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  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Rahimpour Jounghani, Ali;

    Timing is an essential component of human actions, and is the foundation of any sort of sequential behavior, from picking up a glass to playing an instrument or dancing. Because of this, our understanding of how we represent time in the brain (i.e., the human timing system) critically relies on basic research on simple behaviors. Perception of temporal regularities is central to a wide range of basic actions, but also underpins abilities unique to humans such as the creation of complex musical scores. This dissertation is an in-depth examination of endogenously and exogenously guided timing behavior, and how context is a critical component of understanding rhythmic entrainment in humans. We previously validated “gold standard” functional magnetic resonance imaging (fMRI) findings on action-based timing behavior using functional near infrared spectroscopy (fNIRS) (Rahimpour et al., 2020). In particular, we observed significant hemodynamic responses in cortical areas in direct relation to the complexity of the behavior being performed. To do so, we probed multiple levels of contextual influence on action-based timing behavior and patterns of cortical activation as measured using fNIRS. Our findings highlighted several distinct, context-dependent parameters of specific timing behaviors. Here we further interrogate human timing abilities by introducing variations of our original experimental design, observing that subtle contextual variations have a significant impact on the degree of rhythmic entrainment given the presence/absence of metronomic input. We used electroencephalogram (EEG) to further validate our fNIRS findings, demonstrating that single trial neurobiological activity can be used to predict whether behavior is exogenously or endogenously guided. We also found that patterns of neural activity correspond to differential use of the internal timing system, and that specific differences in neural activity correlate with accuracy of action-based timing behavior. These findings emerged from our use of a novel deep learning approach to extract person-specific, neural-based features as predictors of behavioral performance. Finally, we examined whether fNIRS and EEG produced similar localization information, finding that the influence of training factors on cortical localization must be accounted for to make such comparisons.

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao eScholarship - Unive...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao eScholarship - Unive...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Nichols, Eva K.;

    The brain has innate immune myeloid cells (including microglia and border-associated macrophages) that have dynamic roles in homeostasis and the response to tissue injury and infection. Given the ability of brain myeloid cells to sense a variety of environmental cues, several studies have investigated their roles in neurodegenerative disease onset and progression. But, the impact of fetal myeloid cells on neurodevelopmental disorders is relatively unexplored in comparison. We used two mouse models of neurodevelopmental disorders to uncover the impact of fetal myeloid cell immunity to both normal and abnormal brain development. We found that an inflammatory lytic form of cell death, termed pyroptosis, in microglia may be required for establishing certain normal behavioral circuits. With genetic deficiency in the pyroptosis pathway, or upon pharmacological inhibition thereof, mice have attention-deficit/hyperactivity disorder (ADHD)-like behavior changes. Using the maternal immune activation (MIA) model of autism spectrum disorder (ASD), we identified a fetal myeloid responder population, likely to be border-associated macrophages, which directly sense MIA challenge. Thus, we learned that fetal immunity, mediated by myeloid cells, has important consequences for brain formation. Disruption or activation of these roles may constitute an upstream arm in neurodevelopmental disorder etiology.

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao eScholarship - Unive...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao eScholarship - Unive...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Mullen, Brian Romney;

    Functional imaging of neural cell populations at mesoscale is criticalfor mapping intra- and inter-regional network dynamics across the dorsal neocortex. Past lab members produced a flexible work flow for producing high quality segmentations of functional structure across neocortex utilizing Independent Component Analysis (ICA). This unsupervised machine learning decomposition of densely sampled recordings of cortical calcium dynamics, results in a collection of components comprised of neuronal signal sources distinct from optical, movement, and vascular artifacts. In this body of work, I built a supervised learning classifier that automatically separates neural activity and artifact components, using a set of extracted spatial and temporal metrics that characterize the respective components. Control data recorded in glial cell reporter and non-fluorescent mouse lines validates human and machine identification of functional component class.Utilizing the insight from the machine learning analysis, I processed alarge dataset from three different transgenic mouse lines expressing calcium indicators in distinct sub-population of neurons: pan-neuronal, upper, and lower layer specific excitatory neuronal subpopulations. I was able to create domain maps to discretize the cortex into functional units and observe how each domain behaves. The application of this data-driven method ultimately reduced the number of time series, while maintaining the informative structure at a mesoscale. From all these animals, I gain insight into the developing structural changes of circuitry based on age-related functional changes observed in these domain maps.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ eScholarship - Unive...arrow_drop_down
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ eScholarship - Unive...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Lahnakoski, Juha M.; Nolte, Tobias; Solway, Alec; Vilares, Iris; +7 Authors

