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Ruben C. Gur

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YNIMG Journal 2023 Journal Article

ModelArray: An R package for statistical analysis of fixel-wise data

  • Chenying Zhao
  • Tinashe M. Tapera
  • Joëlle Bagautdinova
  • Josiane Bourque
  • Sydney Covitz
  • Raquel E. Gur
  • Ruben C. Gur
  • Bart Larsen

Diffusion MRI is the dominant non-invasive imaging method used to characterize white matter organization in health and disease. Increasingly, fiber-specific properties within a voxel are analyzed using fixels. While tools for conducting statistical analyses of fixel-wise data exist, currently available tools support only a limited number of statistical models. Here we introduce ModelArray, an R package for mass-univariate statistical analysis of fixel-wise data. At present, ModelArray supports linear models as well as generalized additive models (GAMs), which are particularly useful for studying nonlinear effects in lifespan data. In addition, ModelArray also aims for scalable analysis. With only several lines of code, even large fixel-wise datasets can be analyzed using a standard personal computer. Detailed memory profiling revealed that ModelArray required only limited memory even for large datasets. As an example, we applied ModelArray to fixel-wise data derived from diffusion images acquired as part of the Philadelphia Neurodevelopmental Cohort (n = 938). ModelArray revealed anticipated nonlinear developmental effects in white matter. Moving forward, ModelArray is supported by an open-source software development model that can incorporate additional statistical models and other imaging data types. Taken together, ModelArray provides a flexible and efficient platform for statistical analysis of fixel-wise data.

YNIMG Journal 2022 Journal Article

Curation of BIDS (CuBIDS): A workflow and software package for streamlining reproducible curation of large BIDS datasets

  • Sydney Covitz
  • Tinashe M. Tapera
  • Azeez Adebimpe
  • Aaron F. Alexander-Bloch
  • Maxwell A. Bertolero
  • Eric Feczko
  • Alexandre R. Franco
  • Raquel E. Gur

The Brain Imaging Data Structure (BIDS) is a specification accompanied by a software ecosystem that was designed to create reproducible and automated workflows for processing neuroimaging data. BIDS Apps flexibly build workflows based on the metadata detected in a dataset. However, even BIDS valid metadata can include incorrect values or omissions that result in inconsistent processing across sessions. Additionally, in large-scale, heterogeneous neuroimaging datasets, hidden variability in metadata is difficult to detect and classify. To address these challenges, we created a Python-based software package titled "Curation of BIDS" (CuBIDS), which provides an intuitive workflow that helps users validate and manage the curation of their neuroimaging datasets. CuBIDS includes a robust implementation of BIDS validation that scales to large samples and incorporates DataLad--a version control software package for data--as an optional dependency to ensure reproducibility and provenance tracking throughout the entire curation process. CuBIDS provides tools to help users perform quality control on their images' metadata and identify unique combinations of imaging parameters. Users can then execute BIDS Apps on a subset of participants that represent the full range of acquisition parameters that are present, accelerating pipeline testing on large datasets.

YNIMG Journal 2022 Journal Article

Spatially-enhanced clusterwise inference for testing and localizing intermodal correspondence

  • Sarah M. Weinstein
  • Simon N. Vandekar
  • Erica B. Baller
  • Danni Tu
  • Azeez Adebimpe
  • Tinashe M. Tapera
  • Ruben C. Gur
  • Raquel E. Gur

With the increasing availability of neuroimaging data from multiple modalities-each providing a different lens through which to study brain structure or function-new techniques for comparing, integrating, and interpreting information within and across modalities have emerged. Recent developments include hypothesis tests of associations between neuroimaging modalities, which can be used to determine the statistical significance of intermodal associations either throughout the entire brain or within anatomical subregions or functional networks. While these methods provide a crucial foundation for inference on intermodal relationships, they cannot be used to answer questions about where in the brain these associations are most pronounced. In this paper, we introduce a new method, called CLEAN-R, that can be used both to test intermodal correspondence throughout the brain and also to localize this correspondence. Our method involves first adjusting for the underlying spatial autocorrelation structure within each modality before aggregating information within small clusters to construct a map of enhanced test statistics. Using structural and functional magnetic resonance imaging data from a subsample of children and adolescents from the Philadelphia Neurodevelopmental Cohort, we conduct simulations and data analyses where we illustrate the high statistical power and nominal type I error levels of our method. By constructing an interpretable map of group-level correspondence using spatially-enhanced test statistics, our method offers insights beyond those provided by earlier methods.

YNICL Journal 2021 Journal Article

Memory, processing of emotional stimuli, and volume of limbic structures in pediatric-onset multiple sclerosis

  • Tracy L. Fabri
  • Ritobrato Datta
  • Julia O'Mahony
  • Emily Barlow-Krelina
  • Elisea De Somma
  • Giulia Longoni
  • Raquel E. Gur
  • Ruben C. Gur

OBJECTIVE: The limbic system is involved in memory and in processing of emotional stimuli. We measured volume of the hippocampus, amygdala, and thalamus, and assessed their relative contribution to episodic memory and emotion identification in POMS. METHOD: = 18.1 ± 4.6 years; 49 female (64.5%)) completed the Penn Computerized Neurocognitive Battery (PCNB); 59 of 65 POMS participants and 69 out of 76 controls underwent 3 T MRI scanning. We derived age-adjusted Z-scores on accuracy and response time (RT) measures of episodic memory and emotion identification of the PCNB. Magnetic resonance imaging (MRI) volumetrics were normalized using the scaling factor computed by SIENAx. On PCNB tests that differed between groups, we used multiple linear regression to assess relationships between regional brain volumes and either episodic memory or emotion identification outcomes controlling for age, sex, accuracy/RT, and parental education. RESULTS: POMS participants were slower and less accurate than controls on the episodic memory domain but did not differ from controls on emotion outcomes. At the subtest level, POMS participants showed reduced accuracy on Word Memory (p = .002) and slower performance on Face Memory (p = .04) subtests. POMS participants had smaller total and regional brain volumes of the hippocampus, amygdala, and thalamus (p values ≤ 0.01). Collapsing across groups, both hippocampal and thalamic volume were significant predictors of Word Memory accuracy; hippocampal volume (B = 0.24, SE = 0.10, p = .02) was more strongly associated with Word Memory performance than thalamic volume (B = 0.16, SE = 0.05, p = .003), though the estimate with was less precise. CONCLUSIONS: POMS participants showed reduced episodic memory performance compared to controls. Aspects of episodic memory performance were associated with hippocampal and thalamic volume. Emotion identification was intact, despite volume loss in the amygdala.

