Self-Affirmation Improves Problem-Solving under Stress

High levels of acute and chronic stress are known to impair problem-solving and creativity on a broad range of tasks. Despite this evidence, we know little about protective factors for mitigating the deleterious effects of stress on problem-solving. Building on previous research showing that self-affirmation can buffer stress, we tested whether an experimental manipulation of self-affirmation improves problem-solving performance in chronically stressed participants. Eighty undergraduates indicated their perceived chronic stress over the previous month and were randomly assigned to either a self-affirmation or control condition. They then completed 30 difficult remote associate problem-solving items under time pressure in front of an evaluator. Results showed that self-affirmation improved problem-solving performance in underperforming chronically stressed individuals. This research suggests a novel means for boosting problem-solving under stress and may have important implications for understanding how self-affirmation boosts academic achievement in school settings. © 2013 Creswell et al

Dopaminergic modulation of appetitive trace conditioning: the role of D1 receptors in medial prefrontal cortex

Rationale: Trace conditioning may provide a behavioural model suitable to examine the maintenance of ‘on line’ information and its underlying neural substrates. Objectives: Experiment la was run to establish trace conditioning in a shortened procedure which would be suitable to test the effects of dopamine (DA) D1 receptor agents administered by microinjection directly into the brain. Experiment lb examined the effects of the DA D1 agonist SKF81297 and the DA D1 antagonist SCH23390 following systemic administration in pre-trained animals. Experiment 2 went on to test the effects of systemically administered SKF81297 on the acquisition of trace conditioning. In experiment 3, SKF81297 was administered directly in prelimbic (PL) and infralimbic (IL) sub-regions of medial prefrontal cortex (mPFC) to compare the role of different mPFC sub-regions. Results: Whilst treatment with SCH23390 impaired motor responding and/or motivation, SKF81297 had relatively little effect in the pre-trained animals tested in experiment 1b. However, systemic SKF81297 depressed the acquisition function at the 2-s trace interval in experiment 2. Similarly, in experiment 3, SKF81297 (0.1 μg in 1.0 μl) microinjected into either PL or IL mPFC impaired appetitive conditioning at the 2-s trace interval. Conclusions: Impaired trace conditioning under SKF81297 is likely to be mediated in part (but not exclusively) within the IL and PL mPFC sub-regions. The finding that trace conditioning was impaired rather than enhanced under SKF81297 provides further evidence for the inverse U-function which has been suggested to be characteristic of mPFC DA function

Mindfulness-based interventions for young offenders: a scoping review

Youth offending is a problem worldwide. Young people in the criminal justice system have frequently experienced adverse childhood circumstances, mental health problems, difficulties regulating emotions and poor quality of life. Mindfulness-based interventions can help people manage problems resulting from these experiences, but their usefulness for youth offending populations is not clear. This review evaluated existing evidence for mindfulness-based interventions among such populations. To be included, each study used an intervention with at least one of the three core components of mindfulness-based stress reduction (breath awareness, body awareness, mindful movement) that was delivered to young people in prison or community rehabilitation programs. No restrictions were placed on methods used. Thirteen studies were included: three randomized controlled trials, one controlled trial, three pre-post study designs, three mixed-methods approaches and three qualitative studies. Pooled numbers (n = 842) comprised 99% males aged between 14 and 23. Interventions varied so it was not possible to identify an optimal approach in terms of content, dose or intensity. Studies found some improvement in various measures of mental health, self-regulation, problematic behaviour, substance use, quality of life and criminal propensity. In those studies measuring mindfulness, changes did not reach statistical significance. Qualitative studies reported participants feeling less stressed, better able to concentrate, manage emotions and behaviour, improved social skills and that the interventions were acceptable. Generally low study quality limits the generalizability of these findings. Greater clarity on intervention components and robust mixed-methods evaluation would improve clarity of reporting and better guide future youth offending prevention programs

A computational psychiatry approach identifies how alpha-2A noradrenergic agonist Guanfacine affects feature-based reinforcement learning in the macaque

