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Office of Neuroscience Research > Resources and Facilities > WUSTL Neuroscience Publications for the week > Weekly Neuroscience Publications - Archives > WUSTL Neuroscience Publications Archive - June 2014

WUSTL Neuroscience Publications Archive - June 2014

 Scopus weekly reports:

June 16, 2014

June 23, 2014

 

June 23, 2014

Sharma, A. , Lancaster, S. , Bagade, S. , Hildebolt, C.

Early pattern of degenerative changes in individual components of intervertebral discs in stressed and nonstressed segments of lumbar spine: An in vivo magnetic resonance imaging study

(2014) Spine, 39 (13), pp. 1084-1090.

Abstract

STUDY DESIGN.: A retrospective imaging review. OBJECTIVE.: To assess differences in burden and pattern of disc degeneration in segments of lumbar spine with and without signs of increased mechanical stresses. SUMMARY OF BACKGROUND DATA.: Young patients with magnetic resonance imaging signs of increased mechanical stress in pedicles or pars interarticularis provide an excellent in vivo model to study early effects of mechanical stresses on lumbar intervertebral discs without the confounding effects of genetics or environmental factors. Detailed in vivo evaluation for early degenerative changes in all individual disc components of stressed intervertebral discs has not been done. METHODS.: Using magnetic resonance imaging, 2 radiologists assessed intervertebral discs around 93 stressed lumbar spinal segments in 87 patients ( 55 males, 32 females; mean age, 15.3 ± 3.3 yr; range, 5-25 yr) as well as lumbar discs in nonstressed segments for signs of degeneration in annulus fibrosus, nucleus pulposus, and endplates. Differences between stressed, control, and loading-matched control discs were assessed using Wilcoxon signed rank sum test. RESULTS.: Burden of annular tears, radial tears, herniations, and nuclear degeneration was significantly higher in stressed discs ( 0.70 ± 0.34, 0.48 ± 0.39, 0.07 ± 0.19, and 0.17± 0.31, respectively) than control ( 0.29 ± 0.25, 0.09 ± 0.17, 0.01 ± 0.04, and 0.02 ± 0.08, respectively) or loading-matched control discs ( 0.44 ± 0.47, 0.16 ± 0.36, 0.01 ± 0.04, and 0.01 ± 0.11, respectively) ( P < 0.01 for all). Stressed segments did not show any significant increase in endplate degeneration. CONCLUSION.: Intervertebral discs in stressed spinal segments show an increased burden of disc degeneration involving annulus fibrosus and nucleus pulposus, but not the endplates. © 2014, Lippincott Williams and Wilkins. 

Author Keywords

annular tears;  disc degeneration;  nuclear degeneration;  spondylolisthesis;  spondylolysis;  stress fracture;  stress reaction 

Document Type: Article

Source: Scopus

 

Karch, C.M., Goate, A.M.

Alzheimer's Disease Risk Genes and Mechanisms of Disease Pathogenesis

 (2014) Biological Psychiatry, . Article in Press.

 Department of Psychiatry and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri. 

Abstract

We review the genetic risk factors for late-onset Alzheimer's disease (AD) and their role in AD pathogenesis. More recent advances in understanding of the human genome-technologic advances in methods to analyze millions of polymorphisms in thousands of subjects-have revealed new genes associated with AD risk, including ABCA7, BIN1, CASS4, CD33, CD2AP, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB5-DBR1, INPP5D, MS4A, MEF2C, NME8, PICALM, PTK2B, SLC24H4-RIN3, SORL1, and ZCWPW1. Emerging technologies to analyze the entire genome in large data sets have also revealed coding variants that increase AD risk: PLD3 and TREM2. We review the relationship between these AD risk genes and the cellular and neuropathologic features of AD. Understanding the mechanisms underlying the association of these genes with risk for disease will provide the most meaningful targets for therapeutic development to date. © 2014 Society of Biological Psychiatry. 

Author Keywords

Alzheimer's disease;  amyloid precursor protein;  cholesterol metabolism;  endocytosis;  genome-wide association studies;  immune response

Document Type: Article in Press

Source: Scopus

 

Milner, E., Holtzman, J.C., Friess, S., Hartman, R.E., Brody, D.L., Han, B.H., Zipfel, G.J.

Endovascular perforation subarachnoid hemorrhage fails to cause Morris water maze deficits in the mouse

 (2014) Journal of Cerebral Blood Flow and Metabolism, . Article in Press.

Department of Neurological Surgery, Washington University School of Medicine, St Louis, Missouri, USA 

Abstract

Cognitive dysfunction is the primary driver of poor long-term outcome in aneurysmal subarachnoid hemorrhage (SAH) survivors; modeling such deficits preclinically is thus key for mechanistic and translational investigation. Although rat SAH causes long-term deficits in learning and memory, it remains unknown whether similar deficits are seen in the mouse, a species particularly amenable to powerful, targeted genetic manipulation. We thus subjected mice to endovascular perforation SAH and assessed long-term cognitive outcome via the Morris water maze (MWM), the most commonly used metric for rodent neurocognition. No significant differences in MWM performance (by either of two protocols) were seen in SAH versus sham mice. Moreover, SAH caused negligible hippocampal CA1 injury. These results undercut the potential of commonly used methods (of SAH induction and assessment of long-term neurocognitive outcome) for use in targeted molecular studies of SAH-induced cognitive deficits in the mouse.Journal of Cerebral Blood Flow and Metabolism advance online publication, 18 June 2014; doi:10.1038/jcbfm.2014.108.

Document Type: Article in Press

Source: Scopus

 

Blanchard, H. , Taha, A.Y. , Cheon, Y. , Kim, H.-W. , Turk, J , Rapoport, S.I.

iPLA2β Knockout Mouse, a Genetic Model for Progressive Human Motor Disorders, Develops Age-Related Neuropathology

(2014) Neurochemical Research, . Article in Press. 

Abstract

Calcium-independent phospholipase A2 group VIa (iPLA2β) preferentially releases docosahexaenoic acid (DHA) from the sn-2 position of phospholipids. Mutations of its gene, PLA2G6, are found in patients with several progressive motor disorders, including Parkinson disease. At 4 months, PLA2G6 knockout mice (iPLA2β-/-) show minimal neuropathology but altered brain DHA metabolism. By 1 year, they develop motor disturbances, cerebellar neuronal loss, and striatal α-synuclein accumulation. We hypothesized that older iPLA2β-/- mice also would exhibit inflammatory and other neuropathological changes. Real-time polymerase chain reaction and Western blotting were performed on whole brain homogenate from 15 to 20-month old male iPLA2β-/- or wild-type (WT) mice. These older iPLA2β-/- mice compared with WT showed molecular evidence of microglial (CD-11b, iNOS) and astrocytic (glial fibrillary acidic protein) activation, disturbed expression of enzymes involved in arachidonic acid metabolism, loss of neuroprotective brain derived neurotrophic factor, and accumulation of cytokine TNF-α messenger ribonucleic acid, consistent with neuroinflammatory pathology. There was no evidence of synaptic loss, of reduced expression of dopamine active reuptake transporter, or of accumulation of the Parkinson disease markers Parkin or Pink1. iPLA2γ expression was unchanged. iPLA2β deficient mice show evidence of neuroinflammation and associated neuropathology with motor dysfunction in later life. These pathological biomarkers could be used to assess efficacy of dietary intervention, antioxidants or other therapies on disease progression in this mouse model of progressive human motor diseases associated with a PLA2G6 mutation. © 2014 Springer Science+Business Media New York (outside the USA).

Author Keywords

Arachidonic and docosahexaenoic acid;  Brain;  Calcium-independent phospholipase A2 (iPLA2β) knockout;  Motor disturbances;  Neuropathology;  Parkinson disease

Document Type: Article in Press

Source: Scopus

 

Braver, T.S , Krug, M.K. , Chiew, K.S. , Kool, W. , Westbrook, J.A. , Clement, N.J. , Adcock, R.A , Barch, D.M. , Botvinick, M.M. , Carver, C.S. , Cools, R. , Custers, R. , Dickinson, A. , Dweck, C.S. , Fishbach, A. , Gollwitzer, P.M , Hess, T.M. , Isaacowitz, D.M. , Mather, M. , Murayama, K. , Pessoa, L. , Samanez-Larkin, G.R , Somerville, L.H.

Mechanisms of motivation-cognition interaction: challenges and opportunities

 (2014) Cognitive, Affective, & Behavioral Neuroscience, . Article in Press.

Abstract

Recent years have seen a rejuvenation of interest in studies of motivation-cognition interactions arising from many different areas of psychology and neuroscience. The present issue of Cognitive, Affective, & Behavioral Neuroscience provides a sampling of some of the latest research from a number of these different areas. In this introductory article, we provide an overview of the current state of the field, in terms of key research developments and candidate neural mechanisms receiving focused investigation as potential sources of motivation-cognition interaction. However, our primary goal is conceptual: to highlight the distinct perspectives taken by different research areas, in terms of how motivation is defined, the relevant dimensions and dissociations that are emphasized, and the theoretical questions being targeted. Together, these distinctions present both challenges and opportunities for efforts aiming toward a more unified and cross-disciplinary approach. We identify a set of pressing research questions calling for this sort of cross-disciplinary approach, with the explicit goal of encouraging integrative and collaborative investigations directed toward them. © 2014 Psychonomic Society, Inc.

