Search

Background Childhood maltreatment is associated with lifelong psychiatric sequelae. However, our understanding of neurobiological mechanisms responsible for this association is limited. Childhood maltreatment may confer risk for psychopathology by altering neurodevelopmental trajectories during childhood and adolescence. Longitudinal research, which is essential for examining this question, has been limited. Methods We investigated maltreatment-associated alterations in the development of neural circuitry. Associations between cumulative childhood maltreatment (assessed using a dimensional measure of abuse and neglect via the Childhood Trauma Questionnaire) and the longitudinal development of resting-state functional connectivity (rsFC) were examined in 130 community-residing adolescents. Functional magnetic resonance imaging data were acquired at age 16 (T1; mean ± SD age, 16.46 ± 0.52 years; 66 females) and age 19 (T2; mean follow-up period, 2.35 years; n = 90 with functional magnetic resonance imaging data at both time points). Results We found maltreatment to be associated with widespread longitudinal increases in rsFC, primarily between default mode, dorsal attention, and frontoparietal systems. We also found sex-dependent increased maltreatment-associated rsFC in male participants in salience and limbic circuits. Cross-sectional analyses revealed a shift in maltreatment-related rsFC alterations, which were localized to subcortical and sensory circuits at T1 and to frontal circuits at T2. Finally, longitudinal increases in rsFC connectivity mediated the relationship between childhood maltreatment and increased depressive symptoms. Conclusions To our knowledge, this is the first study to examine longitudinal maltreatment-related alterations in rsFC in adolescents. Our findings shed light on the neurodevelopmental consequences of childhood maltreatment and provide evidence for their role in risk for depression.

The hippocampus plays a central role in supporting our coherent and enduring sense of self and our place in the world. Understanding its functional organisation is central to understanding this complex role. Previous studies suggest function varies along a long hippocampal axis, but there is disagreement about the presence of sharp discontinuities or gradual change along that axis. Other open questions relate to the underlying drivers of this variation and the conservation of organisational principles across species. Here, we delineate the primary organisational principles underlying patterns of hippocampal functional connectivity (FC) in the mouse using gradient analysis on resting state fMRI data. We further applied gradient analysis to mouse gene co-expression data to examine the relationship between variation in genomic anatomy and functional organisation. Two principal FC gradients along a hippocampal axis were revealed. The principal gradient exhibited a sharp discontinuity that divided the hippocampus into dorsal and ventral compartments. The second, more continuous, gradient followed the long axis of the ventral compartment. Dorsal regions were more strongly connected to areas involved in spatial navigation while ventral regions were more strongly connected to areas involved in emotion, recapitulating patterns seen in humans. In contrast, gene co-expression gradients showed a more segregated and discrete organisation. Our findings suggest that hippocampal functional organisation exhibits both sharp and gradual transitions and that hippocampal genomic anatomy exerts only a subtle influence on this organisation., NeuroImage, 253, ISSN:1053-8119, ISSN:1095-9572

Objective Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. Methods We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries. Results There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’s d from −0.18 to 0.18) and would not survive study-wide correction for multiple testing. Conclusion Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait., Journal of Child Psychology and Psychiatry, 62 (10), ISSN:0021-9630, ISSN:1469-7610

Patterns of functional connectivity are unique at the individual level, enabling test-retest matching algorithms to identify a subject from among a group using only their functional connectome. Recent findings show that accuracies of these algorithms in children increase with age. Relatedly, the persistence of functional connectivity (FC) patterns across tasks and rest also increases with age. This study investigated the hypothesis that within-subject stability and between-subject similarity of the whole-brain pediatric connectome are developmentally relevant outcomes. Using data from 210 help-seeking children and adolescents, ages 6–21 years (Healthy Brain Network Biobank), we computed whole-brain FC matrices for each participant during two different movies (MovieDM and MovieTP) and two runs of task-free rest (all from a single scan session) and fed these matrices to a test-retest matching algorithm. We replicated the finding that matching accuracies for children and youth (ages 6–21 years) are low (18–44%), and that cross-state and cross-movie accuracies were the lowest. Results also showed that parcellation resolution and the number of volumes used in each matrix affect fingerprinting accuracies. Next, we calculated three measures of whole-connectome stability for each subject: cross-rest (Rest1-Rest2), cross-state (MovieDM-Rest1), and cross-movie (MovieDM-MovieTP), and three measures of within-state between-subject connectome similarity for Rest1, MovieDM, and MovieTP. We show that stability and similarity were correlated, but that these measures were not related to age. A principal component analysis of these measures yielded two components that we used to test for brain-behavior correlations with IQ, general psychopathology, and social skills measures (n = 119). The first component was significantly correlated with the social skills measure (r=-0.26, p = 0.005). Post hoc correlations showed that the social skills measure correlated with both cross-rest stability (r=-0.29, p = 0.001) and with connectome similarity during MovieDM (r=-0.28, p = 0.002). These findings suggest that the stability and similarity of the whole-brain connectome relate to the development of social skills. We infer that the maturation of the functional connectome simultaneously achieves patterns of FC that are distinct at the individual subject level, that are shared across individuals, and that are persistent across states and across runs—features which presumably combine to optimize neural processing during development. Future longitudinal work could reveal the developmental trajectories of stability and similarity of the connectome.

Moment-to-moment reaction time variability on tasks of attention, often quantified by intra-individual response variability (IRV), provides a good indication of the degree to which an individual is vulnerable to lapses in sustained attention. Increased IRV is a hallmark of several disorders of attention, including Attention-Deficit/Hyperactivity Disorder (ADHD). Here, task-based fMRI was used to provide the first examination of how average brain activation and functional connectivity patterns in adolescents are related to individual differences in sustained attention as measured by IRV. We computed IRV in a large sample of adolescents (n = 758) across 'Go' trials of a Stop Signal Task (SST). A data-driven, multi-step analysis approach was used to identify networks associated with low IRV (i.e., good sustained attention) and high IRV (i.e., poorer sustained attention). Low IRV was associated with greater functional segregation (i.e., stronger negative connectivity) amongst an array of brain networks, particularly between cerebellum and motor, cerebellum and prefrontal, and occipital and motor networks. In contrast, high IRV was associated with stronger positive connectivity within the motor network bilaterally and between motor and parietal, prefrontal, and limbic networks. Consistent with these observations, a separate sample of adolescents exhibiting elevated ADHD symptoms had increased fMRI activation and stronger positive connectivity within the same motor network denoting poorer sustained attention, compared to a matched asymptomatic control sample. With respect to the functional connectivity signature of low IRV, there were no statistically significant differences in networks denoting good sustained attention between the ADHD symptom group and asymptomatic control group. We propose that sustained attentional processes are facilitated by an array of neural networks working together, and provide an empirical account of how the functional role of the cerebellum extends to cognition in adolescents. This work highlights the involvement of motor cortex in the integrity of sustained attention, and suggests that atypically strong connectivity within motor networks characterizes poor attentional capacity in both typically developing and ADHD symptomatic adolescents.

