Deficiency in Re-Orienting of Attention in Adults with Attention-Deficit Hyperactivity Disorder.

Objective: To characterize potential brain indexes of attention deficit hyperactivity disorder (ADHD) in adults. Methods: In an effort to develop objective, laboratory-based tests that can help to establish ADHD diagnosis, the brain indexes of distractibility was investigated in a group of adults. We used event-related brain potentials (ERPs) and performance measures in a forced-choice visual task. Results: Behaviorally aberrant distractibility in the ADHD group was significantly higher. Across three ERP components of distraction: N1 enhancement, P300 (P3a), and Reorienting Negativity (RON) the significant difference between ADHD and matched controls was found in the amplitude of the RON. We used non-parametric randomization tests, enabling us to statistically validated this difference between-group. Conclusions: Our main results of this feasibility study suggest that among other ERP components associated with auditory distraction, the RON response is promising index for a potential biomarker of deficient re-orienting of attention in adults s with ADHD.

Auditory-vocal control system is object for predictive processing within seconds time range.

Predictive processing across hierarchically organized time scales is one of the fundamental principles of neural computations in the cerebral cortex. We hypothesize that relatively complex aggregation of auditory and vocal brain systems that use auditory feedback for reflexive control of vocalizations can be an object for predictive processing. We used repetitive patterns of perturbations in auditory feedback during vocalizations to elicit implicit expectations that were violated by surprising direction of perturbations in one of the experimental conditions. Our results provide empirical support for the idea that formation of expectancy for integrated auditory-vocal brain systems, within the time range of seconds, resulted in two sequential neuronal processes. The first process reflects monitoring and error detection in prediction about perturbations in auditory feedback during vocalizations within the time range of seconds. The second neuronal process can be attributed to the optimization of brain predictions for sensory contingencies during vocalizations at separable and distinct timescales.

Effects of deep brain stimulation on vocal fold immobility in Parkinson's disease.

BACKGROUND: Vocal fold (VF) immobility is a rare, potentially fatal complication of advanced Parkinson's disease (PD). Previous reports suggest that subthalamic nucleus deep brain stimulation (STN-DBS) may influence laryngeal function, yet the role of STN-DBS on VF immobility remains unexplored. CASE DESCRIPTION: We report a case of a patient with advanced PD and bilateral VF immobility ultimately requiring a tracheostomy. To assess the effects of STN-DBS on vocal cord function and to correlate these effects with peripheral motor symptoms at different stimulation settings, the patient was evaluated before and after initiation of bilateral STN-DBS. Measures included direct observation of VF mobility via transnasal laryngoscopy, levodopa equivalent dose of anti-PD medication, and motor scores. High frequency (150 Hz) STN-DBS resulted in improved motor scores, reduced medication requirement, and modestly improved right VF abduction although insufficient for safe decannulation. Low frequency (60 Hz) stimulation resulted in lower motor scores, but without worsening VF abduction. CONCLUSIONS: STN-DBS may play an important role in the neuromodulation of PD-induced laryngeal dysfunction, including VF mobility. Characterization of these axial symptoms is important when programming and evaluating responsiveness to DBS.

Expiratory muscle strength training evaluated with simultaneous high-resolution manometry and electromyography.

