Appropriate interpretation of pleasurable, rewarding experiences favors decisions that enhance survival. Conversely, dysfunctional affective brain processing can lead to life-threatening risk behaviors (e.g. addiction) and emotion imbalance (e.g. mood disorders). The state of sleep deprivation continues to be associated with maladaptive emotional regulation, leading to exaggerated neural and behavioral reactivity to negative, aversive experiences. However, such detrimental consequences are paradoxically aligned with the perplexing antidepressant benefit of sleep deprivation, elevating mood in a proportion of patients with major depression. Nevertheless, it remains unknown how sleep loss alters the dynamics of brain and behavioral reactivity to rewarding, positive emotional experiences. Using fMRI, here we demonstrate that sleep deprivation amplifies reactivity throughout human mesolimbic reward brain networks in response to pleasure-evoking stimuli. In addition, this amplified reactivity was associated with enhanced connectivity in early primary visual processing pathways and extended limbic regions, yet with a reduction in coupling with medial- and orbito-frontal regions. These neural changes were accompanied by a biased increase in the number of emotional stimuli judged as pleasant in the sleep-deprived group, the extent of which exclusively correlated with activity in mesolimbic regions. Together, these data support a view that sleep deprivation is not only associated with enhanced reactivity towards negative stimuli, but imposes a bi-directional nature of affective imbalance, associated with amplified reward-relevant reactivity towards pleasure-evoking stimuli also. Such findings may offer a neural foundation on which to consider interactions between sleep loss and emotional reactivity in a variety of clinical mood disorders.
Sleep Deprivation; Positive Emotion; Reward; Brain Reactivity
Biological evolution has struggled to produce mechanisms that can limit blood loss following injury. In humans and other mammals, control of blood loss (hemostasis) is achieved through a combination of plasma proteins, most of which are made in the liver, and platelets, anucleate blood cells that are produced in the bone marrow by megakaryocytes. Much has been learned about the underlying mechanisms, but much remains to be determined. The articles in this series review current ideas about the production of megakaryocytes from undifferentiated hematopoietic precursors, the steps by which megakaryocytes produce platelets, and the molecular mechanisms within platelets that make hemostasis possible. The underlying theme that connects the articles is the intense investigation of a complex system that keeps humans from bleeding to death, but at the same time exposes us to increased risk of thrombosis and vascular disease.
Individuals who express relatively large-magnitude or ‘exaggerated’ blood pressure (BP) reactions to behavioral stressors are presumably at increased risk for cardiovascular disease. As shown by recent neuroimaging studies, individuals who express exaggerated stressor-evoked BP reactivity also express heightened neural activity in corticolimbic brain areas that centrally regulate the cardiovascular system. These studies, however, have exclusively examined BP reactivity and concomitant neural activity during stressor exposure. If exaggerated BP reactivity originates in part from a centrally-regulated and dispositional cardiovascular response tendency, then heightened resting (pre-stressor) corticolimbic activity may predict the subsequent expression of exaggerated stressor-evoked BP reactivity. To test this hypothesis, perfusion magnetic resonance imaging was used to quantify resting regional cerebral blood flow (rCBF; an indirect metabolic measure of neural activity) in men (n=19) and women (n=20) aged 20-37 who subsequently performed cognitive stressor tasks to evoke BP reactivity. Individuals who expressed larger task-induced rises in systolic and diastolic BP also expressed higher resting rCBF in four functionally-related corticolimbic areas: the dorsal and perigenual anterior cingulate, medial prefrontal, and insular cortices. Specifically, resting rCBF in these areas accounted respectively for 40% and 31% of the variance in systolic (P=0.001) and diastolic (P=0.008) BP reactivity, after accounting for total resting CBF, resting BP, task performance, and task-related ratings of unpleasantness, arousal, and perceived psychological control. Heightened resting corticolimbic activity may represent a neurobiological correlate of an individual’s predisposition for exaggerated stressor-evoked BP reactivity and possibly related cardiovascular risk.
