combined with stimuli having onset velocities of 1000 or 330 cents/s. Results confirmed earlier reports that the system is sensitive to velocity of stimulus onset. A simple feedback model reproduced most features of both experiments. These results strongly support previous suggestions that the audio-vocal system monitors auditory feedback and, through closed-loop negative feedback incorporating a delay, adjusts voice F0 so as to cancel unintentional small magnitude fluctuations in F0.

Instructing subjects to make a voluntary response reveals the presence of two components to the audio-vocal reflex.

Previous findings have shown that subjects respond to an alteration, or shift, of auditory feedback pitch with a change in voice fundamental frequency (F0). When pitch shifts exceeding 500 ms in duration were presented, subjects' averaged responses appeared to consist of both an early and a late component. The latency of the second response was long enough to be produced voluntarily. To test the hypothesis that there are two responses to pitch-shift stimuli and to clarify the role of intention, subjects were instructed to change their voice F0 in the opposite direction of the pitch-shift stimulus, in the same direction, or not to respond at all. In a second group, subjects were tested under the above conditions as well as under instructions to raise voice F0 or to lower F0 as rapidly as possible upon hearing a pitch shift. Results showed that, when given instructions to produce a voluntary response, subjects made both an early vocal response (VR1) and a later vocal response (VR2). The second response, VR2, was almost always made in the instructed direction, whereas VR1 was often made incorrectly. The latency of VR1 was reduced under instructions to respond to feedback pitch shifts by changing voice F0 in the opposite direction, compared with that when told to ignore the pitch shifts. Latency and amplitude measures of VR2 differed under the various experimental conditions. These results demonstrate that there are two responses to pitch-shift stimuli. The first is relatively automatic but may be modulated by instructions to the participant. The second response is probably a voluntary one.

Short-latency changes in voice F0 and neck surface EMG induced by mechanical perturbations of the larynx during sustained vowel phonation.

Nineteen healthy young adult males with normal voice and speech attempted to sustain the vowel /u/ at a constant pitch (target: 180 Hz) and a constant and comfortable loudness level while receiving a sudden mechanical perturbation to the larynx (thyroid prominence) via a servo-controlled probe. The probe moved toward or away from the larynx in a ramp-and-hold fashion (3.3-mm displacement, 0.7 N force, 20-ms rise time, 250-ms duration) as the subjects attempted to maintain a constant probe-larynx pressure. Eighty stimuli were applied in each direction, one stimulus per phonation. Pairs of surface electromyography (EMG) electrodes were attached to the skin of the anterior neck over laryngeal, infralaryngeal, and supralaryngeal areas. The rectified EMG signals, the voltage analog of the voice fundamental frequency (VAF0), and the voltage analog of the probe displacement were digitized and signal-averaged relative to the onset of the stimulus. Sudden perturbation of the larynx induced an instantaneous decrease or increase in VAF0, depending on the direction of the probe's movement, and a short-latency increase in the EMG (30-35 ms) and VAF0 (55-65 ms). We argue that the instantaneous VAF0 change was related to a mechanical effect, and the short-latency VAF0 and EMG changes to reflexogenic effects-the latter most likely associated with both intrinsic and extrinsic laryngeal sensorimotor mechanisms. Further physiological studies are needed to elucidate the sources of the VAF0 and EMG responses. Once elucidated, the present method may provide a powerful noninvasive tool for studying laryngeal neurophysiology. The theoretical and clinical implications of the present findings are addressed.

Effects of pitch-shift velocity on voice Fo responses.

Previous studies have shown that voice fundamental frequency (F0) is modified by changes in the pitch of vocal feedback and have demonstrated that the audio-vocal control system has both open- and closed-loop control properties. However, the extent to which this system operates in closed-loop fashion may have been underestimated in previous work. Because the step-type stimuli used were very rapid, and people are physically unable to change their voice F0 as rapidly as the stimuli, feedback responses might have been reduced or suppressed. In the present study, pitch-shift stimuli, consisting of a disparity between voice F0 and feedback pitch of varying ramp onset velocities, were presented to subjects vocalizing a steady /ah/ sound to examine the effect of stimulus onset on voice F0 responses. Results showed that response velocity covaried with stimulus velocity. Response latency and time of the peak response decreased with increases in stimulus velocity, while response magnitude decreased. A simple feedback model reproduced most features of these responses. These results strongly support previous suggestions that the audio-vocal system monitors auditory feedback and, through closed-loop negative feedback, adjusts voice F0 so as to cancel low-level fluctuations in F0.

