Peripheral Blood Gene Expression Profiling Reveals Molecular Pathways Associated with Cervical Artery Dissection.

Cervical artery dissection (CeAD) is the primary cause of ischemic stroke in young adults. Monogenic heritable connective tissue diseases account for fewer than 5% of cases of CeAD. The remaining sporadic cases have known risk factors. The clinical, radiological, and histological characteristics of systemic vasculopathy and undifferentiated connective tissue dysplasia are present in up to 70% of individuals with sporadic CeAD. Genome-wide association studies identified CeAD-associated genetic variants in the non-coding genomic regions that may impact the gene transcription and RNA processing. However, global gene expression profile analysis has not yet been carried out for CeAD patients. We conducted bulk RNA sequencing and differential gene expression analysis to investigate the expression profile of protein-coding genes in the peripheral blood of 19 CeAD patients and 18 healthy volunteers. This was followed by functional annotation, heatmap clustering, reports on gene-disease associations and protein-protein interactions, as well as gene set enrichment analysis. We found potential correlations between CeAD and the dysregulation of genes linked to nucleolar stress, senescence-associated secretory phenotype, mitochondrial malfunction, and epithelial-mesenchymal plasticity.

Age-related changes of interoceptive brain networks: Implications for interoception and alexithymia.

Aging is known to be associated with a decline in interoceptive abilities and changes in emotional processing, including alexithymia. As the brain areas supporting interoceptive awareness participate in the perception of emotion, we suggested that interoceptive decline and alexithymia in older adults may share common neural ground. To test this hypothesis, we administered functional magnetic resonance imaging-based heartbeat detection task to 62 adults of diverse ages (range 18-73) and evaluated a larger sample of older and younger adults using questionnaires characterizing interoceptive sensibility, alexithymia, and depressive attitudes. We found that increasing age was linked to decreased activation during the interoceptive task, including the right insular-opercular and supplementary motor areas (SMAs). Age also affected task-based functional connectivity, with two major effects being a decrease in the connectivity of the SMA-insular network and an increase in the connectivity of the prefrontal-lateral occipital network. Path analysis performed for interoceptive accuracy as the endogenous variable revealed that the impact of age was mediated by the functional activation of the insular cortex and SMA and by the connectivity between these areas. Another path analysis using alexithymia as the endogenous variable while controlling for depressive attitudes showed that the effect of age was mediated by interoceptive decline. The study supports the role of central mechanisms in age-related interoceptive decline and shows its implications for alexithymia. Since alexithymia represents a risk factor for mental and cardiovascular diseases, the study findings may open an important direction toward maintaining older adults' well-being. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Enhancing Brain Connectivity With Infra-Low Frequency Neurofeedback During Aging: A Pilot Study.

Aging is associated with decreased functional connectivity in the main brain networks, which can underlie changes in cognitive and emotional processing. Neurofeedback is a promising non-pharmacological approach for the enhancement of brain connectivity. Previously, we showed that a single session of infra-low frequency neurofeedback results in increased connectivity between sensory processing networks in healthy young adults. In the current pilot study, we aimed to evaluate the possibility of enhancing brain connectivity during aging with the use of infra-low frequency neurofeedback. Nine females aged 52 ± 7 years with subclinical signs of emotional dysregulation, including anxiety, mild depression, and somatoform symptoms, underwent 15 sessions of training. A resting-state functional MRI scan was acquired before and after the training. A hypothesis-free intrinsic connectivity analysis showed increased connectivity in regions in the bilateral temporal fusiform cortex, right supplementary motor area, left amygdala, left temporal pole, and cerebellum. Next, a seed-to-voxel analysis for the revealed regions was performed using the post- vs. pre-neurofeedback contrast. Finally, to explore the whole network of neurofeedback-related connectivity changes, the regions revealed by the intrinsic connectivity and seed-to-voxel analyses were entered into a network-based statistical analysis. An extended network was revealed, including the temporal and occipital fusiform cortex, multiple areas from the visual cortex, the right posterior superior temporal sulcus, the amygdala, the temporal poles, the superior parietal lobule, and the supplementary motor cortex. Clinically, decreases in alexithymia, depression, and anxiety levels were observed. Thus, infra-low frequency neurofeedback appears to be a promising method for enhancing brain connectivity during aging, and subsequent sham-controlled studies utilizing larger samples are feasible.

