Functional Activation Patterns Research Articles

Dorsolateral Prefrontal Functional Connectivity Predicts Working Memory Training Gains.

Background: Normal aging is associated with working memory decline. A decrease in working memory performance is associated with age-related changes in functional activation patterns in the dorsolateral prefrontal cortex (DLPFC). Cognitive training can improve cognitive performance in healthy older adults. We implemented a cognitive training study to assess determinants of generalization of training gains to untrained tasks, a key indicator for the effectiveness of cognitive training. We aimed to investigate the association of resting-state functional connectivity (FC) of DLPFC with working memory performance improvement and cognitive gains after the training.Method: A sample of 60 healthy older adults (mean age: 68 years) underwent a 4-week neuropsychological training, entailing a working memory task. Baseline resting-state functional MRI (rs-fMRI) images were acquired in order to investigate the FC of DLPFC. To evaluate training effects, participants underwent a neuropsychological assessment before and after the training. A second follow-up assessment was applied 12 weeks after the training. We used cognitive scores of digit span backward and visual block span backward tasks representing working memory function. The training group was divided into subjects who had and who did not have training gains, which was defined as a higher improvement in working memory tasks than the control group (N = 19).Results: A high FC of DLPFC of the right hemisphere was significantly associated with training gains and performance improvement in the visuospatial task. The maintenance of cognitive gains was restricted to the time period directly after the training. The training group showed performance improvement in the digit span backward task.Conclusion: Functional activation patterns of the DLPFC were associated with the degree of working memory training gains and visuospatial performance improvement. Although improvement through cognitive training and acquisition of training gains are possible in aging, they remain limited.

On the Issue of Neurophysiological Mechanisms of Giftedness: Creative Type of Personality as an Objective Reality

In the article, from the point of view of evolutionary diatropics, a special cognitive structure of the personality is considered: the versative-ingenational-rapid intellectually gifted individual (VIR-type), which is the author's rethinking of the concept of urethral fixation by Z. Freud. The historical context of the formation of this concept is traced, its modern meaning is revealed, both from the point of view of the psychiatric clinic and from the position of pedagogical psychology. The material of the study of cross-correlation analysis of the electroencephalogram of 36 subjects with a VIR-type of personality demonstrates the features of the neurofunctioning of the cerebral cortex of these individuals: increased interaction of remote areas of the cortex and weakened integration of closely located zones. Illustrates the formation of a specific neurophysiological pattern, dubbed the “ikaric wings” and represents an intensive synchronization of the frontal and occipital lobes of the brain with the enhancement of their interaction both ipsilateral and contralateral. A comparison is made of the resulting pattern of functional activity of the cerebral cortex of the subjects with a VIR-type personality and patients with mental pathology. It is concluded that the presence of signs of mental disorders in the human population is necessary in order to form a special group of highly intelligent, creatively gifted individuals.

A Review of Neuroimaging Studies in Persistent Postural-Perceptual Dizziness (PPPD).

Persistent postural-perceptual dizziness (PPPD) is a functional vestibular disease characterized by persistent dizziness, unsteadiness, and/or non-spinning vertigo, and is the most common vestibular syndrome in young adults. A stiffened postural control strategy, shift to reliance on visual over vestibular information, and hypervigilance to the environment have been suggested as possible pathophysiological mechanisms of PPPD. However, the exact mechanisms remain unclear. Recently, neuroimaging studies using magnetic resonance imaging and single photon emission computed tomography have provided pivotal insights into the pathophysiology of PPPD. The aim of this review was to evaluate and summarize the existing data on neuroimaging studies in PPPD. In summary, these studies fairly consistently reported decreased brain structure, function, and connectivity among the areas involved in multisensory vestibular processing and spatial cognition, and increased function and connectivity in the visual processing areas in patients with PPPD. The detected brain changes might reflect maladaptive and compensatory mechanisms including dysfunctional integration of multisensory vestibular information and visual dependence. Notably, various factors including personality traits (i.e., neuroticism), psychiatric comorbidities (i.e., anxiety and depression), and triggering factors (i.e., peripheral vestibular lesions) seem to modulate brain functional activity and connectivity patterns, possibly accounting for some differences across the results. Future studies should carefully control for these confounding effects in order to draw firm conclusions.

