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Psychoneuroendocrinology Nov 2022Allostatic load (AL) refers to prolonged dysregulation related to chronic stress that affects brain regions such as the hippocampus, amygdala, and prefrontal cortex...
Allostatic load (AL) refers to prolonged dysregulation related to chronic stress that affects brain regions such as the hippocampus, amygdala, and prefrontal cortex (PFC). Higher levels of AL have been associated with poor health outcomes, including psychiatric disorders, cognitive decline, and chronic somatic conditions. However, still little is known about the relationship between AL and the brain, and the mechanisms explaining the damaging effects of stress-related biological dysregulations. Therefore, we aimed to perform a systematic review of studies investigating the association of the AL index with brain structure and functioning in adult populations. PubMed/MEDLINE, CINAHL, Academic Search Complete and Web of Science were searched from their inception until August, 9th 2021. A total of 13 studies were included in the qualitative synthesis. There was a high between-study heterogeneity with respect to the methods used to calculate the AL index and brain parameters. All studies confirmed the associations between a higher AL index and alterations in various brain areas, especially: 1) the hippocampus, white matter volume, gray matter volume, and density in the older adults; 2) the cortex, fornix, hippocampus and choroid plexus in patients with schizophrenia spectrum disorders; and 3) whole-brain white matter tracts, cortical gray matter volume, and cortical thickness in overweight subjects. Overall, the findings of this systematic review imply that an elevated AL index might be associated with various neurostructural and neurofunctional alterations. Some of these associations may appear regardless of clinical or non-clinical populations being investigated (e.g., white matter tracts), whereas others may appear in specific populations (e.g., cortical thinning in overweight/obesity and schizophrenia spectrum disorders). However, additional studies utilizing a consistent approach to calculating the AL index are needed to extend these findings and indicate populations that are most vulnerable to the damaging effects of AL.
Topics: Aged; Allostasis; Brain; Gray Matter; Humans; Overweight; White Matter
PubMed: 36113380
DOI: 10.1016/j.psyneuen.2022.105917 -
Molecular and Cellular Endocrinology May 2021In humans, reticularis cells of the adrenal cortex fuel the production of androgen steroids, constituting the driver of numerous morphological changes during childhood.... (Review)
Review
In humans, reticularis cells of the adrenal cortex fuel the production of androgen steroids, constituting the driver of numerous morphological changes during childhood. These steps are considered a precocious stage of sexual maturation and are grouped under the term "adrenarche". This review describes the molecular and enzymatic characteristics of the zona reticularis, along with the possible signals and mechanisms that control its emergence and the associated clinical features. We investigate the differences between species and discuss new studies such as genetic lineage tracing and transcriptomic analysis, highlighting the rodent inner cortex's cellular and molecular heterogeneity. The recent development and characterization of mouse models deficient for Prkar1a presenting with adrenocortical reticularis-like features prompt us to review our vision of the mouse adrenal gland maturation. We expect these new insights will help increase our understanding of the adrenarche process and the pathologies associated with its deregulation.
Topics: Adrenarche; Androgens; Animals; Female; Gene Expression Profiling; Humans; Mice; Rats; Zona Reticularis
PubMed: 33676986
DOI: 10.1016/j.mce.2021.111239 -
Neuropsychopharmacology : Official... Jan 2022The real world is uncertain, and while ever changing, it constantly presents itself in terms of new sets of behavioral options. To attain the flexibility required to... (Review)
Review
The real world is uncertain, and while ever changing, it constantly presents itself in terms of new sets of behavioral options. To attain the flexibility required to tackle these challenges successfully, most mammalian brains are equipped with certain computational abilities that rely on the prefrontal cortex (PFC). By examining learning in terms of internal models associating stimuli, actions, and outcomes, we argue here that adaptive behavior relies on specific interactions between multiple systems including: (1) selective models learning stimulus-action associations through rewards; (2) predictive models learning stimulus- and/or action-outcome associations through statistical inferences anticipating behavioral outcomes; and (3) contextual models learning external cues associated with latent states of the environment. Critically, the PFC combines these internal models by forming task sets to drive behavior and, moreover, constantly evaluates the reliability of actor task sets in predicting external contingencies to switch between task sets or create new ones. We review different models of adaptive behavior to demonstrate how their components map onto this unifying framework and specific PFC regions. Finally, we discuss how our framework may help to better understand the neural computations and the cognitive architecture of PFC regions guiding adaptive behavior.