    Background: Functional connectivity has garnered interest as a potential biomarker of psychiatric disorders including borderline personality disorder (BPD). However, small sample sizes and lack of within-study replications have led to divergent findings with no clear spatial foci. Aims: Evaluate discriminative performance and generalizability of functional connectivity markers for BPD. Method: Whole-brain fMRI resting state functional connectivity in matched subsamples of 116 BPD and 72 control individuals defined by three grouping strategies. We predicted BPD status using classifiers with repeated cross-validation based on multiscale functional connectivity within and between regions of interest (ROIs) covering the whole brain—global ROI-based network, seed-based ROI-connectivity, functional consistency, and voxel-to-voxel connectivity—and evaluated the generalizability of the classification in the left-out portion of non-matched data. Results: Full-brain connectivity allowed classification (∼70 %) of BPD patients vs. controls in matched inner cross-validation. The classification remained significant when applied to unmatched out-of-sample data (∼61–70 %). Highest seed-based accuracies were in a similar range to global accuracies (∼70–75 %), but spatially more specific. The most discriminative seed regions included midline, temporal and somatomotor regions. Univariate connectivity values were not predictive of BPD after multiple comparison corrections, but weak local effects coincided with the most discriminative seed-ROIs. Highest accuracies were achieved with a full clinical interview while self-report results remained at chance level. Limitations: The accuracies vary considerably between random sub-samples of the population, global signal and covariates limiting the practical applicability. Conclusions: Spatially distributed functional connectivity patterns are moderately predictive of BPD despite heterogeneity of the patient population. Published version

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    VTechWorks
    Other ORP type . 2024
    License: CC BY
    Data sources: VTechWorks
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ VTechWorksarrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      VTechWorks
      Other ORP type . 2024
      License: CC BY
      Data sources: VTechWorks
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Johnston, Kevin;

    Identifying and tracking cell location in long-term longitudinal studies is critical for identifying large-scale time-dependent neuronal activity variations. Population cell tracking across multiple sessions is complicated by non-rigid transformations induced by noise, cell movement and imaging field shifts. In this text we develop SCOUT (Single-Cell SpatiOtemporal LongitUdinal Tracking), a fast, robust cell tracking method utilizing multiple cell-cell similarity metrics, probabilistic inference, and an adaptive clustering methodology to perform cell identification across multiple calcium imaging sessions. We then apply SCOUT to study variations of firing activity coincident with contextual discrimination and neural circuit negation. Next, we investigate the relationship between firing activity and transcriptomics in a single cell type, showing that transcriptional gradients can be associated to subtle variations in neuronal firing activity, which then motivates the development of scGradient, a machine learning algorithm for identifying continuous transcriptional gradients across and within cell types.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ eScholarship - Unive...arrow_drop_down
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ eScholarship - Unive...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Do, Quy-Toan; Das, Jishnu; Friedman, Jed; McKenzie, David;

