Search

In vitro, the novel diazabicyclononane NS 4194 has several thousand-fold selectivity for blocking the transport into rat brain synaptosomes of [3H]-serotonin in comparison to [3H]-dopamine or [3H]-noradrenaline. We have prepared [11C]-NS 4194 in order to test its properties for PET imaging of brain serotonin transporters in comparison with the well-documented tracer [11C]-DASB. Both compounds had rapid clearance from blood to brain of living pigs. The apparent equilibrium distribution volumes in cerebellum were 35 ml g−1 for [11C]-NS 4194 and 11 ml g−1 for [11C]-DASB. Pretreatment of pigs with citalopram did not reduce the uptake of either tracer in cerebellum, validating the use of that tissue as a nonbinding reference tissue for kinetic analysis of specific binding. The binding potential (pB) calculated for [11C]-NS 4194 using arterial input models was close to 0.5 in the telencephalon, and was 60% displaced by citalopram. However, the reference tissue method of Lammertsma was unsuited to calculate pB for this tracer, apparently due to its excessive nonspecific binding. In contrast to the relatively homogeneous binding of [11C]-NS 4194, the pB of [11C]-DASB ranged from 0.6 in frontal cortex to 2 in the mesencephalon when calculated by the method of Lammertsma. Parametric maps of the pB of [11C]-DASB showed a pattern consistent with the known distribution of serotonin transporters in pig brain in vitro, and there was a uniform displacement of 80% of the specific binding after citalopram treatment in vivo. In conclusion, [11C]-DASB is in several respects superior to [11C]-NS 4194 for the detection of serotonin uptake sites by PET. Synapse 49:170–177, 2003. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

In students in grades 4 to 9 (22 males, 20 females), two reading disability groups—dyslexia (n = 20) or oral and written language learning disability (OWL LD) (n = 6)—were compared to each other and two kinds of control groups—typical readers (n = 6) or dysgraphia (n = 10) on word reading/spelling skills and fMRI imaging before and after completing 18 computerized reading lessons. Mixed ANOVAs showed significant time effects on repeated measures within participants and between groups effects on three behavioral markers of reading disabilities—word reading/spelling: All groups improved on the three behavioral measures, but those without disabilities remained higher than those with reading disabilities . On fMRI reading tasks, analyzed for graph theory derived clustering coefficients within a neural network involved in cognitive control functions, on a word level task the time x group interaction was significant in right medial cingulate; on a syntax level task the time x group interaction was significant in left superior frontal and left inferior frontal gyri; and on a multi-sentence text level task the time x group interaction was significant in right middle frontal gyrus. Three white matter-gray matter correlations became significant only after reading instruction: axial diffusivity in left superior frontal region with right inferior frontal gyrus during word reading judgments; mean diffusivity in left superior corona radiata with left middle frontal gyrus during sentence reading judgments; and mean diffusivity in left anterior corona radiata with right middle frontal gyrus during multi-sentence reading judgments. Significance of results for behavioral and brain response to reading instruction (RTI) is discussed.