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Maternal psychological stress during pregnancy is a common risk factor for psychiatric disorders in offspring, but little is known about how heterogeneity of stress trajectories during pregnancy affect brain systems and behavioral phenotypes in infancy. This study was designed to address this gap in knowledge. Maternal anxiety, stress, and depression were assessed at multiple time points during pregnancy in two independent low-risk mother-infant cohorts (N=115 and N=2,156). Trajectories in maternal stress levels in relation to infant negative affect were examined in both cohorts. Neonatal amygdala resting-state functional connectivity MRI was examined in a subset of one cohort (N=60) to explore the potential relationship between maternal stress trajectories and brain systems in infants relevant to negative affect. Four distinct trajectory clusters, characterized by changing patterns of stress over time, and two magnitude clusters, characterized by severity of stress, were identified in the original mother-infant cohort (N=115). The magnitude clusters were not associated with infant outcomes. The trajectory characterized by increasing stress in late pregnancy was associated with blunted development of infant negative affect. This relationship was replicated in the second, larger cohort (N=2,156). In addition, the trajectories that included increasing or peak maternal stress in late pregnancy were related to stronger neonatal amygdala functional connectivity to the anterior insula and the ventromedial prefrontal cortex in the exploratory analysis. The trajectory of maternal stress appears to be important for offspring brain and behavioral development. Understanding heterogeneity in trajectories of maternal stress and their influence on infant brain and behavioral development is critical to developing targeted interventions. [ABSTRACT FROM AUTHOR]

Task-based functional MRI (fMRI) has greatly improved understanding of brain functioning, enabling the identification of brain areas associated with specific cognitive operations. Traditional analyses are limited to associating activation patterns in particular regions with specific cognitive operation, largely ignoring regional cross-talk or dynamic connectivity, which we propose is crucial for characterization of brain function in the context of task fMRI. We use connectotyping, which efficiently models functional brain connectivity to reveal the progression of temporal brain connectivity patterns in task fMRI. Connectotyping was employed on data from twenty-four participants (12 male, mean age 24.8 years, 2.57 std. dev) who performed a widely spaced event-related fMRI word vs. pseudoword decision task, where stimuli were presented every 20 s. After filtering for movement, we ended up with 15 participants that completed each trial and had enough usable data for our analyses. Connectivity matrices were calculated per participant across time for each stimuli type. A Repeated Measures ANOVA applied on the connectotypes was used to characterize differences across time for words and pseudowords. Our group level analyses found significantly different dynamic connectivity patterns during word vs. pseudoword processing between the Fronto-Parietal and Cingulo-Parietal Systems, areas involved in cognitive task control, memory retrieval, and semantic processing. Our findings support the presence of dynamic changes in functional connectivity during task execution and that such changes can be characterized using connectotyping but not with traditional Pearson's correlations. [ABSTRACT FROM AUTHOR]

Nutrition during the first years of life has a significant impact on brain development. This study characterized differences in brain maturation from birth to 6 months of life in infant macaques fed formulas differing in content of lutein, β-carotene, and other carotenoids using Magnetic Resonance Imaging to measure functional connectivity. We observed differences in functional connectivity based on the interaction of diet, age and brain networks. Post hoc analysis revealed significant diet-specific differences between insular-opercular and somatomotor networks at 2 months of age, dorsal attention and somatomotor at 4 months of age, and within somatomotor and between somatomotor-visual and auditory-dorsal attention networks at 6 months of age. Overall, we found a larger divergence in connectivity from the breastfeeding group in infant macaques fed formula containing no supplemental carotenoids in comparison to those fed formula supplemented with carotenoids. These findings suggest that carotenoid formula supplementation influences functional brain development. [ABSTRACT FROM AUTHOR]

Prior work has shown that there is substantial interindividual variation in the spatial distribution of functional networks across the cerebral cortex, or functional topography. However, it remains unknown whether there are sex differences in the topography of individualized networks in youth. Here, we leveraged an advanced machine learning method (sparsity-regularized non-negative matrix factorization) to define individualized functional networks in 693 youth (ages 8 to 23 y) who underwent functional MRI as part of the Philadelphia Neurodevelopmental Cohort. Multivariate pattern analysis using support vector machines classified participant sex based on functional topography with 82.9% accuracy (P < 0.0001). Brain regions most effective in classifying participant sex belonged to association networks, including the ventral attention, default mode, and frontoparietal networks. Mass univariate analyses using generalized additive models with penalized splines provided convergent results. Furthermore, transcriptomic data from the Allen Human Brain Atlas revealed that sex differences in multivariate patterns of functional topography were spatially correlated with the expression of genes on the X chromosome. These results highlight the role of sex as a biological variable in shaping functional topography. [ABSTRACT FROM AUTHOR]