    The social and economic consequences of poor mental health in the developing world are presumed to be significant, yet are largely under-researched. The authors argue that mental health modules can be meaningfully added to multi-purpose household surveys in developing countries, and used to investigate this relationship. Data from nationally representative surveys in Bosnia and Herzegovina, Indonesia, and Mexico, along with special surveys from India and Tonga, show similar patterns of association between mental health and socioeconomic characteristics across countries. Individuals who are older, female, widowed, and report poor physical health are more likely to report worse mental health outcomes. Individuals living with others with poor mental health are also significantly more likely to report worse mental health themselves. In contrast, there is little observed relationship between mental health and poverty or education, common measures of socio-economic status. The results instead suggest that economic and multi-dimensional shocks such as illness or crisis can have a greater impact on mental health than overall levels of poverty. This may have important implications for social protection policy. The authors also find significant associations between poor mental health and lowered labor force participation (especially for women) and higher frequency visits to health centers, suggesting that poor mental health can have significant economic consequences for households and the health system. Finally, the paper discusses how measures of mental health are distinct from general subjective welfare measures such as happiness and indicate useful directions of future research.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Open Knowledge Repos...arrow_drop_down
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Open Knowledge Repos...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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    Authors: Tao, Xin;

    Autism spectrum disorder (ASD) is a developmental disorder characterized by symptoms: intellectual difficulties, motor, and language impairment, altered sensory processing, social impediments, and repetitive behaviors. Only 10-20% ASD have clear genetic causes, and fragile X syndrome (FXS) is one of them. FXS is caused by a lack of fragile X messenger ribonucleoprotein (FMRP) whose expression is transcriptionally silenced due to Frm1 gene hypermethylation. Altered sensory processing across all domains has been widely described in humans with FXS. Most noticeable alterations in auditory processing are auditory hyperactivity and impaired temporal processing. The Fmr1 knockout (KO) mouse is a well characterized animal model for FXS studies which also shows signs of auditory hypersensitivity and impaired temporal processing: increased evoked and induced auditory responses, susceptible to audiogenic seizures (AGS), and reduced phase-locking to temporally modulated sound. The consistent manifestations of auditory hyperactivity and impaired temporal processing between human FXS individuals and Frm1 KO make it possible to evaluate potential FXS treatment with Frm1 KO mice. Previous studies by others implied enhancing serotonin signaling ameliorated auditory hyperactivity, yet they failed to pinpoint the specific serotonin receptor subtypes involved. With a more specific and highly selective post-synaptic serotonin-1A (5-HT1A) receptor agonist, NLX-101, we found the AGS susceptibility in developing Frm1 KO mice is significantly reduced, suggesting enhancing 5-HT1A signaling is effective in reducing auditory hyperactivity at the behavioral level in Frm1 KO mice. Electroencephalography (EEG) data acquired from Frm1 KO mice following NLX-101 treatment showed that enhancing 5-HT1A signaling not only reduced auditory hyperactivity at the network level but also improved temporal processing by increasing consistency of the auditory responses to temporally modulated stimuli. RNAscope results showed mRNA transcripts of 5-HT1A receptors are predominately associated with non-GAD cells, implying NLX-101 may reduce auditory hyperactivity in Frm1 KO mice by hyperpolarizing excitatory neurons through 5-HT1A receptor activation.

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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ eScholarship - Unive...arrow_drop_down
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  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Steinberg, Elizabeth Eugenia;

    Much of the behavior of humans and other animals is directed towards seeking out edible, social, cognitive or drug rewards. Dopamine, a neurotransmitter released by a handful of cells in the brain, is known to be essential for reward-seeking behavior. Yet despite decades of focused investigation, the nature of its influence remains a matter of considerable debate. The precise roles that dopamine neurons play are likely to depend on their afferent and efferent connectivity, the timing and length of neural activation, and the features of the behavior under investigation. Accordingly, it is becoming increasingly appreciated that delineating the specific contributions of dopamine neurons to cellular, circuit, and systems-level phenomena will require more sophisticated control over their patterns of activity than conventional electrophysiological and pharmacological techniques can provide. Recently developed optogenetic tools hold great promise for disentangling these complex issues. In Chapter 2, I describe the development and characterization of a novel transgenic rat line that permits selective opsin expression in ventral tegmental area dopamine neurons, as well as other catecholamine neurons in the rat brain. I then utilize this tool to determine if temporally-precise patterns of dopamine neuron activity are causally related to appetitive behaviors. In Chapter 3, I present data from a series of experiments designed to clarify the role of ventral tegmental area dopamine neurons, or their major efferent projection to the nucleus accumbens, in positive reinforcement. Then in Chapter 4, I describe experiments designed to determine if ventral tegmental area dopamine neurons are capable of supporting associative cue-reward learning. Collectively, my results demonstrate that ventral tegmental dopamine neurons are sufficient to reinforce instrumental responding, and that their ability to influence reward-seeking behavior is at least partly due to the fact that they can drive associative learning directly. As such, they represent an important advance in our understanding of the neural basis of learned appetitive behaviors.

