ABSTRACT
Early brain development is characterized by the formation of a highly organized structural connectome, which underlies brain's cognitive abilities and influences its response to diseases and environmental factors. Hence, quantitative assessment of structural connectivity in the perinatal stage is useful for studying normal and abnormal neurodevelopment. However, estimation of the connectome from diffusion MRI data involves complex computations. For the perinatal period, these computations are further challenged by the rapid brain development, inherently low signal quality, imaging difficulties, and high inter-subject variability. These factors make it difficult to chart the normal development of the structural connectome. As a result, there is a lack of reliable normative baselines of structural connectivity metrics at this critical stage in brain development. In this study, we developed a computational method based on spatio-temporal averaging in the image space for determining such baselines. We used this method to analyze the structural connectivity between 33 and 44 postmenstrual weeks using data from 166 subjects. Our results unveiled clear and strong trends in the development of structural connectivity in the perinatal stage. We observed increases in measures of network integration and segregation, and widespread strengthening of the connections within and across brain lobes and hemispheres. We also observed asymmetry patterns that were consistent between different connection weighting approaches. Connection weighting based on fractional anisotropy and neurite density produced the most consistent results. Our proposed method also showed considerable agreement with an alternative technique based on connectome averaging. The new computational method and results of this study can be useful for assessing normal and abnormal development of the structural connectome early in life.
Subject(s)
Brain , Connectome , Humans , Brain/diagnostic imaging , Brain/growth & development , Female , Connectome/methods , Male , Adult , Diffusion Tensor Imaging/methods , Neural Pathways/diagnostic imaging , Neural Pathways/growth & development , Diffusion Magnetic Resonance Imaging/methods , Image Processing, Computer-Assisted/methods , Young Adult , Nerve Net/diagnostic imaging , Nerve Net/growth & developmentABSTRACT
Is language distinct from other cognition during development? Does neural machinery for language emerge from general-purpose neural mechanisms, becoming tuned for language after years of experience and maturation? Answering these questions will shed light on the origins of domain-specificity in the brain. We address these questions using precision fMRI, scanning young children (35 months to 9 years of age) on an auditory language localizer, spatial working memory localizer (engaging the domain-general multiple demand [MD] network), and a resting-state scan. We create subject-specific functional regions of interest for each network and examine their selectivity, specificity, and functional connectivity. We find young children show domain-specific, left-lateralized language activation, and that the language network is not responsive to domain-general cognitive load. Additionally, the cortically adjacent MD network is selective to cognitive load, but not to language. These networks show higher within versus between-network functional connectivity. This connectivity is stable across ages (examined cross-sectionally and longitudinally), whereas language responses increase with age and across time within subject, reflecting a domain-specific developmental change. Overall, we provide evidence for a double dissociation of the language and MD network throughout development, in both their function and connectivity. These findings suggest that domain-specificity, even for uniquely human cognition like language, develops early and distinctly from mechanisms that presumably support other human cognition.
Subject(s)
Brain , Cognition , Language , Magnetic Resonance Imaging , Humans , Child , Male , Female , Child, Preschool , Cognition/physiology , Brain/diagnostic imaging , Brain/physiology , Brain/growth & development , Brain Mapping , Memory, Short-Term/physiology , Child Development/physiology , Nerve Net/diagnostic imaging , Nerve Net/physiology , Nerve Net/growth & development , Neural Pathways/physiology , Neural Pathways/diagnostic imaging , Neural Pathways/growth & development , Longitudinal Studies , Language DevelopmentABSTRACT
BACKGROUND: The piglet brain has been increasingly used as an excellent surrogate for investigation of pediatric neurodevelopment, nutrition, and traumatic brain injuries. This study intends to establish a piglet brain's structural connectivity model and compare it with the adult pig, enhancing its application for structurally guided functional analysis. METHODS: In this study, diffusion-weighted (DW)-MRI data from piglets (n=11, 3-week-old) was used to establish piglet model and compare with adult pigs. We employed a data-driven independent component analysis (ICA) method to derive piglet-specific tracts. Pearson correlations and Kullback-Leibler (KL) divergences was employed to identify common tracts and unique tracts for piglet. Common tracts were then used in a blueprint connectome study to highlight differences in regions of interest (ROI). RESULTS: The data-driven approach applied to piglet brains revealed 17 common tracts, showing high similarity with adult pigs' white matter (WM) tracts, and identified 3 tracts unique to piglets and 10 negative marker tracts. Additionally, the study highlighted notable differences in 3 ROIs associated with blueprint connectome. COMPARING WITH EXISTING METHODS: This study marks a significant shift from surface-based to voxel-based methodologies in analyzing pig brain structural connectivity and generating connectome blueprints. Additionally, it sheds light on the use of the piglet model for developmental studies, offering new perspectives in this area. CONCLUSION: This study established a piglet brain tract model and conducts a comparative analysis of adult pig's and piglet's structural connectivity. These findings underscore the potential use of the piglet brain model in employing piglet model for developmental studies.