One of the most salient long-term implications of a childhood diagnosis of ADHD is an increased risk for substance use, abuse, or dependence in adolescence and adulthood. The extent to which cannabis use affects ADHD-related alterations in brain functional organization is unknown, however. To address this research gap, we recruited a sample of 75 individuals aged 21–25 years with and without a childhood diagnosis of ADHD Combined Type, who were either frequent users or non-users of cannabis. These participants have been followed longitudinally since age 7–9.9 years as part of a large multi-site longitudinal study of ADHD, the Multimodal Treatment Study of Children with ADHD (MTA). We examined task-independent intrinsic functional connectivity (iFC) within 9 functional networks using a 2 × 2 design, which compared four groups of participants: (1) individuals with a childhood diagnosis of ADHD who currently use cannabis (n = 23); (2) individuals with ADHD who do not currently use cannabis (n = 22); (3) comparisons who currently use cannabis (n = 15); and (4) comparisons who do not currently use cannabis (n = 15). The main effects of childhood ADHD were primarily weakened iFC in networks supporting executive function and somatomotor control. Contrary to expectations, effects of cannabis use were distinct from those of diagnostic group and no interactions were observed. Exploratory brain-behavior analyses suggested that ADHD-related effects were primarily linked with poorer neurocognitive performance. Deficits in the integrity of functional networks supporting executive function and somatomotor control are consistent with the phenotypic and neurocognitive features of ADHD. Our data suggest that cannabis use does not exacerbate ADHD-related alterations, but this finding awaits replication in a larger sample. Longitudinal neuroimaging studies are urgently required to delineate the neurodevelopmental cascade that culminates in positive and negative outcomes for those diagnosed with ADHD in childhood., Highlights • Alterations in functional organization persist in those with childhood ADHD. • Network alterations can be linked with specific aspects of the ADHD phenotype. • Cannabis use does not appear to exacerbate ADHD-related alterations. • Longitudinal studies are required to capture the long-term impact of cannabis use.

Contains fulltext : 204879pub.pdf (Publisher’s version ) (Open Access) Contains fulltext : 204879pos.pdf (Author’s version postprint ) (Open Access) OBJECTIVE: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies. METHODS: Cortical thickness and surface area (based on the Desikan-Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707). RESULTS: In the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen's d=-0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample. CONCLUSIONS: Subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis.

The purposes of this study were to examine the impact of 3 weeks of amphetamine administration on intrinsic connectome-wide connectivity patterns in adults with attention-deficit/hyperactivity disorder (ADHD) and explore the association between stimulant-induced symptom improvement and functional connectivity alteration.Participants included 19 adults (age 20-55 years) diagnosed with ADHD using the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria per the Adult Clinician Diagnostic Scale taking part in amphetamine trials. For each patient, two 6-minute resting-state functional magnetic resonance imaging (R-fMRI) scans were acquired at baseline and after treatment. A fully data-driven multivariate analytic approach (i.e., multivariate distance matrix regression [MDMR]) was applied to R-fMRI data to characterize the distributed pharmacological effects in the entire functional connectome. Clinical efficacy was assessed using ADHD rating scale with adult prompts and the Adult Self-Report Scale v1.1 Symptom Checklist. We linked stimulant-induced functional connectivity changes to symptom amelioration using Spearman's correlation.Three weeks of administration of a stimulant significantly reduced ADHD symptoms. MDMR-based analyses on R-fMRI data highlighted the left dorsolateral prefrontal cortex (DLPFC, a key cognitive control region) and the medial prefrontal cortex (MPFC, the anterior core of default network) whose distributed patterns of functional connectivity across the entire brain were altered by psychostimulants. Follow-up intrinsic functional connectivity revealed that stimulants specifically decreased the positive functional connectivity between DLPFC-insula, DLPFC-anterior cingulate cortex, and MPFC-insula. Importantly, these functional connectivity changes are associated with symptom improvement.These results suggested that ADHD is associated with increased functional integration or decreased functional segregation between core regions of cognitive control, default, and salience networks. The apparent normalization of intrinsic functional interaction in these circuits (i.e., increased functional segregation) may underlie the clinical benefits produced by 3 weeks of amphetamine treatment.

The examination of functional connectivity in fMRI data collected during task-free “rest” has provided a powerful tool for studying functional brain organization. Limitations of this approach include susceptibility to head motion artifacts and participant drowsiness or sleep. These issues are especially relevant when studying young children or clinical populations. Here we introduce a movie paradigm, Inscapes, that features abstract shapes without a narrative or scene-cuts. The movie was designed to provide enough stimulation to improve compliance related to motion and wakefulness while minimizing cognitive load during the collection of functional imaging data. We compare Inscapes to eyes-open rest and to age-appropriate movie clips in healthy adults (Ocean's Eleven, n = 22) and a pilot sample of typically developing children ages 3-7 (Fantasia, n = 13). Head motion was significantly lower during both movies relative to rest for both groups. In adults, movies decreased the number of participants who self-reported sleep. Intersubject correlations, used to quantify synchronized, task-evoked activity across movie and rest conditions in adults, involved less cortex during Inscapes than Ocean's Eleven. To evaluate the effect of movie-watching on intrinsic functional connectivity networks, we examined mean functional connectivity using both whole-brain functional parcellation and network-based approaches. Both inter- and intra-network metrics were more similar between Inscapes and Rest than between Ocean's Eleven and Rest, particularly in comparisons involving the default network. When comparing movies to Rest, the mean functional connectivity of somatomotor, visual and ventral attention networks differed significantly across various analyses. We conclude that low-demand movies like Inscapes may represent a useful intermediate condition between task-free rest and typical narrative movies while still improving participant compliance. Inscapes is publicly available for download at headspacestudios.org/inscapes.

Contains fulltext : 169834.pdf (Publisher’s version ) (Open Access) Contains fulltext : 169834pos.pdf (Author’s version postprint ) (Open Access) BACKGROUND: Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis. METHODS: In this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0.0156. FINDINGS: Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohen's d=-0.15), amygdala (d=-0.19), caudate (d=-0.11), hippocampus (d=-0.11), putamen (d=-0.14), and intracranial volume (d=-0.10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0.95) and thalamus (p=0.39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (21 years): in the accumbens (Cohen's d=-0.19 vs -0.10), amygdala (d=-0.18 vs -0.14), caudate (d=-0.13 vs -0.07), hippocampus (d=-0.12 vs -0.06), putamen (d=-0.18 vs -0.08), and intracranial volume (d=-0.14 vs 0.01). There was no difference between children and adults for the pallidum (p=0.79) or thalamus (p=0.89). Case-control differences in adults were non-significant (all p>0.03). Psychostimulant medication use (all p>0.15) or symptom scores (all p>0.02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0.5). INTERPRETATION: With the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes. FUNDING: National Institutes of Health. 10 p.

The identification of phenotypic associations in high-dimensional brain connectivity data represents the next frontier in the neuroimaging connectomics era. Exploration of brain-phenotype relationships remains limited by statistical approaches that are computationally intensive, depend on a priori hypotheses, or require stringent correction for multiple comparisons. Here, we propose a computationally efficient, data-driven technique for connectome-wide association studies (CWAS) that provides a comprehensive voxel-wise survey of brain-behavior relationships across the connectome; the approach identifies voxels whose whole-brain connectivity patterns vary significantly with a phenotypic variable. Using resting state fMRI data, we demonstrate the utility of our analytic framework by identifying significant connectivity-phenotype relationships for full-scale IQ and assessing their overlap with existent neuroimaging findings, as synthesized by openly available automated meta-analysis (www.neurosynth.org). The results appeared to be robust to the removal of nuisance covariates (i.e., mean connectivity, global signal, and motion) and varying brain resolution (i.e., voxelwise results are highly similar to results using 800 parcellations). We show that CWAS findings can be used to guide subsequent seed-based correlation analyses. Finally, we demonstrate the applicability of the approach by examining CWAS for three additional datasets, each encompassing a distinct phenotypic variable: neurotypical development, Attention-Deficit/Hyperactivity Disorder diagnostic status, and L-DOPA pharmacological manipulation. For each phenotype, our approach to CWAS identified distinct connectome-wide association profiles, not previously attainable in a single study utilizing traditional univariate approaches. As a computationally efficient, extensible, and scalable method, our CWAS framework can accelerate the discovery of brain-behavior relationships in the connectome.

