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Item Associations between regional brain physiology and trait impulsivity, motor inhibition, and impaired control over drinking(Elsevier, 2015-08-30) Weafer, Jessica; Dzemidzic, Mario; Eiler, William J. A. II; Oberlin, Brandon G.; Wang, Yang; Kareken, David A.; Department of Neurology, IU School of MedicineTrait impulsivity and poor inhibitory control are well-established risk factors for alcohol misuse, yet little is known about the associated neurobiological endophenotypes. Here we examined correlations among brain physiology and self-reported trait impulsive behavior, impaired control over drinking, and a behavioral measure of response inhibition. A sample of healthy drinkers (n = 117) completed a pulsed arterial spin labeling (PASL) scan to quantify resting regional cerebral blood flow (rCBF), as well as measures of self-reported impulsivity (Eysenck I7 Impulsivity scale) and impaired control over drinking. A subset of subjects (n = 40) performed a stop signal task during blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging to assess brain regions involved in response inhibition. Eysenck I7 scores were inversely related to blood flow in the right precentral gyrus. Significant BOLD activation during response inhibition occurred in an overlapping right frontal motor/premotor region. Moreover, impaired control over drinking was associated with reduced BOLD response in the same region. These findings suggest that impulsive personality and impaired control over drinking are associated with brain physiology in areas implicated in response inhibition. This is consistent with the idea that difficulty controlling behavior is due in part to impairment in motor restraint systems.Item Brain explorer for connectomic analysis(Springer, 2017-08-23) Li, Huang; Fang, Shiaofen; Contreras, Joey A.; West, John D.; Risacher, Shannon L.; Wang, Yang; Sporns, Olaf; Saykin, Andrew J.; Goñi, Joaquín; Shen, Li; Radiology and Imaging Sciences, School of MedicineVisualization plays a vital role in the analysis of multimodal neuroimaging data. A major challenge in neuroimaging visualization is how to integrate structural, functional, and connectivity data to form a comprehensive visual context for data exploration, quality control, and hypothesis discovery. We develop a new integrated visualization solution for brain imaging data by combining scientific and information visualization techniques within the context of the same anatomical structure. In this paper, new surface texture techniques are developed to map non-spatial attributes onto both 3D brain surfaces and a planar volume map which is generated by the proposed volume rendering technique, spherical volume rendering. Two types of non-spatial information are represented: (1) time series data from resting-state functional MRI measuring brain activation; (2) network properties derived from structural connectivity data for different groups of subjects, which may help guide the detection of differentiation features. Through visual exploration, this integrated solution can help identify brain regions with highly correlated functional activations as well as their activation patterns. Visual detection of differentiation features can also potentially discover image-based phenotypic biomarkers for brain diseases.Item Brain-age prediction: Systematic evaluation of site effects, and sample age range and size(Wiley, 2024) Yu, Yuetong; Cui, Hao-Qi; Haas, Shalaila S.; New, Faye; Sanford, Nicole; Yu, Kevin; Zhan, Denghuang; Yang, Guoyuan; Gao, Jia-Hong; Wei, Dongtao; Qiu, Jiang; Banaj, Nerisa; Boomsma, Dorret I.; Breier, Alan; Brodaty, Henry; Buckner, Randy L.; Buitelaar, Jan K.; Cannon, Dara M.; Caseras, Xavier; Clark, Vincent P.; Conrod, Patricia J.; Crivello, Fabrice; Crone, Eveline A.; Dannlowski, Udo; Davey, Christopher G.; de Haan, Lieuwe; de Zubicaray, Greig I.; Di Giorgio, Annabella; Fisch, Lukas; Fisher, Simon E.; Franke, Barbara; Glahn, David C.; Grotegerd, Dominik; Gruber, Oliver; Gur, Raquel E.; Gur, Ruben C.; Hahn, Tim; Harrison, Ben J.; Hatton, Sean; Hickie, Ian B.; Hulshoff Pol, Hilleke E.; Jamieson, Alec J.; Jernigan, Terry L.; Jiang, Jiyang; Kalnin, Andrew J.; Kang, Sim; Kochan, Nicole A.; Kraus, Anna; Lagopoulos, Jim; Lazaro, Luisa; McDonald, Brenna