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).

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.

OBJECTIVE:To evaluate the relationship of diet and food components with the frequency of migraine attacks. MATERIAL AND METHODS:Sixty patients (mean age 35.5±8.9 years, 85% women) with frequent episodic (EM) and chronic migraine (CM) were examined. Anamnestic information on food triggers was clarified for all participants. The patients kept a food diary for 7 days. For each meal, the content of food components (proteins, fats and carbohydrates) was calculated using tables and an electronic calculator of the Federal State Budgetary Institution «Nutrition and Biotechnology». Based on the data obtained, the average daily consumption of the main components of food and the ratio of their proportions to each other were calculated. The results of the data analysis were used to clarify the relationship between the individual characteristics of the diet in terms of food components and the severity of migraine. RESULTS:The main food triggers of migraine were red wine (43.3%), coffee (35.0%), cheeses (21.7%), spices (20.0%), additives of nitrite or monosodium glutamate (20.0%). The average daily intake of carbohydrates had an inverse relationship (p=0.044, r=-0.275), and fats had a direct relationship (p=0.011, r=0.336) with the number of days with migraine. CONCLUSION:The results indicate the protective role of carbohydrate consumption in the development of migraine, which may correspond to the compensatory strategy of the body aimed at energy supply to the brain. Further study of the cerebral metabolic aspects of migraine should improve the understanding of its pathophysiology and chronicity, which will allow the formation of a correct diet preventive strategy.

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.

OBJECTIVE:To evaluate transforming growth factor beta (TGF-β) in patients with cervical artery dissection (CeAD).MATERIAL AND METHODS:TGF-β was studied by enzyme immunoassay in 74 of 336 patients with CeAD observed at the Research Center of Neurology (Moscow) from 2000 to 2021. The average patient's age at the time of TGF-β study was 41.6±9.8 years; the proportion of women was 51%. TGF-β was studied in the first month of the disease (n=9), for 2-3 months (n=12) and at a later period (mean - 4.3±5.03 years) (n=53). The control group consisted of 20 healthy volunteers, matched for age and sex. Dissection occurred in internal carotid artery (ICA) (n=42), vertebral artery (VA) (n=29), ICA+VA (n=3) and involved 1 artery (n=58) or 2-3 arteries (n=16). Clinical manifestations included ischemic stroke (IS) (n=49), isolated cervical-cephalic headache (n=23), lower cranial nerve palsy (n=2). Pathological CeAD tortuosity was detected by angiography in 13 patients, and a dissecting aneurysm in 15 patients.RESULTS:TGF-β1 and TGF-β2 were elevated in patients with CeAD patients compared with the control: TGF-β1 - 4990 [3950; 7900] pg/ml vs. 3645 [3230; 4250] pg/ml, p=0.001; TGF-β2 - 6120 [4680; 7900] pg/ml vs. 3155 [2605; 4605] pg/ml, p=0.001. The highest TGF-β1 and TGF-β2 levels were noted at 2-3 months of the disease. There was no correlation between the TGF-β level and various clinical and angiographic parameters.CONCLUSION:Increased TGF-β level confirms that CeAD patients have connective tissue disorder that underlies the arterial wall weakness. A higher TGF-β level at 2-3 months of CeAD seems to be connected with an active reparative process in arterial wall after dissection. TGF-β can be used as a biomarker of connective tissue dysplasia in patients with CeAD.

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.

