Jumping To Conclusions, General Intelligence, And Psychosis Liability Findings From The Multi-Centre EU-GEI Case-Control Study, bioRxiv, 2019-05-11
AbstractBackgroundThe “jumping to conclusions” (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.Methods817 FEP patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC (assessed by the number of beads drawn on the probabilistic reasoning “beads” task) and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.ResultsThe estimated proportion of the total effect of casecontrol differences on JTC mediated by IQ was 79%. Schizophrenia Polygenic Risk Score (SZ PRS) was non-significantly associated with a higher number of beads drawn (B= 0.47, 95% CI −0.21 to 1.16, p=0.17); whereas IQ PRS (B=0.51, 95% CI 0.25 to 0.76, p<0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with higher level of psychotic-like experiences (PLE) in controls, including after controlling for IQ (B= −1.7, 95% CI −2.8 to −0.5, p=0.006), but did not relate to delusions in patients.Conclusionsthe JTC reasoning bias in psychosis is not a specific cognitive deficit but is rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to psychotic-like experiences, independent of IQ. The work has potential to inform interventions targeting cognitive biases in early psychosis.
biorxiv neuroscience 0-100-users 2019Levels of Representation in a Deep Learning Model of Categorization, bioRxiv, 2019-05-06
AbstractDeep convolutional neural networks (DCNNs) rival humans in object recognition. The layers (or levels of representation) in DCNNs have been successfully aligned with processing stages along the ventral stream for visual processing. Here, we propose a model of concept learning that uses visual representations from these networks to build memory representations of novel categories, which may rely on the medial temporal lobe (MTL) and medial prefrontal cortex (mPFC). Our approach opens up two possibilities a) formal investigations can involve photographic stimuli as opposed to stimuli handcrafted and coded by the experimenter; b) model comparison can determine which level of representation within a DCNN a learner is using during categorization decisions. Pursuing the latter point, DCNNs suggest that the shape bias in children relies on representations at more advanced network layers whereas a learner that relied on lower network layers would display a color bias. These results confirm the role of natural statistics in the shape bias (i.e., shape is predictive of category membership) while highlighting that the type of statistics matter, i.e., those from lower or higher levels of representation. We use the same approach to provide evidence that pigeons performing seemingly sophisticated categorization of complex imagery may in fact be relying on representations that are very low-level (i.e., retinotopic). Although complex features, such as shape, relatively predominate at more advanced network layers, even simple features, such as spatial frequency and orientation, are better represented at the more advanced layers, contrary to a standard hierarchical view.
biorxiv neuroscience 100-200-users 2019Defined cell types in superior colliculus make distinct contributions to prey capture behavior in the mouse, bioRxiv, 2019-05-04
SummaryThe superior colliculus (SC) mediates rapid orienting to visual stimuli across species. To determine the specific circuits within the SC that drive orienting and approach behavior toward appetitive stimuli, we explored the role of three genetically defined cell types in mediating prey capture in mice. Chemogenetic inactivation of two classically defined cell types, the wide-field (WF) and narrow-field (NF) vertical neurons, revealed that they are involved in distinct aspects of prey capture. WF neurons were required for rapid prey detection and distant approach initiation, whereas NF neurons were required for continuous and accurate orienting during pursuit. In contrast, prey capture did not require parvalbumin-expressing (PV) neurons that have previously been implicated in fear responses. The visual coding of WF and NF cells in the awake mouse and their projection targets were consistent with their roles in prey detection versus pursuit. Thus, our studies link specific neural circuit connectivity and function with stimulus detection and orienting behavior, providing insight into visuomotor and attentional mechanisms mediated by superior colliculus.Highlights<jatslist list-type=bullet><jatslist-item>This study provides the first demonstration of the role of specific cell populations in the superior colliculus in orienting and approach behavior.<jatslist-item><jatslist-item>A genetically targeted population of wide-field vertical neurons in the superior colliculus is required for rapid prey detection and initiation of long-distance approaches.<jatslist-item><jatslist-item>A genetically targeted population of narrow-field vertical neurons is required for approach initiation, accurate targeting, and approach continuity.<jatslist-item><jatslist-item>Visual response properties and projection targets of these cells are consistent with their role in prey capture, linking neural circuit connectivity and function with behavior.<jatslist-item>
