WashU weekly Neuroscience publications: February 21, 2022

Anatomical variability, multi-modal coordinate systems, and precision targeting in the marmoset brain
(2022) NeuroImage, 250, art. no. 118965, . 

Ose, T.^a b , Autio, J.A.^a , Ohno, M.^a , Frey, S.^c , Uematsu, A.^a , Kawasaki, A.^a , Takeda, C.^a , Hori, Y.^a d , Nishigori, K.^a e , Nakako, T.^a e , Yokoyama, C.^a f , Nagata, H.^e , Yamamori, T.^g , Van Essen, D.C.^h , Glasser, M.F.^h i , Watabe, H.^b , Hayashi, T.^a j

^a Laboratory for Brain Connectomics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
^b Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan
^c Rogue Research Inc, Montreal, Canada
^d Department of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan
^e Sumitomo Dainippon Pharma Co. Ltd., Osaka, Japan
^f Faculty of Human life and Environmental Science, Nara women’s University, Nara, Japan
^g Laboratory for Molecular Analysis of Higher Brain Function, RIKEN Center for Brain Science, Wako, Japan
^h Department of Neuroscience, Washington University Medical School, St Louis, MO, United States
ⁱ Department of Radiology, Washington University Medical School, St Louis, MO, United States
^j Department of Brain Connectomics, Kyoto University Graduate School of Medicine, Kyoto, Japan

Abstract
Localising accurate brain regions needs careful evaluation in each experimental species due to their individual variability. However, the function and connectivity of brain areas is commonly studied using a single-subject cranial landmark-based stereotactic atlas in animal neuroscience. Here, we address this issue in a small primate, the common marmoset, which is increasingly widely used in systems neuroscience. We developed a non-invasive multi-modal neuroimaging-based targeting pipeline, which accounts for intersubject anatomical variability in cranial and cortical landmarks in marmosets. This methodology allowed creation of multi-modal templates (MarmosetRIKEN20) including head CT and brain MR images, embedded in coordinate systems of anterior and posterior commissures (AC-PC) and CIFTI grayordinates. We found that the horizontal plane of the stereotactic coordinate was significantly rotated in pitch relative to the AC-PC coordinate system (10 degrees, frontal downwards), and had a significant bias and uncertainty due to positioning procedures. We also found that many common cranial and brain landmarks (e.g., bregma, intraparietal sulcus) vary in location across subjects and are substantial relative to average marmoset cortical area dimensions. Combining the neuroimaging-based targeting pipeline with robot-guided surgery enabled proof-of-concept targeting of deep brain structures with an accuracy of 0.2 mm. Altogether, our findings demonstrate substantial intersubject variability in marmoset brain and cranial landmarks, implying that subject-specific neuroimaging-based localization is needed for precision targeting in marmosets. The population-based templates and atlases in grayordinates, created for the first time in marmoset monkeys, should help bridging between macroscale and microscale analyses. © 2022

Author Keywords
brain;  coordinates;  cranium;  Marmoset;  neurosurgery;  subject variability

Funding details
National Institutes of HealthNIHMH060974
Japan Agency for Medical Research and DevelopmentAMED
Japan Society for the Promotion of ScienceJSPSJP15K08707, JP18K06372, JP20K15945

Measuring retention within the adolescent brain cognitive development (ABCD)SM study
(2022) Developmental Cognitive Neuroscience, 54, art. no. 101081, . 

Feldstein Ewing, S.W.^a , Dash, G.F.^d , Thompson, W.K.^b c , Reuter, C.^b c , Diaz, V.G.^e , Anokhin, A.^f , Chang, L.^g h , Cottler, L.B.ⁱ , Dowling, G.J.^j , LeBlanc, K.^j , Zucker, R.A.^k , Tapert, S.F.^e , Brown, S.A.^e , Garavan, H.^l

^a Department of Psychology and Interdisciplinary Neuroscience, University of Rhode Island, Chafee Hall, 130 Flagg Road, Kingston, RI 02881, United States
^b Center for Human Development, University of California San Diego, 9500 Gilman Drive, MC 0115, La Jolla, CA 92093, United States
^c Herbert Wertheim School of Public Health, University of California San Diego, 9500 Gilman Drive, MC 0115, La Jolla, CA 92093, United States
^d Department of Psychological Sciences, University of Missouri, 210 McAlester Hall, Columbia, MO 65211, United States
^e Departments of Psychology and Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, United States
^f Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Ave, Box 8134, St. Louis, MO 63110, United States
^g Departments of Diagnostic Radiology & Nuclear Medicine, and Neurology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, United States
^h Department of Neurology Johns Hopkins School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, United States
ⁱ Department of Epidemiology, University of Florida, 2004 Mowry Road, Gainesville, FL 32610, United States
^j Division of Extramural Research, National Institute on Drug Abuse, Bethesda, MD 20892, United States
^k Department of Psychiatry, University of Michigan, 1301 Catherine Street, Ann Arbor, MI 48109, United States
^l Department of Psychiatry, University of Vermont, 1 South Prospect Street, MS 446AR7, Burlington, VT 05401, United States

