Development of brain functional connectivity and its relation to infant sustained attention in the first year of life

The study of brain functional connectivity is crucial to understanding the neural mechanisms underlying the improved behavioral performance and amplified ERP responses observed during infant sustained attention. Previous investigations on the development of functional brain connectivity during infancy are primarily confined to the use of functional and structural MRI techniques. The current study examined the relation between infant sustained attention and brain functional connectivity and their development during infancy with high‐density EEG recordings. Fifty‐nine infants were tested at 6 (N = 15), 8 (N =14), 10 (N = 17), and 12 (N = 13) months. Infant sustained attention was defined by measuring infant heart rate changes during infants’ looking. Functional connectivity was estimated from the electrodes on the scalp and with reconstructed cortical source activities in brain regions. It was found that infant sustained attention was accompanied by attenuated functional connectivity in the dorsal attention and default mode networks in the alpha band. Graph theory analyses showed that there was an increase in path length and a decrease in clustering coefficient during infant sustained attention. The functional connectivity within the visual, somatosensory, dorsal attention, and ventral attention networks and graph theory measures of path length and clustering coefficient were found to increase with age. These findings suggest that infant sustained attention is accompanied by distinct patterns of brain functional connectivity. The current findings also suggest the rapid development of functional connectivity in brain networks during infancy.     

Posterior superior temporal cortex connectivity is related to social communication in toddlers

The second year of life is a time when social communication skills typically develop, but this growth may be slower in toddlers with language delay. In the current study, we examined how brain functional connectivity is related to social communication abilities in a sample of 12-24 month-old toddlers including those with typical development (TD) and those with language delays (LD). We used an a-priori, seed-based approach to identify regions forming a functional network with the left posterior superior temporal cortex (LpSTC), a region associated with language and social communication in older children and adults. Social communication and language abilities were assessed using the Communication and Symbolic Behavior Scales (CSBS) and Mullen Scales of Early Learning. We found a significant association between concurrent CSBS scores and functional connectivity between the LpSTC and the right posterior superior temporal cortex (RpSTC), with greater connectivity between these regions associated with better social communication abilities. However, functional connectivity was not related to rate of change or language outcomes at 36 months of age. These data suggest an early marker of low communication abilities may be decreased connectivity between the left and right pSTC. Future longitudinal studies should test whether this neurobiological feature is predictive of later social or communication impairments.     

Creative thinking and brain network development in schoolchildren

Fostering creative minds has always been a premise to ensure adaptation to new challenges of human civilization. While some alternative educational settings (i.e., Montessori) were shown to nurture creative skills, it is unknown how they impact underlying brain mechanisms across the school years. This study assessed creative thinking and resting-state functional connectivity via fMRI in 75 children (4–18 y.o.) enrolled either in Montessori or traditional schools. We found that pedagogy significantly influenced creative performance and underlying brain networks. Replicating past work, Montessori-schooled children showed higher scores on creative thinking tests. Using static functional connectivity analysis, we found that Montessori-schooled children showed decreased within-network functional connectivity of the salience network. Moreover, using dynamic functional connectivity, we found that traditionally-schooled children spent more time in a brain state characterized by high intra-default mode network connectivity. These findings suggest that pedagogy may influence brain networks relevant to creative thinking—particularly the default and salience networks. Further research is needed, like a longitudinal study, to verify these results given the implications for educational practitioners. A video abstract of this article can be viewed at https://www.youtube.com/watch?v=xWV_5o8wB5g .

Research Highlights

• Most executive jobs are prospected to be obsolete within several decades, so creative skills are seen as essential for the near future.
• School experience has been shown to play a role in creativity development, however, the underlying brain mechanisms remained under-investigated yet.
• Seventy-five 4–18 years-old children, from Montessori or traditional schools, performed a creativity task at the behavioral level, and a 6-min resting-state MR scan.
• We uniquely report preliminary evidence for the impact of pedagogy on functional brain networks.

