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Stevenson R.A.,Vanderbilt University | Stevenson R.A.,Vanderbilt Brain Institute | Stevenson R.A.,Vanderbilt Kennedy Center | Stevenson R.A.,University of Toronto | And 4 more authors.
Anesthesia and Analgesia | Year: 2014

The pulse oximeter is a critical monitor in anesthesia practice designed to improve patient safety. Here, we present an approach to improve the ability of anesthesiologists to monitor arterial oxygen saturation via pulse oximetry through an audiovisual training process. Fifteen residents' abilities to detect auditory changes in pulse oximetry were measured before and after perceptual training. Training resulted in a 9% (95% confidence interval, 4%-14%, P = 0.0004, t166 = 3.60) increase in detection accuracy, and a 72-millisecond (95% confidence interval, 40-103 milliseconds, P < 0.0001, t166 = -4.52) speeding of response times in attentionally demanding and noisy conditions that were designed to simulate an operating room. This study illustrates the benefits of multisensory training and sets the stage for further work to better define the role of perceptual training in clinical anesthesiology. Copyright © 2014 International Anesthesia Research Society.

Schauder K.B.,University of Rochester | Muller C.L.,Vanderbilt Brain Institute | Veenstra-VanderWeele J.,Columbia University | Veenstra-VanderWeele J.,New York State Psychiatric Institute | And 3 more authors.
Research in Autism Spectrum Disorders | Year: 2015

Several lines of evidence implicate dysfunction of the serotonin (5-HT) system in autism spectrum disorder (ASD). Specifically, the serotonin transporter (5-HTT, SERT) has been scrutinized as an ASD candidate risk gene. SERT plays key roles in the development of circuits that underlie sensory function, particularly in the somatosensory system. One previous study in ASD found association of a rare, hyperfunctional SERT variant with sensory aversion, but studies of common SERT variants have never examined sensory symptoms in ASD. Using standardized caregiver assessments of sensory function in children, we evaluated patterns of sensory responsiveness in 47 children with ASD and 38 typically developing (TD) children. Study participants were genotyped for the functional SERT promoter polymorphisms, 5-HTTLPR and rs25531, to test the hypothesis that the higher expressing genotypes would be associated with hyperresponsiveness to touch, a common sensory aversion in ASD. All measures of sensory hypo- and hyperresponsiveness were increased in children with ASD, with hyporesponsive sensory patterns negatively correlated to age and hyperresponsive sensory patterns positively correlated to repetitive behavior. Strikingly, high-expressing SERT genotypes were associated with increased tactile hyperresponsiveness in the ASD group. Our findings indicate genetic variation that increases SERT function may specifically impact somatosensory processing in ASD. © 2014 Published by Elsevier Ltd.