Abstract
The Adolescent Brain Cognitive Development (ABCD)SM study aims to retain a demographically diverse sample of youth and one parent across 21 sites throughout its 10-year protocol while minimizing selective (systematic) attrition. To evaluate the effectiveness of these efforts, the ABCD Retention Workgroup (RW) has employed a data-driven approach to examine, track, and intervene via three key metrics: (1) which youth completed visits late; (2) which youth missed visits; and (3) which youth withdrew from the study. The RW actively examines demographic (race, education level, family income) and site factors (visit satisfaction, distance from site, and enrollment in ancillary studies) to strategize efforts that will minimize disengagement and loss of participating youth and parents. Data showed that the most robust primary correlates of late visits were distance from study site, race, and parental education level. Race, lower parental education level, parental employment status, and lower family income were associated with higher odds of missed visits, while being enrolled in one of the ancillary studies was associated with lower odds of missed visits. Additionally, parents who were primary Spanish speakers withdrew at slightly higher rates. These findings provide insight into future targets for proactive retention efforts by the ABCD RW. © 2022

Author Keywords
ABCD study®;  Adolescents;  Longitudinal studies;  Metrics;  Retention

Funding details
National Institutes of HealthNIHF31DA054701, RF1MH120025, U01DA041089, U01DA041106, U01DA041117, U01DA041148-01, U01DA051016, U01DA051039, U24DA041123, U24DA041147, UL1TR001427
U.S. Department of Health and Human ServicesHHS

Long-term effects of PM2.5 components on incident dementia in the northeastern United States
(2022) The Innovation, 3 (2), art. no. 100208, . 

Li, J.^a , Wang, Y.^b , Steenland, K.^b , Liu, P.^c , van Donkelaar, A.^d , Martin, R.V.^d , Chang, H.H.^e , Caudle, W.M.^b , Schwartz, J.^a , Koutrakis, P.^a , Shi, L.^b

^a Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States
^b Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, United States
^c School of Earth and Atmospheric Sciences, Georgia Institute of Technology, Atlanta, GA 30332, United States
^d Department of Energy, Environmental & Chemical Engineering, Washington University at St. LouisMO 63130, United States
^e Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30322, United States

Abstract
Growing evidence has linked long-term fine particulate matter (PM2.5) exposure to neurological disorders. Less is known about the individual effects of PM2.5 components. A population-based cohort study investigated the association between long-term (1-year average) exposure to PM2.5 components and dementia incidence among the elderly population (age, ≥65 years) in the United States. We used data from the Medicare Chronic Conditions Warehouse and a high-resolution PM2.5 components dataset of the northeastern United States (2000–2017). We identified dementia diagnoses from patients’ hospital and medical insurance records and carried out Cox proportional hazards regression to investigate their association with PM2.5 components. Among ∼2 million participants, 15.1% developed dementia. From the single-pollutant models, hazard ratios per interquartile range increase were 1.10 (95% confidence interval [CI]: 1.09–1.11) for black carbon, 1.08 (95% CI: 1.07, 1.10) for inorganic nitrate, 1.03 (95% CI: 1.02, 1.04) for organic matter, 1.13 (95% CI: 1.11, 1.15) for sulfate, 1.07 (95% CI: 1.06, 1.07) for soil particles, and 1.04 (95% CI: 1.03, 1.05) for sea salt. Increase in exposure to black carbon and sulfate per interquartile range had the strongest associations with dementia incidence. Penalized spline models indicated that dementia incidence increased linearly with elevated black carbon concentrations, whereas the incidence of dementia was only elevated significantly following sulfate concentrations above ∼2 μg/m3. Our study suggests that long-term exposure to PM2.5 components is significantly associated with increased dementia incidence and that different components have different neurotoxicity. Reduction of PM2.5 emissions, especially for main sources of black carbon and sulfate, may reduce the burden of dementia in the aging United States population. © 2022 The Author(s)

Author Keywords
air pollution;  cohort study;  dementia;  long-term exposure;  PM2.5 components

Funding details
National Institutes of HealthNIHP30 ES019776, R01 AG074357
National Institute on AgingNIA
National Aeronautics and Space AdministrationNASA80NSSC21K0508
U.S. Environmental Protection AgencyEPARD-835872
Alzheimer’s Disease Research Center, Emory UniversityADRC
Emory UniversityP50 AG025688

Generation of human induced pluripotent stem cell-derived cerebral organoids for cellular and molecular characterization
(2022) STAR Protocols, 3 (1), art. no. 101173, . 

Anastasaki, C., Wilson, A.F., Chen, A.S., Wegscheid, M.L., Gutmann, D.H.

Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States

Abstract
Human induced pluripotent stem cell (hiPSC)-derived cerebral organoids (COs) can serve as an in vitro model for studying normal and pathologic human brain development. Here, we optimized existing protocols to streamline the generation of forebrain COs from hiPSCs. We employ these COs to define the impact of disease-causing mutations on cell fate, differentiation, maturation, and morphology relevant to neurodevelopmental disorders. Although limited to forebrain CO identity, this schema requires minimal external interference and is amenable to low-throughput biochemical assays. For complete details on the use and execution of this profile, please refer to Anastasaki et al. (2020) and Wegscheid et al. (2021). © 2022 The Author(s)

Author Keywords
Cell Biology;  Cell culture;  Developmental biology;  Health Sciences;  Neuroscience;  Organoids;  Stem Cells

Funding details
National Cancer InstituteNCIR50-CA233164-01
National Institute of Neurological Disorders and StrokeNINDSR35-NS097211-01
National Institute of Biomedical Imaging and BioengineeringNIBIBT32-EB028092

Perioperative factors associated with persistent postsurgical pain after hysterectomy, cesarean section, prostatectomy, and donor nephrectomy: a systematic review and meta-analysis
(2022) Pain, 163 (3), pp. 425-435. 

