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Nicholas Allgaier

Bio: Nicholas Allgaier is an academic researcher from University of Vermont. The author has contributed to research in topics: Neuroimaging & Psychology. The author has an hindex of 8, co-authored 31 publications receiving 591 citations.

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Journal ArticleDOI
Donald J. Hagler1, Sean N. Hatton1, M. Daniela Cornejo1, Carolina Makowski2, Damien A. Fair3, Anthony Steven Dick4, Matthew T. Sutherland4, B. J. Casey5, M Deanna6, Michael P. Harms6, Richard Watts5, James M. Bjork7, Hugh Garavan8, Laura Hilmer1, Christopher J. Pung1, Chelsea S. Sicat1, Joshua M. Kuperman1, Hauke Bartsch1, Feng Xue1, Mary M. Heitzeg9, Angela R. Laird4, Thanh T. Trinh1, Raul Gonzalez4, Susan F. Tapert1, Michael C. Riedel4, Lindsay M. Squeglia10, Luke W. Hyde9, Monica D. Rosenberg5, Eric Earl3, Katia D. Howlett11, Fiona C. Baker12, Mary E. Soules9, Jazmin Diaz1, Octavio Ruiz de Leon1, Wesley K. Thompson1, Michael C. Neale7, Megan M. Herting13, Elizabeth R. Sowell13, Ruben P. Alvarez11, Samuel W. Hawes4, Mariana Sanchez4, Jerzy Bodurka14, Florence J. Breslin14, Amanda Sheffield Morris14, Martin P. Paulus14, W. Kyle Simmons14, Jonathan R. Polimeni15, Andre van der Kouwe15, Andrew S. Nencka16, Kevin M. Gray10, Carlo Pierpaoli11, John A. Matochik11, Antonio Noronha11, Will M. Aklin11, Kevin P. Conway11, Meyer D. Glantz11, Elizabeth Hoffman11, Roger Little11, Marsha F. Lopez11, Vani Pariyadath11, Susan R.B. Weiss11, Dana L. Wolff-Hughes, Rebecca DelCarmen-Wiggins, Sarah W. Feldstein Ewing3, Oscar Miranda-Dominguez3, Bonnie J. Nagel3, Anders Perrone3, Darrick Sturgeon3, Aimee Goldstone12, Adolf Pfefferbaum12, Kilian M. Pohl12, Devin Prouty12, Kristina A. Uban17, Susan Y. Bookheimer18, Mirella Dapretto18, Adriana Galván18, Kara Bagot1, Jay N. Giedd1, M. Alejandra Infante1, Joanna Jacobus1, Kevin Patrick1, Paul D. Shilling1, Rahul S. Desikan19, Yi Li19, Leo P. Sugrue19, Marie T. Banich20, Naomi P. Friedman20, John K. Hewitt20, Christian J. Hopfer20, Joseph T. Sakai20, Jody Tanabe20, Linda B. Cottler21, Sara Jo Nixon21, Linda Chang22, Christine C. Cloak22, Thomas Ernst22, Gloria Reeves22, David N. Kennedy23, Steve Heeringa9, Scott Peltier9, John E. Schulenberg9, Chandra Sripada9, Robert A. Zucker9, William G. Iacono24, Monica Luciana24, Finnegan J. Calabro25, Duncan B. Clark25, David A. Lewis25, Beatriz Luna25, Claudiu Schirda25, Tufikameni Brima26, John J. Foxe26, Edward G. Freedman26, Daniel W. Mruzek26, Michael J. Mason27, Rebekah S. Huber28, Erin McGlade28, Andrew P. Prescot28, Perry F. Renshaw28, Deborah A. Yurgelun-Todd28, Nicholas Allgaier8, Julie A. Dumas8, Masha Y. Ivanova8, Alexandra Potter8, Paul Florsheim29, Christine L. Larson29, Krista M. Lisdahl29, Michael E. Charness15, Michael E. Charness30, Michael E. Charness31, Bernard F. Fuemmeler7, John M. Hettema7, Hermine H. Maes7, Joel L. Steinberg7, Andrey P. Anokhin6, Paul E.A. Glaser6, Andrew C. Heath6, Pamela A. F. Madden6, Arielle R. Baskin-Sommers5, R. Todd Constable5, Steven Grant11, Gayathri J. Dowling11, Sandra A. Brown1, Terry L. Jernigan1, Anders M. Dale1 
TL;DR: The baseline neuroimaging processing and subject-level analysis methods used by the Adolescent Brain Cognitive Development Study are described to be a resource of unprecedented scale and depth for studying typical and atypical development.

