Flow is a state of full task engagement that is accompanied with low-levels of self-referential thinking. Flow is considered highly relevant for human performance and well-being and has, therefore, been studied extensively. Yet, the neurocognitive processes of flow remain largely unclear. In the present mini-review we focus on how the brain's locus coeruleus-norepinephrine (LC-NE) system may be involved in a range of behavioral and subjective manifestations of flow. The LC-NE system regulates decisions regarding task engagement vs. disengagement. This is (...) doneviadifferent modes of baseline and stimulus-evoked norepinephrine release. We emphasize the theoretical and empirical overlap between the LC-NE system and flow. For both, a match between a person's skill and task challenge is important in order to induce high levels task-related attention. Moreover, psychophysiological indicators of LC-NE system activity, such as eye pupil diameter and arousal are also sensitive to flow states. Flow is related to arousal in an inverted U-shape. Similarly, in theories on the LC-NE system, task engagement is highest with intermediate levels of arousal. We argue that knowledge about the role of the LC-NE system in establishing the flow experience may help to gain fundamental knowledge of flow and can contribute to unifying various empirical findings on this topic. (shrink)

Aversive experiences have been thought to provoke or exacerbate clinical depression. The present review provides a brief survey of the stress-depression literature and suggests that the effects of stressful experiences on affective state may be related to depletion of several neurotransmitters, including norepinephrine, dopamine, and serotonin. A major element in determining the neurochemical changes is the organism's ability to cope with the aversive stimuli through behavioral means. Aversive experiences give rise to behavioral attempts to cope with the stressor, coupled (...) with increased utilization and synthesis of brain amines to contend with environmental demands. When behavioral coping is possible, neurochemical systems are not overly taxed, and behavioral pathology will not ensue. However, when there can be no behavioral control over the stressful stimuli, or when the aversive experience is perceived as uncontrollable, increased emphasis is placed on coping through endogenous neurochemical mechanisms. Amine utilization increases appreciably and may exceed synthesis, resulting in a net reduction of amine stores, which in turn promotes or exacerbates affective disorder. The processes governing the depletions may be subject to sensitization or conditioning, such that exposure to traumatic experiences may have long-term repercussions when the organism subsequently encounters related stressful stimuli. With continued uncontrollable stimulation, adaptation occurs in the form of increased activity of synthetic enzymes, and levels of amines approach basal values. It is suggested that either the initial amine depletion provoked by aversive experiences or a dysfunction of the adaptive processes, resulting in persistent amine depletion, contributes to behavioral depression. Aside from the contribution of behavioral coping, several organismic, experiential, and environmental variables will influence the effects of aversive experiences on neurochemical activity, and may thus influence vulnerability to depression. (shrink)

A variety of studies show that parental absence early in life leads to deleterious effects on the developing CNS. This is thought to be largely because evolutionary-dependent stimuli are necessary for the appropriate postnatal development of the young brain, an effect sometimes termed the “experience-expectant brain,” with parents providing the necessary input for normative synaptic connections to develop and appropriate neuronal survival to occur. Principal among CNS systems affected by parental input are the monoamine systems. In the present study,N= 434 (...) rhesus monkeys (233 males, 201 females) were reared in one of two conditions: as mother-reared controls (MR;n= 269) or without adults with 24-h access to same-aged peers (PR;n= 165). When subjects were six-months-old, they underwent a separation paradigm involving 4, sequential, four-day social separations from their mothers or peers, with each separation followed by three-day reunions with their mothers or their peers. Prior to the separation paradigm, baseline cisternal CSF samples were obtained, as well as at the end of each the four social separations, and after final separation, during a recovery period. CSF was assayed for concentrations of monoamine metabolites and a blood sample was genotyped for the serotonin transporter (5-HTT) genotype. Replicating earlier landmark findings, PR subjects with thesallele exhibited lower baseline concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), when compared to PR subjects homozygous for theLallele. MR subjects were undifferentiated by genotype. PR subjects exhibited lower CSF 5-HIAA concentrations during baseline, but higher CSF 5-HIAA during social separations, when compared to MR subjects. There were rearing effects for the dopamine metabolite homovanillic acid (HVA) and for the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), with PR subjects showing higher HVA and lower MHPG when compared to MR subjects. These findings indicate that there are long-term deficits in the response of monoamines following early maternal absence. The results of this study confirm and extend earlier findings that early parental absence has deleterious consequences for the development of the monoamine systems, and that these consequences are modulated by the 5-HTT genotype. (shrink)