Sharma, L.R.^a , Schaldemose, E.L.^b , Alaverdyan, H.^a , Nikolajsen, L.^b , Chen, D.^c , Bhanvadia, S.^d , Komen, H.^a , Yaeger, L.^e , Haroutounian, S.^a

^a Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
^b Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
^c University of Sydney School of Medicine, Sydney, Australia
^d School of Medicine, St Louis University, St. Louis, MO, United States
^e Becker Medical Library, Washington University School of Medicine, St. Louis, MO, United States

Abstract
ABSTRACT: Persistent postsurgical pain (PPSP) is a common and often disabling postoperative morbidity, but many questions remain about factors associated with PPSP. This systematic review and meta-analysis aimed to identify preoperative, intraoperative, and postoperative factors associated with PPSP after gynecological surgeries, namely, hysterectomy and cesarean section, and urological surgeries, namely, prostatectomy and donor nephrectomy. Overall, 18 gynecological surgery studies, 4 prostatectomy studies, and 2 donor nephrectomy studies met the review criteria, providing data that could be meta-analyzed. The average (±SD) PPSP occurrence after gynecological surgery was 20 ± 11%; factors associated with increased risk of PPSP included smoking, preoperative abdominal or pelvic pain, preoperative pain elsewhere in the body, longer duration of surgery, more intense acute postoperative pain, and surgical wound infection. The use of neuraxial anesthesia was associated with decreased PPSP risk. The average PPSP occurrence was 20 ± 9% after prostatectomy and 15 ± 2% after donor nephrectomy. For urological procedures, the existing data did not allow for identification of significant factors associated with PPSP, except for laparoscopic and hand-assisted laparoscopic approaches that were associated with lower incidence of PPSP for donor nephrectomy, and the use of neuraxial anesthesia which was associated with lower incidence of PPSP after prostatectomy. Persistent postsurgical pain after gynecological and urological surgeries is common. This systematic review identified important factors associated with cesarean section and hysterectomy that can help identify women who are at high risk of PPSP. More high-quality studies with consistent methodology are needed to understand the factors associated with PPSP risk, particularly for surgeries such as prostatectomy and nephrectomy. Copyright © 2021 International Association for the Study of Pain.

Intracranial internal carotid artery calcification is not predictive of future cognitive decline
(2022) Alzheimer’s Research & Therapy, 14 (1), p. 32. 

Rahmani, F.^a b , Nguyen, M.^a b , Chen, C.D.^a b , McKay, N.^a b , Dincer, A.^a b , Joseph-Mathurin, N.^a b , Chen, G.^a b , Liu, J.^c d , Orlowski, H.L.P.^a , Morris, J.C.^b c , Benzinger, T.L.S.^a b

^a Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, 510 South Kingshighway Boulevard, Campus Box 8131, St. Louis, MO, 63110, USA
^b Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight ADRC), Washington University, St. Louis, MO, USA
^c Department of Neurology, Washington University in Saint Louis, St. Louis, MO, USA
^d Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine (WUSM), St. Louis, MO, USA

Abstract
BACKGROUND: Intracranial internal carotid artery (ICA) calcification is a common incidental finding in non-contrast head CT. We evaluated the predictive value of ICAC (ICAC) for future risk of cognitive decline and compared the results with conventional imaging biomarkers of dementia. METHODS: In a retrospective observational cohort, we included 230 participants with a PET-CT scan within 18 months of a baseline clinical assessment and longitudinal imaging assessments. Intracranial ICAC was quantified on baseline CT scans using the Agatson calcium score, and the association between baseline ICA calcium scores and the risk of conversion from a CDR of zero in baseline to a persistent CDR > 0 at any follow-up visit, as well as longitudinal changes in cognitive scores, were evaluated through linear and mixed regression models. We also evaluated the association of conventional imaging biomarkers of dementia with longitudinal changes in cognitive scores and a potential indirect effect of ICAC on cognition through these biomarkers. RESULTS: Baseline ICA calcium score could not distinguish participants who converted to CDR > 0. ICA calcium score was also unable to predict longitudinal changes in cognitive scores, imaging biomarkers of small vessel disease such as white matter hyperintensities (WMH) volume, or AD such as hippocampal volume, AD cortical signature thickness, and amyloid burden. Severity of intracranial ICAC increased with age and in men. Higher WMH volume and amyloid burden as well as lower hippocampal volume and AD cortical signature thickness at baseline predicted lower Mini-Mental State Exam scores at longitudinal follow-up. Baseline ICAC was indirectly associated with longitudinal cognitive decline, fully mediated through WMH volume. CONCLUSIONS: In elderly and preclinical AD populations, atherosclerosis of large intracranial vessels as demonstrated through ICAC is not directly associated with a future risk of cognitive impairment, or progression of imaging biomarkers of AD or small vessel disease. © 2022. The Author(s).

Author Keywords
11C-Pittsburgh compound B;  Calcification;  Centiloid;  Clinical Dementia Rating;  Internal carotid artery;  Mini-Mental State Exam;  PiB;  White matter hyperintensities

Estimated Population Access to Acute Stroke and Telestroke Centers in the US, 2019
(2022) JAMA Network Open, 5 (2), p. e2145824. 