Author Keywords

Aging;  Cognitive control;  Development;  Dopamine;  Reward 

Document Type: Article in Press

Source: Scopus

 

Ulrich, J.D. , Finn, M.B. , Wang, Y. , Shen, A. , Mahan, T.E. , Jiang, H. , Stewart, F.R. , Piccio, L. , Colonna, M. , Holtzman, D.M.

Altered microglial response to Aβ plaques in APPPS1-21 mice heterozygous for TREM2

(2014) Molecular Neurodegeneration, 9 (1), art. no. 20, .

Abstract

Background: Recent genome-wide association studies linked variants in TREM2 to a strong increase in the odds of developing Alzheimer's disease. The mechanism by which TREM2 influences the susceptibility to Alzheimer's disease is currently unknown. TREM2 is expressed by microglia and is thought to regulate phagocytic and inflammatory microglial responses to brain pathology. Given that a single allele of variant TREM2, likely resulting in a loss of function, conferred an increased risk of developing Alzheimer's disease, we tested whether loss of one functional trem2 allele would affect Aβ plaque deposition or the microglial response to Aβ pathology in APPPS1-21 mice. Results: There was no significant difference in Aβ deposition in 3-month old or 7-month old APPPS1-21 mice expressing one or two copies of trem2. However, 3-month old mice with one copy of trem2 exhibited a marked decrease in the number and size of plaque-associated microglia. While there were no statistically significant differences in cytokine levels or markers of microglial activation in 3- or 7-month old animals, there were trends towards decreased expression of NOS2, C1qa, and IL1a in 3-month old TREM2 vs. TREM2 mice. Conclusions: Loss of a single copy of trem2 had no effect on Aβ pathology, but altered the morphological phenotype of plaque-associated microglia. These data suggest that TREM2 is important for the microglial response to Aβ deposition but that a 50% decrease inTREM2 expression does not affect Aβ plaque burden. © 2014 Ulrich et al.; licensee BioMed Central Ltd. 

Author Keywords

Alzheimer's disease;  Amyloid β;  Microglia;  TREM2 

Document Type: Article

Source: Scopus

 

Zempel, J.M. , Mano, T.

Myoclonic atonic epilepsy: Another generalized epilepsy syndrome that is "not so" generalized

(2014) Neurology, 82 (17), pp. 1486-1487.

Document Type: Editorial

Source: Scopus

 

Giovannoni, G. , Naismith, R.T.

Natalizumab to fingolimod washout in patients at risk of PML: When good intentions yield bad outcomes

 (2014) Neurology, 82 (14), pp. 1196-1197.

Document Type: Editorial

Source: Scopus

 

Ting, S.K.S., Benzinger, T. , Kepe, V. , Fagan, A , Coppola, G. , Porter, V. , Hecimovic, S. , Chakraverty, S. , Alvarez-Retuerto, A. , Goate, A. , Ringman, J.M.

A novel PSEN1 mutation (I238M) associated with early-onset Alzheimer's disease in an African-American woman

 (2014) Journal of Alzheimer's Disease, 40 (2), pp. 271-275.

Abstract

Mutations in PSEN1 are the most common cause of autosomal dominant familial Alzheimer's disease (FAD). We describe an African-American woman with a family history consistent with FAD who began to experience cognitive decline at age 50. Her clinical presentation, MRI, FDG-PET, and PIB-PET scan findings were consistent with AD and she was found to have a novel I238M substitution in PSEN1. As this mutation caused increased production of Aβ42 in an in vitro assay, was not present in two population databases, and is conserved across species, it is likely to be pathogenic for FAD.

Author Keywords

African;  Alzheimer's disease;  autosomal dominant;  familial;  gamma-secretase;  in vitro;  PIB-PET;  presenilin-1;  PSEN1

Document Type: Article

Source: Scopus

 

Vesoulis, Z.A. , Mathur, A.M

Advances in management of neonatal seizures

(2014) Indian Journal of Pediatrics, 81 (6), pp. 592-598. Cited 1 time.

Abstract

Seizures are more common in the neonatal period than any other time in the human lifespan. A high index of suspicion for seizures should be maintained for infants who present with encephalopathy soon after birth, have had a stroke, central nervous system (CNS) infection or intracranial hemorrhage or have a genetic or metabolic condition associated with CNS malformations. Complicating the matter, most neonatal seizures lack a clinical correlate with only subtle autonomic changes and often no clinical indication at all. Over the last three decades, several tools have been developed to enhance the detection and treatment of neonatal seizures. The use of electroencephalography (EEG) and the later development of amplitude-integrated EEG (aEEG), allows for Neurologists and non-Neurologists alike, to significantly increase the sensitivity of seizure detection. When applied to the appropriate clinical setting, time to diagnosis and start of therapy is greatly reduced. Phenobarbital maintains the status of first-line therapy in worldwide use. However, newer anti-epileptic agents such as, levetiracetam, bumetanide, and topiramate are increasingly being applied to the neonatal population, offering the potential for seizure treatment with a significantly better side-effect profile. Seizures in premature infants, continue to confound clinicians and researchers alike. Though the apparent seizure burden is significant and there is an association between seizures and adverse outcomes, the two are not cleanly correlated. Compounding the issue, GABA-ergic anti-epileptic drugs are not only less effective in this age group due to reversed neuronal ion gradients but may cause harm. Selecting an appropriate treatment group remains a challenge. © 2014 Dr. K C Chaudhuri Foundation.

Author Keywords

aEEG;  HIE;  Infants;  Seizures

 Document Type: Review

Source: Scopus

 

Dobrowolska, J.A.i , Michener, M.S. , Wu, G. , Patterson, B.W. , Chott, R , Ovod, V , Pyatkivskyy, Y. , Wildsmith, K.R, Kasten, T. , Mathers, P. , Dancho, M. , Lennox, C. , Smith, B.E , Gilberto, D , McLoughlin, D. , Holder, D.J., Stamford, A.W. , Yarasheski, K.E. , Kennedy, M.E. , Savage, M.J , Bateman, R.J.

CNS Amyloid-β, Soluble APP-α and-β Kinetics during BACE Inhibition

(2014) Journal of Neuroscience, 34 (24), pp. 8336-8346.

Abstract

BACE, aβ-secretase, is an attractive potential disease-modifying therapeutic strategy for Alzheimer's disease (AD) as it results directly in the decrease of amyloid precursor protein (APP) processing through the β-secretase pathway and a lowering of CNS amyloid-β (Aβ) levels. The interaction of the β-secretase and α-secretase pathway-mediated processing of APP in the rhesus monkey (nonhuman primate; NHP) CNS is not understood. We hypothesized that CNS inhibition of BACE would result in decreased newly generated Aβ and soluble APPβ (sAPPβ), with increased newly generated sAPPα. A stable isotope labeling kinetics experiment in NHPs was performed with a 13C6-leucine infusion protocol to evaluate effects of BACE inhibition on CNS APP processing by measuring the kinetics of sAPPα, sAPPβ, andAβ in CSF. EachNHPreceived a low, medium, or high dose of MBI-5 (BACE inhibitor) or vehicle in a four-way crossover design. CSF sAPPα, sAPPβ, andAβ were measured by ELISA and newly incorporated label following immunoprecipitation and liquid chromatography-mass spectrometry. Concentrations, kinetics, and amount of newly generated APP fragments were calculated. sAPPβ and sAPPα kinetics were similar, but both significantly slower than Aβ. BACE inhibition resulted in decreased labeled sAPPβ and Aβ in CSF, without observable changes in labeled CSF sAPPα. ELISA concentrations of sAPPβ and Aβ both decreased and sAPPα increased. sAPPα increased by ELISA, with no difference by labeled sAPPα kinetics indicating increases in product may be due to APP shunting from the β-secretase to the α-secretase pathway. These results provide a quantitative understanding of pharmacodynamic effects of BACE inhibition on NHP CNS, which can inform about target development. © 2014 the authors.

Author Keywords

Amyloid beta;  Amyloid precursor protein;  BACE inhibitor;  SAPP-α sAPP-β;  SILK

Document Type: Article

Source: Scopus

 

Lynskey, M. , Agrawal, A.

Commentary on Vink etal. (2014): The polygenic basis of drug use-does context matter?

 (2014) Addiction, 109 (7), pp. 1152-1153.

Author Keywords

Alcohol;  Cannabis;  Environmental influences;  Genetic and environmental interplay;  Polygenic risk;  Tobacco

Document Type: Article

Source: Scopus

 

Williams, B.J. , Smith, J.S. , Saulle, D. , Ames, C.P. , Lenke, L.G. , Broadstone, P.A. , Vaccaro, A.R. , Polly Jr., D.W. , Shaffrey, C.I.

Complications associated with surgical treatment of traumatic spinal fractures: A review of the scoliosis research society morbidity and mortality database

 (2014) World Neurosurgery, 81 (5-6), pp. 818-824.

