Deep brain stimulation of the subthalamic nucleus modulates sensitivity to decision outcome value in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus in Parkinson's disease is known to cause a subtle but important adverse impact on behaviour, with impulsivity its most widely reported manifestation. However, precisely which computational components of the decision process are modulated is not fully understood. Here we probe a number of distinct subprocesses, including temporal discount, outcome utility, instrumental learning rate, instrumental outcome sensitivity, reward-loss trade-offs, and perseveration. We tested 22 Parkinson's Disease patients both on and off subthalamic nucleus deep brain stimulation (STN-DBS), while they performed an instrumental learning task involving financial rewards and losses, and an inter-temporal choice task for financial rewards. We found that instrumental learning performance was significantly worse following stimulation, due to modulation of instrumental outcome sensitivity. Specifically, patients became less sensitive to decision values for both rewards and losses, but without any change to the learning rate or reward-loss trade-offs. However, we found no evidence that DBS modulated different components of temporal impulsivity. In conclusion, our results implicate the subthalamic nucleus in a modulation of outcome value in experience-based learning and decision-making in Parkinson's disease, suggesting a more pervasive role of the subthalamic nucleus in the control of human decision-making than previously thought.GRF gratefully acknowledges support by the German Research Council (Deutsche Forschungsgemeinschaft, KFO-219). Ray Dolan is supported by the Wellcome Trust (R.J.D., Senior Investigator Award 098362/Z/12/Z) and the the Senate of Berlin (R.J.D., Einstein Fellowship). Ben Seymour is funded by the Wellcome Trust and the National Institute of Information and Communications Technology, Japan; Peter Dayan is funded by the Gatsby Charitable Foundation

The effect of motivation on movement: a study of bradykinesia in Parkinson's disease.

Bradykinesia is a cardinal feature of Parkinson's disease (PD). Despite its disabling impact, the precise cause of this symptom remains elusive. Recent thinking suggests that bradykinesia may be more than simply a manifestation of motor slowness, and may in part reflect a specific deficit in the operation of motivational vigour in the striatum. In this paper we test the hypothesis that movement time in PD can be modulated by the specific nature of the motivational salience of possible action-outcomes

Werner states and the two-spinors Heisenberg anti-ferromagnet

We ascertain, following ideas of Arnesen, Bose, and Vedral concerning thermal entanglement [Phys. Rev. Lett. {\bf 87} (2001) 017901] and using the statistical tool called {\it entropic non-triviality} [Lamberti, Martin, Plastino, and Rosso, Physica A {\bf 334} (2004) 119], that there is a one to one correspondence between (i) the mixing coefficient $x$ of a Werner state, on the one hand, and (ii) the temperature $T$ of the one-dimensional Heisenberg two-spin chain with a magnetic field $B$ along the $z-$axis, on the other one. This is true for each value of $B$ below a certain critical value $B_c$. The pertinent mapping depends on the particular $B-$value one selects within such a range

Generation of broad XUV continuous high harmonic spectra and isolated attosecond pulses with intense mid-infrared lasers

We present experimental results showing the appearance of a near-continuum in the high-order harmonic generation (HHG) spectra of atomic and molecular species as the driving laser intensity of an infrared pulse increases. Detailed macroscopic simulations reveal that these near-continuum spectra are capable of producing IAPs in the far field if a proper spatial filter is applied. Further, our simulations show that the near-continuum spectra and the IAPs are a product of strong temporal and spatial reshaping (blue shift and defocusing) of the driving field. This offers a possibility of producing IAPs with a broad range of photon energy, including plateau harmonics, by mid-IR laser pulses even without carrier-envelope phase stabilization.Comment: 7 pages, 5 figures, submitted to J.Phys. B (Oct 2011

Tendency to Maximum Complexity in a Non-Equilibrium Isolated System

The time evolution equations of a simplified isolated ideal gas, the "tetrahe- dral" gas, are derived. The dynamical behavior of the LMC complexity [R. Lopez-Ruiz, H. L. Mancini, and X. Calbet, Phys. Lett. A 209, 321 (1995)] is studied in this system. In general, it is shown that the complexity remains within the bounds of minimum and maximum complexity. We find that there are certain restrictions when the isolated "tetrahedral" gas evolves towards equilibrium. In addition to the well-known increase in entropy, the quantity called disequilibrium decreases monotonically with time. Furthermore, the trajectories of the system in phase space approach the maximum complexity.Comment: 22 pages, 0 figures. Published in Phys. Rev. E 63, 066116(9) (2001

Dopamine, Salience, and Response Set Shifting in Prefrontal Cortex.