In the absence of external stimuli, neural activity continuously evolves from one configuration to another. Whether these transitions or explorations follow some underlying arrangement or lack a predictable ordered plan remains to be determined. Here, using fMRI data from highly sampled individuals (~5 hours of resting-state data per individual), we aimed to reveal the rules that govern transitions in brain activity at rest. Our Topological Data Analysis based Mapper approach characterized a highly visited transition state of the brain that acts as a switch between different neural configurations to organize the spontaneous brain activity. Further, while the transition state was characterized by a uniform representation of canonical resting-state networks (RSNs), the periphery of the landscape was dominated by a subject-specific combination of RSNs. Altogether, we revealed rules or principles that organize spontaneous brain activity using a precision dynamics approach. Although spontaneous brain activity is complex and clinically relevant, it is still unclear whether transitions in resting brain activity follow an underlying arrangement or whether they are unpredictable. In this work, the authors revealed a transition state of the brain that acts like a switch between states and forms the basis for the continuous evolution of brain activity patterns at rest. [ABSTRACT FROM AUTHOR]

The race of an individual is a salient physical feature that is rapidly processed by the brain and can bias our perceptions of others. How the race of others explicitly impacts our actions toward them during intergroup contexts is not well understood. In the current study, we examined how task-irrelevant race information influences cognitive control in a go/no-go task in a community sample of Black (n = 54) and White (n = 51) participants. We examined the neural correlates of behavioral effects using functional magnetic resonance imaging and explored the influence of implicit racial attitudes on brain-behavior associations. Both Black and White participants showed more cognitive control failures, as indexed by dprime, to Black versus White faces, despite the irrelevance of race to the task demands. This behavioral pattern was paralleled by greater activity to Black faces in the fusiform face area, implicated in processing face and in-group information, and lateral orbitofrontal cortex, associated with resolving stimulus-response conflict. Exploratory brain-behavior associations suggest different patterns in Black and White individuals. Black participants exhibited a negative association between fusiform activity and response time during impulsive errors to Black faces, whereas White participants showed a positive association between lateral OFC activity and cognitive control performance to Black faces when accounting for implicit racial associations. Together our findings propose that attention to race information is associated with diminished cognitive control that may be driven by different mechanisms for Black and White individuals. [ABSTRACT FROM AUTHOR]

Despite the strong link between childhood maltreatment and psychopathology, the underlying neurodevelopmental mechanisms are poorly understood and difficult to disentangle from heritable and prenatal factors. This study used a translational macaque model of infant maltreatment in which the adverse experience occurs in the first months of life, during intense maturation of amygdala circuits important for stress and emotional regulation. Thus, we examined the developmental impact of maltreatment on amygdala functional connectivity (FC) longitudinally, from infancy through the juvenile period. Using resting state functional magnetic resonance imaging (MRI) we performed amygdala–prefrontal cortex (PFC) region-of-interest and exploratory whole-brain amygdala FC analyses. The latter showed (a) developmental increases in amygdala FC with many regions, likely supporting increased processing of socioemotional-relevant stimuli with age; and (b) maltreatment effects on amygdala coupling with arousal and stress brain regions (locus coeruleus, laterodorsal tegmental area) that emerged with age. Maltreated juveniles showed weaker FC than controls, which was negatively associated with infant hair cortisol concentrations. Findings from the region-of-interest analysis also showed weaker amygdala FC with PFC regions in maltreated animals than controls since infancy, whereas bilateral amygdala FC was stronger in maltreated animals. These effects on amygdala FC development may underlie the poor behavioral outcomes associated with this adverse experience. [ABSTRACT FROM AUTHOR]

Migraine is a disease that peaks in late adolescence and early adulthood. The aim of this study was to evaluate age-related brain changes in resting state functional connectivity (rs-FC) in migraineurs vs. age-sex matched healthy controls at two developmental stages: adolescence vs. young adulthood. The effect of the disease was assessed within each developmental group and age- and sex-matched healthy controls and between developmental groups (migraine-related age effects). Globally the within group comparisons indicated more widespread abnormal rs-FC in the adolescents than in the young adults and more abnormal rs-FC associated with sensory networks in the young adults. Direct comparison of the two groups showed a number of significant changes: (1) more connectivity changes in the default mode network in the adolescents than in the young adults; (2) stronger rs-FC in the cerebellum network in the adolescents in comparison to young adults; and (3) stronger rs-FC in the executive and sensorimotor network in the young adults. The duration and frequency of the disease were differently associated with baseline intrinsic connectivity in the two groups. fMRI resting state networks demonstrate significant changes in brain function at critical time point of brain development and that potentially different treatment responsivity for the disease may result. [ABSTRACT FROM AUTHOR]

