Compensatory changes in striatal dopamine neurons following recovery from injury induced by 6-OHDA or methamphetamine: a review of evidence from microdialysis studies

This paper presents evidence from microdialysis experiments that three different behavioural outcomes of depletion of striatal dopamine (DA) by either 6-hydroxydopamine or methamphetamine (sparing of function, recovery of function, and loss of function) may be related to differences in the ability of residual DA neurons to maintain extracellular concentrations of DA. It is shown that when up to 80% of the mesostriatal DA system is destroyed, the remaining DA terminals maintain normal extracellular dopamine concentrations. Following a lesion in the 80-95% range, most animals maintain a relatively normal extracellular concentration of DA, but the ability to respond to increased demand is reduced in some animals. When over 95% of the normal DA input to the striatum is destroyed, there is a sharp drop in the extracellular concentration of DA and a nearly complete loss in the ability to increase DA release upon demand. Thus, this new method of sampling extracellular DA and its metabolites in freely moving animals provides insights into the behavioural capacities of animals and into the neural mechanisms that underlie recovery of function following brain damage.     

Stress management effects on psychological, endocrinological, and immune functioning in men with HIV infection: empirical support for a psychoneuroimmunological model

We present a psychoneuroimmunologic (PNI) model for Human Immunodeficiency Virus (HIV) infection, describe a 10-week group-based cognitive behavioral stress management (CBSM) intervention and summarize research demonstrating the effects of this intervention on mood, neuroendocrine (Hypothalamic Pituitary Adrenal [HPA], Hypothalamic Pituitary Gonadal [HPG] and Sympathetic Nervous System [SNS] hormones) and immune system status (lymphocyte subsets, anti-viral immune function) in HIV-infected persons. This work demonstrates that changes in relaxation skills, cognitive coping strategies and social support may mediate the mood effects of CBSM, and that these mood changes may mediate adrenal hormone regulation indicated by reductions in 24-h urinary cortisol (with reduced depressed mood) and norepinephrine (with reduced anxiety) and increases in serum DHEA-S and testosterone levels (with reduced depressed mood). Results also suggest that CBSM-related changes in production of these hormones may explain, in part, the effects of this intervention on short-term changes in IgG antibody titers to herpesviruses (with increased DHEA-S-to-cortisol ratio), and longer-term changes in lymphocyte subpopulations such as CD8 suppressor/cytotoxic cells (with reductions in urinary noradrenaline output) and transitional na?ve CD4 cells (with reductions in urinary cortisol output). Thus a multi-modal CBSM intervention is associated with alterations in mood, neuroendocrine functioning and immunologic status that may have health implications for HIV infection.     

The functional‐cognitive framework as a tool for accelerating progress in cognitive neuroscience: On the benefits of bridging rather than reducing levels of analyses

The subject matter of neuroscience research is complex, and synthesising the wealth of data from this research to better understand mental processes is challenging. A useful strategy, therefore, may be to distinguish explicitly between the causal effects of the environment on behaviour (i.e. functional analyses) and the mental processes that mediate these effects (i.e. cognitive analyses). In this article, we describe how the functional‐cognitive (F‐C) framework can accelerate cognitive neuroscience and also advance a functional treatment of brain activity. We first highlight that cognitive neuroscience can particularly benefit from the F‐C approach by providing an alternative to the problematic practice of reducing cognitive constructs to behavioural and/or neural proxies. Next, we outline how functional (behaviour–environment) relations can serve as a bridge between cognitive and neural processes by restoring mental constructs to their original role as heuristic tools. Finally, we give some examples of how both cognitive neuroscience and traditional functional approaches can mutually benefit from the F‐C framework.     

Requirement of dopamine signaling in the amygdala and striatum for learning and maintenance of a conditioned avoidance response

Two-way active avoidance (2WAA) involves learning Pavlovian (association of a sound cue with a foot shock) and instrumental (shock avoidance) contingencies. To identify regions where dopamine (DA) is involved in mediating 2WAA, we restored DA signaling in specific brain areas of dopamine-deficient (DD) mice by local reactivation of conditionally inactivated Th genes using viral gene therapy. Among all targeted areas--prefrontal cortex (PFC), amygdala, ventral striatum, dorsal striatum, and whole striatum--only restoration of DA signaling to both the whole striatum together with the amygdala enabled DD mice to acquire 2WAA. However, after prolonged overtraining during which DD mice had DA synthesis systemically reconstituted pharmacologically with L-3,4-dihydroxyphenylalanine (L-Dopa), DA signaling in the striatum alone was sufficient to maintain 2WAA, whereas DA signaling in the PFC together with the amygdala was insufficient to maintain 2WAA. Our results indicate that learning 2WAA requires DA signaling in both the amygdala and the entire striatum; however, after sufficient training, DA signaling in the striatum alone can maintain the learned avoidance behavior.     

