About

David R Roalf, Ph.D., is a Research Associate Professor of Psychiatry at the University of Pennsylvania Perelman School of Medicine. He is also an Associate Fellow at the University of Pennsylvania Institute on Aging and an Associated Faculty member of the Lifespan Brain Institute (LiBI). His research interests include the neural basis of neuropsychiatric disorders and cognitive aging, with a focus on changes in cognition, memory, and decision-making. Dr. Roalf's work is motivated by the need to better understand the pathophysiology of brain dysfunction, utilizing a range of cognitive and behavioral neuroscientific methods such as psychophysical testing, EEG, structural and functional MRI, diffusion tensor imaging, and magnetic resonance spectroscopy. His primary goal is to strengthen empirical knowledge about brain-behavior associations to better understand cognitive disturbances, particularly in neuropsychiatric and aging populations, and to facilitate early identification of individuals at risk for neuropsychiatric or neurodegenerative diseases.

Research topics

• Artificial Intelligence
• Computer Science
• Data Mining
• Psychology
• Neuroscience
• Medicine
• Biology
• Computer vision
• Database
• Physics
• Radiology
• Cognitive psychology
• Audiology
• Developmental psychology

Selected publications

• PennLEAD: Penn Longitudinal Executive functioning in Adolescent Development - QSIPrep Derivatives

  OpenNeuro · 2026-01-01

  datasetOpen access
  PublisherDOI

• The Hidden Architecture of Brain Structural Variability in 22q11.2 Deletion Syndrome: A Multi-site Study

  medRxiv · 2026-05-21

  articleOpen access

  Abstract Importance 22q11.2 deletion syndrome (22q11DS) is among the strongest genetic risk factors for neuropsychiatric disorders and has marked effects on brain structure. Yet, it remains unclear which neuroanatomical features reflect uniform effects of the deletion versus inter-individual biological processes relevant to psychiatric outcomes. Identifying these features is critical for developing targeted treatments and interventions. Objective To identify brain regions where 22q11DS exerts its most consistent and most variable impacts, and to test whether these patterns align with normative neurotransmitter receptor distributions and cortical growth trajectories. Design Multisite cross-sectional case-control study. Setting T1-weighted brain MRI data were obtained across 15 scanners. MRI data underwent standardized processing, quality control procedures and statistical site-adjustment using ComBat. Participants A total of N = 438 individuals with 22q11DS (5-54 years, 48% females) and 380 typically developing controls (6-58 years, 48% females). Main Outcomes and Measures Primary outcomes were global and regional cortical thickness and surface area. Mean and dispersion estimates were calculated using double generalized linear models, correcting for age, age 2 , sex (and intracranial volume for surface area). Quantile shift functions characterized fine-scale distributional differences. Sensitivity analyses adjustedt for co-occurring neuropsychiatric disorders, antipsychotic use and deletion subtype. Secondary outcomes included spatial correspondence between regional structural alterations and normative maps of neurotransmitter receptor density and cortical expansion. Results Compared with controls, individuals with 22q11DS showed widespread mean differences in cortical thickness and surface area. Notably, 22q11DS was associated with greater regional heterogeneity in both measures, except for reduced dispersion in the anterior cingulate. Effects were attenuated after covariate adjustment. Cortical thickness differences spatially overlapped with regions enriched for glutamatergic and GABAergic receptors. There was partial evidence linking surface area dispersion patterns to normative cortical growth trajectories. Conclusions and Relevance 22q11DS exerts broad effects on cortical structure consistent with a global developmental mechanism, reflected in widespread mean shifts. Beyond these, region-specific variability, particularly in cortical thickness, suggests individualized neurobiological processes. The anterior cingulate emerges as a region of consistent structural deviation. Overall, structural variability in 22q11DS aligns with normative patterns of excitatory-inhibitory signaling and cortical development, implicating these pathways as potential targets for intervention. Key points Question Is 22q11.2 deletion syndrome (22q11DS) associated with altered spatial heterogeneity of cortical structure, and do these patterns map onto the brain’s underlying neurochemical and developmental architecture? Findings In this multisite case-control study of 438 22q11DS and 380 controls, 22q11DS showed regionally patterned increases in cortical thickness heterogeneity and lower cortical surface area heterogeneity. Spatial patterns of cortical thickness differences were aligned with cortical gradients of glutamate and GABAergic receptor density. Meaning Although 22q11DS is generally associated with reduced brain volume and increased cortical thickness, the present findings reveal regionally patterned cortical alterations aligned with neurotransmitter-specific cortical organization, suggesting a mechanistic link between excitatory–inhibitory signaling architecture and individualized neuroanatomic effects of 22q11DS.