Ineffective reduction of functional connectivity between the default mode network (DMN) and frontoparietal network (FPN) during cognitive control can interfere with performance in healthy individuals--a phenomenon present in psychiatric disorders, such as depression. Here, this mechanism is studied in healthy adolescents by examining gender differences in task-regressed functional connectivity using functional magnetic resonance imaging (MRI) and a novel task designed to place the DMN--supporting self-referential processing (SRP)--and FPN--supporting cognitive control--into conflict. Compared to boys, girls showed stronger functional connectivity between DMN and FPN during cognitive control in an SRP context (n = 40; boys = 20), a context that also elicited more errors of omission in girls. The gender difference in errors of omission was mediated by higher self-reported co-rumination--the extensive and repetitive discussion of problems and focus on negative feelings with a same-gender peer--by girls, compared to boys. These findings indicate that placing internal and external attentional demands in conflict lead to persistent functional connectivity between FPN and DMN in girls, but not boys; however, deficits in performance during this context were explained by co-rumination, such that youth with higher co-rumination displayed the largest performance deficits. Previous research shows that co-rumination predicts depressive symptoms during adolescence; thus, gender differences in the mechanisms involved with transitioning from internal to external processing may be relevant for understanding heightened vulnerability for depression in adolescent girls. [ABSTRACT FROM AUTHOR]

The development of human cognition results from the emergence of coordinated activity between distant brain areas. Network science, combined with non-invasive functional imaging, has generated unprecedented insights regarding the adult brain's functional organization, and promises to help elucidate the development of functional architectures supporting complex behavior. Here we review what is known about functional network development from birth until adulthood, particularly as understood through the use of resting-state functional connectivity MRI (rs-fcMRI). We attempt to synthesize rs-fcMRI findings with other functional imaging techniques, with macro-scale structural connectivity, and with knowledge regarding the development of micro-scale structure. We highlight a number of outstanding conceptual and technical barriers that need to be addressed, as well as previous developmental findings that may need to be revisited. Finally, we discuss key areas ripe for future research in order to (1) better characterize normative developmental trajectories, (2) link these trajectories to biologic mechanistic events, as well as component behaviors and (3) better understand the clinical implications and pathophysiological basis of aberrant network development. [ABSTRACT FROM AUTHOR]

A better characterization of how an individual’s brain is functionally organized will likely bring dramatic advances to many fields of study. Here we show a model-based approach toward characterizing resting state functional connectivity MRI (rs-fcMRI) that is capable of identifying a so-called “connectotype”, or functional fingerprint in individual participants. The approach rests on a simple linear model that proposes the activity of a given brain region can be described by the weighted sum of its functional neighboring regions. The resulting coefficients correspond to a personalized model-based connectivity matrix that is capable of predicting the timeseries of each subject. Importantly, the model itself is subject specific and has the ability to predict an individual at a later date using a limited number of non-sequential frames. While we show that there is a significant amount of shared variance between models across subjects, the model’s ability to discriminate an individual is driven by unique connections in higher order control regions in frontal and parietal cortices. Furthermore, we show that the connectotype is present in non-human primates as well, highlighting the translational potential of the approach. [ABSTRACT FROM AUTHOR]

Freezing of gait (FoG) is a transient inability to initiate or maintain stepping that often accompanies advanced Parkinson’s disease (PD) and significantly impairs mobility. The current study uses a multimodal neuroimaging approach to assess differences in the functional and structural locomotor neural network in PD patients with and without FoG and relates these findings to measures of FoG severity. Twenty-six PD patients and fifteen age-matched controls underwent resting-state functional magnetic resonance imaging and diffusion tensor imaging along with self-reported and clinical assessments of FoG. After stringent movement correction, fifteen PD patients and fourteen control participants were available for analysis. We assessed functional connectivity strength between the supplementary motor area (SMA) and the following locomotor hubs: 1) subthalamic nucleus (STN), 2) mesencephalic and 3) cerebellar locomotor region (MLR and CLR, respectively) within each hemisphere. Additionally, we quantified structural connectivity strength between locomotor hubs and assessed relationships with metrics of FoG. FoG+ patients showed greater functional connectivity between the SMA and bilateral MLR and between the SMA and left CLR compared to both FoG− and controls. Importantly, greater functional connectivity between the SMA and MLR was positively correlated with i) clinical, ii) self-reported and iii) objective ratings of freezing severity in FoG+, potentially reflecting a maladaptive neural compensation. The current findings demonstrate a re-organization of functional communication within the locomotor network in FoG+ patients whereby the higher-order motor cortex (SMA) responsible for gait initiation communicates with the MLR and CLR to a greater extent than in FoG− patients and controls. The observed pattern of altered connectivity in FoG+ may indicate a failed attempt by the CNS to compensate for the loss of connectivity between the STN and SMA and may reflect a loss of lower-order, automatic control of gait by the basal ganglia. [ABSTRACT FROM AUTHOR]