anterior cingulate cortex; blood pressure reactivity; individual differences; insula; medial prefrontal cortex; stress
A nuclear probabilistic risk or safety assessment (PRA or PSA) is a scientific calculation that uses assumptions and models to determine the likelihood of plant or fuel repository failures and the corresponding releases of radioactivity. Estimated radiation doses to the surrounding population are linked inappropriately to risks of cancer death and congenital malformations. Even though PRAs use very pessimistic assumptions, they demonstrate that nuclear power plants and fuel repositories are very safe compared with the health risks of other generating options or other risks that people readily accept. Because of the frightening negative images and the exaggerated safety and health concerns that are communicated, many people judge nuclear risks to be unacceptable and do not favour nuclear plants. Large-scale tests and experience with nuclear accidents demonstrate that even severe accidents expose the public to only low doses of radiation, and a century of research has demonstrated that such exposures are beneficial to health. A scientific basis for this phenomenon now exists. PRAs are valuable tools for improving plant designs, but if nuclear power is to play a significant role in meeting future energy needs, we must communicate its many real benefits and dispel the negative images formed by unscientific extrapolations of harmful effects at high doses.
Molecular, cellular, and epidemiologic findings suggest that neurohormonal, epigenetic, and microbiologic mechanisms may influence risk for obesity by interacting with socioenvironmental factors. Homeostatic and nonhomeostatic neural controls of energy predispose people to obesity, and this predisposition may be exaggerated by the influence of media, marketing, and sleep patterns. Epigenetic gene regulation may account for the influence of modifiable early life or maternal exposures on obesity risk. Alterations in gut flora caused by infant feeding practices or later diet may influence the absorption and storage of energy. Further exploration of how these molecular-cellular mechanisms might increase obesity risk in response to modifiable socioeconomic factors requires the partnership of laboratory and public health researchers.
A history of early adverse experiences is an important risk factor for adult psychopathology. Changes in stress sensitivity and functioning of the hypothalamic-pituitary-adrenal (HPA) axis may underlie the association between stress and risk for psychiatric disorders. Preclinical work in rodents has linked low levels of maternal care to increased methylation of the promoter region of the glucocorticoid receptor (GR) gene, as well as to exaggerated hormonal and behavioral responses to stress. Recent studies have begun to examine whether early-life stress leads to epigenetic modifications of the GR gene in humans.
We examined the degree of methylation of a region of the promoter of the human GR gene (NR3C1) in leukocyte DNA from 99 healthy adults. Participants reported on their childhood experiences of parental behavior, parental death or desertion, and childhood maltreatment. On a separate day, participants completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, a standardized neuroendocrine challenge test.
Disruption or lack of adequate nurturing, as measured by parental loss, childhood maltreatment, and parental care, was associated with increased NR3C1 promoter methylation (p<.05). In addition, NR3C1 promoter methylation was linked to attenuated cortisol responses to the Dex/CRH test (p<.05).
These findings suggest that childhood maltreatment or adversity may lead to epigenetic modifications of the human GR gene. Alterations in methylation of this gene could underlie the associations between childhood adversity, alterations in stress reactivity, and risk for psychopathology.
Human adults tend to avoid risk. In behavioral economic studies, risk aversion is manifest as a preference for sure gains over uncertain gains. However, children tend to be less averse to risk than adults. Given that many of the brain regions supporting decision-making under risk do not reach maturity until late adolescence or beyond it is possible that mature risk-averse behavior may emerge from the development of decision-making circuitry. To explore this hypothesis, we tested 5- to 8-year-old children, 14- to 16-year-old adolescents, and young adults in a risky-decision task during functional magnetic resonance imaging (fMRI) data acquisition. To our knowledge, this is the youngest sample of children in an fMRI decision-making task. We found a number of decision-related brain regions to increase in activation with age during decision-making, including areas associated with contextual memory retrieval and the incorporation of prior outcomes into the current decision-making strategy, e.g., insula, hippocampus, and amygdala. Further, children who were more risk-averse showed increased activation during decision-making in ventromedial prefrontal cortex and ventral striatum. Our findings indicate that the emergence of adult levels of risk aversion co-occurs with the recruitment of regions supporting decision-making under risk, including the integration of prior outcomes into current decision-making behavior. This pattern of results suggests that individual differences in the development of risk aversion may reflect differences in the maturation of these neural processes.
