Altered brainstem responses to modafinil in schizophrenia: implications for adjunctive treatment of cognition.

Candidate pro-cognitive drugs for schizophrenia targeting several neurochemical systems have consistently failed to demonstrate robust efficacy. It remains untested whether concurrent antipsychotic medications exert pharmacodynamic interactions that mitigate pro-cognitive action in patients. We used functional MRI (fMRI) in a randomized, double-blind, placebo-controlled within-subject crossover test of single-dose modafinil effects in 27 medicated schizophrenia patients, interrogating brainstem regions where catecholamine systems arise to innervate the cortex, to link cellular and systems-level models of cognitive control. Modafinil effects were evaluated both within this patient group and compared to a healthy subject group. Modafinil modulated activity in the locus coeruleus (LC) and ventral tegmental area (VTA) in the patient group. However, compared to the healthy comparison group, these effects were altered as a function of task demands: the control-independent drug effect on deactivation was relatively attenuated (shallower) in the LC and exaggerated (deeper) in the VTA; in contrast, again compared to the comparison group, the control-related drug effects on positive activation were attenuated in LC, VTA and the cortical cognitive control network. These altered effects in the LC and VTA were significantly and specifically associated with the degree of antagonism of alpha-2 adrenergic and dopamine-2 receptors, respectively, by concurrently prescribed antipsychotics. These sources of evidence suggest interacting effects on catecholamine neurons of chronic antipsychotic treatment, which respectively increase and decrease sustained neuronal activity in LC and VTA. This is the first direct evidence in a clinical population to suggest that antipsychotic medications alter catecholamine neuronal activity to mitigate pro-cognitive drug action on cortical circuits

Proactive and reactive cognitive control and dorsolateral prefrontal cortex dysfunction in first episode schizophrenia.

Cognitive control deficits have been consistently documented in patients with schizophrenia. Recent work in cognitive neuroscience has hypothesized a distinction between two theoretically separable modes of cognitive control-reactive and proactive. However, it remains unclear the extent to which these processes are uniquely associated with dysfunctional neural recruitment in individuals with schizophrenia. This functional magnetic resonance imaging (fMRI) study utilized the color word Stroop task and AX Continuous Performance Task (AX-CPT) to tap reactive and proactive control processes, respectively, in a sample of 54 healthy controls and 43 patients with first episode schizophrenia. Healthy controls demonstrated robust dorsolateral prefrontal, anterior cingulate, and parietal cortex activity on both tasks. In contrast, patients with schizophrenia did not show any significant activation during proactive control, while showing activation similar to control subjects during reactive control. Critically, an interaction analysis showed that the degree to which prefrontal activity was reduced in patients versus controls depended on the type of control process engaged. Controls showed increased dorsolateral prefrontal cortex (DLPFC) and parietal activity in the proactive compared to the reactive control task, whereas patients with schizophrenia did not demonstrate this increase. Additionally, patients' DLPFC activity and performance during proactive control was associated with disorganization symptoms, while no reactive control measures showed this association. Proactive control processes and concomitant dysfunctional recruitment of DLPFC represent robust features of schizophrenia that are also directly associated with symptoms of disorganization

New Hamiltonian formalism and quasi-local conservation equations of general relativity