Negative priming 1985 to 2015: a measure of inhibition,the emergence of alternative accounts,and the multiple process challenge

In this article, three generations of authors describe the background to the original article; the subsequent emergence of vigorous debates concerning what negative priming actually reflects, where radically different accounts based on memory retrieval were proposed; and a re-casting of the conceptual issues underlying studies of negative priming. What started as a simple observation (slowed reaction times) and mechanism (distractor inhibition) appears now to be best explained by a multiple mechanism account involving both episodic binding and retrieval processes as well as an inhibitory process. Emerging evidence from converging techniques such as functional magnetic resonance imaging (fMRI), and especially electroencephalography (EEG), is beginning to identify these different processes. The past 30 years of negative priming experiments has revealed the dynamic and complex cognitive processes that mediate what appear to be apparently simple behavioural effects.     

Role of dopamine,the frontal cortex and memory circuits in drug addiction: insight from imaging studies

Drug addiction is characterized by a set of recurring processes (intoxication, withdrawal, craving) that lead to the relapsing nature of the disorder. We have used positron emission tomography to investigate in humans the role of dopamine (DA) and the brain circuits it regulates in these processes. We have shown that increases in DA are associated with the subjective reports of drug reinforcement corroborating the relevance of drug-induced DA increases in the rewarding effects of drugs in humans. During withdrawal we have shown in drug abusers significant reductions in DA D2 receptors and in DA release. We postulate that this hypodopaminergic state would result in a decreased sensitivity to natural reinforcers perpetuating the use of the drug as a means to compensate for this deficit and contributing to the anhedonia and dysphoria seen during withdrawal. Because the D2 reductions are associated with decreased activity in the anterior cingulate gyrus and in the orbitofrontal cortex we postulate that this is one of the mechanisms by which DA disruption leads to compulsive drug administration and the lack of control over drug intake in the drug-addicted individual. This is supported by studies showing that during craving these frontal regions become hyperactive in proportion to the intensity of the craving. Craving is also associated with activation of memory circuits including the amygdala (implicated in conditioned learning), hippocampus (implicated in declarative learning), and dorsal striatum (implicated in habit learning) all of which receive DA innervation. We therefore postulate that dopamine contributes to addiction by disrupting the frontal cortical circuits that regulate motivation, drive, and self-control and by memory circuits that increase the motivational salience of the drug and drug-associated stimuli.     

Regional studies of brain biogenic amines in castrated muricidal and non-muricidal wistar rats

Castrated Wistar rats were isolated for 8 months and their muricidal behavior was investigated. Significantly fewer (35%) of such rats became muricidal (CM) compared to controls. The steady-state levels of 5-HT, 5-HIAA, DA, DOPAC, and NE, as well as the changes in synthesis or utilization rats of 5-HT and DA, were analyzed in 15 brain areas derived from CM rats and non-muricidal (CNM) control subjects. In CM rats, higher 5-HT levels were recorded in 5 areas considered to be involved in muricidal behavior: raphe, amygdala, olfactory tubercles, olfactory bulbs, and striatum. The alterations of serotonergic neurotransmission in castrated muricidal rats differ strikingly from those observed in non-castrated muricidal rats. An increase of 5-HT level and in the 5-HT synthesis index as well as a lower 5-HT utilization index were recorded in the raphe of CM rats. Our data suggest that the decrease of 5-HT levels generally said to be the main alteration in the muricidal rat's brain has to be reconsidered. Increased DA levels were observed in CM rats: raphe (50%), amygdala, olfactory tubercles, striatum, and septum (40%), while DA was decreased in cortical areas. There were slight increases of DA synthesis indices in the septum, olfactory tubercles and striatum with a decreased utilization index in the olfactory tubercles. Few alterations in NE levels were observed in CM rats: a decrease in the olfactory tubercles, superior colliculus, and striatum and an increase in temporal cortex. The monoaminergic alterations correlate with the modulation of muricidal behavior. Some areas (the olfactory tubercles, raphe, striatum, and temporal cortex) seem to be particularly involved. © 1992 Wiley-Liss, Inc.     