fMRI; risk; decision-making; children; adolescence; reward; development; gambling
Neurological diseases represent a medical, social, and economic problem of paramount importance in developed countries. Although their etiology is generally known, developing therapeutic interventions for the central nervous system is challenging due to the impermeability of the blood–brain barrier. Thus, the fight against neurological diseases usually struggles “at the gates” of the brain. Flooding the bloodstream with drugs, where only a minor fraction reaches its target therapeutic site, is an inefficient, expensive, and dangerous procedure, because of the risk of side effects at nontargeted sites. Currently, advances in the field of nanotechnology have enabled development of a generation of multifunctional molecular platforms that are capable of transporting drugs across the blood–brain barrier, targeting specific cell types or functional states within the brain, releasing drugs in a controlled manner, and enabling visualization of processes in vivo using conventional imaging systems. The marriage between drug delivery and molecular imaging disciplines has resulted in a relatively new discipline, known as theranostics, which represents the basis of the concept of personalized medicine. In this study, we review the concepts of the blood–brain barrier and the strategies used to traverse/bypass it, the role of nanotechnology in theranostics, the wide range of nanoparticles (with emphasis on liposomes) that can be used as stealth drug carriers, imaging probes and targeting devices for the treatment of neurological diseases, and the targets and targeting strategies envisaged in the treatment of different types of brain pathology.
nanotechnology; theranostics; blood-brain barrier; brain; central nervous system
Intimate partner violence (IPV) is one of the most common causes of posttraumatic stress disorder (PTSD) in women. Victims of IPV are often preoccupied by the anticipation of impending harm. This investigation tested the hypothesis that IPV-related PTSD individuals show exaggerated insula reactivity to the anticipation of aversive stimuli.
Fifteen women with a history of IPV and consequent PTSD (IPV-PTSD) and 15 non-traumatized control (NTC) women performed a task involving cued anticipation to images of positive and negative events during functional magnetic resonance imaging.
Both groups showed increased activation of bilateral anterior insula during anticipation of negative images minus anticipation of positive images. Activation in right anterior/middle insula was significantly greater in the IPV-PTSD relative to the NTC group. Functional connectivity analysis revealed that changes in activation in right middle insula and bilateral anterior insula were more strongly associated with amygdala activation changes in NTC than in IPV-PTSD subjects.
Increased activation in the anterior/middle insula during negative anticipation in women with IPV-related PTSD. These findings in women with IPV could be a consequence of the IPV exposure, reflect pre-existing differences in insular function, or due to the development of PTSD. Thus, future longitudinal studi4s need to examine these possibilities.
Individuals with generalized social anxiety disorder (GSAD) exhibit exaggerated amygdala reactivity to aversive social stimuli. These findings could be explained by microstructural abnormalities in white matter (WM) tracts that connect the amygdala and prefrontal cortex, which is known to modulate the amygdala’s response to threat. The goal of this study was to investigate brain frontal WM abnormalities by using diffusion tensor imaging (DTI) in patients with social anxiety disorder.
A Turboprop DTI sequence was used to acquire diffusion tensor images in thirty patients with GSAD and thirty matched healthy controls. Fractional anisotropy, an index of axonal organization, within WM was quantified in individual subjects and an automated voxel-based, whole-brain method was used to analyze group differences.
Compared to healthy controls, patients had significantly lower fractional anisotropy localized to the right uncinate fasciculus WM near the orbitofrontal cortex. There were no areas of higher fractional anisotropy in patients than controls.
These findings point to an abnormality in the uncinate fasciculus, the major WM tract connecting the frontal cortex to the amygdala and other limbic temporal regions, in GSAD which could underlie the aberrant amygdala-prefrontal interactions resulting in dysfunctional social threat processing in this illness.
Background: Posttraumatic stress disorder (PTSD) patients show heightened fear responses to trauma reminders and an inability to inhibit fear in the presence of safety reminders. Brain imaging studies suggest that this is in part due to amygdala over-reactivity as well as deficient top-down cortical inhibition of the amygdala. Consistent with these findings, previous studies, using fear-potentiated startle (FPS), have shown exaggerated startle and deficits in fear inhibition in PTSD participants. However, many PTSD studies using the skin conductance response (SCR) report no group differences in fear acquisition. Method: The study included 41 participants with PTSD and 70 without PTSD. The fear conditioning session included a reinforced conditioned stimulus (CS+, danger cue) paired with an aversive airblast, and a nonreinforced conditioned stimulus (CS−, safety cue). Acoustic startle responses and SCR were acquired during the presentation of each CS. Results: The results showed that fear conditioned responses were captured in both the FPS and SCR measures. Furthermore, PTSD participants had higher FPS to the danger cue and safety cue compared to trauma controls. However, SCR did not differ between groups. Finally, we found that FPS to the danger cue predicted re-experiencing symptoms, whereas FPS to the safety cue predicted hyper-arousal symptoms. However, SCR did not contribute to PTSD symptom variance. Conclusions: Replicating earlier studies, we showed increased FPS in PTSD participants. However, although SCR was a good measure of differential conditioning, it did not differentiate between PTSD groups. These data suggest that FPS may be a useful tool for translational research. Depression and Anxiety, 2011. © 2011 Wiley Periodicals, Inc.