YNICL Journal 2020 Journal Article

Altered resting-state functional connectivity in adolescents is associated with PTSD symptoms and trauma exposure

  • Jony Sheynin
  • Elizabeth R. Duval
  • Yana Lokshina
  • J. Cobb Scott
  • Mike Angstadt
  • Daniel Kessler
  • Li Zhang
  • Raquel E. Gur

Alterations in resting-state functional connectivity (rsFC) have been demonstrated in Posttraumatic Stress Disorder (PTSD). However, such reports have primarily focused on adult participants, whereas findings in adolescents with PTSD are mixed and not entirely consistent with the adult literature. Here, we examined rsFC in a non-treatment seeking adolescent sample with posttraumatic stress symptoms (PTSS; n = 59) relative to asymptomatic controls (n = 226). We also examined differences between trauma-exposed and non-exposed control subgroups (TEC n = 73 and Non-TEC n = 153) to examine alterations associated with more general trauma exposure. Finally, we compared the PTSS and TEC groups, to confirm that the reported alterations in PTSS were not driven by trauma exposure. Using a seed-based approach, we examined connectivity of default-mode (DMN) and salience (SN) networks, where alterations have been previously reported. Results suggest that PTSS are associated with less within-DMN connectivity and greater SN-DMN connectivity, as well as altered connectivity with attention regions. Trauma exposure is associated with greater within-SN connectivity. Additionally, we report findings from exploratory connectome-based analysis, which demonstrate a number of topological alterations within DMN in the PTSS group. Overall, our findings replicate prior reports of altered rsFC in PTSD and extend them to non-treatment seeking, trauma-exposed adolescents, who did or did not report PTSS. They specifically highlight SN-DMN desegregation, lower within-DMN and greater within-SN connectivity, as well as altered connectivity with attention regions, in trauma-exposed adolescents. Future research is required to confirm that adolescents with diagnosed PTSD have similar/exacerbated connectivity patterns.

YNICL Journal 2020 Journal Article

Dimensional connectomics of anxious misery, a human connectome study related to human disease: Overview of protocol and data quality

  • Darsol Seok
  • Nathan Smyk
  • Marc Jaskir
  • Philip Cook
  • Mark Elliott
  • Tommaso Girelli
  • J. Cobb Scott
  • Nicholas Balderston

Disparate diagnostic categories from the Diagnostic and Statistical Manual of Mental Disorders (DSM), including generalized anxiety disorder, major depressive disorder and post-traumatic stress disorder, share common behavioral and phenomenological dysfunctions. While high levels of comorbidity and common features across these disorders suggest shared mechanisms, past research in psychopathology has largely proceeded based on the syndromal taxonomy established by the DSM rather than on a biologically-informed framework of neural, cognitive and behavioral dysfunctions. In line with the National Institute of Mental Health's Research Domain Criteria (RDoC) framework, we present a Human Connectome Study Related to Human Disease that is intentionally designed to generate and test novel, biologically-motivated dimensions of psychopathology. The Dimensional Connectomics of Anxious Misery study is collecting neuroimaging, cognitive and behavioral data from a heterogeneous population of adults with varying degrees of depression, anxiety and trauma, as well as a set of healthy comparators (to date, n = 97 and n = 24, respectively). This sample constitutes a dataset uniquely situated to elucidate relationships between brain circuitry and dysfunctions of the Negative Valence construct of the RDoC framework. We present a comprehensive overview of the eligibility criteria, clinical procedures and neuroimaging methods of our project. After describing our protocol, we present group-level activation maps from task fMRI data and independent components maps from resting state data. Finally, using quantitative measures of neuroimaging data quality, we demonstrate excellent data quality relative to a subset of the Human Connectome Project of Young Adults (n = 97), as well as comparable profiles of cortical thickness from T1-weighted imaging and generalized fractional anisotropy from diffusion weighted imaging. This manuscript presents results from the first 121 participants of our full target 250 participant dataset, timed with the release of this data to the National Institute of Mental Health Data Archive in fall 2020, with the remaining half of the dataset to be released in 2021.

YNIMG Journal 2019 Journal Article

Sex differences in network controllability as a predictor of executive function in youth

  • Eli J. Cornblath
  • Evelyn Tang
  • Graham L. Baum
  • Tyler M. Moore
  • Azeez Adebimpe
  • David R. Roalf
  • Ruben C. Gur
  • Raquel E. Gur

Executive function is a quintessential human capacity that emerges late in development and displays different developmental trends in males and females. Sex differences in executive function in youth have been linked to vulnerability to psychopathology as well as to behaviors that impinge on health, wellbeing, and longevity. Yet, the neurobiological basis of these differences is not well understood, in part due to the spatiotemporal complexity inherent in patterns of brain network maturation supporting executive function. Here we test the hypothesis that sex differences in impulsivity in youth stem from sex differences in the controllability of structural brain networks as they rewire over development. Combining methods from network neuroscience and network control theory, we characterize the network control properties of structural brain networks estimated from diffusion imaging data acquired in males and females in a sample of 879 youth aged 8–22 years. We summarize the control properties of these networks by estimating average and modal controllability, two statistics that probe the ease with which brain areas can drive the network towards easy versus difficult-to-reach states. We find that females have higher modal controllability in frontal, parietal, and subcortical regions while males have higher average controllability in frontal and subcortical regions. Furthermore, controllability profiles in males are negatively related to the false positive rate on a continuous performance task, a common measure of impulsivity. Finally, we find associations between average controllability and individual differences in activation during an n-back working memory task. Taken together, our findings support the notion that sex differences in the controllability of structural brain networks can partially explain sex differences in executive function. Controllability of structural brain networks also predicts features of task-relevant activation, suggesting the potential for controllability to represent context-specific constraints on network state more generally.