Zachrison, K.S.^a b , Cash, R.E.^a b , Adeoye, O.^c , Boggs, K.M.^a , Schwamm, L.H.^d e , Mehrotra, A.^f , Camargo, C.A., Jr^a b

^a Department of Emergency Medicine, Massachusetts General Hospital, Boston
^b Department of Emergency Medicine, Harvard Medical School, Boston, MA
^c Department of Emergency Medicine, Washington University, St Louis, MO, United States
^d Department of Neurology, Massachusetts General Hospital, Boston
^e Department of Neurology, Harvard Medical School, Boston, MA
^f Department of Health Care Policy, Harvard Medical School, Boston, MA

Deep residual inception encoder-decoder network for amyloid PET harmonization
(2022) Alzheimer’s and Dementia, . 

Shah, J.^a b , Gao, F.^a b , Li, B.^a b , Ghisays, V.^c , Luo, J.^c , Chen, Y.^c , Lee, W.^c , Zhou, Y.^d , Benzinger, T.L.S.^e , Reiman, E.M.^c , Chen, K.^c , Su, Y.^a b c , Wu, T.^a b

^a ASU-Mayo Center for Innovative Imaging, Arizona State University, 699 S. Mill Ave., Tempe, AZ 85287, United States
^b School of Computing and Augmented Intelligence, Arizona State University, 699 S. Mill Ave., Tempe, AZ 85287, United States
^c Banner Alzheimer’s Institute, 901 E. Willetta Street, Phoenix, AZ 85006, United States
^d Department of Radiology, Mayo Clinic at Arizona, 5777 E Mayo Blvd, Phoenix, AZ 85054, United States
^e Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, 510 South Kingshighway Boulevard, St. Louis, MO 63110, United States

Abstract
Introduction: Multiple positron emission tomography (PET) tracers are available for amyloid imaging, posing a significant challenge to consensus interpretation and quantitative analysis. We accordingly developed and validated a deep learning model as a harmonization strategy. Method: A Residual Inception Encoder-Decoder Neural Network was developed to harmonize images between amyloid PET image pairs made with Pittsburgh Compound-B and florbetapir tracers. The model was trained using a dataset with 92 subjects with 10-fold cross validation and its generalizability was further examined using an independent external dataset of 46 subjects. Results: Significantly stronger between-tracer correlations (P <.001) were observed after harmonization for both global amyloid burden indices and voxel-wise measurements in the training cohort and the external testing cohort. Discussion: We proposed and validated a novel encoder-decoder based deep model to harmonize amyloid PET imaging data from different tracers. Further investigation is ongoing to improve the model and apply to additional tracers. © 2022 The Authors. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association

Author Keywords
Alzheimer’s disease;  amyloid PET;  Centiloid

Funding details
R01AG055444, R01AG058468, R21AG065942, R42AG053149, U19AG024904
National Institutes of HealthNIHP01 AG003991, P01 AG026276, P30 NS098577, P30AG019610, P50 AG005681, R01 AG043434, R01 EB009352, R01AG031581, R01AG069453, UL1 TR000448
Office of Naval ResearchONR
U.S. Department of Homeland SecurityDHSOT2OD026549, P01AG052350, R01AG054671, U01AG016976, U01NS093334, U54MD000507
Alzheimer’s AssociationAAAARG17532945
Flinn Foundation
Novartis
Roche
BrightFocus Foundation
Arizona Department of Health ServicesADHSCTR040636
University of OklahomaOU
Beijing Normal UniversityBNU
NOMIS Stiftung

Cerebral oxygen metabolic stress is increased in children with sickle cell anemia compared to anemic controls
(2022) American Journal of Hematology, . 

Fields, M.E.^a b , Mirro, A.E.^a , Binkley, M.M.^b , Guilliams, K.P.^a b c , Lewis, J.B.^b , Fellah, S.^b , Chen, Y.^b , Hulbert, M.L.^a , An, H.^c , Ford, A.L.^b c , Lee, J.-M.^b c d

^a Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
^b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
^c Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
^d Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Patients with sickle cell anemia (SCA) experience cerebral metabolic stress with an increase in oxygen extraction fraction (OEF) to compensate for reduced oxygen carrying capacity due to anemia. It remains unclear if anemia alone drives this metabolic stress. Using MRI, we collected voxel-wise OEF measurements to test our hypothesis that OEF would be elevated in anemic controls without SCA (AC) compared to healthy controls (HC), but OEF would be even higher in SCA compared to AC. Brain MRIs (N = 159) were obtained in 120 participants (34 HC, 27 AC, 59 SCA). While hemoglobin was lower in AC versus HC (p < 0.001), hemoglobin was not different between AC and SCA cohorts (p = 0.459). Whole brain OEF was higher in AC compared to HC (p < 0.001), but lower compared to SCA (p = 0.001). Whole brain OEF remained significantly higher in SCA compared to HC (p = 0.001) while there was no longer a difference between AC versus HC (p = 0.935) in a multivariate model controlling for age and hemoglobin. OEF peaked within the border zone regions of the brain in both SCA and AC cohorts, but the volume of white matter with regionally elevated OEF in AC was smaller (1.8%) than SCA (58.0%). While infarcts colocalized within regions of elevated OEF, more SCA participants had infarcts than AC (p < 0.001). We conclude that children with SCA experience elevated OEF compared to AC and HC after controlling for the impact of anemia, suggesting that there are other pathophysiologic factors besides anemia contributing to cerebral metabolic stress in children with SCA. © 2022 Wiley Periodicals LLC.