Gray matter abnormalities follow non-random patterns of co-alteration in autism: Meta-connectomic evidence

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by atypical brain anatomy and connectivity. Graph-theoretical methods have mainly been applied to detect altered patterns of white matter tracts and functional brain activation in individuals with ASD. The network topology of gray matter (GM) abnormalities in ASD remains relatively unexplored. MethodsAn innovative meta-connectomic analysis on voxel-based morphometry data (45 experiments, 1,786 subjects with ASD) was performed in order to investigate whether GM variations can develop in a distinct pattern of co-alteration across the brain. This pattern was then compared with normative profiles of structural and genetic co-expression maps. Graph measures of centrality and clustering were also applied to identify brain areas with the highest topological hierarchy and core sub-graph components within the co-alteration network observed in ASD. ResultsIndividuals with ASD exhibit a distinctive and topologically defined pattern of GM co-alteration that moderately follows the structural connectivity constraints. This was not observed with respect to the pattern of genetic co-expression. Hub regions of the co-alteration network were mainly left-lateralized, encompassing the precuneus, ventral anterior cingulate, and middle occipital gyrus. Regions of the default mode network appear to be central in the topology of co-alterations. ConclusionThese findings shed new light on the pathobiology of ASD, suggesting a network-level dysfunction among spatially distributed GM regions. At the same time, this study supports pathoconnectomics as an insightful approach to better understand neuropsychiatric disorders.

Topographic gradients of intrinsic dynamics across neocortex.

The intrinsic dynamics of neuronal populations are shaped by both microscale attributes and macroscale connectome architecture. Here we comprehensively characterize the rich temporal patterns of neural activity throughout the human brain. Applying massive temporal feature extraction to regional haemodynamic activity, we systematically estimate over 6000 statistical properties of individual brain regions' time-series across the neocortex. We identify two robust spatial gradients of intrinsic dynamics, one spanning a ventromedial-dorsolateral axis and dominated by measures of signal autocorrelation, and the other spanning a unimodal-transmodal axis and dominated by measures of dynamic range. These gradients reflect spatial patterns of gene expression, intracortical myelin and cortical thickness, as well as structural and functional network embedding. Importantly, these gradients are correlated with patterns of meta-analytic functional activation, differentiating cognitive versus affective processing and sensory versus higher-order cognitive processing. Altogether, these findings demonstrate a link between microscale and macroscale architecture, intrinsic dynamics, and cognition.

Dorsolateral prefrontal functional connectivity predicts transfer of working memory gains after cognitive training

AbstractBackgroundNormal aging is associated with working memory decline. A decrease in working memory performance is associated with age‐related changes in functional activation patterns in the dorsolateral prefrontal cortex (DLPFC). Cognitive training can improve cognitive performance in healthy older adults. We implemented a cognitive training study to assess determinants of transfer of gains to untrained tasks, a key indicator for the effectiveness of cognitive training. We aimed to investigate the association of resting‐state functional connectivity of DLPFC with working memory performance improvement and successful transfer of gains after training.MethodA sample of 60 healthy older adults (mean age: 68 years) underwent a 4‐week cognitive training of working memory. Baseline resting‐state functional magnetic resonance imaging in order to investigate the functional connectivity of DLPFC. To evaluate transfer and training effects, participants underwent a neuropsychological assessment before and after the training. A second follow‐up assessment was applied 12 weeks after the training. We used cognitive scores of Digit span backwards and Visual block span backwards tasks representing working memory function. The training group was divided in subjects who had and who did not have successful transfer, which was defined as higher improvement in working memory tasks than the control group.ResultA high functional connectivity of DLPFC of the right hemisphere was a significantly associated with successful transfer of gains and performance improvement in the visuospatial task. Transfer effects were limited and maintenance of gains was restricted to the time period directly after the training. The training group showed performance improvement in the Digit span backwards task.ConclusionFunctional activation patterns of DLPFC during visuospatial task contribute to successful transfer and performance improvement. Even though transfer is possible in aging, it remains limited.