Physiologically accurate mouse models of cancer are critical in the pre‐clinical development of novel cancer therapies. However, current standardized animal‐housing temperatures elicit chronic cold‐associated stress in mice, which is further increased in the presence of tumor. This cold‐stress significantly impacts experimental outcomes. Data from our lab and others suggest standard housing fundamentally alters murine physiology, and this can produce altered immune baselines in tumor and other disease models. Researchers may thus underestimate the efficacy of therapies that are benefitted by immune (...) responses. A potential mediator, norepinephrine, also underlies stress pathways common in mice and humans. Therefore, research into mechanisms connecting cold‐stress and norepinephrine signaling with immune depression in mice could highlight new combination therapies for humans to simultaneously target stress while stimulating anti‐tumor immunity. (shrink)

A comparative method of studying the biological bases of personality compares human trait dimensions with likely animal models in terms of genetic determination and common biological correlates. The approach is applied to the trait of sensation seeking, which is defined on the human level by a questionnaire, reports of experience, and observations of behavior, and on the animal level by general activity, behavior in novel situations, and certain types of naturalistic behavior in animal colonies. Moderately high genetic determination has been (...) found for human sensation seeking, and marked strain differences in rodents have been found in open-field behavior that may be related to basic differences in brain neurochemistry. Agonistic and sociable behaviors in both animals and humans and the trait measure of sensation seeking in humans have been related to certain common biological correlates such as gonadal hormones, monoamine oxidase (MAO), and augmenting of the cortical evoked potential.The monoamine systems in the rodent brain are involved in general activity, exploratory behavior, emotionality, socialization, dominance, sexual and consummately behaviors, and intracranial self-stimulation. Preliminary studies have related norepinephrine and enzymes involved in its production and degradation to human sensation seeking. A model is suggested that relates mood, behavioral activity, sociability, and clinical states to activity of the central catecholamine neurotransmitters and to neuroregulators and other transmitters that act in opposite ways on behavior or stabilize activity in the arousal systems. Stimulation and behavioral activity act on the catecholamine systems in a brain–behavior feedback loop. At optimal levels of catecholamine systems activity (CSA) mood is positive and activity and sociability are adaptive. At very low or very high levels of CSA mood is dysphoric, activity is restricted or stereotyped, and the organism is unsocial or aggressively antisocial. Novelty, in the absence of threat, may be rewarding through activation of noradrenergic neurons. (shrink)

Emotionally arousing events reach awareness more easily and evoke greater visual cortex activation than more mundane events. Recent studies have shown that they are also perceived more vividly and that emotionally enhanced perceptual vividness predicts memory vividness. We propose that affect-biased attention (ABA) – selective attention to emotionally salient events – is an endogenous attentional system tuned by an individual's history of reward and punishment. We present the Biased Attention via Norepinephrine (BANE) model, which unifies genetic, neuromodulatory, neural and (...) behavioural evidence to account for ABA. We review evidence supporting BANE's proposal that a key mechanism of ABA is locus coeruleus–norepinephrine (LC–NE) activity, which interacts with activity in hubs of affective salience networks to modulate visual cortex activation and heighten the subjective vividness of emotionally salient stimuli. We further review literature on biased competition and look at initial evidence for its potential as a neural mechanism behind ABA. We also review evidence supporting the role of the LC–NE system as a driving force of ABA. Finally, we review individual differences in ABA and memory including differences in sensitivity to stimulus category and valence. We focus on differences arising from a variant of the ADRA2b gene, which codes for the alpha2b adrenoreceptor as a way of investigating influences of NE availability on ABA in humans. (shrink)

