"Distinct phase-amplitude couplings distinguish cognitive processes in human attention" (2018) NeuroImage
Distinct phase-amplitude couplings distinguish cognitive processes in human attention
(2018) NeuroImage, 175, pp. 111-121.
Chacko, R.V., Kim, B., Jung, S.W., Daitch, A.L., Roland, J.L., Metcalf, N.V., Corbetta, M., Shulman, G.L., Leuthardt, E.C.
Abstract
Spatial attention is the cognitive function that coordinates the selection of visual stimuli with appropriate behavioral responses. Recent studies have reported that phase-amplitude coupling (PAC) of low and high frequencies covaries with spatial attention, but differ on the direction of covariation and the frequency ranges involved. We hypothesized that distinct phase-amplitude frequency pairs have differentiable contributions during tasks that manipulate spatial attention. We investigated this hypothesis with electrocorticography (ECoG) recordings from participants who engaged in a cued spatial attention task. To understand the contribution of PAC to spatial attention we classified cortical sites by their relationship to spatial variables or behavioral performance. Local neural activity in spatial sites was sensitive to spatial variables in the task, while local neural activity in behavioral sites correlated with reaction time. We found two PAC frequency clusters that covaried with different aspects of the task. During a period of cued attention, delta-phase/high-gamma (DH) PAC was sensitive to cue direction in spatial sites. In contrast, theta-alpha-phase/beta-low-gamma-amplitude (TABL) PAC robustly correlated with future reaction times in behavioral sites. Finally, we investigated the origins of TABL PAC and found it corresponded to behaviorally relevant, sharp waveforms, which were also coupled to a low frequency rhythm. We conclude that TABL and DH PAC correspond to distinct mechanisms during spatial attention tasks and that sharp waveforms are elements of a coupled dynamical process. © 2018 The Authors
Author Keywords
Cued attention; Phase-amplitude coupling; Reaction time; Sharp waves
Document Type: Article
Source: Scopus
Access Type: Open Access
"Education-based disparities in knowledge of novel health risks: The case of knowledge gaps in HIV risk perceptions" (2018) British Journal of Health Psychology
Education-based disparities in knowledge of novel health risks: The case of knowledge gaps in HIV risk perceptions
(2018) British Journal of Health Psychology, 23 (2), pp. 420-435.
Kiviniemi, M.T., Orom, H., Waters, E.A., McKillip, M., Hay, J.L.
Abstract
Objective: Risk perception is a key determinant of preventive health behaviour, but when asked, some individuals indicate they do not know their health risk. Low education is associated with both lack of knowledge about health risk and with the persistence and exacerbation of gaps in knowledge about health issues. This study uses the context of an emerging infectious disease threat to explore the hypothesis that the education-don’t know risk relation results from differences in knowledge about the health issue of interest. Specifically, we examine whether patterns of change over time follow theoretical predictions that disparities in risk knowledge would increase over time in less educated sectors of the population (knowledge gap hypothesis). Design: Secondary analysis of population-representative behavioural surveillance survey. Method: We analysed data from the 1993 to 2000 Behavior Risk Factor Surveillance System surveys, which measured education and perceived HIV/AIDS risk in a population sample collected separately in each survey year; don’t know responses were coded. Results: In each year, individuals with higher education were less likely to respond don’t know. The absolute prevalence of don’t know responding dropped over time; nonetheless, there was an increase over time in the magnitude of the pattern of lower education being associated with greater don’t know responding. Conclusions: We found support for the knowledge gap hypothesis. Over time, populations with greater education gained more knowledge about their HIV risk than populations with lower education. Results highlight the need to carefully consider health communication strategies to reach and address those individuals with low education and health knowledge. Statement of contribution What is already known on this subject? A meaningful potion of the population answers ‘don’t know’ when asked to report their risk for health problems, indicating a lack of risk perception in the domain. Previous studies have shown that level of education is associated with don’t know responding – those with lower educational attainment are more likely to respond don’t know. The education-don’t know responding relation suggests that lack of health information and health domain knowledge might be a factor in lacking risk perception, but this mechanism has not been previously tested. What does this study add? Patterns of changes in don’t know responding over time as population-level knowledge of a health risk increase are consistent with the health information/health knowledge hypothesis outlined above. As population knowledge of HIV/AIDS risk in the United States increased over time (indicated by declining overall rates of don’t know responses), the relation of education level to don’t know responding actually became stronger. The pattern of change over time is the classic ‘knowledge gap hypothesis’ pattern, which has not been previously demonstrated for knowledge of personal health risk. The knowledge gap response pattern supports the health information/health knowledge hypothesis. © 2018 The British Psychological Society
Author Keywords
don’t know responding; health knowledge; knowledge gap hypothesis; risk perception
Document Type: Article
Source: Scopus
"Disease-Modifying Treatment in Progressive Multiple Sclerosis" (2018) Current Treatment Options in Neurology
Disease-Modifying Treatment in Progressive Multiple Sclerosis
(2018) Current Treatment Options in Neurology, 20 (5), art. no. 12, .
Ciotti, J.R., Cross, A.H.
Abstract
Purpose of review: Multiple sclerosis (MS) is an immune-mediated disorder that affects the central nervous system (CNS), often first affecting people in early adulthood. Although most MS patients have a relapsing-remitting course (RRMS) at disease onset, a substantial proportion later develop chronic progression, termed secondary progressive MS (SPMS). Approximately 10% of MS patients experience chronic progression from disease onset, termed primary progressive multiple sclerosis (PPMS). Although several disease-modifying treatment (DMT) options exist for relapsing forms of this disease, DMT options are few for progressive MS (PPMS and SPMS). Herein, we strive to define progressive MS, review major clinical trials aimed at progressive MS, and delineate potential strategies in the management of progressive MS. Recent findings: In 2017, the first DMT for PPMS, the B lymphocyte-depleting monoclonal antibody, ocrelizumab, came to market. Ocrelizumab reduced 12-week confirmed disability progression (CDP) by 24% versus placebo. Siponimod, a selective sphingosine-1-phosphate receptor modulator, reduced 3-month CDP by 21% versus placebo in SPMS. Ibudilast slowed brain atrophy in PPMS and SPMS patients in a multicenter phase 2b study. Smaller early phase studies of alpha-lipoic acid and simvastatin each found slowing of rate of whole brain atrophy in SPMS patients. Summary: Reasons now exist for optimism in the search for DMTs for progressive MS. It remains a challenge to identify outcome measures that accurately reflect the underlying pathology in progressive MS, which is less inflammatory and more degenerative than RRMS. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.
Author Keywords
Disease-modifying therapy; Neuroprotection; Progressive multiple sclerosis; Remyelination
Document Type: Review
Source: Scopus
"High constitutive activity accounts for the combination of enhanced direct activation and reduced potentiation in mutated GABAA receptors" (2018) Molecular Pharmacology
High constitutive activity accounts for the combination of enhanced direct activation and reduced potentiation in mutated GABAA receptors
(2018) Molecular Pharmacology, 93 (5), pp. 468-476.
Germann, A.L., Shin, D.J., Kuhrau, C.R., Johnson, A.D., Evers, A.S., Akk, G.