Resting state functional connectivity MRI (rs-fcMRI) may provide a powerful and noninvasive "bridge" for comparing brain function between patients and experimental animal models; however, the relationship between human and macaque rs-fcMRI remains poorly understood. Here, using a novel surface deformation process for species comparisons in the same anatomical space (Van Essen, 2004, 2005), we found high correspondence, but also unique hub topology, between human and macaque functional connectomes. The global functional connectivity match between species was moderate to strong (r = 0.41) and increased when considering the top 15% strongest connections (r = 0.54). Analysis of the match between functional connectivity and the underlying anatomical connectivity, derived from a previous retrograde tracer study done in macaques (Markov et al., 2012), showed impressive structure-function correspondence in both the macaque and human. When examining the strongest structural connections, we found a 70-80% match between structural and functional connectivity matrices in both species. Finally, we compare species on two widely used metrics for studying hub topology: degree and betweenness centrality. The data showed topological agreement across the species, with nodes of the posterior cingulate showing high degree and betweenness centrality. In contrast, nodes in medial frontal and parietal cortices were identified as having high degree and betweenness in the human as opposed to the macaque. Our results provide: (1) a thorough examination and validation for a surface-based interspecies deformation process, (2) a strong theoretical foundation for making interspecies comparisons of rs-fcMRI, and (3) a unique look at topological distinctions between the species. [ABSTRACT FROM AUTHOR]

Clinical investigations of many neuropsychiatric disorders rely on the assumption that diagnostic categories and typical control samples each have within-group homogeneity. However, research using human neuroimaging has revealed that much heterogeneity exists across individuals in both clinical and control samples. This reality necessitates that researchers identify and organize the potentially varied patterns of brain physiology. We introduce an analytical approach for arriving at subgroups of individuals based entirely on their brain physiology. The method begins with Group Iterative Multiple Model Estimation (GIMME) to assess individual directed functional connectivity maps. GIMME is one of the only methods to date that can recover both the direction and presence of directed functional connectivity maps in heterogeneous data, making it an ideal place to start since it addresses the problem of heterogeneity. Individuals are then grouped based on similarities in their connectivity patterns using a modularity approach for community detection. Monte Carlo simulations demonstrate that using GIMME in combination with the modularity algorithm works exceptionally well - on average over 97% of simulated individuals are placed in the accurate subgroup with no prior information on functional architecture or group identity. Having demonstrated reliability, we examine resting-state data of fronto-parietal regions drawn from a sample (N = 80) of typically developing and attention-deficit/hyperactivity disorder (ADHD) -diagnosed children. Here, we find 5 subgroups. Two subgroups were predominantly comprised of ADHD, suggesting that more than one biological marker exists that can be used to identify children with ADHD based from their brain physiology. Empirical evidence presented here supports notions that heterogeneity exists in brain physiology within ADHD and control samples. This type of information gained from the approach presented here can assist in better characterizing patients in terms of outcomes, optimal treatment strategies, potential gene-environment interactions, and the use of biological phenomenon to assist with mental health. [ABSTRACT FROM AUTHOR]

Objective. Cerebral infarction can cause diaschisis, a reduction of blood flow and metabolism in areas of the cortex distant from the site of the lesion. Although the functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) signal is increasingly used to examine the neural correlates of recovery in stroke, its reliability in areas of diaschisis is uncertain. Design. The effect of chronic diaschisis as measured by resting positron emission tomography on task-evoked BOLD responses during word-stem completion in a block design fMRI study was examined in 3 patients, 6 months after a single left hemisphere stroke involving the inferior frontal gyrus and operculum. Results. The BOLD responses were minimally affected in areas of chronic diaschisis. Conclusions. Within the confines of this study, the mechanism underlying the BOLD signal, which includes a mismatch between neuronally driven increases in blood flow and a corresponding increase in oxygen use, appears to be intact in areas of chronic diaschisis. [ABSTRACT FROM AUTHOR]

Symptoms of borderline personality disorder (BPD) often manifest during adolescence, but the underlying relationship between these debilitating symptoms and the development of functional brain networks is not well understood. Here, we aimed to investigate how multivariate patterns of functional connectivity are associated with borderline personality traits in large samples of young adults and adolescents. We used functional magnetic resonance imaging data from young adults and adolescents from the HCP-YA (Human Connectome Project Young Adult) (n = 870, ages 22–37 years, 457 female) and the HCP-D (Human Connectome Project Development) (n = 223, ages 16–21 years, 121 female). A previously validated BPD proxy score was derived from the NEO Five-Factor Inventory. A ridge regression model with cross-validation and nested hyperparameter tuning was trained and tested in HCP-YA to predict BPD scores in unseen data from regional functional connectivity. The trained model was further tested on data from HCP-D without further tuning. Finally, we tested how the connectivity patterns associated with BPD aligned with age-related changes in connectivity. Multivariate functional connectivity patterns significantly predicted out-of-sample BPD scores in unseen data in young adults (HCP-YA p perm u ted =.001) and older adolescents (HCP-D p perm ut ed =.001). Regional predictive capacity was heterogeneous; the most predictive regions were found in functional systems relevant for emotion regulation and executive function, including the ventral attention network. Finally, regional functional connectivity patterns that predicted BPD scores aligned with those associated with development in youth. Individual differences in functional connectivity in developmentally sensitive regions are associated with borderline personality traits. [ABSTRACT FROM AUTHOR]

