Assessing New Methods to Optimally Detect Episodes of Non-metabolic Heart Rate Variability Reduction as an Indicator of Psychological Stress in Everyday Life: A Thorough Evaluation of Six Methods.

Frequent or chronic reduction in heart rate variability (HRV) is a powerful predictor of cardiovascular disease, and psychological stress has been suggested to be a co-determinant of this reduction. Recently, we evaluated various methods to measure additional HRV reduction in everyday life and to relate these reductions to psychological stress. In the current paper, we thoroughly evaluate these methods and add two new methods in both newly acquired and reanalyzed datasets. All of these methods use a subset of 24 h worth of HRV and movement data to do so: either the first 10 min of every hour, the full 24 h, a combination of 10 min from three consecutive hours, a classification of level of movement, the data from day n to detect episodes in day n + 1, or a range of activities during lab calibration. The method that used the full 24 h worth of data detected the largest percentage of episodes of reduced additional HRV that matched with self-reported stress levels, making this method the most promising, while using the first 10 min from three consecutive hours was a good runner-up.

Noradrenergic and Cholinergic Modulation of Belief Updating.

To make optimal predictions in a dynamic environment, the impact of new observations on existing beliefs-that is, the learning rate-should be guided by ongoing estimates of change and uncertainty. Theoretical work has proposed specific computational roles for various neuromodulatory systems in the control of learning rate, but empirical evidence is still sparse. The aim of the current research was to examine the role of the noradrenergic and cholinergic systems in learning rate regulation. First, we replicated our recent findings that the centroparietal P3 component of the EEG-an index of phasic catecholamine release in the cortex-predicts trial-to-trial variability in learning rate and mediates the effects of surprise and belief uncertainty on learning rate (Study 1, n = 17). Second, we found that pharmacological suppression of either norepinephrine or acetylcholine activity produced baseline-dependent effects on learning rate following nonobvious changes in an outcome-generating process (Study 1). Third, we identified two genes, coding for α2A receptor sensitivity (ADRA2A) and norepinephrine reuptake (NET), as promising targets for future research on the genetic basis of individual differences in learning rate (Study 2, n = 137). Our findings suggest a role for the noradrenergic and cholinergic systems in belief updating and underline the importance of studying interactions between different neuromodulatory systems.

New methods to optimally detect episodes of non-metabolic heart rate variability reduction as an indicator of psychological stress in everyday life.

Cardiovascular disease is the leading cause of death in the western world. Frequent or chronic reductions in heart rate variability (HRV) are a powerful predictor of cardiovascular disease. Psychological stress has been suggested to be an important factor in the development of reduced HRV. Recently, Verkuil et al. (2016) introduced a laboratory-based method to measure additional HRV reduction in everyday life, and reductions in HRV related to psychological stress. In the current paper, we discuss alternative methods to detect additional HRV reductions, in real life data sets without the necessity of laboratory-based calibration, and even in existing data sets. All of these methods use a subset of 24h' worth of HRV and movement data to do so: either the first 10min of every hour, the full 24h, a combination of 10min from three consecutive hours, or a classification of level of movement. We also present a method to visualize HRV and movement data to be able to detect episodes of reduced additional HRV optically. The method that used the full 24h' worth of data detected the largest percentage of episodes of reduced additional HRV that actually match with self-reported stress levels, making this method the most promising.

Speed and Lateral Inhibition of Stimulus Processing Contribute to Individual Differences in Stroop-Task Performance.

The Stroop task is a popular neuropsychological test that measures executive control. Strong Stroop interference is commonly interpreted in neuropsychology as a diagnostic marker of impairment in executive control, possibly reflecting executive dysfunction. However, popular models of the Stroop task indicate that several other aspects of color and word processing may also account for individual differences in the Stroop task, independent of executive control. Here we use new approaches to investigate the degree to which individual differences in Stroop interference correlate with the relative processing speed of word and color stimuli, and the lateral inhibition between visual stimuli. We conducted an electrophysiological and behavioral experiment to measure (1) how quickly an individual's brain processes words and colors presented in isolation (P3 latency), and (2) the strength of an individual's lateral inhibition between visual representations with a visual illusion. Both measures explained at least 40% of the variance in Stroop interference across individuals. As these measures were obtained in contexts not requiring any executive control, we conclude that the Stroop effect also measures an individual's pre-set way of processing visual features such as words and colors. This study highlights the important contributions of stimulus processing speed and lateral inhibition to individual differences in Stroop interference, and challenges the general view that the Stroop task primarily assesses executive control.

