Adam Pines

All Publications

• Psychiatric Symptoms, Cognition, and Symptom Severity in Children. JAMA psychiatry Pines, A., Tozzi, L., Bertrand, C., Keller, A. S., Zhang, X., Whitfield-Gabrieli, S., Hastie, T., Larsen, B., Leikauf, J., Williams, L. M. 2024

  Abstract

  Mental illnesses are a leading cause of disability globally, and functional disability is often in part caused by cognitive impairments across psychiatric disorders. However, studies have consistently reported seemingly opposite findings regarding the association between cognition and psychiatric symptoms.To determine if the association between general cognition and mental health symptoms diverges at different symptom severities in children.A total of 5175 children with complete data at 2 time points assessed 2 years apart (aged 9 to 11 years at the first assessment) from the ongoing Adolescent Brain and Cognitive Development (ABCD) study were evaluated for a general cognition factor and mental health symptoms from September 2016 to August 2020 at 21 sites across the US. Polynomial and generalized additive models afforded derivation of continuous associations between cognition and psychiatric symptoms across different ranges of symptom severity. Data were analyzed from December 2022 to April 2024.Aggregate cognitive test scores (general cognition) were primarily evaluated in relation to total and subscale-specific symptoms reported from the Child Behavioral Checklist.The sample included 5175 children (2713 male [52.4%] and 2462 female [47.6%]; mean [SD] age, 10.9 [1.18] years). Previously reported mixed findings regarding the association between general cognition and symptoms may consist of several underlying, opposed associations that depend on the class and severity of symptoms. Linear models recovered differing associations between general cognition and mental health symptoms, depending on the range of symptom severities queried. Nonlinear models confirm that internalizing symptoms were significantly positively associated with cognition at low symptom burdens higher cognition = more symptoms) and significantly negatively associated with cognition at high symptom burdens.The association between mental health symptoms and general cognition in this study was nonlinear. Internalizing symptoms were both positively and negatively associated with general cognition at a significant level, depending on the range of symptom severities queried in the analysis sample. These results appear to reconcile mixed findings in prior studies, which implicitly assume that symptom severity tracks linearly with cognitive ability across the entire spectrum of mental health. As the association between cognition and symptoms may be opposite in low vs high symptom severity samples, these results reveal the necessity of clinical enrichment in studies of cognitive impairment.

  View details for DOI 10.1001/jamapsychiatry.2024.2399

  View details for PubMedID 39196567

• Development of top-down cortical propagations in youth. Neuron Pines, A., Keller, A. S., Larsen, B., Bertolero, M., Ashourvan, A., Bassett, D. S., Cieslak, M., Covitz, S., Fan, Y., Feczko, E., Houghton, A., Rueter, A. R., Saggar, M., Shafiei, G., Tapera, T. M., Vogel, J., Weinstein, S. M., Shinohara, R. T., Williams, L. M., Fair, D. A., Satterthwaite, T. D. 2023

  Abstract

  Hierarchical processing requires activity propagating between higher- and lower-order cortical areas. However, functional neuroimaging studies have chiefly quantified fluctuations within regions over time rather than propagations occurring over space. Here, we leverage advances in neuroimaging and computer vision to track cortical activity propagations in a large sample of youth (n = 388). We delineate cortical propagations that systematically ascend and descend a cortical hierarchy in all individuals in our developmental cohort, as well as in an independent dataset of densely sampled adults. Further, we demonstrate that top-down, descending hierarchical propagations become more prevalent with greater demands for cognitive control as well as with development in youth. These findings emphasize that hierarchical processing is reflected in the directionality of propagating cortical activity and suggest top-down propagations as a potential mechanism of neurocognitive maturation in youth.

  View details for DOI 10.1016/j.neuron.2023.01.014

  View details for PubMedID 36803653

• Dissociable multi-scale patterns of development in personalized brain networks NATURE COMMUNICATIONS Pines, A. R., Larsen, B., Cui, Z., Sydnor, V. J., Bertolero, M. A., Adebimpe, A., Alexander-Bloch, A. F., Davatzikos, C., Fair, D. A., Gur, R. C., Gur, R. E., Li, H., Milham, M. P., Moore, T. M., Murtha, K., Parkes, L., Thompson-Schill, S. L., Shanmugan, S., Shinohara, R. T., Weinstein, S. M., Bassett, D. S., Fan, Y., Satterthwaite, T. D. 2022; 13 (1): 2647

  Abstract

  The brain is organized into networks at multiple resolutions, or scales, yet studies of functional network development typically focus on a single scale. Here, we derive personalized functional networks across 29 scales in a large sample of youths (n = 693, ages 8-23 years) to identify multi-scale patterns of network re-organization related to neurocognitive development. We found that developmental shifts in inter-network coupling reflect and strengthen a functional hierarchy of cortical organization. Furthermore, we observed that scale-dependent effects were present in lower-order, unimodal networks, but not higher-order, transmodal networks. Finally, we found that network maturation had clear behavioral relevance: the development of coupling in unimodal and transmodal networks are dissociably related to the emergence of executive function. These results suggest that the development of functional brain networks align with and refine a hierarchy linked to cognition.

  View details for DOI 10.1038/s41467-022-30244-4

  View details for Web of Science ID 000795171100003

  View details for PubMedID 35551181

  View details for PubMedCentralID PMC9098559

• Sex differences in response to violence: role of salience network expansion and connectivity on depression. Translational psychiatry Butler, E. R., Samia, N. I., Mejia, A. F., Pham, D. D., Pines, A., Nusslock, R. 2025; 15 (1): 427

  Abstract

  Violence is a major risk factor for depression across development. Depression quickly worsens during early adolescence, however, and especially among females, who experience worse depression following threats than males. This may be because they perceive future threats as less controllable. Evidence suggests that features of the salience network may serve as particularly critical mechanisms explaining sex differences on depression in response to threat, as those with depressive disorders have more expansive salience networks than controls, and threatening experiences result in the brain utilizing more tissue for fear generation in rodent models. Using a longitudinal sample of 220 adolescents ages 14-18 from the Chicago area, we test if salience network expansion and connectivity explain the differential impact of violence on depression across the sexes. We found that the association between violence and depression was greater for females than males ( β 3 2 = 0.337 , p = 0.025 ), such that there was a positive association among females, but not males. We did not find an association between violence and salience network expansion or connectivity for females or males. Contrary to our hypotheses, we found that the association between the expansion of the salience network and depression was positive for males ( β 1 5 = 0.242 , p = 0.039 ), as was the association between salience network connectivity and depression ( β 1 6 = 0.238 , p = 0.030 ). Both of these effects remained after controlling for depression two years prior, indicating that exposures that impact males' depression through the salience network may occur during middle adolescence. We did not find an association between salience network expansion or connectivity and depression for females. Through identifying types of exposures, their relevant developmental timing, and mechanisms connecting exposures with depression, this work helps to inform interventions to prevent the onset of depression following adversity, thereby reducing the lifetime burden of depression.

  View details for DOI 10.1038/s41398-025-03614-x

  View details for PubMedID 41120285

  View details for PubMedCentralID PMC12541095

• Reproducible sex differences in personalised functional network topography in youth. The British journal of psychiatry : the journal of mental science Keller, A. S., Sun, K. Y., Francisco, A., Robinson, H., Beydler, E., Bassett, D. S., Cieslak, M., Cui, Z., Davatzikos, C., Fan, Y., Gardner, M., Kishton, R., Kornfield, S. L., Larsen, B., Li, H., Linder, I., Pines, A., Pritschet, L., Raznahan, A., Roalf, D. R., Seidlitz, J., Shafiei, G., Shinohara, R. T., White, L. K., Wolf, D. H., Alexander-Bloch, A., Satterthwaite, T. D., Shanmugan, S. 2025: 1-9

  Abstract

  A key step toward understanding psychiatric disorders that disproportionately impact female mental health is delineating the emergence of sex-specific patterns of brain organisation at the critical transition from childhood to adolescence. Prior work suggests that individual differences in the spatial organisation of functional brain networks across the cortex are associated with psychopathology and differ systematically by sex.We aimed to evaluate the impact of sex on the spatial organisation of person-specific functional brain networks.We leveraged person-specific atlases of functional brain networks, defined using non-negative matrix factorisation, in a sample of n = 6437 youths from the Adolescent Brain Cognitive Development Study. Across independent discovery and replication samples, we used generalised additive models to uncover associations between sex and the spatial layout (topography) of personalised functional networks (PFNs). We also trained support vector machines to classify participants' sex from multivariate patterns of PFN topography.Sex differences in PFN topography were greatest in association networks including the frontoparietal, ventral attention and default mode networks. Machine learning models trained on participants' PFNs were able to classify participant sex with high accuracy.Sex differences in PFN topography are robust, and replicate across large-scale samples of youth. These results suggest a potential contributor to the female-biased risk in depressive and anxiety disorders that emerge at the transition from childhood to adolescence.