Head motion represents one of the greatest technical obstacles in magnetic resonance imaging (MRI) of the human brain. Accurate detection of artifacts induced by head motion requires precise estimation of movement. However, head motion estimates may be corrupted by artifacts due to magnetic main field fluctuations generated by body motion. In the current report, we examine head motion estimation in multiband resting state functional connectivity MRI (rs-fcMRI) data from the Adolescent Brain and Cognitive Development (ABCD) Study and comparison 'single-shot' datasets. We show that respirations contaminate movement estimates in functional MRI and that respiration generates apparent head motion not associated with functional MRI quality reductions. We have developed a novel approach using a band-stop filter that accurately removes these respiratory effects from motion estimates. Subsequently, we demonstrate that utilizing a band-stop filter improves post-processing fMRI data quality. Lastly, we demonstrate the real-time implementation of motion estimate filtering in our FIRMM (Framewise Integrated Real-Time MRI Monitoring) software package. • Respiratory perturbations of the main field inflate fMRI head motion estimates. • Breathing-related head motion artifacts compromise functional connectivity quality. • Notch filtering motion estimates (respiratory frequency band) improves data quality. • Motion estimate filtering can be achieved in real-time with FIRMM software. [ABSTRACT FROM AUTHOR]

Clinical studies suggest that anaesthesia exposure early in life affects neurobehavioural development. We designed a non-human primate (NHP) study to evaluate cognitive, behavioural, and brain functional and structural alterations after isoflurane exposure during infancy. These NHPs displayed decreased close social behaviour and increased astrogliosis in specific brain regions, most notably in the amygdala. Here we hypothesise that resting-state functional connectivity MRI can detect alterations in connectivity of brain areas that relate to these social behaviours and astrogliosis. Imaging was performed in 2-yr-old NHPs under light anaesthesia, after early-in-life (postnatal days 6–12) exposure to 5 h of isoflurane either one or three times, or to room air. Brain images were segmented into 82 regions of interest; the amygdala and the posterior cingulate cortex were chosen for a seed-based resting-state functional connectivity MRI analysis. We found differences between groups in resting-state functional connectivity of the amygdala and the auditory cortices, medial premotor cortex, and posterior cingulate cortex. There were also alterations in resting-state functional connectivity between the posterior cingulate cortex and secondary auditory, polar prefrontal, and temporal cortices, and the anterior insula. Relationships were identified between resting-state functional connectivity alterations and the decrease in close social behaviour and increased astrogliosis. Early-in-life anaesthesia exposure in NHPs is associated with resting-state functional connectivity alterations of the amygdala and the posterior cingulate cortex with other brain regions, evident at the juvenile age of 2 yr. These changes in resting-state functional connectivity correlate with the decrease in close social behaviour and increased astrogliosis. Using resting-state functional connectivity MRI to study the neuronal underpinnings of early-in-life anaesthesia-induced behavioural alterations could facilitate development of a biomarker for anaesthesia-induced developmental neurotoxicity. [ABSTRACT FROM AUTHOR]

The spatial layout of large-scale functional brain networks differs between individuals and is particularly variable in the association cortex, implicated in a broad range of psychiatric disorders. However, it remains unknown whether this variation in functional topography is related to major dimensions of psychopathology in youth. The authors studied 790 youths ages 8 to 23 years who had 27 minutes of high-quality functional magnetic resonance imaging data as part of the Philadelphia Neurodevelopmental Cohort. Four correlated dimensions were estimated using a confirmatory correlated traits factor analysis on 112 item-level clinical symptoms, and one overall psychopathology factor with 4 orthogonal dimensions were extracted using a confirmatory factor analysis. Spatially regularized nonnegative matrix factorization was used to identify 17 individual-specific functional networks for each participant. Partial least square regression with split-half cross-validation was conducted to evaluate to what extent the topography of personalized functional networks encodes major dimensions of psychopathology. Personalized functional network topography significantly predicted unseen individuals' major dimensions of psychopathology, including fear, psychosis, externalizing, and anxious-misery. Reduced representation of association networks was among the most important features for the prediction of all 4 dimensions. Further analysis revealed that personalized functional network topography predicted overall psychopathology (r = 0.16, permutation testing p <.001), which drove prediction of the 4 correlated dimensions. These results suggest that individual differences in functional network topography in association networks is related to overall psychopathology in youth. Such results underscore the importance of considering functional neuroanatomy for personalized diagnostics and therapeutics in psychiatry. [ABSTRACT FROM AUTHOR]