Effects of aging and divided attention on episodic feeling-of-knowing accuracy

This research investigated the effect of aging on episodic feeling-of-knowing (FOK) using a divided attention (DA) paradigm in order to examine whether DA in younger adults mimics the effects of aging when decreasing either memory encoding or monitoring processes. To that end, four groups of participants were tested on the FOK task: young adults (control group), young adults under DA at encoding, young adults under DA when making FOK judgments, and older adults. Our results showed that DA at encoding in young adults mimicked the effect of aging on memory performance, and also on FOK magnitude and accuracy, supporting the memory-constraint hypothesis ( Hertzog et al., 2010). However, our results do not completely contradict the monitoring-deficit hypothesis, as DA during FOK judgments also affected FOK accuracy, but to a lesser extent than the aging effect or DA during encoding. We suggest that the age-related FOK deficit may be due to a lower level of deep encoding, leading to difficulty retrieving target-related contextual details enabling accurate prediction of subsequent recognition.     

Modularity beyond perception: evidence from single task interference paradigms

We combine the Dimension-Action (DA) model with translational models to account for both the Stroop and the flanker effects. The basic assumption of the model is that there are distinct visual modules, each of which is endowed with both perception and response selection processes. We contrast this model with an alternative widespread view, the standard view, according to which the same response selection processes are shared by all tasks. The two views have different predictions concerning the flanker and Stroop tasks. Seven experiments test these predictions. The first five experiments show that there is a fundamental difference between the typical Stroop and flanker effects. Moreover, these experiments show that words denoting colors can affect print colors only when they are required for naming or when participants verbally mediate the print color task. Experiments 6 and 7 show that an analogous interaction between color and shape exists in the flanker task. These experiments as well as previous studies are consistent with the DA model and the modular view and pose serious difficulties for the standard view. Wider implications of a visual modular architecture are discussed as well.     

The triple response approach to assessment: a conceptual and methodological reappraisal

Despite its positive effects on the increased use of multiple assessments and improved assessment validity, the triple-response concept has led to some conceptual and practical confusion. This is mainly due to two problems: (1) a confounding of the content and method of assessment; and (2) an imprecise and vague use of the 'verbal-subjective mode' which has been expanded to include cognitive elements since the introduction of cognitive-behavioural theories and treatments. A new matrix is proposed that clearly distinguishes content and method of assessment. It also defines a separate cognitive/information-processing content area and introduces affect as an additional content area. Thus, four content areas are suggested: behavioural, physiological, cognitive, and affective, which can be measured in three different ways: by means of self-report, observation, and instruments or technical equipment. We point out the implications of these changes for (1) a more appropriate selection of assessment procedures and outcome measures in clinical research; (2) a more adequate individualization of treatment through matching individual response profiles to specific treatments; and (3) an improved understanding of the interrelationship between behavioural, physiological, cognitive, and affective processes in anxiety and depression. Finally, we suggest that the lack of agreement between measures of physiological, cognitive, behavioural and affective changes in some studies may be as much a reflection of the lack of agreement arising from spurious sources of variance within content areas as it is a reflection of the operation of different processes and systems.     

Regulation of behaviour in pursuit of health goals

Abstract

Prediction of health related behaviours and the specification of cognitive processes which might guide development of effective interventions may be promoted by the identification of processes which mediate between intentions and health behaviour. The present commentary addresses theoretical developments concerning the role of cognitive and personality processes in volitional pursuit of health related goals and in the maintenance of behavioural change.     