[EN] Noradrenaline is believed to support cognitive flexibility through the alpha 2A noradrenergic receptor (a2A-NAR) acting in prefrontal cortex. Enhanced flexibility has been inferred from improved working memory with the a2A-NA agonist Guanfacine. But it has been unclear whether Guanfacine improves specific attention and learning mechanisms beyond working memory, and whether the drug effects can be formalized computationally to allow single subject predictions. We tested and confirmed these suggestions in a case study with a healthy nonhuman primate performing a feature-based reversal learning task evaluating performance using Bayesian and Reinforcement learning models. In an initial dose-testing phase we found a Guanfacine dose that increased performance accuracy, decreased distractibility and improved learning. In a second experimental phase using only that dose we examined the faster feature-based reversal learning with Guanfacine with single-subject computational modeling. Parameter estimation suggested that improved learning is not accounted for by varying a single reinforcement learning mechanism, but by changing the set of parameter values to higher learning rates and stronger suppression of non-chosen over chosen feature information. These findings provide an important starting point for developing nonhuman primate models to discern the synaptic mechanisms of attention and learning functions within the context of a computational neuropsychiatry framework.This research was supported by grants from the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Ontario Ministry of Economic Development and Innovation (MEDI). We thank Dr. Hongying Wang for invaluable help with drug administration and animal careHassani, SA.; Oemisch, M.; Balcarras, M.; Westendorff, S.; Ardid-Ramírez, JS.; Van Der Meer, MA.; Tiesinga, P.... (2017). A computational psychiatry approach identifies how alpha-2A noradrenergic agonist Guanfacine affects feature-based reinforcement learning in the macaque. Scientific Reports. 7:1-19. https://doi.org/10.1038/srep40606S1197Arnsten, A. F., Wang, M. J. & Paspalas, C. D. Neuromodulation of thought: flexibilities and vulnerabilities in prefrontal cortical network synapses. Neuron 76, 223–239 (2012).Arnsten, A. F. & Dudley, A. G. Methylphenidate improves prefrontal cortical cognitive function through alpha2 adrenoceptor and dopamine D1 receptor actions: Relevance to therapeutic effects in Attention Deficit Hyperactivity Disorder. Behav Brain Funct 1, 2 (2005).Clark, K. L. & Noudoost, B. The role of prefrontal catecholamines in attention and working memory. Front Neural Circuits 8, 33 (2014).Wang, M. et al. Neuronal basis of age-related working memory decline. Nature 476, 210–213 (2011).Wang, M. et al. Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex. Cell 129, 397–410 (2007).Aston-Jones, G. & Cohen, J. D. An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci 28, 403–450 (2005).Yu, A. J. & Dayan, P. Uncertainty, neuromodulation, and attention. Neuron 46, 681–692 (2005).Mather, M., Clewett, D., Sakaki, M. & Harley, C. W. Norepinephrine ignites local hot spots of neuronal excitation: How arousal amplifies selectivity in perception and memory. Behav Brain Sci, 1–100, doi: 10.1017/S0140525X15000667 (2015).Amemiya, S. & Redish, A. D. Manipulating Decisiveness in Decision Making: Effects of Clonidine on Hippocampal Search Strategies. J Neurosci 36, 814–827 (2016).Doya, K. Metalearning and neuromodulation. Neural Netw 15, 495–506 (2002).Uhlen, S., Muceniece, R., Rangel, N., Tiger, G. & Wikberg, J. E. Comparison of the binding activities of some drugs on alpha 2A, alpha 2B and alpha 2C-adrenoceptors and non-adrenergic imidazoline sites in the guinea pig. Pharmacology & toxicology 76, 353–364 (1995).Mao, Z. M., Arnsten, A. F. & Li, B. M. Local infusion of an alpha-1 adrenergic agonist into the prefrontal cortex impairs spatial working memory performance in monkeys. Biological psychiatry 46, 1259–1265 (1999).Arnsten, A. F. & Goldman-Rakic, P. S. Analysis of alpha-2 adrenergic agonist effects on the delayed nonmatch-to-sample performance of aged rhesus monkeys. Neurobiol Aging 11, 583–590 (1990).Franowicz, J. S. & Arnsten, A. F. The alpha-2a noradrenergic agonist, guanfacine, improves delayed response performance in young adult rhesus monkeys. Psychopharmacology 136, 8–14 (1998).Caetano, M. S. et al. Noradrenergic control of error perseveration in medial prefrontal cortex. Frontiers in Integrative Neuroscience 6, 125 (2012).Kim, S., Bobeica, I., Gamo, N. J., Arnsten, A. F. & Lee, D. Effects of alpha-2A adrenergic receptor agonist on time and risk preference in primates. Psychopharmacology 219, 363–375 (2012).Seu, E., Lang, A., Rivera, R. J. & Jentsch, J. D. Inhibition of the norepinephrine transporter improves behavioral flexibility in rats and monkeys. Psychopharmacology 202, 505–519 (2009).Kawaura, K., Karasawa, J., Chaki, S. & Hikichi, H. Stimulation of postsynapse adrenergic alpha2A receptor improves attention/cognition performance in an animal model of attention deficit hyperactivity disorder. Behav Brain Res 270, 349–356 (2014).Aoki, C., Go, C. G., Venkatesan, C. & Kurose, H. Perikaryal and synaptic localization of alpha 2A-adrenergic receptor-like immunoreactivity. Brain Res 650, 181–204 (1994).Barth, A. M., Vizi, E. S., Zelles, T. & Lendvai, B. Alpha2-adrenergic receptors modify dendritic spike generation via HCN channels in the prefrontal cortex. J Neurophysiol 99, 394–401 (2008).Ji, X. H., Ji, J. Z., Zhang, H. & Li, B. M. Stimulation of alpha2-adrenoceptors suppresses excitatory synaptic transmission in the medial prefrontal cortex of rat. Neuropsychopharmacology 33, 2263–2271 (2008).Yi, F., Liu, S. S., Luo, F., Zhang, X. H. & Li, B. M. Signaling mechanism underlying alpha2A -adrenergic suppression of excitatory synaptic transmission in the medial prefrontal cortex of rats. Eur J Neurosci 38, 2364–2373 (2013).Engberg, G. & Eriksson, E. Effects of alpha 2-adrenoceptor agonists on locus coeruleus firing rate and brain noradrenaline turnover in N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-treated rats. Naunyn-Schmiedeberg’s archives of pharmacology 343, 472–477 (1991).Jakala, P. et al. Guanfacine, but not clonidine, improves planning and working memory performance in humans. Neuropsychopharmacology 20, 460–470 (1999).Jakala, P. et al. Guanfacine and clonidine, alpha 2-agonists, improve paired associates learning, but not delayed matching to sample, in humans. Neuropsychopharmacology 20, 119–130 (1999).Muller, U. et al. Lack of effects of guanfacine on executive and memory functions in healthy male volunteers. Psychopharmacology 182, 205–213 (2005).Scahill, L. et al. A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. The American journal of psychiatry 158, 1067–1074 (2001).Huys, Q. J. M., Maia, T. V. & Frank, M. J. Computational psychiatry as a bridge from neuroscience to clinical applications. Nat Neurosci 19, 404–413 (2016).Stephan, K. E. et al. Computational neuroimaging strategies for single patient predictions. NeuroImage in press (2015).Arnsten, A. F., Cai, J. X. & Goldman-Rakic, P. S. The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: evidence for alpha-2 receptor subtypes. J Neurosci 8, 4287–4298 (1988).Callado, L. F. & Stamford, J. A. Alpha2A- but not alpha2B/C-adrenoceptors modulate noradrenaline release in rat locus coeruleus: voltammetric data. Eur J Pharmacol 366, 35–39 (1999).Millan, M. J. et al. Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nature reviews. Drug discovery 11, 141–168 (2012).Niv, Y. et al. Reinforcement learning in multidimensional environments relies on attention mechanisms. J Neurosci 35, 8145–8157 (2015).Balcarras, M., Ardid, S., Kaping, D., Everling, S. & Womelsdorf, T. Attentional Selection Can Be Predicted by Reinforcement Learning of Task-relevant Stimulus Features Weighted by Value-independent Stickiness. J Cogn Neurosci 28, 333–349 (2016).Redish, A. D., Jensen, S., Johnson, A. & Kurth-Nelson, Z. Reconciling reinforcement learning models with behavioral extinction and renewal: implications for addiction, relapse, and problem gambling. Psychol Rev 114, 784–805 (2007).Nassar, M. R. et al. Rational regulation of learning dynamics by pupil-linked arousal systems. Nat Neurosci 15, 1040–1046 (2012).O’Reilly, J. X. et al. Dissociable effects of surprise and model update in parietal and anterior cingulate cortex. Proc Natl Acad Sci USA 110, 3660–3669 (2013).Shenhav, A., Botvinick, M. M. & Cohen, J. D. The expected value of control: an integrative theory of anterior cingulate cortex function. Neuron 79, 217–240 (2013).Womelsdorf, T. & Everling, S. Long-Range Attention Networks: Circuit Motifs Underlying Endogenously Controlled Stimulus Selection. Trends Neurosci 38, 682–700 (2015).Yang, Y. et al. Nicotinic alpha7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex. Proc Natl Acad Sci USA 110, 12078–12083 (2013).Aston-Jones, G., Rajkowski, J. & Cohen, J. Role of locus coeruleus in attention and behavioral flexibility. Biological psychiatry 46, 1309–1320 (1999).Cole, B. J. & Robbins, T. W. Forebrain norepinephrine: role in controlled information processing in the rat. Neuropsychopharmacology 7, 129–142 (1992).Dalley, J. W., Cardinal, R. N. & Robbins, T. W. Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates. Neuroscience and biobehavioral reviews 28, 771–784 (2004).Devauges, V. & Sara, S. J. Activation of the noradrenergic system facilitates an attentional shift in the rat. Behav Brain Res 39, 19–28 (1990).Connor, D. F., Arnsten, A. F., Pearson, G. S. & Greco, G. F. Guanfacine extended release for the treatment of attention-deficit/hyperactivity disorder in children and adolescents. Expert opinion on pharmacotherapy 15, 1601–1610 (2014).Sallee, F. R. et al. Guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder: a placebo-controlled trial. J Am Acad Child Adolesc Psychiatry 48, 155–165 (2009).Steere, J. C. & Arnsten, A. F. The alpha-2A noradrenergic receptor agonist guanfacine improves visual object discrimination reversal performance in aged rhesus monkeys. Behav Neurosci 111, 883–891 (1997).Doya, K. Modulators of decision making. Nat Neurosci 11, 410–416 (2008).Wang, X. J. & Krystal, J. H. Computational psychiatry. Neuron 84, 638–654 (2014).Wiecki, T. V. et al. A Computational Cognitive Biomarker for Early-Stage Huntington’s Disease. PLoS One 11, e0148409, doi: 10.1371/journal.pone.0148409 (2016).Huys, Q. J., Pizzagalli, D. A., Bogdan, R. & Dayan, P. Mapping anhedonia onto reinforcement learning: a behavioural meta-analysis. Biol Mood Anxiety Disord 3, 12 (2013).Gershman, S. J. & Niv, Y. Learning latent structure: carving nature at its joints. Curr Opin Neurobiol 20, 251–256 (2010).Voon, V. et al. Disorders of compulsivity: a common bias towards learning habits. Mol Psychiatry 20, 345–352 (2015).Maia, T. V. & Frank, M. J. From reinforcement learning models to psychiatric and neurological disorders. Nature Neuroscience 14, 154–162 (2011).Adams, R. A., Huys, Q. J. M. & Roiser, J. P. Computational Psychiatry: towards a mathematically informed understanding of mental illness. Journal of Neurology, Neurosurgery, and Psychiatry 87, 53–63 (2015).Schlagenhauf, F. et al. Striatal dysfunction during reversal learning in unmedicated schizophrenia patients. NeuroImage 89, 171–180 (2014).Harlé, K. M. et al. Bayesian neural adjustment of inhibitory control predicts emergence of problem stimulant use. Brain 138, 3413–3426 (2015).Zhang, J. et al. Different decision deficits impair response inhibition in progressive supranuclear palsy and Parkinson’s disease. Brain 139, 161–173 (2016).Frank, M. J. et al. fMRI and EEG Predictors of Dynamic Decision Parameters during Human Reinforcement Learning. Journal of Neuroscience 35, 485–494 (2015).Smith, A. C. & Brown, E. N. Estimating a state-space model from point process observations. Neural Comput 15, 965–991 (2003).Wilson, R. C. & Niv, Y. Inferring relevance in a changing world. Frontiers in human neuroscience 5, 189 (2011).Rämä, P. et al. Medetomidine, atipamezole, and guanfacine in delayed response performance of aged monkeys. Pharmacology Biochemistry and Behavior 55, 415–422 (1996).Arnsten, A. F. T. & Contant, T. A. Alpha-2 adrenergic agonists decrease distractibility in aged monkeys performing the delayed response task. Psychopharmacology 108, 159–169 (1992).O’Neill, J. et al. Effects of guanfacine on three forms of distraction in the aging macaque. Life Sciences 67, 877–885 (2000).Wang, M., Ji, J.-Z. & Li, B.-M. The α2A-Adrenergic Agonist Guanfacine Improves Visuomotor Associative Learning in Monkeys. Neuropsychopharmacology 29, 86–92 (2004).Witte, E. a. & Marrocco, R. T. Alteration of brain noradrenergic activity in rhesus monkeys affects the alerting component of covert orienting. Psychopharmacology 132, 315–323 (1997).Decamp, E., Clark, K. & Schneider, J. S. Effects of the alpha-2 adrenoceptor agonist guanfacine on attention and working memory in aged non-human primates. European Journal of Neuroscience 34, 1018–1022 (2011)