fear-potentiated startle; skin conductance response; trauma; posttraumatic stress disorders; psychophysiology
Posttraumatic stress disorder (PTSD) patients show heightened fear responses to trauma reminders and an inability to inhibit fear in the presence of safety reminders. Brain imaging studies suggest that this is in part due to amygdala over-reactivity as well as deficient top-down cortical inhibition of the amygdala. Consistent with these findings, previous studies, using fear-potentiated startle (FPS), have shown exaggerated startle and deficits in fear inhibition in PTSD participants. However, many PTSD studies using the skin conductance response (SCR) report no group differences in fear acquisition.
The study included 41 participants with PTSD and 70 without PTSD. The fear conditioning session included a reinforced conditioned stimulus (CS+, danger cue) paired with an aversive airblast, and a nonreinforced CS (CS−, safety cue). Acoustic startle responses and SCR were acquired during the presentation of each CS.
The results showed that fear conditioned responses were captured in both the FPS and SCR measures. Furthermore, PTSD participants had higher FPS to the danger cue and safety cue compared to trauma controls. However, SCR did not differ between groups. Finally, we found that FPS to the danger cue predicted re-experiencing symptoms, whereas FPS to the safety cue predicted hyper-arousal symptoms. However, SCR did not contribute to PTSD symptom variance.
Replicating earlier studies, we showed increased FPS in PTSD participants. However, although SCR was a good measure of differential conditioning, it did not differentiate between PTSD groups. These data suggest that FPS may be a useful tool for translational research.
Fear-potentiated startle; skin conductance response; trauma; posttraumatic stress disorders; psychophysiology
I study the welfare cost of business cycles in a complete-markets economy where some people are more risk averse than others. Relatively more risk-averse people buy insurance against aggregate risk, and relatively less risk-averse people sell insurance. These trades reduce the welfare cost of business cycles for everyone. Indeed, the least risk-averse people benefit from business cycles. Moreover, even infinitely risk-averse people suffer only finite and, in my empirical estimates, very small welfare losses. In other words, when there are complete insurance markets, aggregate fluctuations in consumption are essentially irrelevant not just for the average person – the surprising finding of Lucas (1987) – but for everyone in the economy, no matter how risk averse they are. If business cycles matter, it is because they affect productivity or interact with uninsured idiosyncratic risk, not because aggregate risk per se reduces welfare.
business cycles; risk aversion; risk sharing; heterogeneity
Spectacular images of neutrophils ejecting nuclear chromatin and bactericidal proteins, in response to microbes, were first reported in 2004. As externalized chromatin could entangle bacteria, these structures were named neutrophil extracellular traps (NETs). Subsequent studies identified microorganisms and sterile conditions that stimulate NETs, and additional cell types that release extracellular chromatin. NETs’ release is the most dramatic stage in a cell death process called NETosis. Experimental evidence suggests that NETs participate in pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis and vascular disorders. Exaggerated NETosis or diminished NET clearance likely increases risk of autoreactivity to NET components. The biological significance of NETs is just beginning to be explored. A more complete integration of NETosis within immunology and pathophysiology will require better understanding of NET properties associated with specific disease states and microbial infections. This may lead to the identification of important therapeutic targets.
Neutrophil extracellular traps; autoimmunity; neutrophils; infections
Patients with congenital QT interval prolongation are at risk of ventricular arrhythmias and sudden death. It has been suggested that the susceptibility to arrhythmias in these syndromes may be related to the abnormal dynamics of ventricular repolarisation. The dynamics of ventricular repolarisation, including assessment of the effect of changing heart rate on the QT interval and the duration of the right ventricular monophasic action potential, were studied in eight patients with congenital long QT syndromes. The effects of altered sympathetic tone on these dynamics were investigated with isoprenaline, propranolol, and left stellate ganglion block. The rate adaptation of the QT interval was abnormal in only a few patients and in some patients this feature may be related to the severity of the condition. These abnormalities may be exaggerated by isoprenaline and lessened by propranolol and left stellate ganglion block. Monophasic action potential dynamics were normal in all patients. The hypothesis that impaired QT rate adaptation may play a role in the genesis of ventricular arrhythmias in these syndromes is not, in general, supported by the present data. However, in patients with impaired adaptation the normalisation of QT dynamics after beta blockade and left stellate ganglion block was consistent with the efficacy of these forms of treatment.