Funding details
National Institutes of HealthNIH
National Heart, Lung, and Blood InstituteNHLBIK23HL136904, R01HL129241, R01HL157188
National Institute of Neurological Disorders and StrokeNINDSK23NS099472, U24NS107230
Doris Duke Charitable FoundationDDCF
American Society of HematologyASH
Foundation for Barnes-Jewish Hospital

Five-year outcomes of premature infants randomized to high or standard loading dose caffeine
(2022) Journal of Perinatology, . 

McPherson, C.^a b , Lean, R.E.^c , Cyr, P.E.P.^d , Inder, T.E.^e , Rogers, C.E.^a c , Smyser, C.D.^a d f

^a Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, United States
^b Department of Pharmacy, St. Louis Children’s Hospital, St. Louis, MO, United States
^c Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States
^d Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
^e Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
^f Department of Radiology, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Objective: To examine 5-year outcomes in children enrolled in a pilot randomized controlled trial of a high loading dose of caffeine after preterm birth. Study design: Seventy-four very low birth weight neonates were randomized within the first 24 h of life to receive a high (80 mg/kg) or standard (20 mg/kg) loading dose of caffeine citrate. At 5 years of age, we conducted standardized neurodevelopmental tests and collected parent reports of child socioemotional problems. Result: Seventy-four percent of survivors returned for follow up. Children obtained similar scores on neurodevelopmental and socioemotional evaluations. There was no difference in the incidence of any neurodevelopmental delay after controlling for confounding factors. Conclusion: Five-year follow up of a pilot trial of high loading dose caffeine citrate documented no profound impacts on childhood neurodevelopment or socioemotional outcome. © 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.

Funding details
National Institutes of HealthNIHF30 HD105336, K01 MH122735, K02 NS089852, K12 HD055931-06, K23 MH105179, R01 HD057098, R01 MH113570
Doris Duke Charitable FoundationDDCF
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHDP50 HD103525

Children’s Maternal Representations Moderate the Efficacy of Parent–Child Interaction Therapy—Emotion Development (PCIT-ED) Treatment For Preschool Depression
(2022) Research on Child and Adolescent Psychopathology, . 

Donohue, M.R.^a , Yin, J.^a , Quiñones-Camacho, L.^a b , Hennefield, L.^a , Tillman, R.^a , Gilbert, K.^a , Whalen, D.^a , Barch, D.M.^a , Luby, J.^a

^a Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, United States
^b Department of Educational Psychology, The University of Texas at Austin, Austin, TX, United States

Abstract
A randomized controlled trial (RCT) demonstrated that a novel psychotherapy, Parent–Child Interaction Therapy—Emotion Development (PCIT-ED), effectively treats preschool-onset depression. However, little is known about which children benefit most from PCIT-ED. As positive parent-level factors are associated with lesser depressive symptoms, this study explored the potential moderating role of positive parenting relationships on PCIT-ED efficacy. This study examined mothers and their children aged 3–6 (N = 185) who participated in the PCIT-ED RCT. Children were randomized to immediate PCIT-ED treatment (n = 94) or a waitlist control condition (n = 91) that received treatment after 18 weeks. Prior to treatment, children completed a narrative story completion task that was videotaped and coded for children’s positive and negative representations of their mothers. Parent–child interaction tasks were also completed pre-treatment and videotaped and coded to measure observed parenting. Odds of MDD diagnosis post-treatment were predicted by the interaction of children’s negative maternal representations and treatment group (Estimate = -.68; SE =.27; χ2 = 6.45; p =.01) and the interaction of children’s relatively more positive than negative maternal representations and treatment group (Estimate =.30; SE =.13; χ2 = 5.27; p =.02). Observed parenting measures did not significantly predict odds of MDD diagnosis. Thus, PCIT-ED predicted loss of MDD diagnosis for children who displayed maternal representations that were less negative, and relatively more positive than negative. Results suggest that children with relatively more positive maternal representations may be more likely to benefit from PCIT-ED, whereas children with more negative maternal representations may need targeted work to decrease negative maternal perceptions before initiating PCIT-ED in order for treatment to be most effective. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Author Keywords
Maternal representations;  Parent–child intervention;  Preschool depression;  Randomized controlled trial;  Treatment moderators

Funding details
National Institutes of HealthNIHF32HD093273, K23MH115074, K23MH118426, K23MH125023, R01MH064769-06A1, T32MH100019

Associations between social behaviors and experiences with neural correlates of implicit emotion regulation in middle childhood
(2022) Neuropsychopharmacology, . 

