Evolving super stimuli for real neurons using deep generative networks, bioRxiv, 2019-01-17
Finding the best stimulus for a neuron is challenging because it is impossible to test all possible stimuli. Here we used a vast, unbiased, and diverse hypothesis space encoded by a generative deep neural network model to investigate neuronal selectivity in inferotemporal cortex without making any assumptions about natural features or categories. A genetic algorithm, guided by neuronal responses, searched this space for optimal stimuli. Evolved synthetic images evoked higher firing rates than even the best natural images and revealed diagnostic features, independently of category or feature selection. This approach provides a way to investigate neural selectivity in any modality that can be represented by a neural network and challenges our understanding of neural coding in visual cortex.
biorxiv neuroscience 200-500-users 2019Single-Cell Transcriptomic Evidence for Dense Intracortical Neuropeptide Networks, bioRxiv, 2019-01-14
BrieflyAnalysis of single-cell RNA-Seq data from mouse neocortex exposes evidence for local neuropeptidergic modulation networks that involve every cortical neuron directly.Data Highlights<jatslist list-type=bullet><jatslist-item>At least 98% of mouse neocortical neurons express one or more of 18 neuropeptide precursor proteins (NPP) genes.<jatslist-item><jatslist-item>At least 98% of cortical neurons express one or more of 29 neuropeptide-selective G-protein-coupled receptor (NP-GPCR) genes.<jatslist-item><jatslist-item>Neocortical expression of these 18 NPP and 29 NP-GPCR genes is highly neuron-type-specific and permits exceptionally powerful differentiation of transcriptomic neuron types.<jatslist-item><jatslist-item>Neuron-type-specific expression of 37 cognate NPP NP-GPCR gene pairs predicts modulatory connectivity within 37 or more neuron-type-specific intracortical networks.<jatslist-item>SummarySeeking insight into homeostasis, modulation and plasticity of cortical synaptic networks, we analyzed results from deep RNA-Seq analysis of 22,439 individual mouse neocortical neurons. This work exposes transcriptomic evidence that all cortical neurons participate directly in highly multiplexed networks of modulatory neuropeptide (NP) signaling. The evidence begins with a discovery that transcripts of one or more neuropeptide precursor (NPP) and one or more neuropeptide-selective G-protein-coupled receptor (NP-GPCR) genes are highly abundant in nearly all cortical neurons. Individual neurons express diverse subsets of NP signaling genes drawn from a palette encoding 18 NPPs and 29 NP-GPCRs. Remarkably, these 47 genes comprise 37 cognate NPPNP-GPCR pairs, implying a strong likelihood of dense, cortically localized neuropeptide signaling. Here we use neuron-type-specific NP gene expression signatures to put forth specific, testable predictions regarding 37 peptidergic neuromodulatory networks that may play prominent roles in cortical homeostasis and plasticity.
biorxiv neuroscience 100-200-users 2019Does testosterone impair mens' cognitive empathy? Evidence from two large-scale randomized controlled trials Supplementary material, bioRxiv, 2019-01-13
The capacity to infer the mental states of others (known as cognitive empathy) is essential for social interactions, and a well-known theory proposes that it is negatively affected by intrauterine testosterone exposure. Furthermore, previous studies reported that testosterone administration impaired cognitive empathy in healthy adults, and that a biomarker of prenatal testosterone exposure (finger digit ratios) moderated the effect. However, empirical support for the relationship has relied on small-sample studies with mixed evidence. We investigate the reliability and generalizability of the relationship in two large-scale double-blind placebo-controlled experiments in young men (N=243 and N=400), using two different testosterone administration protocols. We find no evidence that cognitive empathy is impaired by testosterone administration or associated with digit ratios. With an unprecedented combined sample size, these results counter current theories and previous high-profile reports, and demonstrate that previous investigations of this topic have been statistically underpowered.
biorxiv neuroscience 200-500-users 2019Does testosterone impair men’s cognitive empathy? Evidence from two large-scale randomized controlled trials, bioRxiv, 2019-01-13
AbstractThe capacity to infer others’ mental states (known as “mind reading” and “cognitive empathy”) is essential for social interactions across species, and its impairment characterizes psychopathological conditions such as autism spectrum disorder and schizophrenia. Previous studies reported that testosterone administration impaired cognitive empathy in healthy humans, and that a putative biomarker of prenatal testosterone exposure (finger digit ratios) moderated the effect. However, empirical support for the relationship has relied on small-sample studies with mixed evidence. We investigate the reliability and generalizability of the relationship in two large-scale double-blind placebo-controlled experiments in young men (N=243 and N=400), using two different testosterone administration protocols. We find no evidence that cognitive empathy is impaired by testosterone administration or associated with digit ratios. With an unprecedented combined sample size, these results counter current theories and previous high-profile reports, and demonstrate that previous investigations of this topic have been statistically underpowered.
biorxiv neuroscience 200-500-users 2019Insulin enhances presynaptic glutamate release in the nucleus accumbens via opioid receptor-mediated disinhibition, bioRxiv, 2019-01-12
Insulin influences learning and cognition and activity in brain centers that mediate reward and motivation in humans. However, very little is known about how insulin influences excitatory transmission within brain reward centers such as the nucleus accumbens (NAc). Further, insulin dysregulation that accompanies obesity is linked to cognitive decline, depression, anxiety, and aberrant motivation that also rely on excitatory transmission in the NAc, but potential mechanisms are poorly understood. Here we show that insulin receptor activation increases presynaptic glutamate release via a previously unidentified form of opioid receptor-mediated disinhibition, whereas activation of IGF receptors by insulin decreases presynaptic glutamate release in the NAc. Furthermore, obesity results in a loss of the insulin receptor-mediated increases and a reduction in NAc insulin receptor surface expression, while preserving reductions in excitatory transmission mediated by IGF receptors. These results provide the first insights into how insulin influences excitatory transmission in the adult brain and have broad implications for the regulation of motivation and reward related processes by peripheral hormones.
biorxiv neuroscience 0-100-users 2019Individual-Specific fMRI-Subspaces Improve Functional Connectivity Prediction of Behavior Supplemental, bioRxiv, 2019-01-10
There is significant interest in using resting-state functional connectivity (RSFC) to predict human behavior. Good behavioral prediction should in theory require RSFC to be sufficiently distinct across participants; if RSFC were the same across participants, then behavioral prediction would obviously be poor. Therefore, we hypothesize that removing common resting-state functional magnetic resonance imaging (rs-fMRI) signals that are shared across participants would improve behavioral prediction. Here, we considered 803 participants from the human connectome project (HCP) with four rs-fMRI runs. We applied the common and orthogonal basis extraction (COBE) technique to decompose each HCP run into two subspaces a common (group-level) subspace shared across all participants and a subject-specific subspace. We found that the first common COBE component of the first HCP run was localized to the visual cortex and was unique to the run. On the other hand, the second common COBE component of the first HCP run and the first common COBE component of the remaining HCP runs were highly similar and localized to regions within the default network, including the posterior cingulate cortex and precuneus. Overall, this suggests the presence of run-specific (state-specific) effects that were shared across participants. By removing the first and second common COBE components from the first HCP run, and the first common COBE component from the remaining HCP runs, the resulting RSFC improves behavioral prediction by an average of 11.7% across 58 behavioral measures spanning cognition, emotion and personality.
biorxiv neuroscience 0-100-users 2019