Endogenous depression is highly correlated with low levels of serotonin in the central nervous system. Does this imply or suggest that this sort of depression just is this neurochemical deficit? Scorning such an inference, Antonio Damasio writes:If feeling happy or sad … corresponds in part to the cognitive modes under which your thoughts are operating, then the explanation also requires that the chemical acts on the circuits which generate and manipulate [such thoughts]. Which means that reducing depression to a statement (...) about the availability of serotonin or norepinephrine in general- a popular statement in the days and age of Prozac- is unacceptably rude.Damasio's thought is that depression is essentially a modification of how we perceive the world, reason about it, and make decisions about how to act in it - in other words, that it is essentially cognitive. A reduced level of serotonin might cause the said modification, but no adequate account of depression would identify the malady with its cause. A proper account would minimally need to say how cognitive processing is affected by a reduced level of serotonin. (shrink)

Aversive experiences have been thought to provoke or exacerbate clinical depression. The present review provides a brief survey of the stress-depression literature and suggests that the effects of stressful experiences on affective state may be related to depletion of several neurotransmitters, including norepinephrine, dopamine, and serotonin. A major element in determining the neurochemical changes is the organism's ability to cope with the aversive stimuli through behavioral means. Aversive experiences give rise to behavioral attempts to cope with the stressor, coupled (...) with increased utilization and synthesis of brain amines to contend with environmental demands. When behavioral coping is possible, neurochemical systems are not overly taxed, and behavioral pathology will not ensue. However, when there can be no behavioral control over the stressful stimuli, or when the aversive experience is perceived as uncontrollable, increased emphasis is placed on coping through endogenous neurochemical mechanisms. Amine utilization increases appreciably and may exceed synthesis, resulting in a net reduction of amine stores, which in turn promotes or exacerbates affective disorder. The processes governing the depletions may be subject to sensitization or conditioning, such that exposure to traumatic experiences may have long-term repercussions when the organism subsequently encounters related stressful stimuli. With continued uncontrollable stimulation, adaptation occurs in the form of increased activity of synthetic enzymes, and levels of amines approach basal values. It is suggested that either the initial amine depletion provoked by aversive experiences or a dysfunction of the adaptive processes, resulting in persistent amine depletion, contributes to behavioral depression. Aside from the contribution of behavioral coping, several organismic, experiential, and environmental variables will influence the effects of aversive experiences on neurochemical activity, and may thus influence vulnerability to depression. (shrink)

‘Neuroeconomics’ can be broadly defined as the research of how the brain interacts with the environment to make decisions that are functional given individual and contextual constraints. Deciphering such brain-environment transactions requires mechanistic understandings of the neurobiological processes that implement value-dependent decision making. To this end, a common empirical approach is to investigate neural mechanisms of reward-based decision making. Flexible updating of choices and associated expected outcomes in ways that are adaptive for a given task (or a given set of (...) tasks) at hand relies on dynamic neurochemical tuning of the brain’s functional circuitries involved in the representation of tasks, goals and reward prediction. Empirical evidence as well as computational theories indicate that various neurotransmitter systems (e.g., dopamine, norepinephrine, and serotonin) play important roles in reward-based decision making. In light of the apparent aging-related decline in various aspects of the dopaminergic system as well as the effects of neuromodulation on reward-related processes, this article focuses selectively on the literature that highlights the triadic relations between dopaminergic modulation, reward-based decision making, and aging. Directions for future research on aging and neuroeconomoics are discussed. (shrink)