  View details for DOI 10.1192/bjp.2025.135

  View details for PubMedID 40536230

• Reproducible Sex Differences in Personalized Functional Network Topography in Youth Keller, A., Sun, K., Francisco, A., Robinson, H., Beydler, E., Cieslak, M., Cui, Z., Davatzikos, C., Fan, Y., Gardner, M., Kishton, R., Kornfield, S., Larsen, B., Li, H., Linder, I., Pines, A., Pritschett, L., Raznahan, A., Roalf, D., Seidlitz, J., Shafiei, G., Shinohara, R., Wolf, D., Alexander-Bloch, A., Satterthwaite, T., Shanmugan, S. ELSEVIER SCIENCE INC. 2025

  View details for Web of Science ID 001500621800085

• Exploring the effects of cognitive behavioral therapy on cognitive control circuit and behavioral task performance in hoarding disorder. Journal of psychiatric research Muñoz Rodríguez, P. A., Pines, A., Zhang, X., van Roessel, P. J., Mukunda, P., McCarthy, E., Williams, L. M., Rodríguez, C. I. 2025; 186: 423-433

  Abstract

  Hoarding disorder (HD) is characterized by difficulty discarding or parting with possessions and clutter, which causes distress or impairment in important areas of functioning. Cognitive behavioral therapy (CBT) for HD has shown promise; however, little is known about the brain mechanisms underlying symptom reduction. We previously reported the robust clinical effects of the Buried in Treasures workshop (BIT)-a skills-based group which incorporates CBT principles-augmented with uncluttering home visits (BIT+), in a waitlist-controlled trial involving adults with HD. This study examined neural activity within a network of regions associated with cognitive control in a subset of HD participants (n = 19) before and after 18 weeks of BIT+ sessions using task-based fMRI during a response inhibition task. We used a comparison group of healthy controls (HC; n = 49). Our behavioral results show that participants in the HD group made more errors of omission while performing the task but did not differ from HCs in their errors of commission. The neuroimaging findings indicated a correlation between improvements in hoarding symptoms and blood-oxygen-level-dependent (BOLD) signal during errors of commission in the right insula and anterior cingulate cortex of post-treatment HD participants, suggesting that changes in this region may be associated with the effectiveness of BIT+ treatment. This is the first study exploring neural activity changes associated with symptom-neutral inhibitory control before and after BIT+ treatment in a HD population.

  View details for DOI 10.1016/j.jpsychires.2025.04.010

  View details for PubMedID 40315751

• Connectional axis of individual functional variability: Patterns, structural correlates, and relevance for development and cognition. Proceedings of the National Academy of Sciences of the United States of America Yang, H., Wu, G., Li, Y., Xu, X., Cong, J., Xu, H., Ma, Y., Li, Y., Chen, R., Pines, A., Xu, T., Sydnor, V. J., Satterthwaite, T. D., Cui, Z. 2025; 122 (12): e2420228122

  Abstract

  The human cerebral cortex exhibits intricate interareal functional synchronization at the macroscale, with substantial individual variability in these functional connections. However, the spatial organization of functional connectivity (FC) variability across the human connectome edges and its significance in cognitive development remain unclear. Here, we identified a connectional axis in the edge-level FC variability. The variability declined continuously along this axis from within-network to between-network connections and from the edges linking association networks to those linking the sensorimotor and association networks. This connectional axis of functional variability is associated with spatial pattern of structural connectivity variability. Moreover, the connectional variability axis evolves in youth with an flatter axis slope. We also observed that the slope of the connectional variability axis was positively related to the performance in the higher-order cognition. Together, our results reveal a connectional axis in functional variability that is linked with structural connectome variability, refines during development, and is relevant to cognition.

  View details for DOI 10.1073/pnas.2420228122

  View details for PubMedID 40100626

• Sex differences in response to violence: Role of salience network expansion and connectivity on depression. Research square Butler, E. R., Samia, N., Mejia, M., Pham, D., Pines, A., Nusslock, R. 2025

  Abstract

  Violence is a major risk factor for depression across development. Depression quickly worsens during early adolescence, however, and especially among females, who experience worse depression following threats than males. This may be because they perceive future threats as less controllable. Evidence suggests that features of the salience network may serve as particularly critical mechanisms explaining sex differences on depression in response to threat, as those with depressive disorders have more expansive salience networks than controls, and threatening experiences result in the brain utilizing more tissue for fear generation in rodent models. Using a longitudinal sample of 220 adolescents ages 14-18 from the Chicago area, we test if salience network expansion and connectivity explain the differential impact of violence on depression across the sexes. We found that the association between violence and depression was greater for females than males ( β ˆ 3 ( 2 ) = 0.337 , p = 0.025 ) , such that there was a positive association among females, but not males. Contrary to our hypotheses, we found that the association between the expansion of the salience network and depression was positive for males ( β ˆ 1 ( 5 ) = 0.242 , p = 0.039 ) , as was the association between salience network connectivity and depression ( β ˆ 1 ( 6 ) = 0.238 , p = 0.030 ) . Both of these effects remained after controlling for depression two years prior, indicating that exposures that impact males' depression through the salience network likely occur during middle adolescence. Through identifying types of exposures, their relevant developmental timing, and mechanisms connecting exposures with depression, this work helps to inform interventions to prevent the onset of depression following adversity, thereby reducing the lifetime burden of depression.

  View details for DOI 10.21203/rs.3.rs-5822551/v1

  View details for PubMedID 40162208

  View details for PubMedCentralID PMC11952664

• Hierarchical individual variation and socioeconomic impact on personalized functional network topography in children. BMC medicine Zhao, S., Su, H., Cong, J., Wen, X., Yang, H., Chen, P., Wu, G., Fan, Q., Ma, Y., Xu, X., Hu, C., Li, H., Keller, A., Pines, A., Chen, R., Cui, Z. 2024; 22 (1): 556

  Abstract

  The spatial layout of large-scale functional brain networks exhibits considerable inter-individual variability, especially in the association cortex. Research has demonstrated a link between early socioeconomic status (SES) and variations in both brain structure and function, which are further associated with cognitive and mental health outcomes. However, the extent to which SES is associated with individual differences in personalized functional network topography during childhood remains largely unexplored.We used a machine learning approach-spatially regularized non-negative matrix factorization (NMF)-to delineate 17 personalized functional networks in children aged 9-10 years, utilizing high-quality functional MRI data from 6001 participants in the Adolescent Brain Cognitive Development study. Partial least square regression approach with repeated random twofold cross-validation was used to evaluate the association between the multivariate pattern of functional network topography and three SES factors, including family income-to-needs ratio, parental education, and neighborhood disadvantage.We found that individual variations in personalized functional network topography aligned with the hierarchical sensorimotor-association axis across the cortex. Furthermore, we observed that functional network topography significantly predicted the three SES factors from unseen individuals. The associations between functional topography and SES factors were also hierarchically organized along the sensorimotor-association cortical axis, exhibiting stronger positive associations in the higher-order association cortex. Additionally, we have made the personalized functional networks publicly accessible.These results offer insights into how SES influences neurodevelopment through personalized functional neuroanatomy in childhood, highlighting the cortex-wide, hierarchically organized plasticity of the functional networks in response to diverse SES backgrounds.

