Biology subjects

Moore, T.

Publications and source records attributed to Moore, T..

51 records · Page 3Linked to original sources

bioRxiv2020

Top-down coordination of local cortical state during selective attention

Spontaneous fluctuations in cortical excitability influence sensory processing and behavior. These fluctuations, long known to reflect global changes in cortical state, were recently found to be modulated locally within a retinotopic map during spatially selective attention. We found that periods of vigorous (On) and faint (Off) spiking activity, the signature of cortical state fluctuations, were coordinated across brain areas along the visual hierarchy and tightly coupled to their retinotopic alignment. During top-down attention, this interareal coordination was enhanced and progressed along the reverse cortical hierarchy. The extent of local state coordination between areas was predictive of behavioral performance. Our results show that cortical state dynamics are shared across brain regions, modulated by cognitive demands and relevant for behavior. One Sentence SummaryInterareal coordination of local cortical state is retinotopically precise and progresses in a reverse hierarchical manner during selective attention.

neuroscience↗

bioRxiv2020

Frontotemporal Coordination Predicts Working Memory Performance and its Local Neural Signatures

Neurons in some sensory areas reflect the content of working memory (WM) in their spiking activity. However, this spiking activity is seldom related to behavioral performance. We studied the responses of inferotemporal (IT) neurons, which exhibit object-selective activity, along with Frontal Eye Field (FEF) neurons, which exhibit spatially-selective activity, during the delay period of an object WM task. Unlike the spiking activity and local field potentials (LFPs) within these areas, which were poor predictors of behavioral performance, the phase-locking of IT spikes and LFPs with the beta band of FEF LFPs robustly predicted successful WM maintenance. In addition, IT neurons exhibited greater object-selective persistent activity when their spikes were locked to the phase of FEF LFPs. These results demonstrate a key role of coordination between prefrontal and temporal cortex in the successful maintenance of visual information during WM.

neuroscience↗

bioRxiv2020

Novel hemorrhage models of cerebral cavernous malformations

Cerebral cavernous malformations (CCMs) are ectatic capillary-venous malformations that develop in approximately 0.5% of the population. Patients with CCMs may develop headaches, focal neurologic deficits, seizures, and hemorrhages. While symptomatic CCMs, depending upon the anatomic location, can be surgically removed, there is currently no pharmaceutical therapy to treat CCMs. Several mouse models have been developed to better understand CCM pathogenesis and test therapeutics. The most common mouse models induce a large CCM burden that is anatomically restricted to the cerebellum and contributes to lethality in the early days of life. These inducible models thus have a relatively short period for drug administration. We developed an inducible CCM3 mouse model that develops CCMs after weaning and provides a longer period for potential therapeutic intervention. Using this new model, three recently proposed CCM therapies - fasudil, tempol, vitamin D3, and a combination of the three drugs failed to substantially reduce CCM formation when treatment was administered for five weeks, from postnatal day 21 (P21) to P56. We next restricted Ccm3 deletion to the brain vasculature and provided greater time (121 days) for CCMs to develop chronic hemorrhage, recapitulating the human lesions. We also developed the first model of acute CCM hemorrhage by injecting mice harboring CCMs with lipopolysaccharide. These efficient models will enable future drug studies to more precisely target clinically relevant features of CCM disease: CCM formation, chronic hemorrhage, and acute hemorrhage.

