Brain networks and endogenous pain inhibition are modulated by age and sex in healthy rats.
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ABSTRACT:
SUBMITTER: Da Silva JT
PROVIDER: S-EPMC7230015 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Recent studies have demonstrated developmental changes of functional brain networks derived from functional connectivity using graph theoretical analysis, which has been rapidly translated to studies of brain network organization. However, little is known about sex- and IQ-related differences in the topological organization of functional brain networks during development. In this study, resting-state fMRI (rs-fMRI) was used to map the functional brain networks in 51 healthy children. We then investigated the effects of age, sex, and IQ on economic small-world properties and regional nodal properties of the functional brain networks. At a global level of whole networks, we found significant age-related increases in the small-worldness and local efficiency, significant higher values of the global efficiency in boys compared with girls, and no significant IQ-related difference. Age-related increases in the regional nodal properties were found predominately in the frontal brain regions, whereas the parietal, temporal, and occipital brain regions showed age-related decreases. Significant sex-related differences in the regional nodal properties were found in various brain regions, primarily related to the default mode, language, and vision systems. Positive correlations between IQ and the regional nodal properties were found in several brain regions related to the attention system, whereas negative correlations were found in various brain regions primarily involved in the default mode, emotion, and language systems. Together, our findings of the network topology of the functional brain networks in healthy children and its relationship with age, sex, and IQ bring new insights into the understanding of brain maturation and cognitive development during childhood and adolescence.
| S-EPMC3563524 | biostudies-literature
Project description:Old age and female sex are risk factors for the development of osteoarthritis (OA) and chronic pain. We investigated the effects of sex and age on pain modulatory networks in a healthy state and during OA progression. We used functional MRI to determine the effects of sex and age on periaqueductal gray functional connectivity (PAG FC) in a healthy state (pre-OA) and during the early and late phases of monosodium iodoacetate-induced OA in rats. We then examined how sex and age affect longitudinal changes in PAG FC in OA. In a healthy state, females exhibited more widespread PAG FC than males, and this effect was exaggerated with aging. Young males had moderate PAG FC changes during the early phase but recruited additional brain regions, including the rostral anterior cingulate cortex (ACC), during the late phase. Young females exhibited widespread PAG FC in the early phase, which includes connections to insula, caudal ACC, and nucleus accumbens (NAc). Older groups had strong PAG FC with fewer regions in the early phase, but they recruited additional brain regions, including NAc, in the late phase. Overall, our findings show that PAG FC is modulated by sex and age in a healthy state. A widespread PAG network in the early phase of OA pain may contribute to the transition from acute to chronic OA pain and the increased risk of developing chronic pain for females. Enhanced PAG FC with the reward system may represent a potential mechanism underlying chronic OA pain in elderly patients.
| S-EPMC7884031 | biostudies-literature
Project description:AimsAge and sex are important individual factors modifying the clinical symptoms of patients with Parkinson's disease (PD). Our goal is to evaluate the effects of age and sex on brain networks and clinical manifestations of PD patients.MethodsParkinson's disease participants (n = 198) receiving functional magnetic resonance imaging from Parkinson's Progression Markers Initiative database were investigated. Participants were classified into lower quartile group (age rank: 0%~25%), interquartile group (age rank: 26%~75%), and upper quartile group (age rank: 76%~100%) according to their age quartiles to examine how age shapes brain network topology. The differences of brain network topological properties between male and female participants were also investigated.ResultsParkinson's disease patients in the upper quartile age group exhibited disrupted network topology of white matter networks and impaired integrity of white matter fibers compared to lower quartile age group. In contrast, sex preferentially shaped the small-world topology of gray matter covariance network. Differential network metrics mediated the effects of age and sex on cognitive function of PD patients.ConclusionAge and sex have diverse effects on brain structural networks and cognitive function of PD patients, highlighting their roles in the clinical management of PD.
| S-EPMC10324368 | biostudies-literature
Project description:In this study, we investigated age and sex differences in acute and chronic pain in rats. Groups of young (3-6 months) and aged (20-24 months) male and female Fischer 344 rats were used to assess basal thermal and mechanical thresholds, capsaicin-induced acute nocifensive responses and c-Fos expression in the spinal cord, and monoiodoacetate (MIA)-induced knee osteoarthritis (OA)-like pain responses. There was a significant sex, but not age, effect on thermal threshold on the hindpaw and mechanical threshold on the knee joint. No significant age and sex differences in capsaicin-induced nocifensive and c-Fos responses were observed. MIA induced a greater peak reduction of weight-bearing responses in aged males than young rats. Aged females developed the most profound weight-bearing deficit. With knee joint sensitivity as a primary outcome measure, MIA induced more pronounced and longer-lasting hyperalgesia in older rats, with aged female rats showing the worst effect. These data suggest that age may not have significant effect on acute nociceptive processing, but it significantly impacts OA-like pain, making aged rats, especially females, more vulnerable to chronic pain conditions. These preclinical models should provide important tools to investigate basic mechanisms underlying the impact of age and sex in chronic pain conditions.