Dopamine is implicated in multiple functions, including motor execution, action learning for hedonically salient outcomes, maintenance, and switching of behavioral response set. Here, we used a novel within-subject psychopharmacological and combined functional neuroimaging paradigm, investigating the interaction between hedonic salience, dopamine, and response set shifting, distinct from effects on action learning or motor execution. We asked whether behavioral performance in response set shifting depends on the hedonic salience of reversal cues, by presenting these as null (neutral) or salient (monetary loss) outcomes. We observed marked effects of reversal cue salience on set-switching, with more efficient reversals following salient loss outcomes. l-Dopa degraded this discrimination, leading to inappropriate perseveration. Generic activation in thalamus, insula, and striatum preceded response set switches, with an opposite pattern in ventromedial prefrontal cortex (vmPFC). However, the behavioral effect of hedonic salience was reflected in differential vmPFC deactivation following salient relative to null reversal cues. l-Dopa reversed this pattern in vmPFC, suggesting that its behavioral effects are due to disruption of the stability and switching of firing patterns in prefrontal cortex. Our findings provide a potential neurobiological explanation for paradoxical phenomena, including maintenance of behavioral set despite negative outcomes, seen in impulse control disorders in Parkinson's disease

Emotionally Charged Aesthetic Experience

Abstract In traditional aesthetics, the typical characteristic of aesthetic experience is said to be pure disinterested beauty. However, the discussion based on this notion is burdened with the philosophical background assumptions of German idealism. In his Art as Experience John Dewey challenged the classical philosophical tradition and presented the key ideas for developing a new concept of aesthetic experience. In order to understand his pragmatist notion of aesthetic experience it is necessary to discuss a number of topics concerning pragmatist the challenge to classical philosophy. The philosophical naturalism of pragmatism questions the traditional distinction between the changing empirical world and the mind-independent real world as an object of genuine knowledge. There is only one world and we are in it. Dewey’s naturalism is, however, in important respects different from the main trend in contemporary naturalism. Further, the pragmatist conception of experience must be clearly distinguished from the traditional notion of experience as sense experience. Action and practice are modes of experiencing and understanding the world. The third topic concerns the naturalistic denial of any immaterial substances. The mind is necessarily embodied, but this is not enough to remove the classical dichotomy between internal and external. A fourth questionable dichotomy in classical philosophy is related to this: the sharp distinction between reason and experience. The pragmatist notion of meaning undermines this dualism. This notion of meaning also serves as a basis for understanding Dewey’s comments on the meanings typical in art. Finally, the emotionally expressive power of art requires an explanation. A discussion of all these points helps to clarify the character of the pragmatist notion of aesthetic experience developed below.Peer reviewe

Paraoxonase 2 protein is spatially expressed in the human placenta and selectively reduced in labour

Humans parturition involves interaction of hormonal, neurological, mechanical stretch and inflammatory pathways and the placenta plays a crucial role. The paraoxonases (PONs 1–3) protect against oxidative damage and lipid peroxidation, modulation of endoplasmic reticulum stress and regulation of apoptosis. Nothing is known about the role of PON2 in the placenta and labour. Since PON2 plays a role in oxidative stress and inflammation, both features of labour, we hypothesised that placental PON2 expression would alter during labour. PON2 was examined in placentas obtained from women who delivered by cesarean section and were not in labour and compared to the equivalent zone of placentas obtained from women who delivered vaginally following an uncomplicated labour. Samples were obtained from 12 sites within each placenta: 4 equally spaced apart pieces were sampled from the inner, middle and outer placental regions. PON2 expression was investigated by Western blotting and real time PCR. Two PON2 forms, one at 62 kDa and one at 43 kDa were found in all samples. No difference in protein expression of either isoform was found between the three sites in either the labour or non-labour group. At the middle site there was a highly significant decrease in PON2 expression in the labour group when compared to the non-labour group for both the 62 kDa form (p = 0.02) and the 43 kDa form (p = 0.006). No spatial differences were found within placentas at the mRNA level in either labour or non-labour. There was, paradoxically, an increase in PON2 mRNA in the labour group at the middle site only. This is the first report to describe changes in PON2 in the placenta in labour. The physiological and pathological significance of these remains to be elucidated but since PON2 is anti-inflammatory further studies are warranted to understand its role