C.; McDonald, Colm; McMahon, Katie L.; Mwangi, Benson; Piras, Fabrizio; Rodriguez-Cruces, Raul; Royer, Jessica; Sachdev, Perminder S.; Satterthwaite, Theodore D.; Saykin, Andrew J.; Schumann, Gunter; Sevaggi, Pierluigi; Smoller, Jordan W.; Soares, Jair C.; Spalletta, Gianfranco; Tamnes, Christian K.; Trollor, Julian N.; Van't Ent, Dennis; Vecchio, Daniela; Walter, Henrik; Wang, Yang; Weber, Bernd; Wen, Wei; Wierenga, Lara M.; Williams, Steven C. R.; Wu, Mon-Ju; Zunta-Soares, Giovana B.; Bernhardt, Boris; Thompson, Paul; Frangou, Sophia; Ge, Ruiyang; ENIGMA-Lifespan Working Group; Psychiatry, School of MedicineStructural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.Item Cerebral blood flow in acute concussion: preliminary ASL findings from the NCAA-DoD CARE consortium(Springer, 2019-10-01) Wang, Yang; Nencka, Andrew S.; Meier, Timothy B.; Guskiewicz, Kevin; Mihalik, Jason P.; Alison Brooks, M.; Saykin, Andrew J.; Koch, Kevin M.; Wu, Yu-Chien; Nelson, Lindsay D.; McAllister, Thomas W.; Broglio, Steven P.; McCrea, Michael A.; Radiology and Imaging Sciences, School of MedicineSport-related concussion (SRC) has become a major health problem, affecting millions of athletes each year. Despite the increasing occurrence and prevalence of SRC, its underlying mechanism and recovery course have yet to be fully elucidated. The National Collegiate Athletic Association–Department of Defense Grand Alliance: Concussion Assessment, Research and Education (CARE) Consortium is a large-scale, multisite study of the natural history of concussion across multiple sports. The Advanced Research Core (ARC) of CARE is focused on the advanced biomarker assessment of a reduced subject cohort. This paper reports findings from two ARC sites to evaluate cerebral blood flow (CBF) changes in acute SRC, as measured using advanced arterial spin labeling (ASL) magnetic resonance imaging (MRI). We compared relative CBF maps assessed in 24 concussed contact sport athletes obtained at 24–48 h after injury to those of a control group of 24 matched contact sport players. Significantly less CBF was detected in several brain regions in concussed athletes, while clinical assessments also indicated clinical symptom and performance impairments in SRC patients. Correlations were found between decreased CBF in acute SRC and clinical assessments, including Balance Error Scoring System total score and Immediate Post-Concussion Assessment and Cognitive Test memory composite and impulse control composite scores, as well as days from injury to asymptomatic. Although using different ASL MRI sequences, our preliminary results from two sites are consistent with previous reports and suggest that advanced ASL MRI methods might be useful for detecting acute neurobiological changes in acute SRC.Item Cerebral Perfusion and Gray Matter Changes Associated With Chemotherapy-Induced Peripheral Neuropathy(American Society of Clinical Oncology, 2016-03-01) Nudelman, Kelly N.H.; McDonald, Brenna C.; Wang, Yang; Smith, Dori J.; West, John D.; O'Neill, Darren P.; Zanville, Noah R.; Champion, Victoria L.; Schneider, Bryan P.; Saykin, Andrew J.; IU School of NursingPURPOSE: To investigate the longitudinal relationship between chemotherapy-induced peripheral neuropathy (CIPN) symptoms (sx) and brain perfusion changes in patients with breast cancer. Interaction of CIPN-sx perfusion effects with known chemotherapy-associated gray matter density decrease was also assessed to elucidate the relationship between CIPN and previously reported cancer treatment-related brain structural changes. METHODS: Patients with breast cancer treated with (n = 24) or without (n = 23) chemotherapy underwent clinical examination and brain magnetic resonance imaging at the following three time points: before treatment (baseline), 1 month after treatment completion, and 1 year after the 1-month assessment. CIPN-sx were evaluated with the self-reported Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity four-item sensory-specific scale. Perfusion and gray matter density were assessed using voxel-based pulsed arterial spin labeling and morphometric analyses and tested for association with CIPN-sx in the patients who received chemotherapy. RESULTS: Patients who received chemotherapy reported significantly increased CIPN-sx