RESUMO
Vagus nerve stimulation (VNS) is thought to affect neural activity by recruiting brain-wide release of neuromodulators. VNS is used in treatment-resistant epilepsy, and is increasingly being explored for other disorders, such as depression, and as a cognitive enhancer. However, the promise of VNS is only partially fulfilled due to a lack of mechanistic understanding of the transfer function between stimulation parameters and neuromodulatory response, together with a lack of biosensors for assaying stimulation efficacy in real time. We here develop an approach to VNS in head-fixed mice on a treadmill and show that pupil dilation is a reliable and convenient biosensor for VNS-evoked cortical neuromodulation. In an 'optimal' zone of stimulation parameters, current leakage and off-target effects are minimized and the extent of pupil dilation tracks VNS-evoked basal-forebrain cholinergic axon activity in neocortex. Thus, pupil dilation is a sensitive readout of the moment-by-moment, titratable effects of VNS on brain state.
Assuntos
Pupila/fisiologia , Nervo Vago/fisiologia , Animais , Encéfalo , Córtex Cerebelar/fisiologia , Epilepsia/fisiopatologia , Feminino , Locus Cerúleo/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estimulação do Nervo Vago , Vigília/fisiologiaRESUMO
We introduce a novel diagnostic Visual Voiding Device (VVD), which has the ability to visually document urinary voiding events and calculate key voiding parameters such as instantaneous flow rate. The observation of the urinary voiding process along with the instantaneous flow rate can be used to diagnose symptoms of Lower Urinary Tract Dysfunction (LUTD) and improve evaluation of LUTD treatments by providing subsequent follow-up documentations of voiding events after treatments. The VVD enables a patient to have a urinary voiding event in privacy while a urologist monitors, processes, and documents the event from a distance. The VVD consists of two orthogonal cameras which are used to visualize urine leakage from the urethral meatus, urine stream trajectory, and its break-up into droplets. A third, lower back camera monitors a funnel topped cylinder where urine accumulates that contains a floater for accurate readings regardless of the urine color. Software then processes the change in level of accumulating urine in the cylinder and the visual flow properties to calculate urological parameters. Video playback allows for reexamination of the voiding process. The proposed device was tested by integrating a mass flowmeter into the setup and simultaneously measuring the instantaneous flow rate of a predetermined voided volume in order to verify the accuracy of VVD compared to the mass flowmeter. The VVD and mass flowmeter were found to have an accuracy of ±2 and ±3% relative to full scale, respectively. A VVD clinical trial was conducted on 16 healthy male volunteers ages 23-65.