Resolving Cross-modal Semantic Interference among Object Concepts Requires Medial Temporal Lobe Cortex.

The ability to flexibly categorize object concepts is essential to semantic cognition because the features that make two objects similar in one context may be irrelevant and even constitute interference in another. Thus, adaptive behavior in complex and dynamic environments requires the resolution of feature-based interference. In the current case study, we placed visual and functional semantic features in opposition across object concepts in two categorization tasks. Successful performance required the resolution of functional interference in a visual categorization task and the resolution of visual interference in a functional categorization task. In Experiment 1, we found that patient D. A., an individual with bilateral temporal lobe lesions, was unable to categorize object concepts in a context-dependent manner. His impairment was characterized by an increased tendency to incorrectly group objects that were similar on the task-irrelevant dimension, revealing an inability to resolve cross-modal semantic interference. In Experiment 2, D. A.'s categorization accuracy was comparable to controls when lures were removed, indicating that his impairment is unique to contexts that involve cross-modal interference. In Experiment 3, he again performed as well as controls when categorizing simple concepts, suggesting that his impairment is specific to categorization of complex object concepts. These results advance our understanding of the anterior temporal lobe as a system that represents object concepts in a manner that enables flexible semantic cognition. Specifically, they reveal a dissociation between semantic representations that contribute to the resolution of cross-modal interference and those that contribute to the resolution of interference within a given modality.

Perception of Impossible Scenes Reveals Differential Hippocampal and Parahippocampal Place Area Contributions to Spatial Coherency.

Surprisingly little is known about how the brain combines spatial elements to form a coherent percept. Regions that may underlie this process include the hippocampus (HC) and parahippocampal place area (PPA), regions central to spatial perception but whose role in spatial coherency has not been explored. Participants were scanned with functional MRI while they judged whether Escher-like scenes were possible or impossible. Univariate analyses revealed differential HC and PPA involvement, with greater HC activity during spatial incoherency detection and more PPA activity during spatial coherency detection. Recognition and eye-tracking data ruled out long- or short-term memory confounds. Multivariate statistics demonstrated spatial coherency-dependent functional connectivity for the HC, but not PPA, with greater HC connectivity to various brain regions including lateral occipital complex during spatial incoherency detection. We suggest the PPA is preferentially involved during the perception of spatially coherent scenes, whereas the HC binds distinct features to create coherent representations. © 2016 Wiley Periodicals, Inc.

The insular cortex: relationship to skin conductance responses to facial expression of emotion in temporal lobe epilepsy.

The insula plays an important role both in emotion processing and in the generation of epileptic seizures. In the current study we examined thickness of insular cortices and bilateral skin conductance responses (SCR) in healthy subjects in addition to a small number of patients with temporal lobe epilepsy. SCR measures arousal and is used to assess non-conscious responses to emotional stimuli. We used two emotion tasks, one explicitly about emotion and the other implicit. The explicit task required judgments about emotions being expressed in photographs of faces, while the implicit one required judgments about the age of the people in the photographs. Patients and healthy differed in labeling neutral faces, but not other emotions. They also differed in their SCR to emotions, though the profile depended on which hand the recordings were from. Finally, we found relationships between the thickness of the insula and SCR to each task: in the healthy group the thickness of the left insula was related to SCR to the emotion-labeling task; in the patient group it was between the thickness of the right insula and SCR in the age-labeling task. These patterns were evident only for the right hand recordings, thus underscoring the importance of bilateral recordings.

Retinoic acid breakdown is required for proximodistal positional identity during amphibian limb regeneration.

Regenerating limbs retain their proximodistal (PD) positional identity following amputation. This positional identity is genetically encoded by PD patterning genes that instruct blastema cells to regenerate the appropriate PD limb segment. Retinoic acid (RA) is known to specify proximal limb identity, but how RA signaling levels are established in the blastema is unknown. Here, we show that RA breakdown via CYP26B1 is essential for determining RA signaling levels within blastemas. CYP26B1 inhibition molecularly reprograms distal blastemas into a more proximal identity, phenocopying the effects of administering excess RA. We identify Shox as an RA-responsive gene that is differentially expressed between proximally and distally amputated limbs. Ablation of Shox results in shortened limbs with proximal skeletal elements that fail to initiate endochondral ossification. These results suggest that PD positional identity is determined by RA degradation and RA-responsive genes that regulate PD skeletal element formation during limb regeneration.

Optimizing effective dose and image quality in cone beam CT sialography.