Abstract
GABAA receptors activated by the transmitter GABA are potentiated by several allosterically acting drugs, including the intravenous anesthetic propofol. Propofol can also directly activate the receptor, albeit at higher concentrations. Previous functional studies have identified amino acid residues whose substitution reduces potentiation of GABA-activated receptors by propofol while enhancing the ability of propofol to directly activate the receptor. One interpretation of such observations is that the mutation has specific effects on the sites or processes involved in potentiation or activation. We show here that divergent effects on potentiation and direct activation can be mediated by increased constitutive open probability in the mutant receptor without any specific effect on the interactions between the allosteric drug and the receptor. By simulating GABAA receptor activity using the concerted transition model, we demonstrate that the predicted degree of potentiation is reduced as the level of constitutive activity increases. The model further predicts that a potentiating effect of an allosteric modulator is a computable value that depends on the level of constitutive activity, the amplitude of the response to the agonist, and the amplitude of the direct activating response to the modulator. Specific predictions were confirmed by electrophysiological data from the binary a1b3 and concatemeric ternary b2a1g2L1b2a1 GABAA receptors. The corollaries of reduced potentiation due to increased constitutive activity are isobolograms that conform to simple additivity and a loss of separation between the concentration-response relationships for direct activation and potentiation. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.
Document Type: Article
Source: Scopus
"Early infectious exposures are not associated with increased risk of pediatric-onset multiple sclerosis" (2018) Multiple Sclerosis and Related Disorders
Early infectious exposures are not associated with increased risk of pediatric-onset multiple sclerosis
(2018) Multiple Sclerosis and Related Disorders, 22, pp. 103-107.
Suleiman, L., Waubant, E., Aaen, G., Belman, A., Benson, L., Candee, M., Chitnis, T., Gorman, M., Goyal, M., Greenberg, B., Harris, Y., Hart, J., Kahn, I., Krupp, L., Lotze, T., Mar, S., Moodley, M., Ness, J., Nourbakhsh, B., Rensel, M., Rodriguez, M., Rose, J., Rubin, J., Schreiner, T., Tillema, J.-M., Waldman, A., Weinstock-Guttman, B., Casper, T.C., Waltz, M., Graves, J.S., on behalf of the Network of Pediatric Multiple Sclerosis Centers.
Abstract
Objective: We sought to determine if early infectious exposures such as daycare, early use of antibiotics, vaccinations and other germ exposures including pacifier use and playing on grass are associated with multiple sclerosis (MS) risk in children. Methods: This was a case-control study of children with MS or clinically isolated syndrome (CIS) and healthy controls enrolled at sixteen clinics participating in the US Network of Pediatric MS Centers. Parents completed a comprehensive environmental questionnaire that captured early infectious exposures, habits, and illnesses in the first five years of life. A panel of at least two pediatric MS specialists confirmed diagnosis of participants. Association of early infectious variables with diagnosis was assessed via multivariable logistic regression analyses, adjusting for age, sex, race, ethnicity, US birth region, and socioeconomic status (SES). Results: Questionnaire responses for 326 eligible cases (mean age 14.9, 63.5% girls) and 506 healthy pediatric subjects (mean age 14.4, 56.9% girls) were included in analyses. History of flu with high fever before age five (p = 0.01), playing outside in grass and use of special products to treat head lice or scabies (p = 0.04) were associated with increased risk of MS in unadjusted analyses. In the multivariable model adjusted for age, sex, race, ethnicity, and mother’s highest educational attainment, these results were not statistically significant. Notably, antibiotic use (p = 0.22) and regular daycare attendance before age 6 (p = 0.09) were not associated with odds of developing MS. Conclusion: Early infectious factors investigated in this study were not associated with MS risk. © 2018 Elsevier B.V.
Author Keywords
Childhood infection; Epidemiology; Multiple sclerosis; Neonatal exposure
Document Type: Article
Source: Scopus
"Cerebrovascular Events After Continuous-Flow Left Ventricular Assist Devices" (2018) Neurocritical Care
Cerebrovascular Events After Continuous-Flow Left Ventricular Assist Devices
(2018) Neurocritical Care, pp. 1-8. Article in Press.
Tahsili-Fahadan, P., Curfman, D.R., Davis, A.A., Yahyavi-Firouz-Abadi, N., Rivera-Lara, L., Nassif, M.E., LaRue, S.J., Ewald, G.A., Zazulia, A.R.
Abstract
Background: Cerebrovascular events (CVE) are among the most common and serious complications after implantation of continuous-flow left ventricular assist devices (CF-LVAD). We studied the incidence, subtypes, anatomical distribution, and pre- and post-implantation risk factors of CVEs as well as the effect of CVEs on outcomes after CF-LVAD implantation at our institution.Methods: Retrospective analysis of clinical and neuroimaging data of 372 patients with CF-LVAD between May 2005 and December 2013 using standard statistical methods. Results: CVEs occurred in 71 patients (19%), consisting of 35 ischemic (49%), 26 hemorrhagic (37%), and 10 ischemic+hemorrhagic (14%) events. History of coronary artery disease and female gender was associated with higher odds of ischemic CVE (OR 2.84 and 2.5, respectively), and diabetes mellitus was associated with higher odds of hemorrhagic CVE (OR 3.12). While we found a higher rate of ischemic CVEs in patients not taking any antithrombotic medications, no difference was found between patients with ischemic and hemorrhagic CVEs. Occurrence of CVEs was associated with increased mortality (HR 1.62). Heart transplantation was associated with improved survival (HR 0.02). In patients without heart transplantation, occurrence of CVE was associated with decreased survival. Conclusions: LVADs are associated with high rates of CVE, increased mortality, and lower rates of heart transplantation. Further investigations to identify the optimal primary and secondary stroke prevention measures in post-LVAD patients are warranted. © 2018 Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society
Author Keywords
Cardiac transplant; Heart failure; Left ventricular assist device; Stroke
Document Type: Article in Press
Source: Scopus
"Author Correction to: Pooled Analyses of Phase III Studies of ADS-5102 (Amantadine) Extended-Release Capsules for Dyskinesia in Parkinson’s Disease" (2018) CNS Drugs
Author Correction to: Pooled Analyses of Phase III Studies of ADS-5102 (Amantadine) Extended-Release Capsules for Dyskinesia in Parkinson’s Disease
(2018) CNS Drugs, pp. 1-2. Article in Press.
Elmer, L.W., Juncos, J.L., Singer, C., Truong, D.D., Criswell, S.R., Parashos, S., Felt, L., Johnson, R., Patni, R.
Abstract
An Online First version of this article was made available online at http://link.springer.com/journal/40263/onlineFirst/page/1on 12 March 2018. An error was subsequently identified in the article, and the following correction should be noted. © 2018 Springer International Publishing AG, part of Springer Nature
Document Type: Article in Press
Source: Scopus
"Marijuana Promotion Online: an Investigation of Dispensary Practices" (2018) Prevention Science
Marijuana Promotion Online: an Investigation of Dispensary Practices
(2018) Prevention Science, pp. 1-11. Article in Press.
Cavazos-Rehg, P.A., Krauss, M.J., Cahn, E., Lee, K.E., Ferguson, E., Rajbhandari, B., Sowles, S.J., Floyd, G.M., Berg, C., Bierut, L.J.