from baseline to 1 month, with partial recovery by 1 year (P < .001). CIPN-sx increase from baseline to 1 month was significantly greater for patients who received chemotherapy compared with those who did not (P = .001). At 1 month, neuroimaging showed that for the group that received chemotherapy, CIPN-sx were positively associated with cerebral perfusion in the right superior frontal gyrus and cingulate gyrus, regions associated with pain processing (P < .001). Longitudinal magnetic resonance imaging analysis in the group receiving chemotherapy indicated that CIPN-sx and associated perfusion changes from baseline to 1 month were also positively correlated with gray matter density change (P < .005). CONCLUSION: Peripheral neuropathy symptoms after systemic chemotherapy for breast cancer are associated with changes in cerebral perfusion and gray matter. The specific mechanisms warrant further investigation given the potential diagnostic and therapeutic implications.Item Characterizing neurodegeneration in the human connectome: a network science study of hereditary diffuse leukoencephalopathy with spheroids(Office of the Vice Chancellor for Research, 2015-04-17) Contreras, Joey; Rishacher, Shannon L.; West, John D.; Wu, Yu-Chien; Wang, Yang; Murrell, Jill R.; Dzemidzic, Mario; Farlow, Martin R.; Unverzagt, Frederik; Ghetti, Bernardino; Matthews, Brandy R.; Quaid, Kimberly A.; Sporns, Olaf; Saykin, Andrew J.; Goñi, JoaquínAbstract The effect of white matter neurodegeneration on the human connectome and its functional implications is an important topic with clinical applicability of advanced brain network analysis. The aim of this study was to evaluate integration and segregation changes in structural connectivity (SC) that arise as consequence of white matter lesions in hereditary diffuse leukoencephalopathy with spheroids (HDLS). Also, we assessed the relationship between HDLS induced structural changes and changes in restingstate functional connectivity (rsFC). HDLS is a rare autosomal dominant neurodegenerative disorder caused by mutations in the CSF1R gene. HDLS is characterized by severe white matter damage leading to prominent subcortical lesions detectable by structural MRI. Spheroids, an important feature of HDLS, are axonal swellings indicating damage. HDLS causes progressive motor and cognitive decline. The clinical symptoms of HDLS are often mistaken for other diseases such as Alzheimer’s disease, frontotemporal dementia, atypical Parkinsonism or multiple sclerosis. Our study is focused on the follow-up of two siblings, one being a healthy control (HC) and the other one being an HDLS patient. In this study, deterministic fiber-tractography of diffusion MRI with multi-tensor modeling was used in order to obtain reliable and reproducible SC matrices. Integration changes were measured by means of SC shortest-paths (including distance and number of edges), whereas segregation and community organization were measured by means of a multiplex modularity analysis on the SC matrices. Additionally, rsFC was modeled using state of the art preprocessing methods including motion regressors and scrubbing. This allowed us to characterize functional changes associated to the disease. Major integration disruption involved superior frontal (L,R), caudal middle frontal (R), precentral (L,R), inferior parietal (R), insula (R) and paracentral (L) regions. Major segregation changes were characterized by the disruption of a large bilateral module that was observed in the HC that includes the frontal pole (L,R), medial orbitofrontal (L,R), rostral middle frontal (L), superior frontal (L,R), precentral (L,R), paracentral (L,R), rostral anterior cingulate (L,R), caudal anterior cingulate (L,R), posterior cingulate (L,R), postcentral (L), precuneus (L,R), lateral orbitofrontal (R) and parsorbitalis (R). The combination of tractography and network analysis permitted the detection and characterization of profound cortical to cortical changes in integration and segregation associated with HDLS white matter lesions and its relationship with rsFC. Our preliminary findings suggest that advanced network analytic approaches show promising sensitivity to known white matter pathology and progression. Further Indiana Alzheimer Disease Center Symposium. March 6, 