This paper examines how aversion to risk and aversion to intertemporal substitution determine the strength of the precautionary saving motive in a two-period model with Selden/Kreps-Porteus preferences. For small risks, we derive a measure of the strength of the precautionary saving motive which generalizes the concept of “prudence” introduced by Kimball (1990b). For large risks, we show that decreasing absolute risk aversion guarantees that the precautionary saving motive is stronger than risk aversion, regardless of the elasticity of intertemporal substitution. Holding risk preferences fixed, the extent to which the precautionary saving motive is stronger than risk aversion increases with the elasticity of intertemporal substitution. We derive sufficient conditions for a change in risk preferences alone to increase the strength of the precautionary saving motive and for the strength of the precautionary saving motive to decline with wealth. Within the class of constant elasticity of intertemporal substitution, constant-relative risk aversion utility functions, these conditions are also necessary.
Within the last two decades, hemostasis factors have emerged as ‘new’ risk factors for coronary artery disease. Historical studies on the physiology of the sympathetic nervous system (SNS) attributed accelerated blood clotting to the components of the fight-flight response. Although this has not been demonstrated, exaggerated clotting related to SNS hyperactivity might confer an increased arterial thrombotic risk. This review outlines the effects of sympathetic activation as mimicked by adrenergic infusions and as elicited by mental stress and physical exercise, and the molecular mechanisms involved. A selective review of the pertinent literature was undertaken. Sympathetic activation provokes a simultaneous increase in molecules of both the coagulation and fibrinolysis pathways within minutes, resulting in net hypercoagulability as a part of normal human physiology. Catecholamines and adrenergic receptors interact to mediate hemostatic changes. Exaggerated procoagulant changes in individuals with a preexistent atherosclerotic disease, in those experiencing ongoing stressful life circumstances and in the physically untrained might confer a thrombotic threat with sympathetic activation. Initial evidence suggests that nonselective β-adrenergic blockade may attenuate clotting acceleration upon SNS activation. Prospective studies are needed to demonstrate whether exaggerated clotting as elicited by the SNS is associated with an increased risk of cardiovascular morbidity and mortality. If confirmed, intervention studies targeted at reducing this risk, for example with drugs, psychotherapy (including stress management) and regular physical exercise, would be warranted.
Hemostasis; Sympathetic nervous system; Adrenergic activation; Stress; Physical exercise
People with dyslexia, who face lifelong struggles with reading, exhibit numerous associated low-level sensory deficits including deficits in focal attention. Countering this, studies have shown that struggling readers outperform typical readers in some visual tasks that integrate distributed information across an expanse. Though such abilities would be expected to facilitate scene memory, prior investigations using the contextual cueing paradigm failed to find corresponding advantages in dyslexia. We suggest that these studies were confounded by task-dependent effects exaggerating known focal attention deficits in dyslexia, and that, if natural scenes were used as the context, advantages would emerge. Here, we investigate this hypothesis by comparing college students with histories of severe lifelong reading difficulties (SR) and typical readers (TR) in contexts that vary attention load. We find no differences in contextual-cueing when spatial contexts are letter-like objects, or when contexts are natural scenes. However, the SR group significantly outperforms the TR group when contexts are low-pass filtered natural scenes [F(3, 39) = 3.15, p<.05]. These findings suggest that perception or memory for low spatial frequency components in scenes is enhanced in dyslexia. These findings are important because they suggest strengths for spatial learning in a population otherwise impaired, carrying implications for the education and support of students who face challenges in school.