Functional topography of anger and aggression in the human cerebellum

New insights into the functional neuroanatomic correlates of emotions point toward the involvement of the cerebellum in anger and aggression. To identify cerebellar regions commonly activated in tasks examining the experience of anger and threat as well as exerting an aggressive response, two coordinate-based activation likelihood estimation meta-analyses reporting a total of 57 cerebellar activation foci from 819 participants were performed. For anger processing (18 studies), results showed significant clusters in the bilateral posterior cerebellum, overlapping with results from previous meta-analyses on emotion processing, and implying functional connectivity to cognitive, limbic, and social canonic networks in the cerebral cortex. By contrast, active aggression expression (10 studies) was associated with significant clusters in more anterior regions of the cerebellum, overlapping with cerebellar somatosensory and motor regions and displaying functional connectivity with the somatomotor and default mode network. This study not only strengthens the notion that the cerebellum is involved in emotion processing, but also provides the first quantitative evidence for distinct cerebellar functional activation patterns related to anger and aggression.

Role of modularity in self-organization dynamics in biological networks.

Interconnected ensembles of biological entities are perhaps some of the most complex systems that modern science has encountered so far. In particular, scientists have concentrated on understanding how the complexity of the interacting structure between different neurons, proteins, or species influences the functioning of their respective systems. It is well established that many biological networks are constructed in a highly hierarchical way with two main properties: short average paths that join two apparently distant nodes (neuronal, species, or protein patches) and a high proportion of nodes in modular aggregations. Although several hypotheses have been proposed so far, still little is known about the relation of the modules with the dynamical activity in such biological systems. Here we show that network modularity is a key ingredient for the formation of self-organizing patterns of functional activity, independently of the topological peculiarities of the structure of the modules. In particular, we propose a self-organizing mechanism which explains the formation of macroscopic spatial patterns, which are homogeneous within modules. This may explain how spontaneous order in biological networks follows their modular structural organization. We test our results on real-world networks to confirm the important role of modularity in creating macroscale patterns.

Greater Semantic Memory Activation After Exercise Training Cessation in Older Endurance-Trained Athletes.

To examine the effects of a 10-day exercise-training cessation on semantic memory functional activation in older distance runners. Ten master runners (62.6 ± 7.0years) with a long-term endurance-training history (29.0 ± 6.0years) underwent a 10-day training cessation. Before and immediately after the training cessation, semantic memory activation was measured during the famous name recognition task, using functional magnetic resonance imaging. The 10-day training cessation resulted in greater semantic memory activation in three brain regions, including the left inferior frontal gyrus, parahippocampal gyrus, and inferior semilunar lobule. The 10-day training cessation did not significantly alter famous name recognition task performance. The findings demonstrate that even a relatively short period without exercise training alters the functional activation patterns of semantic memory-related neural networks. Increased semantic memory activation after training cessation may indicate reduced neural efficiency during successful memory retrieval.

Tomographic Task-Related Functional Near-Infrared Spectroscopy in Acute Sport-Related Concussion: An Observational Case Study.

Making decisions regarding return-to-play after sport-related concussion (SRC) based on resolution of symptoms alone can expose contact-sport athletes to further injury before their recovery is complete. Task-related functional near-infrared spectroscopy (fNIRS) could be used to scan for abnormalities in the brain activation patterns of SRC athletes and help clinicians to manage their return-to-play. This study aims to show a proof of concept of mapping brain activation, using tomographic task-related fNIRS, as part of the clinical assessment of acute SRC patients. A high-density frequency-domain optical device was used to scan 2 SRC patients, within 72 h from injury, during the execution of 3 neurocognitive tests used in clinical practice. The optical data were resolved into a tomographic reconstruction of the brain functional activation pattern, using diffuse optical tomography. Moreover, brain activity was inferred using single-subject statistical analyses. The advantages and limitations of the introduction of this optical technique into the clinical assessment of acute SRC patients are discussed.