genetics↗

bioRxiv2019

Neurocognitive and Functional Heterogeneity in Depressed Youth

OBJECTIVEDepression is a common psychiatric illness that often begins in youth, and is associated with cognitive symptoms. However, there is significant variability in the cognitive burden, likely reflecting biological heterogeneity. This study sought to identify neurocognitive subtypes in a large sample of depressed youth, and evaluated the neural signatures of these subtypes.\n\nMETHODSParticipants were drawn from the Philadelphia Neurodevelopmental Cohort, including 712 youth with a lifetime history of a major depressive episode and 712 typically developing (TD) youth matched on age and sex. A subset (n=368, TD=200) also completed neuroimaging. Cognition was assessed with the Penn Computerized Neurocognitive Battery. A semi-supervised machine-learning algorithm, HYDRA (Heterogeneity through Discriminative Analysis), was used to delineate neurocognitive subtypes. Subtypes were evaluated for differences in both clinical psychopathology and brain activation during an n-back working memory fMRI task.\n\nRESULTSHYDRA identified three neurocognitive subtypes in the depressed group. Overall, Subtype 1 had better performance than TD comparators across many cognitive tasks (high accuracy, moderate speed), Subtype 2 was cognitively impaired (low accuracy, slow speed), whereas Subtype 3 was impulsive (low accuracy, fast speed). While subtypes did not differ in clinical psychopathology, they diverged in their activation profiles in regions critical for executive function, which mirrored differences in cognition.\n\nCONCLUSIONSUsing a data-driven approach, three neurocognitive subtypes of depression were identified that differed in neural signatures despite similar clinical psychopathology. These data suggest disparate mechanisms of cognitive vulnerability and resilience in depression, which may inform the identification of biomarkers for prognosis and treatment response.

neuroscience↗

bioRxiv2019

Distinct and shared contributions of diagnosis and symptom domains to cognitive performance in severe mental illness

BackgroundSevere mental illness (SMI) diagnoses display overlapping symptomatology and shared genetic risk, motivating trans-diagnostic investigations of disease-relevant quantitative measures. We analyzed relationships between neurocognitive performance, symptom domains, and diagnoses, in a large sample of SMI cases (ascertained agnostic to diagnosis) and healthy controls from a single, homogeneous population. Methods2,406 participants (1,689 cases, 717 controls; mean age 39 years, 64% female) were assessed for speed and accuracy using the Penn Computerized Neurocognitive Battery (CNB). Cases carried structured-interview based diagnoses of schizophrenia (SCZ, n=160), bipolar-I (BP-I, n=519), bipolar-II (BP-II, n=204) and major depressive disorder (MDD, n=806). Linear mixed models, using CNB tests as repeated measures, modeled neurocognition as a function of diagnosis, sex, and all interactions. Follow-up analyses, in cases, included symptom factor scores obtained from exploratory factor analysis of symptom data, as main effects. FindingsBP-I and SCZ displayed nearly identical impairments in accuracy and speed, across cognitive domains. BP-II and MDD performed similarly to controls, with subtle deficits in executive and social cognition. A three-factor model (psychosis, mania, and depression) best represented symptom data. Controlling for diagnosis, premorbid IQ, and disease severity, high lifetime psychosis scores were associated with reduced accuracy and speed across cognitive domains, while high depression scores were associated with increased social cognition accuracy. InterpretationTrans-diagnostic investigations demonstrated that neurocognitive function in SMI is characterized by two distinct profiles (BP-I/SCZ and BP-II/MDD), and is associated with specific symptom domains. These results suggest the utility of this design for elucidating SMI causes and trajectories.

neuroscience↗

bioRxiv2019

Autonomous drones are a viable tool for acoustic bat surveys

Acoustic surveys of bats are currently limited by the detection range of ultrasound microphones. This makes it difficult to survey bats at height, over water, or in other hard to reach locations. Drones, also known as UAVs or UASs, are becoming more affordable and feature rich, resulting in more uptake in conservation, primarily for aerial imagery. In this paper we address current limitations to acoustic bat surveys by developing three autonomous drones for surveying bats; a plane, quadcopter and boat. All three are capable of moving autonomously from one waypoint to another while carrying a bat detector to record bats and are all low cost (under US$950) with large operational ranges that make them suited to aerial transect work.\n\nInitial testing highlighted ultrasound noise generated by the drones as a major issue for recording bats from these systems. This was mitigated through iterative design of the microphone placement and the vehicles themselves. Subsequent testing in real world settings, in the presence of bats, demonstrated that bats could be recorded under autonomous navigation and that the ultrasound interference could be reduced to a negligible level.\n\nAutonomous drones offer an exciting new tool in the tool box of bat workers and researchers. They allow us to study areas previously inaccessible on foot, as well as at heights that have previously been inaccessible. We also discuss current limitations to this technology, including legal considerations, hidden costs and potential impacts on bat behaviour.

