Suppression of Motor Cortical Excitability in Anesthetized Rats by Low Frequency Repetitive Transcranial Magnetic Stimulation

Repetitive transcranial magnetic stimulation (rTMS) is a widely-used method for modulating cortical excitability in humans, by mechanisms thought to involve use-dependent synaptic plasticity. For example, when low frequency rTMS (LF rTMS) is applied over the motor cortex, in humans, it predictably leads to a suppression of the motor evoked potential (MEP), presumably reflecting long-term depression (LTD) – like mechanisms. Yet how closely such rTMS effects actually match LTD is unknown. We therefore sought to (1) reproduce cortico-spinal depression by LF rTMS in rats, (2) establish a reliable animal model for rTMS effects that may enable mechanistic studies, and (3) test whether LTD-like properties are evident in the rat LF rTMS setup. Lateralized MEPs were obtained from anesthetized Long-Evans rats. To test frequency-dependence of LF rTMS, rats underwent rTMS at one of three frequencies, 0.25, 0.5, or 1 Hz. We next tested the dependence of rTMS effects on N-methyl-D-aspartate glutamate receptor (NMDAR), by application of two NMDAR antagonists. We find that 1 Hz rTMS preferentially depresses unilateral MEP in rats, and that this LTD-like effect is blocked by NMDAR antagonists. These are the first electrophysiological data showing depression of cortical excitability following LF rTMS in rats, and the first to demonstrate dependence of this form of cortical plasticity on the NMDAR. We also note that our report is the first to show that the capacity for LTD-type cortical suppression by rTMS is present under barbiturate anesthesia, suggesting that future neuromodulatory rTMS applications under anesthesia may be considered

Beyond CPAP: modifying upper airway output for the treatment of OSA

Obstructive Sleep Apnea (OSA) is exceedingly common but often under-treated. Continuous positive airway pressure (CPAP) has long been considered the gold standard of OSA therapy. Limitations to CPAP therapy include adherence and availability. The 2021 global CPAP shortage highlighted the need to tailor patient treatments beyond CPAP alone. Common CPAP alternative approaches include positional therapy, mandibular advancement devices, and upper airway surgery. Upper airway training consists of a variety of therapies, including exercise regimens, external neuromuscular electrical stimulation, and woodwind instruments. More invasive approaches include hypoglossal nerve stimulation devices. This review will focus on the approaches for modifying upper airway muscle behavior as a therapeutic modality in OSA

Three‐dimensional posture changes of the vocal fold from paired intrinsic laryngeal muscles

Objectives/hypothesisAlthough the geometry of the vocal fold medial surface affects voice quality and is critical in the treatment of glottic insufficiency, the prephonatory shape of the vocal fold medial surface is not well understood. In this study, we activated intrinsic laryngeal muscles individually and in combinations, and recorded the temporal sequence and precise three-dimensional configurational changes of the vocal fold medial surface.Study designIn vivo canine hemilarynx model.MethodsA hemilaryngectomy was performed in an in vivo canine model and ink was used to mark the medial surface of the in situ vocal fold in a grid-like fashion. The thyroarytenoid (TA), lateral cricoarytenoid (LCA), cricothyroid (CT), and posterior cricoarytenoid (PCA) muscles were stimulated individually and in combinations. A right-angle prism whose hypotenuse formed the glottal midline provided two distinct views of the medial surface for a high-speed digital camera. Image-processing package DaVis (LaVision Inc., Goettingen, Germany) allowed time series cross-correlation analysis for three-dimensional deformation calculations of the vocal fold medial surface.ResultsCombined TA and LCA activation yields an evenly adducted rectangular glottal surface. Addition of thyroarytenoid to cricoarytenoid adducts the vocal fold from inferior to superior in a graded fashion allowing formation of a divergent glottis. Posterior cricoarytenoid has a bimodal relationship with thyroarytenoid favoring abduction. Cricothyroid and lateral cricoarytenoid yield unique glottal postures necessary but likely not conducive for efficient phonation.ConclusionsUnderstanding the three-dimensional geometry of the vocal fold medial surface will help us better understand the cause-effect relationship between laryngeal physiology and phonation.Level of evidenceNA Laryngoscope, 127:656-664, 2017

Quantitative Evaluation of the In Vivo Vocal Fold Medial Surface Shape

Objectives/hypothesisGlottal insufficiency is a common clinical problem in otolaryngology and medialization laryngoplasty (ML) procedures remain the primary treatment modality. Although the goal of ML is to restore physiologic glottal posture and achieve optimal phonation, this posture has not been directly measured. In this study, we assessed glottal medial surface contour changes with selective activation of the intrinsic laryngeal muscles (ILMs).Study designBasic science study using an in vivo canine hemilarynx model.MethodsIn an in vivo canine hemilarynx, India ink was used to mark fleshpoints in a grid-like fashion along the medial surface of the vocal fold and ILMs were activated in a graded manner. A right-angled prism provided two views of the medial surface, which were recorded using a high-speed camera and used to reconstruct the 3D posture deformations of the medial surface.ResultsThyroarytenoid (TA) muscle activation results in initial inferomedial bulging and increased glottal channel thickness and then glottal adduction with a final rectangular glottal channel shape. Lateral cricoarytenoid (LCA) activation closes the posterior glottis but final posture remains slightly convergent. Together, TA + LCA forms a rectangular glottis with an increased glottal vertical thickness. Posterior cricoarytenoid activation results in abduction and a slightly divergent glottis, whereas cricothyroid activation elongates the glottis and reduces the glottal channel vertical thickness.ConclusionsA quantitative analysis of in vivo canine vocal fold medial surface upon activation of selective ILMs is provided. This may guide our therapeutic efforts during medialization laryngoplasty, as well as computational modeling of laryngeal physiology