Abstract

Objective: Traumatic spinal fracture is a common indication for surgery, with an associated high incidence of perioperative complications. The literature provides a wide range in the incidence of complications. We seek to assess the perioperative morbidity and mortality of surgery for traumatic spinal fractures and to identify predictors of their occurrence. Methods: We performed a retrospective analysis of all traumatic spinal fracture cases submitted by members of the Scoliosis Research Society from 2004 to 2007. Results: A total of 108,478 cases were submitted from 2004 through 2007, with 6,706 (6.2%) performed for treatment of traumatic fracture. Twenty-two percent of patients had preoperative neurological deficits. Intraoperative neuromonitoring was used in 58% of cases. The overall incidence of complications was 6.9%. The perioperative mortality was 0.5%. There were 59 (0.9%) new postoperative neurological deficits. Multivariate analysis demonstrated preoperative neurological deficit (P =.001; odds ratio [OR] 1.449, 95% confidence interval [CI] [1.156 to 1.817]) and fusion (P =.001; OR 1.12, 95% CI [1.072 to 1.168]) as predictors of complications and use of intraoperative neuromonitoring (P =.016; OR 1.949, 95% CI [1.13 to 3.361]), and preoperative neurological deficit (P <.001; OR 2.964, 95% CI [1.667 to 5.271]) as predictors of new postoperative neurological deficits (P <.001). Conclusions: Overall, surgery for the treatment of spinal fractures was performed with relatively low incidences of perioperative complications (6.9%) and mortality (0.5%). These data may prove useful for patient counseling and ongoing efforts to improve the safety of operative care for patients with spinal fracture. © 2014 Elsevier Inc. All rights reserved.

Author Keywords

Complication;  Fracture;  Mortality;  Spine surgery;  Spine trauma

Document Type: Review

Source: Scopus

 

Piasecki, T.M. , Cooper, M.L. , Wood, P.K. , Sher, K.J. , Shiffman, S. , Heath, A.C

Dispositional drinking motives: Associations with appraised alcohol effects and alcohol consumption in an ecological momentary assessment investigation

(2014) Psychological Assessment, 26 (2), pp. 363-369.  

Abstract

Alcohol use can be understood as a strategic behavior, such that people choose to drink based on the anticipated affective changes produced by drinking relative to those produced by alternative behaviors. This study investigated whether people who report drinking for specific reasons via the Drinking Motives Questionnaire-Revised (DMQ-R; Cooper, 1994) actually experience the alcohol effects they purportedly seek. As a secondary goal, we examined relations between drinking motives and indices of the amount of alcohol consumed. Data were drawn from 3,272 drinking episodes logged by 393 community-recruited drinkers during a 21-day Ecological Momentary Assessment investigation. After accounting for selected covariates, DMQ-R enhancement motives uniquely predicted real-time reports of enhanced drinking pleasure. DMQ-R coping motives were associated with reports of increased drinking-contingent relief and punishment. Enhancement motives uniquely predicted consuming more drinks per episode and higher peak intra-episode estimated blood alcohol concentration. The findings extend the evidence for the validity of the DMQ-R motive scores by demonstrating that internal drinking motives (enhancement and coping) are related to the experienced outcomes of drinking in the manner anticipated by theory. © 2014 American Psychological Association.

Author Keywords

Alcohol;  Amount;  Anticipated effects;  Drinking motives;  Ecological momentary assessment;  Real-world drinking

Document Type: Article

Source: Scopus

 

Kefalov, V.J. , Arshavsky, V.Y.

FASEB Science Research Conference on Biology and Chemistry of Vision

 (2014) FASEB Journal, 28 (6), pp. 2395-2397.

Document Type: Article

Source: Scopus

 

Nasiriavanaki, M., Xing, W., Xia, J., Wang, L.V.

Functional connectivity in the mouse brain imaged by B-mode photoacoustic microscopy

 (2014) Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 8943, art. no. 894364, .

Optical Imaging Laboratory, Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States

Abstract

The increasing use of mouse models for human brain disease studies, coupled with the fact that existing functional imaging modalities cannot be easily applied to mice, presents an emerging need for a new functional imaging modality. Utilizing acoustic-resolution photoacoustic microscopy (AR-PAM), we imaged spontaneous cerebral hemodynamic fluctuations and their associated functional connections in the mouse brain. The images were acquired noninvasively in B-scan mode with a fast frame rate, a large field of view, and a high spatial resolution. At a location relative to the bregma 0, correlations were investigated inter-hemispherically between bilaterally homologous regions, as well as intra-hemispherically within the same functional regions. The functional connectivity in different functional regions was studied. The locations of these regions agreed well with the Paxinos mouse brain atlas. The functional connectivity map obtained in this study can then be used in the investigation of brain disorders such as stroke, Alzheimer's, schizophrenia, multiple sclerosis, autism, and epilepsy. Our experiments show that photoacoustic microscopy is capable to detect connectivities between different functional regions in B-scan mode, promising a powerful functional imaging modality for future brain research. © 2014 SPIE.

Author Keywords

Acoustic-resolution photoacoustic microscopy;  B-scan mode;  Functional imaging;  Resting-state functional connectivity

Document Type: Conference Paper

Source: Scopus

 

Fisher, M.J. , Loguidice, M. , Gutmann, D.H , Listernick, R., Ferner, R.E , Ullrich, N.J. , Packer, R.J. , Tabori, U. , Hoffman, R.O , Ardern-Holmes, S.L , Hummel, T.R , Hargrave, D.R, Bouffet, E , Charrow, J. , Bilaniuk, L.T. , Balcer, L.J. , D'Agostino McGowan, L , Liu, G.T.

Gender as a disease modifier in neurofibromatosis type 1 optic pathway glioma

 (2014) Annals of Neurology, 75 (5), pp. 799-800.

Document Type: Letter

Source: Scopus

 

Dhand, A., Landau, W.M.

Hemicraniectomy for middle-cerebral-artery stroke [1]

 (2014) New England Journal of Medicine, 370 (24), p. 2346.

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

Document Type: Letter

Source: Scopus

  

Rivera-Escalera, F. , Matousek, S.B , Ghosh, S., Olschowka, J.A. , O'banion, M.K

Interleukin-1β mediated amyloid plaque clearance is independent of CCR2 signaling in the APP/PS1 mouse model of Alzheimer's disease

 (2014) Neurobiology of Disease, 69, pp. 124-133.

Abstract

Neuroinflammation is a key component of Alzheimer's disease (AD) pathogenesis. Particularly, the proinflammatory cytokine interleukin-1 beta (IL-1β) is upregulated in human AD and believed to promote amyloid plaque deposition. However, studies from our laboratory have shown that chronic IL-1β overexpression in the APPswe/PSEN1dE9 (APP/PS1) mouse model of AD ameliorates amyloid pathology, increases plaque-associated microglia, and induces recruitment of peripheral immune cells to the brain parenchyma. To investigate the contribution of CCR2 signaling in IL-1β-mediated amyloid plaque clearance, seven month-old APP/PS1/CCR2-/- mice were intrahippocampally transduced with a recombinant adeno-associated virus serotype 2 containing the cleaved form of human IL-1β (rAAV2-IL-1β). Four weeks after rAAV2-IL-1β transduction, we found significant reductions in 6E10 and Congo red staining of amyloid plaques that was confirmed by decreased levels of insoluble Aβ1-42 and Aβ1-40 in the inflamed hippocampus. Bone marrow chimeric studies confirmed the presence of infiltrating immune cells following IL-1β overexpression and revealed that dramatic reduction of CCR2+ peripheral mononuclear cell recruitment to the inflamed hippocampus did not prevent the ability of IL-1β to induce amyloid plaque clearance. These results suggest that infiltrating CCR2+ monocytes do not contribute to IL-1β-mediated amyloid plaque clearance. © 2014 Elsevier Inc.

Author Keywords

Alzheimer's disease;  Bone marrow derived;  CCL2;  CCR2;  Interleukin-1β;  Monocytes;  Neuroinflammation

Document Type: Article

Source: Scopus

 

Mitsuhashi, K., Schoonover, R.W., Huang, C., Wang, L.V., Anastasio, M.A.

Investigation of effective system designs for transcranial photoacoustic tomography of the brain

 (2014) Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 8943, art. no. 894369, .

Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States

Abstract

Photoacoustic computed tomography (PACT) holds great promise for transcranial brain imaging. However, the strong reflection, scattering and attenuation of acoustic waves in the skull present significant challenges to developing this method. We report on a systematic computer-simulation study of transcranial brain imaging using PACT. The goal of this study was to identify an effective imaging system design that can be translated for clinical use. The propagation of photoacoustic waves through a model skull was studied by use of an elastic finite-difference time-domain (FDTD) method. The acoustic radiation pattern from a photoacoustic source just beneath the skull was observed with a ring transducer array that was level with the source. The observed radiation pattern was found to contain stronger contributions from waves that were converted to shear waves in skull than longitudinal waves that did not undergo mode conversion. Images reconstructed from the pressure data that contain shear wave components possess better resolution than images reconstructed from the data that only contain the longitudinal wave signals. These observations revealed that the detection system should be designed to capture photoacoustic signals that travel through the skull in the form of shear waves as well as in the form of longitudinal waves. A preliminary investigation on the effect of the presence of absorption in the skull is also reported. This study provides an insight into the wave phenomena in transcranial PACT imaging, as well as a concrete detection design strategy that mitigates the degraded resolution of reconstructed images. © 2014 SPIE.

Author Keywords

Brain imaging;  Image reconstruction;  Photoacoustic computed tomography

Document Type: Conference Paper

Source: Scopus

 

Lou, Y., Xia, J., Wang, L.V.

Mouse brain imaging using photoacoustic computed tomography

 (2014) Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 8943, art. no. 894340, .

Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States

Abstract

Photoacoustic computed tomography (PACT) provides structural and functional information when used in small animal brain imaging. Acoustic distortion caused by bone structures largely limits the deep brain image quality. In our work, we present ex vivo PACT images of freshly excised mouse brain, intending that can serve as a gold standard for future PACT in vivo studies on small animal brain imaging. Our results show that structures such as the striatum, hippocampus, ventricles, and cerebellum can be clearly di erentiated. An artery feature called the Circle of Willis, located at the bottom of the brain, can also be seen. These results indicate that if acoustic distortion can be accurately accounted for, PACT should be able to image the entire mouse brain with rich structural information. © 2014 SPIE.

Author Keywords

Ex vivo imaging;  Mouse brain structure;  Photoacoustic computed tomography;  Small animal imaging

Document Type: Conference Paper

Source: Scopus

 

Faingold, C.L. , Tupal, S.

Neuronal Network Interactions in the Startle Reflex, Learning Mechanisms, and CNS Disorders, Including Sudden Unexpected Death in Epilepsy

 (2014) Neuronal Networks in Brain Function, CNS Disorders, and Therapeutics, pp. 407-418.

Abstract

As discussed in this book, there are many primary neuronal networks that mediate important physiological functions of the central nervous system (CNS), including vision, hearing, locomotion, and respiration. Each of these normal networks can interact with other primary networks to mediate important cross-network functions, and the interaction can be either additive or competitive. An example of an additive or positive form of network interaction is seen in sensorimotor integration, including the visual-motor interactions that mediate eye movements in response to visual stimuli. Primary networks can also interact with nonprimary conditional multireceptive networks, leading to the emergence of more complex phenomena. These phenomena include certain forms of learning as well as CNS disorders, including, for example, those that can lead to death in epilepsy. Neuronal networks can compete with each other to reduce the network function. This occurs, for example, when an acoustic stimulus can induce cessation of locomotion in a learning paradigm such as fear conditioning. A negative interaction is also seen in the prototypical competitive network interaction that forms the basis of the original and conceptually important network interaction hypothesis, the gate control theory of pain. This network competition mechanism is proposed to be a critical mechanism mediating the therapeutic stimulation paradigms currently used to treat many CNS disorders. Network interactions are mediated by (1) direct electrophysiological connections between network neurons that release endogenous neuroactive substances via synaptic transmission and (2) indirect interactions that release these substances via volume transmission. These network interactions can occur essentially instantaneously or sequentially over a finite time course. The interactions can involve two networks, as in the somatosensory-motor network interactions, which occur in the tactile startle response, and are also seen in the interaction of the pain network with the therapeutic network initiated by certain pain-relieving electrical stimulation therapies. The network interactions can be more complex, involving three or more networks, and examples of multinetwork interaction include fear-potentiated startle, seizure-induced analgesia, and audiogenic seizure kindling. An example of such a multinetwork interaction with fatal consequences is proposed to occur in the CNS disorder of epilepsy called sudden unexpected death in epilepsy (SUDEP). The DBA/1 and DBA/2 mouse models of SUDEP involve additive interactions between the auditory and locomotor networks and a subsequent negative interaction with the respiratory network, which results in respiratory arrest. These network interactions may be mediated, in part, by the release of endogenous neuroactive substances that inhibit (e.g. adenosine) or enhance (e.g. serotonin) the activity of the respiratory network via synaptic and/or volume transmission. Thus, investigations of network interactions in normal situations and in CNS disorders may provide the keys to understanding learning mechanisms and also for treating CNS disorders with stimulation and/or pharmacological paradigms. © 2014 Elsevier Inc. All rights reserved.

Author Keywords

Adenosine;  Analgesia;  Audiogenic seizures;  Auditory network;  DBA mice;  Fear;  GEPRs;  Kindling;  Locomotor network;  Pain;  Respiratory network;  Sensorimotor integration;  Serotonin;  Startle;  SUDEP

Document Type: Book Chapter

Source: Scopus

 

MacIejewski, D.F , Creemers, H.E. , Lynskey, M.T. , Madden, P.A.F., Heath, A.C., Statham, D.J., Martin, N.G., Verweij, K.J.H

Overlapping genetic and environmental influences on nonsuicidal self-injury and suicidal ideation: Different outcomes, same etiology?

 (2014) JAMA Psychiatry, 71 (6), pp. 699-705.

Abstract

IMPORTANCE Nonsuicidal self-injury (NSSI) and suicidal self-injury are very harmful behaviors and are associated with several psychiatric disorders. In the recently developed fifth edition of the DSM, NSSI and suicidal behavior disorder are for the first time introduced as conditions in their own right instead of symptoms of other psychiatric disorders. It is unclear to what extent NSSI and suicidal self-injury share the same underlying biological mechanisms and are influenced by the same environmental factors. OBJECTIVE To determine the relative importance of genetic and environmental influences on the variation in NSSI and suicidal ideation and their covariation. DESIGN, SETTING, AND PARTICIPANTS Classical twin design using a sample of 10 678 male and female adult twins (mean [SD] age, 32.76 [6.99] years) from the Australian Twin Registry, a population-based twin registry. Between 1996 and 2009, the twins participated in semistructured telephone interviews that primarily focused on psychiatric disorders. MAIN OUTCOMES AND MEASURES Lifetime presence of self-reported NSSI and suicidal ideation. RESULTS The prevalences of NSSI and suicidal ideation were 4.7%and 26.5%, respectively, and individuals who engaged in self-harm were much more likely to report suicidal ideation (odds ratio = 8.39; 95%CI, 6.84-10.29). Results from a bivariate genetic model indicated that genetic factors explain a substantial part of the variance in both NSSI (37%for men and 59% for women) and suicidal ideation (41% for men and 55%for women), while residual influences (including nonshared environmental influences and measurement error) explain the remainder of the variance. Shared (family) environment did not seem to play a role. Moreover, both behaviors were strongly correlated (r = 0.49 for men and 0.61 for women), and this correlation was largely explained by overlapping genetic influences (76%for men and 62%for women), whereas residual influences accounted for the remainder of the phenotypic correlation. CONCLUSIONS AND RELEVANCE Results indicated that the substantial correlation between NSSI and suicidal ideation is largely driven by overlapping genetic factors, suggesting that the 2 behaviors share similar biological underpinnings. Overlapping residual influences also explain part of the covariance between the 2 traits. Future research should further investigate which genetic and environmental influences underlie the vulnerability to NSSI and suicidal ideation. Copyright 2014 American Medical Association. All rights reserved.

Document Type: Article

Source: Scopus

 

Hill, P.L. , Payne, B.R. , Jackson, J.J. , Stine-Morrow, E.A.L., Roberts, B.W.

Perceived social support predicts increased conscientiousness during older adulthood

 (2014) Journals of Gerontology - Series B Psychological Sciences and Social Sciences, 69 (4), pp. 543-547.

Abstract

Objectives. This study examined whether perceived social support predicted adaptive personality change in older adulthood, focusing on the trait of conscientiousness. We tested this hypothesis both at the broad domain level and with respect to the specific lower order facets that comprise conscientiousness: order, self-control, industriousness, responsibility, and traditionalism. Methods. A sample of 143 older adults (aged 60-91) completed measures of conscientiousness and social support during 2 assessments 7 months apart. Results. Social support and conscientiousness were positively correlated among older adults. Moreover, older adults who perceived greater social support at baseline were more likely to gain in conscientiousness over time. The magnitude of this effect was relatively similar across the order, self-control, and industriousness facets. Discussion. Perceived social support provides multiple benefits later in life, and the current results add to this literature by showing that it also promotes conscientiousness. As conscientiousness is linked to a variety of positive outcomes later in life, including health, future research should examine whether conscientiousness change may be an important mechanism through which social support enhances resilience in older adulthood. © 2013 The Author.

Author Keywords

Conscientiousness;  Older adulthood;  Personality development;  Social support

Document Type: Article

Source: Scopus

 

Strassmann, J.E., Queller, D.C.

Privatization and property in biology

 (2014) Animal Behaviour, 92, pp. 305-311.

Department of Biology, Washington University, St Louis, MO, United States

Abstract

Organisms evolve to control, preserve, protect and invest in their own bodies. When they do likewise with external resources they privatize those resources and convert them into their own property. Property is a neglected topic in biology, although examples include territories, domiciles and nest structures, food caching, mate guarding, and the resources and partners in mutualisms. Property is important because it represents a solution to the tragedy of the commons; to the extent that an individual exerts long-term control of its property, it can use it prudently, and even invest in it. Resources most worth privatizing are often high in value. To be useful to their owner in the future, they are typically durable and defensible. This may explain why property is relatively rare in animals compared to humans. The lack of institutional property rights in animals also contributes to their rarity, although owner-intruder conventions may represent a simple form of property rights. Resources are often privatized by force or threat of force, but privatization can also be achieved by hiding, by constructing barriers, and by carrying or incorporating the property. Social organisms often have property for two reasons. First, the returns on savings and investments can accrue to relatives, including descendants. Second, social groups can divide tasks among members, so they can simultaneously guard property and forage, for example. Privatization enhances the likelihood that the benefits of cooperation will go to relatives, thus facilitating the evolution of cooperation as in Hamilton's rule or kin selection. Mutualisms often involve exchange of property and privatization of relationships. Privatization ensures the stability of such cooperation. The major transitions in evolution, both fraternal and egalitarian, generally involve the formation of private clubs with something analogous to the nonrivalrous club goods of economics. © 2014 The Association for the Study of Animal Behaviour.

Author Keywords

Evolution;  Investment;  Kin selection;  Ownership;  Privatization;  Property;  Sociality;  Territoriality

Document Type: Article

Source: Scopus

 

Glass, J.E. , Williams, E.C., Bucholz, K.K.

Psychiatric comorbidity and perceived alcohol stigma in a nationally representative sample of individuals with DSM-5 alcohol use disorder

 (2014) Alcoholism: Clinical and Experimental Research, 38 (6), pp. 1697-1705.

 

Abstract

Background: Alcohol use disorder (AUD) is among the most stigmatized health conditions and is frequently comorbid with mood, anxiety, and drug use disorders. Theoretical frameworks have conceptualized stigma-related stress as a predictor of psychiatric disorders. We described profiles of psychiatric comorbidity among people with AUD and compared levels of perceived alcohol stigma across profiles. Methods: Cross-sectional data were analyzed from a general population sample of U.S. adults with past-year DSM-5 AUD (n = 3,368) from the National Epidemiologic Survey on Alcohol and Related Conditions, which was collected from 2001 to 2005. Empirically derived psychiatric comorbidity profiles were established with latent class analysis, and mean levels of perceived alcohol stigma were compared across the latent classes while adjusting for sociodemographic characteristics and AUD severity. Results: Four classes of psychiatric comorbidity emerged within this AUD sample, including those with: (i) high comorbidity, reflecting internalizing (i.e., mood and anxiety disorders) and externalizing (i.e., antisocial personality and drug use disorders) disorders; (ii) externalizing comorbidity; (iii) internalizing comorbidity; and (iv) no comorbidity. Perceived alcohol stigma was significantly higher in those with internalizing comorbidity (but not those with high comorbidity) as compared to those with no comorbidity or externalizing comorbidity. Conclusions: Perceived stigma, as manifested by anticipations of social rejection and discrimination, may increase risk of internalizing psychiatric comorbidity. Alternatively, internalizing psychiatric comorbidity could sensitize affected individuals to perceive more negative attitudes toward them. Future research is needed to understand causal and bidirectional associations between alcohol stigma and psychiatric comorbidity. © 2014 by the Research Society on Alcoholism.

Author Keywords

Alcohol;  Alcoholism Stigma;  Latent Class Analysis;  Perceived Stigma;  Psychiatric Disorders

Document Type: Article

Source: Scopus

 

Diggs-Andrews, K.A. , Brown, J.A. , Gianino, S.M., D'Agostino McGowan, L, Rubin, J.B., Wozniak, D.F., Gutmann, D.H.

Reply

 (2014) Annals of Neurology, 75 (5), pp. 800-801.

Document Type: Letter

Source: Scopus

 

Nasiriavanaki, M. , Xia, J. , Wan, H. , Bauer, A.Q. , Culver, J.P. , Wang, L.V.

Resting-state functional connectivity imaging of the mouse brain using photoacoustic tomography

 (2014) Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 8943, art. no. 89432O, .

Abstract

Resting-state functional connectivity (RSFC) imaging is an emerging neuroimaging approach that aims to identify spontaneous cerebral hemodynamic fluctuations and their associated functional connections. Clinical studies have demonstrated that RSFC is altered in brain disorders such as stroke, Alzheimer's, autism, and epilepsy. However, conventional neuroimaging modalities cannot easily be applied to mice, the most widely used model species for human brain disease studies. For instance, functional magnetic resonance imaging (fMRI) of mice requires a very high magnetic field to obtain a sufficient signal-to-noise ratio and spatial resolution. Functional connectivity mapping with optical intrinsic signal imaging (fcOIS) is an alternative method. Due to the diffusion of light in tissue, the spatial resolution of fcOIS is limited, and experiments have been performed using an exposed skull preparation. In this study, we show for the first time, the use of photoacoustic computed tomography (PACT) to noninvasively image resting-state functional connectivity in the mouse brain, with a large field of view and a high spatial resolution. Bilateral correlations were observed in eight regions, as well as several subregions. These findings agreed well with the Paxinos mouse brain atlas. This study showed that PACT is a promising, non-invasive modality for small-animal functional brain imaging. © 2014 SPIE.

Author Keywords

Electrical Stimulation;  Functional Imaging;  Photoacoustic Tomography

Document Type: Conference Paper

Source: Scopus

 

Melin, A.D. , Young, H.C., Mosdossy, K.N., Fedigan, L.M.

Seasonality, extractive foraging and the evolution of primate sensorimotor intelligence

 (2014) Journal of Human Evolution, 71, pp. 77-86. Cited 1 time. 

Abstract

The parallel evolution of increased sensorimotor intelligence in humans and capuchins has been linked to the cognitive and manual demands of seasonal extractive faunivory. This hypothesis is attractive on theoretical grounds, but it has eluded widespread acceptance due to lack of empirical data. For instance, the effects of seasonality on the extractive foraging behaviors of capuchins are largely unknown. Here we report foraging observations on four groups of wild capuchins (Cebus capucinus) inhabiting a seasonally dry tropical forest. We also measured intra-annual variation in temperature, rainfall, and food abundance. We found that the exploitation of embedded or mechanically protected invertebrates was concentrated during periods of fruit scarcity. Such a pattern suggests that embedded insects are best characterized as a fallback food for capuchins. We discuss the implications of seasonal extractive faunivory for the evolution of sensorimotor intelligence (SMI) in capuchins and hominins and suggest that the suite of features associated with SMI, including increased manual dexterity, tool use, and innovative problem solving are cognitive adaptations among frugivores that fall back seasonally on extractable foods. The selective pressures acting on SMI are predicted to be strongest among primates living in the most seasonal environments. This model is proffered to explain the differences in tool use between capuchin lineages, and SMI as an adaptation to extractive foraging is suggested to play an important role in hominin evolution. © 2014 Elsevier Ltd.

Author Keywords

Capuchin;  Embedded foods;  Fallback food;  Faunivory;  Invertebrate

Document Type: Article

Source: Scopus

 

June 16, 2014

Barnard, N.D., Bush, A. , Ceccarelli, A., Cooper, J., de Jager, C.A., Erickson, K. , Fraser, G , Kesler, S. , Levin, S.M , Lucey, B. , Morris, M.C, Squitti, R

Dietary and lifestyle guidelines for the prevention of Alzheimer's disease

(2014) Neurobiology of Aging, . Article in Press.

Abstract

Risk of developing Alzheimer's disease is increased by older age, genetic factors, and several medical risk factors. Studies have also suggested that dietary and lifestyle factors may influence risk, raising the possibility that preventive strategies may be effective. This body of research is incomplete. However, because the most scientifically supported lifestyle factors for Alzheimer's disease are known factors for cardiovascular diseases and diabetes, it is reasonable to provide preliminary guidance to help individuals who wish to reduce their risk. At the International Conference on Nutrition and the Brain, Washington, DC, July 19-20, 2013, speakers were asked to comment on possible guidelines for Alzheimer's disease prevention, with an aim of developing a set of practical, albeit preliminary, steps to be recommended to members of the public. From this discussion, 7 guidelines emerged related to healthful diet and exercise habits. © 2014 Elsevier Inc. All rights reserved.

Author Keywords

Alzheimer's disease;  Copper;  Dementia;  Exercise;  Iron;  Nutrition;  Prevention;  Saturated fat;  Trans fatty acids;  Vitamin E

Document Type: Article in Press

Source: Scopus

 

Escallier, K.E., Nadelson, M.R., Zhou, D., Avidan, M.S.

Monitoring the brain: Processed electroencephalogram and peri-operative outcomes

(2014) Anaesthesia, . Article in Press.

Abstract

Although the brain is the target organ of general anaesthesia, the utility of intra-operative brain monitoring remains controversial. Ideally, the incorporation of brain monitoring into routine practice would promote the maintenance of an optimal depth of anaesthesia, with an ultimate goal of avoiding the negative outcomes that have been associated with inadequate or excessive anaesthesia. A variety of processed electroencephalogram devices exist, of which the bispectral index is the most widely used, particularly in the research setting. Whether such devices prove to be useful will depend not only on their ability to influence anaesthetic management but also on whether the changes they promote can actually affect clinically important outcomes. This review highlights the evidence for the role of bispectral index monitoring, in particular, in guiding anaesthetic management and influencing clinical outcomes, specifically intra-operative awareness, measures of early recovery, mortality and neurocognitive outcomes. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

Document Type: Article in Press

Source: Scopus

 

Chung, S.S., Fakhoury, T.A., Hogan, R.E., Nagaraddi, V.N., Blatt, I., Lawson, B., Arnold, S., Anders, B., Clark, A.M., Laine, D., Meadows, R.S , Halvorsen, M.B.

Once-daily USL255 as adjunctive treatment of partial-onset seizures: Randomized phase III study

(2014) Epilepsia, . Article in Press.

Abstract

Objective: To evaluate the efficacy and safety of USL255, Qudexy™ XR (topiramate) extended-release capsules, as an adjunctive treatment for refractory partial-onset seizures (POS) in adults taking one to three concomitant antiepileptic drugs. Methods: In this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once-daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥50% reduction in seizure frequency). Seizure freedom was also assessed. Safety (adverse events, clinical and laboratory findings), as well as treatment effects on quality of life (QOLIE-31-P) and clinical global impression of change (CGI-C), were evaluated. Results: Across the entire 11-week treatment phase, USL255 significantly reduced the median percent seizure frequency and significantly improved responder rate compared with placebo. Efficacy over placebo was observed early in treatment, in patients with highly refractory POS, and in those with the most debilitating seizure types (i.e., complex partial, partial secondarily generalized). USL255 was safe and generally well tolerated with a low incidence of neurocognitive adverse events. USL255 was associated with significant clinical improvement without adversely affecting quality of life. Significance: The PREVAIL phase III clinical study demonstrated that once-daily USL255 (200 mg/day) significantly improved seizure control and was safe and generally well tolerated with few neurocognitive side effects. © 2014 The Authors.