     

Electrophysiological measures of resting state functional connectivity and their relationship with working memory capacity in childhood

Functional connectivity is the statistical association of neuronal activity time courses across distinct brain regions, supporting specific cognitive processes. This coordination of activity is likely to be highly important for complex aspects of cognition, such as the communication of fluctuating task goals from higher‐order control regions to lower‐order, functionally specific regions. Some of these functional connections are identifiable even when relevant cognitive tasks are not being performed (i.e. at rest). We used magnetoencephalographic recordings projected into source space to demonstrate that resting state networks in childhood have electrophysiological underpinnings that are evident in the spontaneous fluctuations of oscillatory brain activity. Using the temporal structure of these oscillatory patterns we were able to identify a number of functional resting state networks analogous to those reported in the adult literature. In a second analysis we fused this dynamic temporal information with the spatial information from a functional magnetic resonance imaging analysis of functional connectivity, to demonstrate that inter‐subject variability in these electrophysiological measures of functional connectivity is correlated with individual differences in cognitive ability: the strength of connectivity between a fronto‐parietal network and lower‐level processing areas in inferior temporal cortex was associated with spatial working memory capacity, as measured outside the scanner with educationally relevant standardized assessments. This study represents the first exploration of the electrophysiological mechanisms underpinning resting state functional connectivity in source space in childhood, and the extent to which the strength of particular connections is associated with cognitive ability.     

Evolution of the neural language network

The evolution of language correlates with distinct changes in the primate brain. The present article compares language-related brain regions and their white matter connectivity in the developing and mature human brain with the respective structures in the nonhuman primate brain. We will see that the functional specificity of the posterior portion of Broca’s area (Brodmann area [BA 44]) and its dorsal fiber connection to the temporal cortex, shown to support the processing of structural hierarchy in humans, makes a crucial neural difference between the species. This neural circuit may thus be fundamental for the human syntactic capacity as the core of language.     

语言功能偏侧化及其与利手、功能连接的关系

对大脑语言功能偏侧化的探索起始于早期对脑损伤病人的研究。现代脑影像学研究发现, 语言功能偏侧化涉及额叶、颞叶、扣带回、梭状回和辅助运动区等脑区。语言偏侧化与利手和静息态功能连接之间的关系表现为：右利手的语言优势位于左半球, 而左利手的则分布在左半球、右半球或两个半球; 语言功能偏侧化与利手系数、静息态半球内功能连接之间具有正相关关系, 与半球间功能连接呈负相关, 并且语言功能偏侧化与静息态功能连接之间的关系在左右利手个体之间存在差异。总之, 大脑语言功能偏侧化、利手和静息态功能连接三者之间存在相互影响, 基于脑连接和遗传机制的研究将有望揭示出其底层的神经生理机制。     

Strength of default mode resting-state connectivity relates to white matter integrity in children

A default mode network of brain regions is known to demonstrate coordinated activity during the resting state. While the default mode network is well characterized in adults, few investigations have focused upon its development. We scanned 9-13-year-old children with diffusion tensor imaging and resting-state functional magnetic resonance imaging. We identified resting-state networks using Independent Component Analysis and tested whether the functional connectivity between the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) depends upon the maturation of the underlying cingulum white matter tract. To determine the generalizability of this relationship, we also tested whether functional connectivity depends on white matter maturity between bilateral lateral prefrontal cortex (lateral PFC) within the executive control network. We found a positive relationship between mPFC-PCC connectivity and fractional anisotropy of the cingulum bundle; this positive relationship was moderated by the age of the subjects such that it was stronger in older children. By contrast, no such structure-function relationship emerged between right and left lateral PFC. However, functional and structural connectivity of this tract related positively with cognitive speed, fluency, and set-switching neuropsychological measures.     

Effects of Aging on Functional Connectivity of the Amygdala for Subsequent Memory of Negative Pictures: A Network Analysis of Functional Magnetic Resonance Imaging Data

ABSTRACT— Aging is associated with preserved enhancement of emotional memory, as well as with age-related reductions in memory for negative stimuli, but the neural networks underlying such alterations are not clear. We used a subsequent-memory paradigm to identify brain activity predicting enhanced emotional memory in young and older adults. Activity in the amygdala predicted enhanced emotional memory, with subsequent-memory activity greater for negative stimuli than for neutral stimuli, across age groups, a finding consistent with an overall enhancement of emotional memory. However, older adults recruited greater activity in anterior regions and less activity in posterior regions in general for negative stimuli that were subsequently remembered. Functional connectivity of the amygdala with the rest of the brain was consistent with age-related reductions in memory for negative stimuli: Older adults showed decreased functional connectivity between the amygdala and the hippocampus, but increased functional connectivity between the amygdala and dorsolateral prefrontal cortices. These findings suggest that age-related differences in the enhancement of emotional memory might reflect decreased connectivity between the amygdala and typical subsequent-memory regions, as well as the engagement of regulatory processes that inhibit emotional responses.     