Subject(s)
Connectome , White Matter , Animals , White Matter/diagnostic imaging , White Matter/growth & development , White Matter/anatomy & histology , Swine , Connectome/methods , Diffusion Magnetic Resonance Imaging/methods , Brain/growth & development , Brain/diagnostic imaging , Brain/anatomy & histology , Animals, Newborn , Neural Pathways/growth & development , Neural Pathways/diagnostic imaging , Neural Pathways/anatomy & histology , Male , Female , Image Processing, Computer-Assisted/methods , Diffusion Tensor Imaging/methodsABSTRACT
The COVID-19 pandemic has had profound but incompletely understood adverse effects on youth. To elucidate the role of brain circuits in how adolescents responded to the pandemic's stressors, we investigated their prepandemic organization as a predictor of mental/emotional health in the first ~15 months of the pandemic. We analyzed resting-state networks from n = 2,641 adolescents [median age (interquartile range) = 144.0 (13.0) months, 47.7% females] in the Adolescent Brain Cognitive Development study, and longitudinal assessments of mental health, stress, sadness, and positive affect, collected every 2 to 3 months from May 2020 to May 2021. Topological resilience and/or network strength predicted overall mental health, stress and sadness (but not positive affect), at multiple time points, but primarily in December 2020 and May 2021. Higher resilience of the salience network predicted better mental health in December 2020 (ß = 0.19, 95% CI = [0.06, 0.31], P = 0.01). Lower connectivity of left salience, reward, limbic, and prefrontal cortex and its thalamic, striatal, amygdala connections, predicted higher stress (ß = -0.46 to -0.20, CI = [-0.72, -0.07], P < 0.03). Lower bilateral robustness (higher fragility) and/or connectivity of these networks predicted higher sadness in December 2020 and May 2021 (ß = -0.514 to -0.19, CI = [-0.81, -0.05], P < 0.04). These findings suggest that the organization of brain circuits may have played a critical role in adolescent stress and mental/emotional health during the pandemic.
Subject(s)
Brain , COVID-19 , Magnetic Resonance Imaging , Stress, Psychological , Humans , COVID-19/psychology , Adolescent , Female , Male , Stress, Psychological/physiopathology , Stress, Psychological/psychology , Brain/growth & development , Brain/diagnostic imaging , Resilience, Psychological , Emotions/physiology , Nerve Net/diagnostic imaging , Nerve Net/growth & development , Nerve Net/physiology , Neural Pathways/physiology , Neural Pathways/growth & development , Mental Health , Longitudinal Studies , Adolescent Development/physiology , ChildABSTRACT
This paper explores the potential of rAAV2-retro to deliver gene modifying cargoes to the cells of origin of multiple pathways that are interrupted by spinal cord injury (SCI), summarizing data from previous studies and new data from additional experiments. rAAV-retro exhibits uniquely robust and reliable long-distance retrograde transport from pre-terminal axons and synapses back to neuronal bodies. Previous studies have documented that various AAV-based genetic modifications can enable axon regeneration after SCI, but these have targeted the cells of origin of one pathway at a time. In contrast, rAAV-retro can simultaneously transduce large numbers of neurons of origin of multiple spinal pathways with single injections into the spinal cord. Our initial studies use RosatdTomato and double transgenic PTENf/f; RosatdTomato mice in which transfection with rAAV-retro/Cre deletes PTEN and activates tdT expression in the same neurons. Injections of rAAV-retro/Cre into the cervical, thoracic and lumbar spinal cord led to topographically specific retrograde transduction in cortical motoneurons and neurons in subcortical regions that give rise to different spinal pathways. Our results confirm and extend previous studies indicating selective transduction of neurons that terminate at the level of the injection with minimal retrograde transduction of axons in transit to lower levels. We document feasibility of using rAAV-retro expressing shRNA against PTEN along with a GFP reporter (rAAV-retro-shPTEN/GFP) to effectively knock down PTEN in multiple populations of neurons, which can be used in any species. Some limitations and caveats of currently available rAAV-retros are discussed. Together, our results support the potential applications of rAAV-retro for AAV-based gene-modifications for SCI.
