Biology subjects

Kaplan, R.

Publications and source records attributed to Kaplan, R..

5 recordsLinked to original sources

bioRxiv2018

Hippocampal-entorhinal transformations in abstract frames of reference

Knowing how anothers preferences relate to our own is a central aspect of everyday decision-making, yet how the brain performs this transformation is unclear. Here, we ask whether the putative role of the hippocampal-entorhinal system in transforming relative and absolute spatial coordinates during navigation extends to transformations in abstract decision spaces. During fMRI scanning, subjects learned a strangers preference for an everyday activity - relative to one of three personally known individuals - and subsequently decided how the strangers preference relates to the other two individuals preferences. We found that entorhinal cortex/subiculum signals exhibited reference frame-sensitive responses to the absolute distance between the ratings of the stranger and the familiar choice options. In contrast, striatal signals increased when accurately determining the ordinal position of choice options in relation to the stranger. Paralleling its role in navigation, these data implicate the entorhinal/subicular region in assimilating relatively coded knowledge within abstract metric spaces.

neuroscience↗

bioRxiv2018

Human hippocampal theta oscillations reflect sequential dependencies during spatial planning.

Movement-related theta oscillations in rodent hippocampus coordinate forward sweeps of location-specific neural activity that could be used to evaluate spatial trajectories online. This raises the possibility that increases in human hippocampal theta power accompany the evaluation of upcoming spatial choices. To test this hypothesis, we measured neural oscillations during a spatial planning task that closely resembles a perceptual decision-making paradigm. In this task, participants searched visually for the shortest path between a start and goal location in novel mazes that contained multiple choice points, and were subsequently asked to make a spatial decision at one of those choice points. We observed ~4-8 Hz hippocampal/medial temporal lobe theta power increases specific to sequential planning that were negatively correlated with subsequent decision speed, where decision speed was inversely correlated with choice accuracy. These results implicate the hippocampal theta rhythm in decision tree search during planning in novel environments.

neuroscience↗

bioRxiv2018

Rapid Whole Genome Sequencing Decreases Morbidity and Healthcare Cost of Hospitalized Infants

BACKGROUNDGenetic disorders are a leading cause of morbidity and mortality in infants. Rapid Whole Genome Sequencing (rWGS) can diagnose genetic disorders in time to change acute medical or surgical management (clinical utility) and improve outcomes in acutely ill infants.\n\nMETHODSRetrospective cohort study of acutely ill inpatient infants in a regional childrens hospital from July 2016-March 2017. Forty-two families received rWGS for etiologic diagnosis of genetic disorders. Probands received standard genetic testing as clinically indicated. Primary end-points were rate of diagnosis, clinical utility, and healthcare utilization. The latter was modelled in six infants by comparing actual utilization with matched historical controls and/or counterfactual utilization had rWGS been performed at different time points.\n\nFINDINGSThe diagnostic sensitivity was 43% (eighteen of 42 infants) for rWGS and 10% (four of 42 infants) for standard of care (P=.0005). The rate of clinical utility for rWGS (31%, thirteen of 42 infants) was significantly greater than for standard of care (2%, one of 42; P=.0015). Eleven (26%) infants with diagnostic rWGS avoided morbidity, one had 43% reduction in likelihood of mortality, and one started palliative care. In six of the eleven infants, the changes in management reduced inpatient cost by $800, 000 to $2,000,000.\n\nDISCUSSIONThese findings replicate a prior study of the clinical utility of rWGS in acutely ill inpatient infants, and demonstrate improved outcomes and net healthcare savings. rWGS merits consideration as a first tier test in this setting.

clinical trials↗

bioRxiv2017

Planning and navigation as active inference

This paper introduces an active inference formulation of planning and navigation. It illustrates how the exploitation-exploration dilemma is dissolved by acting to minimise uncertainty (i.e., expected surprise or free energy). We use simulations of a maze problem to illustrate how agents can solve quite complicated problems using context sensitive prior preferences to form subgoals. Our focus is on how epistemic behaviour - driven by novelty and the imperative to reduce uncertainty about the world - contextualises pragmatic or goal-directed behaviour. Using simulations, we illustrate the underlying process theory with synthetic behavioural and electrophysiological responses during exploration of a maze and subsequent navigation to a target location. An interesting phenomenon that emerged from the simulations was a putative distinction between place cells - that fire when a subgoal is reached - and path cells - that fire until a subgoal is reached.

neuroscience↗

bioRxiv2017

Neurohormonal signalling controls insulin sensitivity and specificity in C. elegans

Insulin and insulin-like growth factor signalling regulates a broad spectrum of growth and metabolic responses to a variety of internal and environmental stimuli. Such responses can be tailored to the environment so that changes in insulin signalling result in distinct physiological responses to different stimuli. For example, the inhibition of insulin-like signalling by osmotic stress or by starvation of C. elegans results in physiologically distinct states and patterns of gene expression. How does insulin-like signalling elicit different responses to different environmental stimuli? We report that neurohormonal signalling involving the C. elegans cytosolic sulfotransferase SSU-1 controls developmental arrest in response to osmotic stress but not to starvation; that SSU-1 functions in a single pair of sensory neurons to control signalling via the nuclear hormone receptor NHR-1; that signalling controlled by SSU-1 acts antagonistically to insulin-like signalling; and that the FOXO transcription factor DAF-16, a downstream effector of insulin-like signalling, enters the nucleus in response to osmotic stress but activates gene expression only if SSU-1 is active. We propose that neurohormonal signalling controlled by one or more cytosolic sulfotransferases similarly regulates the specificity of responses to changes in insulin signalling during periods of environmental stress in other organisms and that abnormalities in such sulfotransferase-controlled neurohormonal signalling might contribute to human disorders that involve insulin signalling, such as obesity and type 2 diabetes.

genetics↗