Neurophysiological Capacity in a Working Memory Task Differentiates Dependent from Nondependent Heavy Drinkers and Controls

Background—Determining the brain-behavior profiles that differentiate heavy drinkers who are and are not alcohol dependent will inform treatment efforts. Working memory is linked to substance use disorders and can serve as a representation of the demand placed on the neurophysiology associated with cognitive control. Methods—Behavior and brain activity (via fMRI) were recorded during an N-Back working memory task in controls (CTRL), nondependent heavy drinkers (A-ND) and dependent heavy drinkers (A-D). Typical and novel step-wise analyses examined profiles of working memory load and increasing task demand, respectively. Results—Performance was significantly decreased in A-D during high working memory load (2-Back), compared to CTRL and A-ND. Analysis of brain activity during high load (0-Back vs. 2-Back) showed greater responses in the dorsal lateral and medial prefrontal cortices of A-D than CTRL, suggesting increased but failed compensation. The step-wise analysis revealed that the transition to Low Demand (0-Back to 1-Back) was associated with robust increases and decreases in cognitive control and default-mode brain regions, respectively, in A-D and A-ND but not CTRL. The transition to High Demand (1-Back to 2-Back) resulted in additional engagement of these networks in A-ND and CTRL, but not A-D. Conclusion—Heavy drinkers engaged working memory neural networks at lower demand than controls. As demand increased, nondependent heavy drinkers maintained control performance but relied on additional neurophysiological resources, and dependent heavy drinkers did not display further resource engagement and had poorer performance. These results support targeting these brain areas for treatment interventions

Facilitation of Task Performance and Removal of the Effects of Sleep Deprivation by an Ampakine (CX717) in Nonhuman Primates

The deleterious effects of prolonged sleep deprivation on behavior and cognition are a concern in modern society. Persons at risk for impaired performance and health-related issues resulting from prolonged sleep loss would benefit from agents capable of reducing these detrimental effects at the time they are sleep deprived. Agents capable of improving cognition by enhancing brain activity under normal circumstances may also have the potential to reduce the harmful or unwanted effects of sleep deprivation. The significant prevalence of excitatory α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamatergic receptors in the brain provides a basis for implementing a class of drugs that could act to alter or remove the effects of sleep deprivation. The ampakine CX717 (Cortex Pharmaceuticals), a positive allosteric modulator of AMPA receptors, was tested for its ability to enhance performance of a cognitive, delayed match-to-sample task under normal circumstances in well-trained monkeys, as well as alleviate the detrimental effects of 30–36 h of sleep deprivation. CX717 produced a dose-dependent enhancement of task performance under normal alert testing conditions. Concomitant measures of regional cerebral metabolic rates for glucose (CMR(glc)) during the task, utilizing positron emission tomography, revealed increased activity in prefrontal cortex, dorsal striatum, and medial temporal lobe (including hippocampus) that was significantly enhanced over normal alert conditions following administration of CX717. A single night of sleep deprivation produced severe impairments in performance in the same monkeys, accompanied by significant alterations in task-related CMR(glc) in these same brain regions. However, CX717 administered to sleep-deprived monkeys produced a striking removal of the behavioral impairment and returned performance to above-normal levels even though animals were sleep deprived. Consistent with this recovery, CMR(glc) in all but one brain region affected by sleep deprivation was also returned to the normal alert pattern by the drug. The ampakine CX717, in addition to enhancing cognitive performance under normal alert conditions, also proved effective in alleviating impairment of performance due to sleep deprivation. Therefore, the ability to activate specific brain regions under normal alert conditions and alter the deleterious effects of sleep deprivation on activity in those same regions indicate a potential role for ampakines in sustaining performance under these types of adverse conditions

An importance sampling algorithm for generating exact eigenstates of the nuclear Hamiltonian

We endow a recently devised algorithm for generating exact eigensolutions of large matrices with an importance sampling, which is in control of the extent and accuracy of the truncation of their dimensions. We made several tests on typical nuclei using a correlated basis obtained from partitioning the shell model space. The sampling so implemented allows not only for a substantial reduction of the shell model space but also for an extrapolation to exact eigenvalues and E2 strengths.Comment: A compressed file composed of a text in latex of 19 pages and 9 figures in p

Self-consistent studies of the dipole response in neutron rich nuclei using realistic potentials

The dipole response in neutron rich nuclei is investigated within self-consistent approaches which make direct use of a nucleon-nucleon optimized chiral potential complemented with a density dependent term simulating a three-body force. Hartree-Fock-Bogoliubov plus Tamm-Dancoff and random-phase approximations show that such a potential improves the description of the dipole modes with respect to other realistic interactions. The inclusion of the two-phonon states within an equation of motion method induces a pronounced fragmentation of both giant and pygmy resonances in agreement with recent experiments

Nuclear Spectroscopic Properties within a Selfconsistent Multiphonon Approach

The equation of motion phonon method is adopted to investigate the dipole response in neutron rich nuclei. The calculation is carried out in a space spanned by one- and two-phonon basis states. It makes direct use of a nucleon-nucleon optimized chiral potential complemented with a density dependent term simulating a three-body force and is fully selfconsistent. The inclusion of the two-phonon states induces a pronounced fragmentation of both giant and pygmy resonances consistently with recent experiments

Selfconsistent mean field calculations of the nuclear response using a realistic nucleon-nucleon interaction with a density dependent corrective term

Tamm-Dancoff and random-phase approximations are formulated in the canonical Hartree-Fock-Bogoliubov quasi-particle basis and adopted to compute the E1 response in Ca isotopes using an intrinsic Hamiltonian composed of a Vlowk potential, deduced from the CD-Bonn nucleon-nucleon interaction, corrected with phenomenological density dependent and spin-orbit terms. Attention is focused on the evolution of the dipole strength distribution, including the low-lying transitions associated to the pygmy resonance, in going from the N = Z 40Ca to Ca isotopes with neutron excess

Global and regional brain metabolic scaling and its functional consequences

Background: Information processing in the brain requires large amounts of metabolic energy, the spatial distribution of which is highly heterogeneous reflecting complex activity patterns in the mammalian brain. Results: Here, it is found based on empirical data that, despite this heterogeneity, the volume-specific cerebral glucose metabolic rate of many different brain structures scales with brain volume with almost the same exponent around -0.15. The exception is white matter, the metabolism of which seems to scale with a standard specific exponent -1/4. The scaling exponents for the total oxygen and glucose consumptions in the brain in relation to its volume are identical and equal to $0.86\pm 0.03$, which is significantly larger than the exponents 3/4 and 2/3 suggested for whole body basal metabolism on body mass. Conclusions: These findings show explicitly that in mammals (i) volume-specific scaling exponents of the cerebral energy expenditure in different brain parts are approximately constant (except brain stem structures), and (ii) the total cerebral metabolic exponent against brain volume is greater than the much-cited Kleiber's 3/4 exponent. The neurophysiological factors that might account for the regional uniformity of the exponents and for the excessive scaling of the total brain metabolism are discussed, along with the relationship between brain metabolic scaling and computation.Comment: Brain metabolism scales with its mass well above 3/4 exponen