Abstract
Marijuana product advertising will become more common, as the use of medical and/or recreational marijuana becomes increasingly legal in the USA. In this study, we investigate the marketing tactics being used on marijuana dispensary websites in the USA that could influence substance use behaviors. One hundred dispensary websites were randomly selected from 10 states that allowed the legal use of medical or recreational marijuana and had at least 10 operational dispensaries. Three dispensaries were excluded due to non-functioning websites, leaving a sample of 97 dispensaries. Content analysis was conducted on these dispensaries’ websites, with the primary areas of focus including website age verification, marijuana effects, warnings, and promotional tactics. Among the 97 dispensaries, 75% did not include age verification. Roughly 30% offered online ordering and 21% offered delivery services. Sixty-seven percent made health claims pertaining to medical conditions that could be treated by their marijuana products, with moderate or conclusive evidence to support their claims. Less than half of the dispensaries (45%) advised consumers of possible side effects, and only 18% included warnings about contraindications. Nearly half (44%) offered reduced prices or coupons, 19% offered “buy one get one free” offers, and 16% provided giveaways or free samples. Our findings indicate that marijuana dispensary websites are easily accessible to youth. In addition, only a small amount of the websites advised consumers about possible side effects or contraindications. This study suggests the need for surveillance of marijuana commercialization and online advertising especially in the context of state policy reforms. © 2018 Society for Prevention Research
Author Keywords
Advertising; Marijuana; Online; Policy
Document Type: Article in Press
Source: Scopus
"CANOMAD and other chronic ataxic neuropathies with disialosyl antibodies (CANDA)" (2018) Journal of Neurology
CANOMAD and other chronic ataxic neuropathies with disialosyl antibodies (CANDA)
(2018) Journal of Neurology, pp. 1-8. Article in Press.
Garcia-Santibanez, R., Zaidman, C.M., Sommerville, R.B., Lopate, G., Weihl, C.C., Pestronk, A., Bucelli, R.C.
Abstract
Introduction: CANOMAD/CANDA are syndromes characterized by ataxic neuropathy, ophthalmoplegia, monoclonal gammopathy, cold agglutinins and disialosyl antibodies. Methods: A retrospective review of our neuromuscular autoantibody panel database was performed. Anti-GD1b seropositive patients with ataxia were included. Results: Eleven patients were identified. Median age at onset was 56 years. Median disease duration was 6 years. All patients had gait disorders. Nine had ocular motility abnormalities. Most had a monoclonal protein and all had elevated serum IgM. Electrodiagnostic studies showed a mixed axonal/demyelinating pattern (6), an axonal pattern (4), or a pure demyelinating pattern (1). Ultrasounds showed nerve enlargement patterns consistent with acquired demyelination. A nerve biopsy showed near complete loss of myelinated axons with preservation of smaller axons. Rituximab was the most effective immunotherapy. Conclusion: CANOMAD/CANDA are rare and debilitating disorders with characteristic clinical and diagnostic findings. In our cohort, nerve ultrasound showed regional nerve enlargement and rituximab was the most effective immunomodulatory therapy. © 2018 Springer-Verlag GmbH Germany, part of Springer Nature
Author Keywords
Ataxic neuropathies; CANDA; CANOMAD; Disialosyl antibodies; Immune therapy; Ultrasound
Document Type: Article in Press
Source: Scopus
"Care Wounds: Precarious Vulnerability and the Potential of Exposure" (2018) Culture, Medicine and Psychiatry
Care Wounds: Precarious Vulnerability and the Potential of Exposure
(2018) Culture, Medicine and Psychiatry, pp. 1-19. Article in Press.
Cubellis, L.
Abstract
What does it mean to offer care when the act of caring is wounding to its giver? For peer specialists—individuals with lived experience as patients in the psychiatric system—this question shapes how they use their own histories to provide support for individuals experiencing psychiatric crisis. Peer support is unique in the way it draws on empathetic resonance and depends on carefully deployed vulnerability; where one connects with others through the recognition of shared experience and mutual hurt. For peers, care works when this guidance, reassurance, and “being with”—all of which draw upon their own stories of traumatic history and variegated suffering—mitigate the present crisis being experienced by another. Drawing on twenty-eight months of fieldwork with a peer-staffed crisis respite center in the eastern United States, I argue that the peer specialist becomes the embodiment of a novel intersection of intimacy and compensation; one that poses vulnerability not as a consequence, casualty, or risk factor in the commodification of care, but as its principle vector of resonance and the assumption on which it is based. For peers, care that works—in that it creates a mutual resonance for the recipient—becomes simultaneously care that wounds its giver. © 2018 Springer Science+Business Media, LLC, part of Springer Nature
Author Keywords
Care; Homelessness; Mental health; Peer support; Precarity
Document Type: Article in Press
Source: Scopus
"Evaluation of gene-based family-based methods to detect novel genes associated with familial late onset Alzheimer disease" (2018) Frontiers in Neuroscience
Evaluation of gene-based family-based methods to detect novel genes associated with familial late onset Alzheimer disease
(2018) Frontiers in Neuroscience, 12 (APR), art. no. 209, .
Fernández, M.V., Budde, J., Del-Aguila, J.L., Ibañez, L., Deming, Y., Harari, O., Norton, J., Morris, J.C., Goate, A.M., Cruchaga, C., Mayeux, R., Farlow, M., Foroud, T., Faber, K., Boeve, B.F., Graff-Radford, N.R., Bennett, D.A., Sweet, R.A., Rosenberg, R., Bird, T.D., Silverman, J.M.
Abstract
Gene-based tests to study the combined effect of rare variants on a particular phenotype have been widely developed for case-control studies, but their evolution and adaptation for family-based studies, especially studies of complex incomplete families, has been slower. In this study, we have performed a practical examination of all the latest gene-based methods available for family-based study designs using both simulated and real datasets. We examined the performance of several collapsing, variance-component, and transmission disequilibrium tests across eight different software packages and 22 models utilizing a cohort of 285 families (N = 1,235) with late-onset Alzheimer disease (LOAD). After a thorough examination of each of these tests, we propose a methodological approach to identify, with high confidence, genes associated with the tested phenotype and we provide recommendations to select the best software and model for family-based gene-based analyses. Additionally, in our dataset, we identified PTK2B, a GWAS candidate gene for sporadic AD, along with six novel genes (CHRD, CLCN2, HDLBP, CPAMD8, NLRP9, and MAS1L) as candidate genes for familial LOAD. © 2018 Fernández, Budde, Del-Aguila, Ibañez, Deming, Harari, Norton, Morris, Goate, NIA-LOAD family study group, NCRAD and Cruchaga.
Author Keywords
Alzheimer’s disease; Clustering; Family-based; Gene-based; Rare variants; Transmission disequilibrium; Variance-component; Whole exome sequencing
Document Type: Article
Source: Scopus
"Bioinspired polarization vision enables underwater geolocalization" (2018) Science Advances
Bioinspired polarization vision enables underwater geolocalization
(2018) Science Advances, 4 (4), art. no. eaao6841, .
Powell, S.B., Garnett, R., Marshall, J., Rizk, C., Gruev, V.