  View details for DOI 10.1186/s12916-024-03784-3

  View details for PubMedID 39587556

  View details for PubMedCentralID 10524122

• Reproducible Sex Differences in Personalized Functional Network Topography in Youth. bioRxiv : the preprint server for biology Keller, A. S., Sun, K. Y., Francisco, A., Robinson, H., Beydler, E., Bassett, D. S., Cieslak, M., Cui, Z., Davatzikos, C., Fan, Y., Gardner, M., Kishton, R., Kornfield, S. L., Larsen, B., Li, H., Linder, I., Pines, A., Pritschet, L., Raznahan, A., Roalf, D. R., Seidlitz, J., Shafiei, G., Shinohara, R. T., Wolf, D. H., Alexander-Bloch, A., Satterthwaite, T. D., Shanmugan, S. 2024

  Abstract

  A key step towards understanding psychiatric disorders that disproportionately impact female mental health is delineating the emergence of sex-specific patterns of brain organization at the critical transition from childhood to adolescence. Prior work suggests that individual differences in the spatial organization of functional brain networks across the cortex are associated with psychopathology and differ systematically by sex.We aimed to evaluate the impact of sex on the spatial organization of person-specific functional brain networks.We leveraged person-specific atlases of functional brain networks defined using nonnegative matrix factorization in a sample of n = 6437 youths from the Adolescent Brain Cognitive Development Study. Across independent discovery and replication samples, we used generalized additive models to uncover associations between sex and the spatial layout ("topography") of personalized functional networks (PFNs). Next, we trained support vector machines to classify participants' sex from multivariate patterns of PFN topography. Finally, we leveraged transcriptomic data from the Allen Human Brain Atlas to evaluate spatial correlations between sex differences in PFN topography and gene expression.Sex differences in PFN topography were greatest in association networks including the fronto-parietal, ventral attention, and default mode networks. Machine learning models trained on participants' PFNs were able to classify participant sex with high accuracy. Brain regions with the greatest sex differences in PFN topography were enriched in expression of X-linked genes as well as genes expressed in astrocytes and excitatory neurons.Sex differences in PFN topography are robust, replicate across large-scale samples of youth, and are associated with expression patterns of X-linked genes. These results suggest a potential contributor to the female-biased risk in depressive and anxiety disorders that emerge at the transition from childhood to adolescence.

  View details for DOI 10.1101/2024.09.26.615061

  View details for PubMedID 39386637

  View details for PubMedCentralID PMC11463432

• Adaptive cognitive control circuit changes associated with problem-solving ability and depression symptom outcomes over 24 months. Science translational medicine Zhang, X., Pines, A., Stetz, P., Goldstein-Piekarski, A. N., Xiao, L., Lv, N., Tozzi, L., Lavori, P. W., Snowden, M. B., Venditti, E. M., Smyth, J. M., Suppes, T., Ajilore, O., Ma, J., Williams, L. M. 2024; 16 (763): eadh3172

  Abstract

  Mechanistically targeted behavioral interventions are a much-needed strategy for improving outcomes in depression, especially for vulnerable populations with comorbidities such as obesity. Such interventions may change behavior and outcome by changing underlying neural circuit function. However, it is unknown how these circuit-level modifications unfold over intervention and how individual differences in early circuit-level modifications may explain the heterogeneity of treatment effects. We addressed this need within a clinical trial of problem-solving therapy for participants with depression symptoms and comorbid obesity, focusing on the cognitive control circuit as a putative neural mechanism of action. Functional magnetic resonance imaging was applied to measure the cognitive control circuit activity at five time points over 24 months. Compared with participants who received usual care, those receiving problem-solving therapy showed that attenuations in cognitive control circuit activity were associated with enhanced problem-solving ability, which suggests that this circuit plays a key role in the mechanisms of problem-solving therapy. Attenuations in circuit activity were also associated with improved depression symptoms. Changes in cognitive control circuit activity at 2 months better predicted changes in problem-solving ability and depression symptoms at 6, 12, and 24 months, with predictive improvements ranging from 17.8 to 104.0%, exceeding baseline demographic and symptom characteristics. Our findings suggest that targeting the circuit mechanism of action could enhance the prediction of treatment outcomes, warranting future model refinement and improvement to pave the way for its clinical application.

  View details for DOI 10.1126/scitranslmed.adh3172

  View details for PubMedID 39231241

• Mapping the neurodevelopmental predictors of psychopathology MOLECULAR PSYCHIATRY Jirsaraie, R. J., Gatavins, M. M., Pines, A. R., Kandala, S., Bijsterbosch, J. D., Marek, S., Bogdan, R., Barch, D. M., Sotiras, A. 2025; 30 (2): 478-488

  Abstract

  Neuroimaging research has uncovered a multitude of neural abnormalities associated with psychopathology, but few prediction-based studies have been conducted during adolescence, and even fewer used neurobiological features that were extracted across multiple neuroimaging modalities. This gap in the literature is critical, as deriving accurate brain-based models of psychopathology is an essential step towards understanding key neural mechanisms and identifying high-risk individuals. As such, we trained adaptive tree-boosting algorithms on multimodal neuroimaging features from the Lifespan Human Connectome Developmental (HCP-D) sample that contained 956 participants between the ages of 8 to 22 years old. Our feature space consisted of 1037 anatomical, 1090 functional, and 192 diffusion MRI features, which were used to derive models that separately predicted internalizing symptoms, externalizing symptoms, and the general psychopathology factor. We found that multimodal models were the most accurate, but all brain-based models of psychopathology yielded out-of-sample predictions that were weakly correlated with actual symptoms (r2 < 0.15). White matter microstructural properties, including orientation dispersion indices and intracellular volume fractions, were the most predictive of general psychopathology, followed by cortical thickness and functional connectivity. Spatially, the most predictive features of general psychopathology were primarily localized within the default mode and dorsal attention networks. These results were mostly consistent across all dimensions of psychopathology, except orientation dispersion indices and the default mode network were not as heavily weighted in the prediction of internalizing and externalizing symptoms. Taken with prior literature, it appears that neurobiological features are an important part of the equation for predicting psychopathology but relying exclusively on neural markers is clearly not sufficient, especially among adolescent samples with subclinical symptoms. Consequently, risk factor models of psychopathology may benefit from incorporating additional sources of information that have also been shown to explain individual differences, such as psychosocial factors, environmental stressors, and genetic vulnerabilities.

  View details for DOI 10.1038/s41380-024-02682-7

  View details for Web of Science ID 001285243200002

  View details for PubMedID 39107582

  View details for PubMedCentralID 4709015

• Personalized brain circuit scores identify clinically distinct biotypes in depression and anxiety. Nature medicine Tozzi, L., Zhang, X., Pines, A., Olmsted, A. M., Zhai, E. S., Anene, E. T., Chesnut, M., Holt-Gosselin, B., Chang, S., Stetz, P. C., Ramirez, C. A., Hack, L. M., Korgaonkar, M. S., Wintermark, M., Gotlib, I. H., Ma, J., Williams, L. M. 2024

  Abstract

  There is an urgent need to derive quantitative measures based on coherent neurobiological dysfunctions or 'biotypes' to enable stratification of patients with depression and anxiety. We used task-free and task-evoked data from a standardized functional magnetic resonance imaging protocol conducted across multiple studies in patients with depression and anxiety when treatment free (n = 801) and after randomization to pharmacotherapy or behavioral therapy (n = 250). From these patients, we derived personalized and interpretable scores of brain circuit dysfunction grounded in a theoretical taxonomy. Participants were subdivided into six biotypes defined by distinct profiles of intrinsic task-free functional connectivity within the default mode, salience and frontoparietal attention circuits, and of activation and connectivity within frontal and subcortical regions elicited by emotional and cognitive tasks. The six biotypes showed consistency with our theoretical taxonomy and were distinguished by symptoms, behavioral performance on general and emotional cognitive computerized tests, and response to pharmacotherapy as well as behavioral therapy. Our results provide a new, theory-driven, clinically validated and interpretable quantitative method to parse the biological heterogeneity of depression and anxiety. Thus, they represent a promising approach to advance precision clinical care in psychiatry.

