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- Atkins, Alison Lynn, 1976-, et al.
(författare)
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Stereotypic behaviors in mice selectively bred for high and low methamphetamine-induced stereotypic chewing.
- 2001
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Ingår i: Psychopharmacology. - Heidelberg : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 157:1, s. 96-104
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: At high doses, methamphetamine produces repetitive stereotypic behaviors, and the degree to which this occurs is heritable.OBJECTIVES: Mice of a B6D2F2 genetic background were selectively bred for four generations for high (HMA) and low (LMA) numbers of stereotyped chewing episodes measured for 1 min at 33 min post-injection following 10 mg/kg methamphetamine (changed to 7 mg/kg for the high line and 15 mg/kg for the low line in the third selected generation to avoid ceiling and floor effects, respectively). We sought to determine whether stereotypic behaviors other than number of repetitive chewing episodes were altered by the selective breeding process.METHODS: HMA and LMA mice of the third and fourth selected generations were tested for chewing stereotypy, for a number of other stereotypic behaviors previously observed in rodents, and for several other non-stereotypic responses to methamphetamine. Testing in the third selected generation was conducted by observing behaviors on videotape following 7 mg/kg methamphetamine. In the fourth selected generation, mice were also tested in automated activity monitors following 10 mg/kg methamphetamine and in climbing chimneys following 16 mg/kg methamphetamine. Dose-response curves with doses of 1, 2, 3.5, 7, 10, and 15 mg/kg methamphetamine were constructed for the most commonly observed behaviors.RESULTS: LMA mice, which exhibited low stereotyped chewing, exhibited high stereotyped circling and climbing, and the reverse was true for these behaviors for HMA mice. For most of the other behaviors measured, there were drug effects but no differences between selected lines.CONCLUSIONS: These results suggest that these three stereotyped behaviors, chewing, circling, and climbing, at least partly share the same mechanisms, and therefore are influenced by at least some of the same genes, since animals selectively bred for low methamphetamine-induced stereotyped chewing exhibited high amounts of circling and climbing when given methamphetamine. This also suggests that the other stereotypic behaviors that we measured do not occur by the same genetically determined mechanisms as stereotypic chewing.
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- Wiggermann, Vanessa, et al.
(författare)
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Non-negative least squares computation for in vivo myelin mapping using simulated multi-echo spin-echo T2 decay data
- 2020
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 33:12
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Tidskriftsartikel (refereegranskat)abstract
- Multi‐compartment T2 mapping has gained particular relevance for the study of myelin water in the brain. As a facilitator of rapid saltatory axonal signal transmission, myelin is a cornerstone indicator of white matter development and function. Regularized non‐negative least squares fitting of multi‐echo T2 data has been widely employed for the computation of the myelin water fraction (MWF), and the obtained MWF maps have been histopathologically validated. MWF measurements depend upon the quality of the data acquisition, B1+ homogeneity and a range of fitting parameters. In this special issue article, we discuss the relevance of these factors for the accurate computation of multi‐compartment T2 and MWF maps. We generated multi‐echo spin‐echo T2 decay curves following the Carr‐Purcell‐Meiboom‐Gill approach for various myelin concentrations and myelin T2 scenarios by simulating the evolution of the magnetization vector between echoes based on the Bloch equations. We demonstrated that noise and imperfect refocusing flip angles yield systematic underestimations in MWF and intra−/extracellular water geometric mean T2 (gmT2). MWF estimates were more stable than myelin water gmT2 time across different settings of the T2 analysis. We observed that the lower limit of the T2 distribution grid should be slightly shorter than TE1. Both TE1 and the acquisition echo spacing also have to be sufficiently short to capture the rapidly decaying myelin water T2 signal. Among all parameters of interest, the estimated MWF and intra−/extracellular water gmT2 differed by approximately 0.13–4 percentage points and 3–4 ms, respectively, from the true values, with larger deviations observed in the presence of greater B1+ inhomogeneities and at lower signal‐to‐noise ratio. Tailoring acquisition strategies may allow us to better characterize the T2 distribution, including the myelin water, in vivo.
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- Wiggermann, Vanessa, et al.
(författare)
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Non-negative least squares fitting of multi-exponential T2 decay data: Are we able to accurately measure the fraction of myelin water?
- 2019
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Ingår i: Non-negative least squares fitting of multi-exponential T2 decay data: Are we able to accurately measure the fraction of myelin water?. - 1545-4428. ; 27
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Konferensbidrag (refereegranskat)abstract
- The ability to determine the myelin water fraction (MWF) in vivo is essential to assessments of neurodevelopmental myelination and myelin damage in neurodegenerative diseases. The analysis of multi-exponential T2 decay data relies on the non-negative-least-squares (NNLS) fitting, which may be sensitive to the chosen fitting parameters. We performed simulations to explore the outcomes of NNLS under different parameter selection. The lowest allowed T2 was found to have the largest effect on correctly estimating the T2 of different water pools as well as the MWF. Lower refocusing FAs led to further underestimation of the MWF.
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