2015. research is needed to address the specificity of network profiles for differentiation among white matter pathologies and diseases.Item Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years(Wiley, 2022-01) Frangou, Sophia; Modabbernia, Amirhossein; Williams, Steven C.R.; Papachristou, Efstathios; Doucet, Gaelle E.; Agartz, Ingrid; Aghajani, Moji; Akudjedu, Theophilus N.; Albajes-Eizagirre, Anton; Alnæs, Dag; Alpert, Kathryn I.; Andersson, Micael; Andreasen, Nancy C.; Andreassen, Ole A.; Asherson, Philip; Banaschewski, Tobias; Bargallo, Nuria; Baumeister, Sarah; Baur-Streubel, Ramona; Bertolino, Alessandro; Bonvino, Aurora; Boomsma, Dorret I.; Borgwardt, Stefan; Bourque, Josiane; Brandeis, Daniel; Breier, Alan; Brodaty, Henry; Brouwer, Rachel M.; Buitelaar, Jan K.; Busatto, Geraldo F.; Buckner, Randy L.; Calhoun, Vincent; Canales-Rodríguez, Erick J.; Cannon, Dara M.; Caseras, Xavier; Castellanos, Francisco X.; Cervenka, Simon; Chaim-Avancini, Tiffany M.; Ching, Christopher R.K.; Chubar, Victoria; Clark, Vincent P.; Conrod, Patricia; Conzelmann, Annette; Crespo-Facorro, Benedicto; Crivello, Fabrice; Crone, Eveline A.; Dale, Anders M.; Dannlowski, Udo; Davey, Christopher; de Geus, Eco J.C.; de Haan, Lieuwe; de Zubicaray, Greig I.; den Braber, Anouk; Dickie, Erin W.; Di Giorgio, Annabella; Doan, Nhat Trung; Dørum, Erlend S.; Ehrlich, Stefan; Erk, Susanne; Espeseth, Thomas; Fatouros-Bergman, Helena; Fisher, Simon E.; Fouche, Jean-Paul; Franke, Barbara; Frodl, Thomas; Fuentes-Claramonte, Paola; Glahn, David C.; Gotlib, Ian H.; Grabe, Hans-Jörgen; Grimm, Oliver; Groenewold, Nynke A.; Grotegerd, Dominik; Gruber, Oliver; Gruner, Patricia; Gur, Rachel E.; Gur, Ruben C.; Hahn, Tim; Harrison, Ben J.; Hartman, Catharine A.; Hatton, Sean N.; Heinz, Andreas; Heslenfeld, Dirk J.; Hibar, Derrek P.; Hickie, Ian B.; Ho, Beng-Choon; Hoekstra, Pieter J.; Hohmann, Sarah; Holmes, Avram J.; Hoogman, Martine; Hosten, Norbert; Howells, Fleur M.; Hulshoff Pol, Hilleke E.; Huyser, Chaim; Jahanshad, Neda; James, Anthony; Jernigan, Terry L.; Jiang, Jiyang; Jönsson, Erik G.; Joska, John A.; Kahn, Rene; Kalnin, Andrew; Kanai, Ryota; Klein, Marieke; Klyushnik, Tatyana P.; Koenders, Laura; Koops, Sanne; Krämer, Bernd; Kuntsi, Jonna; Lagopoulos, Jim; Lázaro, Luisa; Lebedeva, Irina; Lee, Won Hee; Lesch, Klaus-Peter; Lochner, Christine; Machielsen, Marise W.J.; Maingault, Sophie; Martin, Nicholas G.; Martínez-Zalacaín, Ignacio; Mataix-Cols, David; Mazoyer, Bernard; McDonald, Colm; McDonald, Brenna C.; McIntosh, Andrew M.; McMahon, Katie L.; McPhilemy, Genevieve; Meinert, Susanne; Menchón, José M.; Medland, Sarah E.; Meyer-Lindenberg, Andreas; Naaijen, Jilly; Najt, Pablo; Nakao, Tomohiro; Nordvik, Jan E.; Nyberg, Lars; Oosterlaan, Jaap; Ortiz-García de la Foz, Víctor; Paloyelis, Yannis; Pauli, Paul; Pergola, Giulio; Pomarol-Clotet, Edith; Portella, Maria J.; Potkin, Steven G.; Radua, Joaquim; Reif, Andreas; Rinker, Daniel A.; Roffman, Joshua L.; Rosa, Pedro G.P.; Sacchet, Matthew D.; Sachdev, Perminder S.; Salvador, Raymond; Sánchez-Juan, Pascual; Sarró, Salvador; Satterthwaite, Theodore D.; Saykin, Andrew J.; Serpa, Mauricio H.; Schmaal, Lianne; Schnell, Knut; Schumann, Gunter; Sim, Kang; Smoller, Jordan W.; Sommer, Iris; Soriano-Mas, Carles; Stein, Dan J.; Strike, Lachlan T.; Swagerman, Suzanne C.; Tamnes, Christian K.; Temmingh, Henk S.; Thomopoulos, Sophia I.; Tomyshev, Alexander S.; Tordesillas-Gutiérrez, Diana; Trollor, Julian N.; Turner, Jessica A.; Uhlmann, Anne; van den Heuvel, Odile A.; van den Meer, Dennis; van der Wee, Nic J.A.; van Haren, Neeltje E.M.; van't Ent, Dennis; van Erp, Theo G.M.; Veer, Ilya M.; Veltman, Dick J.; Voineskos, Aristotle; Völzke, Henry; Walter, Henrik; Walton, Esther; Wang, Lei; Wang, Yang; Wassink, Thomas H.; Weber, Bernd; Wen, Wei; West, John D.; Westlye, Lars T.; Whalley, Heather; Wierenga, Lara M.; Wittfeld, Katharina; Wolf, Daniel H.; Worker, Amanda; Wright, Margaret J.; Yang, Kun; Yoncheva, Yulyia; Zanetti, Marcus V.; Ziegler, Georg C.; Karolinska Schizophrenia Project (KaSP); Thompson, Paul M.; Dima, Danai; Radiology and Imaging Sciences, School of MedicineDelineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.Item Decreased cerebral blood flow in chronic pediatric mild TBI: an MRI perfusion study(Taylor & Francis, 