431 citations

Posted ContentDOI
Donald J. Hagler1, Sean N. Hatton1, Carolina Makowski2, M. Daniela Cornejo3, Damien A. Fair3, Anthony Steven Dick4, Matthew T. Sutherland4, B. J. Casey5, M Deanna6, Michael P. Harms6, Richard Watts5, James M. Bjork7, Hugh Garavan8, Laura Hilmer1, Christopher J. Pung1, Chelsea S. Sicat1, Joshua M. Kuperman1, Hauke Bartsch1, Feng Xue1, Mary M. Heitzeg9, Angela R. Laird4, Thanh T. Trinh1, Raul Gonzalez4, Susan F. Tapert1, Michael C. Riedel4, Lindsay M. Squeglia10, Luke W. Hyde9, Monica D. Rosenberg5, Eric Earl3, Katia D. Howlett11, Fiona C. Baker12, Mary E. Soules9, Jazmin Diaz1, Octavio Ruiz de Leon1, Wesley K. Thompson1, Michael C. Neale7, Megan M. Herting13, Elizabeth R. Sowell13, Ruben P. Alvarez14, Samuel W. Hawes4, Mariana Sanchez4, Jerzy Bodurka15, Florence J. Breslin15, Amanda Sheffield Morris15, Martin P. Paulus15, W. Kyle Simmons15, Jonathan R. Polimeni16, Andre van der Kouwe16, Andrew S. Nencka17, Kevin M. Gray10, Carlo Pierpaoli14, John A. Matochik14, Antonio Noronha14, Will M. Aklin11, Kevin P. Conway11, Meyer D. Glantz11, Elizabeth Hoffman11, Roger Little11, Marsha F. Lopez11, Vani Pariyadath11, Susan R.B. Weiss11, Dana L. Wolff-Hughes, Rebecca DelCarmen-Wiggins, Sarah W. Feldstein Ewing3, Oscar Miranda-Dominguez3, Bonnie J. Nagel3, Anders Perrone3, Darrick Sturgeon3, Aimee Goldstone12, Adolf Pfefferbaum12, Kilian M. Pohl12, Devin Prouty12, Kristina A. Uban1, Susan Y. Bookheimer1, Mirella Dapretto1, Adriana Galván1, Kara Bagot1, Jay N. Giedd1, M. Alejandra Infante1, Joanna Jacobus1, Kevin Patrick1, Paul D. Shilling1, Rahul S. Desikan1, Yi Li1, Leo P. Sugrue1, Marie T. Banich18, Naomi P. Friedman18, John K. Hewitt18, Christian J. Hopfer18, Joseph T. Sakai18, Jody Tanabe18, Linda B. Cottler19, Sara Jo Nixon19, Linda Chang20, Christine C. Cloak20, Thomas Ernst20, Gloria Reeves20, David N. Kennedy21, Steve Heeringa9, Scott Peltier9, John E. Schulenberg9, Chandra Sripada9, Robert A. Zucker9, William G. Iacono22, Monica Luciana22, Finnegan J. Calabro23, Duncan B. Clark23, David A. Lewis23, Beatriz Luna23, Claudiu Schirda23, Tufikameni Brima24, John J. Foxe24, Edward G. Freedman24, Daniel W. Mruzek24, Michael J. Mason25, Rebekah S. Huber26, Erin McGlade26, Andrew P. Prescot26, Perry F. Renshaw26, Deborah A. Yurgelun-Todd26, Nicholas Allgaier8, Julie A. Dumas8, Masha Y. Ivanova8, Alexandra Potter8, Paul Florsheim27, Christine L. Larson27, Krista M. Lisdahl27, Michael E. Charness28, Bernard F. Fuemmeler7, John M. Hettema7, Joel L. Steinberg7, Andrey P. Anokhin6, Paul E.A. Glaser6, Andrew C. Heath6, Pamela A. F. Madden6, Arielle R. Baskin-Sommers5, R. Todd Constable5, Steven Grant11, Gayathri J. Dowling11, Sandra A. Brown1, Terry L. Jernigan1, Anders M. Dale1 
04 Nov 2018-bioRxiv
TL;DR: The baseline neuroimaging processing and subject-level analysis methods used by the ABCD DAIC in the centralized processing and extraction of neuroanatomical and functional imaging phenotypes are described.
Abstract: The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The ABCD Study is a collaborative effort, including a Coordinating Center, 21 data acquisition sites across the United States, and a Data Analysis and Informatics Center (DAIC). The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data will provide a resource of unprecedented scale and depth for studying typical and atypical development. Here, we describe the baseline neuroimaging processing and subject-level analysis methods used by the ABCD DAIC in the centralized processing and extraction of neuroanatomical and functional imaging phenotypes. Neuroimaging processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI.