Adolescence is a developmental period characterized by notable changes in behavior, physical attributes, and an increase in endogenous sex steroid hormones, which may impact cognitive functioning. Moreover, sex differences in brain structure are present, leading to differences in neural function and cognition. Here, we examine sex differences in performance and blood oxygen level-dependent (BOLD) activation in a sample of adolescents during a spatial working memory (SWM) task. We also examine whether endogenous testosterone levels mediate differential brain activity between the sexes. Adolescents between ages 10 and 16 years completed a SWM functional magnetic resonance imaging (fMRI) task, and serum hormone levels were assessed within seven days of scanning. While there were no sex differences in task performance (accuracy and reaction time), differences in BOLD response between girls and boys emerged, with girls deactivating brain regions in the default mode network and boys showing increased response in SWM-related brain regions of the frontal cortex. These results suggest that adolescent boys and girls adopted distinct neural strategies, while maintaining spatial cognitive strategies that facilitated comparable cognitive performance of a SWM task. A nonparametric bootstrapping procedure revealed that testosterone did not mediate sex-specific brain activity, suggesting that sex differences in BOLD activation during SWM may be better explained by other factors, such as early organizational effects of sex steroids or environmental influences. Elucidating sex differences in neural function and the influence of gonadal hormones can serve as a basis of comparison for understanding sexually dimorphic neurodevelopment and inform sex-specific psychopathology that emerges in adolescence. [ABSTRACT FROM AUTHOR]

Abstract: Adolescents with a family history of alcoholism (FHP) are at heightened risk for developing alcohol use disorders (AUDs). The nucleus accumbens (NAcc), a key brain region for reward processing, is implicated in the development of AUDs. Thus, functional connectivity of the NAcc may be an important marker of risk in FHP youth. Resting state functional magnetic resonance imaging (rs-fcMRI) was used to examine the intrinsic connectivity of the NAcc in 47 FHP and 50 family history negative (FHN) youth, ages 10–16 years old. FHP and FHN adolescents showed significant group differences in resting state synchrony between the left NAcc and bilateral inferior frontal gyri and the left postcentral gyrus (PG). Additionally, FHP youth differed from FHN youth in right NAcc functional connectivity with the left orbitofrontal cortex (OFC), left superior temporal gyrus, right cerebellum, left PG, and right occipital cortex. These results indicate that FHP youth have less segregation between the NAcc and executive functioning brain regions, and less integration with reward-related brain areas, such as the OFC. The findings of the current study highlight that premorbid atypical connectivity of appetitive systems, in the absence of heavy alcohol use, may be a risk marker in FHP adolescents. [Copyright &y& Elsevier]

Early adversity influences brain development and emerging behavioral phenotypes relevant for psychiatric disorders. Understanding the effects of adversity before and after conception on brain development has implications for contextualizing current public health crises and pervasive health inequities. The use of functional magnetic resonance imaging (fMRI) to study the brain at rest has shifted understanding of brain functioning and organization in the earliest periods of life. Here we review applications of this technique to examine effects of early life stress (ELS) on neurodevelopment in infancy, and highlight targets for future research. Building on the foundation of existing work in this area will require tackling significant challenges, including greater inclusion of often marginalized segments of society, and conducting larger, properly powered studies. The use of resting state functional connectivity MRI has contributed substantially to understanding of human brain functioning and organization, and revealed emerging large scale brain systems already in early infancy. Recent research shows how early brain system development varies in relation to multiple sources of pre- and postnatal adversity and biological stress mediators. Variability in early developing brain systems has implications for later emerging behaviors relevant for psychiatric disorders. Recent methodological advances promise increased precision in examining individual differences in early emerging functional brain systems. There is need for research examining mechanistic pathways for combined and interactive effects of multiple sources of early adversity on developing brain systems. This line of study is crucial for applying research findings to infants at highest risk of subsequent poor health outcomes. Greater inclusion of individuals facing the highest levels of early adversity in developmental neuroimaging work represents a priority for future research, which will require significant investment and yield critical information to address public health challenges. [ABSTRACT FROM AUTHOR]

A major limitation to structural and functional MRI (fMRI) scans is their susceptibility to head motion artifacts. Even submillimeter movements can systematically distort functional connectivity, morphometric, and diffusion imaging results. In patient care, sedation is often used to minimize head motion, but it incurs increased costs and risks. In research settings, sedation is typically not an ethical option. Therefore, safe methods that reduce head motion are critical for improving MRI quality, especially in high movement individuals such as children and neuropsychiatric patients. We investigated the effects of (1) viewing movies and (2) receiving real-time visual feedback about head movement in 24 children (5–15 years old). Children completed fMRI scans during which they viewed a fixation cross (i.e., rest) or a cartoon movie clip, and during some of the scans they also received real-time visual feedback about head motion. Head motion was significantly reduced during movie watching compared to rest and when receiving feedback compared to receiving no feedback. However, these results depended on age, such that the effects were largely driven by the younger children. Children older than 10 years showed no significant benefit. We also found that viewing movies significantly altered the functional connectivity of fMRI data, suggesting that fMRI scans during movies cannot be equated to standard resting-state fMRI scans. The implications of these results are twofold: (1) given the reduction in head motion with behavioral interventions, these methods should be tried first for all clinical and structural MRIs in lieu of sedation; and (2) for fMRI research scans, these methods can reduce head motion in certain groups, but investigators must keep in mind the effects on functional MRI data. [ABSTRACT FROM AUTHOR]

