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Stuttering is a disorder of speech production whose origins have been traced to the central nervous system. One of the factors that may underlie stuttering is aberrant neural miscommunication within the speech motor network. It is thus argued that disfluency (any interruption in the forward flow of speech) in adults who stutter (AWS) could be associated with anomalous cortical dynamics. Aberrant brain activity has been demonstrated in AWS in the absence of overt disfluency, but recording neural activity during disfluency is more challenging. The paradigm adopted here took an important step that involved overt reading of long and complex speech tokens under continuous EEG recording. Anomalies in cortical dynamics preceding disfluency were assessed by subtracting out neural activity for fluent utterances from their disfluent counterparts. Differences in EEG spectral power involving alpha, beta, and gamma bands, as well as anomalies in phase-coherence involving the gamma band, were observed prior to the production of the disfluent utterances. These findings provide novel evidence for compromised cortical dynamics that directly precede disfluency in AWS.

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Audiomotor integration is a basic form of sensorimotor control for regulating vocal pitch and vocal loudness, but its contribution to general motor control has only been studied minimally. In this paper, auditory feedback for prolonged force control was investigated by comparing manual and oral force generation and testing short-term audiomotor memory for these effectors. Ten healthy volunteers between the ages of 20 and 30 years old were recruited. The participants produced continuous force for 30 sec. with the lip or finger to match auditory targets. In the feedback condition, when auditory feedback was provided for 30 sec., lip force was more variable than finger force. In the memory condition, the force output of both effectors remained stable for approximately 4 sec. after feedback removal, followed by significant decay. A longer short-term memory capacity could facilitate encoding of motor memories for tasks having acoustic goals. The results demonstrate that "audiomotor" integration was effective for sustaining forces, and that audiomotor force memory is comparable to reports of visuomotor force memory.

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The authors examined force control in oral and manual effectors as a function of sensory feedback (i.e., visual and auditory). Participants produced constant isometric force via index finger flexion and lower lip elevation to 2 force levels (10% and 20% maximal voluntary contraction) and received either online visual or online auditory feedback. Mean, standard deviation, and coefficient of variation of force output were used to quantify the magnitude of force variability. Power spectral measures and approximate entropy of force output were calculated to quantify the structure of force variability. Overall, it was found that the oral effector conditions were more variable (e.g., coefficient of variation) than the manual effector conditions regardless of sensory feedback. No effector differences were found for the structure of force variability with visual or auditory feedback. Oral and manual force control appears to involve different control mechanisms regulating continuous force production in the presence of visual or auditory feedback.

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In the typical speech of any language, voicing onset and offset are effortlessly coordinated with articulation as part of the intrinsic coordination of sound production. In this paper, we argue that voicing-articulatory coordination patterns could be shaped by sensory feedback during early speech learning and these patterns persist in mature syllable productions. Our experimental results show that voicing onset is closely associated with the peak velocity and peak amplitude of jaw and upper lip movements for VC syllables in adults. This robust coordination in the onset position may function to increase the salience of VC syllables and provide a phonetically natural explanation for vowels to undergo phonological lengthening and to avoid phonological reduction in word-initial onset position.

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Sensorimotor integration of auditory feedback for oral and manual force control was compared in 10 healthy participants. Based on the notion that auditory-to-motor integration is a more typical form of feedback for oral articulators given their role in speech and singing, it was predicted that oral force generation would be more accurate and less variable on an auditory-motor task compared to manual force generation. However, finger force production showed similar accuracy and lower variability than lip force production. The authors propose that auditory feedback can be used for fine force control of both oral and manual effectors. Differences in performance are considered to arise from physiological differences between the effectors that are reflected in their typical functions. This novel study of oral and manual force control under auditory feedback is an important step in understanding how auditory information can be associated with fine force control.

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Although stuttering is regarded as a speech-specific disorder, there is a growing body of evidence suggesting that subtle abnormalities in the motor planning and execution of non-speech gestures exist in stuttering individuals. We hypothesized that people who stutter (PWS) would differ from fluent controls in their neural responses during motor planning and execution of both speech and non-speech gestures that had auditory targets. Using fMRI with sparse sampling, separate BOLD responses were measured for perception, planning, and fluent production of speech and non-speech vocal tract gestures. During both speech and non-speech perception and planning, PWS had less activation in the frontal and temporoparietal regions relative to controls. During speech and non-speech production, PWS had less activation than the controls in the left superior temporal gyrus (STG) and the left pre-motor areas (BA 6) but greater activation in the right STG, bilateral Heschl's gyrus (HG), insula, putamen, and precentral motor regions (BA 4). Differences in brain activation patterns between PWS and controls were greatest in females and less apparent in males. In conclusion, similar differences in PWS from the controls were found during speech and non-speech; during perception and planning they had reduced activation while during production they had increased activity in the auditory area on the right and decreased activation in the left sensorimotor regions. These results demonstrated that neural activation differences in PWS are not speech-specific.