Abstract
With its never-ending blue color, the underwater environment often seems monotonic and featureless. However, to an animal with polarization-sensitive vision, it is anything but bland. The rich repertoire of underwater polarization patterns—a consequence of light’s air-to-water transmission and in-water scattering—can be exploited both as a compass and for geolocalization purposes. We demonstrate that, by using a bioinspired polarization-sensitive imager, we can determine the geolocation of an observer based on radial underwater polarization patterns. Our experimental data, recorded at various locations around the world, at different depths and times of day, indicate that the average accuracy of our geolocalization is 61 km, or 6 m of error for every 1 km traveled. This proof-of-concept study of our bioinspired technique opens new possibilities in long-distance underwater navigation and suggests additional mechanisms by which marine animals with polarization-sensitive vision might perform both local and long-distance navigation. Copyright © 2018 The Authors.
Document Type: Article
Source: Scopus
"ApoE facilitates the microglial response to amyloid plaque pathology" (2018) Journal of Experimental Medicine
ApoE facilitates the microglial response to amyloid plaque pathology
(2018) Journal of Experimental Medicine, 215 (4), pp. 1047-1058.
Ulrich, J.D., Ulland, T.K., Mahan, T.E., Nyström, S., Peter Nilsson, K., Song, W.M., Zhou, Y., Reinartz, M., Choi, S., Jiang, H., Stewart, F.R., Anderson, E., Wang, Y., Colonna, M., Holtzman, D.M.
Abstract
One of the hallmarks of Alzheimer’s disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-β (Aβ) peptide. Apolipoprotein E (ApoE) influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric Aβ in the brain. In addition to influencing Aβ metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APP PS1ΔE9 and APP PS1-21 transgenic mice. We report that Apoe deficiency reduced fibrillar plaque deposition, consistent with previous studies. However, fibrillar plaques in Apoe-deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct Aβ morphotypes in Apoe-deficient mice. We also observed a significant reduction in fibrillar plaque-associated microgliosis and activated microglial gene expression in Apoe-deficient mice, along with significant increases in dystrophic neurites around fibrillar plaques. Our results suggest that apoE is critical in stimulating the innate immune response to amyloid pathology. © 2018 Ulrich et al.
Document Type: Article
Source: Scopus
"PTSD: A systematic approach to diagnosis and treatment" (2018) Current Psychiatry
PTSD: A systematic approach to diagnosis and treatment
(2018) Current Psychiatry, 17 (4), pp. 35-43.
North, C.S., Hong, B.A., Downs, D.L.
Document Type: Article
Source: Scopus
"De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination" (2018) Journal of Cell Biology
De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination
(2018) Journal of Cell Biology, 217 (4), pp. 1353-1368.
Montani, L., Pereira, J.A., Norrmén, C., Pohl, H.B.F., Tinelli, E., Trötzmüller, M., Figlia, G., Dimas, P., von Niederhäusern, B., Schwager, R., Jessberger, S., Semenkovich, C.F., Köfeler, H.C., Suter, U.
Abstract
Myelination calls for a remarkable surge in cell metabolism to facilitate lipid and membrane production. Endogenous fatty acid (FA) synthesis represents a potentially critical process in myelinating glia. Using genetically modified mice, we show that Schwann cell (SC) intrinsic activity of the enzyme essential for de novo FA synthesis, fatty acid synthase (FASN), is crucial for precise lipid composition of peripheral nerves and fundamental for the correct onset of myelination and proper myelin growth. Upon FASN depletion in SCs, epineurial adipocytes undergo lipolysis, suggestive of a compensatory role. Mechanistically, we found that a lack of FASN in SCs leads to an impairment of the peroxisome proliferator- activated receptor (PPAR) γ-regulated transcriptional program. In agreement, defects in myelination of FASN-deficient SCs could be ameliorated by treatment with the PPARγ agonist rosiglitazone ex vivo and in vivo. Our results reveal that FASN-driven de novo FA synthesis in SCs is mandatory for myelination and identify lipogenic activation of the PPARγ transcriptional network as a putative downstream functional mediator. © 2018 Montani et al.
Document Type: Article
Source: Scopus
Access Type: Open Access
"ACEs and pregnancy: Time to support all expectant mothers" (2018) Pediatrics
ACEs and pregnancy: Time to support all expectant mothers
(2018) Pediatrics, 141 (4), art. no. e20180232, .
Hudziak, J.J.
Document Type: Note
Source: Scopus
"Surgical Fires in Otolaryngology: A Systematic and Narrative Review" (2018) Otolaryngology – Head and Neck Surgery (United States)
Surgical Fires in Otolaryngology: A Systematic and Narrative Review
(2018) Otolaryngology – Head and Neck Surgery (United States), 158 (4), pp. 598-616. Cited 1 time.
Day, A.T., Rivera, E., Farlow, J.L., Gourin, C.G., Nussenbaum, B.
Abstract
Objective: To bring attention to the epidemiology, prevention, management, and consequences of surgical fires in otolaryngology by reviewing the literature. Data Sources: PubMed, EMBASE, Web of Science, and Scopus. Review Methods: Comprehensive search terms were developed, and searches were performed from data source inception through August 2016. A total of 4506 articles were identified; 2351 duplicates were removed; and 2155 titles and abstracts were independently reviewed. Reference review was also performed. Eligible manuscripts described surgical fires involving patients undergoing otolaryngologic procedures. Results: Seventy-two articles describing 87 otolaryngologic surgical fire cases were identified. These occurred during oral cavity or oropharyngeal procedures (11%), endoscopic laryngotracheal procedures (25%), tracheostomies (36%), “other” general anesthesia procedures (3%), and monitored anesthesia care or local procedures (24%). Oxidizing agents consisted of oxygen alone (n = 63 of 81, 78%), oxygen and nitric oxide (n = 17 of 81, 21%), and room air (n = 1 of 81, 1%). The fractional inspired oxygen delivered was >30% in 97% of surgical fires in non–nitrous oxide general anesthesia cases (n = 35 of 36). Laser-safe tubes were used in only 12% of endoscopic laryngotracheal cases with endotracheal tube descriptions (n = 2 of 17). Eighty-six percent of patients experienced acute complications (n = 76 of 87), including 1 intraoperative death, and 22% of patients (n = 17 of 77) experienced long-term complications. Conclusion: Surgical fires in otolaryngology persist despite aggressive multi-institutional efforts to curb their incidence. Guideline recommendations to minimize the concentration of delivered oxygen and use laser-safe tubes when indicated were not observed in many cases. Improved institutional fire safety practices are needed nationally and internationally. © 2017, © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2018.
Author Keywords
fire; fires; head and neck surgery; operating room; otolaryngology; surgical
Document Type: Review
Source: Scopus
"Patch-clamp and perfusion techniques to study ion channels expressed in xenopus oocytes" (2018) Cold Spring Harbor Protocols
Patch-clamp and perfusion techniques to study ion channels expressed in xenopus oocytes
(2018) Cold Spring Harbor Protocols, 2018 (4), pp. 258-267.
Zhang, G., Cui, J.
