To act and survive in an environment, humans and other organisms need to form useful representations of it. Such representations are formed through co-ordinated transformations across areas (or layers), and often change through developmental experience. We find internal representations in trained deep neural networks capture the key features of multi-area neural recordings during a perceptual decision-making task, where minimal sufficient representations of sensory information emerge along a cortical hierarchy. Using our models, we show that these minimal sufficient representations emerge through preferential propagation of task-relevant information between areas.\n To better understand how such representations emerge through learning, we introduce a notion of usable information, and use it to show that a noisy learning process (e.g. Stochastic Gradient Descent) plays an important role in forming these minimal sufficient representations. We find that the learning process is highly nonlinear: semantically meaningful information is initially encoded in the representation, even if it is not needed for the task. Additionally, we show that the ability of a neural network to integrate information from diverse sources hinges critically on being exposed to properly correlated signals during the early stages of learning. In particular we find, using analytical models and through simulations, that depth and competition between sources has a significant effect on critical learning periods observed in biological and artificial networks. \n We further study how multisensory information can be decomposed, and develop novel approximations to compute the redundant information shared between a set of sources about a target, and show that the common information shared between a set of sources can be used to guide the learning of meaningful representations.

Decreased heart rate variability (HRV) has been observed with long term tobacco use in humans, which is attributed to dysfunction in the autonomic nervous system (ANS)specifically sympathetic nervous system (SNS) dominance and parasympathetic nervous system (PNS) suppression brought about by multiple inflammatory mechanisms. Studies showing these HRV changes tend to analyze both sexes together so sex differentiated responses cannot be identified. HRV changes are well studied in cigarette smoking, but the data looking at alternatives such as hookah smoke is sparse in comparison. Furthermore, while there is data showing signs of persistent ANS dysfunction with chronic exposure, there is no detailed analysis on how these changes develop over time. This study aims to assess if there are sex differentiated responses in overall HRV and recovery changes associated with chronic exposure to hookah smoke (HS) using a mouse model. Methods: Six female and nine male ApoE-/- mice were surgically implanted with radiotelemetry devices. The control group consisted of 4 males and 3 females whereas the exposure group consisted of 5 males and 3 females. A nose-only exposure system was used to deliver purified air to controls and hookah smoke to the exposure groups. Exposures occurred during the day and lasted 2 hours a day for 4 consecutive days followed by 3 days of rest for a total of 20 weeks. HRV measurements were taken in the evening hours after the exposure. Changes in HRV were assessed as percent change from baseline. Average percent change from baseline in heart rate, R-R interval, standard deviation of normal-to-normal intervals, root mean square of successive differences, low frequency (LF), and high frequency (HF) ratio were analyzed for change over time. Further analysis compared each mean change of all metrics between rest and exposure periods using Student’s t test and Mann-Whitney U test. A significance level of p < 0.05 was used for all analyses. Results: The female exposure group was the only group that showed significant signs of SNS dominance in all metrics. The male exposure group showed significant signs of SNS dominance in all metrics except for LF and HF which showed a non-significant trend toward PNS improvement. Both control groups showed signs of stress response with female controls maintaining signs of strong PNS activity over time while males trended toward SNS dominance. Both female groups had more significant differences between rest and exposure metrics in LF, HF and LF/HF ratio in over 50% of the analysis. Both male groups had generally non-significant differences in exposure vs. rest periods.

Overall, these results show sex differentiated response to identical stressors which is not readily explainable based on the available data. A closer look at how males and females differ in levels of sex hormones, cortisol, markers of inflammation and oxidative stress may help explain the underlying mechanisms behind these results.