ecology↗

bioRxiv2019

The Contribution of Parietal Cortex to Visual Salience

Unique stimuli stand out. In spite of an abundance of competing sensory stimuli, the detection of the most salient ones occurs without effort, and that detection contributes to the guidance of adaptive behavior. Neurons sensitive to the salience of visual stimuli are widespread throughout the primate visual system and are thought to shape the selection of visual targets. However, mechanisms underlying the representation of salience remain elusive. Among the possible candidates are areas within posterior parietal cortex, which appear to be crucial in the control of visual attention and are thought to play a unique role in representing stimulus salience. Here we show that reversible inactivation of parietal cortex not only selectively reduces the representation of visual salience within the brain, but it also diminishes the influence of salience on visually guided behavior. These results demonstrate a distinct contribution of parietal areas to vision and visual attention.

neuroscience↗

bioRxiv2019

Approach for Semi-Automated Measurement of Fiber Diameter in Murine and Canine Skeletal Muscle

Currently available software tools for automated segmentation and analysis of muscle cross-section images often perform poorly in cases of weak or non-uniform staining conditions. To address these issues, our group has developed the MyoSAT (Myofiber Segmentation and Analysis Tool) image-processing pipeline.\n\nMyoSAT combines several unconventional approaches including advanced background leveling, Perona-Malik anisotropic diffusion filtering, and Stegers line detection algorithm to aid in pre-processing and enhancement of the muscle image. Final segmentation is based upon marker-based watershed segmentation.\n\nValidation tests using collagen V labeled murine and canine muscle tissue demonstrate that MyoSAT can determine mean muscle fiber diameter with an average accuracy of ~97%. The software has been tested to work on full muscle cross-sections and works well even under non-optimal staining conditions.\n\nThe MyoSAT software tool has been implemented as a macro for the freely available ImageJ software platform. This new segmentation tool allows scientists to efficiently analyze large muscle cross-sections for use in research studies and diagnostics.

neuroscience↗

bioRxiv2019

Investigation of the transcriptional profile of human kidneys during machine perfusion reveals potential benefits of haemoadsorption

Transplantation is the optimal treatment for most patients with end stage kidney disease but organ shortage is a major challenge. Normothermic machine perfusion (NMP) has been used to re-condition marginal organs but the mechanisms by which NMP might benefit transplant kidneys are not fully understood. Furthermore, the question of whether removal of pro-inflammatory mediators from the perfusate might offer additional benefits in optimising kidneys prior to transplantation has not been addressed. Using pairs of human kidneys obtained from the same donor, we compared the effect of NMP with that of cold storage on the global transcriptome of kidneys, and then went on to investigate the impact of adding a haemoadsorption device to the NMP circuit. We found that cold storage significantly reduced the expression of inflammatory genes, but also of genes required for energy generation such as those encoding oxidative phosphorylation (OXPHOS) enzymes. In contrast, during NMP, there was marked upregulation OXPHOS genes, as well as a number of immune and inflammatory pathway genes. The induction of inflammatory genes during NMP was substantially attenuated by the addition of a haemoadsorber to the perfusion circuit, which also further increased OXPHOS pathway gene expression. Together, our data suggest that absorption of pro-inflammatory mediators from the perfusate represents a useful intervention that may further improve organ viability and should be tested in clinical practice.\n\nSingle sentence summary: The use of a haemoadsorber during machine perfusion reduces inflammatory gene expression, with potential benefits for kidney transplantation.

physiology↗

bioRxiv2019

The California Environmental DNA \"CALeDNA\" Program

Global change is leading to habitat shifts that threaten species persistence throughout Californias unique ecosystems. Baseline biodiversity data provide opportunities for ecosystems to be managed for community complexity and connectivity. In 2017, the University of California Conservation Genomics Consortium launched the California Environmental DNA (CALeDNA) program, a community science initiative monitoring Californias biodiversity through environmental DNA (eDNA)--DNA shed from organisms through fur, mucus, spores, pollen, etc. Community scientists collect soil and sediment samples, then researchers analyze the eDNA in the samples and share results with the public. The results are catalogues of thousands of organisms per sample, ranging from microbes to mammals. The CALeDNA website presents biodiversity inventories in a platform designed for the public and researchers alike, as well as user-friendly analysis tools and educational modules. Here, we present CALeDNA as a scalable community science framework that can harmonize with future biodiversity research and education initiatives.