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao eScholarship - Unive...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao eScholarship - Unive...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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    Authors: Bell, Clive; van Dillen, Susanne;

    This paper analyzes the effects of all-weather rural roads on households' net output prices, education and health in a poor, drought-prone region of India. Of 30 villages originally surveyed in 2001-02, when two had such roads, a further nine received them between January 2007 and December 2009 under the program Pradhan Mantri Gram Sadak Yojana. Cross-section comparisons involving all villages and 'before and after' comparisons in the nine yielded these findings: (i) net output prices were 5 per cent or more higher; (ii) substantially fewer days of schooling were lost due to bad weather, largely because teachers had fewer absences; (iii) the acutely sick received more timely treatment and were more likely to be treated in a hospital than in the nearest primary health clinic; and (iv) the respondents ranked the resulting benefits in the domains of health and education at least as highly as the 'commercial' ones.

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  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Liang, Carmin Jia Min;

    Prostate cancer is currently the most prevalent noncutaneous cancer in males. An increase in the number of men diagnosed with indolent, organ-confined disease has lead to the increasing numbers of patients and their physicians selecting active surveillance or "delayed definitive treatment" as a viable approach for managing prostate cancer. However, the selection of appropriate patients for active surveillance has been confounded by sampling errors associated with transrectal ultrasound guided biopsies as well as accurate clinical and imaging biomarkers that predict for aggressive, progressive disease at diagnosis. Multiparametric magnetic resonance (MR) imaging may assist in overcoming this problem; it allows for the identification of the whole gland and a combination of T2-weighted MR imaging, proton MR spectroscopic imaging (1H MRSI), and diffusion-weighted imaging (DWI) can be used to better characterize the aggressiveness of intraglandular cancer at diagnosis. In this retrospective study, we quantitatively analyzed multiparametric MR images from a cohort of active surveillance patients (N=119) to determine the combination of MR imaging techniques that best predicted disease progression on active surveillance. Fifty-nine of 119 patients progressed within 43 ± 32 months on active surveillance. Receiver-operator characteristic (ROC) curve analysis indicated that all three techniques (T2 MRI, MRSI, DWI) demonstrated similar modest accuracies in predicting progression on AS (AUC of 0.59, 0.63 and 0.61, respectively). The best prediction of prostate cancer progression in AS patients was when all three techniques were positive for cancer presence, yielding an odds ratio for progression of 2.91 (95% CI 1.19 - 7.08) as compared to all other findings. Whereas a negative finding for all 3 tests for patients that were appropriate for AS yielded an odds ratio for no progression of 2.84 (95% CI = 1.26 - 6.37) as compared to all other findings. In conclusion, multiparametric MR imaging could play a valuable role in better selecting patients for active surveillance.