Control over an aversive experience can greatly impact the organism’s response to subsequent stressors. We compared the effects of escapable (ES) and yoked inescapable (IS) electric tail shocks on the hypothalamic-pituitary-adrenal (HPA) axis hormonal (corticosterone and ACTH), neural (c-fos mRNA) and behavioral (struggling) response to subsequent restraint. We found that although the HPA axis response during restraint of both previously stressed groups were higher than stress-naïve rats and not different from each other, lack of control over the tailshock experience led to an increase in restraint-induced struggling behavior of the IS rats compared to both stress-naïve and ES rats. Additionally, c-fos expression in the basolateral amygdala was increased selectively in the IS group, and relative c-fos mRNA expression in the basolateral amygdala positively correlated with struggling behavior. Restraint-induced c-fos expression in the medial prefrontal cortex, a brain area critical for mediating some of the differential neurochemical and behavioral effects of ES and IS, was surprisingly similar in both ES and IS groups, lower than that of stress-naïve rats, and did not correlate with struggling behavior. Our findings indicate that basolateral amygdala activity may be connected with the differential effects of ES and IS on subsequent behavioral responses to restraint, without contributing to the concurrent HPA axis hormone response.
facilitation; PFC; amygdala; helplessness; anxiety; sensitization
The hemodynamic responses to exercise have been studied to a great extent over the past decades, and an exaggerated blood pressure response during an acute exercise bout has been considered as an indicator of cardiovascular risk. Obesity is a major factor influencing the blood pressure response to exercise since evidence indicates that the arterial pressure response to exercise is exacerbated in obese compared with lean adults. Signs of augmented responses (such as an exaggerated blood pressure response) to physical exertion appear early in life (from the prepubertal years) in obese individuals. Understanding the mechanisms that drive the altered hemodynamic responses during exercise in obese individuals and prevent the progression to hypertension is vitally important. This paper focuses on the evidence linking obesity with alterations of the autonomic nervous system and discusses the potential mechanisms and consequences of the altered sympathetic nervous system behavior in obese individuals at rest and during exercise. Furthermore, this paper presents the alterations in the reflex regulatory mechanisms (“exercise pressor reflex” and baroreflex) in obese children and adults and addresses the effects of training on obesity-related disturbances.
Hyperekplexia (startle disease) is a rare non-epileptic disorder characterised by an exaggerated persistent startle reaction to unexpected auditory, somatosensory and visual stimuli, generalised muscular rigidity, and nocturnal myoclonus. The genetic basis is a mutation usually of the arginine residue 271 leading to neuronal hyperexcitability by impairing glycinergic inhibition. Hyperekplexia is usually familial, most often autosomal dominant with complete penetrance and variable expression. It can present in fetal life as abnormal intrauterine movements, or later at any time from the neonatal period to adulthood. Early manifestations include abnormal responses to unexpected auditory, visual, and somatosensory stimuli such as sustained tonic spasm, exaggerated startle response, and fetal posture with clenched fists and anxious stare. The tonic spasms may mimic generalised tonic seizures, leading to apnoea and death. Consistent generalised flexor spasm in response to tapping of the nasal bridge (without habituation) is the clinical hallmark of hyperekplexia. Electroencephalography may show fast spikes initially during the tonic spasms, followed by slowing of background activity with eventual flattening corresponding to the phase of apnoea bradycardia and cyanosis. Electromyography shows a characteristic almost permanent muscular activity with periods of electrical quietness. Nerve conduction velocity is normal. No specific computed tomography findings have been reported yet. Clonazepam, a gamma aminobutyric acid (GABA) receptor agonist, is the treatment of choice for hypertonia and apnoeic episodes. It, however, may not influence the degree of stiffness significantly. A simple manoeuvre like forced flexion of the head and legs towards the trunk is known to be life saving when prolonged stiffness impedes respiration.
Keywords: hyperekplexia; neonates; startle
Individuals who exhibit exaggerated blood pressure reactions to psychological stressors are at risk for hypertension, ventricular hypertrophy, and premature atherosclerosis; however, the neural systems mediating exaggerated blood pressure reactivity and associated cardiovascular risk in humans remain poorly defined. Animal models indicate that the amygdala orchestrates stressor-evoked blood pressure reactions via reciprocal signaling with corticolimbic and brainstem cardiovascular-regulatory circuits. Based on these models, we used a multimodal neuroimaging approach to determine whether human individual differences in stressor-evoked blood pressure reactivity vary with amygdala activation, gray matter volume, and functional connectivity with corticolimbic and brainstem areas implicated in stressor processing and cardiovascular regulation. We monitored mean arterial pressure (MAP) and concurrent functional magnetic resonance imaging BOLD signal changes in healthy young individuals while they completed a Stroop color-word stressor task, validated previously in epidemiological studies of cardiovascular risk. Individuals exhibiting greater stressor-evoked MAP reactivity showed (1) greater amygdala activation, (2) lower amygdala gray matter volume, and (3) stronger positive functional connectivity between the amygdala and perigenual anterior cingulate cortex and brainstem pons. Individual differences in amygdala activation, gray matter volume, and functional connectivity with corticolimbic and brainstem circuitsmaypartly underpin cardiovascular disease risk by impacting stressor-evoked blood pressure reactivity.