Abstract
The Xenopus oocyte expression system is ideal for electrophysiological characterization of voltage-dependent and ligand-dependent ion channels because of its relatively low background of endogenous channels and the large size of the cell. Here, we present a protocol to study voltage- and ligand-dependent activation of ion channels expressed in Xenopus oocytes using patch-clamp techniques designed to control both the membrane voltage and the intracellular solution. In this protocol, the large conductance voltage- and Ca2+ -activated K+ (BK) channel is studied as an example. After injection of BK channel mRNA, oocytes are incubated for 2–7 d at 18˚C. Inside-out membrane patches containing single or multiple BK channels are excised with perfusion of different solutions during recording. The protocol can be used to study structure–function relations for ion channels and neurotransmitter receptors. © 2018 Cold Spring Harbor Laboratory Press.
Document Type: Article
Source: Scopus
"Ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation" (2018) PLoS ONE
Ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation
(2018) PLoS ONE, 13 (4), art. no. e0195520, .
Sobieski, C., Warikoo, N., Shu, H.-J., Mennerick, S.
Abstract
Neurons require a nearly constant supply of ATP. Glucose is the predominant source of brain ATP, but the direct effects of prolonged glucose deprivation on neuronal viability and function remain unclear. In sparse rat hippocampal microcultures, neurons were surprisingly resilient to 16 h glucose removal in the absence of secondary excitotoxicity. Neuronal survival and synaptic transmission were unaffected by prolonged removal of exogenous glucose. Inhibition of lactate transport decreased microculture neuronal survival during concurrent glucose deprivation, suggesting that endogenously released lactate is important for tolerance to glucose deprivation. Tandem depolarization and glucose deprivation also reduced neuronal survival, and trace glucose concentrations afforded neuroprotection. Mass cultures, in contrast to microcultures, were insensitive to depolarizing glucose deprivation, a difference attributable to increased extracellular lactate levels. Removal of local astrocyte support did not reduce survival in response to glucose deprivation or alter evoked excitatory transmission, suggesting that on-demand, local lactate shuttling is not necessary for neuronal tolerance to prolonged glucose removal. Taken together, these data suggest that endogenously produced lactate available globally in the extracellular milieu sustains neurons in the absence of glucose. A better understanding of resilience mechanisms in reduced preparations could lead to therapeutic strategies aimed to bolster these mechanisms in vulnerable neuronal populations. © 2018 Sobieski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Document Type: Article
Source: Scopus
Access Type: Open Access
"NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease" (2018) Alzheimer's and Dementia
NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease
(2018) Alzheimer’s and Dementia, 14 (4), pp. 535-562. Cited 1 time.
Jack, C.R., Jr., Bennett, D.A., Blennow, K., Carrillo, M.C., Dunn, B., Haeberlein, S.B., Holtzman, D.M., Jagust, W., Jessen, F., Karlawish, J., Liu, E., Molinuevo, J.L., Montine, T., Phelps, C., Rankin, K.P., Rowe, C.C., Scheltens, P., Siemers, E., Snyder, H.M., Sperling, R., Elliott, C., Masliah, E., Ryan, L., Silverberg, N., Contributors
Abstract
In 2011, the National Institute on Aging and Alzheimer’s Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer’s disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer’s Association to update and unify the 2011 guidelines. This unifying update is labeled a “research framework” because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer’s Association Research Framework, Alzheimer’s disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people. © 2018 The Authors
Author Keywords
Alzheimer’s disease diagnosis; Alzheimer’s disease imaging; Amyloid PET; Biomarkers Alzheimer’s disease; CSF biomarkers Alzheimer’s disease; Preclinical Alzheimer’s disease; Tau PET
Document Type: Review
Source: Scopus
Access Type: Open Access
"Retinoid isomerase inhibitors impair but do not block mammalian cone photoreceptor function" (2018) Journal of General Physiology
Retinoid isomerase inhibitors impair but do not block mammalian cone photoreceptor function
(2018) Journal of General Physiology, 150 (4), pp. 571-590.
Kiser, P.D., Zhang, J., Sharma, A., Angueyra, J.M., Kolesnikov, A.V., Badiee, M., Tochtrop, G.P., Kinoshita, J., Peachey, N.S., Li, W., Kefalov, V.J., Palczewski, K.
Abstract
Visual function in vertebrates critically depends on the continuous regeneration of visual pigments in rod and cone photoreceptors. RPE65 is a well-established retinoid isomerase in the pigment epithelium that regenerates rhodopsin during the rod visual cycle; however, its contribution to the regeneration of cone pigments remains obscure. In this study, we use potent and selective RPE65 inhibitors in rod- and cone-dominant animal models to discern the role of this enzyme in cone-mediated vision. We confirm that retinylamine and emixustat-family compounds selectively inhibit RPE65 over DES1, the putative retinoid isomerase of the intraretinal visual cycle. In vivo and ex vivo electroretinography experiments in Gnat1-/- mice demonstrate that acute administration of RPE65 inhibitors after a bleach suppresses the late, slow phase of cone dark adaptation without affecting the initial rapid portion, which reflects intraretinal visual cycle function. Acute administration of these compounds does not affect the light sensitivity of cone photoreceptors in mice during extended exposure to background light, but does slow all phases of subsequent dark recovery. We also show that cone function is only partially suppressed in cone-dominant ground squirrels and wild-type mice by multiday administration of an RPE65 inhibitor despite profound blockade of RPE65 activity. Complementary experiments in these animal models using the DES1 inhibitor fenretinide show more modest effects on cone recovery. Collectively, these studies demonstrate a role for continuous RPE65 activity in mammalian cone pigment regeneration and provide further evidence for RPE65- independent regeneration mechanisms. © 2018 Kiser et al.
Document Type: Article
Source: Scopus
"Positive allosteric modulation as a potential therapeutic strategy in anti-NMDA receptor encephalitis" (2018) Journal of Neuroscience
Positive allosteric modulation as a potential therapeutic strategy in anti-NMDA receptor encephalitis
(2018) Journal of Neuroscience, 38 (13), pp. 3218-3229.
Warikoo, N., Brunwasser, S.J., Benz, A., Shu, H.-J., Paul, S.M., Lewis, M., Doherty, J., Quirk, M., Piccio, L., Zorumski, C.F., Day, G.S., Mennerick, S.
Abstract
N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors important for synaptic plasticity, memory, and neuro-psychiatric health. NMDAR hypofunction contributes to multiple disorders, including anti-NMDAR encephalitis (NMDARE), an autoimmune disease of the CNS associated with GluN1 antibody-mediated NMDAR internalization. Here we characterize the functional/ pharmacological consequences of exposure to CSF from female human NMDARE patients on NMDAR function, and we characterize the effects of intervention with recently described positive allosteric modulators (PAMs) of NMDARs. Incubation (48 h) of rat hippocampal neurons of both sexes in confirmed NMDARE patient CSF, but not control CSF, attenuated NMDA-induced current. Residual NMDAR function was characterized by lack of change in channel open probability, indiscriminate loss of synaptic and extrasynaptic NMDARs, and indiscriminate loss of GluN2B-containing and GluN2B-lacking NMDARs. NMDARs tagged with N-terminal pHluorin fluorescence demonstrated loss of surface receptors. Thus, function of residual NMDARs following CSF exposure was indistinguishable from baseline, and deficits appear wholly accounted for by receptor loss. Coapplication of CSF and PAMs of NMDARs (SGE-301 or SGE-550, oxysterol-mimetic) for 24 h restored NMDAR function following 24 h incubation in patient CSF. Curiously, restoration of NMDAR function was observed despite washout of PAMs before electrophysiological recordings. Subsequent experiments suggested that residual allosteric potentiation of NMDAR function explained the persistent rescue. Further studies of the pathogenesis of NMDARE and intervention with PAMs may inform new treatments for NMDARE and other disorders associated with NMDAR hypofunction. © 2018 the authors.