Risk seeking for losses modulates the functional connectivity of the default mode and left frontoparietal networks in young males

Value-based decision making (VBDM) is a principle that states that humans and other species adapt their behavior according to the dynamic subjective values of the chosen or unchosen options. The neural bases of this process have been extensively investigated using task-based fMRI and lesion studies. However, the growing field of resting-state functional connectivity (RSFC) may shed light on the organization and function of brain connections across different decision-making domains. With this aim, we used independent component analysis to study the brain network dynamics in a large cohort of young males (N = 145) and the relationship of these dynamics with VBDM. Participants completed a battery of behavioral tests that evaluated delay aversion, risk seeking for losses, risk aversion for gains, and loss aversion, followed by an RSFC scan session. We identified a set of large-scale brain networks and conducted our analysis only on the default mode network (DMN) and networks comprising cognitive control, appetitive-driven, and reward-processing regions. Higher risk seeking for losses was associated with increased connectivity between medial temporal regions, frontal regions, and the DMN. Higher risk seeking for losses was also associated with increased coupling between the left frontoparietal network and occipital cortices. These associations illustrate the participation of brain regions involved in prospective thinking, affective decision making, and visual processing in participants who are greater risk-seekers, and they demonstrate the sensitivity of RSFC to detect brain connectivity differences associated with distinct VBDM parameters.     

反刍思维的脑功能网络机制

反刍思维是指个体在经历了消极生活事件后不由自主地反复思考该事件的产生原因、经过和结果, 表现出负性自我参照加工、消极情绪性以及持续性的特点。采用脑功能网络分析方法, 研究者发现反刍思维的上述三个特点分别与默认网络内部的异常活动模式、突显网络功能连接的改变以及注意相关网络之间的异常耦合有关。未来研究应进一步明确反刍思维与相关脑网络活动之间的因果关系, 探究反刍思维脑功能网络的结构基础, 同时也应关注反刍思维及其脑网络的老龄化特征, 并致力于探索有效干预反刍思维的神经调控技术。     

Two distinct neural networks functionally connected to the human hippocampus during pattern separation tasks

Previous studies from the human, rodent, and computational research have identified the hippocampus as a core structure mediating pattern separation. However, these investigations have generally focused on the role of distinct subregions of the hippocampus. Less well-understood is how the human hippocampus interacts with other brain regions to support pattern separation. The purpose of this study was to identify the functional networks connected to the hippocampus during delayed matching-to-sample pattern separation tasks promoting either spatial or temporal interference. Results revealed that the hippocampus was functionally connected to two distinct networks. The first network was characterized by correlated activation with the hippocampus primarily in bilateral temporal regions. This network was differentially related to spatial and temporal conditions, suggesting hippocampal connectivity to this network is modulated by interference type. A secondary network was characterized by correlations between the left hippocampus and several other sparsely distributed brain regions, including bilateral cerebellum and frontal and temporal cortices. This network was not modulated by interference type, suggesting that it may be a domain-general pattern separation network. We suggest that the hippocampus may play a role in integrating information from these networks to support performance on pattern separation tasks.     

Development of the Brain’s Functional Network Architecture

A full understanding of the development of the brain’s functional network architecture requires not only an understanding of developmental changes in neural processing in individual brain regions but also an understanding of changes in inter-regional interactions. Resting state functional connectivity MRI (rs-fcMRI) is increasingly being used to study functional interactions between brain regions in both adults and children. We briefly review methods used to study functional interactions and networks with rs-fcMRI and how these methods have been used to define developmental changes in network functional connectivity. The developmental rs-fcMRI studies to date have found two general properties. First, regional interactions change from being predominately anatomically local in children to interactions spanning longer cortical distances in young adults. Second, this developmental change in functional connectivity occurs, in general, via mechanisms of segregation of local regions and integration of distant regions into disparate subnetworks.     

Anxious personality and functional efficiency of the insular-opercular network: A graph-analytic approach to resting-state fMRI

The brain is an intricate network, not only structurally but also functionally. On the functional level, connectivity in the brain is organized in separable yet interacting networks that support information processing by maintaining a ready state, even in the absence of external stimulation. It has been hypothesized that an insular-opercular network underlies the processing of emotionally salient information and that individual differences in functional connectivity within this network correspond to individual differences in trait anxiety. Here, we tested this relationship by applying graph analysis to multiple regions of interests delineating the insular-opercular network to estimate the characteristic path length that quantifies the overall information exchange efficiency within a given network. We found that people scoring high on the anxiety-related temperament-dimension harm avoidance had decreased insular-opercular network efficiency in the resting state, as indicated by a higher characteristic path length. Furthermore, people scoring high on harm avoidance showed generally reduced functional connectivity between brain regions; the relationship between harm avoidance and insular-opercular network efficiency remained significant when controlling for mean connectivity within this network. No such results were found for other resting-state networks. The results provide insights into how personality is organized in the human brain and point toward clinically relevant endophenotypes for affective and mood disorders.     