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  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Rahimpour Jounghani, Ali;

    Timing is an essential component of human actions, and is the foundation of any sort of sequential behavior, from picking up a glass to playing an instrument or dancing. Because of this, our understanding of how we represent time in the brain (i.e., the human timing system) critically relies on basic research on simple behaviors. Perception of temporal regularities is central to a wide range of basic actions, but also underpins abilities unique to humans such as the creation of complex musical scores. This dissertation is an in-depth examination of endogenously and exogenously guided timing behavior, and how context is a critical component of understanding rhythmic entrainment in humans. We previously validated “gold standard” functional magnetic resonance imaging (fMRI) findings on action-based timing behavior using functional near infrared spectroscopy (fNIRS) (Rahimpour et al., 2020). In particular, we observed significant hemodynamic responses in cortical areas in direct relation to the complexity of the behavior being performed. To do so, we probed multiple levels of contextual influence on action-based timing behavior and patterns of cortical activation as measured using fNIRS. Our findings highlighted several distinct, context-dependent parameters of specific timing behaviors. Here we further interrogate human timing abilities by introducing variations of our original experimental design, observing that subtle contextual variations have a significant impact on the degree of rhythmic entrainment given the presence/absence of metronomic input. We used electroencephalogram (EEG) to further validate our fNIRS findings, demonstrating that single trial neurobiological activity can be used to predict whether behavior is exogenously or endogenously guided. We also found that patterns of neural activity correspond to differential use of the internal timing system, and that specific differences in neural activity correlate with accuracy of action-based timing behavior. These findings emerged from our use of a novel deep learning approach to extract person-specific, neural-based features as predictors of behavioral performance. Finally, we examined whether fNIRS and EEG produced similar localization information, finding that the influence of training factors on cortical localization must be accounted for to make such comparisons.

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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao eScholarship - Unive...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Nichols, Eva K.;

    The brain has innate immune myeloid cells (including microglia and border-associated macrophages) that have dynamic roles in homeostasis and the response to tissue injury and infection. Given the ability of brain myeloid cells to sense a variety of environmental cues, several studies have investigated their roles in neurodegenerative disease onset and progression. But, the impact of fetal myeloid cells on neurodevelopmental disorders is relatively unexplored in comparison. We used two mouse models of neurodevelopmental disorders to uncover the impact of fetal myeloid cell immunity to both normal and abnormal brain development. We found that an inflammatory lytic form of cell death, termed pyroptosis, in microglia may be required for establishing certain normal behavioral circuits. With genetic deficiency in the pyroptosis pathway, or upon pharmacological inhibition thereof, mice have attention-deficit/hyperactivity disorder (ADHD)-like behavior changes. Using the maternal immune activation (MIA) model of autism spectrum disorder (ASD), we identified a fetal myeloid responder population, likely to be border-associated macrophages, which directly sense MIA challenge. Thus, we learned that fetal immunity, mediated by myeloid cells, has important consequences for brain formation. Disruption or activation of these roles may constitute an upstream arm in neurodevelopmental disorder etiology.

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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao eScholarship - Unive...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Mullen, Brian Romney;

    Functional imaging of neural cell populations at mesoscale is criticalfor mapping intra- and inter-regional network dynamics across the dorsal neocortex. Past lab members produced a flexible work flow for producing high quality segmentations of functional structure across neocortex utilizing Independent Component Analysis (ICA). This unsupervised machine learning decomposition of densely sampled recordings of cortical calcium dynamics, results in a collection of components comprised of neuronal signal sources distinct from optical, movement, and vascular artifacts. In this body of work, I built a supervised learning classifier that automatically separates neural activity and artifact components, using a set of extracted spatial and temporal metrics that characterize the respective components. Control data recorded in glial cell reporter and non-fluorescent mouse lines validates human and machine identification of functional component class.Utilizing the insight from the machine learning analysis, I processed alarge dataset from three different transgenic mouse lines expressing calcium indicators in distinct sub-population of neurons: pan-neuronal, upper, and lower layer specific excitatory neuronal subpopulations. I was able to create domain maps to discretize the cortex into functional units and observe how each domain behaves. The application of this data-driven method ultimately reduced the number of time series, while maintaining the informative structure at a mesoscale. From all these animals, I gain insight into the developing structural changes of circuitry based on age-related functional changes observed in these domain maps.