The main aim of our study was to determinate whether a repeated bout (RB) (vs. first bout [FB]) of sprint interval cycling exercise (SIE) is sufficient to mitigate SIE-induced psychological and physiological biomarker kinetics within 48 h after the exercise. Ten physically active men (age, 22.6 ± 5.2 years; VO2max, 44.3 ± 5.7 ml/kg/min) performed the FB of sprint interval cycling exercise (12 repeats of 5 s each) on one day and the RB 2 weeks later. The following parameters were (...) measured: motor performance (voluntary, electrically induced and isokinetic skeletal muscle contraction torque, and central activation ratio [CAR]); stress markers (BDNF, cortisol, norepinephrine, and epinephrine); inflammatory markers (IL-6, IL-10, and TNF-); metabolic markers (glucose and lactate); muscle and rectal temperature; cycling power output; and psychological perceptions. The average cycling power output and neuromuscular fatigue after exercise did not differ between the FB and RB. There were significant decreases in cortisol and BDNF concentration at 12 h (P < 0.05) and 24 h (P < 0.001) after the FB, respectively. The decrease in cortisol concentration observed 12 h after exercise was significantly greater after the RB (P < 0.05) than after the FB. The immune-metabolic response to the RB (vs. FB) SIE was suppressed and accompanied by lower psychological exertion. Most of the changes in psychological and physiological biomarkers in the FB and RB were closely related to the response kinetics of changes in BDNF concentration. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Philosophy, Psychiatry, & Psychology 9.3 (2002) 265-269 [Access article in PDF] The Psychology and Physiology of Depression Walter Glannon Trauma and stressful events can disrupt the physiologic homeostasis of our bodies and brains. The physiologic stress response consists of neural and endocrine mechanisms whose function is to reestablish homeostasis. These mechanisms include the secretion of glucocorticoids (cortisol) and catecholemines (epinephrine and norepinephrine). Once an external event has ceased (...) to be a stressor or threat to a human organism, an integrated system of negative feedback loops inhibits the continued production of these hormones and effectively shuts down the stress response. These mechanisms are adaptive in the sense that they ensure the survival of the organism by reestablishing homeostasis. But prolonged exposure to real or perceived stressors can trigger prolonged secretion of stress hormones, thereby disrupting the feedback systems and causing a cascade of pathogenic events. The stress response is a double-edged sword. An acute stress response can protect an organism from external threats and reestablish homeostasis. But a chronic stress response can cause the body's defenses to become damaging rather than protective and to result in various disorders. Acute stress responses are adaptive. Chronic stress responses are often maladaptive and pathogenic.In "Depression as a Mind-Body Problem," I characterized major clinical depression as a disorder resulting from a maladaptive chronic stress response (Glannon 2003). Specifically, I argued that depression often results when our beliefs and emotions are out of proportion to the true nature of external events. The mind prolongs rather than constrains the physiologic stress response. Depression is not a disorder of the brain alone or the mind alone, however. Endocrine and immune dysfunction can contribute to the dysfunction in the brain and central nervous system that are involved in depression. Moreover, the contents of the mental states that initiate the sequence of events leading to depression are reflections of the person's natural and social environment. Thus, a satisfactory account of depression requires an analysis of the interconnections among the central nervous, endocrine, and immune systems, as well as the mind and the environment. All of these factors support the description of depression as a psychoneuroimmunologic disorder.Mike Martin (Martin 2003) and Thomas Fuchs (Fuchs 2003) discuss important aspects of depression that I did not elaborate in my paper. Martin argues that I fail to distinguish between depression as a mood and depression as a disorder. This is pertinent to the distinction evolutionary psychiatrists draw between moods that are adaptive and moods that are maladaptive. In contrast to my negative characterization of depression, Martin also makes a case for the positive [End Page 265] contributions of depression to meaningful life. Fuchs explores the notion of the brain as an organ of translation enabling patients to have meaningful subjective experience. The emphasis on subjectivity has important implications for potential preventive and therapeutic interventions for depression. For whether a person perceives an external event as a stressor may play a crucial role in the physiologic stress response. I will address the main points of these two authors in turn.Contrary to what Martin claims, I explicitly defined chronic depression as an affective (mood) disorder. My focus was on the clinical definition of major depression as a moderately severe to severe chronic disorder. It consists of affective, cognitive, and even physical dysfunction that interferes with a person's ability to carry out the normal tasks of daily life. This characterization of major chronic depression distinguishes it from milder forms of depression, such as dysthymia. Because these milder forms do not involve the same type or degree of dysfunction as more severe forms, they are not appropriately characterized as pathologies. For this reason, I focused on Nesse's (2000) discussion of depression rather than on his discussion of low mood. In fairness to Nesse and Stevens and Price (2000), not all forms of depression are pathologic according to the evolutionary view they defend. Some passive aspects of mild depression may be useful in alerting us to dangerous or wasteful behavior. It does seem plausible to describe depressed moods as falling along a continuum from those that... (shrink)