276 citations

Journal ArticleDOI
TL;DR: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine.
Abstract: Objective: Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes. Method: Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings. Results: Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects. Conclusions: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine.

176 citations

Journal ArticleDOI
TL;DR: The results suggest that BMI is associated with prefrontal cortex development and diminished executive functions, such as working memory.
Abstract: Importance A total of 25.7 million children in the United States are classified as overweight or obese. Obesity is associated with deficits in executive function, which may contribute to poor dietary decision-making. Less is known about the associations between being overweight or obese and brain development. Objective To examine whether body mass index (BMI) is associated with thickness of the cerebral cortex and whether cortical thickness mediates the association between BMI and executive function in children. Design, Setting, and Participants In this cross-sectional study, cortical thickness maps were derived from T1-weighted structural magnetic resonance images of a large, diverse sample of 9 and 10-year-old children from 21 US sites. List sorting, flanker, matrix reasoning, and Wisconsin card sorting tasks were used to assess executive function. Main Outcomes and Measures A 10-fold nested cross-validation general linear model was used to assess mean cortical thickness from BMI across cortical brain regions. Associations between BMI and executive function were explored with Pearson partial correlations. Mediation analysis examined whether mean prefrontal cortex thickness mediated the association between BMI and executive function. Results Among 3190 individuals (mean [SD] age, 10.0 [0.61] years; 1627 [51.0%] male), those with higher BMI exhibited lower cortical thickness. Eighteen cortical regions were significantly inversely associated with BMI. The greatest correlations were observed in the prefrontal cortex. The BMI was inversely correlated with dimensional card sorting (r = −0.088,P Conclusions and Relevance These results suggest that BMI is associated with prefrontal cortex development and diminished executive functions, such as working memory.

91 citations

Journal ArticleDOI
TL;DR: Evidence is presented suggesting structural brain and cognitive effects of just one or two instances of cannabis use in adolescence and Converging evidence suggests a role for the endocannabinoid system in these effects.
Abstract: Rates of cannabis use among adolescents are high, and are increasing concurrent with changes in the legal status of marijuana and societal attitudes regarding its use. Recreational cannabis use is understudied, especially in the adolescent period when neural maturation may make users particularly vulnerable to the effects of Δ-9-tetrahydrocannabinol (THC) on brain structure. In the current study, we used voxel-based morphometry to compare gray matter volume (GMV) in forty-six 14-year-old human adolescents (males and females) with just one or two instances of cannabis use and carefully matched THC-naive controls. We identified extensive regions in the bilateral medial temporal lobes as well as the bilateral posterior cingulate, lingual gyri, and cerebellum that showed greater GMV in the cannabis users. Analysis of longitudinal data confirmed that GMV differences were unlikely to precede cannabis use. GMV in the temporal regions was associated with contemporaneous performance on the Perceptual Reasoning Index and with future generalized anxiety symptoms in the cannabis users. The distribution of GMV effects mapped onto biomarkers of the endogenous cannabinoid system providing insight into possible mechanisms for these effects. SIGNIFICANCE STATEMENT Almost 35% of American 10th graders have reported using cannabis and existing research suggests that initiation of cannabis use in adolescence is associated with long-term neurocognitive effects. We understand very little about the earliest effects of cannabis use, however, because most research is conducted in adults with a heavy pattern of lifetime use. This study presents evidence suggesting structural brain and cognitive effects of just one or two instances of cannabis use in adolescence. Converging evidence suggests a role for the endocannabinoid system in these effects. This research is particularly timely as the legal status of cannabis is changing in many jurisdictions and the perceived risk by youth associated with smoking cannabis has declined in recent years.