Geckeler, K.C.^a , Barch, D.M.^a b , Karcher, N.R.^a

^a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
^b Washington University in St. Louis, Department of Psychological and Brain Sciences, Washington University, St. Louis, MO, United States

Abstract
Emotion regulation is essential for successful social interactions and function, which are important aspects of middle childhood. The current study is one of the first to examine associations between neural correlates of implicit emotion regulation and indices of social behavior and experience during late middle childhood. We examined neural activation during the implicit emotion regulation condition of the Emotional N-back task using data from 8987 9- to 11-year-olds from the Adolescent Brain Cognitive Development℠ study. The brain regions assessed included areas linked to social cognition, social behavior, and emotion recognition, including the amygdala, insula, middle temporal gyrus, and inferior parietal lobe. Greater number of close friends was associated with significantly higher activation of the fusiform gyrus, insula, temporoparietal junction, inferior parietal lobe, and superior temporal gyrus during implicit emotion regulation. Greater reciprocal social impairments were linked to decreased fusiform gyrus activation during implicit emotion regulation. More experiences of discrimination were associated with a significantly lower activation in the middle temporal gyrus during implicit emotion regulation. This study provides evidence that both positive and negative indices of children’s social experiences and behaviors are associated with neural correlates of implicit emotion regulation during late middle childhood. These findings suggest that both positive and negative indices of social behavior and experience, including those within and not within the youth’s control, are associated with generally unique neural correlates during implicit emotion regulation. © 2022, The Author(s), under exclusive licence to American College of Neuropsychopharmacology.

Funding details
National Institutes of HealthNIHU01DA041022, U01DA041025, U01DA041028, U01DA041048, U01DA041089, U01DA041093, U01DA041106, U01DA041117, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, U24DA041147
National Institute of Mental HealthNIMHK23 MH121792-01, L30 MH120574-01
National Institute on Drug AbuseNIDAU01 DA041120

Neural Signatures of Data-Driven Psychopathology Dimensions at the Transition to Adolescence
(2022) European Psychiatry, . 

Modabbernia, A.^a , Michelini, G.^b , Reichenberg, A.^a c d e , Kotov, R.^f , Barch, D.^g h i , Frangou, S.^a j

^a Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, United States
^b King’s College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, 16 De Crespigny Park, London, United Kingdom
^c Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, United States
^d Seaver Center for Autism Research and Treatment, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, United States
^e Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
^f Department of Psychiatry and Behavioral Health, Stony Brook University, Stony Brook, NY 11790, United States
^g Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, United States
^h Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, United States
ⁱ Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, United States
^j Djavad Mowafaghian Centre for Brain Health, Department of Psychiatry, University of British ColumbiaBC, Canada

Abstract
Background: One of the challenges in human neuroscience is to uncover associations between brain organization and psychopathology in order to better understand the biological underpinnings of mental disorders. Here we aimed to characterize the neural correlates of psychopathology dimensions obtained using two conceptually different data-driven approaches. Methods: Dimensions of psychopathology that were either maximally dissociable or correlated were respectively extracted by independent component analysis (ICA) and exploratory factor analysis (EFA) applied to the Childhood Behavior Checklist (CBCL) items from 9–10-year-olds (n=9983; 47.8% female, 50.8% white) participating in the Adolescent Brain Cognitive Development study. The patterns of brain morphometry, white-matter integrity and resting-state connectivity associated with each dimension were identified using kernel-based regularized least squares and compared between dimensions using Spearman’s correlation coefficient. Results: ICA identified three psychopathology dimensions, representing opposition disinhibition, cognitive dyscontrol, and negative affect, with distinct brain correlates. Opposition-disinhibition was negatively associated with cortical surface area, cognitive dyscontrol was negatively associated with anatomical and functional dysconnectivity while negative affect did not show discernable associations with any neuroimaging measure. EFA identified three dimensions representing broad externalizing, neurodevelopmental, and broad Internalizing problems with partially overlapping brain correlates. All EFA-derived dimensions were negatively associated with cortical surface area, whereas measures of functional and structural connectivity were associated only with the neurodevelopmental dimension. Conclusions This study highlights the importance of cortical surface area and global connectivity for psychopathology in pre-adolescents and provides evidence for dissociable psychopathology dimensions with distinct brain correlates. © 2022 Elsevier Masson SAS. All rights reserved.

Author Keywords
Adolescence;  Development;  Neuroimaging;  Population Neuroscience;  Psychopathology

Prior differences in previous trauma exposure primarily drive the observed racial/ethnic differences in posttrauma depression and anxiety following a recent trauma
(2022) Psychological Medicine, . 

Harnett, N.G.^a b , Dumornay, N.M.^a , Delity, M.^a , Sanchez, L.D.^c d , Mohiuddin, K.^e , Musey, P.I.^f , Seamon, M.J.^g , McLean, S.A.^h i , Kessler, R.C.^j , Koenen, K.C.^k , Beaudoin, F.L.^l , Lebois, L.A.M.^a b , Van Rooij, S.J.H.^m , Sampson, N.A.^j , Michopoulos, V.^m , Maples-Keller, J.L.^m , Haran, J.P.ⁿ , Storrow, A.B.^o , Lewandowski, C.^p , Hendry, P.L.^q , Sheikh, S.^q , Jones, C.W.^r , Punches, B.E.^s t , Kurz, M.C.^u v w , Swor, R.A.^x , McGrath, M.E.^y , Hudak, L.A.^z , Pascual, J.L.^aa ab , House, S.L.^ac , An, X.^ad , Stevens, J.S.^ae , Neylan, T.C.^af , Jovanovic, T.^ag , Linnstaedt, S.D.^ad , Germine, L.T.^b ah , Datner, E.M.^ai aj , Chang, A.M.^ak , Pearson, C.^al , Peak, D.A.^am , Merchant, R.C.^c , Domeier, R.M.^an , Rathlev, N.K.^ao , O’Neil, B.J.^al , Sergot, P.^ap , Bruce, S.E.^aq , Miller, M.W.^ar as , Pietrzak, R.H.^at au , Joormann, J.^av , Barch, D.M.^aw , Pizzagalli, D.A.^a b , Sheridan, J.F.^ax ay , Smoller, J.W.^az ba , Luna, B.^bb , Harte, S.E.^bc bd , Elliott, J.M.^be bf , Ressler, K.J.^a b