Subject(s)
Genetic Therapy/methods , Genetic Vectors/genetics , Neural Pathways/growth & development , Spinal Cord Injuries/therapy , Animals , Axons , Female , Humans , Male , Mice , Mice, Knockout , Mice, Transgenic , Nerve Regeneration/genetics , Neural Pathways/injuries , PTEN Phosphohydrolase/genetics , RNA, Small Interfering/genetics , Rats , Rats, Sprague-DawleyABSTRACT
Adult cortex is organized into distributed functional communities. Yet, little is known about community architecture of children's brains. Here, we uncovered the community structure of cortex in childhood using fMRI data from 670 children aged 9-11 years (48% female, replication sample n=544, 56% female) from the Adolescent Brain and Cognitive Development study. We first applied a data-driven community detection approach to cluster cortical regions into communities, then employed a generative model-based approach called the weighted stochastic block model to further probe community interactions. Children showed similar community structure to adults, as defined by Yeo and colleagues in 2011, in early-developing sensory and motor communities, but differences emerged in transmodal areas. Children have more cortical territory in the limbic community, which is involved in emotion processing, than adults. Regions in association cortex interact more flexibly across communities, creating uncertainty for the model-based assignment algorithm, and perhaps reflecting cortical boundaries that are not yet solidified. Uncertainty was highest for cingulo-opercular areas involved in flexible deployment of cognitive control. Activation and deactivation patterns during a working memory task showed that both the data-driven approach and a set of adult communities statistically capture functional organization in middle childhood. Collectively, our findings suggest that community boundaries are not solidified by middle childhood.
Subject(s)
Brain/physiology , Connectome/methods , Magnetic Resonance Imaging/methods , Brain/growth & development , Child , Cognition/physiology , Female , Humans , Male , Memory, Short-Term/physiology , Models, Neurological , Neural Pathways/growth & development , Neural Pathways/physiologyABSTRACT
Adolescence is a critical period of structural and functional neural maturation among regions serving the cognitive control of emotion. Evidence suggests that this process is guided by developmental changes in amygdala and striatum structure and shifts in functional connectivity between subcortical (SC) and cognitive control (CC) networks. Herein, we investigate the extent to which such developmental shifts in structure and function reciprocally predict one another over time. 179 youth (9-15 years-old) completed annual MRI scans for three years. Amygdala and striatum volumes and connectivity within and between SC and CC resting state networks were measured for each year. We tested for reciprocal predictability of within-person and between-person changes in structure and function using random-intercept cross-lagged panel models. Within-person shifts in amygdala volumes in a given year significantly and specifically predicted deviations in SC-CC connectivity in the following year, such that an increase in volume was associated with decreased SC-CC connectivity the following year. Deviations in connectivity did not predict changes in amygdala volumes over time. Conversely, broader group-level shifts in SC-CC connectivity were predictive of subsequent deviations in striatal volumes. We did not see any cross-predictability among amygdala or striatum volumes and within-network connectivity measures. Within-person shifts in amygdala structure year-to-year robustly predicted weaker SC-CC connectivity in subsequent years, whereas broader increases in SC-CC connectivity predicted smaller striatal volumes over time. These specific structure function relationships may contribute to the development of emotional control across adolescence.
Subject(s)
Amygdala/growth & development , Cognition/physiology , Corpus Striatum/growth & development , Emotions/physiology , Magnetic Resonance Imaging/methods , Neural Pathways/growth & development , Adolescent , Child , Female , Humans , Image Processing, Computer-Assisted/methods , Individuality , Latent Class Analysis , Longitudinal Studies , Male , Organ SizeABSTRACT
Prioritizing memory for valuable information can promote adaptive behavior across the lifespan, but it is unclear how the neurocognitive mechanisms that enable the selective acquisition of useful knowledge develop. Here, using a novel task coupled with functional magnetic resonance imaging, we examined how children, adolescents, and adults (N = 90) learn from experience what information is likely to be rewarding, and modulate encoding and retrieval processes accordingly. We found that the ability to use learned value signals to selectively enhance memory for useful information strengthened throughout childhood and into adolescence. Encoding and retrieval of high- vs. low-value information was associated with increased activation in striatal and prefrontal regions implicated in value processing and cognitive control. Age-related increases in value-based lateral prefrontal cortex modulation mediated the relation between age and memory selectivity. Our findings demonstrate that developmental increases in the strategic engagement of the prefrontal cortex support the emergence of adaptive memory.