YNIMG Journal 2019 Journal Article

System-level matching of structural and functional connectomes in the human brain

  • Yusuf Osmanlıoğlu
  • Birkan Tunç
  • Drew Parker
  • Mark A. Elliott
  • Graham L. Baum
  • Rastko Ciric
  • Theodore D. Satterthwaite
  • Raquel E. Gur

The brain can be considered as an information processing network, where complex behavior manifests as a result of communication between large-scale functional systems such as visual and default mode networks. As the communication between brain regions occurs through underlying anatomical pathways, it is important to define a “traffic pattern” that properly describes how the regions exchange information. Empirically, the choice of the traffic pattern can be made based on how well the functional connectivity between regions matches the structural pathways equipped with that traffic pattern. In this paper, we present a multimodal connectomics paradigm utilizing graph matching to measure similarity between structural and functional connectomes (derived from dMRI and fMRI data) at node, system, and connectome level. Through an investigation of the brain's structure-function relationship over a large cohort of 641 healthy developmental participants aged 8–22 years, we demonstrate that communicability as the traffic pattern describes the functional connectivity of the brain best, with large-scale systems having significant agreement between their structural and functional connectivity patterns. Notably, matching between structural and functional connectivity for the functionally specialized modular systems such as visual and motor networks are higher as compared to other more integrated systems. Additionally, we show that the negative functional connectivity between the default mode network (DMN) and motor, frontoparietal, attention, and visual networks is significantly associated with its underlying structural connectivity, highlighting the counterbalance between functional activation patterns of DMN and other systems. Finally, we investigated sex difference and developmental changes in brain and observed that similarity between structure and function changes with development.

YNIMG Journal 2018 Journal Article

Brain state expression and transitions are related to complex executive cognition in normative neurodevelopment

  • John D. Medaglia
  • Theodore D. Satterthwaite
  • Apoorva Kelkar
  • Rastko Ciric
  • Tyler M. Moore
  • Kosha Ruparel
  • Ruben C. Gur
  • Raquel E. Gur

Adolescence is marked by rapid development of executive function. Mounting evidence suggests that executive function in adults may be driven by dynamic control of neurophysiological processes. Yet, how these dynamics evolve over adolescence and contribute to cognitive development is unknown. In a sample of 780 youth aged 8–22 yr (42. 7% male) from the Philadelphia Neurodevelopment Cohort, we use a dynamic graph approach to extract activation states in BOLD fMRI data from 264 brain regions. We construct a graph in which each observation in time is a node and the similarity in brain states at two different times is an edge. Using this graphical approach, we identify two primary brain states reminiscent of intrinsic and task-evoked systems. We show that time spent in these two states is higher in older adolescents, as is the flexibility with which the brain switches between them. Increasing time spent in primary states and flexibility among states relates to increases in a complex executive accuracy factor score over adolescence. Flexibility is more positively associated with accuracy toward early adulthood. These findings suggest that brain state dynamics are associated with complex executive function across a critical period of adolescence.

YNIMG Journal 2018 Journal Article

Quantitative assessment of structural image quality

  • Adon F.G. Rosen
  • David R. Roalf
  • Kosha Ruparel
  • Jason Blake
  • Kevin Seelaus
  • Lakshmi P. Villa
  • Rastko Ciric
  • Philip A. Cook

Data quality is increasingly recognized as one of the most important confounding factors in brain imaging research. It is particularly important for studies of brain development, where age is systematically related to in-scanner motion and data quality. Prior work has demonstrated that in-scanner head motion biases estimates of structural neuroimaging measures. However, objective measures of data quality are not available for most structural brain images. Here we sought to identify quantitative measures of data quality for T1-weighted volumes, describe how these measures relate to cortical thickness, and delineate how this in turn may bias inference regarding associations with age in youth. Three highly-trained raters provided manual ratings of 1840 raw T1-weighted volumes. These images included a training set of 1065 images from Philadelphia Neurodevelopmental Cohort (PNC), a test set of 533 images from the PNC, as well as an external test set of 242 adults acquired on a different scanner. Manual ratings were compared to automated quality measures provided by the Preprocessed Connectomes Project's Quality Assurance Protocol (QAP), as well as FreeSurfer's Euler number, which summarizes the topological complexity of the reconstructed cortical surface. Results revealed that the Euler number was consistently correlated with manual ratings across samples. Furthermore, the Euler number could be used to identify images scored “unusable” by human raters with a high degree of accuracy (AUC: 0. 98–0. 99), and out-performed proxy measures from functional timeseries acquired in the same scanning session. The Euler number also was significantly related to cortical thickness in a regionally heterogeneous pattern that was consistent across datasets and replicated prior results. Finally, data quality both inflated and obscured associations with age during adolescence. Taken together, these results indicate that reliable measures of data quality can be automatically derived from T1-weighted volumes, and that failing to control for data quality can systematically bias the results of studies of brain maturation.

YNIMG Journal 2018 Journal Article

The impact of in-scanner head motion on structural connectivity derived from diffusion MRI

  • Graham L. Baum
  • David R. Roalf
  • Philip A. Cook
  • Rastko Ciric
  • Adon F.G. Rosen
  • Cedric Xia
  • Mark A. Elliott
  • Kosha Ruparel

Multiple studies have shown that data quality is a critical confound in the construction of brain networks derived from functional MRI. This problem is particularly relevant for studies of human brain development where important variables (such as participant age) are correlated with data quality. Nevertheless, the impact of head motion on estimates of structural connectivity derived from diffusion tractography methods remains poorly characterized. Here, we evaluated the impact of in-scanner head motion on structural connectivity using a sample of 949 participants (ages 8-23 years old) who passed a rigorous quality assessment protocol for diffusion magnetic resonance imaging (dMRI) acquired as part of the Philadelphia Neurodevelopmental Cohort. Structural brain networks were constructed for each participant using both deterministic and probabilistic tractography. We hypothesized that subtle variation in head motion would systematically bias estimates of structural connectivity and confound developmental inference, as observed in previous studies of functional connectivity. Even following quality assurance and retrospective correction for head motion, eddy currents, and field distortions, in-scanner head motion significantly impacted the strength of structural connectivity in a consistency- and length-dependent manner. Specifically, increased head motion was associated with reduced estimates of structural connectivity for network edges with high inter-subject consistency, which included both short- and long-range connections. In contrast, motion inflated estimates of structural connectivity for low-consistency network edges that were primarily shorter-range. Finally, we demonstrate that age-related differences in head motion can both inflate and obscure developmental inferences on structural connectivity. Taken together, these data delineate the systematic impact of head motion on structural connectivity, and provide a critical context for identifying motion-related confounds in studies of structural brain network development.

YNIMG Journal 2017 Journal Article

Benchmarking of participant-level confound regression strategies for the control of motion artifact in studies of functional connectivity

  • Rastko Ciric
  • Daniel H. Wolf
  • Jonathan D. Power
  • David R. Roalf
  • Graham L. Baum
  • Kosha Ruparel
  • Russell T. Shinohara
  • Mark A. Elliott

Since initial reports regarding the impact of motion artifact on measures of functional connectivity, there has been a proliferation of participant-level confound regression methods to limit its impact. However, many of the most commonly used techniques have not been systematically evaluated using a broad range of outcome measures. Here, we provide a systematic evaluation of 14 participant-level confound regression methods in 393 youths. Specifically, we compare methods according to four benchmarks, including the residual relationship between motion and connectivity, distance-dependent effects of motion on connectivity, network identifiability, and additional degrees of freedom lost in confound regression. Our results delineate two clear trade-offs among methods. First, methods that include global signal regression minimize the relationship between connectivity and motion, but result in distance-dependent artifact. In contrast, censoring methods mitigate both motion artifact and distance-dependence, but use additional degrees of freedom. Importantly, less effective de-noising methods are also unable to identify modular network structure in the connectome. Taken together, these results emphasize the heterogeneous efficacy of existing methods, and suggest that different confound regression strategies may be appropriate in the context of specific scientific goals.