^a Division of Depression and Anxiety, McLean Hospital, Belmont, MA 02478, United States
^b Department of Psychiatry, Harvard Medical School, Boston, MA 02115, United States
^c Department of Emergency Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States
^d Department of Emergency Medicine, Harvard Medical School, Boston, MA 02115, United States
^e Department of Emergency Medicine, Einstein Medical Center, Philadelphia, PA 19141, United States
^f Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, United States
^g Department of Surgery, Division of Traumatology, University of PennsylvaniaPA 19104, United States
^h Department of Emergency Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27559, United States
ⁱ Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27559, United States
^j Department of Health Care Policy, Harvard Medical School, Boston, MA 02115, United States
^k Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, United States
^l Department of Emergency Medicine and Department of Health Services, Alpert Medical School of Brown University, Rhode Island Hospital and the Miriam Hospital, Providence, RI 02930, United States
^m Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30332, United States
ⁿ Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, MA 01655, United States
^o Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, United States
^p Department of Emergency Medicine, Henry Ford Health System, Detroit, MI 48202, United States
^q Department of Emergency Medicine, University of Florida College of Medicine-Jacksonville, Jacksonville, FL 32209, United States
^r Department of Emergency Medicine, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
^s Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States
^t College of Nursing, University of Cincinnati, Cincinnati, OH 45221, United States
^u Department of Emergency Medicine, University of Alabama School of Medicine, Birmingham, AL 35294, United States
^v Department of Surgery, Division of Acute Care Surgery, University of Alabama School of Medicine, Birmingham, AL 35294, United States
^w Center for Injury Science, University of Alabama at Birmingham, Birmingham, AL 35294, United States
^x Department of Emergency Medicine, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, United States
^y Department of Emergency Medicine, Boston Medical Center, Boston, MA 02118, United States
^z Department of Emergency Medicine, Emory University School of Medicine, Atlanta, GA 30329, United States
^aa Department of Surgery, Department of Neurosurgery, University of PennsylvaniaPA 19104, United States
^ab Perelman School of Medicine, University of PennsylvaniaPA 19104, United States
^ac Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO 63130, United States
^ad Department of Anesthesiology, Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27559, United States
^ae Departments of Psychiatry and Neurology, University of California San Francisco, San Francisco, CA 94143, United States
^af Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, MI 48202, United States
^ag Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA 02478, United States
^ah Department of Emergency Medicine, Einstein Healthcare NetworkPA 19141, United States
^ai Department of Emergency Medicine, Sidney Kimmel Medical College, Thomas Jefferson UniversityPA 19107, United States
^aj Department of Emergency Medicine, Jefferson University HospitalsPA 19107, United States
^ak Department of Emergency Medicine, Wayne State University, DetroitMA 48202, United States
^al Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA 02114, United States
^am Department of Emergency Medicine, Saint Joseph Mercy Hospital, Ypsilanti, MI 48197, United States
^an Department of Emergency Medicine, University of Massachusetts Medical School-Baystate, Springfield, MA 01107, United States
^ao Department of Emergency Medicine, McGovern Medical School, University of Texas Health, Houston, TX 77030, United States
^ap Department of Psychological Sciences, University of Missouri – St. Louis, St. Louis, MO 63121, United States
^aq National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, MA 02130, United States
^ar Department of Psychiatry, Boston University School of Medicine, Boston, MA 02118, United States
^as National Center for PTSD, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT 06516, United States
^at Department of Psychiatry, Yale School of Medicine, West Haven, CT 06510, United States
^au Department of Psychology, Yale University, West Haven, CT 06520, United States
^av Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, United States
^aw Department of Biosciences, OSU Wexner Medical Center, Columbus, OH 43210, United States
^ax Institute for Behavioral Medicine Research, OSU Wexner Medical Center, Columbus, OH 43211, United States
^ay Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, United States
^az Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA 02142, United States
^ba Affiliation Laboratory of Neurocognitive Development, University of Pittsburgh Medical Center – Western Psychiatric Hospital, Pittsburgh, PA 15213, United States
^bb Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI 48109, United States
^bc Department of Internal Medicine-Rheumatology, University of Michigan Medical School, Ann Arbor, MI 48109, United States
^bd Kolling Institute, University of Sydney, St LeonardsNSW 2065, Australia
^be Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2006, Australia
^bf Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL 60208, United States

Abstract
Background Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time. Methods As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors. Results Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants. Conclusions The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories. Copyright © The Author(s), 2022. Published by Cambridge University Press.

Author Keywords
anxiety;  depression;  Disparities;  ethnicity;  race;  trauma

Funding details
R33AG05654
National Institutes of HealthNIHR01HD079076, R03HD094577
National Institute of Mental HealthNIMHK00MH119603, K01MH118467, U01MH110925
Medical Research and Materiel CommandMRMC
Brain and Behavior Research FoundationBBRF
Boehringer IngelheimBI
AstraZeneca
Blue Cross and Blue Shield of Florida Foundation
National Center for Medical Rehabilitation ResearchNCMRR
Takeda Pharmaceutical Company
Janssen Pharmaceuticals
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD
Hologic
NSW Ministry of Health

The global Alzheimer’s Association round robin study on plasma amyloid β methods
(2021) Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring, 13 (1), art. no. e12242, . 