68 citations


Cited by
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TL;DR: In this article , the authors used three of the largest neuroimaging datasets currently available, with a total sample size of around 50,000 individuals, to quantify brain-wide association studies effect sizes and reproducibility as a function of sample size.
Abstract: Magnetic resonance imaging (MRI) has transformed our understanding of the human brain through well-replicated mapping of abilities to specific structures (for example, lesion studies) and functions1-3 (for example, task functional MRI (fMRI)). Mental health research and care have yet to realize similar advances from MRI. A primary challenge has been replicating associations between inter-individual differences in brain structure or function and complex cognitive or mental health phenotypes (brain-wide association studies (BWAS)). Such BWAS have typically relied on sample sizes appropriate for classical brain mapping4 (the median neuroimaging study sample size is about 25), but potentially too small for capturing reproducible brain-behavioural phenotype associations5,6. Here we used three of the largest neuroimaging datasets currently available-with a total sample size of around 50,000 individuals-to quantify BWAS effect sizes and reproducibility as a function of sample size. BWAS associations were smaller than previously thought, resulting in statistically underpowered studies, inflated effect sizes and replication failures at typical sample sizes. As sample sizes grew into the thousands, replication rates began to improve and effect size inflation decreased. More robust BWAS effects were detected for functional MRI (versus structural), cognitive tests (versus mental health questionnaires) and multivariate methods (versus univariate). Smaller than expected brain-phenotype associations and variability across population subsamples can explain widespread BWAS replication failures. In contrast to non-BWAS approaches with larger effects (for example, lesions, interventions and within-person), BWAS reproducibility requires samples with thousands of individuals.

611 citations

Journal ArticleDOI
TL;DR: In this paper , the authors used three of the largest neuroimaging datasets currently available, with a total sample size of around 50,000 individuals, to quantify brain-wide association studies effect sizes and reproducibility as a function of sample size.
Abstract: Magnetic resonance imaging (MRI) has transformed our understanding of the human brain through well-replicated mapping of abilities to specific structures (for example, lesion studies) and functions1-3 (for example, task functional MRI (fMRI)). Mental health research and care have yet to realize similar advances from MRI. A primary challenge has been replicating associations between inter-individual differences in brain structure or function and complex cognitive or mental health phenotypes (brain-wide association studies (BWAS)). Such BWAS have typically relied on sample sizes appropriate for classical brain mapping4 (the median neuroimaging study sample size is about 25), but potentially too small for capturing reproducible brain-behavioural phenotype associations5,6. Here we used three of the largest neuroimaging datasets currently available-with a total sample size of around 50,000 individuals-to quantify BWAS effect sizes and reproducibility as a function of sample size. BWAS associations were smaller than previously thought, resulting in statistically underpowered studies, inflated effect sizes and replication failures at typical sample sizes. As sample sizes grew into the thousands, replication rates began to improve and effect size inflation decreased. More robust BWAS effects were detected for functional MRI (versus structural), cognitive tests (versus mental health questionnaires) and multivariate methods (versus univariate). Smaller than expected brain-phenotype associations and variability across population subsamples can explain widespread BWAS replication failures. In contrast to non-BWAS approaches with larger effects (for example, lesions, interventions and within-person), BWAS reproducibility requires samples with thousands of individuals.

520 citations

Journal ArticleDOI
TL;DR: In this paper, a data-driven forecasting method for high-dimensional chaotic systems using long short-term memory (LSTM) recurrent neural networks is introduced. But the LSTM neural networks perform inference of highdimensional dynamical systems in their reduced order space and are shown to be an effective set of nonlinear approximators of their attractor.
Abstract: We introduce a data-driven forecasting method for high-dimensional chaotic systems using long short-term memory (LSTM) recurrent neural networks. The proposed LSTM neural networks perform inference of high-dimensional dynamical systems in their reduced order space and are shown to be an effective set of nonlinear approximators of their attractor. We demonstrate the forecasting performance of the LSTM and compare it with Gaussian processes (GPs) in time series obtained from the Lorenz 96 system, the Kuramoto-Sivashinsky equation and a prototype climate model. The LSTM networks outperform the GPs in short-term forecasting accuracy in all applications considered. A hybrid architecture, extending the LSTM with a mean stochastic model (MSM-LSTM), is proposed to ensure convergence to the invariant measure. This novel hybrid method is fully data-driven and extends the forecasting capabilities of LSTM networks.

356 citations

Journal ArticleDOI
TL;DR: This review summarizes the last decade of work by the ENIGMA Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease, and highlights the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings.
Abstract: This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.

