Is Avoiding an Aversive Outcome Rewarding? Neural Substrates of Avoidance Learning in the Human Brain

Avoidance learning poses a challenge for reinforcement-based theories of instrumental conditioning, because once an aversive outcome is successfully avoided an individual may no longer experience extrinsic reinforcement for their behavior. One possible account for this is to propose that avoiding an aversive outcome is in itself a reward, and thus avoidance behavior is positively reinforced on each trial when the aversive outcome is successfully avoided. In the present study we aimed to test this possibility by determining whether avoidance of an aversive outcome recruits the same neural circuitry as that elicited by a reward itself. We scanned 16 human participants with functional MRI while they performed an instrumental choice task, in which on each trial they chose from one of two actions in order to either win money or else avoid losing money. Neural activity in a region previously implicated in encoding stimulus reward value, the medial orbitofrontal cortex, was found to increase, not only following receipt of reward, but also following successful avoidance of an aversive outcome. This neural signal may itself act as an intrinsic reward, thereby serving to reinforce actions during instrumental avoidance

Deep Chandra Monitoring Observations of NGC 4649: II. Wide-Field Hubble Space Telescope Imaging of the Globular Clusters

We present g and z photometry and size estimates for globular clusters (GCs) in the massive Virgo elliptical NGC 4649 (M60) using a five-pointing Hubble Space Telescope/Advanced Camera for Surveys mosaic. The metal-poor GCs show a monotonic negative metallicity gradient of (-0.43 +/- 0.10) dex per dex in radius over the full radial range of the data, out to ~ 24 kpc. There is evidence for substantial color substructure among the metal-rich GCs. The metal-poor GCs have typical sizes ~ 0.4 pc larger than the metal-rich GCs out to large galactocentric distances (~> 20 kpc), favoring an intrinsic explanation for the size difference rather than projection effects. There is no clear relation between half-light radius and galactocentric distance beyond ~ 15 kpc, suggesting that the sizes of GCs are not generically set by tidal limitation. Finally, we identify ~ 20 candidate ultra-compact dwarfs that extend down to surprisingly faint absolute magnitudes (M_z ~ -8.5), and may bridge the gap between this class and "extended clusters" in the Local Group. Three of the brighter candidates have published radial velocities and can be confirmed as bona fide ultra-compact dwarfs; follow-up spectroscopy will determine the nature of the remainder of the candidates.Comment: ApJ in press. For redacted long table 1, see: http://www.pa.msu.edu/~strader/4649/table.te

How to return to subjectivity? Natorp, Husserl, and Lacan on the limits of reflection

This article discusses the recent call within contemporary phenomenology to return to subjectivity in response to certain limitations of naturalistic explanations of the mind. The meaning and feasibility of this call is elaborated by connecting it to a classical issue within the phenomenological tradition concerning the possibility of investigating the first-person perspective through reflection. We will discuss how this methodological question is respectively treated and reconfigured in the works of Natorp, Husserl, and Lacan. Finally, we will lay out some possible consequences of such a cross-reading for the conception of subjectivity and the concomitant effort to account for this dimension of first-person experience in response and in addition to its omission within the standard third-person perspective of psychological research

Hydrogen peroxide generation by mitochondria isolated from regionally ischemic and nonischemic dog myocardium

We occluded the left anterior descending coronary artery of anesthetized, open-chest dogs, for 1 or 2 h. Some hearts were reperfused for 1 h after 1 h of ischemia. We isolated mitochondria from the central ischemic zone (CIZ) and a surrounding nonischemic zone (NIZ) of the left ventricle, and assayed H 2 O 2 production using a horseradish peroxidase-dual wavelength spectrophotometric technique. Mitochondria, studied in the absence of exogenous respiratory chain inhibitors, generated H 2 O 2 during State 4 respiration with succinate as the substrate. NIZ mitochondria in all groups produced ca. 1.5 nmols H 2 O 2 /min/mg protein (no significant differences between groups). The State 4 O 2 consumption rates of NIZ mitochondria from hearts subjected to 1 h ischemia plus reperfusion, or 2 h of ischemia (ca. 30 nmols/min/mg) were significantly higher than that of NIZ mitochondria of hearts subjected to only 1 h of ischemia (23 nmols/min/mg). Thus, the ratio between H 2 O 2 produced and State 4 O 2 consumption fell from 6.5% to 5%. Mitochondria from all CIZ samples had State 4 O 2 consumption rates that were not different from corresponding NIZ values. However CIZ mitochondria of hearts subjected to 1 h ischemia without reperfusion produced less H 2 O 2 (1.1±0.1 nmols/min/mg), and had a slightly reduced H 2 O 2 /O 2 ratio (4.4±0.7%), compared with their NIZ samples (1.5±0.1 nmols/min/mg; 5.3%). Reperfusion after 1 h of ischemia abolished these regional differences. The CIZ mitochondria from hearts subjected to 2 h ischemia produced only 0.75±0.22 nmols H 2 O 2 /min/mg (2.5% of State 4 O 2 consumption). These values were 50% of corresponding NIZ values, and were significantly less than for any other group or tissue region. If similar phenomena occur in conscious animals subjected to incomplete regional ischemia, especially of relatively brief duration or if accompanied by reduced intracellular defenses against oxidants such as H 2 O 2 , they suggest that mitochondria persist as H 2 O 2 sources and so may contribute to the oxidant load and myocardial dysfunction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41749/1/395_2005_Article_BF01907125.pd