Author Keywords

Antiepileptic drug;  Epilepsy;  Extended release;  Topiramate

Document Type: Article in Press

Source: Scopus

 

Duncan, A.E.a b c , Munn-Chernoff, M.A.b c , Hudson, D.L.a , Eschenbacher, M.A.f , Agrawal, A.b c , Grant, J.D.b c , Nelson, E.C.b c , Waldron, M.b d , Glowinski, A.L.b c , Sartor, C.E.b e , Bucholz, K.K.b c , Madden, P.A.F.b c , Heath, A.C.b c

Genetic and Environmental Risk for Major Depression in African-American and European-American Women

(2014) Twin Research and Human Genetics, . Article in Press.

Abstract

It is unknown whether there are racial differences in the heritability of major depressive disorder (MDD) because most psychiatric genetic studies have been conducted in samples comprised largely of white non-Hispanics. To examine potential differences between African-American (AA) and European-American (EA) young adult women in (1) Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) MDD prevalence, symptomatology, and risk factors, and (2) genetic and/or environmental liability to MDD, we analyzed data from a large population-representative sample of twins ascertained from birth records (n = 550 AA and n = 3226 EA female twins) aged 18-28 years at the time of MDD assessment by semi-structured psychiatric interview. AA women were more likely to have MDD risk factors; however, there were no significant differences in lifetime MDD prevalence between AA and EA women after adjusting for covariates (odds ratio = 0.88, 95% confidence interval [CI]: 0.67-1.15). Most MDD risk factors identified among AA women were also associated with MDD at similar magnitudes among EA women. Although the MDD heritability point estimate was higher among AA women than EA women in a model with paths estimated separately by race (56%, 95% CI: 29-78% vs. 41%, 95% CI: 29-52%), the best fitting model was one in which additive genetic and non-shared environmental paths for AA and EA women were constrained to be equal (A = 43%, 33-53% and E = 57%, 47-67%). In spite of a marked elevation in the prevalence of environmental risk exposures related to MDD among AA women, there were no significant differences in lifetime prevalence or heritability of MDD between AA and EA young women. Copyright © The Authors 2014.

Author Keywords

African-American;  depression;  heritability;  race;  twins;  women

Document Type: Article in Press

Source: Scopus

 

Mitra, A., Snyder, A.Z., Hacker, C.D., Raichle, M.E.

Lag structure in resting-state fMRI

(2014) Journal of Neurophysiology, 111 (11), pp. 2374-2391.

 

Abstract

The discovery that spontaneous fluctuations in blood oxygen level-dependent (BOLD) signals contain information about the functional organization of the brain has caused a paradigm shift in neuroimaging. It is now well established that intrinsic brain activity is organized into spatially segregated resting-state networks (RSNs). Less is known regarding how spatially segregated networks are integrated by the propagation of intrinsic activity over time. To explore this question, we examined the latency structure of spontaneous fluctuations in the fMRI BOLD signal. Our data reveal that intrinsic activity propagates through and across networks on a timescale of ~1 s. Variations in the latency structure of this activity resulting from sensory state manipulation (eyes open vs. closed), antecedent motor task (button press) performance, and time of day (morning vs. evening) suggest that BOLD signal lags reflect neuronal processes rather than hemodynamic delay. Our results emphasize the importance of the temporal structure of the brain's spontaneous activity. © 2014 the American Physiological Society.

Author Keywords

Dynamics;  fMRI;  Functional connectivity;  Resting state

Document Type: Article

Source: Scopus

 

Pachman, D.R.a , Watson, J.C.b , Lustberg, M.B.c , Wagner-Johnston, N.D.d , Chan, A.e , Broadfield, L.f , Cheung, Y.T.e , Steer, C.g , Storey, D.J.h , Chandwani, K.D.i , Paice, J.j , Jean-Pierre, P.k , Oh, J.l , Kamath, J.m , Fallon, M.n , Strik, H.o , Koeppen, S.p , Loprinzi, C.L.a

Management options for established chemotherapy-induced peripheral neuropathy

(2014) Supportive Care in Cancer, . Article in Press.

 

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a variety of chemotherapeutic agents. Clinicians are cognizant of the negative impact of CIPN on cancer treatment outcomes and patients' psychosocial functioning and quality of life. In an attempt to alleviate this problem, clinicians and patients try various therapeutic interventions, despite limited evidence to support efficacy of these treatments. The rationale for such use is mostly based on the evidence for the treatment options in non-CIPN peripheral neuropathy syndromes, as this area is more robustly studied than is CIPN treatment. In this manuscript, we examine the existing evidence for both CIPN and non-CIPN treatments and develop a summary of the best available evidence with the aim of developing a practical approach to the treatment of CIPN, based on available literature and clinical practice experience. © 2014 Springer-Verlag Berlin Heidelberg.

Author Keywords

Chemotherapy-induced peripheral neuropathy;  CIPN;  Neuropathy

Document Type: Article in Press

Source: Scopus

 

Cho, Y. , Di Liberto, V. , Carlin, D. , Abe, N., Li, K.H. , Burlingame, A.L., Guan, S., Michaelevski, I. , Cavalli, V

Syntaxin13 expression is regulated by mammalian target of rapamycin (mTOR) in injured neurons to promote axon regeneration

(2014) Journal of Biological Chemistry, 289 (22), pp. 15820-15832.

Abstract

Background: Axon regeneration following nerve injury depends on activation of mTOR. Results: Nerve injury increases the expression of syntaxin13 in an mTOR-dependent manner. Conclusion: Injury-induced synthesis of syntaxin13 is important for axon regeneration. Significance: Learning which proteins are synthesized via mTOR in injured nerves is crucial to our understanding of regenerative mechanisms in peripheral neurons. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Document Type: Article

Source: Scopus

 

Padakanti, P.K., Zhang, X., Li, J. , Parsons, S.M , Perlmutter, J.S. , Tu, Z.

Syntheses and Radiosyntheses of Two Carbon-11 Labeled Potent and Selective Radioligands for Imaging Vesicular Acetylcholine Transporter

(2014) Molecular Imaging and Biology, . Article in Press.

Abstract

Purpose The vesicular acetylcholine transporter (VAChT) is a specific biomarker for imaging presynaptic cholinergic neurons. The syntheses and C-11 labeling of two potent enantiopure VAChT inhibitors are reported here. Procedures Two VAChT inhibitors, (±)-2 and (±)-6, were successfully synthesized. A chiral HPLC column was used to resolve the enantiomers from each corresponding racemic mixture for in vitro characterization. The radiosyntheses of (-)-[11C]2 and (-)-[11C]6 from the corresponding desmethyl phenol precursor was accomplished using [11C]methyl iodide or [11C]methyl triflate, respectively. Results The synthesis of (-)-[11C]2 was accomplished with 40-50 % radiochemical yield (decay-corrected), SA &gt; 480 GBq/μmol (EOB), and radiochemical purity &gt;99 %. Synthesis of (-)-[11C]6 was accomplished with 5-10 % yield, SA &gt; 140 GBq/μmol (EOB), and radiochemical purity &gt;97 %. The radiosynthesis and dose formulation of each tracer was completed in 55-60 min. Conclusions Two potent enantiopure VAChT ligands were synthesized and 11C-labeled with good radiochemical yield and specific activity. © 2014 World Molecular Imaging Society.

Document Type: Article in Press

Source: Scopus

 

Lilienthal, L., Hale, S., Myerson, J.

The effects of environmental support and secondary tasks on visuospatial working memory

(2014) Memory & Cognition, . Article in Press.

 

Abstract

In the present experiments, we examined the effects of environmental support on participants' ability to rehearse locations and the role of such support in the effects of secondary tasks on memory span. In Experiment 1, the duration of interitem intervals and the presence of environmental support for visuospatial rehearsal (i.e., the array of possible memory locations) during the interitem intervals were both manipulated across four tasks. When support was provided, memory spans increased as the interitem interval durations increased, consistent with the hypothesis that environmental support facilitates rehearsal. In contrast, when environmental support was not provided, spans decreased as the duration of the interitem intervals increased, consistent with the hypothesis that visuospatial memory representations decay when rehearsal is impeded. In Experiment 2, the ratio of interitem interval duration to intertrial interval duration was kept the same on all four tasks, in order to hold temporal distinctiveness constant, yet forgetting was still observed in the absence of environmental support, consistent with the decay hypothesis. In Experiment 3, the effects of impeding rehearsal were compared to the effects of verbal and visuospatial secondary processing tasks. Forgetting of locations was greater when presentation of to-be-remembered locations alternated with the performance of a secondary task than when rehearsal was impeded by the absence of environmental support. The greatest forgetting occurred when a secondary task required the processing visuospatial information, suggesting that in addition to decay, both domain-specific and domain-general effects contribute to forgetting on visuospatial working memory tasks. © 2014 Psychonomic Society, Inc.

 

Author Keywords

Decay;  Environmental support;  Interference;  Secondary tasks;  Visuospatial working memory

Document Type: Article in Press

Source: Scopus

 

Williams, J.L. , Holman, D.W. , Klein, R.S.

Chemokines in the balance: Maintenance of homeostasis and protection at CNS barriers

(2014) Frontiers in Cellular Neuroscience, 8 (MAY), art. no. 154, .

Abstract

In the adult central nervous system (CNS), chemokines and their receptors are involved in developmental, physiological and pathological processes. Although most lines of investigation focus on their ability to induce the migration of cells, recent studies indicate that chemokines also promote cellular interactions and activate signaling pathways that maintain CNS homeostatic functions. Many homeostatic chemokines are expressed on the vasculature of the blood brain barrier (BBB) including CXCL12, CCL19, CCL20, and CCL21. While endothelial cell expression of these chemokines is known to regulate the entry of leukocytes into the CNS during immunosurveillance, new data indicate that CXCL12 is also involved in diverse cellular activities including adult neurogenesis and neuronal survival, having an opposing role to the homeostatic chemokine, CXCL14, which appears to regulate synaptic inputs to neural precursors. Neuronal expression of CX3CL1, yet another homeostatic chemokine that promotes neuronal survival and communication with microglia, is partly regulated by CXCL12. Regulation of CXCL12 is unique in that it may regulate its own expression levels via binding to its scavenger receptor CXCR7/ACKR3. In this review, we explore the diverse roles of these and other homeostatic chemokines expressed within the CNS, including the possible implications of their dysfunction as a cause of neurologic disease.

Author Keywords

Blood brain barrier;  Central nervous system;  Chemokines;  Choroid plexus;  Homeostasis;  Meninges;  Neurogenesis;  Vasculature

Document Type: Review

Source: Scopus

 

Padakanti, P.K. , Zhang, X. , Jin, H. , Cui, J. , Wang, R. , Li, J. , Flores, H.P. , Parsons, S.M. , Perlmutter, J.S. , Tu, Z.

In Vitro and In Vivo Characterization of Two C-11-Labeled PET Tracers for Vesicular Acetylcholine Transporter

(2014) Molecular Imaging and Biology, . Article in Press.

 

Abstract

Purpose The vesicular acetylcholine transporter (VAChT) is a specific biomarker for imaging presynaptic cholinergic neurons. Herein, two potent and selective 11C-labeled VAChT inhibitors were evaluated in rodents and nonhuman primates for imaging VAChT in vivo. Procedures For both (-)-[11C]2 and (-)-[11C]6, biodistribution, autoradiography, and metabolism studies were performed in male Sprague Dawley rats. Positron emission tomography (PET) brain studies with (-)-[11C]2 were performed in adult male cynomolgus macaques; 2 h dynamic data was acquired, and the regions of interest were drawn by co-registration of the PET images with the MRI. Results The resolved enantiomers (-)-2 and (-)-6 were very potent and selective for VAChT in vitro (Ki &lt; 5 nM for VAChT with &gt;35-fold selectivity for VAChT vs. σ receptors); both radioligands, (-)-[11C]2 and (-)-[11C]6, demonstrated high accumulation in the VAChT-enriched striatum of rats. (-)-[11C]2 had a higher striatum to cerebellum ratio of 2.4-fold at 60 min; at 30 min, striatal uptake reached 0.550 ± 0.086 %ID/g. Uptake was also specific and selective; following pretreatment with (±)-2, striatal uptake of (-)-[11C]2 in rats at 30 min decreased by 50 %, while pretreatment with a potent sigma ligand had no significant effect on striatal uptake in rats. In addition, (-)-[11C]2 displayed favorable in vivo stability in rat blood and brain. PET studies of (-)-[11C]2 in nonhuman primates indicate that it readily crosses the blood-brain barrier (BBB) and provides clear visualization of the striatum; striatal uptake reaches the maximum at 60 min, at which time the target to nontarget ratio reached ~2-fold. Conclusions The radioligand (-)-[11C]2 has high potential to be a suitable PET radioligand for imaging VAChT in the brain of living subjects. © 2014 World Molecular Imaging Society.

Document Type: Article in Press

Source: Scopus

 

Abernathy, D.G., Yoo, A.S.

MicroRNA-dependent genetic networks during neural development

(2014) Cell and Tissue Research, . Article in Press.

 Abstract

The development of the structurally and functionally diverse mammalian nervous system requires the integration of numerous levels of gene regulation. Accumulating evidence suggests that microRNAs are key mediators of genetic networks during neural development. Importantly, microRNAs are found to regulate both feedback and feedforward loops during neural development leading to large changes in gene expression. These repressive interactions provide an additional mechanism that facilitates the establishment of complexity within the nervous system. Here, we review studies that have enabled the identification of microRNAs enriched in the brain and discuss the way that genetic networks in neural development depend on microRNAs. © 2014 Springer-Verlag Berlin Heidelberg.

 

Author Keywords

Brain;  Direct reprogramming;  Epigenetics;  Genetic networks;  MicroRNAs;  Neural development

Document Type: Article in Press

Source: Scopus

 

Culican, S.M., Rupp, J.D., Margolis, T.P.

Retaining clinician-scientists: Nature versus nurture

(2014) Investigative Ophthalmology and Visual Science, 55 (5), pp. 3219-3222.

 

Abstract

In their IOVS article "Rejuvenating Clinician-Scientist Training" (published March 28, 2014), Balamurali Ambati and Judd Cahoon rightly point out the dearth of new clinician-scientists in ophthalmology. Within the context of their suggestions for increasing the number of successful clinician-scientists, they claim that the traditional MD-PhD training programs and K awards have failed to produce individuals who will carry on the important work of clinically relevant research that will improve patients' lives and sight. In this response we present data, including information on the career paths of graduates of the Washington University ophthalmology residency, that call into question the presumed failure of MD-PhD and K award programs and show that, in fact, graduates of these programs are more likely to succeed as clinician-scientists than are their peers who have not trained in such scientifically rigorous environments. We propose that, rather than a failure of early training programs, it may be obstacles that arise later in training and among junior faculty that prevent promising careers from reaching maturity. Funding, one rather large obstacle, takes the form of imbalanced start-up monies, less National Institutes of Health (NIH) funding awarded to young investigators, and study section composition that may work against those with clinically driven questions. We also explore the challenges faced in the culture surrounding residency and fellowship training. We agree with Ambati and Cahoon that there needs to be more innovation in the way training programs are structured, but we believe that the evidence supports supplementing the current model rather than scrapping it and starting over with unproven initiatives. The data on training programs supports the contention that those who have already made substantial investment and commitment to the clinicianscientist pathway through participation in MSTP or K training programs are the most likely to succeed on this career trajectory. To muffle the siren song of private practice and retain those best prepared for the clinician-scientist pathway requires additional investment as their careers mature through protected research time, mentorship, and advocacy. © 2014 The Association for Research in Vision and Ophthalmology, Inc.

 

Author Keywords

Career development;  Clinician-scientist;  Education

Document Type: Article

Source: Scopus

 

Rachakonda, T. , Shimony, J.S. , Coalson, R.S., Lieu, J.E.C.

Diffusion tensor imaging in children with unilateral hearing loss: A pilot study

(2014) Frontiers in Systems Neuroscience, 8 (MAY), art. no. 87, .

 

Abstract

Objective: Language acquisition was assumed to proceed normally in children with unilateral hearing loss (UHL) since they have one functioning ear. However, children with UHL score poorly on speech-language tests and have higher rates of educational problems compared to normal hearing (NH) peers. Diffusion tensor imaging (DTI) is an imaging modality used to measure microstructural integrity of brain white matter. The purpose of this pilot study was to investigate differences in fractional anisotropy (FA) and mean diffusivity (MD) in hearing- and non-hearing-related structures in the brain between children with UHL and their NH siblings. Study Design: Prospective observational cohort. Setting: Academic medical center. Subjects and Methods: Sixty one children were recruited, tested and imaged. Twenty nine children with severe-to-profound UHL were compared to 20 siblings with NH using IQ and oral language testing, and MRI with DTI. Twelve children had inadequate MRI data. Parents provided demographic data and indicated whether children had a need for an individualized educational program (IEP) or speech therapy (ST). DTI parameters were measured in auditory and non-auditory regions of interest (ROIs). Between-group comparisons were evaluated with non-parametric tests. Results: Lower FA of left lateral lemniscus was observed for children with UHL compared to their NH siblings, as well as trends toward differences in other auditory and non-auditory regions. Correlation analyses showed associations between several DTI parameters and outcomes in children with UHL. Regression analyses revealed relationships between educational outcome variables and several DTI parameters, which may provide clinically useful information for guidance of speech therapy. Discussion/Conclusion: Our data suggests that white matter microstructural patterns in several brain regions are preserved despite unilateral rather than bilateral auditory input which contrasts with findings in patients with bilateral hearing loss. © 2014 Rachakonda, Shimony, Coalson and Lieu.

Author Keywords

Children;  Diffusion tensor imaging;  Hearing loss;  Magnetic resonance imaging;  Unilateral hearing loss

Document Type: Article

Source: Scopus

 

Putnam, A.L., Wahlheim, C.N., Jacoby, L.L.

Memory for flip-flopping: Detection and recollection of political contradictions

(2014) Memory & Cognition, . Article in Press.