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 effects of 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 hypothesis 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.

At macroscopic scales, the human connectome is composed of anatomically distinct brain areas, the structural pathways connecting them, and their functional interactions. Successful annotation of phenotypic associations with variation in the connectome and cataloguing of neurophenotypes promise to transform our understanding of the human brain. This review provides a survey of magnetic resonance imaging-based measurements of functional and structural connectivity. We highlight emerging areas of development and inquiry, and emphasize the importance of integrating structural and functional perspectives on brain architecture.

Background: Individuals with autism spectrum disorders (ASD) often exhibit symptoms of attention-deficit/hyperactivity disorder (ADHD). Across both disorders, observations of distributed functional abnormalities suggest aberrant large-scale brain network connectivity. Yet, common and distinct network correlates of ASD and ADHD remain unidentified. Here, we aimed to examine patterns of dysconnection in school-age children with ASD and ADHD and typically developing children who completed a resting state functional magnetic resonance imaging scan. Methods: We measured voxelwise network centrality, functional connectivity metrics indexing local (degree centrality [DC]) and global (eigenvector centrality) functional relationships across the entire brain connectome, in resting state functional magnetic resonance imaging data from 56 children with ASD, 45 children with ADHD, and 50 typically developing children. A one-way analysis of covariance, with group as fixed factor (whole-brain corrected), was followed by post hoc pairwise comparisons. Results: Cortical and subcortical areas exhibited centrality abnormalities, some common to both ADHD and ASD, such as in precuneus. Others were disorder-specific and included ADHD-related increases in DC in right striatum/pallidum, in contrast with ASD-related increases in bilateral temporolimbic areas. Secondary analyses differentiating children with ASD into those with or without ADHD-like comorbidity (ASD(+) and ASD(-), respectively) revealed that the ASD(+) group shared ADHD-specific abnormalities in basal ganglia. By contrast, centrality increases in temporolimbic areas characterized children with ASD regardless of ADHD-like comorbidity. At the cluster level, eigenvector centrality group patterns were similar to DC. Conclusions: ADHD and ASD are neurodevelopmental disorders with distinct and overlapping clinical presentations. This work provides evidence for both shared and distinct underlying mechanisms at the large-scale network level.

Substance misusers, including adolescent smokers, often have reduced reward system activity during processing of non-drug rewards. Using a psychophysiological interaction approach, we examined functional connectivity with the ventral striatum during reward anticipation in a large (N = 206) sample of adolescent smokers. Increased smoking frequency was associated with (1) increased connectivity with regions involved in saliency and valuation, including the orbitofrontal cortex and (2) reduced connectivity between the ventral striatum and regions associated with inhibition and risk aversion, including the right inferior frontal gyrus. These results demonstrate that functional connectivity during reward processing is relevant to adolescent addiction.

BackgroundBoth Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults.MethodsParticipants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness.ResultsAfter controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness.DiscussionYoung adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD.

One of the grand challenges faced by neuroscience is to delineate the determinants of interindividual variation in the comprehensive structural and functional connection matrices that comprise the human connectome. At present, this endeavor appears most tractable at the macroanatomic scale, where intrinsic brain activity exhibits robust patterns of synchrony that recapitulate core functional circuits at the individual level. Here, we use a classical twin study design to examine the heritability of intrinsic functional network properties in 101 twin pairs, including network activity (i.e., variance of a network's specific temporal fluctuations) and internetwork coherence (i.e., correlation between networks' specific temporal fluctuations). Five of 7 networks exhibited significantly heritable (23.3-65.2%) network activity, 6 of the 21 internetwork coherences were significantly heritable (25.6-42.0%), and 11 of the 21 internetwork coherences were significantly influenced by common environmental factors (18.0-47.1%). These results suggest that the source of interindividual variation in functional connectome has a modular architecture: individual modules represented by intrinsic connectivity networks are genetic controlled, while environmental factors influence the interplays between the modules. This work further provides network-specific hypotheses for discovery of the specific genetic and environmental factors influencing functional specialization and integration of the human brain.

The authors performed a comprehensive meta-analysis of task-based functional MRI studies of attention deficit hyperactivity disorder (ADHD).The authors searched PubMed, Ovid, EMBASE, Web of Science, ERIC, CINAHAL, and NeuroSynth for studies published through June 30, 2011. Significant differences in brain region activation between individuals with ADHD and comparison subjects were detected using activation likelihood estimation meta-analysis. Dysfunctional regions in ADHD were related to seven reference neuronal systems. The authors performed a set of meta-analyses focused on age groups (children and adults), clinical characteristics (history of stimulant treatment and presence of psychiatric comorbidities), and specific neuropsychological tasks (inhibition, working memory, and vigilance/attention).Fifty-five studies were included (39 for children and 16 for adults). In children, hypoactivation in ADHD relative to comparison subjects was observed mostly in systems involved in executive function (frontoparietal network) and attention (ventral attentional network). Significant hyperactivation in ADHD relative to comparison subjects was observed predominantly in the default, ventral attention, and somatomotor networks. In adults, ADHD-related hypoactivation was predominant in the frontoparietal system, while ADHD-related hyperactivation was present in the visual, dorsal attention, and default networks. Significant ADHD-related dysfunction largely reflected task features and was detected even in the absence of comorbid mental disorders or a history of stimulant treatment.A growing literature provides evidence of ADHD-related dysfunction in multiple neuronal systems involved in higher-level cognitive functions but also in sensorimotor processes, including the visual system, and in the default network. This meta-analytic evidence extends early models of ADHD pathophysiology that were focused on prefrontal-striatal circuits.

Item does not contain fulltext BACKGROUND: Emerging neuroscientific and genetic findings emphasize the dimensional rather than the categorical aspects of psychiatric disorders. However, the integration of dimensional approaches within the current categorical diagnostic framework remains unclear. Here, we used resting state functional magnetic resonance imaging to examine whether dimensional measures of psychiatric symptomatology capture brain-behavior relationships unaccounted for by categorical diagnoses. Additionally, we examined whether dimensional brain-behavior relationships are modified by the presence of a categorically defined illness, attention-deficit/hyperactivity disorder (ADHD). METHODS: Resting state functional magnetic resonance imaging scans were collected from 37 typically developing children (aged 10.2 +/- 2; 21 female subjects) and 37 children meeting DSM-IV Text Revision criteria for ADHD (9.7 +/- 2; 11 female subjects). Parent-rated Child Behavior Checklist Externalizing and Internalizing scores served as dimensional measures in our analyses of default network (DN) resting state functional connectivity (RSFC). RESULTS: Regardless of diagnosis, we observed several significant relationships between DN RSFC and both internalizing and externalizing scores. Increased internalizing scores were associated with stronger positive intra-DN RSFC, while increased externalizing scores were associated with reduced negative RSFC between DN and task-positive regions such as dorsal anterior cingulate cortex. Several of these brain-behavior relationships differed depending on the categorical presence of ADHD. CONCLUSIONS: Our findings suggest that while categorical diagnostic boundaries provide an inadequate basis for understanding the pathophysiology of psychiatric disorders, psychiatric illness cannot be viewed simply as an extreme of typical neural or behavioral function. Efforts to understand the neural underpinnings of psychiatric illness should incorporate both categorical and dimensional clinical assessments.