2015-01) Wang, Yang; West, John D.; Bailey, Jessica N.; Westfall, Daniel R.; Xiao, Hui; Arnold, Todd W.; Saykin, Andrew J.; McDonald, Brenna C.; Department of Radiology and Imaging Sciences, IU School of MedicineWe evaluated cerebral blood flow (CBF) in chronic pediatric mild traumatic brain injury (mTBI) using arterial spin labeling (ASL) magnetic resonance imaging perfusion. mTBI patients showed lower CBF than controls in bilateral frontotemporal regions, with no between-group cognitive differences. Findings suggest ASL may be useful to assess functional abnormalities in pediatric mTBI.Item Decreased Prefrontal Activity During a Cognitive Inhibition Task Following Violent Video Game Play: A Multi-Week Randomized Trial(APA, 2019) Hummer, Tom A.; Kronenberger, William G.; Wang, Yang; Mathews, Vincent P.; Psychiatry, School of MedicineThere is substantial evidence that exposure to violent media increases aggressive thoughts and behaviors, potentially due in part to alterations to inhibitory mechanisms mediated by prefrontal cortex. Past research has demonstrated that playing a violent video game for short periods decreases subsequent prefrontal activity during inhibition, yet the impact of long-term game play is unclear. To assess how extensive video game play impacts brain activity, young adult males (n = 49; ages 18–29) with limited video game experience performed a go/no-go task during fMRI for 3 consecutive weeks. Following a baseline scan, these men were randomly assigned to extensively play a violent video game (VG) or avoid all video game play (control) during the subsequent week. After 1 week, inhibition-related activity decreased in right inferior frontal gyrus and right cerebellum in the VG group, compared to the control sample, and self-reported executive functioning problems were higher. VG participants assigned to a second week of game play had similarly reduced bilateral prefrontal activity during inhibition, relative to the control group. However, VG participants assigned to avoid game play or play a cognitive training game during the second week demonstrated similar overall changes from baseline as the control group. This research provides preliminary evidence indicating how long-term video game play may impact brain function during inhibition, which may impair control of aggressive behavior.Item Emotional response inhibition in bipolar disorder: a functional magnetic resonance imaging study of trait- and state-related abnormalities(Elsevier, 2013-01-15) Hummer, Tom A.; Hulvershorn, Leslie A.; Karne, Harish S.; Gunn, Abigail D.; Wang, Yang; Anand, Amit; Psychiatry, School of MedicineBACKGROUND: Impaired response inhibition and poor impulse control are hallmarks of the manic phase of bipolar disorder but are also present during depressive and, to a lesser degree, euthymic periods. The neural mechanisms underlying these impairments are poorly understood, including how mechanisms are related to bipolar trait or state effects. METHODS: One-hundred four unmedicated participants with bipolar mania (BM) (n = 30), bipolar depression (BD) (n = 30), bipolar euthymia (BE) (n = 14), and healthy control subjects (n = 30) underwent functional magnetic resonance imaging during emotional and nonemotional go/no-go tasks. The go/no-go task requires participants to press a button for go stimuli, while inhibiting the response to no-go trials. In separate blocks, participants inhibited the response to happy faces, sad faces, or letters. RESULTS: The BE group had higher insula activity during happy face inhibition and greater activity in left inferior frontal gyrus during sad face inhibition, demonstrating bipolar trait effects. Relative to the BE group, BD and BM groups demonstrated lower insula activity during inhibition of happy faces, though the depressed sample had lower activity than manic patients. The BD and BM groups had a greater response to inhibiting sad faces in emotion processing and regulation regions, including putamen, insula, and lateral prefrontal cortex. The manic group also had higher activity in insula and putamen during neutral letter inhibition. CONCLUSIONS: These results suggest distinct trait- and state-related neural abnormalities during response inhibition in bipolar disorder, with implications for future research and treatment.