Head motion systematically distorts clinical and research MRI data. Motion artifacts have biased findings from many structural and functional brain MRI studies. An effective way to remove motion artifacts is to exclude MRI data frames affected by head motion. However, such post-hoc frame censoring can lead to data loss rates of 50% or more in our pediatric patient cohorts. Hence, many scanner operators collect additional ‘buffer data’, an expensive practice that, by itself, does not guarantee sufficient high-quality MRI data for a given participant. Therefore, we developed an easy-to-setup, easy-to-use F ramewise I ntegrated R eal-time M RI M onitoring (FIRMM) software suite that provides scanner operators with head motion analytics in real-time, allowing them to scan each subject until the desired amount of low-movement data has been collected. Our analyses show that using FIRMM to identify the ideal scan time for each person can reduce total brain MRI scan times and associated costs by 50% or more. [ABSTRACT FROM AUTHOR]

As public access to longitudinal developmental datasets like the Adolescent Brain Cognitive Development StudySM (ABCD Study®) increases, so too does the need for resources to benchmark time-dependent effects. Scan-to-scan changes observed with repeated imaging may reflect development but may also reflect practice effects, day-to-day variability in psychological states, and/or measurement noise. Resources that allow disentangling these time-dependent effects will be useful in quantifying actual developmental change. We present an accelerated adult equivalent of the ABCD Study dataset (a-ABCD) using an identical imaging protocol to acquire magnetic resonance imaging (MRI) structural, diffusion-weighted, resting-state and task-based data from eight adults scanned five times over five weeks. We report on the task-based imaging data (n = 7). In-scanner stop-signal (SST), monetary incentive delay (MID), and emotional n -back (EN-back) task behavioral performance did not change across sessions. Post-scan recognition memory for emotional n -back stimuli, however, did improve as participants became more familiar with the stimuli. Functional MRI analyses revealed that patterns of task-based activation reflecting inhibitory control in the SST, reward success in the MID task, and working memory in the EN-back task were more similar within individuals across repeated scan sessions than between individuals. Within-subject, activity was more consistent across sessions during the EN-back task than in the SST and MID task, demonstrating differences in fMRI data reliability as a function of task. The a-ABCD dataset provides a unique testbed for characterizing the reliability of brain function, structure, and behavior across imaging modalities in adulthood and benchmarking neurodevelopmental change observed in the open-access ABCD Study. [ABSTRACT FROM AUTHOR]

T1- and T2-weighted (T1w and T2w) images are essential for tissue classification and anatomical localization in Magnetic Resonance Imaging (MRI) analyses. However, these anatomical data can be challenging to acquire in non-sedated neonatal cohorts, which are prone to high amplitude movement and display lower tissue contrast than adults. As a result, one of these modalities may be missing or of such poor quality that they cannot be used for accurate image processing, resulting in subject loss. While recent literature attempts to overcome these issues in adult populations using synthetic imaging approaches, evaluation of the efficacy of these methods in pediatric populations and the impact of these techniques in conventional MR analyses has not been performed. In this work, we present two novel methods to generate pseudo-T2w images: the first is based in deep learning and expands upon previous models to 3D imaging without the requirement of paired data, the second is based in nonlinear multi-atlas registration providing a computationally lightweight alternative. We demonstrate the anatomical accuracy of pseudo-T2w images and their efficacy in existing MR processing pipelines in two independent neonatal cohorts. Critically, we show that implementing these pseudo-T2w methods in resting-state functional MRI analyses produces virtually identical functional connectivity results when compared to those resulting from T2w images, confirming their utility in infant MRI studies for salvaging otherwise lost subject data. [ABSTRACT FROM AUTHOR]

The importance of motion correction when processing resting state functional magnetic resonance imaging (rs-fMRI) data is well-established in adult cohorts. This includes adjustments based on self-limited, large amplitude subject head motion, as well as factitious rhythmic motion induced by respiration. In adults, such respiration artifact can be effectively removed by applying a notch filter to the motion trace, resulting in higher amounts of data retained after frame censoring (e.g., "scrubbing") and more reliable correlation values. Due to the unique physiological and behavioral characteristics of infants and toddlers, rs-fMRI processing pipelines, including methods to identify and remove colored noise due to subject motion, must be appropriately modified to accurately reflect true neuronal signal. These younger cohorts are characterized by higher respiration rates and lower-amplitude head movements than adults; thus, the presence and significance of comparable respiratory artifact and the subsequent necessity of applying similar techniques remain unknown. Herein, we identify and characterize the consistent presence of respiratory artifact in rs-fMRI data collected during natural sleep in infants and toddlers across two independent cohorts (aged 8–24 months) analyzed using different pipelines. We further demonstrate how removing this artifact using an age-specific notch filter allows for both improved data quality and data retention in measured results. Importantly, this work reveals the critical need to identify and address respiratory-driven head motion in fMRI data acquired in young populations through the use of age-specific motion filters as a mechanism to optimize the accuracy of measured results in this population. [ABSTRACT FROM AUTHOR]