biorxiv neuroscience 0-100-users 2019Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits, bioRxiv, 2019-05-03
SummaryHow neural circuits develop in the human brain has remained almost impossible to study at the neuronal level. Here we investigate human cortical neuron development, plasticity and function, using a mousehuman chimera model in which xenotransplanted human cortical pyramidal neurons integrate as single cells into the mouse cortex. Combined neuronal tracing, electrophysiology, and in vivo structural and functional imaging revealed that the human neurons develop morphologically and functionally following a prolonged developmental timeline, revealing the cell-intrinsic retention of juvenile properties of cortical neurons as an important mechanism underlying human brain neoteny. Following maturation, human neurons transplanted in the visual cortex display tuned responses to visual stimuli that are similar to those of mouse neurons, indicating capacity for physiological synaptic integration of human neurons in mouse cortical circuits. These findings provide new insights into human neuronal development, and open novel experimental avenues for the study of human neuronal function and diseases.Highlights<jatslist list-type=bullet><jatslist-item>Coordinated morphological and functional maturation of ESC-derived human cortical neurons transplanted in the mouse cortex.<jatslist-item><jatslist-item>Transplanted neurons display prolonged juvenile features indicative of intrinsic species-specific neoteny.<jatslist-item><jatslist-item>Transplanted neurons develop elaborate dendritic arbors, stable spine patterns and long-term synaptic plasticity.<jatslist-item><jatslist-item>In the visual cortex transplanted neurons display tuned visual responses that resemble those of the host cortical neurons.<jatslist-item>
biorxiv neuroscience 0-100-users 2019A Spatiomolecular Map of the Striatum, bioRxiv, 2019-05-02
SUMMARYThe striatum is organized into two major outputs formed by striatal projection neuron (SPN) subtypes with distinct molecular identities. In addition, the histochemical division into patch and matrix compartments represents an additional spatial organization, proposed to mirror a functional specialization in a motor-motivation dimension. To map the molecular diversity of SPNs in the context of the patch and matrix division, we genetically labeled mu-opioid receptor (Oprm1) expressing striatal neurons and performed single-nucleus RNA sequencing (snRNA-seq). This allowed us to establish new molecular definitions of the patch-matrix compartments, resulting in a molecular code for mapping patch SPNs at the cellular level. In addition, Oprm1 expression labeled exopatch SPNs, which we found to be molecularly distinct from both patch as well as neighboring matrix SPNs, thereby forming a separate molecular entity. At the cell-type level, we found an unexpected SPN diversity, leading to the identification of a new Col11a1+ striatonigral SPN type. At the tissue level, we found that mapping the spatial expression of a number of markers revealed new definitions of spatial domains in the striatum, which were conserved in the non-human primate brain. Interestingly, the spatial markers were cell-type independent and instead represented a spatial code that was found across all SPNs within a spatially restricted domain. This spatiomolecular map establishes a formal system for targeting and studying the striatal subregions and SPNs subtypes, beyond the classical striatonigral and striatopallidal division.
biorxiv neuroscience 0-100-users 2019Functional integration of “undead” neurons in the olfactory system, bioRxiv, 2019-05-02
AbstractProgrammed cell death (PCD) is widespread during neurodevelopment, typically countering the surpluses of neuronal production. We examined, in the Drosophila olfactory system, the potential of cells fated to die to contribute to circuit evolution. Inhibition of PCD is sufficient to generate many new cells that express neural markers and exhibit odor-evoked activity. These “undead” neurons express a subset of olfactory receptors, enriched for recent receptor duplicates, and including those normally found in other chemosensory organs and life-stages. Moreover, undead neuron axons integrate into the olfactory circuitry in the brain. Comparison of homologous olfactory lineages across drosophilids reveals natural examples of fate changes from death to a functional neuron. These results reveal the remarkable potential of alterations in patterns of PCD to evolve novel neural pathways.
biorxiv neuroscience 0-100-users 2019