State-Dependent Regulation of Cortical Processing Speed via Gain Modulation

To thrive in dynamic environments, animals must be capable of rapidly and flexibly adapting behavioral responses to a changing context and internal state. Examples of behavioral flexibility include faster stimulus responses when attentive and slower responses when distracted. Contextual or state-dependent modulations may occur early in the cortical hierarchy and may be implemented via top-down projections from corticocortical or neuromodulatory pathways. However, the computational mechanisms mediating the effects of such projections are not known. Here, we introduce a theoretical framework to classify the effects of cell type-specific top-down perturbations on the information processing speed of cortical circuits. Our theory demonstrates that perturbation effects on stimulus processing can be predicted by intrinsic gain modulation, which controls the timescale of the circuit dynamics. Our theory leads to counterintuitive effects, such as improved performance with increased input variance. We tested the model predictions using large-scale electrophysiological recordings from the visual hierarchy in freely running mice, where we found that a decrease in single-cell intrinsic gain during locomotion led to an acceleration of visual processing. Our results establish a novel theory of cell type-specific perturbations, applicable to top-down modulation as well as optogenetic and pharmacological manipulations. Our theory links connectivity, dynamics, and information processing via gain modulation.SIGNIFICANCE STATEMENT To thrive in dynamic environments, animals adapt their behavior to changing circumstances and different internal states. Examples of behavioral flexibility include faster responses to sensory stimuli when attentive and slower responses when distracted. Previous work suggested that contextual modulations may be implemented via top-down inputs to sensory cortex coming from higher brain areas or neuromodulatory pathways. Here, we introduce a theory explaining how the speed at which sensory cortex processes incoming information is adjusted by changes in these top-down projections, which control the timescale of neural activity. We tested our model predictions in freely running mice, revealing that locomotion accelerates visual processing. Our theory is applicable to internal modulation as well as optogenetic and pharmacological manipulations and links circuit connectivity, dynamics, and information processing.     

Running bodies and the affective spaces of health in and beyond marathon running in China

This paper explores the affective formation of health and space/place through an examination of the affective and bodily practices of marathon runners in China. By elaborating the idea of “affective spaces of health”, we investigate not only how the affective potential of running bodies enables a therapeutic and individualised form of selfhood in response to China's post-socialist transformation, but also how affective atmospheres might condition and discipline runners' affective capacities for health. The paper therefore questions the simplistic association of health with particular qualities of place, and calls for research to focus on the affective, dispersed and fluid spaces of health instead.     

Impact of COVID-19 in solid organ transplant recipients

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exploded onto the world stage in early 2020. The impact on solid organ transplantation (SOT) has been profound affecting potential donors, candidates, and recipients. Importantly, decreased donations and the pressure of limited resources placed on health care by the pandemic also disrupted transplant systems. We address the impact of COVID-19 on organ transplantation globally and review current understanding of the epidemiology, outcomes, diagnosis, and treatment of COVID-19 in SOT recipients.     

Microbiota and immunoregulation: A focus on regulatory B lymphocytes and transplantation

The microbiota plays a major role in the regulation of the host immune functions thus establishing a symbiotic relationship that maintains immune homeostasis. Among immune cells, regulatory B cells (Bregs), which can inhibit effector T cell responses, may be involved in the intestinal homeostasis. Recent works suggest that the interaction between the microbiota and Bregs appears to be important to limit autoimmune diseases and help to maintain tolerance in transplantation. Short-chain fatty acids (SCFAs), recognized as major metabolites of the microbiota, seem to be involved in the generation of a pro-tolerogenic environment in the gut, particularly through the regulation of B cell differentiation, limiting mature B cells and promoting the function of Bregs. In this review, we show that this B cells–microbiota interaction may open a path toward new potential therapeutic applications not only for patients with autoimmune diseases but also in transplantation.     

Hippocampal spike‐time correlations and place field overlaps during open field foraging

Phase precessing place cells encode spatial information on fine timescales via the timing of their spikes. This phase code has been extensively studied on linear tracks and for short runs in the open field. However, less is known about the phase code on unconstrained trajectories lasting tens of minutes, typical of open field foraging. In previous work (Monsalve‐Mercado and Leibold, Physical Review Letters, 119, 38101 (2017)), an analytic expression was derived for the spike‐time cross‐correlation between phase precessing place cells during natural foraging in the open field. This expression makes two predictions on how this phase code differs from the linear track case: cross‐correlations are symmetric with respect to time, and they represent the distance between pairs of place fields in that the theta‐filtered cross‐correlations around zero time lag are positive for cells with nearby fields while they are negative for those with fields further apart. Here we analyze several available open field recordings and show that these predictions hold for pairs of CA1 place cells. We also show that the relationship remains during remapping in CA1, and it is also present in place cells in area CA3. For CA1 place cells of Fmr1‐null mice, which exhibit normal place fields but somewhat weaker temporal coordination with respect to theta compared to wild type, the cross‐correlations still remain symmetric but the relationship to place field overlap is largely lost. The relationship discussed here describes how spatial information is communicated by place cells to downstream areas in a finer theta‐timescale, relevant for learning and memory formation in behavioral tasks lasting tens of minutes in the open field.     

On the functions,mechanisms, and malfunctions of intracortical contextual modulation

A broad neuron-centric conception of contextual modulation is reviewed and re-assessed in the light of recent neurobiological studies of amplification, suppression, and synchronization. Behavioural and computational studies of perceptual and higher cognitive functions that depend on these processes are outlined, and evidence that those functions and their neuronal mechanisms are impaired in schizophrenia is summarized. Finally, we compare and assess the long-term biological functions of contextual modulation at the level of computational theory as formalized by the theories of coherent infomax and free energy reduction. We conclude that those theories, together with the many empirical findings reviewed, show how contextual modulation at the neuronal level enables the cortex to flexibly adapt the use of its knowledge to current circumstances by amplifying and grouping relevant activities and by suppressing irrelevant activities.     

“Having the heart to be evaluated”: The differential effects of fears of positive and negative evaluation on emotional and cardiovascular responses to social threat

Accumulating evidence supports fear of evaluation in general as important in social anxiety, including fear of positive evaluation (FPE) and fear of negative evaluation (FNE). The present study examined state responses to an impromptu speech task with a sample of 81 undergraduates. This study is the first to compare and contrast physiological responses associated with FPE and FNE, and to examine both FPE- and FNE-related changes in state anxiety/affect in response to perceived social evaluation during a speech. FPE uniquely predicted (relative to FNE/depression) increases in mean heart rate during the speech; in contrast, neither FNE nor depression related to changes in heart rate. Both FPE and FNE related uniquely to increases in negative affect and state anxiety during the speech. Furthermore, pre-speech state anxiety mediated the relationship between trait FPE and diminished positive affect during the speech. Implications for the theoretical conceptualization and treatment of social anxiety are discussed.