OBJECTIVE: To examine feasibility of a simultaneous high-resolution pharyngeal manometry (HRM) and electromyography (EMG) experimental paradigm to detect swallowing-related patterns of palatal, laryngeal, and pharyngeal muscle activity during expiratory training. STUDY DESIGN: Technical report. METHODS: Simultaneous HRM, surface submental, and intramuscular EMG were acquired in two healthy participants during five tasks: 10-cc water swallow, maximum expiratory pressure (MEP) testing, and expiratory muscle strength training (EMST) at three pressure levels (sham, 50%, and 75% MEP). RESULTS: Experimental conditions were feasible. Velopharyngeal closing pressure, palate EMG activity, and pharyngeal EMG activity increased as expiratory load increased. In contrast, thyroarytenoid EMG activity was low during the expiratory task, consistent with glottic opening during exhalation. Submental EMG patterns were more variable during expiratory tasks. Intraluminal air pressures recorded with HRM were correlated with measured expiratory pressures and target valve-opening pressures of the EMST device. CONCLUSION: Results suggest that a simultaneous HRM/EMG/EMST paradigm may be used to detect previously unquantified swallowing-related muscle activity during EMST, particularly in the palate and pharynx. Our approach and initial findings will be helpful to guide future hypothesis-driven studies and may enable investigators to evaluate other muscle groups active during these tasks. Defining mechanisms of action is a critical next step toward refining therapeutic algorithms using EMST and other targeted treatments for populations with dysphagia and airway disorders. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:797-804, 2017.

Modulation of Upper Esophageal Sphincter (UES) Relaxation and Opening During Volume Swallowing.

UES opening occurs following cricopharyngeus deactivation and submental muscle contraction causing hyolaryngeal elevation and UES distraction. During impedance manometry, the inverse of impedance (admittance) can be used to measure bolus presence and infer UES opening. We hypothesized that the temporal relationship between UES relaxation, opening and hyolaryngeal elevation would change with increasing bolus volume. Simultaneous intramuscular cricopharyngeal (CP) electromyography (EMG), surface submental EMG (SM-EMG), and high-resolution impedance manometry were recorded in eight (aged 27 ± 7 years, 5 M) healthy volunteers, while swallowing 0.9 % saline boluses of 2, 5, 10, and 20 ml. Data were exported and analyzed via Matlab. Statistical analysis comprised repeated measures one-way ANOVA and Pearson correlation. A P value of <0.05 was considered significant. Duration of CP deactivation increased at 20 ml volume (P < 0.001). UES relaxation and opening increased with increasing bolus volume (P < 0.001); however, overall duration of SM activation did not change. As UES opening occurs progressively earlier with increasing volumes, peak SM-EMG activity occurs relatively later (P < 0.001) and shifts from occurring before to following peak UES distention. During healthy swallowing, there is sensory modulation of cricopharyngeal and submental muscle activity. Intrabolus pressures, transmitted from the tongue base and pharynx, play a progressively more important role in sphincter opening with increasing volume. The findings may explain why some healthy elderly and patients with oropharyngeal dysphagia have difficulty swallowing larger while tolerating smaller bolus volumes.

Predicting the activation states of the muscles governing upper esophageal sphincter relaxation and opening.

The swallowing muscles that influence upper esophageal sphincter (UES) opening are centrally controlled and modulated by sensory information. Activation and deactivation of neural inputs to these muscles, including the intrinsic cricopharyngeus (CP) and extrinsic submental (SM) muscles, results in their mechanical activation or deactivation, which changes the diameter of the lumen, alters the intraluminal pressure, and ultimately reduces or promotes flow of content. By measuring the changes in diameter, using intraluminal impedance, and the concurrent changes in intraluminal pressure, it is possible to determine when the muscles are passively or actively relaxing or contracting. From these "mechanical states" of the muscle, the neural inputs driving the specific motor behaviors of the UES can be inferred. In this study we compared predictions of UES mechanical states directly with the activity measured by electromyography (EMG). In eight subjects, pharyngeal pressure and impedance were recorded in parallel with CP- and SM-EMG activity. UES pressure and impedance swallow profiles correlated with the CP-EMG and SM-EMG recordings, respectively. Eight UES muscle states were determined by using the gradient of pressure and impedance with respect to time. Guided by the level and gradient change of EMG activity, mechanical states successfully predicted the activity of the CP muscle and SM muscle independently. Mechanical state predictions revealed patterns consistent with the known neural inputs activating the different muscles during swallowing. Derivation of "activation state" maps may allow better physiological and pathophysiological interpretations of UES function.

A multisensor approach to improve manometric analysis of the upper esophageal sphincter.