Drawing on the brain: An ALE meta-analysis of functional brain activation during drawing

Art therapy researchers and practitioners are increasingly interested in the brain mechanisms underlying art therapy, an investigation area associated with almost no neuroimaging research. Lusebrink (2010) hypothesized that expression at different levels of the Expressive Therapies Continuum (ETC) would be supported by different patterns of functional brain activation. In the current study, we tested Lusebrink’s (2010) hypotheses through an activation likelihood estimation (ALE) meta-analysis of past neuroimaging research as participants engaged in different drawing tasks. Results supported our predictions that cognitive drawing, operationalized by internally-cued drawing stimuli or objective drawing content, would be associated with activation of the prefrontal and cingulate cortices. However, results failed to support our predictions that perceptual drawing, operationalized by externally-cued drawing stimuli and nonobjective drawing content, would be associated with activation of the ventral visual pathway in the temporal lobe. Perceptual drawing was associated with cerebellum, frontal, and parietal lobe activation (including the motor and somatosensory cortices). The dorsal visual pathway, largely in the parietal lobe, was engaged during cognitive and perceptual drawing. Our findings on patterns of brain activation can inform broader neuroscientific conceptualizations of the ETC framework and future directions for art therapy research and practice.

White Matter Microstructure Predicts Focal and Broad Functional Brain Dedifferentiation in Normal Aging.

Ventral visual cortex exhibits highly organized and selective patterns of functional activity associated with visual processing. However, this specialization decreases in normal aging, with functional responses to different visual stimuli becoming more similar with age, a phenomenon termed "dedifferentiation." The current study tested the hypothesis that age-related degradation of the inferior longitudinal fasciculus (ILF), a white matter pathway involved in visual perception, could account for dedifferentiation of both localized and distributed brain activity in ventral visual cortex. Participants included 281 adults, ages 20-89 years, from the Dallas Lifespan Brain Study who underwent diffusion-weighted imaging to measure white matter diffusivity, as well as fMRI to measure functional selectivity to viewing photographs from different categories (e.g., faces, houses). In general, decreased ILF anisotropy significantly predicted both focal and broad functional dedifferentiation. Specifically, there was a localized effect of structure on function, such that decreased anisotropy in a smaller mid-fusiform region of ILF predicted less selective (i.e., more dedifferentiated) response to viewing faces in a proximal face-responsive region of fusiform. On the other hand, the whole ILF predicted less selective response across broader ventral visual cortex for viewing animate (e.g., human faces, animals) versus inanimate (e.g., houses, chairs) images. This structure-function relationship became weaker with age and was no longer significant after the age of 70 years. These findings indicate that decreased white matter anisotropy is associated with maladaptive differences in proximal brain function and is an important variable to consider when interpreting age differences in functional selectivity.

Sex classification using long-range temporal dependence of resting-state functional MRI time series.

A thorough understanding of sex differences that exist in the brains of healthy individuals is crucial for the study of neurological illnesses that exhibit phenotypic differences between males and females. Here we evaluate sex differences in regional temporal dependence of resting‐state brain activity in 195 adult male–female pairs strictly matched for total grey matter volume from the Human Connectome Project. We find that males have more persistent temporal dependence in regions within temporal, parietal, and occipital cortices. Machine learning algorithms trained on regional temporal dependence measures achieve sex classification accuracies up to 81%. Regions with the strongest feature importance in the sex classification task included cerebellum, amygdala, and frontal and occipital cortices. Secondarily, we show that even after strict matching of total gray matter volume, significant volumetric sex differences persist; males have larger absolute cerebella, hippocampi, parahippocampi, thalami, caudates, and amygdalae while females have larger absolute cingulates, precunei, and frontal and parietal cortices. Sex classification based on regional volume achieves accuracies up to 85%, highlighting the importance of strict volume‐matching when studying brain‐based sex differences. Differential patterns in regional temporal dependence between the sexes identifies a potential neurobiological substrate or environmental effect underlying sex differences in functional brain activation patterns.