Exogenous Visual Orienting Is Associated with Specific Neurotransmitter Genetic Markers: A Population-Based Genetic Association Study

Background: Currently, there is a sense that the spatial orienting of attention is related to genotypic variations in cholinergic genes but not to variations in dopaminergic genes. However, reexamination of associations with both cholinergic and dopaminergic genes is warranted because previous studies used endogenous rather than exogenous cues and costs and benefits were not analyzed separately. Examining costs (increases in response time following an invalid precue) and benefits (decreases in response time following a valid pre-cue) separately could be important if dopaminergic genes (implicated in disorders such as attention deficit disorder) independently influence the different processes of orienting (e.g., disengage, move, engage). Methodology/Principal Findings: We tested normal subjects (N = 161) between 18 and 61 years. Participants completed a computer task in which pre-cues preceded the presence of a target. Subjects responded (with a key press) to the location of the target (right versus left of fixation). The cues could be valid (i.e., appear where the target would appear) or invalid (appear contralateral to where the target would appear). DNA sequencing assays were performed on buccal cells to genotype known genetic markers and these were examined for association with task scores. Here we show significant associations between visual orienting and genetic markers (on COMT, DAT1, and APOE; R 2 s from 4 % to 9%). Conclusions/Significance: One measure in particular – the response time cost of a single dim, invalid cue – was associate

