We recorded activity of dopamine (DA) neurons in the substantia nigra pars compacta in unrestrained mice while monitoring their movements with video tracking. Our approach allows an unbiased examination of the continuous relationship between single unit activity and behavior. Although DA neurons show characteristic burst firing following cue or reward presentation, as previously reported, their activity can be explained by the representation of actual movement kinematics. Unlike neighboring pars reticulata GABAergic output neurons, which can represent vector components of position, DA neurons represent vector components of velocity or acceleration. We found neurons related to movements in four directions—up, down, left, right. For horizontal movements, there is significant lateralization of neurons: the left nigra contains more rightward neurons, whereas the right nigra contains more leftward neurons. The relationship between DA activity and movement kinematics was found on both appetitive trials using sucrose and aversive trials using air puff, showing that these neurons belong to a velocity control circuit that can be used for any number of purposes, whether to seek reward or to avoid harm. In support of this conclusion, mimicry of the phasic activation of DA neurons with selective optogenetic stimulation could also generate movements. Contrary to the popular hypothesis that DA neurons encode reward prediction errors, our results suggest that nigrostriatal DA plays an essential role in controlling the kinematics of voluntary movements. We hypothesize that DA signaling implements gain adjustment for adaptive transition control, and describe a new model of the basal ganglia (BG) in which DA functions to adjust the gain of the transition controller. This model has significant implications for our understanding of movement disorders implicating DA and the BG.
The basal ganglia (BG) are implicated in many movement disorders, yet how they contribute to movement remains unclear. Using wireless in vivo recording, we measured BG output from the substantia nigra pars reticulata (SNr) in mice while monitoring their movements with video tracking. The firing rate of most nigral neurons reflected Cartesian coordinates (either x-or y-coordinates) of the animal's head position during movement. The firing rates of SNr neurons are either positively or negatively correlated with the coordinates. Using an egocentric reference frame, four types of neurons can be classified: each type increases firing during movement in a particular direction (left, right, up, down), and decreases firing during movement in the opposite direction. Given the high correlation between the firing rate and the x and y components of the position vector, the movement trajectory can be reconstructed from neural activity. Our results therefore demonstrate a quantitative and continuous relationship between BG output and behavior. Thus, a steady BG output signal from the SNr (i.e., constant firing rate) is associated with the lack of overt movement, when a stable posture is maintained by structures downstream of the BG. Any change in SNr firing rate is associated with a change in position (i.e., movement). We hypothesize that the SNr output quantitatively determines the direction, velocity, and amplitude of voluntary movements. By changing the reference signals to downstream position control systems, the BG can produce transitions in body configurations and initiate actions.
The contribution of basal ganglia outputs to consummatory behavior remains poorly understood. We recorded from the substantia nigra pars reticulata (SNR), the major basal ganglia output nucleus, during self-initiated drinking. The firing rates of many lateral SNR neurons were time-locked to individual licks. These neurons send GABAergic projections to the deep layers of the orofacial region of the lateral tectum (superior colliculus, SC). Many tectal neurons are also time-locked to licking, but their activity is usually antiphase to that of SNR neurons, suggesting inhibitory nigrotectal projections. We used optogenetics to selectively activate the GABAergic nigrotectal afferents in the deep layers of the SC. Photo-stimulation of the nigrotectal projections transiently inhibited the activity of the lick-related tectal neurons, disrupted their licking-related oscillatory pattern, and suppressed self-initiated drinking. These results demonstrate that GABAergic nigrotectal projections play a crucial role in coordinating drinking behavior.