Swallowing and tongue function following treatment for oral and oropharyngeal cancer.

This study examined tongue function and its relation to swallowing in 13 subjects with oral or oropharyngeal cancer treated with primary radiotherapy +/- chemotherapy and 13 age- and sex-matched control subjects. Measures of swallowing and tongue function were obtained using videofluoroscopy, pretreatment and 2 months posttreatment. Maximum isometric strength and endurance at 50% of maximum strength were obtained with the Iowa Oral Performance Instrument (IOPI). Control subjects were tested once. All subjects with head and neck cancer were evaluated pretreatment and 2 months posttreatment. No significant differences were found for the tongue function measures pre- and 2 months posttreatment in the group with head and neck cancer. Significantly higher tongue strength was observed in the control than in the group with head and neck cancer both pre- and posttreatment. No significant differences were found for the 2 groups for tongue endurance measures. Significant correlations of tongue strength and endurance and some swallow measures were found pre- and posttreatment for the group with head and neck cancer and for the control group. These correlations included oral and pharyngeal temporal swallow measures and oropharyngeal swallow efficiency. Pretreatment differences between the 2 groups in tongue strength were likely related to tumor bulk, pain, and soreness. Two-month posttreatment differences were likely related to radiation +/- chemotherapy changes to the oral and pharyngeal mucosa. This study provides support for the hypothesis that tongue strength plays a role in oropharyngeal swallowing, particularly related to the oral phase of the swallow.

Electromyographic response of the labial muscles during normal liquid swallows using a spoon, a straw, and a cup.

In this investigation, surface electromyographic (EMG) recordings were used to make qualitative and quantitative analyses of labial muscle activity during three swallowing tasks, incorporating the use of various drinking implements. EMG was recorded from four quadrants of the perioral region and from the submental muscle complex in 11 normal adult females. Swallowing tasks included liquid extraction from a spoon, a straw, and a cup and posterior bolus propulsion of a 5 ml, thin liquid. Average EMG values obtained during a maximal lip compression task were used to normalize labial muscle responses for each subject thus allowing between-subject comparisons. Variable activity patterns were noted in the perioral muscles once the lips were contacted by a drinking implement. Subjects used a greater percentage of maximal labial muscle activity to remove liquid from an implement than to swallow the liquid. A greater level of EMG was recorded in the lips during straw usage as compared with spoon or cup usage. Significant intrasubject and intersubject variability in labial function occurred during liquid removal using a drinking implement and during the oral swallow in these normal subjects.

Voice F0 responses to manipulations in pitch feedback.

Recent studies have shown that when phonating subjects hear their voice pitch feedback shift upward or downward, they respond with a change in voice fundamental frequency (F0) output. Three experiments were performed to improve our understanding of this response and to explore the effects of different stimulus variables on voice F0 responses to pitch-shift stimuli. In experiment 1, it was found that neither the absolute level of feedback intensity nor the presence of pink masking noise significantly affect magnitude or latency of the voice F0 response. In experiment 2, changes in stimulus magnitude led to no systematic differences in response magnitudes or latencies. However, as stimulus magnitude was increased from 25 to 300 cents, the proportion of responses that changed in the direction opposite that of the stimulus ("opposing" response) decreased. A corresponding increase was observed in the proportion of same direction responses ("following" response). In experiment 3, increases in pitch-shift stimulus durations from 20 to 100 ms led to no differences in the F0 response. Durations between 100 and 500 ms led to longer duration voice F0 responses with greater response magnitude, and suggested the existence of a second F0 response with a longer latency than the first.

Voice F0 responses to pitch-shifted auditory feedback: a preliminary study.

Auditory feedback has been suggested to be important for voice fundamental frequency (F0) control. The present study featured a new technique for testing this hypothesis by which the pitch of a subject's voice was modulated, fed back over earphones, and the resultant change in the emitted voice F0 was measured. The responses of 67 normal, healthy young adults were recorded as they attempted to ignore intermittent upward or downward shifts in pitch feedback while they sustained steady vowel sounds (/a/) or sang musical scales. Ninety-six percent of subjects increased their F0 when the feedback pitch was decreased, and 78% of subjects decreased their F0 when the pitch feedback was increased. Latencies of responses ranged from 104 to 223 ms. Results indicate people normally rely on pitch feedback to control voice F0.

Analysis of neuro-behavioral Discovery data on the Macintosh computer.