Subject(s)
Adolescent Development , Association Learning , Child Development , Cognition , Memory , Neural Pathways/growth & development , Prefrontal Cortex/growth & development , Adolescent , Adult , Age Factors , Brain Mapping , Child , Female , Humans , Magnetic Resonance Imaging , Male , Neural Pathways/diagnostic imaging , Neuropsychological Tests , Prefrontal Cortex/diagnostic imaging , Young AdultABSTRACT
The zebra finch (Taeniopygia guttata) is a socially monogamous and colonial opportunistic breeder with pronounced sexual differences in singing and plumage coloration. Its natural history has led to it becoming a model species for research into sex differences in vocal communication, as well as behavioral, neural and genomic studies of imitative auditory learning. As scientists tap into the genetic and behavioral diversity of both wild and captive lineages, the zebra finch will continue to inform research into culture, learning, and social bonding, as well as adaptability to a changing climate.
Subject(s)
Finches , Neural Pathways , Vocalization, Animal , Animals , Biological Evolution , Female , Finches/genetics , Finches/growth & development , Finches/physiology , Genome/genetics , Genomics , Learning , Male , Neural Pathways/growth & development , Neural Pathways/physiology , Sex Characteristics , Social BehaviorABSTRACT
Individual variability exists in both brain function and behavioral performance. However, changes in individual variability in brain functional connectivity and capability across adult development and aging have not yet been clearly examined. Based on resting-state functional magnetic resonance imaging data from a large cohort of participants (543 adults, aged 18-88 years), brain functional connectivity was analyzed to characterize the spatial distribution and differences in individual variability across the adult lifespan. Results showed high individual variability in the association cortex over the adult lifespan, whereas individual variability in the primary cortex was comparably lower in the initial stage but increased with age. Individual variability was also negatively correlated with the strength/number of short-, medium-, and long-range functional connections in the brain, with long-range connections playing a more critical role in increasing global individual variability in the aging brain. More importantly, in regard to specific brain regions, individual variability in the motor cortex was significantly correlated with differences in motor capability. Overall, we identified specific patterns of individual variability in brain functional structure during the adult lifespan and demonstrated that functional variability in the brain can reflect behavioral performance. These findings advance our understanding of the underlying principles of the aging brain across the adult lifespan and suggest how to characterize degenerating behavioral capability using imaging biomarkers.
Subject(s)
Nerve Net/growth & development , Nerve Net/physiology , Neural Pathways/growth & development , Neural Pathways/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Aging , Brain Mapping , Databases, Factual , Female , Humans , Individuality , Longevity , Magnetic Resonance Imaging , Male , Middle Aged , Motor Cortex/diagnostic imaging , Motor Cortex/growth & development , Motor Cortex/physiology , Nerve Net/diagnostic imaging , Neural Pathways/diagnostic imaging , Psychomotor Performance/physiology , Young AdultABSTRACT
Adolescence is a critical time for the continued maturation of brain networks. Here, we assessed structural connectome development in a large longitudinal sample ranging from childhood to young adulthood. By projecting high-dimensional connectomes into compact manifold spaces, we identified a marked expansion of structural connectomes, with strongest effects in transmodal regions during adolescence. Findings reflected increased within-module connectivity together with increased segregation, indicating increasing differentiation of higher-order association networks from the rest of the brain. Projection of subcortico-cortical connectivity patterns into these manifolds showed parallel alterations in pathways centered on the caudate and thalamus. Connectome findings were contextualized via spatial transcriptome association analysis, highlighting genes enriched in cortex, thalamus, and striatum. Statistical learning of cortical and subcortical manifold features at baseline and their maturational change predicted measures of intelligence at follow-up. Our findings demonstrate that connectome manifold learning can bridge the conceptual and empirical gaps between macroscale network reconfigurations, microscale processes, and cognitive outcomes in adolescent development.