OBJECTIVES: The purpose of this study was to develop protocols that optimize patient radiation dose and image quality for cone beam computed tomographic (CBCT) sialography for the major salivary glands. STUDY DESIGN: Radiation absorbed dose measurements were repeated in triplicate using 25 sites in the head and neck of a Radiation ANalog DOsimetry system (RANDO) phantom, and effective doses were calculated across a range of peak kilovoltage (kVp) and milliamperage (mA) settings using an 8 cm (diameter) by 5 cm (height) field of view (FOV) for submandibular imaging and an 8 cm (diameter) by 8 cm (height) FOV for parotid imaging. Image signal difference-to-noise ratio (SDNR) was determined, and the figure-of-merit (FOM), a measure of image quality, was calculated. RESULTS: For submandibular sialography, 85 kVp and 6 mA were chosen as the optimal exposure parameters, resulting in a mean effective dose of 82.47 µSv and a mean SDNR of 13.86, with a mean FOM of 2.33 µSv-1. For parotid sialography, 70 kVp and 6 mA were chosen, and these settings resulted in a mean effective dose of 39.99 µSv, a mean SDNR of 17.43, and a mean FOM of 7.60 µSv-1. CONCLUSIONS: Low-dose 3-dimensional sialography with high image quality and minimal effective dose can be delivered using CBCT with localized, small FOVs.

The anterior insular cortex represents breaches of taste identity expectation.

Despite the importance of breaches of taste identity expectation for survival, its neural correlate is unknown. We used fMRI in 16 women to examine brain response to expected and unexpected receipt of sweet taste and tasteless/odorless solutions. During expected trials (70%), subjects heard "sweet" or "tasteless" and received the liquid indicated by the cue. During unexpected trials (30%), subjects heard sweet but received tasteless or they heard tasteless but received sweet. After delivery, subjects indicated stimulus identity by pressing a button. Reaction time was faster and more accurate after valid cuing, indicating that the cues altered expectancy as intended. Tasting unexpected versus expected stimuli resulted in greater deactivation in fusiform gyri, possibly reflecting greater suppression of visual object regions when orienting to, and identifying, an unexpected taste. Significantly greater activation to unexpected versus expected stimuli occurred in areas related to taste (thalamus, anterior insula), reward [ventral striatum (VS), orbitofrontal cortex], and attention [anterior cingulate cortex, inferior frontal gyrus, intraparietal sulcus (IPS)]. We also observed an interaction between stimulus and expectation in the anterior insula (primary taste cortex). Here response was greater for unexpected versus expected sweet compared with unexpected versus expected tasteless, indicating that this region is preferentially sensitive to breaches of taste expectation. Connectivity analyses confirmed that expectation enhanced network interactions, with IPS and VS influencing insular responses. We conclude that unexpected oral stimulation results in suppression of visual cortex and upregulation of sensory, attention, and reward regions to support orientation, identification, and learning about salient stimuli.

Bilateral skin conductance responses to emotional faces.

Skin conductance responses (SCR) measure objective arousal in response to emotionally-relevant stimuli. Central nervous system influence on SCR is exerted differentially by the two hemispheres. Differences between SCR recordings from the left and right hands may therefore be expected. This study focused on emotionally expressive faces, known to be processed differently by the two hemispheres. Faces depicting neutral, happy, sad, angry, fearful or disgusted expressions were presented in two tasks, one with an explicit emotion judgment and the other with an age judgment. We found stronger responses to sad and happy faces compared with neutral from the left hand during the implicit task, and stronger responses to negative emotions compared with neutral from the right hand during the explicit task. Our results suggest that basic social stimuli generate distinct responses on the two hands, no doubt related to the lateralization of social function in the brain.

Development of intravenously administered synthetic RNA virus immunotherapy for the treatment of cancer.

The therapeutic effectiveness of oncolytic viruses (OVs) delivered intravenously is limited by the development of neutralizing antibody responses against the virus. To circumvent this limitation and to enable repeated systemic administration of OVs, here we develop Synthetic RNA viruses consisting of a viral RNA genome (vRNA) formulated within lipid nanoparticles. For two Synthetic RNA virus drug candidates, Seneca Valley virus (SVV) and Coxsackievirus A21, we demonstrate vRNA delivery and replication, virus assembly, spread and lysis of tumor cells leading to potent anti-tumor efficacy, even in the presence of OV neutralizing antibodies in the bloodstream. Synthetic-SVV replication in tumors promotes immune cell infiltration, remodeling of the tumor microenvironment, and enhances the activity of anti-PD-1 checkpoint inhibitor. In mouse and non-human primates, Synthetic-SVV is well tolerated reaching exposure well above the requirement for anti-tumor activity. Altogether, the Synthetic RNA virus platform provides an approach that enables repeat intravenous administration of viral immunotherapy.