Topics: Adaptation, Psychological; Animals; Computer Simulation; Learning; Prefrontal Cortex; Reproducibility of Results
PubMed: 34389808
DOI: 10.1038/s41386-021-01123-1 -
Brain Communications 2023Post-stroke depression affects about 30% of stroke patients and often hampers functional recovery. The diagnosis of depression encompasses heterogeneous symptoms at...
Post-stroke depression affects about 30% of stroke patients and often hampers functional recovery. The diagnosis of depression encompasses heterogeneous symptoms at emotional, motivational, cognitive, behavioural or somatic levels. Evidence indicates that depression is caused by disruption of bio-aminergic fibre tracts between prefrontal and limbic or striatal brain regions comprising different functional networks. Voxel-based lesion-symptom mapping studies reported discrepant findings regarding the association between infarct locations and depression. Inconsistencies may be due to the usage of sum scores, thereby mixing different symptoms of depression. In this cross-sectional study, we used multivariate support vector regression for lesion-symptom mapping to identify regions significantly involved in distinct depressive symptom domains and global depression. MRI lesion data were included from 200 patients with acute first-ever ischaemic stroke (mean 0.9 ± 1.5 days of post-stroke). The Montgomery-Åsberg Depression Rating interview assessed depression severity in five symptom domains encompassing motivational, emotional and cognitive symptoms deficits, anxiety and somatic symptoms and was examined 8.4 days of post-stroke (±4.3). We found that global depression severity, irrespective of individual symptom domains, was primarily linked to right hemispheric lesions in the dorsolateral prefrontal cortex and inferior frontal gyrus. In contrast, when considering distinct symptom domains individually, the analyses yielded much more sensitive results in regions where the correlations with the global depression score yielded no effects. Accordingly, motivational deficits were associated with lesions in orbitofrontal cortex, dorsolateral prefrontal cortex, pre- and post-central gyri and basal ganglia, including putamen and pallidum. Lesions affecting the dorsal thalamus, anterior insula and somatosensory cortex were significantly associated with emotional symptoms such as sadness. Damage to the dorsolateral prefrontal cortex was associated with concentration deficits, cognitive symptoms of guilt and self-reproach. Furthermore, somatic symptoms, including loss of appetite and sleep disturbances, were linked to the insula, parietal operculum and amygdala lesions. Likewise, anxiety was associated with lesions impacting the central operculum, insula and inferior frontal gyrus. Interestingly, symptoms of anxiety were exclusively left hemispheric, whereas the lesion-symptom associations of the other domains were lateralized to the right hemisphere. In conclusion, this large-scale study shows that in acute stroke patients, differential post-stroke depression symptom domains are associated with specific structural correlates. Our findings extend existing concepts on the neural underpinnings of depressive symptoms, indicating that differential lesion patterns lead to distinct depressive symptoms in the first weeks of post-stroke. These findings may facilitate the development of personalized treatments to improve post-stroke rehabilitation.
PubMed: 37908237
DOI: 10.1093/braincomms/fcad275 -
Nature Neuroscience Jan 2022Learned associations between stimuli in different sensory modalities can shape the way we perceive these stimuli. However, it is not well understood how these...
Learned associations between stimuli in different sensory modalities can shape the way we perceive these stimuli. However, it is not well understood how these interactions are mediated or at what level of the processing hierarchy they occur. Here we describe a neural mechanism by which an auditory input can shape visual representations of behaviorally relevant stimuli through direct interactions between auditory and visual cortices in mice. We show that the association of an auditory stimulus with a visual stimulus in a behaviorally relevant context leads to experience-dependent suppression of visual responses in primary visual cortex (V1). Auditory cortex axons carry a mixture of auditory and retinotopically matched visual input to V1, and optogenetic stimulation of these axons selectively suppresses V1 neurons that are responsive to the associated visual stimulus after, but not before, learning. Our results suggest that cross-modal associations can be communicated by long-range cortical connections and that, with learning, these cross-modal connections function to suppress responses to predictable input.
Topics: Acoustic Stimulation; Animals; Auditory Cortex; Learning; Mice; Photic Stimulation; Visual Cortex
PubMed: 34857950
DOI: 10.1038/s41593-021-00974-7 -
The Journal of Neuroscience : the... Nov 2022Human childhood is characterized by dramatic changes in the mind and brain. However, little is known about the large-scale intrinsic cortical network changes that occur...