  View details for DOI 10.1038/s41591-024-03057-9

  View details for PubMedID 38886626

  View details for PubMedCentralID 7653736

• Mapping the Neurobiological Markers of Psychopathology Jirsaraie, R., Gatavins, M., Pines, A., Kandala, S., Bijsterbosch, J., Marek, S., Bogdan, R., Barch, D., Sotiras, A. ELSEVIER SCIENCE INC. 2024: S186-S187

  View details for Web of Science ID 001282811900436

• Understanding Cognitive Development by Capturing Complex, Multidimensional, Childhood Environments and Individual-Specific Patterns of Functional Brain Network Organization Keller, A., Moore, T. M., Luo, A., Visoki, E., Gatavins, M., Shetty, A., Cui, Z., Fan, Y., Feczko, E., Houghton, A., Li, H., Mackey, A. P., Miranda-Dominguez, O., Pines, A., Shinohara, R. T., Sun, K. Y., Fair, D. A., Satterthwaite, T. D., Barzilay, R. ELSEVIER SCIENCE INC. 2024: S85

  View details for Web of Science ID 001282811900195

• Functional connectivity development along the sensorimotor-association axis enhances the cortical hierarchy. Nature communications Luo, A. C., Sydnor, V. J., Pines, A., Larsen, B., Alexander-Bloch, A. F., Cieslak, M., Covitz, S., Chen, A. A., Esper, N. B., Feczko, E., Franco, A. R., Gur, R. E., Gur, R. C., Houghton, A., Hu, F., Keller, A. S., Kiar, G., Mehta, K., Salum, G. A., Tapera, T., Xu, T., Zhao, C., Salo, T., Fair, D. A., Shinohara, R. T., Milham, M. P., Satterthwaite, T. D. 2024; 15 (1): 3511

  Abstract

  Human cortical maturation has been posited to be organized along the sensorimotor-association axis, a hierarchical axis of brain organization that spans from unimodal sensorimotor cortices to transmodal association cortices. Here, we investigate the hypothesis that the development of functional connectivity during childhood through adolescence conforms to the cortical hierarchy defined by the sensorimotor-association axis. We tested this pre-registered hypothesis in four large-scale, independent datasets (total n = 3355; ages 5-23 years): the Philadelphia Neurodevelopmental Cohort (n = 1207), Nathan Kline Institute-Rockland Sample (n = 397), Human Connectome Project: Development (n = 625), and Healthy Brain Network (n = 1126). Across datasets, the development of functional connectivity systematically varied along the sensorimotor-association axis. Connectivity in sensorimotor regions increased, whereas connectivity in association cortices declined, refining and reinforcing the cortical hierarchy. These consistent and generalizable results establish that the sensorimotor-association axis of cortical organization encodes the dominant pattern of functional connectivity development.

  View details for DOI 10.1038/s41467-024-47748-w

  View details for PubMedID 38664387

  View details for PubMedCentralID 4879139

• A general exposome factor explains individual differences in functional brain network topography and cognition in youth. Developmental cognitive neuroscience Keller, A. S., Moore, T. M., Luo, A., Visoki, E., Gataviņš, M. M., Shetty, A., Cui, Z., Fan, Y., Feczko, E., Houghton, A., Li, H., Mackey, A. P., Miranda-Dominguez, O., Pines, A., Shinohara, R. T., Sun, K. Y., Fair, D. A., Satterthwaite, T. D., Barzilay, R. 2024; 66: 101370

  Abstract

  Childhood environments are critical in shaping cognitive neurodevelopment. With the increasing availability of large-scale neuroimaging datasets with deep phenotyping of childhood environments, we can now build upon prior studies that have considered relationships between one or a handful of environmental and neuroimaging features at a time. Here, we characterize the combined effects of hundreds of inter-connected and co-occurring features of a child's environment ("exposome") and investigate associations with each child's unique, multidimensional pattern of functional brain network organization ("functional topography") and cognition. We apply data-driven computational models to measure the exposome and define personalized functional brain networks in pre-registered analyses. Across matched discovery (n=5139, 48.5% female) and replication (n=5137, 47.1% female) samples from the Adolescent Brain Cognitive Development study, the exposome was associated with current (ages 9-10) and future (ages 11-12) cognition. Changes in the exposome were also associated with changes in cognition after accounting for baseline scores. Cross-validated ridge regressions revealed that the exposome is reflected in functional topography and can predict performance across cognitive domains. Importantly, a single measure capturing a child's exposome could more accurately and parsimoniously predict cognition than a wealth of personalized neuroimaging data, highlighting the importance of children's complex, multidimensional environments in cognitive neurodevelopment.

  View details for DOI 10.1016/j.dcn.2024.101370

  View details for PubMedID 38583301

• Personalized functional brain network topography is associated with individual differences in youth cognition. Nature communications Keller, A. S., Pines, A. R., Shanmugan, S., Sydnor, V. J., Cui, Z., Bertolero, M. A., Barzilay, R., Alexander-Bloch, A. F., Byington, N., Chen, A., Conan, G. M., Davatzikos, C., Feczko, E., Hendrickson, T. J., Houghton, A., Larsen, B., Li, H., Miranda-Dominguez, O., Roalf, D. R., Perrone, A., Shetty, A., Shinohara, R. T., Fan, Y., Fair, D. A., Satterthwaite, T. D. 2023; 14 (1): 8411

  Abstract

  Individual differences in cognition during childhood are associated with important social, physical, and mental health outcomes in adolescence and adulthood. Given that cortical surface arealization during development reflects the brain's functional prioritization, quantifying variation in the topography of functional brain networks across the developing cortex may provide insight regarding individual differences in cognition. We test this idea by defining personalized functional networks (PFNs) that account for interindividual heterogeneity in functional brain network topography in 9-10 year olds from the Adolescent Brain Cognitive Development℠ Study. Across matched discovery (n = 3525) and replication (n = 3447) samples, the total cortical representation of fronto-parietal PFNs positively correlates with general cognition. Cross-validated ridge regressions trained on PFN topography predict cognition in unseen data across domains, with prediction accuracy increasing along the cortex's sensorimotor-association organizational axis. These results establish that functional network topography heterogeneity is associated with individual differences in cognition before the critical transition into adolescence.

  View details for DOI 10.1038/s41467-023-44087-0

  View details for PubMedID 38110396

  View details for PubMedCentralID PMC10728159

• Functional imaging studies of acute administration of classic psychedelics, ketamine, and MDMA: Methodological limitations and convergent results. Neuroscience and biobehavioral reviews Linguiti, S., Vogel, J. W., Sydnor, V. J., Pines, A., Wellman, N., Basbaum, A., Eickhoff, C. R., Eickhoff, S. B., Edwards, R. R., Larsen, B., McKinstry-Wu, A., Scott, J. C., Roalf, D. R., Sharma, V., Strain, E. C., Corder, G., Dworkin, R. H., Satterthwaite, T. D. 2023: 105421

  Abstract

  Functional magnetic resonance imaging (fMRI) is increasingly used to non-invasively study the acute impact of psychedelics on the human brain. While fMRI is a promising tool for measuring brain function in response to psychedelics, it also has known methodological challenges. We conducted a systematic review of fMRI studies examining acute responses to experimentally administered psychedelics in order to identify convergent findings and characterize heterogeneity in the literature. We reviewed 91 full-text papers; these studies were notable for substantial heterogeneity in design, task, dosage, drug timing, and statistical approach. Data recycling was common, with 51 unique samples across 91 studies. Fifty-seven studies (54%) did not meet contemporary standards for Type I error correction or control of motion artifact. Psilocybin and LSD were consistently reported to moderate the connectivity architecture of the sensorimotor-association cortical axis. Studies also consistently reported that ketamine administration increased activation in the dorsomedial prefrontal cortex. Moving forward, use of best practices such as pre-registration, standardized image processing and statistical testing, and data sharing will be important in this rapidly developing field.