Objectives/Hypothesis Opioid‐related deaths in the United States have increased 200% since 2000, in part due to prescription diversion from patients who had a surgical procedure. The purpose of this study was to characterize provider prescription patterns and assess patient‐reported opioid use after endoscopic sinus surgery (ESS). Study Design Retrospective chart review. Methods Patients who underwent ESS between May 2017 and May 2018 were included. Opioid prescription, operative details, and postoperative opioid use data were extracted. The Massachusetts Prescription Awareness Tool (MassPAT) was queried to determine if patients filled their prescription. Results One hundred fifty‐five patients were included. Nearly all patients received an opioid prescription (94.8%). An average of 15.6 tablets was prescribed per patient. Among 116 patients with MassPAT data, 91.4% filled their prescription. Among 67 patients who reported the number of tablets they had used at the time of first follow‐up appointment, 73.1% reported taking no opioids. Mean number of tablets prescribed was significantly greater among patients who underwent primary versus revision surgery (16.5 vs. 13.5, P = .0111) and those who had splints placed (21.5 vs. 15.1, P = .0037). Predictors of opioid use included concurrent turbinate reduction (58.3% vs. 14.3%, P < .0001) and concurrent septoplasty (45.5% vs. 21.6%, P = .039). Conclusions Nearly all patients who underwent ESS were prescribed an opioid, and nearly all patients filled their prescription. However, the vast majority of patients did not require any opioid medication for postoperative pain control. As the opioid epidemic continues to persist, these findings have immediate relevance to current prescribing patterns and pain management practices. Level of Evidence 4 Laryngoscope, 129:1046–1052, 2019
The basal ganglia have long been implicated in action initiation. Using three-dimensional motion capture, we quantified the effects of optogenetic stimulation of the striatonigral (direct) pathway on movement kinematics. We generated transgenic mice with channelrhodopsin-2 expression in striatal neurons that express the D1-like dopamine receptor. With optic fibres placed in the sensorimotor striatum, an area known to contain movement velocity-related single units, photo-stimulation reliably produced movements that could be precisely quantified with our motion capture programme. A single light pulse was sufficient to elicit movements with short latencies (< 30 ms). Increasing stimulation frequency increased movement speed, with a highly linear relationship. These findings support the hypothesis that the sensorimotor striatum is part of a velocity controller that controls rate of change in body configurations.
In January 2019, the Centers for Medicare and Medicaid Services (CMS) began legally requiring hospitals to pub-lish chargemasters online to promote price transparency. 1 Hospital chargemasters list gross charges for all items and services, which are the undiscounted prices hospitals bill patients who are uninsured, self pay, or have out-of-network insurance.
Objective: To determine the prevalence of radiographic cochlear–facial nerve dehiscence (CFD). Study Design: Retrospective radiological study. Setting: Two tertiary-referral centers. Patients: Two hundred six temporal-bone computed tomography (CT) scans (405 total ears) of otology/neurotology patients from two academic institutions between the years 2014 and 2017. Intervention: Diagnostic. Main Outcome Measures: The cochlear–facial nerve partition width (CFPW) was measured on coronal CT sections and defined as the shortest distance between the cochlear basal turn and facial nerve (FN) labyrinthine segment. We used logistics regression analyses to determine positive predictors for radiographic evidence of CFD. Results: The overall prevalence of radiographic CFD was 5.4% (22/406 ears). 9.2% of patients (19/206) had CFD. Of these 19 patients, only one patient had mixed hearing loss that could not be explained by any other vestibular or auditory etiology. Three out of 206 patients had dehiscence in both ears (1.4%). The average CFPW was 0.6 ± 0.2 mm, and fallopian canal width was 1.1 ± 0.02 mm (n = 405). Older age, use of traditional CT scans, and thinner CT slice thickness were significant predictors for radiographic CFD. Conclusions: The radiographic prevalence of CFD is higher than what is reported in histologic studies, and may over-estimate the true prevalence of CFD. The clinician should keep this in mind when considering this as potential cause for third-window symptoms.
Objective: The term "labyrinthine concussion" has evolved to mean audiovestibular dysfunction in the absence of a temporal bone fracture (TBF). Despite a multitude of case descriptions of labyrinthine concussion, the precise pathophysiology remains poorly understood. Herein, we explore the historical otopathologic underpinnings of the diagnosis of labyrinthine concussion with a focus on the auditory pathway during the late 19th to the mid-20th centuries and conclude with a discussion of its contemporary relevance.Methods and Data Sources: A review of primary and secondary medical sources written in English, German, and French on otopathology labyrinthine concussion studies from the late-19th to the mid-20th centuries. Results: Around the turn of the 20th century, otopathologists identified histologic changes in the temporal bones of individuals that sustained head injury without TBFs. Based on these otopathologic findings in humans, early experiments investigating the pathophysiology of labyrinthine concussion were performed in animals through either the delivery of blows to the head or direct introduction of a pressure wave into the labyrinthine fluid. Collectively, otopathologists hypothesized that predominant mechanisms for labyrinthine concussion included inner ear hemorrhage, cochleovestibular nerve traction injury, direct damage from a labyrinthine fluid pressure wave, or vasomotor dysfunction. Conclusion: Historical study shows a variety of inner ear pathologies potentially responsible for auditory dysfunction following head injury. Understanding the history and otopathology of labyrinthine concussion may help clinicians focus on new pathways toward novel research and improved patient care. K E Y W O R D S chronic traumatic encephalopathy, dementia pugilistica, head injury, hearing loss, history of otology, inner ear concussion, labyrinthine concussion
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