Characteristics Of Resting State Networks Of Elite Skating Athletes: An ICA Analysis

Long-term motor skill learning can lead neuro plasticity changes. Until now, this conclusion is mainly proved by task fMRI and spontaneous brain activity evidence. However, these methods heavily rely on prior knowledge and hypotheses, and exist algorithm limitations. PURPOSE: To investigate the differences of resting state networks (RSNs) between elite skating athletes and non-athlete controls by means of data-driven approach. METHODS: Resting state fMRI data were acquired by Philips Achieva 3.0T scanner with a standard 32 channel head coil from 15 Chinese national level skating athletes (all men, 20.87±1.78 years old, with an average training year of 9.67±3.50) and 15 demographically matched healthy controls (all men, 20.85±1.83 years old). Gift was used to perform ICA (independent component analysis) arithmetic calculations and identify RSNs, including default mode network, somatomotor network, dorsal attention network, left fronto-parietal network and visual network. A two-sample t-test was then conducted using SPM12 to investigate whether there were significant differences between two groups. Results were reported when voxel significant at a level of p < 0.01. Cluster-level whole-brain family wise error (FWE) was applied for multiple comparison correction (cluster p< 0.01). Coordinates are given in Montreal Neurological Institute(MNI) space. RESULTS: 1. Athletes showed higher spontaneous activity in postcentral gyrus (cluster size =230, peak coordinate =69, -12,18, peak t =11.88) and cingulate gyrus (cluster size =167, peak coordinate= 6, -3,39, peak t =6.65) in somatomotor network. 2. Athletes showed higher spontaneous activity in precuneus (cluster size =337, peak coordinate =30, -66,39, peak t =10.38) in dorsal attention network. CONCLUSIONS: Elite skating athletes showed better functional connectivity in somatomotor network and dorsal attention network, which may further indicate that long-term specialized motor training may promote functional network activation patterns.

Analysis of the pattern of functional activation of the cerebellum and its topographical correlation

ObjectivesTo describe the normal patterns of cerebellar activation in specific cerebral functions (motor, language, memory) and their topographical correlations in the cerebellar cortex on functional magnetic resonance imaging. Materials and methodsWe evaluated 25 healthy subjects (8 women and 17 men; 23 right-handed and 2 left-handed; age range, 16–64 years), who did language, memory, and motor tasks while undergoing 1.5T functional magnetic resonance imaging. ResultsWe assessed functional activity of the cerebellum associated with motor, language, and memory components, describing their relations with topographical regions of the cerebellum and their functional relations with areas in the cerebral cortex. ConclusionsKnowledge of the normal patterns of morphological characteristics and functional behaviour in the cerebellum as well as their relations with the brain is important for radiologists and clinicians evaluating the cerebellum and possible pathological conditions that affect it.

Impact of ageing on the brain regions of the schizophrenia patients: an fMRI study using evolutionary approach

Schizophrenia is a mental disorder that results in adverse functional and biochemical changes in the brain. Although normal ageing significantly affects the brain of a person structurally as well as functionally, the functional activation pattern in the brain of a schizophrenia patient may change differentially with age. To the best of our knowledge, this is the first of its kind fMRI-based study to find the functional changes in the brain of schizophrenia patients associated with ageing. In this study, we aim to compare the age-related variations in the functional activation pattern in the brain of schizophrenia patients vis a vis the healthy controls. For this study, we have used 1.5T fMRI data of 60 subjects and 3T fMRI data of 50 subjects, having an equal number of schizophrenia and healthy subjects. We have split this dataset into multiple age-groups. We applied a three-stage methodology comprising the application of the general linear model, followed by statistical hypothesis testing, and a finally bi-objective NSGA-II algorithm for selection of relevant voxels. The proposed methodology yielded a set of relevant voxels in the brain that demonstrate the age related variations in activation patterns. Specifically, it revealed increased functional activations in elderly patients suffering from schizophrenia in multiple brain regions, mostly located in areas like frontal lobe, temporal lobe and parietal lobe as compared to the young schizophrenic patients. These findings may help in making decisions for differential clinical management of younger patients as compared to the elderly ones.