Pediatric poisonings in children younger than five years responded to by paramedics.

BACKGROUND: Treatment of poisonings in children has been well studied, but few data are available on the various causes of the poisoning episodes in the pediatric population. OBJECTIVES: To describe the incidence and demographics of accidental poisonings incurred by children<5 years old in the County of San Diego, California who accessed paramedics through the 9-1-1 system. METHODS: Eight years of prehospital records for children<5 years of age were searched for poisoning cases. Detailed narrative information was abstracted to determine the circumstances surrounding the incident. RESULTS: There were more than 40,000 paramedic transport calls for patients 5 years and younger over the study period; 996 (2.5%) of these calls had the chief complaint of poisoning. Of the calls classified as poisonings, 38% involved a 1-year-old and 35% involved a 2-year-old. Fifty-six percent of these poisonings involved either prescription or over-the-counter medications. An additional 16% were due to household cleaners. Eighty-eight percent of all calls were classified as mild in acuity, with 13% of poisoning calls for children under a year of age classified as moderate or acute; 50% of moderate or acute poisoning calls were to children 2 years of age. July and March were the months with the highest incidence of poisoning calls. The fewest calls were received on Saturdays and Sundays. CONCLUSIONS: Children 1 year of age had the highest incidence of unintentional poisonings. Among all age groups, medications were the number one cause of unintentional poisonings. Other unintentional poisonings could be prevented if hazardous materials were out of reach of children; many of the cases in this study happened in front of the parent with the parent watching.

End-tidal partial pressure of carbon dioxide and acute mountain sickness in the first 24 hours upon ascent to Cusco Peru (3326 meters).

OBJECTIVE: To explore the association of end-title partial pressure (Petco(2)) and oxygen saturation (Spo(2)) with the development of AMS in travelers rapidly ascending to Cusco, Peru (3326 m). METHODS: Using the 715 TIDAL WAVE Sp handheld, portable capnometer/oximeter, we measured Spo(2) and Petco(2) in 175 subjects upon ascent to Cusco, Peru (3326 m) from Lima (sea level) (a mean time of 3.9 hours.) Symptoms of AMS were recorded at the same initial time on arrival to altitude and 24 hours later using the Environmental Symptoms Questionnaire (ESQ). RESULTS: This study showed that no subjects with the lowest Petco(2) of 23 to 30 mm Hg had AMS (P <.044). The data also demonstrate that subjects with a higher Petco(2) (36-40 mm Hg) and lower Sao(2) (72%-86%) have a higher incidence of AMS. CONCLUSION: The most important finding of this study is that Petco(2) upon ascent was found to have a more significant effect than Spo(2) on a subject's ultimate ESQ score. This study demonstrates that those individuals with a brisk ventilatory response upon ascent to moderate altitude, as measured by Petco(2), did not develop AMS, whereas a blunted ventilatory response, as reflected in the highest Petco(2), was related to the subsequent development of AMS.

Integrative and distinctive coding of visual and conceptual object features in the ventral visual stream.

A significant body of research in cognitive neuroscience is aimed at understanding how object concepts are represented in the human brain. However, it remains unknown whether and where the visual and abstract conceptual features that define an object concept are integrated. We addressed this issue by comparing the neural pattern similarities among object-evoked fMRI responses with behavior-based models that independently captured the visual and conceptual similarities among these stimuli. Our results revealed evidence for distinctive coding of visual features in lateral occipital cortex, and conceptual features in the temporal pole and parahippocampal cortex. By contrast, we found evidence for integrative coding of visual and conceptual object features in perirhinal cortex. The neuroanatomical specificity of this effect was highlighted by results from a searchlight analysis. Taken together, our findings suggest that perirhinal cortex uniquely supports the representation of fully specified object concepts through the integration of their visual and conceptual features.

Hyperventilation following aero-medical rapid sequence intubation may be a deliberate response to hypoxemia.