YNIMG Journal 2017 Journal Article

Harmonization of multi-site diffusion tensor imaging data

  • Jean-Philippe Fortin
  • Drew Parker
  • Birkan Tunç
  • Takanori Watanabe
  • Mark A. Elliott
  • Kosha Ruparel
  • David R. Roalf
  • Theodore D. Satterthwaite

Diffusion tensor imaging (DTI) is a well-established magnetic resonance imaging (MRI) technique used for studying microstructural changes in the white matter. As with many other imaging modalities, DTI images suffer from technical between-scanner variation that hinders comparisons of images across imaging sites, scanners and over time. Using fractional anisotropy (FA) and mean diffusivity (MD) maps of 205 healthy participants acquired on two different scanners, we show that the DTI measurements are highly site-specific, highlighting the need of correcting for site effects before performing downstream statistical analyses. We first show evidence that combining DTI data from multiple sites, without harmonization, may be counter-productive and negatively impacts the inference. Then, we propose and compare several harmonization approaches for DTI data, and show that ComBat, a popular batch-effect correction tool used in genomics, performs best at modeling and removing the unwanted inter-site variability in FA and MD maps. Using age as a biological phenotype of interest, we show that ComBat both preserves biological variability and removes the unwanted variation introduced by site. Finally, we assess the different harmonization methods in the presence of different levels of confounding between site and age, in addition to test robustness to small sample size studies.

YNICL Journal 2016 Journal Article

Disrupted anatomic networks in the 22q11.2 deletion syndrome

  • J. Eric Schmitt
  • James Yi
  • Monica E. Calkins
  • Kosha Ruparel
  • David R. Roalf
  • Amy Cassidy
  • Margaret C. Souders
  • Theodore D. Satterthwaite

The 22q11.2 deletion syndrome (22q11DS) is an uncommon genetic disorder with an increased risk of psychosis. Although the neural substrates of psychosis and schizophrenia are not well understood, aberrations in cortical networks represent intriguing potential mechanisms. Investigations of anatomic networks within 22q11DS are sparse. We investigated group differences in anatomic network structure in 48 individuals with 22q11DS and 370 typically developing controls by analyzing covariance patterns in cortical thickness among 68 regions of interest using graph theoretical models. Subjects with 22q11DS had less robust geographic organization relative to the control group, particularly in the occipital and parietal lobes. Multiple global graph theoretical statistics were decreased in 22q11DS. These results are consistent with prior studies demonstrating decreased connectivity in 22q11DS using other neuroimaging methodologies.

YNIMG Journal 2016 Journal Article

MUSE: MUlti-atlas region Segmentation utilizing Ensembles of registration algorithms and parameters, and locally optimal atlas selection

  • Jimit Doshi
  • Guray Erus
  • Yangming Ou
  • Susan M. Resnick
  • Ruben C. Gur
  • Raquel E. Gur
  • Theodore D. Satterthwaite
  • Susan Furth

Atlas-based automated anatomical labeling is a fundamental tool in medical image segmentation, as it defines regions of interest for subsequent analysis of structural and functional image data. The extensive investigation of multi-atlas warping and fusion techniques over the past 5 or more years has clearly demonstrated the advantages of consensus-based segmentation. However, the common approach is to use multiple atlases with a single registration method and parameter set, which is not necessarily optimal for every individual scan, anatomical region, and problem/data-type. Different registration criteria and parameter sets yield different solutions, each providing complementary information. Herein, we present a consensus labeling framework that generates a broad ensemble of labeled atlases in target image space via the use of several warping algorithms, regularization parameters, and atlases. The label fusion integrates two complementary sources of information: a local similarity ranking to select locally optimal atlases and a boundary modulation term to refine the segmentation consistently with the target image's intensity profile. The ensemble approach consistently outperforms segmentations using individual warping methods alone, achieving high accuracy on several benchmark datasets. The MUSE methodology has been used for processing thousands of scans from various datasets, producing robust and consistent results. MUSE is publicly available both as a downloadable software package, and as an application that can be run on the CBICA Image Processing Portal (https: //ipp. cbica. upenn. edu), a web based platform for remote processing of medical images.

YNIMG Journal 2016 Journal Article

Sex differences in the functional connectivity of the amygdalae in association with cortisol

  • Lydia Kogler
  • Veronika I. Müller
  • Eva-Maria Seidel
  • Roland Boubela
  • Klaudius Kalcher
  • Ewald Moser
  • Ute Habel
  • Ruben C. Gur

Human amygdalae are involved in various behavioral functions such as affective and stress processing. For these behavioral functions, as well as for psychophysiological arousal including cortisol release, sex differences are reported. Here, we assessed cortisol levels and resting-state functional connectivity (rsFC) of left and right amygdalae in 81 healthy participants (42 women) to investigate potential modulation of amygdala rsFC by sex and cortisol concentration. Our analyses revealed that rsFC of the left amygdala significantly differed between women and men: Women showed stronger rsFC than men between the left amygdala and left middle temporal gyrus, inferior frontal gyrus, postcentral gyrus and hippocampus, regions involved in face processing, inner-speech, fear and pain processing. No stronger connections were detected for men and no sex difference emerged for right amygdala rsFC. Also, an interaction of sex and cortisol appeared: In women, cortisol was negatively associated with rsFC of the amygdalae with striatal regions, mid-orbital frontal gyrus, anterior cingulate gyrus, middle and superior frontal gyri, supplementary motor area and the parietal–occipital sulcus. Contrarily in men, positive associations of cortisol with rsFC of the left amygdala and these structures were observed. Functional decoding analyses revealed an association of the amygdalae and these regions with emotion, reward and memory processing, as well as action execution. Our results suggest that functional connectivity of the amygdalae as well as the regulatory effect of cortisol on brain networks differs between women and men. These sex-differences and the mediating and sex-dependent effect of cortisol on brain communication systems should be taken into account in affective and stress-related neuroimaging research. Thus, more studies including both sexes are required.