The oscillatory mechanisms associated with syntactic binding in healthy ageing

Older adults frequently display differential patterns of brain activity compared to young adults in the same task, alongside widespread neuroanatomical changes. Differing functional activity patterns in older adults are commonly interpreted as being compensatory (e.g., Cabeza et al., 2002). We examined the oscillatory activity in the EEG during syntactic binding in young and older adults, as well as the relationship between oscillatory activity and behavioural performance on a syntactic judgement task within the older adults. 19 young and 41 older adults listened to two-word sentences that differentially load onto morpho-syntactic binding: correct syntactic binding (morpho-syntactically correct, e.g., “I dotch”); incorrect syntactic binding (morpho-syntactic agreement violation, e.g., “they dotches”) and no syntactic binding (minimizing morpho-syntactic binding, e.g., “dotches spuff”). Behavioural performance, assessed in a syntactic judgement task, was characterized by inter-individual variability especially in older adults, with accuracy ranging from 76 to 100% in young adults and 58–100% in older adults. Compared to young adults, older adults were slower, but not less accurate. Functional neural signatures for syntactic binding were assessed as the difference in oscillatory power between the correct and no syntactic binding condition. In older adults, syntactic binding was associated with a smaller increase in theta (4–7 Hz), alpha (8–12 Hz) and beta (15–20 Hz) power in a time window surrounding the second word. There was a significant difference between the older and young adults: in the alpha range, the condition difference seemed to be in the opposite direction for older versus young adults. Our findings thus suggest that the neural signature associated with syntactic binding in older adults is different from young adults. However, we found no evidence of a significant association between behavioural performance and the neural signatures of syntactic binding for older adults, which does not readily support the predictions of compensatory models of language and ageing.

The association between cognitive reserve and performance-related brain activity during episodic encoding and retrieval across the adult lifespan

Remembering associations between encoded items and their contextual setting is a feature of episodic memory. Although this ability generally deteriorates with age, there is substantial variability in how older individuals perform on episodic memory tasks. A current topic of debate in the cognitive neuroscience of aging literature revolves around whether this variability may stem from genetic and/or environmental factors related to reserve, allowing some individuals to compensate for age-related decline through differential recruitment of brain regions. In this fMRI study spanning a large adult lifespan sample (N = 154), we tested whether higher cognitive reserve was associated with better task-fMRI context memory performance, and functional compensatory activity patterns in the aging brain. We used multivariate Behaviour Partial Least Squares (B-PLS) analysis to examine how age, retrieval accuracy, and a proxy measure of cognitive reserve [i.e., a composite score consisting of years of education (EDU) and crystallized IQ], impacted brain activity during the encoding and retrieval of spatial and temporal contextual details. The results indicated that age-related increases in encoding activity within anterior and lateral frontal, inferior parietal, occipito-temporal and medial temporal cortices, was correlated with better subsequent memory performance; and may be indicative of age-related functional compensation at encoding. Interestingly this compensatory pattern was not correlated with our proxy measure of cognitive reserve but was associated with total brain volume (a measure of brain reserve). However, cognitive reserve was associated with age-invariant and task-general activity in superior temporal, occipital, and left inferior frontal regions. We conclude that the relationship between cognitive reserve, brain reserve and age-related functional compensation is complex, and that EDU and IQ may not fully account for individual differences in cognitive reserve when studying well educated, healthy aging cohorts.

