RESUMEN

Monitoring representative fractions of neurons from multiple brain circuits in behaving animals is necessary for understanding neuronal computation. Here, we describe a system that allows high-channel-count recordings from a small volume of neuronal tissue using a lightweight signal multiplexing headstage that permits free behavior of small rodents. The system integrates multishank, high-density recording silicon probes, ultraflexible interconnects, and a miniaturized microdrive. These improvements allowed for simultaneous recordings of local field potentials and unit activity from hundreds of sites without confining free movements of the animal. The advantages of large-scale recordings are illustrated by determining the electroanatomic boundaries of layers and regions in the hippocampus and neocortex and constructing a circuit diagram of functional connections among neurons in real anatomic space. These methods will allow the investigation of circuit operations and behavior-dependent interregional interactions for testing hypotheses of neural networks and brain function.

Asunto(s)

RESUMEN

The rodent somatosensory barrel cortex (S1bf) has proved a valuable model for studying neural plasticity in vivo. It has been observed that sensory deprivation or conditioning reorganizes sensory-driven activity within S1bf. These observations suggest a role for S1bf in somatosensory learning. This study evaluated the hypothesis that the response properties of extracellularly recorded neurons in S1bf would change as subjects learned to respond to stimulation of S1bf. Intracortical microstimulation (ICMS) of S1bf was used as a means for bypassing feedforward drive from the sensory periphery, midbrain, and thalamus while exciting local cortical networks. To separate the learning of this conditioned stimulus-conditioned response (CS-CR) from other elements of the task, we employed a cross-modal transfer schedule. Long-Evans rats were initially trained to respond to an auditory stimulus. All subjects were then implanted in both S1bfs with chronic microwire arrays for recording neural activity and delivering ICMS. Next, this association was transferred to ICMS of one hemisphere's S1bf. S1bf responded to ICMS with a brief increase in firing rate followed by a longer reduction in activity. We observed that the duration of reduced activity elicited by ICMS increased as the subjects began to respond correctly more often than expected by chance, and the magnitude of the initial positive response increased as they consolidated this CS-CR. Subsequent ICMS of the opposite S1bf revealed that this CS-CR did not generalize across hemispheres. These results suggest that a mechanism involving a single hemisphere's S1bf tunes cortical responses in concert with changes in rodent behavior during somatosensory learning.

Asunto(s)

RESUMEN

The ability to learn new skills and perfect them with practice applies not only to physical skills but also to abstract skills, like motor planning or neuroprosthetic actions. Although plasticity in corticostriatal circuits has been implicated in learning physical skills, it remains unclear if similar circuits or processes are required for abstract skill learning. Here we use a novel behavioural task in rodents to investigate the role of corticostriatal plasticity in abstract skill learning. Rodents learned to control the pitch of an auditory cursor to reach one of two targets by modulating activity in primary motor cortex irrespective of physical movement. Degradation of the relation between action and outcome, as well as sensory-specific devaluation and omission tests, demonstrate that these learned neuroprosthetic actions are intentional and goal-directed, rather than habitual. Striatal neurons change their activity with learning, with more neurons modulating their activity in relation to target-reaching as learning progresses. Concomitantly, strong relations between the activity of neurons in motor cortex and the striatum emerge. Specific deletion of striatal NMDA receptors impairs the development of this corticostriatal plasticity, and disrupts the ability to learn neuroprosthetic skills. These results suggest that corticostriatal plasticity is necessary for abstract skill learning, and that neuroprosthetic movements capitalize on the neural circuitry involved in natural motor learning.

Asunto(s)

RESUMEN

The growing use of multi-channel neural recording techniques in behaving animals has produced rich datasets that hold immense potential for advancing our understanding of how the brain mediates behavior. One limitation of these techniques is they do not provide important information about the underlying anatomical connections among the recorded neurons within an ensemble. Inferring these connections is often intractable because the set of possible interactions grows exponentially with ensemble size. This is a fundamental challenge one confronts when interpreting these data. Unfortunately, the combination of expert knowledge and ensemble data is often insufficient for selecting a unique model of these interactions. Our approach shifts away from modeling the network diagram of the ensemble toward analyzing changes in the dynamics of the ensemble as they relate to behavior. Our contribution consists of adapting techniques from signal processing and Bayesian statistics to track the dynamics of ensemble data on time-scales comparable with behavior. We employ a Bayesian estimator to weigh prior information against the available ensemble data, and use an adaptive quantization technique to aggregate poorly estimated regions of the ensemble data space. Importantly, our method is capable of detecting changes in both the magnitude and structure of correlations among neurons missed by firing rate metrics. We show that this method is scalable across a wide range of time-scales and ensemble sizes. Lastly, the performance of this method on both simulated and real ensemble data is used to demonstrate its utility.

