Enriched Environment Prevents Surgery-Induced Persistent Neural Inhibition and Cognitive Dysfunction

Perioperative neurocognitive disorders (PND) encompass short-term delirium and long-term cognitive dysfunction. Aging increases the susceptibility to PND, yet the neural mechanism is not known. In this study, we monitored the dynamic changes of neuronal activity in the prelimbic cortex before and after surgery. We found that anesthesia combined with surgery, but not anesthesia alone, induced a prolonged decrease in neuronal activity during the post-operation period in the aged mice, but not in the adult mice. The prolonged decrease in neuronal activity was accompanied by surgery-induced microglial activation and proinflammatory cytokines expression. Importantly, we found that the enriched environment (EE) completely prevented both the prolonged neural inhibition and neuroinflammation, and improved cognitive function in the aged mice. These results indicate that the prolonged neural inhibition correlated to PND and that EE before the surgery could effectively alleviate the surgery- induced cognitive dysfunction.

Neural excitation/inhibition imbalance and the treatment of severe depression

An influential hypothesis holds that depression is related to a neural excitation/inhibition imbalance, but its role in the treatment of depression remains unclear. Here, we show that unmedicated patients with severe depression demonstrated reduced inhibition of brain-wide resting-state networks relative to healthy controls. Patients using antidepressants showed inhibition that was higher than unmedicated patients and comparable to controls, but they still suffered from severe depression. Subsequent treatment with electroconvulsive therapy (ECT) reduced depressive symptoms, but its effectiveness did not depend on changes in network inhibition. Concomitant pharmacotherapy increased the effectiveness of ECT, but only when the strength of neural inhibition before ECT was within the normal range and not when inhibition was excessive. These findings suggest that reversing the excitation/inhibition imbalance may not be sufficient nor necessary for the effective treatment of severe depression, and that brain-state informed pharmacotherapy management may enhance the effectiveness of ECT.

Functional network antagonism through the prism of theories of consciousness

The brainʼs spontaneous activity changes across states of consciousness. A particular consciousness-mediated brain configuration is the antagonistic relationship between the default mode network (encompassing mainly midline cortical regions) and frontoparietal areas (DMN anticorrelations). Functional anticorrelations especially have been shown to be important for behavior and consciousness, as they are absent or substantially reduced in early developmental stages, states of anesthesia, and disorders of consciousness. To date, though, theories of consciousness do not frame the anticorrelations in a comprehensive manner. Here, by tackling their biological origins, we suggest that neural inhibition is the underlying mechanism which mediates the emerging architecture of the fMRI anticorrelations. We go on to propose that neural inhibition reflects the process of functional segregation, namely the capacity of the brain to show selectivity in the areas which will be functionally connected. We then see how this view of segregation is met in the Global Neuronal Workspace Theory (GNWT, inhibition) and the Integrated Information Theory (IIT, differentiation) and propose that the anticorrelations can be considered as the quantifiable counterpart of these theoretical notions. We believe that this stance on functional anticorrelations will shed more light on what inter-network antagonism means for consciousness, and will open discussions about pragmatic quantifications of theoretical notions within consciousness research.

Auditory Sensory Gating of Speech and Nonspeech Stimuli

Purpose Auditory sensory gating is a neural measure of inhibition and is typically measured with a click or tonal stimulus. This electrophysiological study examined if stimulus characteristics and the use of speech stimuli affected auditory sensory gating indices. Method Auditory event-related potentials were elicited using natural speech, synthetic speech, and nonspeech stimuli in a traditional auditory gating paradigm in 15 adult listeners with normal hearing. Cortical responses were recorded at 64 electrode sites, and peak amplitudes and latencies to the different stimuli were extracted. Individual data were analyzed using repeated-measures analysis of variance. Results Significant gating of P1–N1–P2 peaks was observed for all stimulus types. N1–P2 cortical responses were affected by stimulus type, with significantly less neural inhibition of the P2 response observed for natural speech compared to nonspeech and synthetic speech. Conclusions Auditory sensory gating responses can be measured using speech and nonspeech stimuli in listeners with normal hearing. The results of the study indicate the amount of gating and neural inhibition observed is affected by the spectrotemporal characteristics of the stimuli used to evoke the neural responses.

Does Cortical Inhibition Explain the Correlation Between Bistable Perception Paradigms?

When observers view a perceptually bistable stimulus, their perception changes stochastically. Various studies have shown across-observer correlations in the percept durations for different bistable stimuli including binocular rivalry stimuli and bistable moving plaids. Previous work on binocular rivalry posits that neural inhibition in the visual hierarchy is a factor involved in the perceptual fluctuations in that paradigm. Here, in order to investigate whether between-observer variability in cortical inhibition underlies correlated percept durations between binocular rivalry and bistable moving plaid perception, we used center-surround suppression as a behavioral measure of cortical inhibition. We recruited 217 participants in a test battery that included bistable perception paradigms as well as a center-surround suppression paradigm. While we were able to successfully replicate the correlations between binocular rivalry and bistable moving plaid perception, we did not find a correlation between center-surround suppression strength and percept durations for any form of bistable perception. Moreover, the results from a mediation analysis indicate that center-surround suppression is not the mediating factor in the correlation between binocular rivalry and bistable moving plaids. These results do not support the idea that cortical inhibition can explain the between-observer correlation in mean percept duration between binocular rivalry and bistable moving plaid perception.

An excitatory ventromedial hypothalamus to paraventricular thalamus circuit that suppresses food intake

It is well recognized that ventromedial hypothalamus (VMH) serves as a satiety center in the brain. However, the feeding circuit for the VMH regulation of food intake remains to be defined. Here, we combine fiber photometry, chemo/optogenetics, virus-assisted retrograde tracing, ChR2-assisted circuit mapping and behavioral assays to show that selective activation of VMH neurons expressing steroidogenic factor 1 (SF1) rapidly inhibits food intake, VMH SF1 neurons project dense fibers to the paraventricular thalamus (PVT), selective chemo/optogenetic stimulation of the PVT-projecting SF1 neurons or their projections to the PVT inhibits food intake, and chemical genetic inactivation of PVT neurons diminishes SF1 neural inhibition of feeding. We also find that activation of SF1 neurons or their projections to the PVT elicits a flavor aversive effect, and selective optogenetic stimulation of ChR2-expressing SF1 projections to the PVT elicits direct excitatory postsynaptic currents. Together, our data reveal a neural circuit from VMH to PVT that inhibits food intake.