Affective empathy (AE) is distinguished clinically and neurally from cognitive empathy (CE). While AE is selectively disrupted in psychopathy, autism is associated with deficits in CE. Despite such dissociations, AE and CE together contribute to normal human empathic experience. A dimensional measure of individual differences in AE 'relative to' CE captures this interaction and may reveal brain-behavior relationships beyond those detectable with AE and CE separately. Using resting-state fMRI and measures of empathy in healthy adults, we show that relative empathic ability (REA) is reflected in the brain's intrinsic functional dynamics. Dominance of AE was associated with stronger functional connectivity among social-emotional regions (ventral anterior insula, orbitofrontal cortex, amygdala, perigenual anterior cingulate). Dominance of CE was related to stronger connectivity among areas implicated in interoception, autonomic monitoring and social-cognitive processing (brainstem, superior temporal sulcus, ventral anterior insula). These patterns were distinct from those observed with AE and CE separately. Finally, REA and the strength of several functional connections were associated with symptoms of psychopathology. These findings suggest that REA provides a dimensional index of empathic function and pathological tendencies in healthy adults, which are reflected in the intrinsic functional dynamics of neural systems associated with social and emotional cognition.

Risk avoidance is a hallmark of psychopathological conditions such as anxiety disorders. Yet few studies have examined its neural basis. The present work sought to identify the neural correlates of risk avoidance. While functional MRI scans were acquired, healthy adults ( N = 23) played a Wheel of Fortune game during which they chose to bet or pass on each of 104 proposed gamble trials. Participants also completed the Cognitive Appraisal of Risky Events (CARE, Fromme et al., 1997 ), a self-report measure of “real world” risky behavior. As expected, decision-making was associated with activation, as measured by increased BOLD responses, of the striatum, insula, anterior cingulate cortex, dorsolateral prefrontal cortex, and parietal lobe. Risk avoidance during probabilistic trials (percent of trials passed) was significantly correlated with precuneus and striatal responses to trials with a certain outcome (No-Risk). Similarly, “real world” risk avoidance, as measured by the CARE, was significantly correlated with precuneus activity during No-Risk trials. Collectively, these data suggest that precuneus and striatal responses to decision-making under certainty represent putative neural markers of risk avoidance in the laboratory and in the “real world.” Further, they underline the need to extend neuroimaging research on risk avoidance, and associated anxiety disorders, to posterior cortical regions.

The brain's energy economy excessively favors intrinsic, spontaneous neural activity over extrinsic, evoked activity, presumably to maintain its internal organization. Emerging hypotheses capable of explaining such an investment posit that the brain's intrinsic functional architecture encodes a blueprint for its repertoire of responses to the external world. Yet, there is little evidence directly linking intrinsic and extrinsic activity in the brain. Here we relate differences among individuals in the magnitude of task-evoked activity during performance of an Eriksen flanker task, to spontaneous oscillatory phenomena observed during rest. Specifically, we focused on the amplitude of low-frequency oscillations (LFO, 0.01-0.1 Hz) present in the BOLD signal. LFO amplitude measures obtained during rest successfully predicted the magnitude of task-evoked activity in a variety of regions that were all activated during performance of the flanker task. In these regions, higher LFO amplitude at rest predicted higher task-evoked activity. LFO amplitude measures obtained during rest were also found to have robust predictive value for behavior. In midline cingulate regions, LFO amplitudes predicted not only the speed and consistency of performance but also the magnitude of the behavioral congruency effect embedded in the flanker task. These results support the emerging hypothesis that the brain's repertoire of responses to the external world are represented and updated in the brain's intrinsic functional architecture.

Resting-state functional magnetic resonance imaging (fMRI) has provided a novel approach for examining interhemispheric interaction, demonstrating a high degree of functional connectivity between homotopic regions in opposite hemispheres. However, heterotopic resting-state functional connectivity (RSFC) remains relatively uncharacterized. In the present study, we examine non-homotopic regions, characterizing heterotopic RSFC and comparing it to intrahemispheric RSFC, to examine the impact of hemispheric separation on the integration and segregation of processing in the brain. Resting-state fMRI scans were acquired from 59 healthy participants to examine inter-regional correlations in spontaneous low frequency fluctuations in BOLD signal. Using a probabilistic atlas, we correlated probability-weighted time series from 112 regions (56 per hemisphere) distributed throughout the entire cerebrum. We compared RSFC for pairings of non-homologous regions located in different hemispheres (heterotopic connectivity) to RSFC for the same pairings when located within hemisphere (intrahemispheric connectivity). For positive connections, connectivity strength was greater within each hemisphere, consistent with integrated intrahemispheric processing. However, for negative connections, RSFC strength was greater between the hemispheres, consistent with segregated interhemispheric processing. These patterns were particularly notable for connections involving frontal and heteromodal regions. The distribution of positive and negative connectivity was nearly identical within and between the hemispheres, though we demonstrated detailed regional variation in distribution. We discuss implications for leading models of interhemispheric interaction. The future application of our analyses may provide important insight into impaired interhemispheric processing in clinical and aging populations.

Functional homotopy, the high degree of synchrony in spontaneous activity between geometrically corresponding interhemispheric (i.e., homotopic) regions, is a fundamental characteristic of the intrinsic functional architecture of the brain. However, despite its prominence, the lifespan development of the homotopic resting-state functional connectivity (RSFC) of the human brain is rarely directly examined in functional magnetic resonance imaging studies. Here, we systematically investigated age-related changes in homotopic RSFC in 214 healthy individuals ranging in age from 7 to 85 years. We observed marked age-related changes in homotopic RSFC with regionally specific developmental trajectories of varying levels of complexity. Sensorimotor regions tended to show increasing homotopic RSFC, whereas higher-order processing regions showed decreasing connectivity (i.e., increasing segregation) with age. More complex maturational curves were also detected, with regions such as the insula and lingual gyrus exhibiting quadratic trajectories and the superior frontal gyrus and putamen exhibiting cubic trajectories. Sex-related differences in the developmental trajectory of functional homotopy were detected within dorsolateral prefrontal cortex (Brodmann areas 9 and 46) and amygdala. Evidence of robust developmental effects in homotopic RSFC across the lifespan should serve to motivate studies of the physiological mechanisms underlying functional homotopy in neurodegenerative and psychiatric disorders.

Analytic tools for addressing spontaneous brain activity, as acquired with fMRI during the “resting-state,” have grown dramatically over the past decade. Along with each new technique, novel hypotheses about the functional organization of the brain are also available to researchers. We review six prominent categories of resting-state fMRI data analysis: seed-based functional connectivity, independent component analysis, clustering, pattern classification, graph theory, and two “local” methods. In surveying these methods, we address their underlying assumptions, methodologies, and novel applications.