RESUMEN

Corticostriatal dynamics exhibit gross alterations over the course of natural motor learning, yet little is known about the role they play in neuroprosthetic tasks. We therefore investigated interactions between the striatum and primary motor cortex while rats learned to control a brain-machine interface. Striatal firing rates increased greatly from early to late in learning, suggesting that the striatum underlies similar functions in both natural and neuroprosthetic motor learning. In addition, spike-field coherence between neurons in primary motor cortex and local field potentials in the striatum increased greatly in the alpha band in late learning relative to early learning, suggesting the development of functional interactions in corticostriatal networks over the course of learning.

Asunto(s)

RESUMEN

There is growing interest in intracortical microstimulation as a means of providing sensory input in neuroprosthetic systems. We believe that precisely controlling the timing and parameters of stimulation in closed loop can significantly improve the efficacy of this technique. Here, we present a system for closed-loop microstimulation in awake rodents chronically implanted with multielectrode arrays. The system interfaces with existing commercial recording and stimulating hardware. Using custom-made hardware, we can stimulate and record from electrodes on the same implanted array and significantly reduce the stimulation artifact. Stimulation sequences can either be preprogrammed or triggered by neural or behavioral events. Specifically, this system can provide feedback stimulation in response to action potentials or features in the local field potential recorded on any of the electrodes within 15 ms. It can also trigger stimulation based on behavioral events, such as real-time tracking of rat whiskers captured with high-speed video. We believe that this system, which can be recreated easily, will help to significantly refine the technique of intracortical microstimulation and advance the field of neuroprostheses.

Asunto(s)

RESUMEN

Nonerosive reflux disease (NERD) is the most common phenotype of gastroesophageal reflux disease. By definition, patients with NERD have typical reflux symptoms caused by the intraesophageal reflux of gastric contents but have no visible esophageal mucosal injury. This is in contrast to patients with reflux esophagitis, also known as erosive reflux disease, and Barrett's esophagus, who have obvious esophageal mucosal injury on endoscopy. Only 50% of patients with NERD have pathologic esophageal acid contact time (ACT) as detected on 24-hour pH monitoring (ie, NERD-positive). NERD patients with physiologic esophageal ACT and good temporal correlation of symptoms with reflux events (symptom index > 50% or symptom-association probability > 95%) are considered to have esophageal hypersensitivity (ie, NERD-negative). Finally, patients with physiologic esophageal ACT but poor symptom-reflux correlation are now considered to have functional heartburn and not NERD. NERD-positive patients have motor dysfunction and acidic reflux abnormalities that are similar to patients with reflux esophagitis and Barrett's esophagus, whereas NERD-negative patients have minimal abnormalities that are not much different than healthy controls. The histopathologic feature most indicative of NERD is the presence of dilated intercellular spaces within squamous epithelium, an ultrastructural abnormality readily identified on transmission electron microscopy and on light microscopy.

Asunto(s)

RESUMEN

Wireless sensors were designed which are small and light enough to be worn by small animals such as rats. These sensors are used to record three axes acceleration data from animals during natural behavior in a cage. The behavior of the animal is further extracted from the recorded acceleration data using neural network based pattern recognition algorithms. Successful recognition of eating, grooming and standing are demonstrated using this approach. Finally another potential application of this research is demonstrated in behavioral neuroscience by showing correlations between action potentials recorded from the motor cortex of a rat and acceleration data.