This paper describes a suite of routines using IgorPro, a powerful analysis and graphing software package for the Macintosh computer, to enhance the ability to analyze, manipulate, and display data recorded with the Discovery acquisition software marketed by DataWave Technologies. The routines are able to time-align fast and slow data channels, and are especially useful for analyses that involve both neural and behavioral data. The software was designed for eyeblink conditioning and vocalization experiments, but it can easily be used for analyzing other types of neurobehavioral data. The data are first prepared on the PC with routines that inspect the header of the data file and translate the data file into a compact binary format that can be read by IgorPro. An option is also available to splice out data from unnecessary portions of an intertrial interval. The new file is then put on the Macintosh computer for display and analysis by IgorPro. These routines enable both neural and behavioral data to be quickly and easily reduced, manipulated, and statistically and graphically summarized.

Neurons of the anterior mesial cortex related to faciovocal activity in the awake monkey.

1. The anterior mesial cortex, including the cingulate region, is thought to be involved in the voluntary control of vocalization. Previous recording studies have demonstrated that anterior mesial neurons discharge before conditioned and spontaneous vocalizations, but questions remain regarding the location and functional properties of these neurons. The present study was performed to provide a more complete description of the location and discharge properties of anterior mesial neurons involved in faciovocal behaviors. 2. Single-unit activity was recorded from neurons in the anterior mesial cortex of monkeys during performance of self-paced vocalizations and jaw openings. Cells were also tested for responsiveness to acoustic stimulation, and attempts were made to elicit vocalization through stimulation of the cortex surrounding related cells. Discharge properties of the cells were statistically analyzed, and correlation analysis was performed between measure of cell discharge and vocalization. 3. A total of 145 neurons were observed to modulate their discharge in association with vocalization or jaw opening. Four general classes of neurons were observed: neurons related only to vocalization, neurons related only to jaw opening, neurons related to both vocalization and jaw opening, and neurons related to other oromotor activities such as lip movements or reinforcement consumption. 4. Vocalization-related cells typically discharged tonically at a low frequency (mean 22 Hz), and many instances of long-lead activity (lead time > 500 ms) were noted. No neurons responded to acoustic stimulation, and electrical stimulation failed to elicit vocalization. Neural activity was not correlated with any measure of vocalization. 5. Neurons related to faciovocal behavior were located in the anterior cingulate sulcus and adjacent cortex of the mesial wall at a level just rostral to the genu of the arcuate sulcus. This region roughly corresponds to the rostral cingulate motor area and is located caudal to the traditionally described cingulate vocalization region. 6. In the present study we demonstrate the existence of an additional region in the medial wall that is involved in a variety of faciovocal behaviors such as vocalization, jaw opening, lip movements, and reinforcement consumption. The neurons do not appear to be strongly coupled to the execution of these acts. These results suggest that the activity of neurons in the anterior mesial cortex may relate to faciovocal behavior in a more global way than the activity of neurons in other motor areas.

Modification in activity of medullary respiratory-related neurons for vocalization and swallowing.

1. The medullary ventral respiratory group (VRG) in and near the nucleus ambiguus contains neurons related to respiration. Also found here are neurons related to vocalization and swallowing as well as motoneurons of laryngeal, pharyngeal, palatal, and esophageal muscles. Previous reports in anesthetized animals have characterized discharge properties of neurons as they relate to a single behavior, e.g., respiration. Relatively few studies have documented discharge properties during more than one behavior, e.g., respiration and swallowing. Neurons were recorded extracellularly from awake Macaca nemestrina monkeys engaged in a vocalization task. The present paper describes how respiratory-related neurons (RRNs) modify their discharge during vocalization and swallowing. 2. The temporal relation between vocalization, subglottal pressure (SP), and diaphragm electromyogram (EMG) was established from recordings in anesthetized monkeys. Vocalization was elicited by electrical stimulation of the midbrain periaqueductal gray (PAG). Vocalization is preceded by deep inspiration and a brief pause in diaphragm EMG and begins with a rapid increase in positive SP. 3. Extracellularly recorded neural potential from the VRG in three awake monkeys were related to respiration by correlating their discharge with EMGs from the posterior cricoarytenoid or intercostal muscles during quiet respiration. Neurons were classified as inspiratory (INSP; N = 27), phase spanning (PS; N = 20), or expiratory (N = 6) on this basis. 4. A fourth category of cells was defined as a subgroup of INSP cells on the basis of their discharge during vocalization. This group, inspiratory-pause (INSP-PS; N = 10), paused for approximately 100 ms just before vocalization and resumed their activity during vocalization. 5. Of 63 fully analyzed RRNs, 40 (63%) also modulated their activity with vocalization and 3 (5%) with swallowing. Thirteen (21%) RRNs modulated with vocalization, respiration, and swallowing. Seven (11%) cells were modulated only with respiration. 6. Most cells demonstrated a shorter period of activity and a higher discharge rate associated with vocalization in comparison with quiet respiration. Six (30%) of the PS cells demonstrated an augmenting discharge pattern before vocalization, which was different from the other PS cells and different from their pattern during quiet respiration. Thirteen RRNs showed a pause in activity during vocal fold closure associated with swallowing, whereas three cells gave a burst at this time. 7. The higher discharge rate and shorter burst duration preceding vocalization, compared with quiet respiration, may be related to the greater positive SP necessary to support vocalization.(ABSTRACT TRUNCATED AT 400 WORDS)