OBJECTIVES/HYPOTHESIS: High-resolution manometry (HRM) improves on previous manometric systems by including a greater number of sensors that are more densely placed. Due to deglutitive movement of the HRM catheter and upper esophageal sphincter (UES), it is unclear which HRM sensors capture pressure in the UES. To address this issue, we present two complementary studies to describe UES pressure patterns using HRM + videofluoroscopy and HRM + electromyography (EMG). STUDY DESIGN: Case series involving a new analysis method. METHODS: Study 1: Simultaneous HRM + videofluoroscopy were performed in 11 healthy subjects swallowing five 10-mL thin-liquid boluses. HRM catheter and UES movement were tracked to identify UES pressure patterns over multiple HRM sensors. Study 2: Simultaneous HRM + cricopharyngeal EMGs were performed in six healthy subjects swallowing five 10-mL water boluses. HRM and EMG outputs were correlated over individual and multiple HRM sensors. RESULTS: HRM sensors move prior to UES movement (P < .001) and to a lesser extent in rostral and ventral directions (P ≤ .01) than the UES. UES closure pressure is captured with two distinct patterns: 1) a rostral UES pattern with short durations and fast rate of pressure release, depicting UES descent along the catheter as it closes; and 2) a caudal UES pattern with tonic pressures at baseline and a deglutitive nadir. The HRM + EMG multisensor correlation (r = 0.88) was significantly stronger than the single-sensor correlation (r = 0.80; P = .02). CONCLUSIONS: During deglutition, the HRM catheter and the UES rise above baseline positions and create a distinctive, multisensor manometric trace. Accurate deglutitive UES pressure evaluation must include multiple manometric sensors. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:657-664, 2016.

Evaluating the tongue-hold maneuver using high-resolution manometry and electromyography.

The tongue-hold maneuver is a widely used clinical technique designed to increase posterior pharyngeal wall movement in individuals with dysphagia. It is hypothesized that the tongue-hold maneuver results in increased contraction of the superior pharyngeal constrictor. However, an electromyographic study of the pharynx and tongue during the tongue-hold is still needed to understand whether and how swallow muscle activity and pressure may change with this maneuver. We tested eight healthy young participants using simultaneous intramuscular electromyography with high-resolution manometry during three task conditions including (a) saliva swallow without maneuver, (b) saliva swallow with the tongue tip at the lip, and (c) saliva swallow during the tongue-hold maneuver. We tested the hypothesis that tongue and pharyngeal muscle activity would increase during the experimental tasks, but that pharyngeal pressure would remain relatively unchanged. We found that the pre-swallow magnitude of tongue, pharyngeal constrictor, and cricopharyngeus muscle activity increased. During the swallow, the magnitude and duration of tongue and pharyngeal constrictor muscle activity each increased. However, manometric pressures and durations remained unchanged. These results suggest that increased superior pharyngeal constrictor activity may serve to maintain relatively stable pharyngeal pressures in the absence of posterior tongue movement. Thus, the tongue-hold maneuver may be a relatively simple but robust example of how the medullary swallow center is equipped to dynamically coordinate actions between tongue and pharynx. Our findings emphasize the need for combined modality swallow assessment to include high-resolution manometry and intramuscular electromyography to evaluate the potential benefit of the tongue-hold maneuver for clinical populations.

Quantifying contributions of the cricopharyngeus to upper esophageal sphincter pressure changes by means of intramuscular electromyography and high-resolution manometry.

OBJECTIVES: We sought to determine whether the association between cricopharyngeus muscle activity and upper esophageal sphincter pressure may change in a task-dependent fashion. We hypothesized that more automated tasks related to swallow or airway protection would yield a stronger association than would more volitional tasks related to tidal breathing or voice production. METHODS: Six healthy adult subjects underwent simultaneous intramuscular electromyography of the cricopharyngeus muscle and high-resolution manometry of the upper esophageal sphincter. Correlation coefficients were calculated to characterize the association between the time-linked series. RESULTS: Cricopharyngeus muscle activity was most strongly associated with upper esophageal sphincter pressure during swallow and effortful exhalation tasks (r = 0.77 and 0.79, respectively; P < .01). The association was also less variable during swallow and effortful exhalation. CONCLUSIONS: These findings suggest a greater coupling for the more automatic tasks, and may suggest less coupling and more flexibility for the more volitional, voice-related tasks. These findings support the important role of central patterning for respiratory- and swallow-related tasks.