The resting brain exhibits coherent patterns of spontaneous low-frequency BOLD fluctuations. These so-called resting-state functional connectivity (RSFC) networks are posited to reflect intrinsic representations of functional systems commonly implicated in cognitive function. Yet, the direct relationship between RSFC and the BOLD response induced by task performance remains unclear. Here we examine the relationship between a region's pattern of RSFC across participants and that same region's level of BOLD activation during an Eriksen Flanker task. To achieve this goal we employed a voxel-matched regression method, which assessed whether the magnitude of task-induced activity at each brain voxel could be predicted by measures of RSFC strength for the same voxel, across 26 healthy adults. We examined relationships between task-induced activation and RSFC strength for six different seed regions [Fox, M.D., Snyder, A.Z., Vincent, J.L., Corbetta, M., Van Essen, D.C., Raichle, M.E., 2005. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc. Natl. Acad. Sci. U. S. A. 102, 9673–9678.], as well as the “default mode” and “task-positive” resting-state networks in their entirety. Our results indicate that, for a number of brain regions, inter-individual differences in task-induced BOLD activity were predicted by one of two resting-state properties: (1) the region's positive connectivity strength with the task-positive network, or (2) its negative connectivity with the default mode network. Strikingly, most of the regions exhibiting a significant relationship between their RSFC properties and task-induced BOLD activity were located in transition zones between the default mode and task-positive networks. These results suggest that a common mechanism governs many brain regions' neural activity during rest and its neural activity during task performance.

Split-brain patients present a unique opportunity to address controversies regarding subcortical contributions to interhemispheric coordination. We characterized residual functional connectivity in a complete commissurotomy patient by examining patterns of low-frequency BOLD functional MRI signal. Using independent components analysis and region-of-interest-based functional connectivity analyses, we demonstrate bilateral resting state networks in a patient lacking all major cerebral commissures. Compared with a control group, the patient's interhemispheric correlation scores fell within the normal range for two out of three regions examined. Thus, we provide evidence for bilateral resting state networks in a patient with complete commissurotomy. Such continued interhemispheric interaction suggests that, at least in part, cortical networks in the brain can be coordinated by subcortical mechanisms.

Pathophysiologic models of attention-deficit/hyperactivity disorder (ADHD) have focused on frontal-striatal circuitry with alternative hypotheses relatively unexplored. On the basis of evidence that negative interactions between frontal foci involved in cognitive control and the non-goal-directed "default-mode" network prevent attentional lapses, we hypothesized abnormalities in functional connectivity of these circuits in ADHD.Resting-state blood oxygen level-dependent functional magnetic resonance imaging (fMRI) scans were obtained at 3.0-Tesla in 20 adults with ADHD and 20 age- and sex-matched healthy volunteers.Examination of healthy control subjects verified presence of an antiphasic or negative relationship between activity in dorsal anterior cingulate cortex (centered at x = 8, y = 7, z = 38) and in default-mode network components. Group analyses revealed ADHD-related compromises in this relationship, with decreases in the functional connectivity between the anterior cingulate and precuneus/posterior cingulate cortex regions (p.0004, corrected). Secondary analyses revealed an extensive pattern of ADHD-related decreases in connectivity between precuneus and other default-mode network components, including ventromedial prefrontal cortex (p3 x 10(-11), corrected) and portions of posterior cingulate (p.02, corrected).Together with prior unbiased anatomic evidence of posterior volumetric abnormalities, our findings suggest that the long-range connections linking dorsal anterior cingulate to posterior cingulate and precuneus should be considered as a candidate locus of dysfunction in ADHD.

The default mode network (DMN), based in ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC), exhibits higher metabolic activity at rest than during performance of externally-oriented cognitive tasks. Recent studies have suggested that competitive relationships between the DMN and various task-positive networks involved in task performance are intrinsically represented in the brain in the form of strong negative correlations (anticorrelations) between spontaneous fluctuations in these networks. Most neuroimaging studies characterize the DMN as a homogenous network, thus few have examined the differential contributions of DMN components to such competitive relationships. Here we examined functional differentiation within the default mode network, with an emphasis on understanding competitive relationships between this and other networks. We used a seed correlation approach on resting-state data to assess differences in functional connectivity between these two regions and their anticorrelated networks. While the positively correlated networks for the vmPFC and PCC seeds largely overlapped, the anticorrelated networks for each showed striking differences. Activity in vmPFC negatively predicted activity in parietal visual spatial and temporal attention networks, whereas activity in PCC negatively predicted activity in prefrontal-based motor control circuits. Granger causality analyses suggest that vmPFC and PCC exert greater influence on their anticorrelated networks than the other way around, suggesting that these two default mode nodes may directly modulate activity in task-positive networks. Thus, the two major nodes comprising the default mode network are differentiated with respect to the specific brain systems with which they interact, suggesting greater heterogeneity within this network than is commonly appreciated.

Increased intraindividual variability (IIV) is a hallmark of disorders of attention. Recent work has linked these disorders to abnormalities in a "default mode" network, comprising brain regions routinely deactivated during goal-directed cognitive tasks. Findings from a study of the neural basis of attentional lapses suggest that a competitive relationship between the "task-negative" default mode network and regions of a "task-positive" attentional network is a potential locus of dysfunction in individuals with increased IIV. Resting state studies have shown that this competitive relationship is intrinsically represented in the brain, in the form of a negative correlation or antiphase relationship between spontaneous activity occurring in the two networks. We quantified the negative correlation between these two networks in 26 subjects, during active (Eriksen flanker task) and resting state scans. We hypothesized that the strength of the negative correlation is an index of the degree of regulation of activity in the default mode and task-positive networks and would be positively related to consistent behavioral performance. We found that the strength of the correlation between the two networks varies across individuals. These individual differences appear to be behaviorally relevant, as interindividual variation in the strength of the correlation was significantly related to individual differences in response time variability: the stronger the negative correlation (i.e., the closer to 180 degrees antiphase), the less variable the behavioral performance. This relationship was moderately consistent across resting and task conditions, suggesting that the measure indexes moderately stable individual differences in the integrity of functional brain networks. We discuss the implications of these findings for our understanding of the behavioral significance of spontaneous brain activity, in both healthy and clinical populations.

Anterior cingulate cortex (ACC) is a nexus of information processing and regulation in the brain. Reflecting this central role, ACC is structurally and functionally heterogeneous, a fact long appreciated in studies of non-human primates. Human neuroimaging studies also recognize this functional heterogeneity, with meta-analyses and task-based studies demonstrating the existence of motor, cognitive and affective subdivisions. In contrast to task-based approaches, examinations of resting-state functional connectivity enable the characterization of task-independent patterns of correlated activity. In a novel approach to understanding ACC functional segregation, we systematically mapped ACC functional connectivity during rest. We examined patterns of functional connectivity for 16 seed ROIs systematically placed throughout caudal, rostral, and subgenual ACC in each hemisphere. First, our data support the commonly observed rostral/caudal distinction, but also suggest the existence of a dorsal/ventral functional distinction. For each of these distinctions, more fine-grained patterns of differentiation were observed than commonly appreciated in human imaging studies. Second, we demonstrate the presence of negatively predicted relationships between distinct ACC functional networks. In particular, we highlight negative relationships between rostral ACC-based affective networks (including the “default mode network”) and dorsal–caudal ACC-based frontoparietal attention networks. Finally, interhemispheric activations were more strongly correlated between homologous regions than in non-homologous regions. We discuss the implications of our work for understanding ACC function and potential applications to clinical populations.