BACKGROUND: Recent studies document a high incidence of hyperventilation by prehospital providers, with a potentially detrimental effect on outcome in traumatic brain injury (TBI). PURPOSE: To document the incidence of hyperventilation by aero-medical providers and explore a possible relationship between hyperventilation episodes and desaturations or impending hypoxemia. METHODS: This was a prospective, descriptive study using TBI patients undergoing prehospital RSI by aero-medical crews. Continuous data regarding end-tidal CO2 (EtCO2), ventilatory rate, and oxygen saturation (SpO2) were downloaded from hand-held oximeter-capnometer devices. Two investigators independently assessed oximetry/capnometry data to identify the following occurrences: desaturation during RSI (SpO2 < 90%), impending hypoxemia (SpO2 decrease by >or=3% to a value <95%) following intubation, loss of SpO2 signal, hyperventilation (EtCO2<30 mm Hg), and severe hyperventilation (EtCO2 < 25 mm Hg). Covariate analysis was used to explore the possible association between hyperventilation episodes and either desaturation, impending hypoxemia, or loss of SpO2 signal. RESULTS: A total of 32 aero-medical patients were enrolled with a mean duration of ventilation monitoring of 14.8 min. The incidence of hyperventilation or severe hyperventilation was substantially lower than previously documented with ground paramedics. A total of 28 hyperventilation episodes were identified in 16 patients; 13 of these were associated with impending hypoxemia following intubation, five were associated with desaturation during RSI, and seven were associated with loss of SpO2 signal. The remaining three occurred immediately following intubation without desaturation during RSI. Desaturation was observed in 62% of patients; of note, desaturation was recorded on the quality improvement document in only 23% of these. Covariate analysis revealed an association between hyperventilation episodes and either desaturatios during RSI, impending hypoxemia following intubation, or loss of SpO2 signal. CONCLUSIONS: The incidence of hyperventilation by aeromedical crews was lower than reported for ground paramedics and appears to occur in response to desaturation, impending hypoxemia, or loss of SpO2 signal.

The effects of incubation temperature and experimental design on heart rates of lizard embryos.

Many studies of phenotypic plasticity alter environmental conditions during embryonic development, yet only measure phenotypes at the neonatal stage (after embryonic development). However, measuring aspects of embryo physiology enhances our understanding of how environmental factors immediately affect embryos, which aids our understanding of developmental plasticity. While current research on reptile developmental plasticity has demonstrated that fluctuating incubation temperatures affect development differently than constant temperatures, most research on embryo physiology is still performed with constant temperature experiments. In this study, we noninvasively measured embryonic heart rates of the brown anole (Anolis sagrei), across ecologically relevant fluctuating temperatures. We incubated eggs under temperatures measured from potential nests in the field and examined how heart rates change through a diel cycle and throughout embryonic development. We also evaluated how experimental design (e.g., repeated vs. single measures designs, constant vs. fluctuating temperatures) and different protocols (e.g., removing eggs from incubators) might influence heart rate. We found that heart rates were correlated with daily temperature and increased through development. Our findings suggest that experimenters have reasonable flexibility in choosing an experimental design to address their questions; however, some aspects of design and protocol can potentially influence estimations of heart rates. Overall, we present the first ecologically relevant measures of anole embryonic heart rates and provide recommendations for experimental designs for future experiments.

Traumatic brain injury outcomes in pre- and post- menopausal females versus age-matched males.

Gender differences in outcomes from major trauma have been described previously, and exogenous female hormone administration appears to be neuroprotective following traumatic brain injury (TBI). This analysis explored outcomes in pre- and post-menopausal females versus age-matched males. A total of 13,437 patients (n = 3,178 females, n = 10,259 males) with moderate-to-severe TBI (head AIS > or = 3) were identified from our county trauma registry. Overall mortality was similar between males and females (22% for both). Logistic regression was used to compare gender outcome differences, with a separate analysis performed for premenopausal (< 50 years) versus postmenopausal (> or = 50 years) patients, and after stratification by decade of life. No statistically significant difference in outcomes was observed for pre-menopausal females versus males (odds ratio [OR] 1.06; 95% confidence interval [CI] 0.83, 1.35; p = 0.633), but outcomes were significantly better in postmenopausal females versus males (OR 0.63, 95% CI 0.48-0.81, p < 0.001) after adjusting for age, mechanism of injury, Glasgow Coma Scale (GCS), hypotension (SBP < or = 90 mm Hg), head Abbreviated Injury Score (AIS), and Injury Severity Score (ISS). Stratification by decade of life revealed the gender survival differential inflection point to occur between ages 40-49 (OR 1.06, 95% CI 0.66-1.71, p = 0.798) and ages 50-59 (OR 0.38, 95% CI 0.20-0.74, p = 0.005). In addition, Revised Trauma Score and Injury Severity Score (TRISS) was used to calculate probability of survival (PS); all patients were then stratified by decade of life, and males and females were compared with regard to mean survival differential (outcome - PS). The identical pattern of improved outcomes in post-menopausal but not pre-menopausal females versus age-matched males was observed. These data suggest that endogenous female sex hormone production is not neuroprotective.