OBJECTIVE:To assess the effectiveness and safety of Erenumab, a monoclonal antibody to calcitonin gene-related peptide receptors, in patients with high-frequency episodic migraine (HFEM) in real-life study.MATERIAL AND METHODS:35 patients with HFEM without aura (≥8-14 attacks per month) (30 females, mean age 32.4±8.1) received monthly subcutaneous administration of Erenumab 70 mg for 3 months. The primary endpoint was the change in monthly migraine days (MMDs) from baseline, the secondary endpoint was the proportion of patients who achieved a 50% reduction in the number of days with headache. The change in pain intensity, change in the number of days of use of acute migraine-specific medication, the effect on daily activity (HIT-6 scale, MIDAS), anxiety and depression (the Hospital Anxiety and Depression Scale) were assessed.RESULTS:At the end of the third month Erenumab decreased MMDs by 5±3.6 (p=0.00000). A 50% reduction in the mean number of migraine days per month was achieved for 60% of patients, the intensity of headache according to the visual analogue scale from 8±1.2 points to 5±2 points (p=0.00000), monthly analgesics intake passed from 11±7 to 4.5±3.7 (p=0.000001). 25.7% of patients did not respond to treatment, showing less than a 30% decrease in the number of days with headache. A decrease in pain intensity correlated with a decrease in anxiety (from 8±4 to 6±4 points (p=0.003)) and depression (from 6±4 to 4±3 points (p=0.0004)) according to HADS, reduced HIT-6 scale from 65±6 to 55±7 points (p=0.00000) and MIDAS from 45 [33; 67] points to 16 [5; 33] (p=0.000004)). Patients reported good tolerability of Erenumab. 25.7% of patients noted a tendency to constipation. No patient discontinued treatment due to adverse events.CONCLUSION:Real-life study confirmed the efficacy and safety of Erenumab in the treatment of HFEM, a decrease in the severity of comorbid anxiety and depression, and social maladjustment.

Cervical artery dissection (CeAD) due to arterial wall weakness (dysplasia) is one of the most common causes of ischemic stroke (IS) at a young age. A rare and little known cause of CeAD is Turner's syndrome (TS)-is an inherited disease caused by completely or partially missing X chromosome. In this paper, we describe 2 female patients, aged 27 and 33 years, with genetically confirmed TS (karyotype 45X0) and internal carotid artery dissection(ICAD).TS frequency among our 304 patients with CeAD was 0.07%. Both patients had short stature, received hormone replacement therapy from the age of 14 and had arterial hypertension. In addition, the first patient suffered from hypothyroidism, osteoporosis and survived a nephrectomy for hydronephrosis. ICAD in first patient manifested by IS. MRI of the neck arteries, MRA and CTA revealed intramural hematoma, hemodynamically significant stenosis, which regressed in 4 months. In the second patient, dissection was manifested by local symptoms (Horner's syndrome, cervicocephalic pain on the dissection side). MRA and CTA revealed a precranial dissected aneurysm of the left ICA (on the side of local symptoms), fusiform expansion of the right ICA, and pathological tortuosity of both ICA. The paper discusses the cause of vasculopathy in TS. It is assumed that connective tissue damage is associated with a deficiency of biglycan - extracellular matrix protein, which interacts with collagen and elastin to strengthen the arterial wall. Biglycan gene is linked to X-chromosome which is completely or partlially missing in TS resulting in a biglycan deficiency. The role of sex hormone deficiency as a cause of arterial wall weakness is unlikely.

The diagnostic value of white matter hyperintensities (WMH) in different types of migraineare unknown. To evaluate the WMH pattern of different subtypes in migraine patients with no vascular risk factors. 92 migraine patients (73 females, mean age 34.6 ± 8.9; 61 episodic migraine, 31 chronic migraine, 36 migraine with aura, 56 migraine without aura) without vascular risk factors underwent brain MRI (3 T). We also included a matched healthy control group with no migraine (n = 24). The prevalence of WMH in different types of migraine was similar and ranged from 38.7 to 44.4%; the control group showed no WMH at all. Lesions were located within frontal, parietal and temporal lobes (in order of decreasing incidence) in juxtacortical and/or deep white matter. WMH appeared as round or slightly elongated foci with a median size of 2.5 mm [1.5; 3]. Total number, size and prevalence of WMH by lobes and white matter regions were similar between groups, and no interaction with age or sex was found. The number of lesions within the frontal lobe juxtacortical white matter correlated with the age of patients (r = 0.331, p = 0.001) and the duration since migraine onset (r = 0.264, p = 0.012). Patients with different migraine subtypes and without vascular risk factors are characterized by a similar pattern of WMH in the absence of subclinical infarctions or microbleedings. Therefore, WMH have no relevant prognostic value regarding the course of migraine and vascular complications. WMH pattern may be used to differentiate migraine as a primary disorder and other disorders with migraine-like headache and WMH.