  View details for DOI 10.1016/j.neubiorev.2023.105421

  View details for PubMedID 37802267

• Individual differences in delay discounting are associated with dorsal prefrontal cortex connectivity in children, adolescents, and adults. Developmental cognitive neuroscience Mehta, K., Pines, A., Adebimpe, A., Larsen, B., Bassett, D. S., Calkins, M. E., Baller, E. B., Gell, M., Patrick, L. M., Shafiei, G., Gur, R. E., Gur, R. C., Roalf, D. R., Romer, D., Wolf, D. H., Kable, J. W., Satterthwaite, T. D. 2023; 62: 101265

  Abstract

  Delay discounting is a measure of impulsive choice relevant in adolescence as it predicts many real-life outcomes, including obesity and academic achievement. However, resting-state functional networks underlying individual differences in delay discounting during youth remain incompletely described. Here we investigate the association between multivariate patterns of functional connectivity and individual differences in impulsive choice in a large sample of children, adolescents, and adults. A total of 293 participants (9-23 years) completed a delay discounting task and underwent 3T resting-state fMRI. A connectome-wide analysis using multivariate distance-based matrix regression was used to examine whole-brain relationships between delay discounting and functional connectivity. These analyses revealed that individual differences in delay discounting were associated with patterns of connectivity emanating from the left dorsal prefrontal cortex, a default mode network hub. Greater delay discounting was associated with greater functional connectivity between the dorsal prefrontal cortex and other default mode network regions, but reduced connectivity with regions in the dorsal and ventral attention networks. These results suggest delay discounting in children, adolescents, and adults is associated with individual differences in relationships both within the default mode network and between the default mode and networks involved in attentional and cognitive control.

  View details for DOI 10.1016/j.dcn.2023.101265

  View details for PubMedID 37327696

  View details for PubMedCentralID PMC10285090

• Connectional Hierarchy in Human Brain Revealed by Individual Variability of Functional Network Edges. bioRxiv : the preprint server for biology Yang, H., Wu, G., Li, Y., Ma, Y., Chen, R., Pines, A., Xu, T., Sydnor, V. J., Satterthwaite, T. D., Cui, Z. 2023

  Abstract

  The human cerebral cortex is connected by intricate inter-areal wiring at the macroscale. The cortical hierarchy from primary sensorimotor to higher-order association areas is a unifying organizational principle across various neurobiological properties; however, previous studies have not clarified whether the connections between cortical regions exhibit a similar hierarchical pattern. Here, we identify a connectional hierarchy indexed by inter-individual variability of functional connectivity edges, which continuously progresses along a hierarchical gradient from within-network connections to between-network edges connecting sensorimotor and association networks. We found that this connectional hierarchy of variability aligns with both hemodynamic and electromagnetic connectivity strength and is constrained by structural connectivity strength. Moreover, the patterning of connectional hierarchy is related to inter-regional similarity in transcriptional and neurotransmitter receptor profiles. Using the Neurosynth cognitive atlas and cortical vulnerability maps in 13 brain disorders, we found that the connectional hierarchy of variability is associated with similarity networks of cognitive relevance and that of disorder vulnerability. Finally, we found that the prominence of this hierarchical gradient of connectivity variability declines during youth. Together, our results reveal a novel hierarchal organizational principle at the connectional level that links multimodal and multiscale human connectomes to individual variability in functional connectivity.

  View details for DOI 10.1101/2023.03.08.531800

  View details for PubMedID 36945479

  View details for PubMedCentralID PMC10028904

• Hierarchical functional system development supports executive function. Trends in cognitive sciences Keller, A. S., Sydnor, V. J., Pines, A., Fair, D. A., Bassett, D. S., Satterthwaite, T. D. 2023; 27 (2): 160-174

  Abstract

  In this perspective, we describe how developmental improvements in youth executive function (EF) are supported by hierarchically organized maturational changes in functional brain systems. We first highlight evidence that functional brain systems are embedded within a hierarchical sensorimotor-association axis of cortical organization. We then review data showing that functional system developmental profiles vary along this axis: systems near the associative end become more functionally segregated, while those in the middle become more integrative. Developmental changes that strengthen the hierarchical organization of the cortex may support EF by facilitating top-down information flow and balancing within- and between-system communication. We propose a central role for attention and frontoparietal control systems in the maturation of healthy EF and suggest that reduced functional system differentiation across the sensorimotor-association axis contributes to transdiagnostic EF deficits.

  View details for DOI 10.1016/j.tics.2022.11.005

  View details for PubMedID 36437189

  View details for PubMedCentralID PMC9851999

• Linking Individual Differences in Personalized Functional Network Topography to Psychopathology in Youth BIOLOGICAL PSYCHIATRY Cui, Z., Pines, A. R., Larsen, B., Sydnor, V. J., Li, H., Adebimpe, A., Alexander-Bloch, A. F., Bassett, D. S., Bertolero, M., Calkins, M. E., Davatzikos, C., Fair, D. A., Gur, R. C., Gur, R. E., Moore, T. M., Shanmugan, S., Shinohara, R. T., Vogel, J. W., Xia, C. H., Fan, Y., Satterthwaite, T. D. 2022; 92 (12): 973-983

  Abstract

  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.

  View details for DOI 10.1016/j.biopsych.2022.05.014

  View details for Web of Science ID 000929617200010

  View details for PubMedID 35927072

  View details for PubMedCentralID PMC10040299

• Caregiver monitoring, but not caregiver warmth, is associated with general cognition in two large sub-samples of youth DEVELOPMENTAL SCIENCE Keller, A. S., Mackey, A. P., Pines, A., Fair, D., Feczko, E., Hoffman, M. S., Salum, G. A., Barzilay, R., Satterthwaite, T. D. 2023; 26 (3): e13337

  Abstract

  Individual differences in cognitive abilities emerge early during development, and children with poorer cognition are at increased risk for adverse outcomes as they enter adolescence. Caregiving plays an important role in supporting cognitive development, yet it remains unclear how specific types of caregiving behaviors may shape cognition, highlighting the need for large-scale studies. In the present study, we characterized replicable yet specific associations between caregiving behaviors and cognition in two large sub-samples of children ages 9-10 years old from the Adolescent Brain Cognitive Development Study® (ABCD). Across both discovery and replication sub-samples, we found that child reports of caregiver monitoring (supervision or regular knowledge of the child's whereabouts) were positively associated with general cognition abilities, after covarying for age, sex, household income, neighborhood deprivation, and parental education. This association was specific to the type of caregiving behavior (caregiver monitoring, but not caregiver warmth), and was most strongly associated with a broad domain of general cognition (but not executive function or learning/memory). Additionally, we found that caregiver monitoring partially mediated the association between household income and cognition, furthering our understanding of how socioeconomic disparities may contribute to disadvantages in cognitive development. Together, these findings underscore the influence of differences in caregiving behavior in shaping youth cognition. RESEARCH HIGHLIGHTS: Caregiver monitoring, but not caregiver warmth, is associated with cognitive performance in youth Caregiver monitoring partially mediates the association between household income and cognition Results replicated across two large matched samples from the Adolescent Brain Cognitive Development Study® (ABCD).