The accessory stimulus effect is mediated by phasic arousal: A pupillometry study.

People usually respond faster to a visual stimulus when it is immediately preceded by a task-irrelevant, auditory accessory stimulus (AS). This AS effect occurs even in choice reaction time tasks, despite the fact that the AS carries no information about the correct response. Researchers often assume that the AS effect is mediated by a phasic arousal burst evoked by the AS, but direct evidence for that assumption is lacking. We conducted a pupillometry study to directly test the phasic arousal hypothesis. Participants carried out a demanding choice reaction time task with accessory stimuli occurring on 25% of the trials. Pupil diameter, a common index of arousal, was measured throughout the task. Standard analyses of task performance and pupil diameter showed that participants exhibited the typical AS effect, and that accessory stimuli evoked a reliable early pupil dilation on top of the more protracted dilation associated with the imperative stimulus. Moreover, regression analyses at the single-trial level showed that variation in reaction times on AS trials was selectively associated with pupil dilation during the early time window within which the AS had an effect, such that particularly large AS-evoked dilations were associated with especially fast responses. These results provide the first evidence that the AS effect is mediated by AS-evoked phasic arousal.

Effects of clonidine and scopolamine on multiple target detection in rapid serial visual presentation.

RATIONALE: The specific role of neuromodulator systems in regulating rapid fluctuations of attention is still poorly understood. OBJECTIVES: In this study, we examined the effects of clonidine and scopolamine on multiple target detection in a rapid serial visual presentation task to assess the role of the central noradrenergic and cholinergic systems in temporal attention. METHOD: Eighteen healthy volunteers took part in a crossover double-dummy study in which they received clonidine (150/175 µg), scopolamine (1.2 mg), and placebo by mouth in counterbalanced order. A dual-target attentional blink task was administered at 120 min after scopolamine intake and 180 min after clonidine intake. The electroencephalogram was measured during task performance. RESULTS: Clonidine and scopolamine both impaired detection of the first target (T1). For clonidine, this impairment was accompanied by decreased amplitudes of the P2 and P3 components of the event-related potential. The drugs did not impair second-target (T2) detection, except if T2 was presented immediately after T1. The attentional blink for T2 was not affected, in line with a previous study that found no effect of clonidine on the attentional blink. CONCLUSIONS: These and other results suggest that clonidine and scopolamine may impair temporal attention through a decrease in tonic alertness and that this decrease in alertness can be temporarily compensated by a phasic alerting response to a salient stimulus. The comparable behavioral effects of clonidine and scopolamine are consistent with animal studies indicating close interactions between the noradrenergic and cholinergic neuromodulator systems.

Noradrenergic and cholinergic modulation of late ERP responses to deviant stimuli.

Researchers have proposed several hypotheses about the neuromodulator systems involved in generating P3 components of the ERP. To test some of these hypotheses, we conducted a randomized placebo-controlled crossover study in which we investigated how the late positive ERP response to deviant stimuli is modulated by (a) clonidine, an α2 agonist that attenuates baseline noradrenergic activity; and (b) scopolamine, a muscarinic antagonist of acetylcholine receptors. We collected EEG data from 18 healthy volunteers during the performance of an auditory oddball task with several active and passive task conditions. We then used temporospatial principal component analysis (PCA) to decompose the ERP waveforms. The PCA revealed two distinct late positive ERP components: the classic parietal P300 and the frontal novelty P3. Statistical analysis of the temporospatial factor scores indicated that in most conditions the amplitude of the classic P300 was increased by clonidine and scopolamine. In contrast, the amplitude of the novelty P3 was decreased by both drugs. The similar pattern of results for clonidine and scopolamine probably reflects the strong interactions between the noradrenergic and cholinergic systems. The results, in combination with previous pharmacological studies, suggest a critical role for both neuromodulator systems in the generation of the P300 and the novelty P3.

Beta receptor-mediated modulation of the oddball P3 but not error-related ERP components in humans.