Age-related features of the pattern of lymphocyte subpopulations and functional activity of peripheral blood mononuclear cells in patients with chronic kidney disease before and after transplantation

Objective : to analyze the features of the pattern of lymphocyte subpopulations and the functional activity of peripheral blood mononuclear cells in older adult patients with chronic kidney disease. Materials and methods . The study featured 21 patients with chronic kidney disease (CKD), over 55 years of age, who underwent kidney transplantation (KT) from unrelated suboptimal donors. The average age was 61.4 ± 4.5 years (55 to 69). Comorbidity was assessed using the CIRS-G scale; the average number of points was 13.6 ± 5.09. The control group consisted of 21 volunteers, aged 55–70, without acute inflammatory diseases and signs of chronic kidney disease (CKD). The average age was 61.1 ± 4.4 years, the average CIRS-G score was 12.11 ± 6.04. In all patients, the pattern of lymphocyte subpopulations of peripheral blood was evaluated by flow cytometry. Vital computer laser cytomorphometry was used to assess the functional state of peripheral blood mononuclear cells. The Functional Activities Index (FAI) was evaluated to indirectly assess the degree of functional activity of cells. Results . In CKD patients before KT, there was a decrease in the proportion of CD4 cells (p = 0.009), an increase in the proportion of CD8 cells (p = 0.02), a decrease in the CD4/CD8 ratio (p = 0.017), an increase in the proportion of natural killers (p = 0.025) compared with healthy volunteers. Moreover, a decrease in the total proportion of CD3 cells, an increase in HLA-DR expression on CD3 cells, and an increase in the proportion of B cells were statistically insignificant: p = 0.137, p = 0.072 and p = 0.135, respectively. On the fifth day after KT, the proportion of CD3 cells increased (p = 0.017) mainly due to an increase in the proportion of CD4 cells (p = 0.002) compared to the pre- KT index. The proportion of natural killers (p = 0.002) and HLA-DR expression on CD3 cells (p &lt; 0.0001) also increased. An increase in the proportion of CD8 cells and in the CD4/CD8 ratio, and a decrease in the proportion of B cells were statistically insignificant: p = 0.439, p = 0.277, and p = 0.236, respectively. A decrease in FAI was noted in patients with CKD before KT in comparison with healthy volunteers (p = 0.0138). After ATP, this indicator significantly increased compared to the pre-KT value (p &lt; 0.0001) and exceeded the FAI value in healthy volunteers (p &lt; 0.0001). In healthy volunteers, there was no significant correlation between the functional activity of peripheral blood mononuclear cells and age (r = –0.263 [95% CI –0.6236; 0.1907], p = 0.264, r2 = 0.069). At the same time, significant negative correlation between FAI and age was noted in CKD patients: r = –0.52 [95% CI –0.7771; –0.1135], p = 0.0157, r2 = 0.27 before KT; r = –0.418 [95% CI –0.7559; –0.06256], p = 0.0272, r2 = 0.175 after KT. Conclusion . Older adult CKD patients before and after KT were likely to have significant changes in the morphofunctional state of peripheral blood mononuclear cells and pattern of lymphocyte subpopulations. Moreover, the severity of changes in the functional state of these cells had a strong correlation with age, which was not observed in the group of healthy volunteers. This should be considered when choosing immunosuppressive therapy in older kidney transplant recipients.

Neurobehavioural characterisation and stratification of reinforcement-related behaviour.

Reinforcement-related cognitive processes, such as reward processing, inhibitory control and social-emotional regulation are critical components of externalising and internalising behaviours. It is unclear to what extent the deficit in each of these processes contributes to individual behavioural symptoms, how their neural substrates give rise to distinct behavioural outcomes and whether neural activation profiles across different reinforcement-related processes might differentiate individual behaviours. We created a statistical framework that enabled us to directly compare functional brain activation during reward anticipation, motor inhibition and viewing emotional faces in the European IMAGEN cohort of 2,000 14-year-old adolescents. We observe significant correlations and modulation of reward anticipation and motor inhibition networks in hyperactivity, impulsivity, inattentive behaviour and conduct symptoms, and we describe neural signatures across cognitive tasks that differentiate these behaviours. We thus characterise shared and distinct functional brain activation patterns underling different externalising symptoms and identify neural stratification markers, while accounting for clinically observed comorbidity.