  View details for DOI 10.1111/desc.13337

  View details for Web of Science ID 000881624600001

  View details for PubMedID 36305770

• An analysis-ready and quality controlled resource for pediatric brain white-matter research. Scientific data Richie-Halford, A., Cieslak, M., Ai, L., Caffarra, S., Covitz, S., Franco, A. R., Karipidis, I. I., Kruper, J., Milham, M., Avelar-Pereira, B., Roy, E., Sydnor, V. J., Yeatman, J. D., Fibr Community Science Consortium, Satterthwaite, T. D., Rokem, A., Abbott, N. J., Anderson, J. A., Gagana, B., Bleile, M., Bloomfield, P. S., Bottom, V., Bourque, J., Boyle, R., Brynildsen, J. K., Calarco, N., Castrellon, J. J., Chaku, N., Chen, B., Chopra, S., Coffey, E. B., Colenbier, N., Cox, D. J., Crippen, J. E., Crouse, J. J., David, S., Leener, B. D., Delap, G., Deng, Z., Dugre, J. R., Eklund, A., Ellis, K., Ered, A., Farmer, H., Faskowitz, J., Finch, J. E., Flandin, G., Flounders, M. W., Fonville, L., Frandsen, S. B., Garic, D., Garrido-Vasquez, P., Gonzalez-Escamilla, G., Grogans, S. E., Grotheer, M., Gruskin, D. C., Guberman, G. I., Haggerty, E. B., Hahn, Y., Hall, E. H., Hanson, J. L., Harel, Y., Vieira, B. H., Hettwer, M. D., Hobday, H., Horien, C., Huang, F., Huque, Z. M., James, A. R., Kahhale, I., Kamhout, S. L., Keller, A. S., Khera, H. S., Kiar, G., Kirk, P. A., Kohl, S. H., Korenic, S. A., Korponay, C., Kozlowski, A. K., Kraljevic, N., Lazari, A., Leavitt, M. J., Li, Z., Liberati, G., Lorenc, E. S., Lossin, A. J., Lotter, L. D., Lydon-Staley, D. M., Madan, C. R., Magielse, N., Marusak, H. A., Mayor, J., McGowan, A. L., Mehta, K. P., Meisler, S. L., Michael, C., Mitchell, M. E., Morand-Beaulieu, S., Newman, B. T., Nielsen, J. A., O'Mara, S. M., Ojha, A., Omary, A., Ozarslan, E., Parkes, L., Peterson, M., Pines, A. R., Pisanu, C., Rich, R. R., Sahoo, A. K., Samara, A., Sayed, F., Schneider, J. T., Shaffer, L. S., Shatalina, E., Sims, S. A., Sinclair, S., Song, J. W., Hogrogian, G. S., Tooley, U. A., Tripathi, V., Turker, H. B., Valk, S. L., Wall, M. B., Walther, C. K., Wang, Y., Wegmann, B., Welton, T., Wiesman, A. I., Wiesman, A. G., Wiesman, M., Winters, D. E., Yuan, R., Zacharek, S. J., Zajner, C., Zakharov, I., Zammarchi, G., Zhou, D., Zimmerman, B., Zoner, K. 2022; 9 (1): 616

  Abstract

  We created a set of resources to enable research based on openly-available diffusion MRI (dMRI) data from the Healthy Brain Network (HBN) study. First, we curated the HBN dMRI data (N=2747) into the Brain Imaging Data Structure and preprocessed it according to best-practices, including denoising and correcting for motion effects, susceptibility-related distortions, and eddy currents. Preprocessed, analysis-ready data was made openly available. Data quality plays a key role in the analysis of dMRI. To optimize QC and scale it to this large dataset, we trained a neural network through the combination of a small data subset scored by experts and a larger set scored by community scientists. The network performs QC highly concordant with that of experts on a held out set (ROC-AUC=0.947). A further analysis of the neural network demonstrates that it relies on image features with relevance to QC. Altogether, this work both delivers resources to advance transdiagnostic research in brain connectivity and pediatric mental health, and establishes a novel paradigm for automated QC of large datasets.

  View details for DOI 10.1038/s41597-022-01695-7

  View details for PubMedID 36224186

• Deciphering the functional specialization of whole- brain spatiomolecular gradients in the adult brain PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA W. Vogel, J., Bloch, A., Wagstyl, K., Bertolero, M. A., Markello, R. D., Pines, A., Sydnor, V. J., Diaz-Papkovich, A., Hansen, J. Y., Evans, A. C., Bernhardt, B., Misic, B., Satterthwaite, T. D., Seidlitz, J. 2022; 121 (25): e2219137121

  Abstract

  Cortical arealization arises during neurodevelopment from the confluence of molecular gradients representing patterned expression of morphogens and transcription factors. However, whether similar gradients are maintained in the adult brain remains unknown. Here, we uncover three axes of topographic variation in gene expression in the adult human brain that specifically capture previously identified rostral-caudal, dorsal-ventral, and medial-lateral axes of early developmental patterning. The interaction of these spatiomolecular gradients i) accurately reconstructs the position of brain tissue samples, ii) delineates known functional territories, and iii) can model the topographical variation of diverse cortical features. The spatiomolecular gradients are distinct from canonical cortical axes differentiating the primary sensory cortex from the association cortex, but radiate in parallel with the axes traversed by local field potentials along the cortex. We replicate all three molecular gradients in three independent human datasets as well as two nonhuman primate datasets and find that each gradient shows a distinct developmental trajectory across the lifespan. The gradients are composed of several well-known transcription factors (e.g., PAX6 and SIX3), and a small set of genes shared across gradients are strongly enriched for multiple diseases. Together, these results provide insight into the developmental sculpting of functionally distinct brain regions, governed by three robust transcriptomic axes embedded within brain parenchyma.

  View details for DOI 10.1073/pnas.2219137121

  View details for Web of Science ID 001250875900001

  View details for PubMedID 38861593

  View details for PubMedCentralID PMC11194492

• Mobile footprinting: linking individual distinctiveness in mobility patterns to mood, sleep, and brain functional connectivity NEUROPSYCHOPHARMACOLOGY Xia, C., Barnett, I., Tapera, T. M., Adebimpe, A., Baker, J. T., Bassett, D. S., Brotman, M. A., Calkins, M. E., Cui, Z., Leibenluft, E., Linguiti, S., Lydon-Staley, D. M., Martin, M., Moore, T. M., Murtha, K., Piiwaa, K., Pines, A., Roalf, D. R., Rush-Goebel, S., Wolf, D. H., Ungar, L. H., Satterthwaite, T. D. 2022; 47 (9): 1662-1671

  Abstract

  Mapping individual differences in behavior is fundamental to personalized neuroscience, but quantifying complex behavior in real world settings remains a challenge. While mobility patterns captured by smartphones have increasingly been linked to a range of psychiatric symptoms, existing research has not specifically examined whether individuals have person-specific mobility patterns. We collected over 3000 days of mobility data from a sample of 41 adolescents and young adults (age 17-30 years, 28 female) with affective instability. We extracted summary mobility metrics from GPS and accelerometer data and used their covariance structures to identify individuals and calculated the individual identification accuracy-i.e., their "footprint distinctiveness". We found that statistical patterns of smartphone-based mobility features represented unique "footprints" that allow individual identification (p < 0.001). Critically, mobility footprints exhibited varying levels of person-specific distinctiveness (4-99%), which was associated with age and sex. Furthermore, reduced individual footprint distinctiveness was associated with instability in affect (p < 0.05) and circadian patterns (p < 0.05) as measured by environmental momentary assessment. Finally, brain functional connectivity, especially those in the somatomotor network, was linked to individual differences in mobility patterns (p < 0.05). Together, these results suggest that real-world mobility patterns may provide individual-specific signatures relevant for studies of development, sleep, and psychopathology.

  View details for DOI 10.1038/s41386-022-01351-z

  View details for Web of Science ID 000805757700001

  View details for PubMedID 35660803

  View details for PubMedCentralID PMC9163291

• Article Developmental coupling of cerebral blood flow and fMRI fluctuations in youth CELL REPORTS Baller, E. B., Valcarcel, A. M., Adebimpe, A., Alexander-Bloch, A., Cui, Z., Gur, R. C., Gur, R. E., Larsen, B. L., Linn, K. A., O'Donnell, C. M., Pines, A. R., Raznahan, A., Roalf, D. R., Sydnor, V. J., Tapera, T. M., Tisdall, M., Vandekar, S., Xia, C. H., Detre, J. A., Shinohara, R. T., Satterthwaite, T. D. 2022; 38 (13): 110576

  Abstract

  The functions of the human brain are metabolically expensive and reliant on coupling between cerebral blood flow (CBF) and neural activity, yet how this coupling evolves over development remains unexplored. Here, we examine the relationship between CBF, measured by arterial spin labeling, and the amplitude of low-frequency fluctuations (ALFF) from resting-state magnetic resonance imaging across a sample of 831 children (478 females, aged 8-22 years) from the Philadelphia Neurodevelopmental Cohort. We first use locally weighted regressions on the cortical surface to quantify CBF-ALFF coupling. We relate coupling to age, sex, and executive functioning with generalized additive models and assess network enrichment via spin testing. We demonstrate regionally specific changes in coupling over age and show that variations in coupling are related to biological sex and executive function. Our results highlight the importance of CBF-ALFF coupling throughout development; we discuss its potential as a future target for the study of neuropsychiatric diseases.