Subject(s)
Adolescent Behavior , Adolescent Development , Brain/growth & development , Connectome , Neural Pathways/growth & development , Neurogenesis , Adolescent , Adult , Age Factors , Brain/diagnostic imaging , Brain/metabolism , Cognition , Female , Gene Expression Profiling , Gene Expression Regulation, Developmental , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Models, Neurological , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neural Pathways/diagnostic imaging , Neural Pathways/metabolism , Transcriptome , Young AdultABSTRACT
With the increase of life span, normal aging and age-related memory decline are affecting an increasing number of people; however, many aspects of these processes are still not fully understood. Although vertebrate models have provided considerable insights into the molecular and electrophysiological changes associated with brain aging, invertebrates, including the widely recognized molluscan model organism, the great pond snail (Lymnaea stagnalis), have proven to be extremely useful for studying mechanisms of aging at the level of identified individual neurons and well-defined circuits. Its numerically simpler nervous system, well-characterized life cycle, and relatively long life span make it an ideal organism to study age-related changes in the nervous system. Here, we provide an overview of age-related studies on L. stagnalis and showcase this species as a contemporary choice for modeling the molecular, cellular, circuit, and behavioral mechanisms of aging and age-related memory impairment.
Subject(s)
Aging/physiology , Disease Models, Animal , Lymnaea/growth & development , Memory Disorders/physiopathology , Age Factors , Animals , Epigenesis, Genetic/genetics , Lymnaea/genetics , Lymnaea/physiology , Neural Pathways/growth & development , Neural Pathways/physiology , Neurons/physiologyABSTRACT
The presence of heterogeneity/subgroups in infants and older populations against single-domain brain or behavioral measures has been previously characterized. However, few attempts have been made to explore heterogeneity at the brain-behavior relationship level. Such a hypothesis posits that different subgroups of infants may possess qualitatively different brain-behavior relationships that could ultimately contribute to divergent developmental outcomes even with relatively similar brain phenotypes. In this study, we aimed to explore such relationship-level heterogeneity and delineate the subgrouping structure of newborns with differential brain-behavior associations based on a typically developing sample of 81 infants with 3-week resting-state functional magnetic resonance imaging scans and 4-year intelligence quotient (IQ) measures. Our results not only confirmed the existence of relationship-level heterogeneity in newborns but also revealed divergent developmental outcomes associated with two subgroups showing similar brain functional connectivity but contrasting brain-behavior relationships. Importantly, further analyses unveiled an intriguing pattern that the subgroup with higher 4-year IQ outcomes possessed brain-behavior relationships that were congruent to their functional connectivity pattern in neonates while the subgroup with lower 4-year IQ not, providing potential explanations for the observed IQ differences. The characterization of heterogeneity at the brain-behavior relationship level may not only improve our understanding of the patterned intersubject variability during infancy but could also pave the way for future development of heterogeneity-inspired, personalized, subgroup-specific models for better prediction.
Subject(s)
Behavior/physiology , Brain/growth & development , Cognition/physiology , Neural Pathways/growth & development , Brain/physiology , Brain Mapping/methods , Female , Humans , Infant , Infant, Newborn , Intelligence Tests , Magnetic Resonance Imaging/methods , Male , Neural Pathways/physiologyABSTRACT
Prematurity disrupts brain development during a critical period of brain growth and organization and is known to be associated with an increased risk of neurodevelopmental impairments. Investigating whole-brain structural connectivity alterations accompanying preterm birth may provide a better comprehension of the neurobiological mechanisms related to the later neurocognitive deficits observed in this population. Using a connectome approach, we aimed to study the impact of prematurity on neonatal whole-brain structural network organization at term-equivalent age. In this cohort study, twenty-four very preterm infants at term-equivalent age (VPT-TEA) and fourteen full-term (FT) newborns underwent a brain MRI exam at term age, comprising T2-weighted imaging and diffusion MRI, used to reconstruct brain connectomes by applying probabilistic constrained spherical deconvolution whole-brain tractography. The topological properties of brain networks were quantified through a graph-theoretical approach. Furthermore, edge-wise connectivity strength was compared between groups. Overall, VPT-TEA infants' brain networks evidenced increased segregation and decreased integration capacity, revealed by an increased clustering coefficient, increased modularity, increased characteristic path length, decreased global efficiency and diminished rich-club coefficient. Furthermore, in comparison to FT, VPT-TEA infants had decreased connectivity strength in various cortico-cortical, cortico-subcortical and intra-subcortical networks, the majority of them being intra-hemispheric fronto-paralimbic and fronto-limbic. Inter-hemispheric connectivity was also decreased in VPT-TEA infants, namely through connections linking to the left precuneus or left dorsal cingulate gyrus - two regions that were found to be hubs in FT but not in VPT-TEA infants. Moreover, posterior regions from Default-Mode-Network (DMN), namely precuneus and posterior cingulate gyrus, had decreased structural connectivity in VPT-TEA group. Our finding that VPT-TEA infants' brain networks displayed increased modularity, weakened rich-club connectivity and diminished global efficiency compared to FT infants suggests a delayed transition from a local architecture, focused on short-range connections, to a more distributed architecture with efficient long-range connections in those infants. The disruption of connectivity in fronto-paralimbic/limbic and posterior DMN regions might underlie the behavioral and social cognition difficulties previously reported in the preterm population.