Spatial and temporal characteristics of circumferential flow-function relations during acute myocardial ischemia in the conscious dog

In the anesthetized open-chest dog the ischemic area produced by coronary occlusion is surrounded by an area of nonischemic contractile dysfunction, identified as the functional border zone. To establish whether a similar functional border zone exists in the conscious animal during acute regional ischemia and to determine its spatial dimensions and temporal changes, we performed simultaneous two-dimensional echocardiography and radioactive microsphere studies in nine chronically instrumented dogs. We produced circumferential flow-function maps at 22.5-degree intervals over the full circumference of the left ventricle at the midpapillary muscle level during control conditions, 5 minutes after left circumflex occlusion, and 2.5 hours after left circumflex occlusion. After occlusion there was no change in left ventricular end-diastolic area, an increase in left ventricular end-systolic area (p p p p < 0.01) in the functional border zone, there was no difference in subendocardial blood flow between the functional border zone and the control nonischemic area. We conclude that a discrete functional border zone exists in the conscious dog during acute regional ischemia produced by circumflex coronary occlusion, which does not change during the early evolution of myocardial infarction. The functional border zone likely contributes to minor overestimation of infarct size in the early hours after myocardial infarction if extent of left ventricular dysfunction is used as an index of infarction in humans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27055/1/0000045.pd

ATP precursor depletion and postischemic myocardial recovery

Although cardioplegia reduces myocardial metabolism during ischemia, adenosine triphosphate (ATP) depletion occurs, which may contribute to poor functional recovery after reperfusion. Augmenting myocardial adenosine during ischemia is successful in improving ATP repletion and myocardial recovery following ischemia. If adenosine is an important determinant of ischemic tolerance, then depletion or elimination of myocardial adenosine should lead to poor functional and metabolic recovery after ischemia. To test this hypothesis, isolated, perfused rabbit hearts were subjected to 120 min of 34[deg]C ischemia. Hearts received St. Thomas cardioplegia alone or cardioplegia containing 200 [mu]M adenosine, or cardioplegia containing 15, 5, 2.5, or 0.025 [mu]g/ml adenosine deaminase (ADA), which catalyzes the breakdown of adenosine to inosine, making adenosine unavailable as an ATP precursor. Functional recovery was determined and myocardial nucleotide levels were measured before, during, and after ischemia. Following ischemia and reperfusion, control hearts recovered to 51 +/- 3% of preischemic developed pressure (DP). There was significantly better recovery in adenosine-augmented hearts (68 +/- 7%), while ADA hearts had significantly worse recovery. Hearts treated with 0.025 [mu]g/ml ADA recovered to only 29 +/- 5% of DP and higher dose ADA hearts failed to demonstrate any recovery of systolic function. Furthermore, adenosine enhanced metabolic recovery, whereas ADA resulted in greatly depleted ATP and precursor reserves. Postischemic developed pressure closely paralleled the availability of myocardial adenosine, consistent with the hypothesis that myocardial adenosine levels at end ischemia and early reperfusion are important determinants of functional recovery after global ischemia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29313/1/0000378.pd

Creating and observing N-partite entanglement with atoms

The Mermin inequality provides a criterion for experimentally ruling out local-realistic descriptions of multiparticle systems. A violation of this inequality means that the particles must be entangled, but does not, in general, indicate whether N-partite entanglement is present. For this, a stricter bound is required. Here we discuss this bound and use it to propose two different schemes for demonstrating N-partite entanglement with atoms. The first scheme involves Bose-Einstein condensates trapped in an optical lattice and the second uses Rydberg atoms in microwave cavities.Comment: 12 pages, 4 figure

Absence of detectable xanthine oxidase in human myocardium

The enzyme xanthine oxidase has been implicated as a generator of toxic oxygen metabolites that contribute to ischemic injury. Because substantial species variability has been demonstrated and because there are minimal human data available, the relevance of xanthine oxidase to human heart damage has been in doubt. We report the absence of xanthine oxidase activity in nine human heart biopsy specimens obtained during cardiac surgery, and in two larger samples obtained during heart transplantation. A sensitive radiochemical assay was used to assess enzyme activity. Our findings imply that oxygen free radicals generated by xanthine oxidase are not relevent in terms of human myocardial injury.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28034/1/0000473.pd