Cortical plasticity associated with stuttering therapy

Neuroimaging studies have indicated that persistent developmental stuttering (PDS) may be associated both with an abnormality in white matter of left-hemispheric speech areas and a right-hemispheric hyperactivity. The latter may compensate for the deficient structural connectivity in the left hemisphere. To investigate the effects of stuttering therapy on brain activity nine male adults with PDS underwent functional magnetic resonance imaging (fMRI) before and within 12 weeks after fluency shaping therapy. Brain response differences during overt sentence reading before and after therapy were assessed by utilizing random effects analyses. After therapy, a more widespread activation was observed in frontal speech and language regions and temporal areas of both hemispheres, particularly and more pronounced on the left side. Interestingly, distinct posttreatment left-sided activation increases were located directly adjacent to a recently detected area of white matter anomaly [M. Sommer, M.A. Koch, W. Paulus, C. Weiller, C. Buchel (2002). Disconnection of speech-relevant brain areas in persistent developmental stuttering. The Lancet, 360, 380-383] suggesting that fluency shaping techniques reorganize neuronal communication between left-sided speech motor planning, motor execution, and temporal areas. Hence, a therapeutic mechanism can be assumed to remodel brain circuitry close to the source of the dysfunction instead of reinforcing compensation via homologous contralateral brain networks. EDUCATIONAL OBJECTIVES: The reader will learn about and be able to: (1) describe brain activation changes detected shortly after fluency-shaping therapy; (2) identify left-hemispheric regions where a (re)functionalization after fluency-shaping therapy seems to occur adjacent to a recently described abnormal white matter region in PDS subjects; and (3) discuss how an effective cerebral compensation mechanism for stuttering could work.     

A rigorous approach for testing the constructionist hypotheses of brain function

Although the target article provides strong evidence against the locationist view, evidence for the constructionist view is inconclusive, because co-activation of brain regions does not necessarily imply connectivity between them. We propose a rigorous approach wherein connectivity between co-activated regions is first modeled using exploratory Granger causality, and then confirmed using dynamic causal modeling or Bayesian modeling.     

Strengthening Connections: Functional Connectivity and Brain Plasticity

The ascendancy of functional neuroimaging has facilitated the addition of network-based approaches to the neuropsychologist’s toolbox for evaluating the sequelae of brain insult. In particular, intrinsic functional connectivity (iFC) mapping of resting state fMRI (R-fMRI) data constitutes an ideal approach to measuring macro-scale networks in the human brain. Beyond the value of iFC mapping for charting how the functional topography of the brain is altered by insult and injury, iFC analyses can provide insights into experience-dependent plasticity at the macro level of large-scale functional networks. Such insights are foundational to the design of training and remediation interventions that will best facilitate recovery of function. In this review, we consider what is currently known about the origin and function of iFC in the brain, and how this knowledge is informative in neuropsychological settings. We then summarize studies that have examined experience-driven plasticity of iFC in healthy control participants, and frame these findings in terms of a schema that may aid in the interpretation of results and the generation of hypotheses for rehabilitative studies. Finally, we outline some caveats to the R-fMRI approach, as well as some current developments that are likely to bolster the utility of the iFC paradigm for neuropsychology.     

Brain hyper‐connectivity and operation‐specific deficits during arithmetic problem solving in children with developmental dyscalculia