OBJECTIVE:To study the frequency, angiographic and clinical features of aneurysms and tortuosity (T) in patients with internal carotid artery (ICA) and vertebral artery (VA) dissection.MATERIAL AND METHODS:Three hundred and twenty-seven patients (average age - 37.8±9.1 years, women - 57%) with ICA/VA dissection verified by neuroimaging were studied. Repeated neuroimaging in 2.4±3.3 years was performed in 254 patients. In one case, tortuous ICA fragment resected at the surgery complicated by dissection was histologically studied.RESULTS:ICA/VA aneurysms were found in 46 (14%) patients. At repeated neuroimaging aneurysms did not change (38%), increased (11%) or decreased in size (8%), were not detected (38%) or were detected for the first time (5%). Patients with aneurysms compared with those without aneurysms more often had multiple dissections (44% vs. 20%, p=0.001) and T (35% vs. 13%, p=0.001), but less frequently the artery lumen occlusion in the acute period (15% vs. 40%, p=0.001). T was found in 53 (16%) patients. Patients with T compared with patients without T were older (40.6±8.1 vs. 37.3±9.3 years, p=0.039), more often had aneurysms (30% vs. 11%, p=0.001) and recanalization of occlusion observed in the acute period (89% vs. 54%, p=0.006). Dissection more often occurred in tortuous than in non-tortuous artery (79% vs 21%, p=0.001). During 4.8±3.6 years of follow-up, TIA developed inone patient (2%) with an aneurysm. Histological examination of tortuous ICA fragment, which also contained a small aneurysm, revealed dysplastic changes.CONCLUSION:The association between aneurism and T in patients with ICA/VA dissection suggests their common basis - the arterial wall weakness due to dysplasia. Age-related changes are also important for T development. T is a risk factor for ICA/VA dissection. Aneurysms formed after ICA/VA dissection have a benign course.

OBJECTIVE:To study the frequency of CeAD that developed during pregnancy or in post partum period among all CeADs in women; to study the course of pregnancy in women with prior CeAD. MATERIAL AND METHODS:162 women (mean age 37.1±4.1 years) with CeAD we examined at the Research Center of Neurology (Moscow), 98% women were studied during last 15 years. 140 women were of childbearing age (≤45 years, mean age - 35±2.8 years). All patients were interviewed whether or not CeAD occurred during pregnancy or in post partum period (CeADPPP). Obstetric history before and after CeAD was studied in 57 women of childbearing age (average age - 35.9±7.3 years at CeAD development). RESULTS:CeADPPP developed in 6 out of 162 all female patients (3.7%) or of 140 childbearing age patients (4.3%). It occurred 2-6 months (4 patients) and 10 days after delivery (1 patient), or on the 25th week of pregnancy (1 patient). CeADPPP patients were younger than patients with CeAD out of pregnancy or postpartum period (29.8±8 years vs 35.1±6.7 years, p>0.05). CeADPPP in comparison with CeAD outside these periods more often involved internal carotid artery (ICA) (50% vs 35%, p=0.666), more often occurred in 2-3 arteries (50% vs 31%, p=0.386) and more often was accompanied by dissecting aneurysm development (50% vs 8%, p=0.013). After CeAD, 18 out of 57 patients in whom obstetric history was studied, including 3 patients with postpartum dissection had 29 pregnancies. The pregnancy outcomes were as follows: childbirth (17 pregnancies, 59%), fetal loss (8 pregnancies, 27%) and medical abortion (4 pregnancies, 14%). Delivery occurred on average 4.5±2.061 years after CeAD in women aged 33.0±4.25 years (cesarean section - 15 patients). Fetal loss occurred at 7.4±3.5 weeks of pregnancy in women aged 37.6±3.13 years on average 2.7±1.4 years after CeAD. Fetal loss frequency after CeAD was higher than before it (27% vs 7%, p=0.016). There were no CeAD recurrences during pregnancy and postpartum period in women who had previously undergone CeAD. CONCLUSION:CeADPPP frequency among all dissections in women is 3.7-4.3%. The risk of CeAD recurrence during pregnancy or the postpartum period after prior CeAD is very low. The risk of fetal loss during 2.7±1.4 years after CeAD is higher than before it (27% vs 7%). Hormonal and growth factors associated with pregnancy and the postpartum period is suggested to contribute to cervical artery wall damage. It is possible that the prolonged action of some of these factors may disrupt the placental vessels formation, predisposing to miscarriage.