 

Abstract

During political campaigns, candidates often change their positions on controversial issues. Does changing positions create confusion and impair memory for a politician's current position? In 3 experiments, two political candidates held positions on controversial issues in two debates. Across the debates, their positions were repeated, changed, or held only in the second debate (control). Relative to the control condition, recall of the most recent position on issues was enhanced when change was detected and recollected, whereas recall was impaired when change was not recollected. Furthermore, examining the errors revealed that subjects were more likely to intrude a Debate 1 response than to recall a blend of the two positions, and that recollecting change decreased Debate 1 intrusions. We argue that detecting change produces a recursive representation that embeds the original position in memory along with the more recent position. Recollecting change then enhances memory for the politician's positions and their order of occurrence by accessing the recursive trace. © 2014 Psychonomic Society, Inc.

 

Author Keywords

Change detection;  Contradiction;  Politics;  Proactive interference;  Recursive reminding

Document Type: Article in Press

Source: Scopus

 

Huff, M.J. , Bodner, G.E. , Fawcett, J.M

Effects of distinctive encoding on correct and false memory:A meta-analytic review of costs and benefits and their origins in the DRM paradigm

(2014) Psychonomic Bulletin & Review, . Article in Press.

 

Abstract

We review and meta-analyze how distinctive encoding alters encoding and retrieval processes and, thus, affects correct and false recognition in the Deese-Roediger-McDermott (DRM) paradigm. Reductions in false recognition following distinctive encoding (e.g., generation), relative to a nondistinctive read-only control condition, reflected both impoverished relational encoding and use of a retrieval-based distinctiveness heuristic. Additional analyses evaluated the costs and benefits of distinctive encoding in within-subjects designs relative to between-group designs. Correct recognition was design independent, but in a within design, distinctive encoding was less effective at reducing false recognition for distinctively encoded lists but more effective for nondistinctively encoded lists. Thus, distinctive encoding is not entirely "cost free" in a within design. In addition to delineating the conditions that modulate the effects of distinctive encoding on recognition accuracy, we discuss the utility of using signal detection indices of memory information and memory monitoring at test to separate encoding and retrieval processes. © 2014 The Author(s).

 

Author Keywords

Distinctiveness;  DRM paradigm;  Encoding;  Meta-analysis;  Recognition;  Retrieval

Document Type: Article in Press

Source: Scopus

 

Nestojko, J.F. , Bui, D.C. , Kornell, N. , Bjork, E.L

Expecting to teach enhances learning and organization of knowledge in free recall of text passages

(2014) Memory & Cognition, . Article in Press.

 Abstract

The present research assessed the potential effects of expecting to teach on learning. In two experiments, participants studied passages either in preparation for a later test or in preparation for teaching the passage to another student who would then be tested. In reality, all participants were tested, and no one actually engaged in teaching. Participants expecting to teach produced more complete and better organized free recall of the passage (Experiment 1) and, in general, correctly answered more questions about the passage than did participants expecting a test (Experiment 1), particularly questions covering main points (Experiment 2), consistent with their having engaged in more effective learning strategies. Instilling an expectation to teach thus seems to be a simple, inexpensive intervention with the potential to increase learning efficiency at home and in the classroom. © 2014 Psychonomic Society, Inc.

 

Author Keywords

Memory;  Recall;  Text processing

Document Type: Article in Press

Source: Scopus

 

Hirose, K. , Li, S.-Z , Ohlemiller, K.K., Ransohoff, R.M.

Systemic Lipopolysaccharide Induces Cochlear Inflammation and Exacerbates the Synergistic Ototoxicity of Kanamycin and Furosemide

(2014) Journal of the Association for Research in Otolaryngology, . Article in Press.

 

Abstract

Aminoglycoside antibiotics are highly effective agents against gram-negative bacterial infections, but they cause adverse effects on hearing and balance dysfunction as a result of toxicity to hair cells of the cochlea and vestibular organs. While ototoxicity has been comprehensively studied, the contributions of the immune system, which controls the host response to infection, have not been studied in antibiotic ototoxicity. Recently, it has been shown that an inflammatory response is induced by hair cell injury. In this study, we found that lipopolysaccharide (LPS), an important component of bacterial endotoxin, when given in combination with kanamycin and furosemide, augmented the inflammatory response to hair cell injury and exacerbated hearing loss and hair cell injury. LPS injected into the peritoneum of experimental mice induced a brisk cochlear inflammatory response with recruitment of mononuclear phagocytes into the spiral ligament, even in the absence of ototoxic agents. While LPS alone did not affect hearing, animals that received LPS prior to ototoxic agents had worse hearing loss compared to those that did not receive LPS pretreatment. The poorer hearing outcome in LPS-treated mice did not correlate to changes in endocochlear potential. However, LPS-treated mice demonstrated an increased number of CCR2+ inflammatory monocytes in the inner ear when compared with mice treated with ototoxic agents alone. We conclude that LPS and its associated inflammatory response are harmful to the inner ear when coupled with ototoxic medications and that the immune system may contribute to the final hearing outcome in subjects treated with ototoxic agents. © 2014 Association for Research in Otolaryngology.

 

Author Keywords

cochlea;  inflammation;  LPS;  macrophage;  monocyte;  ototoxicity

Document Type: Article in Press

Source: Scopus

 

Admon, R. , Nickerson, L.D. , Dillon, D.G. , Holmes, A.J. , Bogdan, R. , Kumar, P. , Dougherty, D.D. , Iosifescu, D.V , Mischoulon, D. , Fava, M. , Pizzagalli, D.A.

Dissociable cortico-striatal connectivity abnormalities in major depression in response to monetary gains and penalties

(2014) Psychological Medicine, . Article in Press.

Abstract

Background: Individuals with major depressive disorder (MDD) are characterized by maladaptive responses to both positive and negative outcomes, which have been linked to localized abnormal activations in cortical and striatal brain regions. However, the exact neural circuitry implicated in such abnormalities remains largely unexplored. Method: In this study 26 unmedicated adults with MDD and 29 matched healthy controls (HCs) completed a monetary incentive delay task during functional magnetic resonance imaging (fMRI). Psychophysiological interaction (PPI) analyses probed group differences in connectivity separately in response to positive and negative outcomes (i.e. monetary gains and penalties). Results: Relative to HCs, MDD subjects displayed decreased connectivity between the caudate and dorsal anterior cingulate cortex (dACC) in response to monetary gains, yet increased connectivity between the caudate and a different, more rostral, dACC subregion in response to monetary penalties. Moreover, exploratory analyses of 14 MDD patients who completed a 12-week, double-blind, placebo-controlled clinical trial after the baseline fMRI scans indicated that a more normative pattern of cortico-striatal connectivity pre-treatment was associated with greater improvement in symptoms 12 weeks later. Conclusions: These results identify the caudate as a region with dissociable incentive-dependent dACC connectivity abnormalities in MDD, and provide initial evidence that cortico-striatal circuitry may play a role in MDD treatment response. Given the role of cortico-striatal circuitry in encoding action-outcome contingencies, such dysregulated connectivity may relate to the prominent disruptions in goal-directed behavior that characterize MDD. Copyright © Cambridge University Press 2014.

 

Author Keywords

Caudate;  cingulate;  depression;  PPI;  reward;  treatment prediction

Document Type: Article in Press

Source: Scopus

 

van den Berg, S.M. , de Moor, M.H.M. , McGue, M., Pettersson, E., Terracciano, A , Verweij, K.J.H , Amin, N , Derringer, J. , Esko, T. , van Grootheest, G. , Hansell, N.K. , Huffman, J. , Konte, B. , Lahti, J. , Luciano, M. , Matteson, L.K. , Viktorin, A. , Wouda, J., Agrawal, A., Allik, J., Bierut, L , Broms, U. , Campbell, H , Smith, G.D , Eriksson, J.G , Ferrucci, L , Franke, B. , Fox, J.-P., de Geus, E.J.C. , Giegling, , Gow, A.J. , Grucza, R. , Hartmann, A.M , Heath, A.C , Heikkilä, K. , Iacono, W.G , Janzing, J. , Jokela, M. , Kiemeney, L. , Lehtimäki, T. , Madden, P.A.F. , Magnusson, P.K.E , Northstone, K. , Nutile, T. , Ouwens, K.G. , Palotie, A., Pattie, A , Pesonen, A.-K. , Polasek, O. , Pulkkinen, L. , Pulkki-Råback, L. , Raitakari, O.T., Realo, A. , Rose, R.J. , Ruggiero, D. , Seppälä,  , Slutske, W.S. , Smyth, D.C. , Sorice, R. , Starr, J.M. , Sutin, A.R , Tanaka, T. , Verhagen, J. , Vermeulen, S. , Vuoksimaa, E. , Widen, E. Willemsen, G. , Wright, M.J., Zgaga, L , Rujescu, D. , Metspalu, A , Wilson, J.F , Ciullo, M. , Hayward, C , Rudan, I., Deary, I.J., Räikkönen, K. , Arias Vasquez, A. , Costa, P.T. , Keltikangas-Järvinen, L. , van Duijn, C.M , Penninx, B.W.J.H. , Krueger, R.F , Evans, D.M., Kaprio, J. , Pedersen, N.L. , Martin, N.G., Boomsma, D.I.

Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory

(2014) Behavior Genetics, . Article in Press.

 

Abstract

Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized. © 2014 The Author(s).

 

Author Keywords

Consortium;  Genome-wide association studies;  Item-Response Theory;  Measurement;  Meta-analysis;  Personality

Document Type: Article in Press

 Source: Scopus