Glossopharyngeal evoked potentials in normal subjects following mechanical stimulation of the anterior faucial pillar.

The anterior faucial pillar, which is innervated by the glossopharyngeal nerve, is thought to be important in eliciting the pharyngeal swallow in awake humans. Glossopharyngeal evoked potentials (GPEP), elicited by mechanically stimulating this structure, were recorded from 30 normal adults using standard averaging techniques and a recording montage of 16 scalp electrodes. Ten of the subjects experienced a desire to swallow in response to stimulation. Repeatable responses were recorded from all 30 subjects. The GPEPs recorded from the posterior scalp were W-shaped and consisted of P1, N1, P2, N2 and P3 peaks. Mean latencies of P1, N1 and P2 were 11, 16 and 22 msec, respectively, for both left and right pillar stimulation. In contrast, latencies of N2 and P3 varied significantly between left and right pillar stimulation. Mean latencies of N2 and P3 were 27 and 34 msec for left, and 29 and 35 msec for right pillar stimulation. Topographical maps acquired at peak latencies for P1, N1 and P2 revealed consistent asymmetrical voltage distributions between the two hemispheres; the largest responses were recorded from the hemisphere ipsilateral to the side of stimulation. The scalp topography of N2 and P3 varied between male and female subjects as well as between left and right pillar stimulation. These findings support the hypothesis that mechanical stimulation to the anterior faucial pillar alone can elicit repeatable responses from the central nervous system. The integration of this subcortical/cortical activity with that of the medullary swallowing center may play an important role in eliciting the pharyngeal swallow.

Neuronal activity in nucleus ambiguous during deglutition and vocalization in conscious monkeys.

Extracellular recordings were made from the nucleus ambiguous in three conscious Macaca nemestrina monkeys during spontaneous vocalizations and swallows. The temporal relationship of neuronal activity to swallowing was inferred through correlation with the thyroarytenoid electromyographic (EMG) activity. Videofluoroscopic analysis of a fourth monkey during swallows of barium-impregnated fruit juice established the temporal relationship between swallowing and thyroarytenoid EMG activity. Of 691 cells recorded from the nucleus ambiguous and its adjacent area, the neuronal activity of 80 cells showed modulation during swallowing. Sixty-two cells were classified as "active" cells, with increased activity in relation to swallowing, while 18 cells were classified as "suppressed" cells, with tonic activity that reduced with swallowing. A continuum of latency was seen between the onset of modulation of these cells and the onset of swallowing, from "early" before the swallow to "late" after the swallow onset with most of the cells (44 cells) showing modulation near the onset of the swallow. A majority (37) of the 62 active swallowing-related cells also discharged with vocalization, but they demonstrated a lower discharge frequency and a longer burst duration during swallowing. Of the 18 suppressed swallowing-related cells, 11 cells discharged phasically with the respiratory cycle and may be a part of the ventral medullary respiratory center. This chronic awake primate model would preserve the many sensory inputs that may modify the oropharyngeal swallow and may better approximate human physiology.

Multifunctional properties of ambiguous neurons identified electrophysiologically during vocalization in the awake monkey.