scientific communication and education↗

bioRxiv2018

SUCCESSFUL DEMONSTRATION OF ASSISTED GENE FLOW IN THE THREATENED CORAL ACROPORA PALMATA ACROSS GENETICALLY-ISOLATED CARIBBEAN POPULATIONS USING CRYOPRESERVED SPERM

Global change will compromise the population sizes, species ranges, and survival of economically-important plants and animals, including crops, aquaculture species, and foundational ecosystem builders. Scleractinian reef-building corals are a particular concern because they are slow-growing, long-lived, environmentally-sensitive, and concentrated in the warmest regions of the ocean. Assisted Gene Flow (AGF) is considered a viable tool to help natural plant and animal populations, including corals, adapt to changing environments. Our goal was to test for the first time whether cryopreserved coral sperm could be used to facilitate assisted gene flow between genetically-isolated populations of a Caribbean coral. We collected, pooled, and cryopreserved coral sperm from the threatened Caribbean coral Acropora palmata in the western Caribbean (Key Largo, FL), central Caribbean (Rincon, Puerto Rico), and eastern Caribbean (Curacao). Alongside freshly-collected sperm from Curacao, the cryopreserved sperm from each of these populations was used for in vitro fertilization experiments with freshly-collected eggs from Curacao. Across five egg donors, average fertilization success was 91 to 99% for CUR x CUR (fresh sperm) crosses, 37 to 82% for CUR x CUR (frozen sperm) crosses, 3 to 19% for CUR x FL (frozen sperm) crosses and 0 to 24% for CUR x PR (frozen sperm) crosses. Notably, fertilization was achieved in all four categories of crosses, showing for the first time through direct evidence that populations of A. palmata are reproductively compatible, and that genetic diversity can be transferred from one population to another for the purposes of assisted gene flow. The resulting larvae were reared in Curacao for up to 7 days, then the swimming larvae were transported to Florida for settlement and grow-out at two separate facilities, which achieved larval settlement rates of 37 to 60% across all cohorts. Larvae were reared and settled in Florida to acclimate them to the ambient water quality, microbial environment, and temperature regimes of the western genetic A. palmata population as early in their life cycle as possible. At one month, over 54% all settlers had survived, including over 3500 settlers from CUR x CUR (frozen sperm), 1200 settlers from CUR x FL (frozen sperm), and 230 settlers from CUR x PR (frozen sperm). These experiments represent the first-ever pan-Caribbean coral crosses produced in captivity and the first direct evidence that geographically-separated and genetically-isolated populations of any Caribbean coral are reproductively compatible. Moreover, with over 4700 A. palmata settlers produced using cryopreserved sperm, this represents the largest living wildlife population ever created from cryopreserved material. Together, these findings demonstrate that cryopreservation of coral sperm can enable efficient, large-scale assisted gene flow in corals. This form of assisted migration can not only help to preserve the population-level genetic diversity of extant coral populations but also help to increase population resilience to global change.