YNIMG Journal 2016 Journal Article

Subject-level measurement of local cortical coupling

  • Simon N. Vandekar
  • Russell T. Shinohara
  • Armin Raznahan
  • Ryan D. Hopson
  • David R. Roalf
  • Kosha Ruparel
  • Ruben C. Gur
  • Raquel E. Gur

The human cortex is highly folded to allow for a massive expansion of surface area. Notably, the thickness of the cortex strongly depends on cortical topology, with gyral cortex sometimes twice as thick as sulcal cortex. We recently demonstrated that global differences in thickness between gyral and sulcal cortex continue to evolve throughout adolescence. However, human cortical development is spatially heterogeneous, and global comparisons lack power to detect localized differences in development or psychopathology. Here we extend previous work by proposing a new measure – local cortical coupling – that is sensitive to differences in the localized topological relationship between cortical thickness and sulcal depth. After estimation, subject-level coupling maps can be analyzed using standard neuroimaging analysis tools. Capitalizing on a large cross-sectional sample (n =932) of youth imaged as part of the Philadelphia Neurodevelopmental Cohort, we demonstrate that local coupling is spatially heterogeneous and exhibits nonlinear development-related trajectories. Moreover, we uncover sex differences in coupling that indicate divergent patterns of cortical topology. Developmental changes and sex differences in coupling support its potential as a neuroimaging phenotype for investigating neuropsychiatric disorders that are increasingly conceptualized as disorders of brain development. R code to estimate subject-level coupling maps from any two cortical surfaces generated by FreeSurfer is made publicly available along with this manuscript.

YNIMG Journal 2016 Journal Article

The impact of quality assurance assessment on diffusion tensor imaging outcomes in a large-scale population-based cohort

  • David R. Roalf
  • Megan Quarmley
  • Mark A. Elliott
  • Theodore D. Satterthwaite
  • Simon N. Vandekar
  • Kosha Ruparel
  • Efstathios D. Gennatas
  • Monica E. Calkins

Background Diffusion tensor imaging (DTI) is applied in investigation of brain biomarkers for neurodevelopmental and neurodegenerative disorders. However, the quality of DTI measurements, like other neuroimaging techniques, is susceptible to several confounding factors (e. g. , motion, eddy currents), which have only recently come under scrutiny. These confounds are especially relevant in adolescent samples where data quality may be compromised in ways that confound interpretation of maturation parameters. The current study aims to leverage DTI data from the Philadelphia Neurodevelopmental Cohort (PNC), a sample of 1601 youths with ages of 8–21 who underwent neuroimaging, to: 1) establish quality assurance (QA) metrics for the automatic identification of poor DTI image quality; 2) examine the performance of these QA measures in an external validation sample; 3) document the influence of data quality on developmental patterns of typical DTI metrics. Methods All diffusion-weighted images were acquired on the same scanner. Visual QA was performed on all subjects completing DTI; images were manually categorized as Poor, Good, or Excellent. Four image quality metrics were automatically computed and used to predict manual QA status: Mean voxel intensity outlier count (MEANVOX), Maximum voxel intensity outlier count (MAXVOX), mean relative motion (MOTION) and temporal signal-to-noise ratio (TSNR). Classification accuracy for each metric was calculated as the area under the receiver-operating characteristic curve (AUC). A threshold was generated for each measure that best differentiated visual QA status and applied in a validation sample. The effects of data quality on sensitivity to expected age effects in this developmental sample were then investigated using the traditional MRI diffusion metrics: fractional anisotropy (FA) and mean diffusivity (MD). Finally, our method of QA is compared with DTIPrep. Results TSNR (AUC=0. 94) best differentiated Poor data from Good and Excellent data. MAXVOX (AUC=0. 88) best differentiated Good from Excellent DTI data. At the optimal threshold, 88% of Poor data and 91% Good/Excellent data were correctly identified. Use of these thresholds on a validation dataset (n=374) indicated high accuracy. In the validation sample 83% of Poor data and 94% of Excellent data was identified using thresholds derived from the training sample. Both FA and MD were affected by the inclusion of poor data in an analysis of an age, sex and race matched comparison sample. In addition, we show that the inclusion of poor data results in significant attenuation of the correlation between diffusion metrics (FA and MD) and age during a critical neurodevelopmental period. We find higher correspondence between our QA method and DTIPrep for Poor data, but we find our method to be more robust for apparently high-quality images. Conclusion Automated QA of DTI can facilitate large-scale, high-throughput quality assurance by reliably identifying both scanner and subject induced imaging artifacts. The results present a practical example of the confounding effects of artifacts on DTI analysis in a large population-based sample, and suggest that estimates of data quality should not only be reported but also accounted for in data analysis, especially in studies of development.

YNIMG Journal 2016 Journal Article

The Philadelphia Neurodevelopmental Cohort: A publicly available resource for the study of normal and abnormal brain development in youth

  • Theodore D. Satterthwaite
  • John J. Connolly
  • Kosha Ruparel
  • Monica E. Calkins
  • Chad Jackson
  • Mark A. Elliott
  • David R. Roalf
  • Ryan Hopson

The Philadelphia Neurodevelopmental Cohort (PNC) is a large-scale study of child development that combines neuroimaging, diverse clinical and cognitive phenotypes, and genomics. Data from this rich resource is now publicly available through the Database of Genotypes and Phenotypes (dbGaP). Here we focus on the data from the PNC that is available through dbGaP and describe how users can access this data, which is evolving to be a significant resource for the broader neuroscience community for studies of normal and abnormal neurodevelopment.

YNIMG Journal 2016 Journal Article

When opportunity meets motivation: Neural engagement during social approach is linked to high approach motivation

  • Sina Radke
  • Eva-Maria Seidel
  • Simon B. Eickhoff
  • Ruben C. Gur
  • Frank Schneider
  • Ute Habel
  • Birgit Derntl

Social rewards are processed by the same dopaminergic-mediated brain networks as non-social rewards, suggesting a common representation of subjective value. Individual differences in personality and motivation influence the reinforcing value of social incentives, but it remains open whether the pursuit of social incentives is analogously supported by the neural reward system when positive social stimuli are connected to approach behavior. To test for a modulation of neural activation by approach motivation, individuals with high and low approach motivation (BAS) completed implicit and explicit social approach–avoidance paradigms during fMRI. High approach motivation was associated with faster implicit approach reactions as well as a trend for higher approach ratings, indicating increased approach tendencies. Implicit and explicit positive social approach was accompanied by stronger recruitment of the nucleus accumbens, middle cingulate cortex, and (pre-)cuneus for individuals with high compared to low approach motivation. These results support and extend prior research on social reward processing, self-other distinctions and affective judgments by linking approach motivation to the engagement of reward-related circuits during motivational reactions to social incentives. This interplay between motivational preferences and motivational contexts might underlie the rewarding experience during social interactions.