Abstract: Adult functional magnetic resonance imaging (fMRI) literature suggests that a left–right hemispheric dissociation may exist between verbal and spatial working memory (WM), respectively. However, investigation of this type has been obscured by incomparable verbal and spatial WM tasks and/or visual inspection at arbitrary thresholds as means to assess lateralization. Furthermore, it is unclear whether this hemispheric lateralization is present during adolescence, a time in which WM skills are improving, and whether there is a developmental association with laterality of brain functioning. This study used comparable verbal and spatial WM n-back tasks during fMRI and a bootstrap analysis approach to calculate lateralization indices (LIs) across several thresholds to examine the potential of a left–right WM hemispheric dissociation in healthy adolescents. We found significant left hemispheric lateralization for verbal WM, most notably in the frontal and parietal lobes, as well as right hemisphere lateralization for spatial WM, seen in frontal and temporal cortices. Although no significant relationships were observed between LI and age or LI and performance, significant age-related patterns of brain activity were demonstrated during both verbal and spatial WM. Specifically, increased adolescent age was associated with less activity in the default mode brain network during verbal WM. In contrast, increased adolescent age was associated with greater activity in task-positive posterior parietal cortex during spatial working memory. Our findings highlight the importance of utilizing non-biased statistical methods and comparable tasks for determining patterns of functional lateralization. Our findings also suggest that, while a left–right hemispheric dissociation of verbal and spatial WM is apparent by early adolescence, age-related changes in functional activation during WM are also present. [Copyright &y& Elsevier]

• Non-human primate MRI standardization. • Poor reproducibility in non-human primate resting-state fMRI. • Guidelines enable improved and more reproducible MRI measures. • Convergence between non-human primate and human neuroimaging strategies. Recent methodological advances in MRI have enabled substantial growth in neuroimaging studies of non-human primates (NHPs), while open data-sharing through the PRIME-DE initiative has increased the availability of NHP MRI data and the need for robust multi-subject multi-center analyses. Streamlined acquisition and analysis protocols would accelerate and improve these efforts. However, consensus on minimal standards for data acquisition protocols and analysis pipelines for NHP imaging remains to be established, particularly for multi-center studies. Here, we draw parallels between NHP and human neuroimaging and provide minimal guidelines for harmonizing and standardizing data acquisition. We advocate robust translation of widely used open-access toolkits that are well established for analyzing human data. We also encourage the use of validated, automated pre-processing tools for analyzing NHP data sets. These guidelines aim to refine methodological and analytical strategies for small and large-scale NHP neuroimaging data. This will improve reproducibility of results, and accelerate the convergence between NHP and human neuroimaging strategies which will ultimately benefit fundamental and translational brain science. [ABSTRACT FROM AUTHOR]

B Background: b Recent large-scale GWAS meta-analyses and follow-up studies have demonstrated the association of polygenic risk burden with ADHD and other intermediate phenotypes (e.g. executive function). Brain connectivity was summarized as the first principal component of: (1) connectivity measures between all ROIs within each of the 13 networks (within-network connectivity measures; N=13), or (2) connectivity measures between all pairs of networks (between-network connectivity measures; N=78). The genetic variate explained 16.3% of the variance of retrosplenial connectivity (p=5.4e-14), and the connectivity variate explained 4.6% of the variance in the autophagy-related ADHD sub-PRS (p=7.3e-5). [Extracted from the article]

The spatial distribution of large-scale functional networks on the cerebral cortex differs between individuals and is particularly variable in association networks that are responsible for higher-order cognition. However, it remains unknown how this functional topography evolves in development and supports cognition. Capitalizing on advances in machine learning and a large sample imaged with 27 min of high-quality functional MRI (fMRI) data (n = 693, ages 8–23 years), we delineate how functional topography evolves during youth. We found that the functional topography of association networks is refined with age, allowing accurate prediction of unseen individuals' brain maturity. The cortical representation of association networks predicts individual differences in executive function. Finally, variability of functional topography is associated with fundamental properties of brain organization, including evolutionary expansion, cortical myelination, and cerebral blood flow. Our results emphasize the importance of considering the plasticity and diversity of functional neuroanatomy during development and suggest advances in personalized therapeutics. • Functional topography is most variable in association cortex in youth • Functional topography is refined during youth and encodes brain maturity • Association network functional topography predicts executive function Cui et al. demonstrate that individual-specific functional networks are refined during youth in humans. Furthermore, the functional topography of association networks predicts individual differences in executive function. [ABSTRACT FROM AUTHOR]