A Signature of Cortical Information Processing Underlies Shifts in Global States of Consciousness

Post by Soumilee Chaudhuri

The takeaway

Altered global states of consciousness are based on a top-down information processing signature in the cortex and influenced by a) spontaneous brain activity as well as b) regional brain organization. So, consciousness is determined by a hierarchical brain-region and brain-activity dependent signature.

What's the science?

Classically, consciousness has been understood as a neural manifestation of subjective experiences and linked to several dynamic neural processes in the brain. We  know that breakdowns in consciousness (during sleep, sedation, etc.) elicit complex changes in regional brain coordination and neural processing. However, we do not understand the exact relationship between shifts in global states of consciousness and brain activity in certain regions of the brain. This week in Nature Communications, Dr. Ang Li and colleagues unravel the complexity of shifting states of global consciousness by combining behavioral, neuroimaging, electrophysiological, and transcriptomic experiments.  

How did they do it?

The authors hypothesized that the shift in states of global consciousness might result from differential step-by-step processing of brain activity in different regions of the cortex (the brain’s gray matter-containing outer layer). They combined several functional Magnetic Resonance imaging (fMRI) approaches to capture altered consciousness — from deep sleep to full wakefulness — in recruited volunteers. In the first step, the authors captured the change in cortical activity over space and time in three distinct conditions: a) medication induced sedation, b) normal sleep, and c) awake, resting quietly. After this, they compared the cortical fluctuations between these conditions minute by minute. The authors also performed the exact same protocol for volunteers a) on caffeine or after fasting, b) administered a psychedelic drug and c) with neuropsychiatric disorders. They also used fMRI data from the Human Connectome Project to validate the spatiotemporal signatures obtained from the experiments. Electrocorticography (ECoG) recordings from Macaque monkeys were also used to compare to obtained hierarchical signatures. Additionally, the authors used spatial transcriptomic analyses from the Allen Brain Atlas to comment on specific regional contributions to wakefulness in subjects.

What did they find?

After looking at all of the evidence across different conditions, species, and timescales, the authors found that shifts in global state of consciousness can be attributed to changes in cortical neural variability, over time. This means that the global state of consciousness hierarchically associates with the disparity in neural responses across an experiment. Additionally, these complex shifts in consciousness can be translated to a simplified low-dimensional signature, enabling understanding of changes in consciousness in individual people. The authors also noted significant elevations of this hierarchical signature in abnormal states of consciousness (such as on psychedelics, in neuropsychiatric disorders, etc.). This signature also corresponded with the complex patterns of coordination that happen during wakefulness. The authors also found that the heterogeneity in the obtained hierarchical cortical neural variability across different conditions and species was modulated by a) spontaneous waves of cortical activities and b) the histaminergic system, a system that mediates inflammation.

What's the impact?

This study is the first to show that global states of consciousness rely on top-down hierarchical information processing in the cortex. The results also provide critical preliminary evidence of the association between the histaminergic system and hierarchical cortical processing. Most importantly, the authors find that at a global level, consciousness maps to top-down information processing by the cortex and that this may not be dependent on a specific neuroanatomical location in the brain. These findings provide a holistic understanding of the neural mechanisms of different conscious states such as sleeping, caffeinated or on psychedelics. This information may help to guide  therapeutic and behavioral interventions targeting disorders of consciousness, such as sleep disorders, addictions to psychedelics or psychiatric disorders.

Access the original scientific publication here

The Connection Between Psychological Stress and Gut Inflammation

Post by Megan McCullough

The takeaway

Psychological stress can exacerbate gut inflammation through chronically elevated glucocorticoid levels that induce inflammatory glia and immaturity in gut neurons. This leads to impairments in the digestive system and increased inflammation mediated by monocytes, a type of immune cell.

What's the science?

Previous research has shown that symptoms of inflammation in diseases such as inflammatory bowel disease (IBD) are worsened by stressful life events. Although studies have shown a link between psychological stress and IBD severity, the explanation for how this effect is mediated is unclear. Due to the enteric nervous system, the gut can function independently of the brain; thus, new studies are examining the relationship between stress signals from the brain and inflammatory responses in the gut. This week in Cell, Schneider and colleagues investigated the role of the enteric nervous system in mediating the effect of chronic stress on inflammation in the intestine, using both mouse models and health information from individuals diagnosed with IBD.

How did they do it?

To study the connection between psychological stress and intestinal inflammation, the authors utilized a mouse model that underwent prolonged psychological stress. The authors then measured the weight of the mice over time, observed their behavior, and conducted RNA sequencing to study any changes in gene expression in the colon. To identify the specific cells responsible for any inflammation due to stress, single cell RNA sequencing was run on immune cells in the gut on both the stressed mice and the control mice.

Once a positive relationship was established between psychological stress and gut inflammation, the authors studied how stress signals were relayed from the brain to the intestines. Stress hormone levels were measured in the blood of mice in the stressed group and compared to hormone levels of mice in the control group. The authors then studied the relationship between stress and gut inflammation in humans using UK Biobank data. Data was analyzed from disease-free control patients, patients with an inflammatory disease located outside the gut, and from individuals with an inflammatory intestinal disease.

What did they find?