  View details for DOI 10.1016/j.celrep.2022.110576

  View details for Web of Science ID 000779794000010

  View details for PubMedID 35354053

  View details for PubMedCentralID PMC9006592

• Associations between neighborhood socioeconomic status, parental education, and executive system activation in youth CEREBRAL CORTEX Murtha, K., Larsen, B., Pines, A., Parkes, L., Moore, T. M., Adebimpe, A., Alexander-Bloch, A., Calkins, M. E., Davila, D. G., Lindquist, M. A., Mackey, A. P., Roalf, D. R., Scott, J., Wolf, D. H., Gur, R. C., Gur, R. E., Barzilay, R., Satterthwaite, T. D. 2022

  Abstract

  Socioeconomic status (SES) can impact cognitive performance, including working memory (WM). As executive systems that support WM undergo functional neurodevelopment during adolescence, environmental stressors at both individual and community levels may influence cognitive outcomes. Here, we sought to examine how SES at the neighborhood and family level impacts task-related activation of the executive system during adolescence and determine whether this effect mediates the relationship between SES and WM performance. To address these questions, we studied 1,150 youths (age 8-23) that completed a fractal n-back WM task during functional magnetic resonance imaging at 3T as part of the Philadelphia Neurodevelopmental Cohort. We found that both higher neighborhood SES and parental education were associated with greater activation of the executive system to WM load, including the bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and precuneus. The association of neighborhood SES remained significant when controlling for task performance, or related factors like exposure to traumatic events. Furthermore, high-dimensional multivariate mediation analysis identified distinct patterns of brain activity within the executive system that significantly mediated the relationship between measures of SES and task performance. These findings underscore the importance of multilevel environmental factors in shaping executive system function and WM in youth.

  View details for DOI 10.1093/cercor/bhac120

  View details for Web of Science ID 000784116100001

  View details for PubMedID 35348659

• A developmental reduction of the excitation:inhibition ratio in association cortex during adolescence SCIENCE ADVANCES Larsen, B., Cui, Z., Adebimpe, A., Pines, A., Alexander-Bloch, A., Bertolero, M., Calkins, M. E., Gur, R. E., Gur, R. C., Mahadevan, A. S., Moore, T. M., Roalf, D. R., Seidlitz, J., Sydnor, V. J., Wolf, D. H., Satterthwaite, T. D. 2022; 8 (5): eabj8750

  Abstract

  Adolescence is hypothesized to be a critical period for the development of association cortex. A reduction of the excitation:inhibition (E:I) ratio is a hallmark of critical period development; however, it has been unclear how to assess the development of the E:I ratio using noninvasive neuroimaging techniques. Here, we used pharmacological fMRI with a GABAergic benzodiazepine challenge to empirically generate a model of E:I ratio based on multivariate patterns of functional connectivity. In an independent sample of 879 youth (ages 8 to 22 years), this model predicted reductions in the E:I ratio during adolescence, which were specific to association cortex and related to psychopathology. These findings support hypothesized shifts in E:I balance of association cortices during a neurodevelopmental critical period in adolescence.

  View details for DOI 10.1126/sciadv.abj8750

  View details for Web of Science ID 000799992000005

  View details for PubMedID 35119918

  View details for PubMedCentralID PMC8816330

• Neurodevelopment of the association cortices: Patterns, mechanisms, and implications for psychopathology NEURON Sydnor, V. J., Larsen, B., Bassett, D. S., Alexander-Bloch, A., Fair, D. A., Liston, C., Mackey, A. P., Milham, M. P., Pines, A., Roalf, D. R., Seidlitz, J., Xu, T., Raznahan, A., Satterthwaite, T. D. 2021; 109 (18): 2820-2846

  Abstract

  The human brain undergoes a prolonged period of cortical development that spans multiple decades. During childhood and adolescence, cortical development progresses from lower-order, primary and unimodal cortices with sensory and motor functions to higher-order, transmodal association cortices subserving executive, socioemotional, and mentalizing functions. The spatiotemporal patterning of cortical maturation thus proceeds in a hierarchical manner, conforming to an evolutionarily rooted, sensorimotor-to-association axis of cortical organization. This developmental program has been characterized by data derived from multimodal human neuroimaging and is linked to the hierarchical unfolding of plasticity-related neurobiological events. Critically, this developmental program serves to enhance feature variation between lower-order and higher-order regions, thus endowing the brain's association cortices with unique functional properties. However, accumulating evidence suggests that protracted plasticity within late-maturing association cortices, which represents a defining feature of the human developmental program, also confers risk for diverse developmental psychopathologies.

  View details for DOI 10.1016/j.neuron.2021.06.016

  View details for Web of Science ID 000716332300005

  View details for PubMedID 34270921

  View details for PubMedCentralID PMC8448958

• QSIPrep: an integrative platform for preprocessing and reconstructing diffusion MRI data. Nature methods Cieslak, M., Cook, P. A., He, X., Yeh, F., Dhollander, T., Adebimpe, A., Aguirre, G. K., Bassett, D. S., Betzel, R. F., Bourque, J., Cabral, L. M., Davatzikos, C., Detre, J. A., Earl, E., Elliott, M. A., Fadnavis, S., Fair, D. A., Foran, W., Fotiadis, P., Garyfallidis, E., Giesbrecht, B., Gur, R. C., Gur, R. E., Kelz, M. B., Keshavan, A., Larsen, B. S., Luna, B., Mackey, A. P., Milham, M. P., Oathes, D. J., Perrone, A., Pines, A. R., Roalf, D. R., Richie-Halford, A., Rokem, A., Sydnor, V. J., Tapera, T. M., Tooley, U. A., Vettel, J. M., Yeatman, J. D., Grafton, S. T., Satterthwaite, T. D. 2021

  Abstract

  Diffusion-weighted magnetic resonance imaging (dMRI) is the primary method for noninvasively studying the organization of white matter in the human brain. Here we introduce QSIPrep, an integrative software platform for the processing of diffusion images that is compatible with nearly all dMRI sampling schemes. Drawing on a diverse set of software suites to capitalize on their complementary strengths, QSIPrep facilitates the implementation of best practices for processing of diffusion images.

  View details for DOI 10.1038/s41592-021-01185-5

  View details for PubMedID 34155395

• Sex Differences in Functional Topography of Association Networks Shanmugan, S., Seidlitz, J., Cui, Z., Adebimpe, A., Bassett, D. S., Bertolero, M. A., Davatzikos, C., Fair, D. A., Gur, R. E., Gur, R. C., Li, H., Pines, A., Raznahan, A., Roalf, D. R., Shinohara, R. T., Vogel, J., Wolf, D. H., Fan, Y., Alexander-Bloch, A., Satterthwaite, T. D. ELSEVIER SCIENCE INC. 2021: S178

  View details for Web of Science ID 000645683800428

• Pairwise maximum entropy model explains the role of white matter structure in shaping emergent co-activation states COMMUNICATIONS BIOLOGY Ashourvan, A., Shah, P., Pines, A., Gu, S., Lynn, C. W., Bassett, D. S., Davis, K. A., Litt, B. 2021; 4 (1): 210

  Abstract

  A major challenge in neuroscience is determining a quantitative relationship between the brain's white matter structural connectivity and emergent activity. We seek to uncover the intrinsic relationship among brain regions fundamental to their functional activity by constructing a pairwise maximum entropy model (MEM) of the inter-ictal activation patterns of five patients with medically refractory epilepsy over an average of ~14 hours of band-passed intracranial EEG (iEEG) recordings per patient. We find that the pairwise MEM accurately predicts iEEG electrodes' activation patterns' probability and their pairwise correlations. We demonstrate that the estimated pairwise MEM's interaction weights predict structural connectivity and its strength over several frequencies significantly beyond what is expected based solely on sampled regions' distance in most patients. Together, the pairwise MEM offers a framework for explaining iEEG functional connectivity and provides insight into how the brain's structural connectome gives rise to large-scale activation patterns by promoting co-activation between connected structures.