A neurobehavioral model of affiliative bonding: implications for conceptualizing a human trait of affiliation

Because little is known about the human trait of affiliation, we provide a novel neurobehavioral model of affiliative bonding. Discussion is organized around processes of reward and memory formation that occur during approach and consummatory phases of affiliation. Appetitive and consummatory reward processes are mediated independently by the activity of the ventral tegmental area (VTA) dopamine (DA)-nucleus accumbens shell (NAS) pathway and the central corticolimbic projections of the u-opiate system of the medial basal arcuate nucleus, respectively, although these two projection systems functionally interact across time. We next explicate the manner in which DA and glutamate interact in both the VTA and NAS to form incentive-encoded contextual memory ensembles that are predictive of reward derived from affiliative objects. Affiliative stimuli, in particular, are incorporated within contextual ensembles predictive of affiliative reward via: (a) the binding of affiliative stimuli in the rostral circuit of the medial extended amygdala and subsequent transmission to the NAS shell; (b) affiliative stimulus-induced opiate potentiation of DA processes in the VTA and NAS; and (c) permissive or facilitatory effects of gonadal steroids, oxytocin (in interaction with DA), and vasopressin on (i) sensory, perceptual, and attentional processing of affiliative stimuli and (ii) formation of social memories. Among these various processes, we propose that the capacity to experience affiliative reward via opiate functioning has a disproportionate weight in determining individual differences in affiliation. We delineate sources of these individual differences, and provide the first human data that support an association between opiate functioning and variation in trait affiliation.     

A behavioral and genetic dissection of two forms of olfactory plasticity in Caenorhabditis elegans: adaptation and habituation

Continuous presentation of an olfactory stimulus causes a decrement of the chemotaxis response in the nematode Caenorhabditis elegans. However, the differences between the learning process of habituation (a readily reversible decrease in behavioral response) and other types of olfactory plasticity such as adaptation (a decrement in response due to sensory fatigue, which cannot be dishabituated) have not been addressed. The volatile odorant diacetyl (DA) was used within a single paradigm to assess the distinct processes of olfactory adaptation and habituation. Preexposing and testing worms to 100% DA vapors caused a chemotaxis decrement that was not reversible despite the presentation of potentially dishabituating stimuli. This DA adaptation was abolished in worms with an odr-10 mutation (encoding a high-affinity DA receptor on the AWA neuron), even though naive chemotaxis remained unaffected. Conversely, DA adaptation remained intact in odr-1 mutants (defective in AWC neuron-mediated olfactory behavior), even though naive chemotaxis to DA decreased. Surprisingly, exposure to vapors of intermediate concentrations of DA (0.01% and 25%) did not cause worms to exhibit any response decrement. In contrast to preexposure to high DA concentrations, preexposure to low DA concentrations (0.001%) produced habituation of the chemotaxis response (a dishabituating stimulus could reverse the response decrement back to baseline levels). The distinct behavioral effects produced by DA preexposure highlight a concentration-dependent dissociation between two decremental olfactory processes: adaptation at high DA concentrations versus habituation at low DA concentrations.     

Behavioural phenotyping of transgenic mice

This paper reviews the current work on mouse genetics, brain, and behaviour in my laboratory. It starts with an historical account of our research and shows how certain research themes, such as olfaction, learning, social behaviour, and environmental effects in rodents have led to our current research on behavioural phenotyping of inbred, mutant, knockout, and transgenic mice. We are concerned with finding neural and behavioural sequelae to genetic manipulations in mice and use a battery of tests to detect behaviours that are altered in genetically modified mice. In this way we are working to dissociate neural and behavioural effects of different gene manipulations in mouse models of neurodegenerative diseases. Sensory, motor, cognitive, affective, and social behaviours may all be affected by gene manipulation, thus careful behavioural techniques, with attention to the mice themselves, the apparatus, and procedure, experimenter variables, and environmental effects are necessary in order to determine a reliable and valid mouse behavioural phenotype. As both the genome and the environment have significant effects on the behavioural phenotype, our future research will utilize an epigenetic approach to examine how environmental cues modulate gene expression in the behavioural phenotyping of transgenic mice.     

Cognitive sources of evidence for neuroticism's link to punishment-reactivity processes

Theories of neuroticism emphasise its close potential link to punishment-reactivity processes, yet cognitive sources of evidence for this proposed processing basis are surprisingly scarce. The present two studies (N = 123) sought to rectify this important gap in the literature in terms of reactivity to error feedback. Study 1 found that individuals high in neuroticism were faster to switch behavioural responses following errors, whereas an opposite pattern was found among individuals low in neuroticism. Study 2 extended this error-reactivity perspective to the realm of behavioural decision making. Individuals high in neuroticism switched their behavioural predictions following error feedback, whereas this tendency was non-significant among individuals low in neuroticism. Together, the studies present novel, but theory-informed, cognitive paradigms for assessing punishment-reactivity processes, confirm neuroticism's link to such processes, and do so in the realms of both reaction time (Study 1) and behavioural predictions (Study 2). The discussion focuses on the utility of modelling punishment-reactivity processes in cognitive terms and highlights relevant directions for future research.     