Author Keywords
Autoimmune; Glutamate; NMDA receptor; Schizophrenia
Document Type: Article
Source: Scopus
"Use of a video scoring anchor for rapid serial assessment of social communication in toddlers" (2018) Journal of Visualized Experiments
Use of a video scoring anchor for rapid serial assessment of social communication in toddlers
(2018) Journal of Visualized Experiments, 2018 (133), art. no. e57041, .
Marrus, N., Kennon-McGill, S., Harris, B., Zhang, Y., Glowinski, A.L., Constantino, J.N.
Abstract
Reciprocal social behavior (RSB), an early-emerging capacity to engage in social contingency—which is foundational for both social learning and social competency—is hypothesized to be disrupted in autism spectrum disorder (ASD). The ability to quantify the full range of RSB during the toddler period, when core symptoms of ASD often arise, is pivotal for evaluating early risk for ASD, characterizing social development, and tracking response to early interventions. However, important parameters of variation in RSB—especially prior to the development of verbal language—can be nuanced and difficult to characterize using questionnaire-based methods. To address this challenge, we developed a system for measuring quantitative variation in RSB in toddlers (ages 18 – 30 months) that incorporated not only standard questionnaire data from caregivers but also a novel set of video-referenced items, through which a respondent compares the behavior of a subject to that observed in a short video of a young child manifesting a highly competent level of social communication. Testing of this measure in a general population sample of twins confirmed that both the video-referenced items and the RSB Total Score (video-referenced items plus non-video-referenced items) displayed unimodal, continuous distributions, strong internal consistency, marked preservation of individual differences, and extremely high heritability. In addition, video-referenced items were particularly sensitive to quantifying incremental changes in social communication, a major element of RSB, over the course of early childhood development. Scores on the vrRSB clearly differentiated children with and without ASD and these data comprise an initial validation of this promising method for quantifying early RSB—cross-sectionally, over time, and as a function of early intervention. © 2018, Journal of Visualized Experiments. All rights reserved.
Author Keywords
Autism; Behavior; Issue 133; Reciprocal Social Behavior; Social Communication; Toddler; Video; Video-Referenced
Document Type: Article
Source: Scopus
"Reflections on the Resurgence of Interest in the Testing Effect" (2018) Perspectives on Psychological Science
Reflections on the Resurgence of Interest in the Testing Effect
(2018) Perspectives on Psychological Science, 13 (2), pp. 236-241. Cited 1 time.
Roediger, H.L., III, Karpicke, J.D.
Abstract
We discuss the findings from our 2006 article in Psychological Science on the testing effect and describe how the project arose. The testing effect (or retrieval-practice effect) was first reported in the experimental literature about a century before our article was published, and the effect had been replicated (and sometimes discovered anew) many times over the years. Our experiments used prose materials (unlike most prior research) and produced a more powerful effect than prior research even though we used a conservative control condition for comparison. In our discussion, we drew out possible implications for educational practice. We also reported that students in the experiment could not predict the effect; this lack of metacognitive awareness represented a new finding in this context. In a companion article the same year, we provided an historical review of the testing effect. We believe the synergistic effect of the two articles accounts in part for the resurgence in interest in this phenomenon and its application in educational settings. © 2017, © The Author(s) 2017.
Author Keywords
application; cognition; education; memory
Document Type: Article
Source: Scopus
"Psychotropic drugs and falls in older adults: What do we do now?" (2018) Psychiatric Times
Psychotropic drugs and falls in older adults: What do we do now?
(2018) Psychiatric Times, 35 (3), pp. 19-20.
Lenze, E.J.
Document Type: Short Survey
Source: Scopus
"Postpartum Depressive Symptoms: Gestational Weight Gain as a Risk Factor for Adolescents Who Are Overweight or Obese" (2018) Journal of Midwifery and Women's Health
Postpartum Depressive Symptoms: Gestational Weight Gain as a Risk Factor for Adolescents Who Are Overweight or Obese
(2018) Journal of Midwifery and Women’s Health, 63 (2), pp. 178-184.
Cunningham, S.D., Mokshagundam, S., Chai, H., Lewis, J.B., Levine, J., Tobin, J.N., Ickovics, J.R.
Abstract
Introduction: Obesity is a risk factor for adverse physical health outcomes during pregnancy. Much less is known about the association between obesity and maternal mental health. Evidence suggests that prenatal depression is associated with excessive weight gain during pregnancy and that this relationship may vary according to pregravid body mass index (BMI). Young women may be particularly vulnerable to postpartum depression. The objective of this study is to examine the association between prepregnancy BMI, gestational weight gain, and postpartum depressive symptoms among adolescents. Methods: Participants were 505 pregnant adolescents aged 14 to 21 years followed during pregnancy and 6 months postpartum. Data were collected via interviews and medical record abstraction. Multilevel linear mixed models were used to test the association between excessive gestational weight gain as defined by National Academy of Medicine Guidelines and postpartum depressive symptoms measured via the validated Center for Epidemiologic Studies Depression (CES-D) scale. Analyses controlled for sociodemographic factors (maternal age, race, ethnicity, relationship status), health behaviors (nutrition, physical activity), prenatal depressive symptoms, and postpartum weight retention. Results: Prepregnancy BMI was classified as follows: 11% underweight, 53% healthy weight, 19% overweight, and 18% obese. One-half (50%) of participants exceeded recommended guidelines for gestational weight gain. Adolescents with excessive gestational weight gain who entered pregnancy overweight or obese had significantly higher postpartum depressive symptoms (β, 2.41; SE, 1.06 vs β, 2.58; SE, 1.08, respectively; both P <.05) compared with those with healthy prepregnancy BMI and appropriate gestational weight gain. Adolescents who gained gestational weight within clinically recommended guidelines were not at risk for increased depressive symptoms. Discussion: Adolescents who enter pregnancy overweight or obese and experience excessive weight gain may be at increased risk for postpartum depressive symptoms. Health care providers should offer preventive interventions during pregnancy and the interconceptional period to support healthy weight gain and safeguard women’s mental health. © 2018 by the American College of Nurse-Midwives
Author Keywords
adolescent; gestational weight gain; obesity; postpartum depressive symptoms; pregnancy
Document Type: Article
Source: Scopus
"The category size bias: A mere misunderstanding" (2018) Judgment and Decision Making
The category size bias: A mere misunderstanding
(2018) Judgment and Decision Making, 13 (2), pp. 170-184.
Perfecto, H., Nelson, L.D., Moore, D.A.