355 citations

Journal ArticleDOI
Martine Hoogman1, Ryan L. Muetzel2, João P.O.F.T. Guimarães1, Elena Shumskaya1, Maarten Mennes1, Marcel P. Zwiers1, Neda Jahanshad3, Gustavo Sudre4, Thomas Wolfers1, Eric Earl5, Juan Carlos Soliva Vila6, Yolanda Vives-Gilabert7, Sabin Khadka8, Stephanie E. Novotny8, Catharina A. Hartman9, Dirk J. Heslenfeld10, Lizanne J. S. Schweren9, Sara Ambrosino, Bob Oranje, Patrick de Zeeuw, Tiffany M. Chaim-Avancini11, Pedro G.P. Rosa11, Marcus V. Zanetti11, Charles B Malpas12, Gregor Kohls13, Georg G. von Polier, Jochen Seitz13, Joseph Biederman14, Alysa E. Doyle15, Anders M. Dale16, Theo G.M. van Erp17, Jeffery N. Epstein18, Terry L. Jernigan16, Ramona Baur-Streubel, Georg C. Ziegler19, Kathrin C. Zierhut19, Anouk Schrantee20, Marie F. Høvik21, Astri J. Lundervold22, Clare Kelly23, Hazel McCarthy24, Norbert Skokauskas25, Ruth O'Gorman Tuura26, Anna Calvo27, Sara Lera-Miguel27, Rosa Nicolau27, Kaylita Chantiluke28, Anastasia Christakou29, Alasdair Vance12, Mara Cercignani30, Matt C. Gabel30, Philip Asherson28, Sarah Baumeister31, Daniel Brandeis26, Sarah Hohmann31, Ivanei E. Bramati, Fernanda Tovar-Moll32, Andreas J. Fallgatter33, Bernd Kardatzki33, Lena Schwarz33, Anatoly Anikin, A.A. Baranov, Tinatin Gogberashvili, Dmitry Kapilushniy, Anastasia Solovieva, Hanan El Marroun34, Tonya White2, Georgii Karkashadze, Leyla Namazova-Baranova35, Thomas Ethofer33, Paulo Mattos32, Tobias Banaschewski31, David Coghill12, Kerstin J. Plessen36, Jonna Kuntsi28, Mitul A. Mehta28, Yannis Paloyelis28, Neil A. Harrison37, Neil A. Harrison38, Mark A. Bellgrove39, Timothy J. Silk40, Ana Cubillo28, Katya Rubia28, Luisa Lázaro27, Silvia Brem41, Susanne Walitza41, Thomas Frodl42, Mariam Zentis43, Francisco X. Castellanos44, Yuliya N. Yoncheva2, Yuliya N. Yoncheva1, Jan Haavik1, Jan Haavik2, L. Reneman2, L. Reneman1, Annette Conzelmann19, Klaus-Peter Lesch1, Klaus-Peter Lesch2, Paul Pauli19, Andreas Reif45, Leanne Tamm1, Leanne Tamm34, Kerstin Konrad, Eileen Oberwelland Weiss, Geraldo F. Busatto2, Geraldo F. Busatto1, Mario Rodrigues Louzã2, Mario Rodrigues Louzã1, Sarah Durston1, Sarah Durston2, Pieter J. Hoekstra9, Jaap Oosterlaan46, Michael C. Stevens47, J. Antoni Ramos-Quiroga6, Oscar Vilarroya48, Damien A. Fair2, Damien A. Fair1, Joel T. Nigg2, Joel T. Nigg1, Paul M. Thompson1, Paul M. Thompson2, Jan K. Buitelaar2, Jan K. Buitelaar1, Stephen V. Faraone49, Philip Shaw2, Philip Shaw1, Henning Tiemeier14, Janita Bralten1, Barbara Franke1 
Radboud University Nijmegen1, Erasmus University Medical Center2, University of Southern California3, National Institutes of Health4, Oregon Health & Science University5, Autonomous University of Barcelona6, Polytechnic University of Valencia7, Hartford Hospital8, University of Groningen9, VU University Amsterdam10, University of São Paulo11, University of Melbourne12, RWTH Aachen University13, Harvard University14, VA Boston Healthcare System15, University of California, San Diego16, University of California, Irvine17, University of Cincinnati18, University of Würzburg19, University of Amsterdam20, Haukeland University Hospital21, University of Bergen22, New York University23, Trinity College, Dublin24, Norwegian University of Science and Technology25, University of Zurich26, University of Barcelona27, University of London28, University of Reading29, University of Brighton30, Heidelberg University31, Federal University of Rio de Janeiro32, University of Tübingen33, Erasmus University Rotterdam34, Russian National Research Medical University35, University Hospital of Lausanne36, University of Sussex37, Brighton and Sussex University Hospitals NHS Trust38, Monash University39, Deakin University40, ETH Zurich41, German Center for Neurodegenerative Diseases42, University of Regensburg43, Nathan Kline Institute for Psychiatric Research44, Goethe University Frankfurt45, VU University Medical Center46, Yale University47, Pompeu Fabra University48, State University of New York System49
TL;DR: Subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention.
Abstract: OBJECTIVE: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies. METHODS: Cortical thickness and surface area (based on the Desikan-Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707). RESULTS: In the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen's d=-0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample. CONCLUSIONS: Subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis.

231 citations