The authors found that mice subject to prolonged psychological stress had increased intestinal inflammation as observed by weight loss and colonoscopy results. The RNA sequencing of gut tissue in the stressed mice group showed changes in gene expression. Genes promoting immunity were downregulated and IBD associated genes were upregulated. Results from numerous mouse models suggested that although psychological stress wasn't enough to induce inflammation on its own, it preconditions the gut to be in a pro-inflammatory state and when coupled with another trigger, exacerbates disease symptoms. When the authors ran single-cell RNA sequencing, they found that T cells, monocytes, and lymphoid cells were differentially expressed genes in the guts of the stressed mice, suggesting these cells are potential drivers for stress-induced gut inflammation. Further analysis provided evidence that the accumulation of inflammatory monocytes led to increases in inflammation.

The authors then studied what was mediating this buildup of monocytes. Through blocking adrenal corticosteroid release pharmacologically, the authors found that glucocorticoids mediated the negative effects of stress on the gut. Over time, stress leads to a chronic buildup of glucocorticoids which triggers inflammatory enteric glia cells which then promote the accumulation of monocytes that increases gut inflammation. When the authors looked at health data in humans, they found that patients with chronic stressors had a higher risk of developing IBD than participants with less life stressors. In patients with IBD, a stressed lifestyle led to lower health outcomes and increased symptoms. 

What's the impact?

This study provides further evidence that stress leads to increases in gut inflammation and provides an explanation for the mechanism behind this connection. Psychological stress leads to elevated glucocorticoids and chronic signaling of this steroid hormone induces inflammatory glia in the enteric nervous system. Inflammatory glia then promote the recruitment of monocytes, eventually leading to inflammation and dysfunction in the gut. The results of this study suggest that mental health treatment and stress reduction could be a powerful avenue for the treatment of inflammatory gut diseases such as IBD.

Access the original scientific publication here

Cannabis Use Disorder and its Relation to Affective Mood Disorders

Post by Baldomero B. Ramirez Cantu

The takeaway

Individuals diagnosed with cannabis use disorder (CUD) were found to have a higher risk of developing any type of unipolar depression and bipolar disorder, including both psychotic and non-psychotic forms.

What's the science?

Cannabis use disorder is characterized by persistent marijuana use despite adverse health and social consequences. The relationship between CUD and psychiatric disorders has long been a subject of debate. While CUD is often observed in individuals with affective mood disorders, the exact nature of this relationship remains unclear. Specifically, it raises the question: Does cannabis use disorder contribute to the development of affective mood disorders, or do pre-existing affective mood disorders increase the likelihood of CUD? This week in JAMA Psychiatry, Jefesen et al. investigate whether there is an association between cannabis use disorder and an increased risk of two types of mood disorders: psychotic and non-psychotic unipolar depression, as well as bipolar disorder.

How did they do it?

The authors utilized longitudinal data from nationwide Danish health registers to address their questions. These registers provided valuable information, including basic demographic data (such as date of birth, age, and vital status), psychiatric and substance use information, and data on parental factors. A total of 6,651,765 individuals were included and followed up over 119, 526, 786 person-years (50.3% female; 49.7% male).

The authors collected additional data on variables such as alcohol use disorder (AUD), substance use disorder (SUD), sex, country of birth, parental history of CUD, AUD, and SUD, parental affective disorders, and highest level of parental education. Information on affective mood disorders and their psychotic features was obtained from national health registries.

Individuals were included in the study on their 16th birthday or on January 1, 1995, whichever occurred later. To examine the risk of presenting affective disorders based on CUD exposure, the authors employed Cox proportional hazards regression and calculated hazard ratios (HRs). The analysis incorporated appropriate controls to account for confounding factors related to the use and abuse of other substances and the influence of other variables on hazard rate changes. In essence, Cox proportional hazards regression allowed the researchers to assess the relationship between cannabis exposure and the probability or risk of developing affective disorders, as reflected in the hazard ratios.

What did they find?

Among individuals diagnosed with cannabis use disorder (CUD), 40.7% also received a diagnosis of unipolar depression. The majority (96.1%) of these cases were classified as non-psychotic unipolar depression, while a smaller proportion was classified as psychotic unipolar depression (3.9%). After adjusting for factors such as sex, alcohol use disorder (AUD), substance use disorder (SUD), birthplace, parental CUD, SUD, AUD, and affective mood disorders, the analysis revealed that individuals with CUD had a higher risk of developing any type of unipolar depression compared to those without a record of CUD (HR 1.84). Elevated risks were also observed for both psychotic depression (HR 1.97) and nonpsychotic depression (HR 1.83).

Furthermore, the study found that 14.1% of individuals diagnosed with CUD eventually received a diagnosis of bipolar disorder. The majority (90.2%) of these cases were diagnosed with nonpsychotic bipolar disorder, while 9.8% were diagnosed with psychotic bipolar disorder. The increased risk of bipolar disorder following a CUD diagnosis was observed in both men and women. The highest risk of bipolar diagnosis occurred within the first 6 months after a CUD diagnosis, but the risk remained elevated even after 10 or more years following the diagnosis.

What's the impact?

Cannabis is one of the most prevalent psychoactive substances globally, and has witnessed legalization and regulation in numerous countries over the past few decades. Gaining a comprehensive understanding of the associated risks and impacts is crucial for informing policy decisions on cannabis regulation and educating the general population about its potential risks.

Access the original scientific publication here.