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The issue of whether speech is supported by the same neural substrates as non-speech vocal tract gestures has been contentious. In this fMRI study we tested whether producing non-speech vocal tract gestures in humans shares the same functional neuroanatomy as non-sense speech syllables. Production of non-speech vocal tract gestures, devoid of phonological content but similar to speech in that they had familiar acoustic and somatosensory targets, was compared to the production of speech syllables without meaning. Brain activation related to overt production was captured with BOLD fMRI using a sparse sampling design for both conditions. Speech and non-speech were compared using voxel-wise whole brain analyses, and ROI analyses focused on frontal and temporoparietal structures previously reported to support speech production. Results showed substantial activation overlap between speech and non-speech function in regions. Although non-speech gesture production showed greater extent and amplitude of activation in the regions examined, both speech and non-speech showed comparable left laterality in activation for both target perception and production. These findings posit a more general role of the previously proposed "auditory dorsal stream" in the left hemisphere--to support the production of vocal tract gestures that are not limited to speech processing.

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Cough and sniff are both spontaneous respiratory behaviors that can be initiated voluntarily in humans. Disturbances of cough may be life threatening, while inability to sniff impairs the sense of smell in neurological patients. Cortical mechanisms of voluntary cough and sniff production have been predicted to exist; however, the localization and function of supramedullary areas responsible for these behaviors are poorly understood. We used functional magnetic resonance imaging to identify the central control of voluntary cough and sniff compared with breathing. We determined that both voluntary cough and sniff require a widespread pattern of sensorimotor activation along the Sylvian fissure convergent with voluntary breathing. Task-specific activation occurred in a pontomesencephalic region during voluntary coughing and in the hippocampus and piriform cortex during voluntary sniffing. Identification of the localization of cortical activation for cough control in humans may help potential drug development to target these regions in patients with chronic cough. Understanding the sensorimotor sniff control mechanisms may provide a new view on the cerebral functional reorganization of olfactory control in patients with neurological disorders.

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Phonation is defined as a laryngeal motor behavior used for speech production, which involves a highly specialized coordination of laryngeal and respiratory neuromuscular control. During speech, brief periods of vocal fold vibration for vowels are interspersed by voiced and unvoiced consonants, glottal stops and glottal fricatives (/h/). It remains unknown whether laryngeal/respiratory coordination of phonation for speech relies on separate neural systems from respiratory control or whether a common system controls both behaviors. To identify the central control system for human phonation, we used event-related fMRI to contrast brain activity during phonation with activity during prolonged exhalation in healthy adults. Both whole-brain analyses and region of interest comparisons were conducted. Production of syllables containing glottal stops and vowels was accompanied by activity in left sensorimotor, bilateral temporoparietal and medial motor areas. Prolonged exhalation similarly involved activity in left sensorimotor and temporoparietal areas but not medial motor areas. Significant differences between phonation and exhalation were found primarily in the bilateral auditory cortices with whole-brain analysis. The ROI analysis similarly indicated task differences in the auditory cortex with differences also detected in the inferolateral motor cortex and dentate nucleus of the cerebellum. A second experiment confirmed that activity in the auditory cortex only occurred during phonation for speech and did not depend upon sound production. Overall, a similar central neural system was identified for both speech phonation and voluntary exhalation that primarily differed in auditory monitoring.

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UNLABELLED: A deficiency in sensorimotor integration in a person who stutters may be a factor in the pathophysiology of developmental stuttering. To test oral sensorimotor function in adults who stutter, we used a task that requires the coordination of a jaw-opening movement with phonation onset. The task was adapted from previous limb coordination studies, which show that movement coordination depends on intact proprioception. We hypothesized that adult stutterers would show deficient jaw-phonatory coordination relative to control participants. The task required initiation of phonation as a jaw-opening movement passed through a narrow spatial target. Target amplitude and jaw movement speed were varied. The stuttering group showed significantly higher movement error and spatial variability in jaw-phonatory coordination compared to the control group, but group differences in movement velocity or duration were not found. The aberrant jaw-phonatory coordination of the stuttering participants suggests that stuttering is associated with an oral proprioceptive limitation, although, the findings are also consistent with a motor control deficit. LEARNING OUTCOMES: As a result of this activity, reader will (1) learn about a hypothesis and evidence supporting the view that a sensorimotor deficit contributes to chronic developmental stuttering and (2) will obtain information about the role of proprioception in multi-articulatory coordination and how it can be tested using an oral-phonatory coordination task.