Human childhood is characterized by dramatic changes in the mind and brain. However, little is known about the large-scale intrinsic cortical network changes that occur during childhood because of methodological challenges in scanning young children. Here, we overcome this barrier by using sophisticated acquisition and analysis tools to investigate functional network development in children between the ages of 4 and 10 years ([Formula: see text]; 50 female, 42 male). At multiple spatial scales, age is positively associated with brain network segregation. At the system level, age was associated with segregation of systems involved in attention from those involved in abstract cognition, and with integration among attentional and perceptual systems. Associations between age and functional connectivity are most pronounced in visual and medial prefrontal cortex, the two ends of a gradient from perceptual, externally oriented cortex to abstract, internally oriented cortex. These findings suggest that both ends of the sensory-association gradient may develop early, in contrast to the classical theories that cortical maturation proceeds from back to front, with sensory areas developing first and association areas developing last. More mature patterns of brain network architecture, controlling for age, were associated with better visuospatial reasoning abilities. Our results suggest that as cortical architecture becomes more specialized, children become more able to reason about the world and their place in it. Anthropologists have called the transition from early to middle childhood the "age of reason", when children across cultures become more independent. We employ cutting-edge neuroimaging acquisition and analysis approaches to investigate associations between age and functional brain architecture in childhood. Age was positively associated with segregation between cortical systems that process the external world and those that process abstract phenomena like the past, future, and minds of others. Surprisingly, we observed pronounced development at both ends of the sensory-association gradient, challenging the theory that sensory areas develop first and association areas develop last. Our results open new directions for research into how brains reorganize to support rapid gains in cognitive and socioemotional skills as children reach the age of reason.
Topics: Humans; Child; Male; Female; Child, Preschool; Cognition; Brain Mapping; Brain; Sensation; Problem Solving; Magnetic Resonance Imaging
PubMed: 36192151
DOI: 10.1523/JNEUROSCI.0511-22.2022 -
Journal of Psychiatric Research Oct 2021Resilience is a crucial factor preventing the onset of mental illness and contributing to the well-being and healthy longevity, whose neural bases are not fully...
Association between resilience and cortical thickness in the posterior cingulate cortex and the temporal pole in Japanese older people: A population-based cross-sectional study.
BACKGROUND
Resilience is a crucial factor preventing the onset of mental illness and contributing to the well-being and healthy longevity, whose neural bases are not fully elucidated in older people. The present study aimed to identify the cortical thickness associating with resilience in older adults.
METHODS
This is a part of the cross-sectional Arakawa geriatric cohort study for people aged 65 years or older, consisting of 1001 individuals. A Self-Reported Resilience Scale (RS), neuropsychological batteries, face-to-face interviews for diagnosis, and a three-dimensional T1-weighted magnetic resonance imaging were conducted. Cortical thickness was computed by the FreeSurfer. The relationships among cortical thickness, total RS score, and clinico-demographic data were investigated using univariate and multivariable regression analyses.
RESULTS
The total RS score was correlated with age, education, and scores of the Mini-Mental State Examination (MMSE) and Geriatric Depression Scale (GDS) in univariate analyses. The total RS score was associated with cortical thicknesses in the left posterior cingulate (β [95 % CI of B] = 0.07 [0.16-14.84]) and the left temporal pole (β [95 % CI of B] = 0.08 [0.63-9.93]) after adjusting sex, age, imaging acquisition site, education, MMSE and GDS scores, hypertension, hyperlipidemia, diabetes mellitus, Barthel index, BMI, and living situation in multivariable regression analyses.
CONCLUSION
The present analyses suggest that the resilience capacity may be related to the cortical thickness in the posterior cingulate and temporal cortices in older adults. Our findings warrant further longitudinal studies to confirm the causal relationship between stress events, resilience, and brain structures.
Topics: Aged; Cerebral Cortex; Cohort Studies; Cross-Sectional Studies; Gyrus Cinguli; Humans; Japan; Magnetic Resonance Imaging; Temporal Lobe
PubMed: 34330025
DOI: 10.1016/j.jpsychires.2021.07.026 -
Glia Aug 2023Cerebral blood flow (CBF) is important for the maintenance of brain function and its dysregulation has been implicated in Alzheimer's disease (AD). Microglia...