Voice-related modulation of mechanosensory detection thresholds in the human larynx.

Rapidly adapting mechanoreceptors within the laryngeal mucosa provide the central nervous system with perceptual and proprioceptive afference for a variety of essential yet diverse human functions including voice sound production and airway protection. It is unknown why mechanosensory information that yields a defensive response when an individual breathes may go largely unnoticed when the individual voices. Therefore, a central question is whether there is voice-related modulation of laryngeal mechanosensory detection. Such modulation would be consistent with current models of afferent laryngeal control, and may be important to maintain fluent voice in the presence of potentially distracting sensory input. Therefore, we employed endoscopic assessment of laryngeal mechanosensory detection thresholds in ten healthy adults during tidal breathing and a voice task. We tested the hypothesis that laryngeal mechanosensory detection thresholds would be higher during the voice task. We found that thresholds were significantly higher for all participants during the voice task and that these changes were significantly more modest in women. Our findings suggest that the laryngeal sensorium may modulate mechanosensory afference to attenuate the potentially distracting influence of sensory input during voice. The finding that women maintain a greater sensitivity during the voice task than men (lower thresholds) may have important implications for the higher prevalence of sensorimotor voice disturbances in women. Our results are consistent with the presence of mechanosensory modulation in other motor systems and with observed sensory differences between women and men. Such modulation has important implications for understanding the underlying neural mechanisms of laryngeal control and how these mechanisms may operate in individuals with laryngeal disturbances.

Aerodynamic assessment of phonatory onset in Parkinson's disease: evidence of decreased scaling of laryngeal and respiratory control.

BACKGROUND: Phonatory onset is important for speech and voice and may be substantially impaired in people with Parkinson's Disease (PD). However, the physiologic contributions of laryngeal and respiratory control to phonatory onset in PD are not well understood. Acoustic measurement of phonatory onset in neurological disease has been limited due to the confounding effects of dysarthria and the limited yield of physiologic detail. OBJECTIVE: The purpose of this study was to test whether air flow measures would be useful to characterize respiratory and laryngeal contributions to phonatory onset, whether acoustic and air flow measures of phonatory onset were aberrant in PD, and whether deficits were significantly associated with voice severity. METHODS: Twenty-one PD participants were tested and compared with 25 healthy controls. Testing included acoustic and air flow measures of phonatory onset during syllable production ([pa]) and measures of voice severity. RESULTS: Air flow assessment was possible for all participants; acoustic assessment was only possible for 86% of PD participants. Air flow and acoustic measures revealed shorter phonatory onset times for PD participants than controls. Air flow measures also revealed that PD participants expelled less lung air volume per syllable. Aberrant timing of phonatory onset and reduced lung air volume were associated with increased voice severity. CONCLUSIONS: These findings suggest that air flow measures may be useful to assess the laryngeal and respiratory contributions to phonatory onset. These results also suggest that both respiratory and laryngeal control deficits may contribute to phonatory errors in PD, and that phonatory onset deficits are associated with voice severity.

Airway somatosensory deficits and dysphagia in Parkinson's disease.