Can noninvasive brain stimulation enhance cognition in neuropsychiatric disorders?

Cognitive impairment is a core symptom of many neuropsychiatric diseases and a key contributor to the patient's quality of life. However, an effective therapeutic strategy has yet to be developed. Noninvasive brain stimulation techniques, namely transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), are promising techniques that are under investigation for a variety of otherwise treatment-resistant neuropsychiatric diseases. Notably, these tools can induce alterations in neural networks subserving cognitive operations and thus may provide a means for cognitive restoration. The purpose of this article is to review the available evidence concerning cognitive enhancing properties of noninvasive brain stimulation in neuropsychiatry. We specifically focus on major depression. Alzheimer's disease, schizophrenia, autism and attention deficit hyperactivity disorder (ADHD), where cognitive dysfunction is a major symptom and some studies have been completed with promising results. We provide a critical assessment of the available research and suggestions to guide future efforts

Dynamics of Intrinsic Laryngeal Muscle Contraction.

ObjectivesLaryngeal function requires neuromuscular activation of the intrinsic laryngeal muscles (ILMs). Rapid activation of the ILMs occurs in cough, laughter, and voice-unvoiced-voiced segments in speech and singing. Abnormal activation is observed in hyperfunctional disorders such as vocal tremor and dystonia. In this study, we evaluate the dynamics of ILM contraction.Study/designBasic science study in an in vivo canine model.MethodsThe following ILMs were stimulated: thyroarytenoid (TA), lateral cricoarytenoid/interarytenoid (LCA/IA), cricothyroid (CT), all laryngeal adductors (LCA/IA/TA), and the posterior cricoarytenoid (PCA). Neuromuscular stimulation was performed via the respective nerves at current levels needed to achieve maximum vocal fold posture change. Muscle contraction and posture changes were recorded with high speed video (HSV). HSV frames were then analyzed to measure response times required from the onset of muscle contraction to the time the vocal folds achieved maximum posture change.ResultsIn all muscles, the onset of posture change occurred within 10 to 12 milliseconds after neuromuscular stimulation. The average times ( ± standard deviation) to achieve final posture were as follows: TA 34.5 ± 6 ms (N = 15), LCA/IA 55 ± 12 ms (N = 14), recurrent laryngeal nerve 43 ± 8 ms (N = 18), CT 100.8 ± 17 ms (N = 26), and PCA 91.2 ± 8 ms (N = 3). Data distribution appeared normal.ConclusionResults showed a difference in muscle activation time between different ILMs consistent with reported differences in muscle fiber composition. These data also provide an estimate of the limits of laryngeal contraction frequency in physiologic and pathologic laryngeal states.Level of evidenceNA Laryngoscope, 129:E21-E25, 2019

Noninvasive Brain Stimulation in Traumatic Brain Injury

Objective: To review novel techniques of noninvasive brain stimulation (NBS), which may have value in assessment and treatment of traumatic brain injury (TBI). Methods: Review of the following techniques: transcranial magnetic stimulation, transcranial direct current stimulation, low-level laser therapy, and transcranial Doppler sonography. Furthermore, we provide a brief overview of TMS studies to date. Main findings: We describe the rationale for the use of these techniques in TBI, discuss their possible mechanisms of action, and raise a number of considerations relevant to translation of these methods to clinical use. Depending on the stimulation parameters, NBS may enable suppression of the acute glutamatergic hyperexcitability following TBI and/or counter the excessive GABAergic effects in the subacute stage. In the chronic stage, brain stimulation coupled to rehabilitation may enhance behavioral recovery, learning of new skills, and cortical plasticity. Correlative animal models and comprehensive safety trials seem critical to establish the use of these modalities in TBI. Conclusions: Different forms of NBS techniques harbor the promise of diagnostic and therapeutic utility, particularly to guide processes of cortical reorganization and enable functional restoration in TBI. Future lines of safety research and well-designed clinical trials in TBI are warranted to determine the capability of NBS to promote recovery and minimize disability.Supported in part by a BBVA Translational Research Chair in Biomedicine, a grant from the International Brain Research Foundation (IBRF), and National Institutes of Health grant K 24 RR018875 to A.P.L., and grant PI082004 from the Instituto de Salud Carlos III. A.M.V.-H. is a Howard Hughes Medical Institute medical research training fellowMedicin