| S-EPMC7357590 | biostudies-literature
Project description:The resource modulation hypothesis suggests that the influence of genes on cognitive functioning increases with age. The KIBRA single nucleotide polymorphism rs17070145, associated with episodic memory and working memory, has been suggested to follow such a pattern, but few studies have tested this assertion directly. The present study investigated the relationship between KIBRA alleles (T carriers vs. CC homozygotes), cognitive performance, and brain volumes in three groups of cognitively healthy adults-middle aged (ages 52-64, n = 38), young old (ages 65-72, n = 45), and older old (ages 73-92, n = 62)-who were carefully matched on potentially confounding variables including apolipoprotein ?4 status and hypertension. Consistent with our prediction, T carriers maintained verbal memory performance with increasing age while CC homozygotes declined. Voxel-based morphometric analysis of magnetic resonance images showed an advantage for T carriers in frontal white matter volume that increased with age. Focusing on the older old group, this advantage for T carriers was also evident in left lingual gyrus gray matter and several additional frontal white matter regions. Contrary to expectations, neither KIBRA nor the interaction between KIBRA and age predicted hippocampal volumes. None of the brain regions investigated showed a CC homozygote advantage. Taken together, these data suggest that KIBRA results in decreased verbal memory performance and lower brain volumes in CC homozygotes compared to T carriers, particularly among the oldest old, consistent with the resource modulation hypothesis.
| S-EPMC5767716 | biostudies-literature
Project description:Age and sex can influence brain iron levels. We studied the influence of these variables on deep gray matter magnetic susceptibilities. In 183 healthy volunteers (44.7 ± 14.2 years, range 20-69, ? 49%), in vivo quantitative susceptibility mapping (QSM) at 1.5T was performed to estimate brain iron accumulation in the following regions of interest (ROIs): caudate nucleus (Cd), putamen (Pt), globus pallidus (Gp), thalamus (Th), pulvinar (Pul), red nucleus (Rn), substantia nigra (Sn) and the cerebellar dentate nuclei (Dn). We gauged the influence of age and sex on magnetic susceptibility by specifying a series of structural equation models. The distributions of susceptibility varied in degree across the structures, conforming to histologic findings (Hallgren and Sourander, 1958), with the highest degree of susceptibility in the Gp and the lowest in the Th. Iron increase correlated across several ROIs, which may reflect an underlying age-related process. Advanced age was associated with a particularly strong linear rise of susceptibility in the striatum. Nonlinear age trends were found in the Rn, where they were the most pronounced, followed by the Pul and Sn, while minimal nonlinear trends were observed for the Pt, Th, and Dn. Moreover, sex related variations were observed, so that women showed lower levels of susceptibility in the Sn after accounting for age. Regional susceptibility of the Pul increased linearly with age in men but exhibited a nonlinear association with age in women with a leveling off starting from midlife. Women expected to be post menopause (+51 years) showed lower total magnetic susceptibility in the subcortical gray matter. The current report not only is consistent with previous reports of age related variations of brain iron, but also adds to the current knowledge by reporting age-related changes in less studied, smaller subcortical nuclei. This is the first in-vivo report to show lower total subcortical brain iron levels selectively in women from midlife, compared to men and younger women. These results encourage further assessment of sex differences in brain iron. We anticipate that age and sex are important co-factors to take into account when establishing a baseline level for differentiating pathologic neurodegeneration from healthy aging. The variations in regional susceptibility reported herein should be evaluated further using a longitudinal study design to determine within-person changes in aging.
| S-EPMC4737643 | biostudies-literature
Project description:The aim of this study was to examine structural brain networks using regional gray matter volume, as well as to investigate changes in small-world and modular organization with normal aging. We constructed structural brain networks composed of 90 regions in young, middle, and old age groups. We randomly selected 350 healthy subjects for each group from a Japanese magnetic resonance image database. Structural brain networks in three age groups showed economical small-world properties, providing high global and local efficiency for parallel information processing at low connection cost. The small-world efficiency and node betweenness varied significantly and revealed a U- or inverted U-curve model tendency among three age groups. Results also demonstrated that structural brain networks exhibited a modular organization in which the connections between regions are much denser within modules than between them. The modular organization of structural brain networks was similar between the young and middle age groups, but quite different from the old group. In particular, the old group showed a notable decrease in the connector ratio and the intermodule connections. Combining the results of small-world efficiency, node betweenness and modular organization, we concluded that the brain network changed slightly, developing into a more distributed organization from young to middle age. The organization eventually altered greatly, shifting to a more localized organization in old age. Our findings provided quantitative insights into topological principles of structural brain networks and changes related to normal aging.