YNIMG Journal 2015 Journal Article

Identifying Sparse Connectivity Patterns in the brain using resting-state fMRI

  • Harini Eavani
  • Theodore D. Satterthwaite
  • Roman Filipovych
  • Raquel E. Gur
  • Ruben C. Gur
  • Christos Davatzikos

The human brain processes information via multiple distributed networks. An accurate model of the brain's functional connectome is critical for understanding both normal brain function as well as the dysfunction present in neuropsychiatric illnesses. Current methodologies that attempt to discover the organization of the functional connectome typically assume spatial or temporal separation of the underlying networks. This assumption deviates from an intuitive understanding of brain function, which is that of multiple, inter-dependent spatially overlapping brain networks that efficiently integrate information pertinent to diverse brain functions. It is now increasingly evident that neural systems use parsimonious formations and functional representations to efficiently process information while minimizing redundancy. Hence we exploit recent advances in the mathematics of sparse modeling to develop a methodological framework aiming to understand complex resting-state fMRI connectivity data. By favoring networks that explain the data via a relatively small number of participating brain regions, we obtain a parsimonious representation of brain function in terms of multiple “Sparse Connectivity Patterns” (SCPs), such that differential presence of these SCPs explains inter-subject variability. In this manner the sparsity-based framework can effectively capture the heterogeneity of functional activity patterns across individuals while potentially highlighting multiple sub-populations within the data that display similar patterns. Our results from simulated as well as real resting state fMRI data show that SCPs are accurate and reproducible between sub-samples as well as across datasets. These findings substantiate existing knowledge of intrinsic functional connectivity and provide novel insights into the functional organization of the human brain.

YNIMG Journal 2015 Journal Article

Psychosocial versus physiological stress — Meta-analyses on deactivations and activations of the neural correlates of stress reactions

  • Lydia Kogler
  • Veronika I. Müller
  • Amy Chang
  • Simon B. Eickhoff
  • Peter T. Fox
  • Ruben C. Gur
  • Birgit Derntl

Stress is present in everyday life in various forms and situations. Two stressors frequently investigated are physiological and psychosocial stress. Besides similar subjective and hormonal responses, it has been suggested that they also share common neural substrates. The current study used activation-likelihood-estimation meta-analysis to test this assumption by integrating results of previous neuroimaging studies on stress processing. Reported results are cluster-level FWE corrected. The inferior frontal gyrus (IFG) and the anterior insula (AI) were the only regions that demonstrated overlapping activation for both stressors. Analysis of physiological stress showed consistent activation of cognitive and affective components of pain processing such as the insula, striatum, or the middle cingulate cortex. Contrarily, analysis across psychosocial stress revealed consistent activation of the right superior temporal gyrus and deactivation of the striatum. Notably, parts of the striatum appeared to be functionally specified: the dorsal striatum was activated in physiological stress, whereas the ventral striatum was deactivated in psychosocial stress. Additional functional connectivity and decoding analyses further characterized this functional heterogeneity and revealed higher associations of the dorsal striatum with motor regions and of the ventral striatum with reward processing. Based on our meta-analytic approach, activation of the IFG and the AI seems to indicate a global neural stress reaction. While physiological stress activates a motoric fight-or-flight reaction, during psychosocial stress attention is shifted towards emotion regulation and goal-directed behavior, and reward processing is reduced. Our results show the significance of differentiating physiological and psychosocial stress in neural engagement. Furthermore, the assessment of deactivations in addition to activations in stress research is highly recommended.

YNIMG Journal 2014 Journal Article

Neuroimaging of the Philadelphia Neurodevelopmental Cohort

  • Theodore D. Satterthwaite
  • Mark A. Elliott
  • Kosha Ruparel
  • James Loughead
  • Karthik Prabhakaran
  • Monica E. Calkins
  • Ryan Hopson
  • Chad Jackson

The Philadelphia Neurodevelopmental Cohort (PNC) is a large-scale, NIMH funded initiative to understand how brain maturation mediates cognitive development and vulnerability to psychiatric illness, and understand how genetics impacts this process. As part of this study, 1445 adolescents ages 8–21 at enrollment underwent multimodal neuroimaging. Here, we highlight the conceptual basis for the effort, the study design, and the measures available in the dataset. We focus on neuroimaging measures obtained, including T1-weighted structural neuroimaging, diffusion tensor imaging, perfusion neuroimaging using arterial spin labeling, functional imaging tasks of working memory and emotion identification, and resting state imaging of functional connectivity. Furthermore, we provide characteristics regarding the final sample acquired. Finally, we describe mechanisms in place for data sharing that will allow the PNC to become a freely available public resource to advance our understanding of normal and pathological brain development.

YNIMG Journal 2013 Journal Article

An improved framework for confound regression and filtering for control of motion artifact in the preprocessing of resting-state functional connectivity data

  • Theodore D. Satterthwaite
  • Mark A. Elliott
  • Raphael T. Gerraty
  • Kosha Ruparel
  • James Loughead
  • Monica E. Calkins
  • Simon B. Eickhoff
  • Hakon Hakonarson

Several recent reports in large, independent samples have demonstrated the influence of motion artifact on resting-state functional connectivity MRI (rsfc-MRI). Standard rsfc-MRI preprocessing typically includes regression of confounding signals and band-pass filtering. However, substantial heterogeneity exists in how these techniques are implemented across studies, and no prior study has examined the effect of differing approaches for the control of motion-induced artifacts. To better understand how in-scanner head motion affects rsfc-MRI data, we describe the spatial, temporal, and spectral characteristics of motion artifacts in a sample of 348 adolescents. Analyses utilize a novel approach for describing head motion on a voxelwise basis. Next, we systematically evaluate the efficacy of a range of confound regression and filtering techniques for the control of motion-induced artifacts. Results reveal that the effectiveness of preprocessing procedures on the control of motion is heterogeneous, and that improved preprocessing provides a substantial benefit beyond typical procedures. These results demonstrate that the effect of motion on rsfc-MRI can be substantially attenuated through improved preprocessing procedures, but not completely removed.