Currently, the developmental trajectories of neural circuits implicated in autism spectrum disorders (ASD) are largely unknown. Here, we specifically focused on age-related changes in the functional circuitry of the posterior superior temporal sulcus (pSTS), a key hub underlying social-cognitive processes known to be impaired in ASD. Using a cross-sectional approach, we analysed resting-state functional magnetic resonance imaging (fMRI) data collected from children, adolescents and adults available through the autism brain imaging data exchange repository [n ¼ 106 with ASD and n ¼ 109 typical controls (TC), ages 7–30 years]. The observed age-related changes of pSTS intrinsic functional connectivity (iFC) suggest that no single developmental pattern characterizes ASD. Instead, pSTS circuitry displayed a complex developmental picture, with some functional circuits showing patterns consistent with atypical development in ASD relative to TC (pSTS-iFC with fusiform gyrus and angular gyrus) and others showing delayed maturation (pSTS-iFC with regions of the action perception network). Distinct developmental trajectories in different functional circuits in ASD likely reflect differential age-related changes in the socio-cognitive processes they underlie. Increasing insight on these mechanisms is a critical step in the development of age-specific interventions in ASD. ispartof: Social Cognitive and Affective Neuroscience vol:10 issue:10 pages:1413-1423 ispartof: location:England status: published

Highlights • Children with or without ADHD have moderate/high R-fMRI test–retest reliability. • Reliability is greater in controls than ADHD across most R-fMRI metrics. • Regional differences in ICC related to diagnostic groups reflect underlying pathophysiology for ADHD affecting both inter and intra subject variability., To date, only one study has examined test–retest reliability of resting state fMRI (R-fMRI) in children, none in clinical developing groups. Here, we assessed short-term test–retest reliability in a sample of 46 children (11–17.9 years) with attention-deficit/hyperactivity disorder (ADHD) and 57 typically developing children (TDC). Our primary test–retest reliability measure was the intraclass correlation coefficient (ICC), quantified for a range of R-fMRI metrics. We aimed to (1) survey reliability within and across diagnostic groups, and (2) compare voxel-wise ICC between groups. We found moderate-to-high ICC across all children and within groups, with higher-order functional networks showing greater ICC. Nearly all R-fMRI metrics exhibited significantly higher ICC in TDC than in children with ADHD for one or more regions. In particular, posterior cingulate and ventral precuneus exhibited group differences in ICC across multiple measures. In the context of overall moderate-to-high test–retest reliability in children, regional differences in ICC related to diagnostic groups likely reflect the underlying pathophysiology for ADHD. Our currently limited understanding of the factors contributing to inter- and intra-subject variability in ADHD underscores the need for large initiatives aimed at examining their impact on test–retest reliability in both clinical and developing populations.

We propose a novel method for neurodevelopmental brain mapping that displays how an individual's values for a quantity of interest compare with age-specific norms. By estimating smoothly age-varying distributions at a set of brain regions of interest, we derive age-dependent region-wise quantile ranks for a given individual, which can be presented in the form of a brain map. Such quantile rank maps could potentially be used for clinical screening. Bootstrap-based confidence intervals are proposed for the quantile rank estimates. We also propose a recalibrated Kolmogorov–Smirnov test for detecting group differences in the age-varying distribution. This test is shown to be more robust to model misspecification than a linear regression-based test. The proposed methods are applied to brain imaging data from the Nathan Kline Institute Rockland Sample and from the Autism Brain Imaging Data Exchange (ABIDE) sample.

Kelly C, Foxe JJ, Garavan H. Patterns of normal human brain plasticity after practice and their implications for neurorehabilitation. Objectives To illustrate how our knowledge about normal patterns of experience-induced plasticity can provide insights into the mechanisms of neurorehabilitation; to provide an overview of the practice-effects literature in order to simplify and amalgamate a large number of heterogeneous findings and identify typical patterns of practice effects and their determining factors; and to concentrate on the impact of practice on higher cognitive functions, such as working memory, and present some preliminary but promising behavioral data that show how practice on a complex cognitive task can benefit cognitive functioning more generally. Data Sources We performed a systematic search for peer-reviewed journal articles using computerized databases (PubMed, ISI Web of Science, PsycINFO). Data Selection Neuroimaging studies using functional magnetic resonance imaging (fMRI) or positron-emission tomography (PET) to examine functional activation changes as a result of practice on sensory, motor, or cognitive tasks in normal (healthy) populations were included in the review. Further studies were identified that examined the effects of rehabilitative training on functional activations in clinical populations using fMRI or PET. Data Extraction Important characteristics of the selected studies were summarized in a systematic manner so to enable the extraction of specific factors impacting on the pattern of practice effects observed. Data Synthesis We identified a number of factors that impact on the patterns of practice effects observed and discuss how the insights gained from the study of healthy populations can by applied to rehabilitation of cognitive deficits in clinical populations. Conclusions Progress in our understanding of neurorehabilitative plasticity will be enabled by neuroimaging examinations of cognitive rehabilitation training grounded in a knowledge of normal (healthy) patterns of brain activation and practice-induced plasticity.

Brain activations underlying cognitive processes are subject to modulation as a result of increasing cognitive demands, individual differences, and practice. The present study investigated these modulatory effects in a cognitive control task which required inhibition of prepotent responses based on the contents of working memory (WM) and which enabled a novel dissociation of item-specific and task-skill effects resulting from brief practice. Distinct responses in areas underlying WM and inhibitory control in the absence of behavioral changes reflected different effects of item repetition and general task practice on tonic working memory and phasic inhibitory processes. Item repetition was associated with decreases in both unique and common areas subserving WM and inhibitory control. In contrast, general task practice was reflected in decreases in the level of tonic WM activity required to maintain a consistently high level of task performance but increased activity in a number of core inhibitory regions including dorsolateral and inferior PFC and inferior parietal cortex. Furthermore, both practice and individual differences in task performance were associated with the ability to modulate and maintain activity in frontostriatal areas mediating attentional control, suggesting that the areas that differ between individuals can be modulated by practice within an individual. These results raise the possibility that a fundamental human ability, reflexive cognitive control, is amenable to practice.

Efforts to identify meaningful functional imaging-based biomarkers are limited by the ability to reliably characterize inter-individual differences in human brain function. Although a growing number of connectomics-based measures are reported to have moderate to high test-retest reliability, the variability in data acquisition, experimental designs, and analytic methods precludes the ability to generalize results. The Consortium for Reliability and Reproducibility (CoRR) is working to address this challenge and establish test-retest reliability as a minimum standard for methods development in functional connectomics. Specifically, CoRR has aggregated 1,629 typical individuals’ resting state fMRI (rfMRI) data (5,093 rfMRI scans) from 18 international sites, and is openly sharing them via the International Data-sharing Neuroimaging Initiative (INDI). To allow researchers to generate various estimates of reliability and reproducibility, a variety of data acquisition procedures and experimental designs are included. Similarly, to enable users to assess the impact of commonly encountered artifacts (for example, motion) on characterizations of inter-individual variation, datasets of varying quality are included.