  PublisherOA PDFDOI

• 253. Examining Anxiety and Depression in Relation to Experiential Negative Symptom Domains in Clinical High Risk for Psychosis

  Biological Psychiatry · 2026-04-25

  article
  PublisherDOI

• Penn LEAD: Penn Longitudinal Executive functioning in Adolescent Development - fMRIPrep Functional Derivatives

  OpenNeuro · 2026-01-01

  datasetOpen access
  PublisherDOI

• Penn LEAD: Penn Longitudinal Executive functioning in Adolescent Development - QSIRecon Derivatives

  OpenNeuro · 2026-01-01

  datasetOpen access
  PublisherDOI

• 402. Age and Sex-Specific Patterns of Cognitive Performance During Midlife in People With Multiple Sclerosis

  Biological Psychiatry · 2026-04-25

  article
  PublisherDOI

• ASLPrep: A Robust Preprocessing Pipeline for ASL Data

  Zenodo (CERN European Organization for Nuclear Research) · 2026-03-16

  otherOpen access

  Arterial spin labeled (ASL) magnetic resonance imaging (MRI) is the primary method for noninvasively measuring regional brain perfusion in humans. We introduce ASLPrep, a suite of software pipelines that ensure the reproducible and generalizable processing of ASL MRI data.

  PublisherDOI

• The PMADS Project: A Longitudinal Multimodal Cohort Study to Understand Risk for Perinatal Mood and Anxiety Disorders

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-14

  articleOpen access

  Abstract Background Perinatal mood and anxiety disorders (PMADs) are among the most common and consequential complications of pregnancy. The perinatal period is also characterized by profound hormonal fluctuations and large-scale brain plasticity. However, the mechanisms linking these neurobiological changes to psychiatric risk are poorly understood. Prospective, clinically informed studies are needed to identify quantitative biomarkers and clarify pathways linking perinatal neurobiology to PMADs risk. Methods This report describes the design of a prospective, longitudinal cohort study integrating multimodal neuroimaging, biofluid sampling, and deep clinical phenotyping to enable precision characterization of neurobiological trajectories of PMADs risk. Twenty-five individuals at elevated risk for PMADs will be recruited prior to conception and followed across six in-person timepoints spanning the menstrual cycle, pregnancy, and early postpartum, with additional remote follow-ups through the first postpartum year. Data collection includes high-resolution structural MRI, functional brain mapping using multi-echo resting-state fMRI, diffusion MRI, arterial spin labeling, ultra-high field MR-based techniques for measuring glutamate (GluCEST and 1 HMRS), biofluid sampling, and comprehensive clinical, behavioral, and cognitive assessments. Structured clinical interviews assess categorical diagnoses while dimensional symptom measures capture heterogeneity and transdiagnostic features of perinatal psychopathology. Longitudinal analyses will model nonlinear trajectories of brain and symptom change across the perinatal period as well as evaluate whether preconception network features and menstrual cycle-related brain changes are associated with subsequent perinatal symptom emergence. Discussion This cohort study establishes a longitudinal, multimodal framework for investigating neurobiological changes across the transition to pregnancy in individuals at elevated risk for PMADs. By anchoring pregnancy-related brain changes to preconception and menstrual cycle-related variability within the same individuals, this study is designed to evaluate associations between preconception hormone sensitivity, pregnancy-induced neuroplasticity, and PMADs risk. The resulting dataset will provide a deeply phenotyped longitudinal resource for investigating brain-behavior relationships across the perinatal period. Findings are expected to inform future larger-scale studies aimed at advancing mechanistic understanding of PMADs, improving individualized risk stratification, and supporting development of personalized preventive and neuromodulatory interventions.

