Adam Pines, Ph.D., is a postdoctoral fellow in the Stanford PanLab for Precision Psychiatry and Translational Neuroscience with Director Leanne M. Williams, PhD. Adam completed his Ph.D. in Neuroscience at the University of Pennsylvania in Philadelphia (2017-2022). At UPenn, Adam’s work centered on measuring hierarchical cortical development and organization. In the PanLab, Adam is investigating the role of deficits in hierarchical cortical function in cognitive psychopathology. His other research interests include developmental neuroscience, brain-environment interactions, and adaptive plasticity in the brain.
Honors & Awards
NRSA F31: Personalized Mapping of Affective Lability, NIMH (2021-2022)
Jameson-Hurvich Award in Behavioral Neuroscience, University of Pennsylvania (2021)
Doctor of Philosophy, University of Pennsylvania (2022)
PhD, University of Pennsylvania, Neuroscience (2022)
BA, Loyola Marymount University, Psychology (2015)
Leanne Williams, Postdoctoral Faculty Sponsor
Development of top-down cortical propagations in youth.
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
Linking Individual Differences in Personalized Functional Network Topography to Psychopathology in Youth
2022; 92 (12): 973-983
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
Dissociable multi-scale patterns of development in personalized brain networks
2022; 13 (1): 2647
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
A developmental reduction of the excitation:inhibition ratio in association cortex during adolescence
2022; 8 (5): eabj8750
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
Functional imaging studies of acute administration of classic psychedelics, ketamine, and MDMA: Methodological limitations and convergent results.
Neuroscience and biobehavioral reviews
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
2023; 62: 101265
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
Caregiver monitoring, but not caregiver warmth, is associated with general cognition in two large sub-samples of youth
2023; 26 (3): e13337
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.
2022; 9 (1): 616
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
Mobile footprinting: linking individual distinctiveness in mobility patterns to mood, sleep, and brain functional connectivity
2022; 47 (9): 1662-1671
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
2022; 38 (13): 110576
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
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
Neurodevelopment of the association cortices: Patterns, mechanisms, and implications for psychopathology
2021; 109 (18): 2820-2846
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.
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
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
2021; 4 (1): 210
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
2020; 43: 100788
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
WILEY. 2019: S261-S262
View details for Web of Science ID 000488891800409
Characterizing the role of the structural connectome in seizure dynamics
2019; 142: 1955-1972
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 2018; 8
- 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 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
2017; 8: 2116
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