Abstract
Redundant or excessive information can sometimes lead people to lean on it unnecessarily. Certain experimental designs can sometimes bias results in the researcher’s favor. And, sometimes, interesting effects are too small to be studied, practically, or are simply zero. We believe a confluence of these factors led to a recent paper (Isaac & Brough, 2014, JCR). This initial paper proposed a new means by which probability judgments can be led astray: the category size bias, by which an individual event coming from a large category is judged more likely to occur than an event coming from a small one. Our work shows that this effect may be due to instructional and mechanical confounds, rather than interesting psychology. We present eleven studies with over ten times the sample size of the original in support of our conclusion: We replicate three of the five original studies and reduce or eliminate the effect by resolving these methodological issues, even significantly reversing the bias in one case (Study 6). Studies 7-8c suggest the remaining two studies are false positives. We conclude with a discussion of the subtleties of instruction wording, the difficulties of correcting the record, and the importance of replication and open science. © 2018, Society for Judgment and Decision making. All rights reserved.
Author Keywords
Bias; Estimation; Judgment; Replication; Subjective probability
Document Type: Article
Source: Scopus
"Programming of Schwann Cells by Lats1/2-TAZ/YAP Signaling Drives Malignant Peripheral Nerve Sheath Tumorigenesis" (2018) Cancer Cell
Programming of Schwann Cells by Lats1/2-TAZ/YAP Signaling Drives Malignant Peripheral Nerve Sheath Tumorigenesis
(2018) Cancer Cell, 33 (2), pp. 292-308.e7. Cited 2 times.
Wu, L.M.N., Deng, Y., Wang, J., Zhao, C., Wang, J., Rao, R., Xu, L., Zhou, W., Choi, K., Rizvi, T.A., Remke, M., Rubin, J.B., Johnson, R.L., Carroll, T.J., Stemmer-Rachamimov, A.O., Wu, J., Zheng, Y., Xin, M., Ratner, N., Lu, Q.R.
Abstract
Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive Schwann cell (SC)-lineage-derived sarcomas. Molecular events driving SC-to-MPNST transformation are incompletely understood. Here, we show that human MPNSTs exhibit elevated HIPPO-TAZ/YAP expression, and that TAZ/YAP hyperactivity in SCs caused by Lats1/2 loss potently induces high-grade nerve-associated tumors with full penetrance. Lats1/2 deficiency reprograms SCs to a cancerous, progenitor-like phenotype and promotes hyperproliferation. Conversely, disruption of TAZ/YAP activity alleviates tumor burden in Lats1/2-deficient mice and inhibits human MPNST cell proliferation. Moreover, genome-wide profiling reveals that TAZ/YAP-TEAD1 directly activates oncogenic programs, including platelet-derived growth factor receptor (PDGFR) signaling. Co-targeting TAZ/YAP and PDGFR pathways inhibits tumor growth. Thus, our findings establish a previously unrecognized convergence between Lats1/2-TAZ/YAP signaling and MPNST pathogenesis, revealing potential therapeutic targets in these untreatable tumors. Wu et al. find that HIPPO-TAZ/YAP expression is elevated in malignant peripheral nerve sheath tumors (MPNST). Lats1/2 deficiency in Schwann cells induces hyperactivation of TAZ/YAP and increased PDGFR signaling, leading to the development of MPNST in mice. Inhibition of TAZ/YAP and PDGFR reduces MPNST growth. © 2018 Elsevier Inc.
Author Keywords
hippo signaling; Lats1/2; MPNST; murine models; PDGF signaling; peripheral nerve sheath tumor; Schwann cells; TAZ; tumor suppressor; YAP
Document Type: Article
Source: Scopus
"The Mouse Cortical Connectome, Characterized by an Ultra-Dense Cortical Graph, Maintains Specificity by Distinct Connectivity Profiles" (2018) Neuron
The Mouse Cortical Connectome, Characterized by an Ultra-Dense Cortical Graph, Maintains Specificity by Distinct Connectivity Profiles
(2018) Neuron, 97 (3), pp. 698-715.e10.
Gămănuţ, R., Kennedy, H., Toroczkai, Z., Ercsey-Ravasz, M., Van Essen, D.C., Knoblauch, K., Burkhalter, A.
Abstract
The inter-areal wiring pattern of the mouse cerebral cortex was analyzed in relation to a refined parcellation of cortical areas. Twenty-seven retrograde tracer injections were made in 19 areas of a 47-area parcellation of the mouse neocortex. Flat mounts of the cortex and multiple histological markers enabled detailed counts of labeled neurons in individual areas. The observed log-normal distribution of connection weights to each cortical area spans 5 orders of magnitude and reveals a distinct connectivity profile for each area, analogous to that observed in macaques. The cortical network has a density of 97%, considerably higher than the 66% density reported in macaques. A weighted graph analysis reveals a similar global efficiency but weaker spatial clustering compared with that reported in macaques. The consistency, precision of the connectivity profile, density, and weighted graph analysis of the present data differ significantly from those obtained in earlier studies in the mouse. Gămănuţ et al. investigate anatomical cortico-cortical connections in the mouse at the meso-scale level and show that almost all possible connections exist. Efficiency of the network and specificity of the connections are ensured by the existence of weighted connectivity profiles. © 2017 Elsevier Inc.
Author Keywords
anatomy; connectivity; log-normal; neocortex; retrograde; rodent; tract-tracing
Document Type: Article
Source: Scopus
"Functional Brain Networks Are Dominated by Stable Group and Individual Factors, Not Cognitive or Daily Variation" (2018) Neuron
Functional Brain Networks Are Dominated by Stable Group and Individual Factors, Not Cognitive or Daily Variation
(2018) Neuron, . Article in Press.
Gratton, C., Laumann, T.O., Nielsen, A.N., Greene, D.J., Gordon, E.M., Gilmore, A.W., Nelson, S.M., Coalson, R.S., Snyder, A.Z., Schlaggar, B.L., Dosenbach, N.U.F., Petersen, S.E.
Abstract
The organization of human brain networks can be measured by capturing correlated brain activity with fMRI. There is considerable interest in understanding how brain networks vary across individuals or neuropsychiatric populations or are altered during the performance of specific behaviors. However, the plausibility and validity of such measurements is dependent on the extent to which functional networks are stable over time or are state dependent. We analyzed data from nine high-quality, highly sampled individuals to parse the magnitude and anatomical distribution of network variability across subjects, sessions, and tasks. Critically, we find that functional networks are dominated by common organizational principles and stable individual features, with substantially more modest contributions from task-state and day-to-day variability. Sources of variation were differentially distributed across the brain and differentially linked to intrinsic and task-evoked sources. We conclude that functional networks are suited to measuring stable individual characteristics, suggesting utility in personalized medicine. Gratton et al. comprehensively measure individual, day-to-day, and task variance in functional brain networks, revealing that networks are dominated by stable individual factors, not cognitive content. These findings suggest utility of functional network measurements in personalized medicine. © 2018 Elsevier Inc.
Author Keywords
brain networks; fMRI; functional connectivity; individual differences
Document Type: Article in Press
Source: Scopus
"Autoimmune Encephalitis with Multiple Autoantibodies: A Diagnostic and Therapeutic Challenge" (2018) Neurologist
Autoimmune Encephalitis with Multiple Autoantibodies: A Diagnostic and Therapeutic Challenge
(2018) Neurologist, 23 (2), pp. 55-59.