zoology↗

bioRxiv2018

Transcranial ultrasound selectively biases decision-making in primates

Transcranial focused ultrasound has the promise to evolve into a transformative noninvasive way to modulate activity of neuronal circuits deep in the brain. The approach may enable systematic and causal mapping of how individual brain circuits are involved in specific behaviors and behavioral disorders. Previous studies demonstrated neuromodulatory potential, but the effect polarity, size, and spatial specificity have been difficult to assess. Here, we engaged non-human primates (macaca mulatta) in an established task that provides a well defined framework to characterize the neuromodulatory effects. In this task, subjects decide whether to look at a right or a left target, guided by one the targets appearing first. Previous studies showed that excitation/inhibition of oculomotor circuits leads to contralateral/ipsilateral biases in this choice behavior. We found that brief, low-intensity ultrasound stimuli (300 ms, 0.6 MPa, 270 kHz) delivered to the animals left/right frontal eye fields bias the animals decisions to the right/left visual hemifield. The effect was modest, about on the order of that produced when injecting moderate amounts of potent neuromodulatory drugs into the same regions in this task. The polarity of the effects suggested a neuronal excitation within the stimulated regions. No effects were observed when we applied the same stimuli to control brain regions not involved in oculomotor target selection. Together, using an established paradigm, we found that transcranial ultrasound is capable of modulating neurons to the extent of biasing choice behavior of non-human primates. A demonstration of tangible, double-dissociated effects on behavior of primates constitutes a critical step toward applying this noninvasive neuromodulation method in investigations of how specific neural circuits are involved in specific behaviors or disease signs.

neuroscience↗

bioRxiv2018

Laminar Segregation of Sensory Coding and Behavioral Readout in Macaque V4

Neurons in sensory areas of the neocortex are known to represent information both about sensory stimuli and behavioral state, but how these two disparate signals are integrated across cortical layers is poorly understood. To study this issue, we measured the coding of visual stimulus orientation and of behavioral state by neurons within superficial and deep layers of area V4 in monkeys while they covertly attended or prepared eye movements to visual stimuli. We show that single neurons and neuronal populations in superficial layers convey more information about the orientation of visual stimuli, whereas single neurons and neuronal populations in deep layers convey greater information about the behavioral relevance of those stimuli. In particular, deep layer neurons encode greater information about the direction of prepared eye movements. These results reveal a division of labor between laminae in the coding of visual input and visually guided behavior.

neuroscience↗

bioRxiv2017

Diminished Cortical Thickness is Associated with Impulsive Choice in Adolescence

Adolescence is characterized by both maturation of brain structure and increased risk of negative outcomes from behaviors associated with impulsive decision-making. One important index of impulsive choice is delay discounting (DD), which measures the tendency to prefer smaller rewards available soon over larger rewards delivered after a delay. However, it remains largely unknown how individual differences in structural brain development may be associated with impulsive choice during adolescence. Leveraging a unique large sample of 427 human youths (208 males and 219 females) imaged as part of the Philadelphia Neurodevelopmental Cohort, we examined associations between delay discounting and cortical thickness within structural covariance networks. These structural networks were derived using non-negative matrix factorization, an advanced multivariate technique for dimensionality reduction, and analyzed using generalized additive models with penalized splines to capture both linear and nonlinear developmental effects. We found that impulsive choice, as measured by greater discounting, was most strongly associated with diminished cortical thickness in structural brain networks that encompassed the ventromedial prefrontal cortex, orbitofrontal cortex, temporal pole, and temporoparietal junction. Furthermore, structural brain networks predicted DD above and beyond cognitive performance. Taken together, these results suggest that reduced cortical thickness in regions known to be involved in value-based decision-making is a marker of impulsive choice during the critical period of adolescence.\n\nSIGNIFICANCERisky behaviors during adolescence, such as initiation of substance use or reckless driving, are a major source of morbidity and mortality. In this study, we present evidence from a large sample of youths that diminished cortical thickness in specific structural brain networks is associated with impulsive choice. Notably, the strongest association between impulsive choice and brain structure was seen in regions implicated in value-based decision-making; namely, the ventromedial prefrontal and orbitofrontal cortices. Moving forward, such neuroanatomical markers of impulsivity may aid in the development of personalized interventions targeted to reduce risk of negative outcomes resulting from impulsivity during adolescence.

neuroscience↗

bioRxiv2017

Light Guided In-vivo Activation of Innate Immune Cells with Photocaged TLR 2/6 Agonist

The complexity of the immune system creates challenges in exploring its importance and robustness. To date, there have been few techniques developed to manipulate individual components of the immune system in an in vivo environment. Here we show a light-based dendritic cell (DC) activation allowing spatial and temporal control of immune activation in vivo. Additionally, we show time dependent changes in RNA profiles of the draining lymph node, suggesting a change in cell profile following DC migration and indicating that the cells migrating have been activated towards antigen presentation.

immunology↗