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Anomalies in oral movement control have been identified in stuttering, which suggest this speech disorder involves a sensorimotor deficit. To test whether adults who stutter (AWS) display aberrant proprioceptive function, masseter tendon vibration was used to manipulate jaw proprioception as AWS and normal speakers performed a jaw-opening task. A movement amplitude reduction in the vibration condition was observed in both groups indicating the movements of AWS and controls were influenced in a similar manner by altering masseter proprioception. However, the undershoot magnitude was reduced in AWS relative to the control participants indicating a subtle difference in proprioceptive integration among the stuttering participants. Our interpretation is that AWS use proprioceptive information less efficiently than normal speakers, which could interfere with sensorimotor integration during speech production.

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The current study was based on the hypothesis that chronic developmental stuttering in adults involves a deficiency in oral kinesthesia. The authors used a target-accuracy task to compare oral kinesthesia in adults who stutter (n = 17) and in normal speakers (n = 17). During the task, participants were instructed to make accurate jaw-opening movements in visual and nonvisual feedback conditions. The authors further contrasted oral movement control in a normal response time condition with that in a reaction time condition. Overall, the adults who stutter consistently made significantly less accurate and more variable movements than the control participants in the nonvisual condition, but particularly in the reaction time condition. In general, the present findings suggest that chronic developmental stuttering involves an oral kinesthetic deficiency, although without direct measures of somatosensory function, one cannot exclude a motor deficit interpretation.

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Speakers may use laryngeal sensory feedback to adjust vocal fold tension and length before initiating voice. The mechanism for accurately initiating voice at an intended pitch is unknown, given the absence of laryngeal muscle spindles in animals and conflicting findings regarding their existence in humans. Previous reports of rapid changes in voice fundamental frequency following thyroid cartilage displacement suggest that changes in vocal fold length modulate laryngeal muscle contraction in humans. We tested the hypothesis that voice changes resulting from mechanical perturbation are due to rapid responses in the intrinsic laryngeal muscles. Hooked wire electrodes were used to record from the thyroarytenoid, cricothyroid, and sternothyroid muscles along with surface electrodes on the skin overlying the thyroid cartilage in 10 normal adults. Servomotor displacements produced consistent changes in the subjects' vocal fundamental frequency at 70-80 ms, demonstrating changes in vocal fold length and tension. No simultaneous electromyographic responses occurred in the thyroarytenoid or cricothyroid muscles in any subjects. Instead, short-latency responses at 25-40 ms following stimulus onset occurred in the sternothyroid muscles, simultaneous with responses in the surface recordings. The sternothyroid responses may modulate long-latency changes in voice fundamental frequency (approximately 150 ms). The absence of intrinsic laryngeal muscle responses is consistent with a lack of spindles in these muscles. Our results suggest that other sensory receptors, such as mucosal mechanoreceptors, provide feedback for voice control.

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PURPOSE: To examine the costs and benefits of routine follow-up evaluation in patients treated with radiation therapy for early-stage Hodgkin's disease. PATIENTS AND METHODS: We retrospectively examined patterns of follow-up evaluation and methods of relapse detection among 709 patients with stage I and II Hodgkin's disease treated with primary radiotherapy between 1969 and 1994. We determined the probability of relapse detection for seven routine follow-up procedures, compared their relative costs, and determined the impact of each procedure on the likelihood of survival following salvage therapy. RESULTS: Relapse has occurred in 157 patients (22%) at a median 1.9 years (range, 0 to 13 years) posttreatment. Relapse was suspected primarily by history (Hx) in 55% of patients, physical examination (PE) in 14%, chest x-ray (CXR) in 23%, and abdominal x-ray (KUB) in 7%. Only one relapse (1%) was identified by a routine laboratory study. The rate of relapse detection was highest for a combination of Hx and PE (78 of 10,000 examinations) followed by CXR (26 of 10,000 examinations). The projected charges (1995 dollars) per relapse detected by routine follow-up Hx and PE were $11,000 compared with $68,000 for CXR and $142,000 for KUB. The 10-year actuarial survival rate following salvage therapy was 65% overall, 65% for patients in whom relapse was detected by Hx or PE, and 69% for patients in whom relapse was detected by radiographs (P = not significant). CONCLUSION: The majority of relapses occurred within 5 years of treatment and were identified by Hx and PE. CXR was useful during the first 3 years of follow-up evaluation. KUB, CBC, and laboratory studies accounted for nearly half of all follow-up charges and rarely led to the detection of relapse. Their routine use as a method of relapse detection is questionable. In general, the method of relapse detection did not have a significant impact on the likelihood of successful salvage therapy.

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A new antibacterial antibiotic, designated simaomicin alpha (LL-D42067 alpha) was isolated from the fermentation broth of an actinomycete strain. Based on cultural, physiological, morphological and chemical characteristics, culture LL-D42067 was identified as a new subspecies of Actinomadura madurae. Simaomicin alpha demonstrated potent activity against Gram-positive bacteria and was active in vivo against a variety of Eimeria species causing coccidiosis in chickens.

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