YNIMG Journal 2013 Journal Article

Heterogeneous impact of motion on fundamental patterns of developmental changes in functional connectivity during youth

  • Theodore D. Satterthwaite
  • Daniel H. Wolf
  • Kosha Ruparel
  • Guray Erus
  • Mark A. Elliott
  • Simon B. Eickhoff
  • Efstathios D. Gennatas
  • Chad Jackson

Several independent studies have demonstrated that small amounts of in-scanner motion systematically bias estimates of resting-state functional connectivity. This confound is of particular importance for studies of neurodevelopment in youth because motion is strongly related to subject age during this period. Critically, the effects of motion on connectivity mimic major findings in neurodevelopmental research, specifically an age-related strengthening of distant connections and weakening of short-range connections. Here, in a sample of 780 subjects ages 8–22, we re-evaluate patterns of change in functional connectivity during adolescent development after rigorously controlling for the confounding influences of motion at both the subject and group levels. We find that motion artifact inflates both overall estimates of age-related change as well as specific distance-related changes in connectivity. When motion is more fully accounted for, the prevalence of age-related change as well as the strength of distance-related effects is substantially reduced. However, age-related changes remain highly significant. In contrast, motion artifact tends to obscure age-related changes in connectivity associated with segregation of functional brain modules; improved preprocessing techniques allow greater sensitivity to detect increased within-module connectivity occurring with development. Finally, we show that subject’s age can still be accurately estimated from the multivariate pattern of functional connectivity even while controlling for motion. Taken together, these results indicate that while motion artifact has a marked and heterogeneous impact on estimates of connectivity change during adolescence, functional connectivity remains a valuable phenotype for the study of neurodevelopment.

YNIMG Journal 2013 Journal Article

Inhibitory control and trait aggression: Neural and behavioral insights using the emotional stop signal task

  • Christina M. Pawliczek
  • Birgit Derntl
  • Thilo Kellermann
  • Nils Kohn
  • Ruben C. Gur
  • Ute Habel

Deficits in response inhibition and heightened impulsivity have been linked to psychiatric disorders and aggression. They have been investigated in clinical groups as well as individuals with trait characteristics, yielding insights into the underlying neural and behavioral mechanisms of response inhibition and impulsivity. The motor inhibition tasks employed in most studies, however, have lacked an emotional component, which is crucial given that both response inhibition and impulsivity attain salience within a socio-emotional context. For this fMRI study, we selected a group with high trait aggression (HA, n=17) and one with low trait aggression (LA, n=16) from 550 males who had completed an Aggression Questionnaire. Neural activation was compared to an emotional version (including angry and neutral faces) of the stop signal task. Behavioral results revealed impaired response inhibition in HA, associated with higher motor impulsivity. This was accompanied by attenuated activation in brain regions involved in response inhibition, including the pre-supplementary motor area (SMA) and motor cortex. Together, these findings offer evidence that a reduced inhibition capacity is present in HA. Notably, response inhibition improved during anger trials in both groups, suggesting a facilitation effect through heightened activation in the related brain regions. In both groups, inclusion of the anger stimuli enhanced the activation of the motor and somatosensory areas, which modulate executive control, and of limbic regions including the amygdala. In summary, the investigation of response inhibition in individuals with high and low trait characteristics affords useful insights into the underlying distinct processing mechanisms. It can contribute to the investigation of trait markers in a clinical context without having to deal with the complex mechanisms of a clinical disorder itself. In contrast, the mechanisms of emotional response inhibition did not differ between groups. Hence, the specific emotional influence is not interacting with trait aggression.

YNIMG Journal 2012 Journal Article

Being right is its own reward: Load and performance related ventral striatum activation to correct responses during a working memory task in youth

  • Theodore D. Satterthwaite
  • Kosha Ruparel
  • James Loughead
  • Mark A. Elliott
  • Raphael T. Gerraty
  • Monica E. Calkins
  • Hakon Hakonarson
  • Ruben C. Gur

The ventral striatum (VS) is a critical brain region for reinforcement learning and motivation. Intrinsically motivated subjects performing challenging cognitive tasks engage reinforcement circuitry including VS even in the absence of external feedback or incentives. However, little is known about how such VS responses develop with age, relate to task performance, and are influenced by task difficulty. Here we used fMRI to examine VS activation to correct and incorrect responses during a standard n-back working memory task in a large sample (n=304) of healthy children, adolescents and young adults aged 8–22. We found that bilateral VS activates more strongly to correct than incorrect responses, and that the VS response scales with the difficulty of the working memory task. Furthermore, VS response was correlated with discrimination performance during the task, and the magnitude of VS response peaked in mid-adolescence. These findings provide evidence for scalable intrinsic reinforcement signals during standard cognitive tasks, and suggest a novel link between motivation and cognition during adolescent development.

YNIMG Journal 2012 Journal Article

Impact of in-scanner head motion on multiple measures of functional connectivity: Relevance for studies of neurodevelopment in youth

  • Theodore D. Satterthwaite
  • Daniel H. Wolf
  • James Loughead
  • Kosha Ruparel
  • Mark A. Elliott
  • Hakon Hakonarson
  • Ruben C. Gur
  • Raquel E. Gur

It has recently been reported (Van Dijk et al. , 2011) that in-scanner head motion can have a substantial impact on MRI measurements of resting-state functional connectivity. This finding may be of particular relevance for studies of neurodevelopment in youth, confounding analyses to the extent that motion and subject age are related. Furthermore, while Van Dijk et al. demonstrated the effect of motion on seed-based connectivity analyses, it is not known how motion impacts other common measures of connectivity. Here we expand on the findings of Van Dijk et al. by examining the effect of motion on multiple types of resting-state connectivity analyses in a large sample of children and adolescents (n=456). Following replication of the effect of motion on seed-based analyses, we examine the influence of motion on graphical measures of network modularity, dual-regression of independent component analysis, as well as the amplitude and fractional amplitude of low frequency fluctuation. In the entire sample, subject age was highly related to motion. Using a subsample where age and motion were unrelated, we demonstrate that motion has marked effects on connectivity in every analysis examined. While subject age was associated with increased within-network connectivity even when motion was accounted for, controlling for motion substantially attenuated the strength of this relationship. The results demonstrate the pervasive influence of motion on multiple types functional connectivity analysis, and underline the importance of accounting for motion in studies of neurodevelopment.