1. The nucleus ambiguus (NA) of the medulla contains motoneurons (MNs) for muscles of the larynx, palate, pharynx, and esophagus. Previous studies in anesthetized animals have demonstrated neural discharge correlated closely with respiration, swallowing, and electrical stimulation-elicited vocalization. A preliminary study confirming the above findings was done by recording NA motoneuron extracellular potentials from awake vocalizing monkeys. The present study was undertaken to quantitatively describe discharge properties of a large number of NA neurons recorded from awake, vocalizing monkeys (Macaca nemestrina). 2. In monkeys trained to vocalize for a food reward, extracellular recordings of neurons in and around the nucleus ambiguus were correlated with laryngeal electromyographic activity during vocalization. A nerve cuff electrode on the ipsilateral recurrent laryngeal nerve allowed identification of laryngeal MNs by antidromic activation of laryngeal MNs and the collision test. 3. Most laryngeal MNs became active 100-200 ms before vocalization. They ceased discharging during or immediately after vocalization. Some MNs discharged in close synchrony with bursts of EMG associated with variations in the vocalization. The mean discharge rate of MNs during vocalization was 18 Hz, and the maximum rate in many cells was over 100 Hz. MNs were also active during swallowing. One MN was related only to respiration and one exclusively to swallowing. 4. Some non-motoneurons (Non-MNs) and cells that may possibly be MNs (PossMNs), recorded in and near the NA, showed properties similar to MNs. Many (147) were active only with vocalization, whereas others were active with swallowing (23); respiration (9); vocalization and swallowing (32); vocalization and respiration (40); or vocalization, swallowing, and respiration (17). 5. The present study demonstrates the importance of studying laryngeal MNs in the chronic preparation. Namely, it is shown that both MNs and Non-MNs of the NA are active with more than one activity. Moreover, some Non-MNs are active for only one activity, e.g., vocalization or swallowing. These findings imply the existence of subsets of medullary neurons involved in multiple behaviors for control of generalized laryngeal functions and other subsets related to specific behaviors.

Laryngeal and respiratory activity during vocalization in macaque monkeys.

The present study describes the laryngeal and respiratory muscle activity associated with vocalizations in macaque monkeys. During the bark vocalization, a short, aperiodic call, the cricothyroid, thyroarytenoid, rectus abdominis, and intercostals were active while the posterior cricoarytenoid and diaphragm were quiet. During the coo vocalization, a longer, clear call, the cricothyroid, thyroarytenoid, intercostals, rectus abdominis, and diaphragm were active. In one monkey, the posterior cricoarytenoid was also active during the call, while in another monkey it was not. Laryngeal muscle activity was correlated with the amplitude and duration of the coo call. Results suggest that the amplitude and duration differences between calls are determined primarily by laryngeal modification of the airflow, and that the differences in posterior cricoarytenoid activity may be due to differences in voice intensity.

Cerebral averaged potentials preceding oral movement.

The "readiness potential" is an event-related potential that shows increasing negativity at vertex and motor strip scalp recording sites prior to voluntary, unilateral limb movements. Though speech involves movement on both sides of the midline, recent recordings of prespeech potentials suggest a pattern of bilateral activation that lateralizes to the dominant hemisphere just prior to the onset of articulatory movement. To determine whether this pattern of dominant hemisphere activation is present prior to a stereotyped, nonspeech movement of the mouth, the averaged potentials preceding a lip protrusion task were recorded at the cranial vertex and over the right and left motor cortex. Results were compared to potentials preceding a right finger extension task performed by the same subjects. Both the finger and the lip movements were initially preceded by slow negative potentials. Prior to the finger extension task, the negative amplitude became greatest over the left motor cortex, contralateral to the side of movement. Prior to the lip protrusion task, the amplitude of the potential remained even over the right and left motor cortices. The results suggest that, for this nonspeech movement of a midline structure, bilateral cortical control takes place. Control of lip movement is apparently not necessarily a dominant hemisphere function, though dominance may become part of the motor control strategy for more complex movements such as those used during speech.

On the relation of PAG neurons to laryngeal and respiratory muscles during vocalization in the monkey.

Despite evidence from previous unit recording, microstimulation, lesioning and anatomical studies, the functions of the midbrain periaqueductal gray (PAG) remain unclear. We attempted to clarify the function of the PAG by recording activity of PAG units along with laryngeal and respiratory electromyograms (EMG) during vocalization in awake monkeys. PAG units were classified with respect to vocalization on the basis of their discharge patterns as 'early burst', 'late burst', 'tonic-increase' and 'tonic-off', with the vast majority being of the early- and late-burst type. Early-burst cells were correlated most frequently with inspiratory muscles of the respiratory system and laryngeal abductor muscles. Late-burst cells were most clearly correlated with laryngeal adductor and expiratory respiratory muscles. Data from spike-triggered averaging and parametric correlations indicate that most cells are related to single muscles, but a significant number were related to functionally related groups of two or more muscles. The results suggest that the PAG determines qualitative aspects of vocalization by the multisynaptic action its cells have on laryngeal and respiratory motoneurons.