ERP evidence suggests executive dysfunction in ecstasy polydrug users

Background: Deficits in executive functions such as access to semantic/long-term memory have been shown in ecstasy users in previous research. Equally, there have been many reports of equivocal findings in this area. The current study sought to further investigate behavioural and electro-physiological measures of this executive function in ecstasy users. Method: Twenty ecstasy–polydrug users, 20 non-ecstasy–polydrug users and 20 drug-naïve controls were recruited. Participants completed background questionnaires about their drug use, sleep quality, fluid intelligence and mood state. Each individual also completed a semantic retrieval task whilst 64 channel Electroencephalography (EEG) measures were recorded. Results: Analysis of Variance (ANOVA) revealed no between-group differences in behavioural performance on the task. Mixed ANOVA on event-related potential (ERP) components P2, N2 and P3 revealed significant between-group differences in the N2 component. Subsequent exploratory univariate ANOVAs on the N2 component revealed marginally significant between-group differences, generally showing greater negativity at occipito-parietal electrodes in ecstasy users compared to drug-naïve controls. Despite absence of behavioural differences, differences in N2 magnitude are evidence of abnormal executive functioning in ecstasy–polydrug users

Imbalanced decision hierarchy in addicts emerging from drug-hijacked dopamine spiraling circuit

Despite explicitly wanting to quit, long-term addicts find themselves powerless to resist drugs, despite knowing that drug-taking may be a harmful course of action. Such inconsistency between the explicit knowledge of negative consequences and the compulsive behavioral patterns represents a cognitive/behavioral conflict that is a central characteristic of addiction. Neurobiologically, differential cue-induced activity in distinct striatal subregions, as well as the dopamine connectivity spiraling from ventral striatal regions to the dorsal regions, play critical roles in compulsive drug seeking. However, the functional mechanism that integrates these neuropharmacological observations with the above-mentioned cognitive/behavioral conflict is unknown. Here we provide a formal computational explanation for the drug-induced cognitive inconsistency that is apparent in the addicts' “self-described mistake”. We show that addictive drugs gradually produce a motivational bias toward drug-seeking at low-level habitual decision processes, despite the low abstract cognitive valuation of this behavior. This pathology emerges within the hierarchical reinforcement learning framework when chronic exposure to the drug pharmacologically produces pathologicaly persistent phasic dopamine signals. Thereby the drug hijacks the dopaminergic spirals that cascade the reinforcement signals down the ventro-dorsal cortico-striatal hierarchy. Neurobiologically, our theory accounts for rapid development of drug cue-elicited dopamine efflux in the ventral striatum and a delayed response in the dorsal striatum. Our theory also shows how this response pattern depends critically on the dopamine spiraling circuitry. Behaviorally, our framework explains gradual insensitivity of drug-seeking to drug-associated punishments, the blocking phenomenon for drug outcomes, and the persistent preference for drugs over natural rewards by addicts. The model suggests testable predictions and beyond that, sets the stage for a view of addiction as a pathology of hierarchical decision-making processes. This view is complementary to the traditional interpretation of addiction as interaction between habitual and goal-directed decision systems

Increased Photosynthesis Contributes towards Improved Ovule-to-Seed Ratio in IAA Treated Range Grasses

Poor ovule-to-seed ratio is one of the major constraints in quality seed production in range grasses. Plant hormones per se or in the influence of external cues were known regulate the seed setting and their subsequent maturation in many crops. External application of hormones on the standing crops has shown very promising results but the physiological and biochemical phenomenon underlying such changes are not studied in detail. Exogenous application of different chemicals particularly during anthesis and post anthesis phases has increased the seed set in a number of species. Improved seed germination in Panicum maximum after foliar spray of indole acetic acid (IAA) has been reported by Malaviya et al., (2013). but the reason for improved seed germination was not very much clear. Auxin application has also been shown to induce fruit-set in many crops. Auxins with its prominent role in cell division have been implicated to play vital role in integument growth during early seed formation (Wu et al., 2006) and increased integuments has been correlated with increased seed size in Arabidopsis (Schruff et al., 2006) where they postulate that increased integument provides larger seed cavity which in turn provides a greater area of contact for endosperm with the seed coat, leading to increased nutrient uptake. Increase in photosynthesis rate due to foliar application of many phytohormones has also been reported in many crops and understanding source sink relationship as influenced by different growth regulators might lead to significant breakthrough in understanding the seed production as a whole and seed filling in particular. Though the role of plant growth regulators in seed production is well researched in many crops but not much work has been undertaken to improve the production and quality of seeds in range grasses. Panicum maximum and Cenchrus ciliaris are two most important range grasses of irrigated and non-irrigated conditions respectively and both produces seeds of very poor quality in terms of germination. Therefore, in present study we try to improve seed filling through foliar application of IAA in these crops and studied the photosynthesis behaviour post treatment