Kim, A.E., Kang, P., Bucelli, R.C., Ferguson, C.J., Schmidt, R.E., Varadhachary, A.S., Day, G.S.
Abstract
Introduction: Indications for autoantibody testing in patients with rapid-onset cognitive impairment have expanded in step with the growing number of disease-associated autoantibodies and clinical syndromes. Although increased access to autoantibody testing has broadened our understanding of the spectrum of autoimmune encephalitis (AE), it has also produced new challenges associated with deciphering the contributions of disease-associated autoantibodies in patients with atypical clinical features and/or multiple autoantibodies. These challenges are illustrated through presentation of a patient with AE associated with autoantibodies against intracellular and cell-surface neuronal antigens. The implications of detection of multiple autoantibodies are considered in the context of relevant literature, and used to frame a diagnostic and therapeutic approach. Case Report: A previously well 67-year-old man presented with encephalopathy and psychosis, impaired visual fixation, and ataxia, emerging over 3 months. Hu, CRMP-5, and NMDAR autoantibodies were identified in the cerebrospinal fluid. No malignancy was discovered despite extensive investigations. An aggressive course of immunotherapy temporarily stabilized his course; however, the patient succumbed to his illness 10 months after symptom onset. Lack of sustained response to immunotherapy and neuropathologic findings suggested that AE associated with Hu antibodies was primarily responsible for this patient’s progressive decline. Conclusions: Multiple autoantibodies may be detected in patients with AE. When antibodies targeting intracellular and cell-surface antigens are detected together, investigation and treatment of syndromes associated with intracellular antibodies should be prioritized, acknowledging the link between these antibodies and irreversible neuronal injury. In paraneoplastic cases, prognosis may be tied to early detection and treatment of the underlying malignancy. © 2018 Wolters Kluwer Health, Inc. All rights reserved.
Author Keywords
autoimmune encephalitis; Hu antibody; NMDA receptor antibody; rapidly progressive dementia
Document Type: Article
Source: Scopus
"Non-meningothelial meningeal tumours with meningioangiomatosis-like pattern of spread' (2018) Neuropathology and Applied Neurobiology
Non-meningothelial meningeal tumours with meningioangiomatosis-like pattern of spread
(2018) Neuropathology and Applied Neurobiology, . Article in Press.
Iorgulescu, J.B., Ferris, S., Agarwal, A., Casavilca Zambrano, S., Hill, D.A., Schmidt, R., Perry, A.
Document Type: Article in Press
Source: Scopus
"Quantitative positron emission tomography reveals regional differences in aerobic glycolysis within the human brain" (2018) Journal of Cerebral Blood Flow and Metabolism
Quantitative positron emission tomography reveals regional differences in aerobic glycolysis within the human brain
(2018) Journal of Cerebral Blood Flow and Metabolism, . Article in Press.
Blazey, T., Snyder, A.Z., Su, Y., Goyal, M.S., Lee, J.J., Vlassenko, A.G., Arbeláez, A.M., Raichle, M.E.
Abstract
Glucose and oxygen metabolism are tightly coupled in the human brain, with the preponderance of the brain’s glucose supply used to generate ATP via oxidative phosphorylation. A fraction of glucose is consumed outside of oxidative phosphorylation despite the presence of sufficient oxygen to do so. We refer to this process as aerobic glycolysis. A recent positron emission tomography study reported that aerobic glycolysis is uniform within gray matter. Here, we analyze the same data and demonstrate robust regional differences in aerobic glycolysis within gray matter, a finding consistent with previously published data. © 2018, The Author(s) 2018.
Author Keywords
Brain imaging; energy metabolism; glucose; metabolism; positron emission tomography
Document Type: Article in Press
Source: Scopus
"Triggered recruitment of ESCRT machinery promotes endolysosomal repair" (2018) Science
Triggered recruitment of ESCRT machinery promotes endolysosomal repair
(2018) Science, 360 (6384), art. no. eaar5078, . Cited 1 time.
Skowyra, M.L., Schlesinger, P.H., Naismith, T.V., Hanson, P.I.
Abstract
Endolysosomes can be damaged by diverse materials. Terminally damaged compartments are degraded by lysophagy, but pathways that repair salvageable organelles are poorly understood. Here we found that the endosomal sorting complex required for transport (ESCRT) machinery, known to mediate budding and fission on endolysosomes, also plays an essential role in their repair. ESCRTs were rapidly recruited to acutely injured endolysosomes through a pathway requiring calcium and ESCRT-activating factors that was independent of lysophagy. We used live-cell imaging to demonstrate that ESCRTs responded to small perforations in endolysosomal membranes and enabled compartments to recover from limited damage. Silica crystals that disrupted endolysosomes also triggered ESCRT recruitment. ESCRTs thus provide a defense against endolysosomal damage likely to be relevant in physiological and pathological contexts. © 2018 American Association for the Advancement of Science. All Rights Reserved.
Document Type: Article
Source: Scopus
"Non-canonical Opioid Signaling Inhibits Itch Transmission in the Spinal Cord of Mice" (2018) Cell Reports
Non-canonical Opioid Signaling Inhibits Itch Transmission in the Spinal Cord of Mice
(2018) Cell Reports, . Article in Press.
Munanairi, A., Liu, X.-Y., Barry, D.M., Yang, Q., Yin, J.-B., Jin, H., Li, H., Meng, Q.-T., Peng, J.-H., Wu, Z.-Y., Yin, J., Zhou, X.-Y., Wan, L., Mo, P., Kim, S., Huo, F.-Q., Jeffry, J., Li, Y.-Q., Bardoni, R., Bruchas, M.R., Chen, Z.-F.
Abstract
Chronic itch or pruritus is a debilitating disorder that is refractory to conventional anti-histamine treatment. Kappa opioid receptor (KOR) agonists have been used to treat chronic itch, but the underlying mechanism remains elusive. Here, we find that KOR and gastrin-releasing peptide receptor (GRPR) overlap in the spinal cord, and KOR activation attenuated GRPR-mediated histamine-independent acute and chronic itch in mice. Notably, canonical KOR-mediated Gαi signaling is not required for desensitizing GRPR function. In vivo and in vitro studies suggest that KOR activation results in the translocation of Ca2+-independent protein kinase C (PKC)δ from the cytosol to the plasma membrane, which in turn phosphorylates and inhibits GRPR activity. A blockade of phospholipase C (PLC) in HEK293 cells prevented KOR-agonist-induced PKCδ translocation and GRPR phosphorylation, suggesting a role of PLC signaling in KOR-mediated GRPR desensitization. These data suggest that a KOR-PLC-PKCδ-GRPR signaling pathway in the spinal cord may underlie KOR-agonists-induced anti-pruritus therapies. Munanairi et al. show that the kappa opioid receptor (KOR) agonists inhibit nonhistaminergic itch transmission by attenuating the function of the gastrin-releasing peptide receptor (GRPR), an itch receptor in the spinal cord. KOR activation causes the translocation of PKCδ from plasma to membrane, which phosphorylates GRPR to dampen itch transmission. © 2018 The Authors
Author Keywords
GPCR cross-signaling; GRPR; itch; KOR; mouse; phosphorylation; PKC; spinal cord
Document Type: Article in Press
Source: Scopus