| S-EPMC6870030 | biostudies-literature
Project description:Endogenous pain inhibition is often deficient in adults with chronic pain conditions including irritable bowel syndrome (IBS). It is unclear whether deficiencies in pain inhibition are present in young children with IBS. The present study compared endogenous pain inhibition, somatic pain threshold, and psychosocial distress in young girls with IBS versus controls. Girls with IBS did not show significant endogenous pain inhibition of heat pain threshold during a cold-pressor task in contrast to controls, who had significant pain inhibition. Girls with IBS did not differ from peers on measures of somatic pain but had more symptoms of depression, somatization, and anxiety than controls. When psychological variables were included as covariates, the difference in pain inhibition was no longer significant, although poor achieved power limits interpretation of these results. Higher-order cognitive processes including psychological variables may be contributing to observed pain inhibition. In girls with IBS, pain inhibition was positively related to the number of days without a bowel movement. To our knowledge, this is the first study to demonstrate deficiencies of endogenous pain inhibition in young children with IBS. Findings have implications for better understanding of onset and maintenance of IBS and other chronic pain conditions.This study found that young girls with IBS have deficient endogenous pain inhibition compared to healthy girls, which is consistent with the literature on adults. This information can facilitate clinicians in identification of risk factors for onset/maintenance of IBS and other chronic pain conditions.
| S-EPMC3759538 | biostudies-literature
Project description:IntroductionSuccessful inhibition of distracting emotions is important for preserving well-being and daily functioning. There is conflicting evidence regarding the impact of healthy aging on emotional inhibition, and possible age-related alterations in the neuronal underpinnings of emotional interference processing are unexplored.MethodsThirty younger (mean age 26 years; 15 women) and 30 older (mean age 71 years; 13 women) healthy adults performed a face-word emotional Stroop task while undergoing functional magnetic resonance imaging of the brain. A resting-state scan was acquired for calculating the amplitude of low-frequency fluctuations as an estimate of vascular reactivity. Comparisons of brain activation during the task were assessed in a whole-brain, voxel-wise analysis, contrasting congruent, and incongruent conditions. The canonical regions of the frontoparietal, salience, dorsal attention, and default mode networks were used as seed regions for assessing functional connectivity within and between large-scale brain networks. Task performance was evaluated using response accuracy and response time.ResultsThe older adults had longer response times and lower task accuracy than the younger adults, but the emotional interference effect was not significantly different between the groups. Whole-brain analysis revealed no significant age-related differences in brain activation patterns. Rescaling the data for estimated variability in vascular reactivity did not affect the results. In older adults, there was relatively stronger functional connectivity with the default mode network, the sensorimotor network, and the dorsal attention network for the frontoparietal and salience network seeds during the task. Conversely, younger adults had relatively stronger connections within and between the frontoparietal and salience networks.ConclusionIn this first fMRI study of emotional Stroop interference in older and younger adults, we found that the emotional interference effect was unchanged in healthy aging and replicated the finding from non-emotional task studies that older adults have greater between-network and less within-network connectivity compared to younger adults.
| S-EPMC8119855 | biostudies-literature
Project description:Brain development and aging are dynamic processes that unfold over years on multiple levels in both healthy and disordered individuals. Recent studies have revealed a disparity between the chronological brain age and the 'data-driven' brain age using functional MRI (fMRI) and diffusion MRI (dMRI). Particularly, predicting the 'brain age' from connectomic data might help identify relevant connectional biomarkers of neurological disorders that emerge early or late in the lifespan. While prior brain-age prediction studies have relied exclusively on either structural or functional connectomic data, here we unprecedentedly propose to predict the morphological age of the brain by solely using morphological brain networks (derived from T1-weighted images) in both healthy and disordered populations. Besides, although T1-weighted MRI was widely used for brain age prediction, it was leveraged from an image-based analysis perspective not from a connectomic perspective. Our method includes the following steps: (i) building multi-view morphological brain networks (M-MBN), (ii) feature extraction and selection, (iii) training a machine-learning regression model to predict age from M-MBN data, and (iv) utilizing our model to identify connectional brain features related to age in both autistic and healthy populations. We demonstrate that our method significantly outperforms existing approaches and discovered brain connectional morphological features that fingerprint the age of brain cortical morphology in both autistic and healthy individuals. In particular, we discovered that the connectional cortical thickness best predicts the morphological age of the autistic brain.
| S-EPMC6609705 | biostudies-literature