YNIMG Journal 2011 Journal Article

Cognitive versus automatic mechanisms of mood induction differentially activate left and right amygdala

  • Miriam Dyck
  • James Loughead
  • Thilo Kellermann
  • Frank Boers
  • Ruben C. Gur
  • Klaus Mathiak

The amygdala plays a key role in emotional processing. The specific contribution of the amygdala during the experience of one's own emotion, however, remains controversial and requires clarification. There is a long-standing debate on hemispheric lateralization of emotional processes, yet few studies to date directly investigated differential activation patterns for the left and right amygdala. Limited evidence supports right amygdala involvement in automatic processes of emotion and left amygdala involvement in conscious and cognitively controlled emotion processing. The present study investigated differential contributions of the left and right amygdala to cognitive and automatic mechanisms of mood induction. Using functional magnetic resonance imaging (fMRI), we examined hemispheric amygdala responses during two mood induction paradigms: a purely visual method presenting face stimuli and an audiovisual method using faces and music. Amygdala responses in 30 subjects (16 females) showed differences in lateralization patterns depending on the processing mode. The left amygdala exhibited comparable activation levels for both methods. The right amygdala, in contrast, showed increased activity only for the audiovisual condition and this activity was increasing over time. The left amygdala showed augmented activity with higher intensity ratings of negative emotional valence. These results support a left-lateralized cognitive and intentional control of mood and a right-sided more automatic induction of emotion that relies less on explicit reflection processes. The modulation of the left amygdala responses by subjective experience may reflect individual differences in the cognitive effort used to induce the mood. Thus, the central role of the amygdala may not be restricted to the perception of emotion in others but also extend into processes involved in regulation of mood.

AIIM Journal 2003 Journal Article

Fuzzy cluster analysis of high-field functional MRI data

  • Christian Windischberger
  • Markus Barth
  • Claus Lamm
  • Lee Schroeder
  • Herbert Bauer
  • Ruben C. Gur
  • Ewald Moser

Functional magnetic resonance imaging (fMRI) based on blood–oxygen level dependent (BOLD) contrast today is an established brain research method and quickly gains acceptance for complementary clinical diagnosis. However, neither the basic mechanisms like coupling between neuronal activation and haemodynamic response are known exactly, nor can the various artifacts be predicted or controlled. Thus, modeling functional signal changes is non-trivial and exploratory data analysis (EDA) may be rather useful. In particular, identification and separation of artifacts as well as quantification of expected, i. e. stimulus correlated, and novel information on brain activity is important for both, new insights in neuroscience and future developments in functional MRI of the human brain. After an introduction on fuzzy clustering and very high-field fMRI we present several examples where fuzzy cluster analysis (FCA) of fMRI time series helps to identify and locally separate various artifacts. We also present and discuss applications and limitations of fuzzy cluster analysis in very high-field functional MRI: differentiate temporal patterns in MRI using (a) a test object with static and dynamic parts, (b) artifacts due to gross head motion artifacts. Using a synthetic fMRI data set we quantitatively examine the influences of relevant FCA parameters on clustering results in terms of receiver–operator characteristics (ROC) and compare them with a commonly used model-based correlation analysis (CA) approach. The application of FCA in analyzing in vivo fMRI data is shown for (a) a motor paradigm, (b) data from multi-echo imaging, and (c) a fMRI study using mental rotation of three-dimensional cubes. We found that differentiation of true “neural” from false “vascular” activation is possible based on echo time dependence and specific activation levels, as well as based on their signal time-course. Exploratory data analysis methods in general and fuzzy cluster analysis in particular may help to identify artifacts and add novel and unexpected information valuable for interpretation, classification and characterization of functional MRI data which can be used to design new data acquisition schemes, stimulus presentations, neuro(physio)logical paradigms, as well as to improve quantitative biophysical models.

YNIMG Journal 2002 Journal Article

Brain Activation during Facial Emotion Processing

  • Ruben C. Gur
  • Lee Schroeder
  • Travis Turner
  • Claire McGrath
  • Robin M. Chan
  • Bruce I. Turetsky
  • David Alsop
  • Joseph Maldjian

Functional neuroimaging studies have helped identify neural systems involved in cognitive processing and more recently have indicated limbic activation to emotional stimuli. Some functional magnetic resonance imaging (fMRI) studies have reported increased amygdala response during exposure to emotional stimuli while others have not shown such activation. The present study was designed to test the hypothesis that activation of the amygdala is related to the relevance of the emotional valence of stimuli. Healthy young participants (7 men, 7 women) were studied in a high-field (4 tesla) scanner using blood oxygenation-level dependent (BOLD) signal changes in a blocked “box car” design. They viewed facial displays of happiness, sadness, anger, fear, and disgust as well as neutral faces obtained from professional actors and actresses of diverse ethnicity and age. Their task alternated between emotion discrimination (indicating whether the emotion was positive or negative) and age discrimination (indicating whether the poser was older or younger than 30). Blocks contained the same proportion of emotional and neutral faces. Limbic response was greater during the emotion than during the age discrimination conditions. The response was most pronounced in the amygdala, but was also present in the hippocampus and circumscribed voxels in other limbic regions. These results support the central role of the amygdala in emotion processing, and indicate its sensitivity to the task relevance of the emotional display.

YNIMG Journal 2000 Journal Article

Hemispheric Activation of Anterior and Inferior Prefrontal Cortex during Verbal Encoding and Recognition: A PET Study of Healthy Volunteers

  • J.Daniel Ragland
  • Ruben C. Gur
  • Mark G. Lazarev
  • Robin J. Smith
  • Lee Schroeder
  • Jonathan Raz
  • Bruce I. Turetsky
  • Abass Alavi

Evidence of bilateral prefrontal activation during memory encoding and retrieval has increased attention given to anatomical subdivisions within the prefrontal cortex. The current study examined anterior and inferior aspects of the prefrontal cortex to determine their degree of functional and hemispheric overlap during encoding and recognition. Cerebral blood flow of 25 healthy volunteers was measured using PET 15O-water methods during four conditions: resting baseline, sequential finger movement, word encoding, and word recognition. Resting and motor images were averaged to provide a single reference that was subtracted from encoding and recognition using statistical parametric mapping (SPM96). Memory conditions were also subtracted from each other to identify differences in regional activity. Subjects performed well (86% correct) and had a slightly conservative response bias. Baseline subtraction from encoding revealed focal activation of left inferior prefrontal cortex (area 45) without significant contralateral activation. Recognition minus baseline subtraction produced a focal right anterior prefrontal activation (areas 9 and 10) that was not present in the left hemisphere. Bilateral effects were seen in area 45 during recognition. Subtraction of memory tasks from each other did not reveal any areas of greater activity during encoding. However, the recognition task produced greater activation in right area 9 extending into the anterior cingulate. Greater activity during recognition was also observed in left insula and bilateral visual integration areas. These results are discussed in relation to the prevailing model of prefrontal hemispheric asymmetry during episodic memory.

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