Chronic pain is a complex physiological and psychological phenomenon. Implicit learning mechanisms contribute to the development of chronic pain and to persistent changes in the central nervous system. We hypothesized that these central abnormalities can be remedied with Cognitive Behavioral Therapy (CBT). Specifically, since regions of the anterior Default Mode Network (DMN) are centrally involved in emotional regulation via connections with limbic regions, such as the amygdala, remediation of maladaptive behavioral and cognitive patterns as a result of CBT for chronic pain would manifest itself as a change in the intrinsic functional connectivity (iFC) between these prefrontal and limbic regions. Resting-state functional neuroimaging was performed in patients with chronic pain before and after 11-week CBT (n = 19), as well as a matched (ages 19–59, both sexes) active control group of patients who received educational materials (n = 19). Participants were randomized prior to the intervention. To investigate the differential impact of treatment on intrinsic functional connectivity (iFC), we compared pre–post differences in iFC between groups. In addition, we performed exploratory whole brain analyses of changes in fractional amplitude of low frequency fluctuations (fALFF). The course of CBT led to significant improvements in clinical measures of pain and self-efficacy for coping with chronic pain. Significant group differences in pre–post changes in both iFC and fALFF were correlated with clinical outcomes. Compared to control patients, iFC between the anterior DMN and the amygdala/periaqueductal gray decreased following CBT, whereas iFC between the basal ganglia network and the right secondary somatosensory cortex increased following CBT. CBT patients also had increased post-therapy fALFF in the bilateral posterior cingulate and the cerebellum. By delineating neuroplasticity associated with CBT-related improvements, these results add to mounting evidence that CBT is a valuable treatment option for chronic pain.

Analyses of intrinsic fMRI BOLD signal fluctuations reliably reveal correlated and anticorrelated functional networks in the brain. Because the BOLD signal is an indirect measure of neuronal activity and anticorrelations can be introduced by preprocessing steps, such as global signal regression, the neurophysiological significance of correlated and anticorrelated BOLD fluctuations is a source of debate. Here, we address this question by examining the correspondence between the spatial organization of correlated BOLD fluctuations and correlated fluctuations in electrophysiological high γ power signals recorded directly from the cortical surface of 5 patients. We demonstrate that both positive and negative BOLD correlations have neurophysiological correlates reflected in fluctuations of spontaneous neuronal activity. Although applying global signal regression to BOLD signals results in some BOLD anticorrelations that are not apparent in the ECoG data, it enhances the neuronal-hemodynamic correspondence overall. Together, these findings provide support for the neurophysiological fidelity of BOLD correlations and anticorrelations.

BACKGROUND AND PURPOSE: CC is extensively involved in MS with interhemispheric dysfunction. The purpose of this study was to determine whether interhemispheric correlation is altered in MS by use of a recently developed RS-fMRI homotopy technique and whether these homotopic changes correlate with CC pathology. MATERIALS AND METHODS: Twenty-four patients with relapsing-remitting MS and 24 age-matched healthy volunteers were studied with RS-fMRI and DTI acquired at 3T. The Pearson correlation of each pair of symmetric interhemispheric voxels of RS-fMRI time-series data was performed to compute VMHC, and z-transformed for subsequent group-level analysis. In addition, 5 CC segments in the midsagittal area and DTI-derived FA were measured to quantify interhemispheric microstructural changes and correlate with global and regional VMHC in MS. RESULTS: Relative to control participants, patients with MS exhibited an abnormal homotopic pattern with decreased VMHC in the primary visual, somatosensory, and motor cortices and increased VMHC in several regions associated with sensory processing and motor control including the insula, thalamus, pallidum, and cerebellum. The global VMHC correlates moderately with the average FA of the entire CC for all participants in both groups (r = 0.3; P = .03). CONCLUSIONS: Our data provide preliminary evidence of the potential usefulness of VMHC analyses for the detection of abnormalities of interhemispheric coordination in MS. We demonstrated that the whole-brain homotopic RS-fMRI pattern was altered in patients with MS, which was partially associated with the underlying structural degenerative changes of CC measured with FA.

This observational, cross-sectional study investigates cortical signatures of developmental dyslexia, particularly from the perspective of behavioral remediation. We employed resting-state fMRI, and compared intrinsic functional connectivity (iFC) patterns of known reading regions (seeds) among three dyslexia groups characterized by (a) no remediation (current reading and spelling deficits), (b) partial remediation (only reading deficit remediated), and (c) full remediation (both reading and spelling deficits remediated), and a group of age- and IQ-matched typically developing children (TDC) (total N = 44, age range = 7–15 years). We observed significant group differences in iFC of two seeds located in the left posterior reading network – left intraparietal sulcus (L.IPS) and left fusiform gyrus (L.FFG). Specifically, iFC between L.IPS and left middle frontal gyrus was significantly weaker in all dyslexia groups, irrespective of remediation status/literacy competence, suggesting that persistent dysfunction in the fronto-parietal attention network characterizes dyslexia. Additionally, relative to both TDC and the no remediation group, the remediation groups exhibited stronger iFC between L.FFG and right middle occipital gyrus (R.MOG). The full remediation group also exhibited stronger negative iFC between the same L.FFG seed and right medial prefrontal cortex (R.MPFC), a core region of the default network These results suggest that behavioral remediation may be associated with compensatory changes anchored in L.FFG, which reflect atypically stronger coupling between posterior visual regions (L.FFG-R.MOG) and greater functional segregation between task-positive and task-negative regions (L.FFG-R.MPFC). These findings were bolstered by significant relationships between the strength of the identified functional connections and literacy scores. We conclude that examining iFC can reveal cortical signatures of dyslexia with particular promise for monitoring neural changes associated with behavioral remediation.

his installment of Translations introduces a modality of functional magnetic resonance T imaging (fMRI), often called resting state fMRI (R-fMRI), and discusses its relevance to child psychiatry. The authors provide an introduction to R-fMRI, point out the salient differences between standard task-based fMRI and R-fMRI, outline its major strengths and weaknesses, and discuss potential ramifications of this approach from a clinical and developmental perspective. As reviewed by several investigators, multiple lines of neuroimaging research converged in the 1990s to create renewed interest in brain activity that occurs during “rest.” The idea of using neuroimaging to study spontaneous as opposed to evoked brain activity initially met with resistance. In process, it ran counter to the scientific precept of testing two experimental conditions against each other, which, in the context of functional neuroimaging, has been transformative for cognitive neuroscience. By content, the idea of measuring spontaneous brain activity was immediately complicated by ideas of consciousness and the many historical layers of the mind-brain dialectic. Despite these thorny beginnings, R-fMRI approaches have rapidly proliferated in clinical neuroscience over the past 5 years. R-fMRI data are based on the same blood oxygen level–dependent (BOLD) signal that is collected in the magnet during task-based fMRI (Table 1 lists acronyms commonly used in the field). However, R-fMRI focuses on spontaneous fluctuations in the BOLD signal that are usually treated as “noise” or “baseline” in task-based fMRI studies. These fluctuations are extremely slow (generally fewer than six cycles per minute) and exhibit amplitudes that are often more than one order of magnitude larger than the evoked signal changes observed with task-based fMRI. The most common way to record these signal

Background: Default network (DN) abnormalities have been identified in patients with chronic schizophrenia using "resting state" functional magnetic resonance imaging (R-fMRI). Here, we examined the integrity of the DN in patients experiencing their first episode of psychosis (FEP) compared with sex-and age-matched healthy controls. Methods: We collected R-fMRI data from 19 FEP patients (mean age 24.9 +/- 4.8 yrs, 14 males) and 19 healthy controls (26.1 +/- 4.8 yrs, 14 males) at 3 T. Following standard preprocessing, we examined the functional connectivity (FC) of two DN subsystems and the two DN hubs (P

Idiopathic generalized epilepsy (IGE) is associated with widespread cortical network abnormalities on electroencephalography. Resting state functional connectivity (RSFC), based on fMRI, can assess the brain's global functional organization and its disruption in clinical conditions. We compared RSFC associated with the 'default mode network' (DMN) between people with IGE and healthy controls. Strength of functional connectivity within the DMN associated with seeds in the posterior cingulate cortex (PCC) and medial prefrontal cortices (MPFC) was compared between people with IGE and healthy controls and was correlated with seizure duration, age of seizure onset and age at scan. Those with IGE showed markedly reduced functional network connectivity between anterior and posterior cortical seed regions. Seizure duration positively correlates with RSFC between parahippocampal gyri and the PCC but negatively correlates with connectivity between the PCC and frontal lobe. The observed pattern of disruption provides evidence for integration- and segregation-type network abnormalities and supports aberrant network organization among people with IGE.

