Modeling neurocognitive and neurobiological recovery in addiction

This book focuses on "what to know" and "how to apply" information, prioritizing novel principles and delineating cutting-edge assessment, phenotyping and treatment tools

Hippocampal GABA enables inhibitory control over unwanted thoughts.

Intrusive memories, images, and hallucinations are hallmark symptoms of psychiatric disorders. Although often attributed to deficient inhibitory control by the prefrontal cortex, difficulty in controlling intrusive thoughts is also associated with hippocampal hyperactivity, arising from dysfunctional GABAergic interneurons. How hippocampal GABA contributes to stopping unwanted thoughts is unknown. Here we show that GABAergic inhibition of hippocampal retrieval activity forms a key link in a fronto-hippocampal inhibitory control pathway underlying thought suppression. Subjects viewed reminders of unwanted thoughts and tried to suppress retrieval while being scanned with functional magnetic resonance imaging. Suppression reduced hippocampal activity and memory for suppressed content. 1H magnetic resonance spectroscopy revealed that greater resting concentrations of hippocampal GABA predicted better mnemonic control. Higher hippocampal, but not prefrontal GABA, predicted stronger fronto-hippocampal coupling during suppression, suggesting that interneurons local to the hippocampus implement control over intrusive thoughts. Stopping actions did not engage this pathway. These findings specify a multi-level mechanistic model of how the content of awareness is voluntarily controlled

Excitatory neurotransmitters in brain regions in interictal migraine patients

<p>Abstract</p> <p>Objective</p> <p>To examine biochemical differences in the anterior cingulate cortex (ACC) and insula during the interictal phase of migraine patients. We hypothesized that there may be differences in levels of excitatory amino acid neurotransmitters and/or their derivatives in migraine group based on their increased sensitivity to pain.</p> <p>Methods</p> <p>2D <it>J</it>-resolved proton magnetic resonance spectroscopy (¹H-MRS) data were acquired at 4.0 Tesla (T) from the ACC and insula in 10 migraine patients (7 women, 3 men, age 43 ± 11 years) and 8 age gender matched controls (7 women, 3 men, age 41 ± 9 years).</p> <p>Results</p> <p>Standard statistical analyses including analysis of variance (ANOVA) showed no significant metabolite differences between the two subject cohorts in the ACC nor the insula. However, linear discriminant analysis (LDA) introduced a clear separation between subject cohorts based on N-acetyl aspartylglutamate (NAAG) and glutamine (Gln) in the ACC and insula.</p> <p>Conclusion</p> <p>These results are consistent with glutamatergic abnormalities in the ACC and insula in migraine patients during their interictal period compared to healthy controls. An alteration in excitatory amino acid neurotransmitters and their derivatives may be a contributing factor for migraineurs for a decrease in sensitivity for migraine or a consequence of the chronic migraine state. Such findings, if extrapolated to other regions of the brain would offer new opportunities to modulate central system as interictal or preemptive medications in these patients.</p

Stamen-derived bioactive gibberellin is essential for male flower development of Cucurbita maxima L.

Gibberellin (GA) signalling during pumpkin male flower development is highly regulated, including biosynthetic, perception, and transduction pathways. GA 20-oxidases, 3-oxidases, and 2-oxidases catalyse the final part of GA synthesis. Additionally, 7-oxidase initiates this part of the pathway in some cucurbits including Cucurbita maxima L. (pumpkin). Expression patterns for these GA-oxidase-encoding genes were examined by competitive reverse transcription-PCR (RT-PCR) and endogenous GA levels were determined during pumpkin male flower development. In young flowers, GA20ox3 transcript levels are high in stamens, followed by high levels of the GA precursor GA9. Later, just before flower opening, transcript levels for GA3ox3 and GA3ox4 increase in the hypanthium and stamens, respectively. In the stamen, following GA3ox4 expression, bioactive GA4 levels rise dramatically. Accordingly, catabolic GA2ox2 and GA2ox3 transcript levels are low in developing flowers, and increase in mature flowers. Putative GA receptor GID1b and DELLA repressor GAIPb transcript levels do not change in developing flowers, but increase sharply in mature flowers. Emasculation arrests floral development completely and leads to abscission of premature flowers. Application of GA4 (but not of its precursors GA12-aldehyde or GA9) restores normal growth of emasculated flowers. These results indicate that de novo GA4 synthesis in the stamen is under control of GA20ox3 and GA3ox4 genes just before the rapid flower growth phase. Stamen-derived bioactive GA is essential and sufficient for male flower development, including the petal and the pedicel growth

Hadronic Structure in the Decay τ−→ντπ−π0π0\tau^{-}\to \nu_{\tau}\pi^{-}\pi^{0}\pi^{0} and the Sign of the Tau Neutrino Helicity

Based on a sample corresponding to 4.3 million produced tau-pair events, we have studied hadronic dynamics in the decay tau- --> nu_tau pi- pi0 pi0 in data recorded by the CLEO II detector operating at the CESR e+e- collider. The decay is dominated by the process tau --> nu_tau a_1(1260), with the a_1 meson decaying to three pions predominantly via the lowest dimensional (mainly S-wave) a_1 --> rho pi Born amplitude. From fits to the Dalitz plot and angular observables, we find significant additional contributions from amplitudes for a_1 decay to sigma pi, f_0(1370) pi and f_2(1270) pi, as well as higher dimensional a_1 --> rho pi and rho' pi amplitudes. The squared sigma pi amplitude accounts for ~15% of the total tau- --> nu_tau pi- pi0 pi0 rate in the models considered. We have searched for additional contributions from tau --> nu_tau pi'(1300). We place 90% confidence level upper limits on the branching fraction for this channel of between 1.0*10^{-4} and 1.9*10^{-4}, depending on the pi' decay mode. The pi- pi0 pi0 mass spectrum is parametrized by a Breit-Wigner form with a mass-dependent width which is specified according to the results of the Dalitz plot fits plus a coupling to an a_1 --> K* K amplitude. From a chi^2 fit, we extract the pole mass and width of the a_1, as well as the magnitude of the K* K coupling. We have also investigated the impact of a possible contribution from the a_1'(1700) meson on this spectrum. Finally, exploiting the parity-violating angular asymmetry in a_1 --> 3pi decay, we determine the signed value of the tau neutrino helicity to be h_{\nu_\tau} = -1.02 +- 0.13(stat.) +- 0.03(syst.+model), confirming the left-handedness of the tau neutrino.Comment: 44 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN