WashU weekly Neuroscience publications

The architecture of functional lateralisation and its relationship to callosal connectivity in the human brain
(2019) Nature Communications, 10 (1), art. no. 1417, . 

Karolis, V.R., Corbetta, M., Thiebaut de Schotten, M.

Abstract
Functional lateralisation is a fundamental principle of the human brain. However, a comprehensive taxonomy of functional lateralisation and its organisation in the brain is missing. Here, we report the first complete map of functional hemispheric asymmetries in the human brain, reveal its low dimensional structure, and its relationship with structural inter-hemispheric connectivity. Our results suggest that the lateralisation of brain functions is distributed along four functional axes: symbolic communication, perception/action, emotion, and decision-making. The similarity between this finding and recent work on neurological symptoms give rise to new hypotheses on the mechanisms that support brain recovery after a brain lesion. We also report that cortical regions showing asymmetries in task-evoked activity have reduced connections with the opposite hemisphere. This latter result suggests that during evolution, brain size expansion led to functional lateralisation to avoid excessive conduction delays between the hemispheres. © 2019, The Author(s).

Document Type: Article
Publication Stage: Final
Source: Scopus

Cardiac Denial and Expectations Associated With Depression in Adults With Congenital Heart Disease
(2019) American Journal of Cardiology, . 

Huntley, G.D., Tecson, K.M., Sodhi, S., Saef, J., White, K.S., Ludbrook, P.A., Cedars, A.M., Ko, J.M.

Abstract
Depression in adults with congenital heart disease is highly prevalent and strongly associated with adverse prognosis. Better management of risk factors for depression may improve clinical outcomes in this population. We conducted a single-site, cross-sectional study of 78 adults with congenital heart disease followed at Washington University School of Medicine. Data considered in the analyses included retrospectively obtained clinical information and patients’ self-assessed psychosocial functioning and health status. To identify the clinical and psychosocial variables associated with depression, we built a stepwise multivariate model to measure the relative contribution of these variables to depression status. The prevalence of depression in our sample was 26%. Our model accounted for approximately 67% of the variability in depression scores. The final model consisted of the Cardiac Denial of Impact Scale, expectations domain of Barriers to Care, and the energy and social domains of the Rand 36-Item Short Form Health Survey. Clinical variables did not predict variability in depression scores. In conclusion, greater cardiac denial and negative expectations of the healthcare team were associated with increased depression symptoms in ACHD. © 2019 Elsevier Inc.

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

Evidence of causal effect of major depression on alcohol dependence: Findings from the psychiatric genomics consortium
(2019) Psychological Medicine, . 

Polimanti, R., Peterson, R.E., Ong, J.-S., MacGregor, S., Edwards, A.C., Clarke, T.-K., Frank, J., Gerring, Z., Gillespie, N.A., Lind, P.A., Maes, H.H., Martin, N.G., Mbarek, H., Medland, S.E., Streit, F., Agrawal, A., Edenberg, H.J., Kendler, K.S., Lewis, C.M., Sullivan, P.F., Wray, N.R., Gelernter, J., Derks, E.M.

Abstract
BackgroundDespite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.MethodsLinkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).ResultsPositive genetic correlation was observed between MD and AD (rg MD-AD = + 0.47, P = 6.6 × 10 -10 ). AC-quantity showed positive genetic correlation with both AD (rg AD-AC quantity = + 0.75, P = 1.8 × 10 -14 ) and MD (rg MD-AC quantity = + 0.14, P = 2.9 × 10 -7 ), while there was negative correlation of AC-frequency with MD (rg MD-AC frequency = -0.17, P = 1.5 × 10 -10 ) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10 -6 ). There was no evidence for reverse causation.ConclusionThis study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts. © 2019 Cambridge University Press.

Author Keywords
Alcohol consumption;  alcohol dependence;  genetic correlation;  genome-wide association;  major depression;  Mendelian randomization

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

The effect of ApoE ε4 on longitudinal brain region-specific glucose metabolism in patients with mild cognitive impairment: a FDG-PET study
(2019) NeuroImage: Clinical, 22, art. no. 101795, . 

Paranjpe, M.D., Chen, X., Liu, M., Paranjpe, I., Leal, J.P., Wang, R., Pomper, M.G., Wong, D.F., Benzinger, T.L.S., Zhou, Y., for the Alzheimer’s Disease Neuroimaging Initiative

Abstract
While the ApoE ε4 allele is a known risk factor for mild cognitive impairment (MCI) and Alzheimer’s disease, brain region specific effects remain elusive. In this study, we investigate whether the ApoE ε4 allele exhibits brain region specific effects in longitudinal glucose uptake among patients with MCI from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Preprocessed FDG PET images, MRIs, and demographic information were downloaded from the ADNI database. An iterative reblurred Van Cittertiteration method was used for partial volume correction (PVC) on all PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. Longitudinal changes in ROI FDG standardized uptake value ratio (SUVR) relative to cerebellum in 24 ApoE ε4 carriers and 24 age-matched ApoE ε4 non-carriers were measured for up to 84-months (median 72 months, SD = 11.2 months) and compared using a generalized linear mixed effects model controlling for gender, education, baseline age, and follow-up period. Additionally, voxelwise analysis was performed by implementing a paired t-test comparing matched baseline and 72 month FDG SUVR images in ApoE carriers and non-carriers separately. Results with PVC were compared with ones from non-PVC based analysis. After applying PVC, the superior fontal, parietal, lateral temporal, medial temporal, caudate, thalamus, and post-cingulate, and amygdala regions had greater longitudinal decreases in FDG uptake in ApoE ε4 carriers with MCI compared to non-carriers with MCI. Similar forebrain and limbic clusters were found through voxelwise analysis. Compared to the PVC based analysis, fewer significant ApoE-associated regions and clusters were found in the non-PVC based PET analysis. Our findings suggest that the ApoE ε4 genotype is associated with a longitudinal decline in glucose uptake in 8 forebrain and limbic brain regions in the context of MCI. In conclusion, this 84-months longitudinal FDG PET study demonstrates a novel ApoE ε4-associated brain-region specific glucose metabolism pattern in patients with MCI. Partial volume correction improved FDG PET quantification. © 2019 The Authors

Author Keywords
Alzheimer’s disease;  ApoE ε4;  FDG PET;  Longitudinal;  Mild cognitive impairment;  Partial volume correction

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

It is time to share (some) qualitative data: Reply to Guishard (2018), McCurdy and Ross (2018), and Roller and Lavrakas (2018)
(2018) Qualitative Psychology, 5 (3), pp. 412-415. 

DuBois, J.M., Walsh, H., Strait, M.

Abstract
In this article, we offer a reply to the three commentaries on our article, “Is It Time to Share Qualitative Research Data?” (DuBois, Strait, & Walsh, 2018). We agree with the commenters on many points, including the need to honor relationships with communities, the need to protect participants from harm, and the usefulness of having a framework for data sharing that is informed by quality standards. We also respond to several areas of apparent disagreement regarding the need to be accountable to those who fund and consume science, the possibility that many participants-much like authors-prefer that their contributions to science be broadly disseminated and presented in proper context, and the common legal fact of institutional ownership of research data in the United States. We conclude that it will not be possible to share all data in a responsible manner but that this does not prevent a change in our default assumption regarding qualitative data sharing. In general, data should be shared unless compelling concerns exist that cannot be addressed adequately. © 2017 American Psychological Association.

Author Keywords
Data sharing;  Qualitative research;  Research ethics

Document Type: Note
Publication Stage: Final
Source: Scopus