Biases in the Explore-Exploit Tradeoff in Addictions: The Role of Avoidance of Uncertainty.

We focus on exploratory decisions across disorders of compulsivity, a potential dimensional construct for the classification of mental disorders. Behaviors associated with the pathological use of alcohol or food, in alcohol use disorders (AUD) or binge-eating disorder (BED), suggest a disturbance in explore-exploit decision-making, whereby strategic exploratory decisions in an attempt to improve long-term outcomes may diminish in favor of more repetitive or exploitatory choices. We compare exploration vs exploitation across disorders of natural (obesity with and without BED) and drug rewards (AUD). We separately acquired resting state functional MRI data using a novel multi-echo planar imaging sequence and independent components analysis from healthy individuals to assess the neural correlates underlying exploration. Participants with AUD showed reduced exploratory behavior across gain and loss environments, leading to lower-yielding exploitatory choices. Obese subjects with and without BED did not differ from healthy volunteers but when compared with each other or to AUD subjects, BED had enhanced exploratory behaviors particularly in the loss domain. All subject groups had decreased exploration or greater uncertainty avoidance to losses compared with rewards. More exploratory decisions in the context of reward were associated with frontal polar and ventral striatal connectivity. For losses, exploration was associated with frontal polar and precuneus connectivity. We further implicate the relevance and dimensionality of constructs of compulsivity across disorders of both natural and drug rewards.The study was funded by the Wellcome Trust Fellowship grant for VV (093705/Z/10/Z) and Cambridge NIHR Biomedical Research Centre. VV and NAH are Wellcome Trust (WT) intermediate Clinical Fellows. LSM is in receipt of an MRC studentship. The BCNI is supported by a WT and MRC grant. MF is funded by NIMH and NSF grants and is consultant for Hoffman LaRoche pharmaceuticals. The remaining authors declare no competing financial interests.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/npp.2015.20

Dopamine, affordance and active inference.

The role of dopamine in behaviour and decision-making is often cast in terms of reinforcement learning and optimal decision theory. Here, we present an alternative view that frames the physiology of dopamine in terms of Bayes-optimal behaviour. In this account, dopamine controls the precision or salience of (external or internal) cues that engender action. In other words, dopamine balances bottom-up sensory information and top-down prior beliefs when making hierarchical inferences (predictions) about cues that have affordance. In this paper, we focus on the consequences of changing tonic levels of dopamine firing using simulations of cued sequential movements. Crucially, the predictions driving movements are based upon a hierarchical generative model that infers the context in which movements are made. This means that we can confuse agents by changing the context (order) in which cues are presented. These simulations provide a (Bayes-optimal) model of contextual uncertainty and set switching that can be quantified in terms of behavioural and electrophysiological responses. Furthermore, one can simulate dopaminergic lesions (by changing the precision of prediction errors) to produce pathological behaviours that are reminiscent of those seen in neurological disorders such as Parkinson's disease. We use these simulations to demonstrate how a single functional role for dopamine at the synaptic level can manifest in different ways at the behavioural level

Integrating Impedance Control and Nonlinear Disturbance Observer for Robot-Assisted Arthroscope Control in Elbow Arthroscopic Surgery