The impact of open and closed mindsets on evaluative priming

In the present research, we argue that open versus closed mindsets, accompanying ongoing versus completed mental jobs on the prime, determine the size of congruity effects in the evaluative priming paradigm. More specifically, we hypothesised that disfluent primes that resist an easily completed encoding process should induce an open mindset and thereby result in stronger congruity effects than fluent primes that induce closed mindsets. Across two experiments, we applied two different manipulations of prime fluency: gradual demasking (Experiment 1) and colour contrast (Experiment 2). As expected, in both experiments we found robust congruity effects, but only on trials with disfluent (vs. fluent) primes. Results of a follow-up experiment suggest that these effects are not due to attentional processes. We conclude that the mindsets resulting from individuals' activities during encoding are crucial in determining the outcome of evaluative priming effects.     

Improving intergroup relations with extended and vicarious forms of indirect contact

Research in social psychology has provided impressive evidence that intergroup contact reduces prejudice. However, to the extent that strategies based on direct contact are sometimes difficult to implement, scholars have more recently focused on indirect contact. An effective form of indirect contact is extended contact. According to the extended contact hypothesis, simply knowing that ingroup members have outgroup friends (extended contact), or observing these friendships vicariously (vicarious contact), can improve intergroup relations. Since its initial formulation a large body of studies has supported the validity of the extended contact hypothesis. In reviewing the available literature on two forms of indirect contact (extended and vicarious), we outline a model that identifies their antecedents and consequences, spanning from cognitive to affective to behavioural outcomes. In addition to identifying the main moderators of indirect contact, we also distinguish two different routes, one cognitive and one affective, that underlie what processes mediate their effects. Finally, we indicate some possible avenues for future research and we consider how direct and indirect contact strategies can be used in combination to improve intergroup relations.     

The role of message framing in promoting MMR vaccination: evidence of a loss-frame advantage

This study examined the effects of message framing on intentions to obtain the measles, mumps and rubella (MMR) vaccine for one's child and investigated whether Theory of Planned Behaviour (TPB) and perceived outcome efficacy variables mediate and/or moderate message framing effects. One hundred and forty women read either a loss-framed or gain-framed message and then completed measures assessing their intentions to obtain the MMR vaccine for their child, and TPB and outcome efficacy variables. Exposure to the loss frame increased intentions to obtain the MMR vaccine and influenced perceptions of outcome efficacy. This suggests that outcome efficacy, but not other TPB variables may mediate framing effects within the context of MMR vaccination. Message frame, in addition to TPB variables, significantly predicted unique variance in behavioural intentions. These findings are discussed within the context of Prospect Theory, perceived risk and prevention/detection behaviours.     

Modulation of stress consequences by hippocampal monoaminergic, glutamatergic and nitrergic neurotransmitter systems

Several findings relate the hippocampal formation to the behavioural consequences of stress. It contains a high concentration of corticoid receptors and undergoes plastic modifications, including decreased neurogenesis and cellular remodelling, following stress exposure. Various major neurotransmitter systems in the hippocampus are involved in these effects. Serotonin (5-HT) seems to exert a protective role in the hippocampus and attenuates the behavioural consequences of stress by activating 5-HT1A receptors in this structure. These effects may mediate the therapeutic actions of several antidepressants. The role of noradrenaline is less clear and possibly depends on the specific hippocampal region (dorsal vs. ventral). The deleterious modifications induced in the hippocampus by stress might involve a decrease in neurotrophic factors such as brain derived neurotrophic factor (BDNF) following glutamate N-methyl-D-aspartate (NMDA) receptor activation. In addition to glutamate, nitric oxide (NO) could also be related to these effects. Systemic and intra-hippocampal administration of nitric oxide synthase (NOS) inhibitors attenuates stress-induced behavioural consequences. The challenge for the future will be to integrate results related to these different neurotransmitter systems in a unifying theory about the role of the hippocampus in mood regulation, depressive disorder and antidepressant effects.