Subject(s)
Brain/diagnostic imaging , Connectome , Brain/growth & development , Brain/physiopathology , Case-Control Studies , Female , Functional Neuroimaging , Gestational Age , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/growth & development , Gyrus Cinguli/physiopathology , Humans , Infant, Newborn , Infant, Premature , Magnetic Resonance Imaging , Male , Neural Pathways/diagnostic imaging , Neural Pathways/growth & development , Neural Pathways/physiopathology , Parietal Lobe/diagnostic imaging , Parietal Lobe/growth & development , Parietal Lobe/physiopathology , Thalamus/diagnostic imaging , Thalamus/growth & development , Thalamus/physiopathologyABSTRACT
Disrupted-in-schizophrenia 1 (DISC1) gene represents an intracellular hub of developmental processes. When combined with early environmental stressors, such as maternal immune activation, but not in the absence of thereof, whole-brain DISC1 knock-down leads to memory and executive deficits as result of impaired prefrontal-hippocampal communication throughout development. While synaptic dysfunction in neonatal prefrontal cortex (PFC) has been recently identified as one source of abnormal long-range coupling, the contribution of hippocampus (HP) is still unknown. Here, we aim to fill this knowledge gap by combining in vivo electrophysiology and optogenetics with morphological and behavioral assessment of immune-challenged mice with DISC1 knock-down either in the whole brain (GE) or restricted to pyramidal neurons in hippocampal CA1 area (GHPE). We found abnormal network activity, sharp-waves, and neuronal firing in CA1 that complement the deficits in upper layer of PFC. Moreover, optogenetic activating CA1 pyramidal neurons fails to activate the prefrontal local circuits. These deficits that persist till prejuvenile age relate to dendrite sparsification and loss of spines of CA1 pyramidal neurons. As a long-term consequence, DISC1 knock-down in HP leads to poorer recognition memory at prejuvenile age. Thus, DISC1-controlled developmental processes in HP in immune-challenged mice are critical for circuit function and cognitive behavior.
Subject(s)
Cognition/physiology , Exploratory Behavior/physiology , Gene Knockdown Techniques/methods , Hippocampus/growth & development , Nerve Tissue Proteins/deficiency , Prefrontal Cortex/growth & development , Animals , Animals, Newborn , Female , Hippocampus/immunology , Male , Mice , Mice, Inbred C57BL , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/immunology , Neural Pathways/growth & development , Neural Pathways/immunology , Prefrontal Cortex/immunology , Pregnancy , Pyramidal Cells/physiologyABSTRACT
The brain undergoes a protracted, metabolically expensive maturation process from childhood to adulthood. Therefore, it is crucial to understand how network cost is distributed among different brain systems as the brain matures. To address this issue, here we examined developmental changes in wiring cost and brain network topology using resting-state functional magnetic resonance imaging (rsfMRI) data longitudinally collected in awake rats from the juvenile age to adulthood. We found that the wiring cost increased in the vast majority of cortical connections but decreased in most subcortico-subcortical connections. Importantly, the developmental increase in wiring cost was dominantly driven by long-range cortical, but not subcortical connections, which was consistent with more pronounced increase in network integration in the cortical network. These results collectively indicate that there is a non-uniform distribution of network cost as the brain matures, and network resource is dominantly consumed for the development of the cortex, but not subcortex from the juvenile age to adulthood.
