Associating Heart and Brain Health using MRI

Post by Laura Maile

The takeaway

Evidence suggests a relationship between heart and brain health. The authors identified associations between structural and functional traits of the heart and brain that share genetic signatures with cardiac and brain diseases. 

What's the science?

Cardiovascular disease is often clinically associated with brain diseases, but the underlying genetic, structural, and functional connections between the heart and the brain remain unknown. Magnetic resonance imaging (MRI) has been used to identify structural and functional abnormalities that are associated with disease in individual organs, though few studies have analyzed MRI data from both the heart and the brain to find correlations between the two. 

This week in Science, Zhao and colleagues used multiorgan MRI to examine the connections between heart MRI features and structural and functional patterns in the brain. They then used genome-wide association studies (GWAS) to correlate these findings with genetic variants associated with both heart MRI traits and brain diseases. 

How did they do it?

The authors analyzed MRI data from >40,000 participants in the UK Biobank study. They identified 82 cardiac MRI traits that included measurements of the four cardiac chambers, the ascending and descending aortas, and wall thickness of different regions of the heart. A variety of brain MRI traits were also identified using imaging techniques that examine both structure and functional connectivity of different brain regions at rest and during specific tasks. Next the authors used statistical association and correlation analyses to explore associations between the identified traits. 

The authors then performed GWASs to identify specific genetic variations associated with the cardiac MRI traits. They repeated the GWAS on several different datasets to confirm the associations in a wider population. Next, they completed association and colocalization studies on the significant genetic variants to determine whether the cardiac and brain MRI traits shared genetic signatures. Finally, they sought to determine a genetic causal relationship between the heart and brain by applying Mendelian Randomization to the 82 cardiac MRI traits and several brain-related clinical outcome databases. 

What did they find?

The authors found 4193 significant associations between the 82 identified cardiac MRI traits and brain MRI traits such as cortical thickness, white matter microstructure, and volume of specific brain regions. Associations were also observed between cardiac MRI traits and the functional connectivity between certain brain networks. GWASs identified associations of 49 cardiac MRI traits at 80 genomic loci, which were found to be repeated across several datasets, indicating the generalizability of the findings across populations. They identified genetic variants that were shared across the cardiac and brain MRI traits that had been associated with diseases of the heart and brain. Mendelian randomization analysis revealed a causal relationship between genetic signals associated with heart traits and neuropsychiatric disorders. 

What's the impact?

This study found associations between heart and brain MRI traits that shared common genetic signatures. These findings denote a causal relationship between heart and brain health. This suggests that early intervention and treatment of heart conditions may improve brain health outcomes. 

Access the original scientific publication here. 

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