Cerebral blood flow (CBF) is important for the maintenance of brain function and its dysregulation has been implicated in Alzheimer's disease (AD). Microglia associations with capillaries suggest they may play a role in the regulation of CBF or the blood-brain-barrier (BBB). We explored the relationship between microglia and pericytes, a vessel-resident cell type that has a major role in the control of CBF and maintenance of the BBB, discovering a spatially distinct subset of microglia that closely associate with pericytes. We termed these pericyte-associated microglia (PEM). PEM are present throughout the brain and spinal cord in NG2DsRed × CX CR1 mice, and in the human frontal cortex. Using in vivo two-photon microscopy, we found microglia residing adjacent to pericytes at all levels of the capillary tree and found they can maintain their position for at least 28 days. PEM can associate with pericytes lacking astroglial endfeet coverage and capillary vessel width is increased beneath pericytes with or without an associated PEM, but capillary width decreases if a pericyte loses a PEM. Deletion of the microglia fractalkine receptor (CX CR1) did not disrupt the association between pericytes and PEM. Finally, we found the proportion of microglia that are PEM declines in the superior frontal gyrus in AD. In summary, we identify microglia that specifically associate with pericytes and find these are reduced in number in AD, which may be a novel mechanism contributing to vascular dysfunction in neurodegenerative diseases.
Topics: Mice; Humans; Animals; Pericytes; Mice, Transgenic; Microglia; Brain; Blood-Brain Barrier; Alzheimer Disease
PubMed: 36994950
DOI: 10.1002/glia.24371 -
Hippocampus Jul 2021The perirhinal cortex is situated on the border between sensory association cortex and the hippocampal formation. It serves an important function as a transition area... (Review)
Review
The perirhinal cortex is situated on the border between sensory association cortex and the hippocampal formation. It serves an important function as a transition area between the sensory neocortex and the medial temporal lobe. While the perirhinal cortex has traditionally been associated with object coding and the "what" pathway of the temporal lobe, current evidence suggests a broader function of the perirhinal cortex in solving feature ambiguity and processing complex stimuli. Besides fulfilling functions in object coding, recent neurophysiological findings in freely moving rodents indicate that the perirhinal cortex also contributes to spatial and contextual processing beyond individual sensory modalities. Here, we address how these two opposing views on perirhinal cortex-the object-centered and spatial-contextual processing hypotheses-may be reconciled. The perirhinal cortex is consistently recruited when different features can be merged perceptually or conceptually into a single entity. Features that are unitized in these entities include object information from multiple sensory domains, reward associations, semantic features and spatial/contextual associations. We propose that the same perirhinal network circuits can be flexibly deployed for multiple cognitive functions, such that the perirhinal cortex performs similar unitization operations on different types of information, depending on behavioral demands and ranging from the object-related domain to spatial, contextual and semantic information.
Topics: Cerebral Cortex; Cognition; Hippocampus; Perirhinal Cortex; Spatial Processing
PubMed: 33523577
DOI: 10.1002/hipo.23304 -
Journal of Alzheimer's Disease : JAD 2023The association between poor oral health and the risk of incident dementia remains unclear.
BACKGROUND
The association between poor oral health and the risk of incident dementia remains unclear.
OBJECTIVE
To investigate the associations of poor oral health with incident dementia, cognitive decline, and brain structure in a large population-based cohort study.
METHODS
A total of 425,183 participants free of dementia at baseline were included from the UK Biobank study. The associations between oral health problems (mouth ulcers, painful gums, bleeding gums, loose teeth, toothaches, and dentures) and incident dementia were examined using Cox proportional hazards models. Mixed linear models were used to investigate whether oral health problems were associated with prospective cognitive decline. We examined the associations between oral health problems and regional cortical surface area using linear regression models. We further explored the potential mediating effects underlying the relationships between oral health problems and dementia.
RESULTS
Painful gums (HR = 1.47, 95% CI [1.317-1.647], p < 0.001), toothaches (HR = 1.38, 95% CI [1.244-1.538], p < 0.001), and dentures (HR = 1.28, 95% CI [1.223-1.349], p < 0.001) were associated with increased risk of incident dementia. Dentures were associated with a faster decline in cognitive functions, including longer reaction time, worse numeric memory, and worse prospective memory. Participants with dentures had smaller surface areas of the inferior temporal cortex, inferior parietal cortex, and middle temporal cortex. Brain structural changes, smoking, alcohol drinking, and diabetes may mediate the associations between oral health problems and incident dementia.
CONCLUSION
Poor oral health is associated with a higher risk of incident dementia. Dentures may predict accelerated cognitive decline and are associated with regional cortical surface area changes. Improvement of oral health care could be beneficial for the prevention of dementia.
Topics: Humans; Dementia; Oral Health; Cohort Studies; Prospective Studies; Toothache; Cognitive Dysfunction; Risk Factors
PubMed: 37212101
DOI: 10.3233/JAD-221176