Subject(s)
Brain/growth & development , Neural Pathways/growth & development , Amygdala/diagnostic imaging , Amygdala/growth & development , Animals , Brain/diagnostic imaging , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/growth & development , Corpus Striatum/diagnostic imaging , Corpus Striatum/growth & development , Functional Neuroimaging , Globus Pallidus/diagnostic imaging , Globus Pallidus/growth & development , Hippocampus/diagnostic imaging , Hippocampus/growth & development , Hypothalamus/diagnostic imaging , Hypothalamus/growth & development , Longitudinal Studies , Magnetic Resonance Imaging , Neural Pathways/diagnostic imaging , Rats , Rest , Sensorimotor Cortex/diagnostic imaging , Sensorimotor Cortex/growth & development , Thalamus/diagnostic imaging , Thalamus/growth & developmentABSTRACT
The human parenting brain network mediates caregiving behaviors. When exposed to the stimuli of their infants, compared with non-parents, both fathers and mothers exhibit distinct patterns of neural activation. As human males, relative to females, do not undergo robust physiological changes during pregnancy, when and how the paternal brain networks begin to form remains unclear. Thus, using functional MRI, we examined brain activation in response to infant-interaction videos in two groups, childless males and first-time expectant fathers during their partners' early pregnancy before remarkable changes in their partners' appearances commenced. Multivoxel pattern analysis revealed that expectant fathers' left anterior insula and inferior frontal gyrus showed incipient changes in response to parenthood during early pregnancy. Furthermore, these changes were associated with several paternal traits, such as a negative image toward parenting. Such external factors might influence the paternal brain's development during early pregnancy.
Subject(s)
Brain/diagnostic imaging , Fathers , Paternal Behavior/physiology , Adult , Anxiety/psychology , Brain/growth & development , Brain/physiology , Case-Control Studies , Depression/psychology , Female , Functional Neuroimaging , Humans , Japan , Magnetic Resonance Imaging , Male , Neural Pathways/diagnostic imaging , Neural Pathways/growth & development , Object Attachment , Parent-Child Relations , Parenting/psychology , Paternal Behavior/psychology , Pregnancy , Pregnancy Trimester, SecondABSTRACT
Importance: Maturation of white matter fiber systems subserves cognitive, behavioral, emotional, and motor development during adolescence. Hazardous drinking during this active neurodevelopmental period may alter the trajectory of white matter microstructural development, potentially increasing risk for developing alcohol-related dysfunction and alcohol use disorder in adulthood. Objective: To identify disrupted adolescent microstructural brain development linked to drinking onset and to assess whether the disruption is more pronounced in younger rather than older adolescents. Design, Setting, and Participants: This case-control study, conducted from January 13, 2013, to January 15, 2019, consisted of an analysis of 451 participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence cohort. Participants were aged 12 to 21 years at baseline and had at least 2 usable magnetic resonance diffusion tensor imaging (DTI) scans and up to 5 examination visits spanning 4 years. Participants with a youth-adjusted Cahalan score of 0 were labeled as no-to-low drinkers; those with a score of greater than 1 for at least 2 consecutive visits were labeled as heavy drinkers. Exploratory analysis was conducted between no-to-low and heavy drinkers. A between-group analysis was conducted between age- and sex-matched youths, and a within-participant analysis was performed before and after drinking. Exposures: Self-reported alcohol consumption in the past year summarized by categorical drinking levels. Main Outcomes and Measures: Diffusion tensor imaging measurement of fractional anisotropy (FA) in the whole brain and fiber systems quantifying the developmental change of each participant as a slope. Results: Analysis of whole-brain FA of 451 adolescents included 291 (64.5%) no-to-low drinkers and 160 (35.5%) heavy drinkers who indicated the potential for a deleterious association of alcohol with microstructural development. Among the no-to-low drinkers, 142 (48.4%) were boys with mean (SD) age of 16.5 (2.2) years and 149 (51.2%) were girls with mean (SD) age of 16.5 (2.1) years and 192 (66.0%) were White participants. Among the heavy drinkers, 86 (53.8%) were boys with mean (SD) age of 20.1 (1.5) years and 74 (46.3%) were girls with mean (SD) age of 20.5 (2.0) years and 142 (88.8%) were White participants. A group analysis revealed FA reduction in heavy-drinking youth compared with age- and sex-matched controls (t154 = -2.7, P = .008). The slope of this reduction correlated with log of days of drinking since the baseline visit (r156 = -0.21, 2-tailed P = .008). A within-participant analysis contrasting developmental trajectories of youths before and after they initiated heavy drinking supported the prediction that drinking onset was associated with and potentially preceded disrupted white matter integrity. Age-alcohol interactions (t152 = 3.0, P = .004) observed for the FA slopes indicated that the alcohol-associated disruption was greater in younger than older adolescents and was most pronounced in the genu and body of the corpus callosum, regions known to continue developing throughout adolescence. Conclusions and Relevance: This case-control study of adolescents found a deleterious association of alcohol use with white matter microstructural integrity. These findings support the concept of heightened vulnerability to environmental agents, including alcohol, associated with attenuated development of major white matter tracts in early adolescence.