Developmental dyscalculia (DD) is marked by specific deficits in processing numerical and mathematical information despite normal intelligence (IQ) and reading ability. We examined how brain circuits used by young children with DD to solve simple addition and subtraction problems differ from those used by typically developing (TD) children who were matched on age, IQ, reading ability, and working memory. Children with DD were slower and less accurate during problem solving than TD children, and were especially impaired on their ability to solve subtraction problems. Children with DD showed significantly greater activity in multiple parietal, occipito‐temporal and prefrontal cortex regions while solving addition and subtraction problems. Despite poorer performance during subtraction, children with DD showed greater activity in multiple intra‐parietal sulcus (IPS) and superior parietal lobule subdivisions in the dorsal posterior parietal cortex as well as fusiform gyrus in the ventral occipito‐temporal cortex. Critically, effective connectivity analyses revealed hyper‐connectivity, rather than reduced connectivity, between the IPS and multiple brain systems including the lateral fronto‐parietal and default mode networks in children with DD during both addition and subtraction. These findings suggest the IPS and its functional circuits are a major locus of dysfunction during both addition and subtraction problem solving in DD, and that inappropriate task modulation and hyper‐connectivity, rather than under‐engagement and under‐connectivity, are the neural mechanisms underlying problem solving difficulties in children with DD. We discuss our findings in the broader context of multiple levels of analysis and performance issues inherent in neuroimaging studies of typical and atypical development.     

Unraveling Brain Functional Connectivity of encoding and retrieval in the context of education

Human memory is an enigmatic component of cognition which many researchers have attempted to comprehend. Accumulating studies on functional connectivity see brain as a complex dynamic unit with positively and negatively correlated networks in perfect coherence during a task. We aimed to examine coherence of network connectivity during visual memory encoding and retrieval in the context of education. School Educated (SE) and College Educated (CE) healthy volunteers (n = 60) were recruited and assessed for visual encoding and retrieval. Functional connectivity using seed to voxel based connectivity analysis of the posterior cingulate cortex (PCC) was evaluated. We noticed that there were reciprocal dynamic changes in both dorsolateral prefrontal cortex (DLPFC) region and PCC regions during working memory encoding and retrieval. In agreement with the previous studies, there were more positively correlated regions during retrieval compared to encoding. The default mode network (DMN) networks showed greater negative correlations during more attentive task of visual encoding. In tune with the recent studies on cognitive reserve we also found that number of years of education was a significant factor influencing working memory connectivity. SE had higher positive correlation to DLPFC region and lower negative correlation to DMN in comparison with CE during encoding and retrieval.     

Task-related functional connectivity of the caudate mediates the association between trait mindfulness and implicit learning in older adults

Accumulating evidence shows a positive relationship between mindfulness and explicit cognitive functioning, i.e., that which occurs with conscious intent and awareness. However, recent evidence suggests that there may be a negative relationship between mindfulness and implicit types of learning, or those that occur without conscious awareness or intent. Here we examined the neural mechanisms underlying the recently reported negative relationship between dispositional mindfulness and implicit probabilistic sequence learning in both younger and older adults. We tested the hypothesis that the relationship is mediated by communication, or functional connectivity, of brain regions once traditionally considered to be central to dissociable learning systems: the caudate, medial temporal lobe (MTL), and prefrontal cortex (PFC). We first replicated the negative relationship between mindfulness and implicit learning in a sample of healthy older adults (60–90 years old) who completed three event-related runs of an implicit sequence learning task. Then, using a seed-based connectivity approach, we identified task-related connectivity associated with individual differences in both learning and mindfulness. The main finding was that caudate-MTL connectivity (bilaterally) was positively correlated with learning and negatively correlated with mindfulness. Further, the strength of task-related connectivity between these regions mediated the negative relationship between mindfulness and learning. This pattern of results was limited to the older adults. Thus, at least in healthy older adults, the functional communication between two interactive learning-relevant systems can account for the relationship between mindfulness and implicit probabilistic sequence learning.     

The study of autism as a distributed disorder

Past autism research has often been dedicated to tracing the causes of the disorder to a localized neurological abnormality, a single functional network, or a single cognitive-behavioral domain. In this review, I argue that autism is a "distributed disorder" on various levels of study (genetic, neuroanatomical, neurofunctional, behavioral). "Localizing" models are therefore not promising. The large array of potential genetic risk factors suggests that multiple (or all) emerging functional brain networks are affected during early development. This is supported by widespread growth abnormalities throughout the brain. Interactions during development between affected functional networks and atypical experiential effects (associated with atypical behavior) in children with autism further complicate the neurological bases of the disorder, resulting in an "exponentially distributed" profile. Promising approaches to a better characterization of neural endophenotypes in autism are provided by techniques investigating white matter and connectivity, such as MR spectroscopy, diffusion-tensor imaging (DTI), and functional connectivity MRI. According to a recent hypothesis, the autistic brain is generally characterized by "underconnectivity." However, not all findings are consistent with this view. The concepts and methodology of functional connectivity need to be refined and results need to be corroborated by anatomical studies (such as DTI tractography) before definitive conclusions can be drawn.