BACKGROUND: Individuals with Parkinson's disease (PD) often experience substantial impairment of swallow control, and are typically unaware of the presence or severity of their impairments suggesting that these individuals may also experience airway sensory deficits. However, the degree to which impaired swallow function in PD may relate to airway sensory deficits has yet to be formally tested. OBJECTIVE: The purpose of this study was to examine whether airway sensory function is associated with swallow impairment in PD. METHODS: Eighteen PD participants and 18 healthy controls participated in this study and underwent endoscopic assessment of airway somatosensory function, endoscopic assessment of swallow function, and clinical ratings of swallow and disease severity. RESULTS: PD participants exhibited abnormal airway somatosensory function and greater swallow impairment compared with healthy controls. Swallow and sensory deficits in PD were correlated with disease severity. Moreover, PD participants reported similar self-rated swallow function as healthy controls, and swallow deficits were correlated with sensory function suggesting an association between impaired sensory function and poor self-awareness of swallow deficits in PD. CONCLUSIONS: These results suggest that control of swallow is influenced by airway somatosensory function, that swallow-related deficits in PD are related to abnormal somatosensation, and that swallow and airway sensory function may degrade as a function of disease severity. Therefore, the basal ganglia and related neural networks may play an important role to integrate airway sensory input for swallow-related motor control. Furthermore, the airway deficits observed in PD suggest a disintegration of swallow-related sensory and motor control.

Videofluorographic assessment of deglutitive behaviors in a rat model of aging and Parkinson disease.

Dysphagia is commonly associated with aging and Parkinson disease and can have a significant impact on a person's quality of life. In some cases, dysphagia may be life-threatening. Animal models may be used to study underlying mechanisms of dysphagia, but paradigms that allow adequate imaging of the swallow in combination with measurement of physiological variables have not been forthcoming. To begin development of methods that allow this, we used videofluorography to record the deglutition behaviors of 22 Fisher 344/Brown Norway rats in young adult (9 months old), old (32 months old), and parkinsonian (unilateral lesion to the medial forebrain bundle) groups. We hypothesized that the old and parkinsonian rats would manifest deficits in deglutition behaviors analogous to those found in human clinical populations. Our results supported our hypothesis in that the old group demonstrated reductions in bolus transport speeds and mastication rate while the parkinsonian rats showed impairments in oral processing. Interpretation of these results should consider the particular animal model, lesion type, and videofluorographic protocol used in this work. Future studies will link swallow imaging data of this kind with physiological and anatomical data in a manner not possible with human participants.

Subthalamic nucleus deep brain stimulation changes velopharyngeal control in Parkinson's disease.

PURPOSE: Adequate velopharyngeal control is essential for speech, but may be impaired in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves limb function in PD, but the effects on velopharyngeal control remain unknown. We tested whether STN DBS would change aerodynamic measures of velopharyngeal control, and whether these changes were correlated with limb function and stimulation settings. METHODS: Seventeen PD participants with bilateral STN DBS were tested within a morning session after a minimum of 12h since their most recent dose of anti-PD medication. Testing occurred when STN DBS was on, and again 1h after STN DBS was turned off, and included aerodynamic measures during syllable production, and standard neurological ratings of limb function. RESULTS: We found that PD participants exhibited changes with STN DBS, primarily consistent with increased intraoral pressure (n=7) and increased velopharyngeal closure (n=5). These changes were modestly correlated with measures of limb function, and were correlated with stimulation frequency. CONCLUSION: Our findings suggest that STN DBS may change velopharyngeal control during syllable production in PD, with greater benefit associated with low frequency stimulation. However, DBS demonstrates a more subtle influence on speech-related velopharyngeal control than limb motor control. This distinction and its underlying mechanisms are important to consider when assessing the impact of STN DBS on PD. LEARNING OUTCOMES: As a result of this activity, the participant will be able to (1) describe the effects of deep brain stimulation on limb and speech function; (2) describe the effects of deep brain stimulation on velopharyngeal control; and (3) discuss the possible reasons for differences in limb outcomes compared with speech function with deep brain stimulation of the subthalamic nucleus.

Ultrasonic output from the excised rat larynx.

The source of ultrasonic vocalizations (USVs) produced by rats is thought to be within the larynx. The purpose of this investigation was to determine if the rat larynx is capable of producing ultrasounds with the full range of frequencies reported in vivo. Acoustic output of excised rat larynges with and without vocal fold constriction was measured. At biologically-reasonable airflow rates and pressures, only larynges with a constriction produced the full range of ultrasounds reported in vivo, providing support for the hypothesis that a constriction within the larynx is likely the source of rat USVs.