  PublisherOA PDFDOI

• Transient gray matter decline during antarctic isolation: Roles of sleep, exercise, and cognition

  npj Microgravity · 2025-07-11 · 4 citations

  articleOpen access1st authorCorresponding

  Astronauts face significant stress in space, and understanding its neurobiological basis is key to assessing risk and resilience. Analogue environments, like the Antarctic Concordia Station, replicate isolated, confined, and extreme (ICE) conditions. This study assessed brain structure changes in 25 crewmembers who spent 12 months at Concordia, with MRI scans conducted before, immediately after, and five months post-mission. The study included 25 controls scanned over a similar interval and 4 "flying phantom" individuals who were scanned at all sites. Gray matter in the temporal and parietal lobes, hippocampus, pallidum, and thalamus as well as global white matter decreased during the mission in crewmembers, with all but the thalamus returning to baseline after five months. Brain ventricle volume increased, and better sleep correlated with less brain volume loss, highlighting its potentially protective role. These findings emphasize the importance of understanding mechanisms driving brain changes, particularly with growing interest in extended space missions in ICE environments.

  PublisherOA PDFDOI

• Anatomical White Matter Tracts Span the Cortical Hierarchy to Support Cognitive Diversity

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-22

  articleOpen access

  Long-range white matter (WM) tracts support cognition by enabling communication between distant cortical regions, which are organized along a hierarchy defined by the sensorimotor-to-association (S-A) axis. However, it remains unknown how WM tracts are positioned within the cortical hierarchy to support cognition. Here, we show that WM tracts are differentially positioned in the cortical hierarchy to support specific cognitive functions, and that tracts spanning the hierarchy connect regions with greater cognitive diversity. Moreover, tracts situated within the same hierarchical level connect biologically similar regions, while those crossing the hierarchy bridge distinct biological milieux to support diverse cognitive functions. The placement of tracts in the cortical hierarchy also reflects developmental variation in tract microstructure and individual differences in cognition. Together, these findings provide a framework that moves beyond conventional categories of association or projection tracts and links WM tract anatomy to cortical organization, cognitive function, cortical neurobiology, and neurodevelopment. We anticipate that this cortex-anchored framework for describing WM tracts may aid the interpretation of individual differences in WM structure related to development and behavior.

  PublisherOA PDFDOI

Recent grants

• Glutamate Chemical Exchange Saturation Transfer (GluCEST) Imaging in Cognitive Aging

  NIH · $533k · 2020–2022

• NIH Grant K01MH102609

  NIH · $685k · 2018

• Olfactory and facial markers of developmental risk for psychosis in 22q11 deletion syndrome

  NIH · $3.5M · 2019–2025

• Ultra-high field GluCEST MRI and MRS in youth at risk for psychosis

  NIH · $3.8M · 2020–2026

Frequent coauthors

• Raquel E. Gur

  Children's Hospital of Philadelphia

  472 shared

• Ruben C. Gur

  Children's Hospital of Philadelphia

  444 shared

• Theodore D. Satterthwaite

  Children's Hospital of Philadelphia

  436 shared

• Tyler M. Moore

  California University of Pennsylvania

  301 shared

• Monica E. Calkins

  University of Pennsylvania

  219 shared

• Kosha Ruparel

  208 shared

• Daniel H. Wolf

  University of Pennsylvania

  191 shared

• Russell T. Shinohara

  145 shared

Labs

• Brain Behavior LaboratoryPI

Awards & honors

• Associate Fellow, University of Pennsylvania Institute on Ag…
• Associated Faculty, Lifespan Brain Institute (LiBI)