News Article | October 27, 2016

The probe, which was developed by a team of Vanderbilt scientists, is a genetically modified form of luciferase, the enzyme that a number of other species including fireflies use to produce light. It is described in a paper published in the journal Nature Communications on Oct. 27. The scientists created the technique as a new and improved method for tracking the interactions within large neural networks in the brain. "For a long time neuroscientists relied on electrical techniques for recording the activity of neurons. These are very good at monitoring individual neurons but are limited to small numbers of neurons. The new wave is to use optical techniques to record the activity of hundreds of neurons at the same time," said Carl Johnson, Stevenson Professor of Biological Sciences, who headed the effort. "Most of the efforts in optical recording use fluorescence, but this requires a strong external light source which can cause the tissue to heat up and can interfere with some biological processes, particularly those that are light sensitive," he said. Based on their research on bioluminescence in "a scummy little organism, the green alga Chlamydomonas, that nobody cares much about" Johnson and his colleagues realized that if they could combine luminescence with optogenetics -- a new biological technique that uses light to control cells, particularly neurons, in living tissue -- they could create a powerful new tool for studying brain activity. "There is an inherent conflict between fluorescent techniques and optogenetics. The light required to produce the fluorescence interferes with the light required to control the cells," said Johnson. "Luminescence, on the other hand, works in the dark!" Johnson and his collaborators -- Associate Professor Donna Webb, Research Assistant Professor Shuqun Shi, post-doctoral student Jie Yang and doctoral student Derrick Cumberbatch in biological sciences and Professor Danny Winder and postdoctoral student Samuel Centanni in molecular physiology and biophysics - genetically modified a type of luciferase obtained from a luminescent species of shrimp so that it would light up when exposed to calcium ions. Then they hijacked a virus that infects neurons and attached it to their sensor molecule so that the sensors are inserted into the cell interior. The researchers picked calcium ions because they are involved in neuron activation. Although calcium levels are high in the surrounding area, normally they are very low inside the neurons. However, the internal calcium level spikes briefly when a neuron receives an impulse from one of its neighbors. They tested their new calcium sensor with one of the optogenetic probes (channelrhodopsin) that causes the calcium ion channels in the neuron's outer membrane to open, flooding the cell with calcium. Using neurons grown in culture they found that the luminescent enzyme reacted visibly to the influx of calcium produced when the probe was stimulated by brief light flashes of visible light. To determine how well their sensor works with larger numbers of neurons, they inserted it into brain slices from the mouse hippocampus that contain thousands of neurons. In this case they flooded the slices with an increased concentration of potassium ions, which causes the cell's ion channels to open. Again, they found that the sensor responded to the variations in calcium concentrations by brightening and dimming. "We've shown that the approach works," Johnson said. "Now we have to determine how sensitive it is. We have some indications that it is sensitive enough to detect the firing of individual neurons, but we have to run more tests to determine if it actually has this capability." The work was funded by National Institutes of Health grants R21 DA034446, R21 MH107713, R01 GM092914, National Science Foundation grant DBI-1450897 and a grant from the Vanderbilt Brain Institute.

Altieri N.,Idaho State University | Stevenson R.A.,Vanderbilt University | Stevenson R.A.,Vanderbilt Brain Institute | Stevenson R.A.,University of Toronto | And 3 more authors.
Brain Topography | Year: 2013

The ability to effectively combine sensory inputs across modalities is vital for acquiring a unified percept of events. For example, watching a hammer hit a nail while simultaneously identifying the sound as originating from the event requires the ability to identify spatio-temporal congruencies and statistical regularities. In this study, we applied a reaction time and hazard function measure known as capacity (e.g., Townsend and AshbyCognitive Theory 200-239, 1978) to quantify the extent to which observers learn paired associations between simple auditory and visual patterns in a model theoretic manner. As expected, results showed that learning was associated with an increase in accuracy, but more significantly, an increase in capacity. The aim of this study was to associate capacity measures of multisensory learning, with neural based measures, namely mean global field power (GFP). We observed a co-variation between an increase in capacity, and a decrease in GFP amplitude as learning occurred. This suggests that capacity constitutes a reliable behavioral index of efficient energy expenditure in the neural domain. © 2013 Springer Science+Business Media New York.

Stevenson R.A.,Vanderbilt University | Stevenson R.A.,Vanderbilt Kennedy Center | Stevenson R.A.,Vanderbilt Brain Institute | Schlesinger J.J.,Vanderbilt Kennedy Center | And 2 more authors.
Anesthesiology | Year: 2013

Background: Anesthesiology requires performing visually oriented procedures while monitoring auditory information about a patient's vital signs. A concern in operating room environments is the amount of competing information and the effects that divided attention has on patient monitoring, such as detecting auditory changes in arterial oxygen saturation via pulse oximetry. Methods: The authors measured the impact of visual attentional load and auditory background noise on the ability of anesthesia residents to monitor the pulse oximeter auditory display in a laboratory setting. Accuracies and response times were recorded reflecting anesthesiologists' abilities to detect changes in oxygen saturation across three levels of visual attention in quiet and with noise. Results: Results show that visual attentional load substantially affects the ability to detect changes in oxygen saturation concentrations conveyed by auditory cues signaling 99 and 98% saturation. These effects are compounded by auditory noise, up to a 17% decline in performance. These deficits are seen in the ability to accurately detect a change in oxygen saturation and in speed of response. Conclusions: Most anesthesia accidents are initiated by small errors that cascade into serious events. Lack of monitor vigilance and inattention are two of the more commonly cited factors. Reducing such errors is thus a priority for improving patient safety. Specifically, efforts to reduce distractors and decrease background noise should be considered during induction and emergence, periods of especially high risk, when anesthesiologists has to attend to many tasks and are thus susceptible to error. © 2013, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.