Dissection of the internal carotid artery and vertebral artery (ICA/VA) is one of the leading causes of ischaemic stroke in young people. The reason for the arterial wall weakness leading to its dissection remains unclear. Morphological study of the ICA/VA, and clinical data, indicate the presence of connective tissue dysplasia in patients, which is not associated with any known hereditary diseases. In this article, the authors summarize the results of their studies (histological and histochemical examination of muscle biopsies, electron microscopy of skin arteries) and observations (stroke-like episode, A3243G mutation in the mitochondrial genome in a patient with repeat ICA/VA dissections; increased peak lactate during MR spectroscopy in a patient who suffered an ICA dissection, then lobar hemorrhages a few years later). Based on these, the authors propose mitochondrial arteriopathy as the cause of arterial wall dysplasia leading to dissection. This article provides data on the presence of mitochondrial disorders in patients with ICA/VA dissection.

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.

Наблюдаемая во всем мире тенденция к хронизации головных болей (ГБ) является важной медицинской и социальной проблемой в связи с частой психологической и социальной дезадаптацией этой категории пациентов. Хронические ГБ снижают качество жизни и трудоспособность пациентов. Тенденция к нарастанию хронизации ГБ в значительной степени связана с ускорением темпа жизни, постоянной социальной и информационной напряженностью, приводящими к нарушениям в эмоциональной сфере (депрессия, тревожность, астенизация). Разовые медикаментозные мероприятия не приводят к стойкому успеху: такие пациенты нуждаются в проведении длительной комплексной реабилитации, учитывающей характер ГБ, причины их обострения, наличие коморбидных состояний. Реабилитационные мероприятия должны включать длительную адекватную медикаментозную терапию, направленную на профилактику обострений ГБ. При необходимости могут применяться ботулинотерапия, физиотерапия (средствами выбора являются биологическая обратная связь, транскраниальная магнитная стимуляция, транскраниальная электрическая стимуляция), психотерапия, выявление и лечение коморбидных состояний, рекомендации по здоровому образу жизни.

The worldwide trend towards headache (HA) chronization is an important medical and social problem due to frequent psychological and social maladaptation of patients. Chronic HAs reduce quality of life and patients ability to work. The trend towards headache chronization is largely associated with acceleration of the pace of life, constant social and informational tension, leading to emotional disturbances, such as depression, anxiety, and asthenia. Single medical interventions do not seem to have a lasting effect. Thus, such patients require long-term comprehensive rehabilitation with regard to the type and characteristic features of HA, as well as triggers and comorbid condition. Rehabilitation should include adequate long-term drug therapy aimed at preventing exacerbations of HA. Additional approaches may include botulinum neurotoxin injections, physiotherapy (biofeedback, transcranial magnetic stimulation, transcranial electrical stimulation), psychotherapy, comorbid conditions diagnosis and treatment, lifestyle intervention.

Impairments to nociception are currently regarded as the pathogenetic mechanism of psychosomatic disorders and as a potential therapeutic target. An aim of the present work was to investigate the functional cerebral grounds linking the perception of internal sensations and emotional intelligence. The interoceptive paradigm for detection of the heartbeat was modified, adapted to Russian, and used in conditions of functional MRI in middle-aged and elderly people without neurological or mental illness. All subjects carried out the Mayer–Salovey–Caruso emotional intelligence test. The level of emotional intelligence and the accuracy of heart rhythm detection were linked with activation of the right anterior insular cortex. This mediator role of the right anterior insular cortex in the interaction between interoception and emotional processing indicates that it can be regarded as a neural correlate of this interaction in developing approaches to the prophylaxis and treatment of psychosomatic disorders.