Interoception during aging: Functional neuroimaging data from a heartbeat detection task.

Interoception is critically important for allostatic adaptation and emotional regulation, and aberrant interoceptive processing is increasingly recognized to be involved in the pathogenesis of neurological, psychiatric and cardiovascular diseases. Despite the fact that interoceptive abilities decline with age, the corresponding neural correlates and clinical consequences of these age-related changes have yet to be discovered. We present a dataset that contains task-based functional neuroimaging data from 50 adults aged 40-65 years and 12 adults aged 18-25 years who performed an fMRI-based heartbeat-detection task. Of the 62, 38 participants also took part in a rubber hand illusion experiment outside the scanner. While the dataset was mainly created to study age-related changes in interoception, it can also be used in body perception research in general. The provided group data may serve as a reference for clinical studies on interoception involving older adults.

Sensory integration in interoception: Interplay between top-down and bottom-up processing.

Although the neural systems supporting interoception have been outlined in general, the exact processes underlying the integration of visceral signals still await research. Based on the predictive coding concept, we aimed to reveal the neural networks responsible for the bottom-up (stimulus-dependent) and top-down (model-dependent) processing of interoceptive information. In a study of 30 female participants, we utilized two classical body perception experiments-the rubber hand illusion and a heartbeat detection task (cardioception), with the latter being implemented in fMRI settings. We interpreted a stronger rubber hand illusion, as measured by higher proprioceptive drift, as a tendency to rely on actual sensory experience, i.e., bottom-up processing, while lower proprioceptive drift served as an indicator of the prevalence of top-down, model-based influences. To reveal the bottom-up and top-down processes in cardioception, we performed a seed-based connectivity analysis of the heartbeat detection task, using as seeds the areas with known roles in sensory integration and entering proprioceptive drift as a covariate. The results revealed a left thalamus-dependent network positively associated with proprioceptive drift (bottom-up processing) and a left amygdala-dependent network negatively associated with drift (top-down processing). Bottom-up processing was related to thalamic connectivity with the left frontal operculum and anterior insula, anterior cingulate cortex, hypothalamus, right planum polare and right inferior frontal gyrus. Top-down processing was related to amygdalar connectivity with the rostral prefrontal cortex and an area involving the left frontal opercular and anterior insular cortex, with the latter area being an intersection of the two networks. Thus, we revealed the neural mechanisms underlying the integration of interoceptive information through the interaction between the current sensory experience and internal models.

The ability to understand emotions is associated with interoception-related insular activation and white matter integrity during aging.

Cerebral small vessel disease (SVD) is a major cause of cognitive impairment in elderly people. While most research focuses on the role of the classical vascular risk factors in SVD, a description of the psychophysiological mechanisms leading to the age-related brain damage may open new possibilities for prophylaxis. In the current study, we evaluated the associations between emotional abilities, interoception, and age-related vascular white matter degeneration. The work was influenced, first, by multiple studies recognizing alexithymia as a cardiovascular risk factor; second, by theories of emotions linking body's allostasis and emotional regulation; and third, by neuroimaging data highlighting the shared role of the insular cortex in interoceptive and emotional processing. In a sample of older female adults (N = 30), we performed the Mayer-Salovey-Caruso Emotional Intelligence Test, functional MRI using the heartbeat detection task, and evaluation of white matter microstructural integrity using diffusion weighted imaging. The ability to understand and analyze emotions-one of the four components of emotional intelligence-was found to be associated with higher interoception-related activation of the right anterior insula and preserved white matter microstructure. We interpret these results in light of the concept of Embodied Predictive Interoception Coding, which proposes that emotional processing, interoception, and allostasis (antecedent top-down regulation of the body's internal milieu) may rely on the shared neural mechanisms of predictive coding. The study demonstrates feasibility of the investigation of cerebrovascular diseases form a psychophysiological perspective and calls for future research.