Asunto(s)

RESUMEN

The most appropriate diagnostic and therapeutic approach to patients with heartburn that persists despite the use of proton-pump inhibitor (PPI) therapy currently is not known. In general, patients with heartburn refractory to PPIs may have more than one explanation for their persistent symptoms. These include uncontrolled esophageal acid exposure ("PPI failure") in a small subset of patients, as well as other potential etiologies in the majority of patients who have controlled esophageal acid exposure on PPI therapy ("PPI success"). Some potential explanations for persistent heartburn in this latter group include hypersensitivity to acid reflux, nonacidic or duodenogastric esophageal reflux, as well as functional heartburn. Patients who present with heartburn refractory to PPIs should be investigated further to determine the potential cause. We believe the diagnostic modality with the most clinical usefulness is 24-hour pH and multichannel intraluminal impedance monitoring with symptom index performed while the patient is on high-dose PPI therapy. This approach allows the patient to be properly categorized and also identifies a substantial proportion of patients who will have functional heartburn, a condition that should discourage the use of endoscopic or surgical therapies. Therapeutic options for patients with heartburn refractory to PPIs are limited and have not been thoroughly studied. As a result of the paucity of information, we favor a therapeutic approach based on the outcome of diagnostic testing.

RESUMEN

Long-term synaptic modification depends on the relative timing of individual pre- and postsynaptic spikes, but the rules governing the effects of multispike bursts remain to be fully understood. In particular, some studies suggest that the spike timing dependence of synaptic modification breaks down with high-frequency bursts. In this study, we characterized the effects of pre- and postsynaptic bursts on long-term modification of layer 2/3 synapses in visual cortical slices from young rats. We found that, while pairing-induced synaptic modification depends on the burst frequency, this dependence can be explained in terms of the timing of individual pre- and postsynaptic spikes. Later spikes in each burst are less effective in synaptic modification, but spike efficacy is regulated differently in pre- and postsynaptic bursts. Presynaptically, spike efficacy is progressively weakened, in parallel with short-term synaptic depression. Postsynaptically, spike efficacy is suppressed to a lesser extent, and it depends on postsynaptic potassium channel activation. Such timing-dependent interaction among multiple spikes can account for synaptic modifications induced by a variety of spike trains, including the frequency-dependent transition from depression to potentiation induced by a postsynaptic burst preceding a presynaptic burst.

Asunto(s)

RESUMEN

OBJECTIVE: To determine the efficacy of proton-pump inhibitor (PPI) therapy for chronic laryngo-pharyngitis treated with lifestyle modification. STUDY DESIGN AND METHODS: Double-blind, randomized trial comparing two-month Rabeprazole (20 mg b.i.d.) to placebo control. RESULTS: Compared to baseline, both PPI and control patients had significant improvement in total reflux symptoms (P = 0.002 and P = 0.03 respectively), with significant improvement in "laryngo-pharyngeal" but not "typical" reflux symptoms. No significant difference was noted for change in reflux symptoms between PPI-treated and control patients (P = 0.44). Significant global improvement was noted by 50% of control and 53% of PPI-treated patients (P = 1.0). No significant differences were noted within or between treatment groups for change in health status or videostrobolaryngoscopy grade. Lifestyle modification compliance correlated significantly with global improvement. CONCLUSION: Compared to baseline, lifestyle modification for 2 months significantly improved chronic laryngo-pharyngitis symptoms. When compared to control, treatment with a PPI failed to demonstrate significantly greater improvement in reflux symptoms, health status, or laryngeal appearance.

Asunto(s)

RESUMEN

The approach to treatment of adult patients with tracheoesophageal fistulas depends on whether the fistula is congenital or acquired in origin. Most adults have acquired tracheoesophageal fistulas, and treatment depends on whether the fistula is a result of a benign process or a malignancy, with the latter usually primary esophageal cancer. For patients with benign tracheoesophageal fistulas, treatment is almost always initially supportive followed by definitive surgical correction. In general, depending on the size and location of the tracheal aspect of the fistula, surgical therapy involves primary repair of the fistula and, if necessary, resection and reconstruction of the trachea. For patients with malignant tracheoesophageal fistulas, treatment depends on whether the patient is resectable and/or medically fit for surgical therapy. However, most patients with malignant trach-eoesophageal fistulas have advanced disease and can only be treated with palliative measures. The current standard of palliative therapy for patients with malignant tracheoesophageal fistulas is the endoscopic or radiologic placement of covered self-expanding metallic stents (SEMS), which allow closure of the fistula. All three types of commercially available covered SEMS have been used in this capacity with success. Other, less common treatment options for selected patients with malignant tracheoesophageal fistulas include chemotherapy and radiation, surgical bypass, esophageal exclusion, and fistula resection and repair.

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)