Fougnie D.,Vanderbilt University | Asplund C.L.,Vanderbilt Brain Institute | Marois R.,Vanderbilt University
Journal of Vision | Year: 2010

An influential theory suggests that integrated objects, rather than individual features, are the fundamental units that limit our capacity to temporarily store visual information (S. J. Luck & E. K. Vogel, 1997). Using a paradigm that independently estimates the number and precision of items stored in working memory (W. Zhang & S. J. Luck, 2008), here we show that the storage of features is not cost-free. The precision and number of objects held in working memory was estimated when observers had to remember either the color, the orientation, or both the color and orientation of simple objects. We found that while the quantity of stored objects was largely unaffected by increasing the number of features, the precision of these representations dramatically decreased. Moreover, this selective deterioration in object precision depended on the multiple features being contained within the same objects. Such fidelity costs were even observed with change detection paradigms when those paradigms placed demands on the precision of the stored visual representations. Taken together, these findings not only demonstrate that the maintenance of integrated features is costly; they also suggest that objects and features affect visual working memory capacity differently. © ARVO.

Blackford J.U.,Vanderbilt University | Clauss J.A.,Vanderbilt University | Clauss J.A.,Vanderbilt Brain Institute | Avery S.N.,Vanderbilt University | And 4 more authors.
Biological Psychology | Year: 2014

The tendency to approach or avoid novel people is a fundamental human behavior and is a core dimension of social anxiety. Resting state fMRI was used to test for an association between social inhibition and intrinsic connectivity in 40 young adults ranging from low to high in social inhibition. Higher levels of social inhibition were associated with specific patterns of reduced amygdala-cingulate cortex connectivity. Connectivity was reduced between the superficial amygdala and the rostral cingulate cortex and between the centromedial amygdala and the dorsal anterior cingulate cortex. Social inhibition also modulated connectivity in several well-established intrinsic networks; higher social inhibition correlated with reduced connectivity with default mode and dorsal attention networks and enhanced connectivity in salience and executive control networks. These findings provide important preliminary evidence that social inhibition reflects differences in the underlying intrinsic connectivity of the brain in the absence of social stimuli or stressors. © 2014 Elsevier B.V.

Conrad K.L.,Vanderbilt University | Davis A.R.,Vanderbilt University | Silberman Y.,Vanderbilt University | Sheffler D.J.,Vanderbilt University | And 9 more authors.
Neuropsychopharmacology | Year: 2012

The alpha2 adrenergic receptor (α2-AR) antagonist yohimbine is a widely used tool for the study of anxiogenesis and stress-induced drug-seeking behavior. We previously demonstrated that yohimbine paradoxically depresses excitatory transmission in the bed nucleus of the stria terminalis (BNST), a region critical to the integration of stress and reward pathways, and produces an impairment of extinction of cocaine-conditioned place preference (cocaine-CPP) independent of α2-AR signaling. Recent studies show yohimbine-induced drug-seeking behavior is attenuated by orexin receptor 1 (OX1 R) antagonists. Moreover, yohimbine-induced cocaine-seeking behavior is BNST-dependent. Here, we investigated yohimbine-orexin interactions. Our results demonstrate yohimbine-induced depression of excitatory transmission in the BNST is unaffected by alpha1-AR and corticotropin-releasing factor receptor-1 (CRFR1) antagonists, but is (1) blocked by OxR antagonists and (2) absent in brain slices from orexin knockout mice. Although the actions of yohimbine were not mimicked by the norepinephrine transporter blocker reboxetine, they were by exogenously applied orexin A. We find that, as with yohimbine, orexin A depression of excitatory transmission in BNST is OX 1 R-dependent. Finally, we find these ex vivo effects are paralleled in vivo, as yohimbine-induced impairment of cocaine-CPP extinction is blocked by a systemically administered OX1 R antagonist. These data highlight a new mechanism for orexin on excitatory anxiety circuits and demonstrate that some of the actions of yohimbine may be directly dependent upon orexin signaling and independent of norepinephrine and CRF in the BNST. © 2012 American College of Neuropsychopharmacology. All rights reserved.