RATIONALE: The P3 is a ubiquitous component of stimulus-driven neural activity that can be observed in scalp electrophysiological recordings. Multiple lines of evidence suggest an important role for the noradrenergic system in the generation of the P3. However, pharmacological studies of the P3 using noradrenergic manipulations have so far been limited to agents that affect α2-receptor signaling. OBJECTIVES: The present study investigated whether ß-adrenergic receptors are involved in the generation of the P3 and the error positivity (Pe), a component of the event-related potential that is elicited by errors and that bears many similarities to the P3. METHODS: We used a double-blind, placebo-controlled, crossover design in which we examined in human participants (N = 16) the effect of a single dose of propranolol (80 mg) on the amplitudes of the P3 observed in visual and auditory oddball tasks and the Pe observed in a flanker task. RESULTS: We found that P3s to auditory stimuli were increased in amplitude following treatment with propranolol. Propranolol also modulated the P3 to visual stimuli, but in a direction dependent on participants' level of trait anxiety: In participants with lower trait anxiety, propranolol resulted in a (non-significant) decrease in P3 amplitudes; in participants with higher trait anxiety, propranolol significantly enhanced P3 amplitude. Propranolol did not modulate the amplitude of the Pe or behavioral measures of conflict/error-related performance adjustments. CONCLUSIONS: These results provide the first evidence for involvement of ß-adrenergic receptors in P3 generation. We speculate that propranolol affected the P3 through actions at ß2-receptors in the locus coeruleus.

Noradrenergic and cholinergic effects on speed and sensitivity measures of phasic alerting.

An intense but task-irrelevant auditory accessory stimulus that is presented almost simultaneously with a visual imperative stimulus can reduce reaction times (RTs) to that stimulus. The information-processing locus and neural underpinnings underlying this phasic alerting effect are still poorly understood. The authors investigated a possible noradrenergic or cholinergic basis of the accessory stimulus effect in a double-blind pharmacological study (N = 18), in which healthy participants received a single dose of clonidine (an α2-adrenergic agonist), scopolamine (a muscarinic antagonist), and placebo in separate test sessions. A backward-masking procedure was used to examine, for the first time, the effect of accessory stimuli on perceptual sensitivity. The authors found that accessory stimuli enhanced perceptual sensitivity and decreased RTs to target stimuli, consistent with a recent hypothesis that phasic alerting speeds up stimulus encoding. In contrast to the authors' expectations, clonidine increased the accessory stimulus effect, a finding that seems at odds with earlier proposals that phasic alerting effects are mediated by a phasic noradrenergic response. Furthermore, the accessory stimulus effect was modulated to a similar extent by clonidine and scopolamine, suggesting that the effect of clonidine was not specific to the noradrenergic system. The results instead suggest that clonidine and scopolamine decrease general alertness and that these drug-related reductions in alertness yield room for compensatory performance improvements by phasic alerting.

Effects of arousal on cognitive control: empirical tests of the conflict-modulated Hebbian-learning hypothesis.

An increasing number of empirical phenomena that were previously interpreted as a result of cognitive control, turn out to reflect (in part) simple associative-learning effects. A prime example is the proportion congruency effect, the finding that interference effects (such as the Stroop effect) decrease as the proportion of incongruent stimuli increases. While this was previously regarded as strong evidence for a global conflict monitoring-cognitive control loop, recent evidence has shown that the proportion congruency effect is largely item-specific and hence must be due to associative learning. The goal of our research was to test a recent hypothesis about the mechanism underlying such associative-learning effects, the conflict-modulated Hebbian-learning hypothesis, which proposes that the effect of conflict on associative learning is mediated by phasic arousal responses. In Experiment 1, we examined in detail the relationship between the item-specific proportion congruency effect and an autonomic measure of phasic arousal: task-evoked pupillary responses. In Experiment 2, we used a task-irrelevant phasic arousal manipulation and examined the effect on item-specific learning of incongruent stimulus-response associations. The results provide little evidence for the conflict-modulated Hebbian-learning hypothesis, which requires additional empirical support to remain tenable.

The discriminatory cost of ICD-10-CM transition between clinical specialties: metrics, case study, and mitigating tools.