Pannee, J.^a b , Shaw, L.M.^c , Korecka, M.^c , Waligorska, T.^c , Teunissen, C.E.^d , Stoops, E.^e , Vanderstichele, H.M.J.^f , Mauroo, K.^e , Verberk, I.M.W.^d , Keshavan, A.^g , Pesini, P.^h , Sarasa, L.^h , Pascual-Lucas, M.^h , Fandos, N.^h , Allué, J.-A.^h , Portelius, E.^a b , Andreasson, U.^a b , Yoda, R.ⁱ , Nakamura, A.^j , Kaneko, N.ⁱ , Yang, S.-Y.^k , Liu, H.-C.^k , Palme, S.^l , Bittner, T.^m , Mawuenyega, K.G.ⁿ , Ovod, V.ⁿ , Bollinger, J.ⁿ , Bateman, R.J.ⁿ , Li, Y.ⁿ , Dage, J.L.^o , Stomrud, E.^p q , Hansson, O.^p q , Schott, J.M.^g , Blennow, K.^a b , Zetterberg, H.^a b r s

^a Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
^b Clinical Neurochemistry Lab, Sahlgrenska University Hospital, Mölndal, Sweden
^c Perelman School of Medicine, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States
^d Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
^e ADx NeuroSciences, Ghent, Belgium
^f Biomarkable, Ghent, Belgium
^g Dementia Research Centre, UCL Queen Square Institute of Neurology, London, United Kingdom
^h Araclon Biotech, Zaragoza, Spain
ⁱ Koichi Tanaka Mass Spectrometry Research Laboratory, Shimadzu Corporation, Kyoto, Japan
^j Department of Biomarker Research, National Center for Geriatrics and Gerontology, Aichi, Obu, Japan
^k MagQu Co., Ltd., New Taipei City, Taiwan
^l Roche Diagnostics GmbH, Penzberg, Germany
^m F. Hoffmann-La Roche Ltd, Basel, Switzerland
ⁿ Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
^o Eli Lilly and Company, Indianapolis, IN, United States
^p Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden
^q Memory Clinic, Skåne University Hospital, Malmö, Sweden
^r Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, United Kingdom
^s UK Dementia Research Institute, London, United Kingdom

Abstract
Introduction: Blood-based assays to measure brain amyloid beta (Aβ) deposition are an attractive alternative to the cerebrospinal fluid (CSF)–based assays currently used in clinical settings. In this study, we examined different blood-based assays to measure Aβ and how they compare among centers and assays. Methods: Aliquots from 81 plasma samples were distributed to 10 participating centers. Seven immunological assays and four mass-spectrometric methods were used to measure plasma Aβ concentrations. Results: Correlations were weak for Aβ42 while Aβ40 correlations were stronger. The ratio Aβ42/Aβ40 did not improve the correlations and showed weak correlations. Discussion: The poor correlations for Aβ42 in plasma might have several potential explanations, such as the high levels of plasma proteins (compared to CSF), sensitivity to pre-analytical sample handling and specificity, and cross-reactivity of different antibodies. Different methods might also measure different pools of plasma Aβ42. We, however, hypothesize that greater correlations might be seen in future studies because many of the methods have been refined during completion of this study. © 2021 The Authors. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer’s Association

Author Keywords
Alzheimer’s disease;  amyloid beta;  biomarkers;  method comparison;  plasma

Video feedback intervention for cognitively impaired older drivers: A randomized clinical trial
(2021) Alzheimer’s and Dementia: Translational Research and Clinical Interventions, 7 (1), art. no. e12140, . 

Ott, B.R.^a , Papandonatos, G.D.^b , Burke, E.M.^c , Erdman, D.^d , Carr, D.B.^e , Davis, J.D.^c

^a Department of Neurology, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, United States
^b Department of Biostatistics, Brown University, Providence, RI, United States
^c Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, United States
^d Spaulding Cape Cod, Driving Assessment Program, East SandwichMA, United States
^e Department of Medicine and Neurology, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Introduction: This clinical trial aimed to determine whether in-car video feedback about unsafe driving events (UDE) to cognitively impaired older drivers and family members leads to a reduction in such driving behaviors. Methods: We randomized 51 cognitively impaired older drivers to receive either (1) a weekly progress report with recommendations and access to their videos, or (2) video monitoring alone without feedback over 3 months. Results: UDE frequency/1000 miles was reduced by 12% in feedback (rate ratio [RR] = 0.88, 95% confidence interval [CI] =.58–1.34), while remaining constant with only monitoring (RR = 1.01, 95% CI =.68–1.51). UDE severity/1000 miles was reduced by 37% in feedback (RR = 0.63, 95% CI =.31–1.27), but increased by 40% in monitoring (RR = 1.40, 95% CI =.68–2.90). Cognitive impairment moderated intervention effects (P =.03) on UDE frequency. Discussion: Results suggest the potential to improve driving safety among mild cognitively impaired older drivers using a behavior modification approach aimed at problem behaviors detected in their natural driving environment. © 2021 The Authors. Alzheimer’s & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer’s Association.

Author Keywords
Alzheimer’s disease;  clinical trial;  dementia;  driving;  mild cognitive impairment