  View details for DOI 10.1038/s42003-021-01700-6

  View details for Web of Science ID 000620961500001

  View details for PubMedID 33594239

  View details for PubMedCentralID PMC7887247

• Leveraging multi-shell diffusion for studies of brain development in youth and young adulthood DEVELOPMENTAL COGNITIVE NEUROSCIENCE Pines, A. R., Cieslak, M., Larsen, B., Baum, G. L., Cook, P. A., Adebimpe, A., Davila, D. G., Elliott, M. A., Jirsaraie, R., Murtha, K., Oathes, D. J., Piiwaa, K., Rosen, A. F. G., Rush, S., Shinohara, R. T., Bassett, D. S., Roalf, D. R., Satterthwaite, T. D. 2020; 43: 100788

  Abstract

  Diffusion weighted imaging (DWI) has advanced our understanding of brain microstructure evolution over development. Recently, the use of multi-shell diffusion imaging sequences has coincided with advances in modeling the diffusion signal, such as Neurite Orientation Dispersion and Density Imaging (NODDI) and Laplacian-regularized Mean Apparent Propagator MRI (MAPL). However, the relative utility of recently-developed diffusion models for understanding brain maturation remains sparsely investigated. Additionally, despite evidence that motion artifact is a major confound for studies of development, the vulnerability of metrics derived from contemporary models to in-scanner motion has not been described. Accordingly, in a sample of 120 youth and young adults (ages 12-30) we evaluated metrics derived from diffusion tensor imaging (DTI), NODDI, and MAPL for associations with age and in-scanner head motion at multiple scales. Specifically, we examined mean white matter values, white matter tracts, white matter voxels, and connections in structural brain networks. Our results revealed that multi-shell diffusion imaging data can be leveraged to robustly characterize neurodevelopment, and demonstrate stronger age effects than equivalent single-shell data. Additionally, MAPL-derived metrics were less sensitive to the confounding effects of head motion. Our findings suggest that multi-shell imaging data and contemporary modeling techniques confer important advantages for studies of neurodevelopment.

  View details for DOI 10.1016/j.dcn.2020.100788

  View details for Web of Science ID 000538169600008

  View details for PubMedID 32510347

  View details for PubMedCentralID PMC7200217

• Characterizing the Role of the Structural Connectome in Seizure Dynamics Shah, P., Ashourvan, A., Mikhail, F., Pines, A., Kini, L., Shinohara, R. T., Bassett, D., Litt, B., Davis, K. A. WILEY. 2019: S261-S262

  View details for Web of Science ID 000488891800409

• Characterizing the role of the structural connectome in seizure dynamics BRAIN Shah, P., Ashourvan, A., Mikhail, F., Pines, A., Kini, L., Oechsel, K., Das, S. R., Stein, J. M., Shinohara, R. T., Bassett, D. S., Litt, B., Davis, K. A. 2019; 142: 1955-1972

  Abstract

  How does the human brain's structural scaffold give rise to its intricate functional dynamics? This is a central question in translational neuroscience that is particularly relevant to epilepsy, a disorder affecting over 50 million subjects worldwide. Treatment for medication-resistant focal epilepsy is often structural-through surgery or laser ablation-but structural targets, particularly in patients without clear lesions, are largely based on functional mapping via intracranial EEG. Unfortunately, the relationship between structural and functional connectivity in the seizing brain is poorly understood. In this study, we quantify structure-function coupling, specifically between white matter connections and intracranial EEG, across pre-ictal and ictal periods in 45 seizures from nine patients with unilateral drug-resistant focal epilepsy. We use high angular resolution diffusion imaging (HARDI) tractography to construct structural connectivity networks and correlate these networks with time-varying broadband and frequency-specific functional networks derived from coregistered intracranial EEG. Across all frequency bands, we find significant increases in structure-function coupling from pre-ictal to ictal periods. We demonstrate that short-range structural connections are primarily responsible for this increase in coupling. Finally, we find that spatiotemporal patterns of structure-function coupling are highly stereotyped for each patient. These results suggest that seizures harness the underlying structural connectome as they propagate. Mapping the relationship between structural and functional connectivity in epilepsy may inform new therapies to halt seizure spread, and pave the way for targeted patient-specific interventions.

  View details for DOI 10.1093/brain/awz125

  View details for Web of Science ID 000481420100021

  View details for PubMedID 31099821

  View details for PubMedCentralID PMC6598625

• Multi-unit relations among neural, self-report, and behavioral correlates of emotion regulation in comorbid depression and obesity SCIENTIFIC REPORTS Pines, A. R., Sacchet, M. D., Kullar, M., Ma, J., Williams, L. M. 2018; 8

  View details for DOI 10.1038/s41598-018-32394-2

  View details for Web of Science ID 000445031200015

• Multi-unit relations among neural, self-report, and behavioral correlates of emotion regulation in comorbid depression and obesity. Scientific reports Pines, A. R., Sacchet, M. D., Kullar, M., Ma, J., Williams, L. M. 2018; 8 (1): 14032

  Abstract

  Depression is a leading cause of disability and is commonly comorbid with obesity. Emotion regulation is impaired in both depression and obesity. In this study, we aimed to explicate multi-unit relations among brain connectivity, behavior, and self-reported trait measures related to emotion regulation in a comorbid depressed and obese sample (N=77). Brain connectivity was quantified as fractional anisotropy (FA) of the uncinate fasciculi, a white matter tract implicated in emotion regulation and in depression. Use of emotion regulation strategies was assessed using the Emotion Regulation Questionnaire (ERQ). We additionally measured reaction times to identifying negative emotions, a behavioral index of depression-related emotion processing biases. We found that greater right uncinate fasciculus FA was related to greater usage of suppression (r=0.27, p=0.022), and to faster reaction times to identifying negative emotions, particularly sadness (r=-0.30, p=0.010) and fear (r=-0.35, p=0.003). These findings suggest that FA of the right uncinate fasciculus corresponds to maladaptive emotion regulation strategies and emotion processing biases that are relevant to co-occurring depression and obesity. Interventions that consider these multi-unit associations may prove to be useful for subtyping and improving clinical outcomes for comorbid depression and obesity.

  View details for PubMedID 30232351

• The ENGAGE study: Integrating neuroimaging, virtual reality and smartphone sensing to understand self-regulation for managing depression and obesity in a precision medicine model Behaviour Research and Therapy Williams, L., Pines, A., Goldstein-Piekarski, A., Goldman-Rosas, L., Kullar, M., Sachet, M., Gevaert, O., Bailenson, J., Lavori, P., Dagum, P., Wandell, B., Correa, C., Greenleaf, W., Suppes, T., Michael Perry, L., Smyth, J., Lewis, M., Venditti, E., Snowden, M., Simmons, J., Ma, J. 2018: 58-70
• A Public Database of Immersive VR Videos with Corresponding Ratings of Arousal, Valence, and Correlations between Head Movements and Self Report Measures FRONTIERS IN PSYCHOLOGY Li, B. J., Bailenson, J. N., Pines, A., Greenleaf, W. J., Williams, L. M. 2017; 8: 2116

  Abstract

  Virtual reality (VR) has been proposed as a methodological tool to study the basic science of psychology and other fields. One key advantage of VR is that sharing of virtual content can lead to more robust replication and representative sampling. A database of standardized content will help fulfill this vision. There are two objectives to this study. First, we seek to establish and allow public access to a database of immersive VR video clips that can act as a potential resource for studies on emotion induction using virtual reality. Second, given the large sample size of participants needed to get reliable valence and arousal ratings for our video, we were able to explore the possible links between the head movements of the observer and the emotions he or she feels while viewing immersive VR. To accomplish our goals, we sourced for and tested 73 immersive VR clips which participants rated on valence and arousal dimensions using self-assessment manikins. We also tracked participants' rotational head movements as they watched the clips, allowing us to correlate head movements and affect. Based on past research, we predicted relationships between the standard deviation of head yaw and valence and arousal ratings. Results showed that the stimuli varied reasonably well along the dimensions of valence and arousal, with a slight underrepresentation of clips that are of negative valence and highly arousing. The standard deviation of yaw positively correlated with valence, while a significant positive relationship was found between head pitch and arousal. The immersive VR clips tested are available online as supplemental material.

  View details for PubMedID 29259571