The Impact of Acute Psychosocial Stress on Magnetoencephalographic Correlates of Emotional Attention and Exogenous Visual Attention

Stress-induced acute activation of the cerebral catecholaminergic systems has often been found in rodents. However, little is known regarding the consequences of this activation on higher cognitive functions in humans. Theoretical inferences would suggest increased distractibility in the sense of increased exogenous attention and emotional attention. The present study investigated the influence of acute stress responses on magnetoencephalographic (MEG) correlates of visual attention. Healthy male subjects were presented emotional and neutral pictures in three subsequent MEG recording sessions after being exposed to a TSST-like social stressor, intended to trigger a HPA-response. The subjects anticipation of another follow-up stressor was designed to sustain the short-lived central catecholaminergic stress reactions throughout the ongoing MEG recordings. The heart rate indicates a stable level of anticipatory stress during this time span, subsequent cortisol concentrations and self-report measures of stress were increased. With regard to the MEG correlates of attentional functions, we found that the N1m amplitude remained constantly elevated during stressor anticipation. The magnetic early posterior negativity (EPNm) was present but, surprisingly, was not at all modulated during stressor anticipation. This suggests that a general increase of the influence of exogenous attention but no specific effect regarding emotional attention in this time interval. Regarding the time course of the effects, an influence of the HPA on these MEG correlates of attention seems less likely. An influence of cerebral catecholaminergic systems is plausible, but not definite

Cognitive function during early abstinence from opioid dependence: a comparison to age, gender, and verbal intelligence matched controls

BACKGROUND: Individuals with opioid dependence have cognitive deficits during abuse period in attention, working memory, episodic memory, and executive function. After protracted abstinence consistent cognitive deficit has been found only in executive function. However, few studies have explored cognitive function during first weeks of abstinence. The purpose of this study was to study cognitive function of individuals with opioid dependence during early abstinence. It was hypothesized that cognitive deficits are pronounced immediately after peak withdrawal symptoms have passed and then partially recover. METHODS: Fifteen patients with opioid dependence and fifteen controls matched for, age, gender, and verbal intelligence were tested with a cognitive test battery When patients performed worse than controls correlations between cognitive performance and days of withdrawal, duration of opioid abuse, duration of any substance abuse, or opioid withdrawal symptom inventory score (Short Opiate Withdrawal Scale) were analyzed. RESULTS: Early abstinent opioid dependent patients performed statistically significantly worse than controls in tests measuring complex working memory, executive function, and fluid intelligence. Their complex working memory and fluid intelligence performances correlated statistically significantly with days of withdrawal. CONCLUSION: The results indicate a rather general neurocognitive deficit in higher order cognition. It is suggested that cognitive deficit during early abstinence from opioid dependence is related to withdrawal induced neural dysregulation in the prefrontal cortex and is partly transient

Ih Current Is Necessary to Maintain Normal Dopamine Fluctuations and Sleep Consolidation in Drosophila

HCN channels are becoming pharmacological targets mainly in cardiac diseases. But apart from their well-known role in heart pacemaking, these channels are widely expressed in the nervous system where they contribute to the neuron firing pattern. Consequently, abolishing Ih current might have detrimental consequences in a big repertoire of behavioral traits. Several studies in mammals have identified the Ih current as an important determinant of the firing activity of dopaminergic neurons, and recent evidences link alterations in this current to various dopamine-related disorders. We used the model organism Drosophila melanogaster to investigate how lack of Ih current affects dopamine levels and the behavioral consequences in the sleep∶activity pattern. Unlike mammals, in Drosophila there is only one gene encoding HCN channels. We generated a deficiency of the DmIh core gene region and measured, by HPLC, levels of dopamine. Our data demonstrate daily variations of dopamine in wild-type fly heads. Lack of Ih current dramatically alters dopamine pattern, but different mechanisms seem to operate during light and dark conditions. Behaviorally, DmIh mutant flies display alterations in the rest∶activity pattern, and altered circadian rhythms. Our data strongly suggest that Ih current is necessary to prevent dopamine overproduction at dark, while light input allows cycling of dopamine in an Ih current dependent manner. Moreover, lack of Ih current results in behavioral defects that are consistent with altered dopamine levels