amygdala; blood pressure reactivity; cardiovascular disease risk; functional connectivity; individual differences; gray matter volume; stress
Risk aversion is associated with several important real world outcomes. Although the neurobiological correlates of risk aversion have been studied in young persons, little is known of the neurobiological correlates of risk aversion among older persons. Resting-state functional MRI data were collected on 134 non-demented participants of the Rush Memory and Aging Project, a community-based cohort study of aging. Risk aversion was measured using a series of standard questions in which participants were asked to choose between a certain monetary payment ($15) versus a gamble in which they could gain more than $15 or gain nothing, with potential gains varied across questions. Participants determined to be “high” (n=27) and “low” (n=27) in risk aversion were grouped accordingly. Using a spherical seed region of interest in the anterior cingulate cortex, voxel-wise functional connectivity network similarities were observed in bilateral frontal, anterior and posterior cingulate, insula, basal ganglia, temporal, parietal, and thalamic regions. Differences in functional connectivity were observed such that those low in risk aversion had greater connectivity to clusters in the superior, middle, and medial frontal regions, as well as cerebellar, parietal, occipital, and inferior temporal regions. Those high in risk aversion had greater connectivity to clusters in the inferior and orbital frontal, parahippocampal, and insula regions, as well as thalamic, parietal, precentral gyrus, postcentral gyrus, and middle temporal regions. Similarities and differences in functional connectivity patterns may reflect the historical recruitment of specific brain regions as a network in the active processing of risk in older adults.
risk aversion; aging; resting state fMRI; functional connectivity; anterior cingulate
Epidemiology is struggling increasingly with problems with correlated exposures and small relative risks. As a consequence, some scholars have strongly emphasized molecular epidemiology, whereas others have argued for the importance of the population context and the reintegration of epidemiology into public health. Environmental epidemiology has several unique features that make these debates especially pertinent to it. The very large number of environmental exposures require prioritization, and the relative risks are usually very low. Furthermore, many environmental exposures can be addressed only by comparing populations rather than individuals, and the disruption of both local and global ecosystems requires us to develop new methods of study design. The population context is also very important to consider in risk management decisions because of the involuntary nature of most environmental exposures and the diversity of possible outcomes, both health- and nonhealth-related. Studies at the individual or molecular level tend to focus the research hypotheses and subsequent interventions at that level, even when research and interventions at other levels may be more appropriate. Thus, only by starting from the population and ecosystem levels can we ensure that these are given appropriate consideration. Although better research is needed at all levels, it is crucially important to choose the most appropriate level, or levels, of research for a particular problem. Only by conducting research at all these levels and by developing further methods to combine evidence from these different levels can we hope to address the challenges facing environmental epidemiology today.
There is an increased awareness about patients’ involvement in the clinical decision process where uncertainty is an unavoidable condition. The impact of psychological factors like risk aversion, risk aversion and time, asymmetry in risk aversion, and risk and control on shared decision-making is discussed. In addition to differences in risk estimates, doctors and patients may exhibit a difference in perception of time perspectives, and losses versus gains.
A summary of valuation factors in shared decision-making is presented: (a) the doctors tend to follow expected value combinations more closely, while the patient is more risk aversive; (b) unwillingness to take risks increases for rare outcomes; (c) there is an increased tendency to take risks with delayed outcomes of the decisions; (d) the doctor is generally well informed about risk and time aspects for different diseases, whereas this might not always be the case with the patient; (e) rheumatoid arthritis and diabetes mellitus are chronic diseases, and both create a vulnerability to a variety of complications over time; (f) rheumatoid arthritis demands different combinations of treatments sequentially over time, whereas diabetes mellitus is treated with insulin; (g) many diseases, like rheumatoid arthritis and diabetes mellitus, are not completely affected by control, as the disease may constantly progress.
shared; decision-making; risk; aversion; time; control