Rinker D.C.,Vanderbilt University | Zhou X.,Vanderbilt University | Pitts R.J.,Vanderbilt University | Rokas A.,Vanderbilt University | And 2 more authors.
BMC Genomics | Year: 2013

Background: Two sibling members of the Anopheles gambiae species complex display notable differences in female blood meal preferences. An. gambiae s.s. has a well-documented preference for feeding upon human hosts, whereas An. quadriannulatus feeds on vertebrate/mammalian hosts, with only opportunistic feeding upon humans. Because mosquito host-seeking behaviors are largely driven by the sensory modality of olfaction, we hypothesized that hallmarks of these divergent host seeking phenotypes will be in evidence within the transcriptome profiles of the antennae, the mosquito's principal chemosensory appendage. Results: To test this hypothesis, we have sequenced antennal mRNA of non-bloodfed females from each species and observed a number of distinct quantitative and qualitative differences in their chemosensory gene repertoires. In both species, these gene families show higher rates of sequence polymorphisms than the overall rates in their respective transcriptomes, with potentially important divergences between the two species. Moreover, quantitative differences in odorant receptor transcript abundances have been used to model potential distinctions in volatile odor receptivity between the two sibling species of anophelines.Conclusion: This analysis suggests that the anthropophagic behavior of An. gambiae s.s. reflects the differential distribution of olfactory receptors in the antenna, likely resulting from a co-option and refinement of molecular components common to both species. This study improves our understanding of the molecular evolution of chemoreceptors in closely related anophelines and suggests possible mechanisms that underlie the behavioral distinctions in host seeking that, in part, account for the differential vectorial capacity of these mosquitoes. © 2013 Rinker et al.; licensee BioMed Central Ltd.

Whyte A.,Vanderbilt Brain Institute | Jessen T.,Vanderbilt University | Varney S.,Vanderbilt University | Carneiro A.M.D.,Vanderbilt University
Neurochemistry International | Year: 2014

Dysfunctions in serotonin (5-hydroxytryptamine, 5-HT) systems have been associated with several psychiatric illnesses, including anxiety, depression, obsessive-compulsive disorders and autism spectrum disorders. Convergent evidence from genetic analyses of human subjects has implicated the integrin β3 subunit gene (ITGB3) as a modulator of serotonergic systems via genetic interactions with the 5-HT transporter gene (SLC6A4, SERT). While genetic interactions may result from contributions of each gene at several levels, we hypothesize that ITGB3 modulates the 5-HT system at the level of the synapse, through the actions of integrin αvβ3. Here we utilized a genetic approach in mouse models to examine Itgb3 contributions to SERT function both in the context of normal and reduced SERT expression. As integrin αvβ3 is expressed in postsynaptic membranes, we isolated synaptoneurosomes, which maintain intact pre- and post-synaptic associations. Citalopram binding revealed significant Slc6a4-driven reductions in SERT expression in midbrain synapses, whereas no significant changes were observed in hippocampal or cortical projections. Expecting corresponding changes to SERT function, we also measured 5-HT uptake activity in synaptoneurosomal preparations. Itgb3 single heterozygous mice displayed significant reductions in 5-HT Vmax, with no changes in Km, in midbrain preparations. However, in the presence of both Itgb3 and Slc6a4 heterozygozity, 5-HT uptake was similar to wild-type levels, revealing a significant Slc6a4 by Itgb3 genetic interaction in the midbrain. Similar findings were observed in cortical preparations, whereas in the hippocampus, most Vmax changes were driven solely by Slc6a4. Our findings provide evidence that integrin αvβ3 is involved in the regulation of serotonergic systems in some, but not all 5-HT synapses, revealing novel contributions to synaptic specificity within the central nervous system. © 2013 Elsevier Ltd. All rights reserved.

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