I describe the Einstein's gravitation of 3+1 dimensional spacetimes using the (2,2) formalism without assuming isometries. In this formalism, quasi-local energy, linear momentum, and angular momentum are identified from the four Einstein's equations of the divergence-type, and are expressed geometrically in terms of the area of a two-surface and a pair of null vector fields on that surface. The associated quasi-local balance equations are spelled out, and the corresponding fluxes are found to assume the canonical form of energy-momentum flux as in standard field theories. The remaining non-divergence-type Einstein's equations turn out to be the Hamilton's equations of motion, which are derivable from the {\it non-vanishing} Hamiltonian by the variational principle. The Hamilton's equations are the evolution equations along the out-going null geodesic whose {\it affine} parameter serves as the time function. In the asymptotic region of asymptotically flat spacetimes, it is shown that the quasi-local quantities reduce to the Bondi energy, linear momentum, and angular momentum, and the corresponding fluxes become the Bondi fluxes. The quasi-local angular momentum turns out to be zero for any two-surface in the flat Minkowski spacetime. I also present a candidate for quasi-local {\it rotational} energy which agrees with the Carter's constant in the asymptotic region of the Kerr spacetime. Finally, a simple relation between energy-flux and angular momentum-flux of a generic gravitational radiation is discussed, whose existence reflects the fact that energy-flux always accompanies angular momentum-flux unless the flux is an s-wave.Comment: 36 pages, 3 figures, RevTex

Relative Yields and Nutritive Value of Whole Crop Rice Harvested on Four Successive Dates for Forage in Korea

About four million tons of forages are fed to ruminants in Korea, but half of them rely on rice straw as roughage and 0.6 million tons of forage was imported. The lack of forage results in increased imports of concentrate feeds and increased production cost. Now, Korea has about 1.1 million ha of rice fields, but as a consequence of world trade negotiation, Korea will open the rice market from next year. It is expected that due to aging farmers and lower rice price, about 0.2 million ha of paddy field will not be cultivated for grain rice. Therefore, we suggest that whole-crop rice cultivation for feeding beef and dairy cattle. The purpose of this study was to investigate relative yield and nutritive value of whole-crop rice grown in paddy fields in Korea

Broader Visual Orientation Tuning in Patients with Schizophrenia

Reduced gamma-aminobutyric acid (GABA) levels in cerebral cortex are thought to contribute to information processing deficits in patients with schizophrenia (SZ), and we have previously reported lower in vivo GABA levels in the visual cortex of patients with SZ. GABA-mediated inhibition plays a role in sharpening orientation tuning of visual cortical neurons. Therefore, we predicted that tuning for visual stimulus orientation would be wider in SZ. We measured orientation tuning with a psychophysical procedure in which subjects performed a target detection task of a low-contrast oriented grating, following adaptation to a high-contrast grating. Contrast detection thresholds were determined for a range of adapter–target orientation offsets. For both SZ and healthy controls, contrast thresholds decreased as orientation offset increased, suggesting that this tuning curve reflects the selectivity of visual cortical neurons for stimulus orientation. After accounting for generalized deficits in task performance in SZ, there was no difference between patients and controls for detection of target stimuli having either the same orientation as the adapter or orientations far from the adapter. However, patients’ thresholds were significantly higher for intermediate adapter–target offsets. In addition, the mean width parameter of a Gaussian fit to the psychophysical orientation tuning curves was significantly larger for the patient group. We also present preliminary data relating visual cortical GABA levels, as measured with magnetic resonance spectroscopy, and orientation tuning width. These results suggest that our finding of broader orientation tuning in SZ may be due to diminished visual cortical GABA levels

Complex Capacitance Analysis on Leakage Current Appearing in Electric Double-layer Capacitor Carbon Electrode

imaginary capacitance profiles(Cim vs. log f) were theoretically derived for a cylindrical pore and multiple pore systems of nonuniform pore geometry. The parallel RC circuit was assumed for the interfacial impedance, where R is the charge-transfer resistance for leakage current and C the double-layer capacitance. The theoretical derivation illustrated that the resistive tail relevant to the leakage current appears in addition to the capacitive peak, which was in accordance with the experimental data taken on the porous carbon electrode. The electric double-layer capacitor (EDLC) parameters such as the extent of leakage current, total capacitance, and rate capability were visually estimated from the imaginary capacitance profiles. The more quantitative EDLC parameters were obtained by a nonlinear fitting to the experimental data.This work was supported by KOSEF through the Research Center for Energy Conversion and Storage and also by the Division of Advanced Batteries in NGE Program (project no. 10016446)