Subject(s)
Adolescent Development , Alcoholism , Frontal Lobe , Underage Drinking , White Matter , Adolescent , Adolescent Development/physiology , Adult , Alcoholism/complications , Alcoholism/diagnostic imaging , Alcoholism/pathology , Anisotropy , Case-Control Studies , Child , Diffusion Tensor Imaging , Female , Frontal Lobe/diagnostic imaging , Frontal Lobe/growth & development , Frontal Lobe/pathology , Humans , Longitudinal Studies , Male , Neural Pathways/diagnostic imaging , Neural Pathways/growth & development , Neural Pathways/pathology , White Matter/diagnostic imaging , White Matter/growth & development , White Matter/pathology , Young AdultABSTRACT
In complex everyday environments, action selection is critical for optimal goal-directed behavior. This refers to the process of choosing a proper action from the range of possible alternatives. The neural mechanisms underlying action selection and how these are affected by normal aging remain to be elucidated. In the present cross-sectional study, we studied processes of effector selection during a multilimb reaction time task in a lifespan sample of healthy human adults (N = 89; 20-75 years; 48 males, 41 females). Participants were instructed to react as quickly and accurately as possible to visually cued stimuli representing single-limb or combined upper and/or lower limb motions. Diffusion MRI was used to study structural connectivity between prefrontal and striatal regions as critical nodes for action selection. Behavioral findings revealed that increasing age was associated with slowing of action selection performance. At the neural level, aging had a negative impact on prefronto-striatal connectivity. Importantly, mediation analyses revealed that the negative association between action selection performance and age was mediated by prefronto-striatal connectivity, specifically the connections between left rostral medial frontal gyrus and left nucleus accumbens as well as right frontal pole and left caudate. These results highlight the potential role of prefronto-striatal white matter decline in poorer action selection performance of older adults.SIGNIFICANCE STATEMENT As a result of enhanced life expectancy, researchers have devoted increasing attention to the study of age-related alterations in cognitive and motor functions. Here we study associations between brain structure and behavior to reveal the impact of central neural white matter changes as a function of normal aging on action selection performance. We demonstrate the critical role of a reduction in prefronto-striatal structural connectivity in accounting for action selection performance deficits in healthy older adults. Preserving this cortico-subcortical pathway may be critical for behavioral flexibility and functional independence in older age.
Subject(s)
Neostriatum/anatomy & histology , Neostriatum/physiology , Neural Pathways/anatomy & histology , Neural Pathways/physiology , Prefrontal Cortex/anatomy & histology , Prefrontal Cortex/physiology , Adult , Aged , Aging/physiology , Caudate Nucleus/physiology , Cross-Sectional Studies , Cues , Decision Making , Diffusion Magnetic Resonance Imaging , Female , Humans , Male , Middle Aged , Movement/physiology , Neostriatum/growth & development , Neural Pathways/growth & development , Nucleus Accumbens/physiology , Photic Stimulation , Prefrontal Cortex/growth & development , Reaction Time/physiology , Young AdultABSTRACT
It is currently unclear whether early life stress (ELS) affects males and females differently. However, a growing body of work has shown that sex moderates responses to stress and injury, with important insights into sex-specific mechanisms provided by work in rodents. Unfortunately, most of the ELS studies in rodents were conducted only in males, a bias that is particularly notable in translational work that has used human imaging. Here we examine the effects of unpredictable postnatal stress (UPS), a mouse model of complex ELS, using high resolution diffusion magnetic resonance imaging. We show that UPS induces several neuroanatomical alterations that were seen in both sexes and resemble those reported in humans. In contrast, exposure to UPS induced fronto-limbic hyper-connectivity in males, but either no change or hypoconnectivity in females. Moderated-mediation analysis found that these sex-specific changes are likely to alter contextual freezing behavior in males but not in females.