Subthalamic nucleus deep brain stimulation changes speech respiratory and laryngeal control in Parkinson's disease.

Adequate respiratory and laryngeal motor control are essential for speech, but may be impaired in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves limb function in PD, but the effects on respiratory and laryngeal control remain unknown. We tested whether STN DBS would change aerodynamic measures of respiratory and laryngeal control, and whether these changes were correlated with limb function and stimulation parameters. Eighteen PD participants with bilateral STN DBS were tested within a morning session after a minimum of 12 h since their most recent dose of anti-PD medication. Testing occurred when DBS was on, and again 1 h after DBS was turned off, and included aerodynamic measures during syllable production, and standard clinical ratings of limb function. We found that PD participants exhibited changes with DBS, consistent with increased respiratory driving pressure (n = 9) and increased vocal fold closure (n = 9). However, most participants exceeded a typical operating range for these respiratory and laryngeal control variables with DBS. Changes were uncorrelated with limb function, but showed some correlation with stimulation frequency and pulse width, suggesting that speech may benefit more from low-frequency stimulation and shorter pulse width. Therefore, high-frequency STN DBS may be less beneficial for speech-related respiratory and laryngeal control than for limb motor control. It is important to consider these distinctions and their underlying mechanisms when assessing the impact of STN DBS on PD.

Laryngeal somatosensory deficits in Parkinson's disease: implications for speech respiratory and phonatory control.

Parkinson's disease (PD) is often associated with substantial impairment of speech respiratory and phonatory control. However, the degree to which these impairments are related to abnormal laryngeal sensory function is unknown. This study examined whether individuals with PD exhibited abnormal and more asymmetric laryngeal somatosensory function compared with healthy controls, and whether these deficits were associated with disease and voice severity. Nineteen PD participants were tested and compared with 18 healthy controls. Testing included endoscopic assessment of laryngeal somatosensory function, with aerodynamic and acoustic assessment of respiratory and phonatory control, and clinical ratings of voice and disease severity. PD participants exhibited significantly abnormal and asymmetric laryngeal somatosensory function compared with healthy controls. Sensory deficits were significantly associated with timing of phonatory onset, voice intensity, respiratory driving pressure, laryngeal resistance, lung volume expended per syllable, disease severity, and voice severity. These results suggest that respiratory and phonatory control are influenced by laryngeal somatosensory function, that speech-related deficits in PD are related to abnormal laryngeal somatosensory function, and that this function may degrade as a function of disease severity. Thus, PD may represent a model of airway sensorimotor disintegration, highlighting the important role of the basal ganglia and related neural networks in the integration of laryngeal sensory input for speech-related motor control.

Design of a new somatosensory stimulus delivery device for measuring laryngeal mechanosensory detection thresholds in humans.

Laryngeal control is essential for airway protection, breathing, deglutition, speech, and voice. Unfortunately, integration of laryngeal sensory assessment in research and clinical practice is limited by technical and practical limitations of commercially available technology. A commercial device is available, but reported limitations include procedural complexity requiring two or three individuals to operate, limited stimulus dynamic range, device generated noise, and questionable stimulus reproducibility. The objective of this study was to design a new laryngeal somatosensory stimulus delivery device that provides direct, reliable control over the timing, duration, and dynamic range of stimulus presentation, and test the device in individuals who may manifest a laryngeal sensory deficit. The new device operates silently and has more than four times greater stimulus dynamic range than the commercial device. Testing with the new device revealed laryngeal mechanosensory detection thresholds in an individual with Parkinson's disease that were seven times higher than those of healthy controls. These data would have otherwise gone undetected due to limited stimulus dynamic range in the commercial device. The new design resulted in a new assessment instrument that is simple to use for routine clinical assessment, yet sufficiently versatile for integration within rigorous clinical research protocols.