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Lahnakoski, Juha M.; Nolte, Tobias; Solway, Alec; Vilares, Iris; +7 Authors

    Background: Functional connectivity has garnered interest as a potential biomarker of psychiatric disorders including borderline personality disorder (BPD). However, small sample sizes and lack of within-study replications have led to divergent findings with no clear spatial foci. Aims: Evaluate discriminative performance and generalizability of functional connectivity markers for BPD. Method: Whole-brain fMRI resting state functional connectivity in matched subsamples of 116 BPD and 72 control individuals defined by three grouping strategies. We predicted BPD status using classifiers with repeated cross-validation based on multiscale functional connectivity within and between regions of interest (ROIs) covering the whole brain—global ROI-based network, seed-based ROI-connectivity, functional consistency, and voxel-to-voxel connectivity—and evaluated the generalizability of the classification in the left-out portion of non-matched data. Results: Full-brain connectivity allowed classification (∼70 %) of BPD patients vs. controls in matched inner cross-validation. The classification remained significant when applied to unmatched out-of-sample data (∼61–70 %). Highest seed-based accuracies were in a similar range to global accuracies (∼70–75 %), but spatially more specific. The most discriminative seed regions included midline, temporal and somatomotor regions. Univariate connectivity values were not predictive of BPD after multiple comparison corrections, but weak local effects coincided with the most discriminative seed-ROIs. Highest accuracies were achieved with a full clinical interview while self-report results remained at chance level. Limitations: The accuracies vary considerably between random sub-samples of the population, global signal and covariates limiting the practical applicability. Conclusions: Spatially distributed functional connectivity patterns are moderately predictive of BPD despite heterogeneity of the patient population. Published version

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    Authors: Johnston, Kevin;

    Identifying and tracking cell location in long-term longitudinal studies is critical for identifying large-scale time-dependent neuronal activity variations. Population cell tracking across multiple sessions is complicated by non-rigid transformations induced by noise, cell movement and imaging field shifts. In this text we develop SCOUT (Single-Cell SpatiOtemporal LongitUdinal Tracking), a fast, robust cell tracking method utilizing multiple cell-cell similarity metrics, probabilistic inference, and an adaptive clustering methodology to perform cell identification across multiple calcium imaging sessions. We then apply SCOUT to study variations of firing activity coincident with contextual discrimination and neural circuit negation. Next, we investigate the relationship between firing activity and transcriptomics in a single cell type, showing that transcriptional gradients can be associated to subtle variations in neuronal firing activity, which then motivates the development of scGradient, a machine learning algorithm for identifying continuous transcriptional gradients across and within cell types.

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    Authors: Do, Quy-Toan; Das, Jishnu; Friedman, Jed; McKenzie, David;

    The social and economic consequences of poor mental health in the developing world are presumed to be significant, yet are largely under-researched. The authors argue that mental health modules can be meaningfully added to multi-purpose household surveys in developing countries, and used to investigate this relationship. Data from nationally representative surveys in Bosnia and Herzegovina, Indonesia, and Mexico, along with special surveys from India and Tonga, show similar patterns of association between mental health and socioeconomic characteristics across countries. Individuals who are older, female, widowed, and report poor physical health are more likely to report worse mental health outcomes. Individuals living with others with poor mental health are also significantly more likely to report worse mental health themselves. In contrast, there is little observed relationship between mental health and poverty or education, common measures of socio-economic status. The results instead suggest that economic and multi-dimensional shocks such as illness or crisis can have a greater impact on mental health than overall levels of poverty. This may have important implications for social protection policy. The authors also find significant associations between poor mental health and lowered labor force participation (especially for women) and higher frequency visits to health centers, suggesting that poor mental health can have significant economic consequences for households and the health system. Finally, the paper discusses how measures of mental health are distinct from general subjective welfare measures such as happiness and indicate useful directions of future research.

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