Emissions-related particulate matter exposures are thought to be associated with thousands of excess deaths per year, many of which are related to cardiovascular disease. Ultrafine particles contain a large proportion of redox-active organic compounds that can exist in either the vapor or particle phase and are considered SVOCs. After inhalation, these compounds may be responsible for initiating a cascade of oxidative stress and inflammation in the body that can promote atherosclerotic plaque development that can lead to CAD. The goal of this project was to investigate the mechanisms of how exposure to particle associated SVOCs promotes atherosclerosis. ApoE -/- mice, which are prone to developing atherosclerosis, were exposed to unmodified UF CAPs, deCAPs with the SVOC components removed by a thermodenuder, or adjCAPs that was adjusted to match the concentration of deCAPs. Mice were exposed for nine weeks for five hours per day, four days per week at the UC Irvine campus. A control group was exposed to purified, filtered air. A higher percentage of mice exposed to adjCAPs formed arterial plaques compared to deCAPs and air exposed mice. Furthermore there was greater vascular wall thickening and fibrosis in the arteries of mice exposed to CAPs compared to deCAPs. IL-6 was increased in the serum of mice exposed to adjCAPs relative to deCAPs, indicating that the SVOCs are promoting atherosclerosis through a pro-inflammatory mechanism. Furthermore, adjCAPs exposure increased the ratio of LDL to HDL cholesterol, so SVOCs may be related to pro-atherogenic alterations to lipid metabolism. The power in the high frequency component of HRV, a measure of cardiac parasympathetic activity, was acutely reduced in mice exposed to CAPs, and daily changes in HF HRV were associated with the O:C ratio of the UF fraction of CAPs. These associations implicated POA, which comprises a major component of SVOCs, as potentially driving the toxic effects. The attenuation of atherosclerostic plaque formation with deCAPs exposure indicates that SVOCs in CAPs exposures are important contributors to toxic cardiovascular effects and these components deserve consideration in discussions of regulation of primary PM emissions and human exposure reduction strategies to protect public health.

Introduction: Chronic exposure to particulate matter (PM) has been associated with increased risks for several cardiovascular (CV) diseases which can culminate in higher morbidity and mortality. This research will test the effects of particle chemistry on the mouse electrocardiogram (ECG) by investigating adverse cardiac outcomes following exposures 1) during different seasons (winter/summer), and 2) to whole concentrated ambient particle (CAPs; containing organic species) or denuded CAPs (DeCAPs; PM thermally stripped of organic species) with/without the addition of ozone (O3), a ubiquitous environmental pollutant.

Methods: A Versatile Aerosol Concentration Enrichment System (VACES) was used to concentrated PM atmospheres. Hyperlipidemic mice (apoE-/-) were exposed via whole body inhalation chambers for 5 hrs./day, 4 days/wk. All ECG parameters were acquired from freely moving, conscious mice and assessed at the same time every evening. An aerosol mass spectrometer (AMS) provided single-particle size and chemical composition as well as cumulative size-classified mass concentrations in real-time for non-refractory sub-micron aerosol particles. The oxidative potential of different types of PM was analyzed using the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GR).

Results: Electrocardiogram (ECG) anomalies were exacerbated during periods with high ambient O3 levels suggesting that increased atmospheric interaction with O3 and other atmospheric pollutants generates more biologically active PM. CAPs exposure was found to be more cardiotoxic than DeCAPs exposure. Adding O3 to either CAPs or DeCAPs failed to elicit more severe adverse health effects compared to single pollutant exposures. Particles containing semi-volatile organic compounds (SVOCs) produced dissimilar inhibitory responses in GPx and GR suggesting that oxidative stress could be altered via GSH accumulation. Levels of enzymatic impairment were similar in response to PM+O3 mixtures regardless of PM-bound SVOCs present suggesting that O3 is reacting with a more stable PM-bound constituents.

Conclusion: This report describes how inhaled ambient PM is linked to alterations in cardiac electrophysiology and provides useful insight into particle characterization and cardiac dysfunction in relation to specific PM fractions and/or PM+O3 mixtures. Information about particle oxidative stress would be a valued addition to air quality legislation which currently relies on particle size as a main toxicological risk factor.