The functional MRI (fMRI) community has zealously embraced resting state or intrinsic functional connectivity approaches to mapping brain organization. Having demonstrated their utility for charting the large-scale functional architecture of the brain, the field is now leveraging task-independent methods for the investigation of phenotypic variation and the identification of biomarkers for clinical conditions. Enthusiasm aside, questions regarding the significance and validity of intrinsic brain phenomena remain. Here, we discuss these challenges and outline current developments that, in moving the field toward discovery science, permit a shift from cartography toward a mechanistic understanding of the neural bases of variation in cognition, emotion and behavior.

Task-based neuroimaging studies face the challenge of developing tasks capable of equivalently probing reading networks across different age groups. Resting-state fMRI, which requires no specific task, circumvents these difficulties. Here, in 25 children (8-14 years) and 25 adults (21-46 years), we examined the extent to which individual differences in reading competence can be related to resting-state functional connectivity (RSFC) of regions implicated in reading. In both age groups, reading standard scores correlated positively with RSFC between the left precentral gyrus and other motor regions, and between Broca's and Wernicke's areas. This suggests that, regardless of age group, stronger coupling among motor regions, as well as between language/speech regions, subserves better reading, presumably reflecting automatized articulation. We also observed divergent RSFC-behavior relationships in children and adults, particularly those anchored in the left fusiform gyrus (FFG) (the visual word form area). In adults, but not children, better reading performance was associated with stronger positive correlations between FFG and phonology-related regions (Broca's area and the left inferior parietal lobule), and with stronger negative relationships between FFG and regions of the "task-negative" default network. These results suggest that both positive RSFC (functional coupling) between reading regions and negative RSFC (functional segregation) between a reading region and default network regions are important for automatized reading, characteristic of adult readers. Together, our task-independent RSFC findings highlight the importance of appreciating developmental changes in the neural correlates of reading competence, and suggest that RSFC may serve to facilitate the identification of reading disorders in different age groups.

Adaptive brain function is characterized by dynamic interactions within and between neuronal circuits, often occurring at the time scale of milliseconds. These complex interactions between adjacent and noncontiguous brain areas depend on a functional architecture that is maintained even in the absence of input. Functional MRI studies carried out during rest (R-fMRI) suggest that this architecture is represented in low-frequency (

Neuroscience is increasingly focusing on developmental factors related to human structural and functional connectivity. Unfortunately, to date, diffusion-based imaging approaches have only contributed modestly to these broad objectives, despite the promise of diffusion-based tractography. Here, we report a novel data-driven approach to detect similarities and differences among white matter tracts with respect to their developmental trajectories, using 64-direction diffusion tensor imaging. Specifically, using a cross-sectional sample comprising 144 healthy individuals (7 to 48 years old), we applied k-means cluster analysis to separate white matter voxels based on their age-related trajectories of fractional anisotropy. Optimal solutions included 5-, 9- and 14-clusters. Our results recapitulate well-established tracts (e.g., internal and external capsule, optic radiations, corpus callosum, cingulum bundle, cerebral peduncles) and subdivisions within tracts (e.g., corpus callosum, internal capsule). For all but one tract identified, age-related trajectories were curvilinear (i.e., inverted 'U-shape'), with age-related increases during childhood and adolescence followed by decreases in middle adulthood. Identification of peaks in the trajectories suggests that age-related losses in fractional anisotropy occur as early as 23 years of age, with mean onset at 30 years of age. Our findings demonstrate that data-driven analytic techniques may be fruitfully applied to extant diffusion tensor imaging datasets in normative and neuropsychiatric samples.

Background The recent upsurge in interest about pediatric bipolar disorder (BD) has spurred the need for greater understanding of its neurobiology. Structural and functional magnetic resonance imaging studies have implicated fronto-temporal dysfunction in pediatric BD. However, recent data suggest that task-dependent neural changes account for a small fraction of the brain's energy consumption. We now report the first use of task-independent spontaneous resting state functional connectivity (RSFC) to study the neural underpinnings of pediatric BD. Methods We acquired task-independent RSFC blood oxygen level-dependent functional magnetic resonance imaging scans while participants were at rest and also a high-resolution anatomical image (both at three Tesla) in BD and control youths ( n = 15 of each). We focused, on the basis of prior research, on the left dorsolateral prefrontal cortex (DLPFC), amygdala, and accumbens. Image processing and group-level analyses followed that of prior work. Results Our primary analysis showed that pediatric BD participants had significantly greater negative RSFC between the left DLPFC and the right superior temporal gyrus versus control subjects. Secondary analyses using partial correlation showed that BD and control youths had opposite phase relationships between spontaneous RSFC fluctuations in the left DLPFC and right superior temporal gyrus. Conclusions Our data indicate that pediatric BD is characterized by altered task-independent functional connectivity in a fronto-temporal circuit that is also implicated in working memory and learning. Further study is warranted to determine the effects of age, gender, development, and treatment on this circuit in pediatric BD.

Models of autism spectrum disorders (ASD) as neural disconnection syndromes have been predominantly supported by examinations of abnormalities in corticocortical networks in adults with autism. A broader body of research implicates subcortical structures, particularly the striatum, in the physiopathology of autism. Resting state functional magnetic resonance imaging has revealed detailed maps of striatal circuitry in healthy and psychiatric populations and vividly captured maturational changes in striatal circuitry during typical development.Using resting state functional magnetic resonance imaging, we examined striatal functional connectivity (FC) in 20 children with ASD and 20 typically developing children between the ages of 7.6 and 13.5 years. Whole-brain voxelwise statistical maps quantified within-group striatal FC and between-group differences for three caudate and three putamen seeds for each hemisphere.Children with ASD mostly exhibited prominent patterns of ectopic striatal FC (i.e., functional connectivity present in ASD but not in typically developing children), with increased functional connectivity between nearly all striatal subregions and heteromodal associative and limbic cortex previously implicated in the physiopathology of ASD (e.g., insular and right superior temporal gyrus). Additionally, we found striatal functional hyperconnectivity with the pons, thus expanding the scope of functional alterations implicated in ASD. Secondary analyses revealed ASD-related hyperconnectivity between the pons and insula cortex.Examination of FC of striatal networks in children with ASD revealed abnormalities in circuits involving early developing areas, such as the brainstem and insula, with a pattern of increased FC in ectopic circuits that likely reflects developmental derangement rather than immaturity of functional circuits.