ABSTRACT: Robot-assisted arthroscopic surgery is transforming the tradition in orthopaedic surgery. Compliance and stability are essential features that a surgical robot must have for safe physical human-robot interaction (pHRI). Surgical tools attached at the robot end-effector and human-robot interaction will affect the robot dynamics inevitably. This could undermine the utility and stability of the robotic system if the varying robot dynamics are not identified and updated in the robot control law. In this paper, an integrated framework for robot impedance control and nonlinear disturbance observer (NDOB)-based compensation of uncertain dynamics is proposed, where the former ensures compliant robot behavior and the latter compensates for dynamic uncertainties when necessary. The combination of impedance controller and NDOB is analyzed theoretically in three scenarios. A complete simulation and experimental studies involving three common conditions are then conducted to evaluate the theoretical analyses. A preliminary pHRI application on arthroscopic surgery is designed to implement the proposed framework on a robotic surgeon-assist system and evaluate its effectiveness experimentally. By integrating impedance controller with NDOB, the proposed framework allows an accurate impedance control when dynamic model inaccuracy and external disturbance exist

Towards neuro-inspired symbolic models of cognition: linking neural dynamics to behaviors through asynchronous communications

A computational architecture modeling the relation between perception and action is proposed. Basic brain processes representing synaptic plasticity are first abstracted through asynchronous communication protocols and implemented as virtual microcircuits. These are used in turn to build mesoscale circuits embodying parallel cognitive processes. Encoding these circuits into symbolic expressions gives finally rise to neuro-inspired programs that are compiled into pseudo-code to be interpreted by a virtual machine. Quantitative evaluation measures are given by the modification of synapse weights over time. This approach is illustrated by models of simple forms of behaviors exhibiting cognition up to the third level of animal awareness. As a potential benefit, symbolic models of emergent psychological mechanisms could lead to the discovery of the learning processes involved in the development of cognition. The executable specifications of an experimental platform allowing for the reproduction of simulated experiments are given in “Appendix”

Conditioned task-set competition:Neural mechanisms of emotional interference in depression

Depression has been associated with increased response times at the incongruent, neutral, and negative-word trials of the classical and emotional Stroop tasks (Epp et al., 2012). Response time slow-down effects at incongruent and negative-word trials of the Stroop tasks were reported to correlate with depressive severity, indicating strong relevance of the effects to the symptomatology. The current study proposes a novel integrative computational model of neural mechanisms of both the classical and the emotional Stroop effects, drawing on the previous prominent theoretical explanations of performance at the classical Stroop task (Cohen et al., 1990; Herd et al., 2006), and in addition suggesting that negative emotional words represent conditioned stimuli for future negative outcomes. The model is shown to explain the classical Stroop effect and the slow (between-trial) emotional Stroop effect with biologically-plausible mechanisms, providing an advantage over the previous theoretical accounts (Matthews and Harley, 1996; Wyble et al., 2008). Simulation results suggested a candidate mechanism responsible for the pattern of depressive performance at the classical and the emotional Stroop tasks. Hyperactivity of the amygdala, together with increased inhibitory influence of the amygdala over dopaminergic neurotransmission, could be at the origin of the performance deficits

Recruitment of lateral rostral prefrontal cortex in spontaneous and task-related thoughts

Behavioural and neuroimaging studies suggest that spontaneous and task-related thought processes share common cognitive mechanisms and neural bases. Lateral rostral prefrontal cortex (RPFC) is a brain region that has been implicated both in spontaneous thought and in high-level cognitive control processes, such as goal/subgoal integration and the manipulation of self-generated thoughts. We therefore propose that the recruitment of lateral RPFC may follow a U-shaped function of cognitive demand: relatively high in low-demand situations conducive to the emergence of spontaneous thought, and in high-demand situations depending on processes supported by this brain region. We used functional magnetic resonance imaging to investigate brain activity while healthy participants performed two tasks, each with three levels of cognitive demands, in a block design. The frequency of task-unrelated thoughts, measured by questionnaire, was highest in the low cognitive demand condition. Low and high cognitive demand conditions were each compared to the intermediate level. Lateral RPFC and superior parietal cortex were recruited in both comparisons, with additional activations specific to each contrast. These results suggest that RPFC is involved both when (a) task demands are low, and the mind wanders, and (b) the task requires goal/subgoal integration and manipulation of self-generated thoughts