It's no joke: Study identifies brain circuitry involved in our grasp of sarcasm

Stress is associated with numerous chronic diseases, beginning in fetal development with in utero exposures (prenatal stress) impacting offspring’s risk for disorders later in life. In previous studies, we demonstrated adverse maternal in utero immune activity on sex differences in offspring neurodevelopment at age seven and adult risk for major depression and psychoses. Here, we hypothesized that in utero exposure to maternal proinflammatory cytokines has sex-dependent effects on specific brain circuitry regulating stress and immune function in the offspring that are retained across the lifespan. Using a unique prenatal cohort, we tested this hypothesis in 80 adult offspring, equally divided by sex, followed from in utero development to midlife. Functional MRI results showed that exposure to proinflammatory cytokines in utero was significantly associated with sex differences in brain activity and connectivity during response to negative stressful stimuli 45 y later. Lower maternal TNF-α levels were significantly associated with higher hypothalamic activity in both sexes and higher functional connectivity between hypothalamus and anterior cingulate only in men. Higher prenatal levels of IL-6 were significantly associated with higher hippocampal activity in women alone. When examined in relation to the anti-inflammatory effects of IL-10, the ratio TNF-α:IL-10 was associated with sex-dependent effects on hippocampal activity and functional connectivity with the hypothalamus. Collectively, results suggested that adverse levels of maternal in utero proinflammatory cytokines and the balance of pro- to anti-inflammatory cytokines impact brain development of offspring in a sexually dimorphic manner that persists across the lifespan.

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A Robust and Reproducible Connectome Fingerprint of Ketamine is Highly Associated with the Connectomic Signature of Antidepressants

10.1101/2020.04.10.20061085 ◽

2020 ◽

Author(s):

Chadi G. Abdallah ◽

Kyung-Heup Ahn ◽

Lynnette A. Averill ◽

Samaneh Nemati ◽

Christopher L. Averill ◽

...

Keyword(s):

Brain Connectivity ◽

Imaging Study ◽

Seed Selection ◽

Major Depressive ◽

Brain Circuitry ◽

Brain Functional Connectivity ◽

The Brain ◽

Healthy Participants ◽

Placebo Cohort ◽

Model Approach

ABSTRACTOver the past decade, various N-Methyl-D-Aspartate modulators have failed in clinical trials, underscoring the challenges of developing novel rapid-acting antidepressants based solely on the receptor or regional targets of ketamine. Thus, identifying the effect of ketamine on the brain circuitry and networks is becoming increasingly critical. In this longitudinal functional magnetic resonance imaging study of data from 265 participants, we used a validated predictive model approach that allows the full assessment of brain functional connectivity, without the need for seed selection or connectivity summaries. First, we identified a connectome fingerprint (CFP) in healthy participants (Cohort A, n=25) during intravenous infusion of a subanesthetic dose of ketamine, compared to normal saline. We then demonstrated the robustness and reproducibility of the discovered Ketamine CFP in two separate healthy samples (Cohort B, n=22; Cohort C, n=18). Finally, we investigated the Ketamine CFP connectivity at 1-week post treatment in major depressive disorder patients randomized to 8 weeks of sertraline or placebo (Cohort D, n=200). We found a significant, robust, and reproducible Ketamine CFP, consistent with reduced connectivity within the primary cortices and within the executive network, but increased connectivity between the executive network and the rest of the brain. Compared to placebo, the Ketamine CFP connectivity changes at 1-week predicted response to sertraline at 8-weeks. In each of Cohort A-C, ketamine significantly increased connectivity in a previously identified Antidepressant CFP. Investigating the brain connectivity networks, we successfully identified a robust and reproducible ketamine biomarker that is related to the mechanisms of antidepressants.Graphical Abstract

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A time-stamp mechanism may provide temporal information necessary for egocentric to allocentric spatial transformations

eLife ◽

10.7554/elife.36769 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 16

Author(s):

Avner Wallach ◽

Erik Harvey-Girard ◽

James Jaeyoon Jun ◽

André Longtin ◽

Len Maler

Keyword(s):

Spatial Learning ◽

Spatial Organization ◽

Spatial Information ◽

Spatial Relations ◽

Temporal Information ◽

Accurate Estimation ◽

Neural Recordings ◽

Brain Circuitry ◽

Learning Circuits ◽

Thalamic Region

Learning the spatial organization of the environment is essential for most animals’ survival. This requires the animal to derive allocentric spatial information from egocentric sensory and motor experience. The neural mechanisms underlying this transformation are mostly unknown. We addressed this problem in electric fish, which can precisely navigate in complete darkness and whose brain circuitry is relatively simple. We conducted the first neural recordings in the preglomerular complex, the thalamic region exclusively connecting the optic tectum with the spatial learning circuits in the dorsolateral pallium. While tectal topographic information was mostly eliminated in preglomerular neurons, the time-intervals between object encounters were precisely encoded. We show that this reliable temporal information, combined with a speed signal, can permit accurate estimation of the distance between encounters, a necessary component of path-integration that enables computing allocentric spatial relations. Our results suggest that similar mechanisms are involved in sequential spatial learning in all vertebrates.

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