OBJECTIVE: Applying the science of networks to quantify the discriminatory impact of the ICD-9-CM to ICD-10-CM transition between clinical specialties. MATERIALS AND METHODS: Datasets were the Center for Medicaid and Medicare Services ICD-9-CM to ICD-10-CM mapping files, general equivalence mappings, and statewide Medicaid emergency department billing. Diagnoses were represented as nodes and their mappings as directional relationships. The complex network was synthesized as an aggregate of simpler motifs and tabulation per clinical specialty. RESULTS: We identified five mapping motif categories: identity, class-to-subclass, subclass-to-class, convoluted, and no mapping. Convoluted mappings indicate that multiple ICD-9-CM and ICD-10-CM codes share complex, entangled, and non-reciprocal mappings. The proportions of convoluted diagnoses mappings (36% overall) range from 5% (hematology) to 60% (obstetrics and injuries). In a case study of 24 008 patient visits in 217 emergency departments, 27% of the costs are associated with convoluted diagnoses, with 'abdominal pain' and 'gastroenteritis' accounting for approximately 3.5%. DISCUSSION: Previous qualitative studies report that administrators and clinicians are likely to be challenged in understanding and managing their practice because of the ICD-10-CM transition. We substantiate the complexity of this transition with a thorough quantitative summary per clinical specialty, a case study, and the tools to apply this methodology easily to any clinical practice in the form of a web portal and analytic tables. CONCLUSIONS: Post-transition, successful management of frequent diseases with convoluted mapping network patterns is critical. The http://lussierlab.org/transition-to-ICD10CM web portal provides insight in linking onerous diseases to the ICD-10 transition.

Functional significance of the emotion-related late positive potential.

The late positive potential (LPP) is an event-related potential (ERP) component over visual cortical areas that is modulated by the emotional intensity of a stimulus. However, the functional significance of this neural modulation remains elusive. We conducted two experiments in which we studied the relation between LPP amplitude, subsequent perceptual sensitivity to a non-emotional stimulus (Experiment 1) and visual cortical excitability, as reflected by P1/N1 components evoked by this stimulus (Experiment 2). During the LPP modulation elicited by unpleasant stimuli, perceptual sensitivity was not affected. In contrast, we found some evidence for a decreased N1 amplitude during the LPP modulation, a decreased P1 amplitude on trials with a relatively large LPP, and consistent negative (but non-significant) across-subject correlations between the magnitudes of the LPP modulation and corresponding changes in d-prime or P1/N1 amplitude. The results provide preliminary evidence that the LPP reflects a global inhibition of activity in visual cortex, resulting in the selective survival of activity associated with the processing of the emotional stimulus.

Beta receptor-mediated modulation of the late positive potential in humans.

RATIONALE: Electrophysiological studies have identified a scalp potential, the late positive potential (LPP), which is modulated by the emotional intensity of observed stimuli. Previous work has shown that the LPP reflects the modulation of activity in extrastriate visual cortical structures, but little is known about the source of that modulation. OBJECTIVES: The present study investigated whether beta-adrenergic receptors are involved in the generation of the LPP. METHODS: We used a genetic individual differences approach (experiment 1) and a pharmacological manipulation (experiment 2) to test the hypothesis that the LPP is modulated by the activation of ß-adrenergic receptors. RESULTS: In experiment 1, we found that LPP amplitude depends on allelic variation in the ß1-receptor gene polymorphism. In experiment 2, we found that LPP amplitude was modulated by the ß-blocker propranolol in a direction dependent on subjects' level of trait anxiety: In participants with lower trait anxiety, propranolol led to a (nonsignificant) decrease in the LPP modulation; in participants with higher trait anxiety, propranolol increased the emotion-related LPP modulation. CONCLUSIONS: These results provide initial support for the hypothesis that the LPP reflects the downstream effects, in visual cortical areas, of ß-receptor-mediated activation of the amygdala.

Aging and the neuroeconomics of decision making: A review.

Neuroeconomics refers to a combination of paradigms derived from neuroscience, psychology, and economics for the study of decision making and is an area that has received considerable scientific attention in the recent literature. Using realistic laboratory tasks, researchers seek to study the neurocognitive processes underlying economic decision making and outcome-based decision learning, as well as individual differences in these processes and the social and affective factors that modulate them. To this point, one question has remained largely unanswered: What happens to decision-making processes and their neural substrates during aging? After all, aging is associated with neurocognitive change, which may affect outcome-based decision making. In our study, we use the subjective expected utility model-a well-established decision-making model in economics-as a descriptive framework. After a short survey of the brain areas and neurotransmitter systems associated with outcome-based decision making-and of the effects of aging thereon-we review a number of decision-making studies. Their general data pattern indicates that the decision-making process is changed by age: The elderly perform less efficiently than younger participants, as demonstrated, for instance, by the smaller total rewards that the elderly acquire in lab tasks. These findings are accounted for in terms of age-related deficiencies in the probability and value parameters of the subjective expected utility model. Finally, we discuss some implications and suggestions for future research.