The effects of acute tryptophan depletion on human decision-making suggest that serotonin modulates the processing of rewards and punishments. However, few studies have assessed which of the many types of serotonin receptors are responsible. Using a within-subject, double-blind, sham-controlled design in 26 subjects, we examined whether individual differences in serotonin system gene transcription, measured in peripheral blood, predicted the effect of acute tryptophan depletion on decision-making. Participants performed a task in which they chose between successive pairs of fixed, lower-stakes (control) and variable, higher-stakes (experimental) gambles, each involving wins or losses. In 21 participants, mRNA from 9 serotonin system genes was measured in whole blood prior to acute tryptophan depletion: 5-HT1B, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT3A, 5-HT3E, 5-HT7 (serotonin receptors), 5-HTT (the serotonin transporter), and tryptophan hydroxylase 1. Acute tryptophan depletion did not significantly influence participants’ sensitivity to probability, wins, or losses, although there was a trend for a lower tendency to choose experimental gambles overall following depletion. Significant positive correlations, which survived correction for multiple comparisons, were detected between baseline 5-HT1B mRNA levels and acute tryptophan depletion-induced increases in both the overall tendency to choose the experimental gamble and sensitivity to wins. No significant relationship was observed with any other peripheral serotonin system markers. Computational analyses of decision-making data provided results consistent with these findings. These results suggest that the 5-HT1B receptor may modulate the effects of acute tryptophan depletion on risky decision-making. Peripheral levels of serotonin markers may predict response to treatments that act upon the serotonin system, such as selective serotonin reuptake inhibitors.
The feeling of body ownership is a fundamental aspect of self-consciousness. The underlying neural mechanisms can be studied by using the illusion where a person is made to feel that a rubber hand is his or her own hand by brushing the person's hidden real hand and synchronously brushing the artificial hand that is in full view. Here we show that threat to the rubber hand can induce a similar level of activity in the brain areas associated with anxiety and interoceptive awareness (insula and anterior cingulate cortex) as when the person's real hand is threatened. We further show that the stronger the feeling of ownership of the artificial hand, the stronger the threat-evoked neuronal responses in the areas reflecting anxiety. Furthermore, across subjects, activity in multisensory areas reflecting ownership predicted the activity in the interoceptive system when the hand was under threat. Finally, we show that there is activity in medial wall motor areas, reflecting an urge to withdraw the artificial hand when it is under threat. These findings suggest that artificial limbs can evoke the same feelings as real limbs and provide objective neurophysiological evidence that the rubber hand is fully incorporated into the body. These findings are of fundamental importance because they suggest that the feeling of body ownership is associated with changes in the interoceptive systems.
The question of whether recognition memory judgments with and without recollection reflect dissociable patterns of brain activity is unresolved. We used event-related, functional magnetic resonance imaging (fMRI) of 12 healthy volunteers to measure hemodynamic responses associated with both studying and recognizing words. Volunteers made one of three judgments to each word during recognition: whether they recollected seeing it during study (R judgments), whether they experienced a feeling of familiarity in the absence of recollection (K judgments), or whether they did not remember seeing it during study (N judgments). Both R and K judgments for studied words were associated with enhanced responses in left prefrontal and left parietal cortices relative to N judgments for unstudied words. The opposite pattern was observed in bilateral temporoccipital regions and amygdalae. R judgments for studied words were associated with enhanced responses in anterior left prefrontal, left parietal, and posterior cingulate regions relative to K judgments. At study, a posterior left prefrontal region exhibited an enhanced response to words subsequently given R versus K judgments, but the response of this region during recognition did not differentiate R and K judgments. K judgments for studied words were associated with enhanced responses in right lateral and medial prefrontal cortex relative to both R judgments for studied words and N judgments for unstudied words, a difference we attribute to greater monitoring demands when memory judgments are less certain. These results suggest that the responses of different brain regions do dissociate according to the phenomenology associated with memory retrieval.
BackgroundInflammation is associated with psychological, emotional, and behavioral disturbance, known as sickness behavior. Inflammatory cytokines are implicated in coordinating this central motivational reorientation accompanying peripheral immunologic responses to pathogens. Studies in rodents suggest an afferent interoceptive neural mechanism, although comparable data in humans are lacking.MethodsIn a double-blind, randomized crossover study, 16 healthy male volunteers received typhoid vaccination or saline (placebo) injection in two experimental sessions. Profile of Mood State questionnaires were completed at baseline and at 2 and 3 hours. Two hours after injection, participants performed a high-demand color word Stroop task during functional magnetic resonance imaging. Blood samples were performed at baseline and immediately after scanning.ResultsTyphoid but not placebo injection produced a robust inflammatory response indexed by increased circulating interleukin-6 accompanied by a significant increase in fatigue, confusion, and impaired concentration at 3 hours. Performance of the Stroop task under inflammation activated brain regions encoding representations of internal bodily state. Spatial and temporal characteristics of this response are consistent with interoceptive information flow via afferent autonomic fibers. During performance of this task, activity within interoceptive brain regions also predicted individual differences in inflammation-associated but not placebo-associated fatigue and confusion. Maintenance of cognitive performance, despite inflammation-associated fatigue, led to recruitment of additional prefrontal cortical regions.ConclusionsThese findings suggest that peripheral infection selectively influences central nervous system function to generate core symptoms of sickness and reorient basic motivational states. Inflammation is associated with psychological, emotional, and behavioral disturbance, known as sickness behavior. Inflammatory cytokines are implicated in coordinating this central motivational reorientation accompanying peripheral immunologic responses to pathogens. Studies in rodents suggest an afferent interoceptive neural mechanism, although comparable data in humans are lacking. In a double-blind, randomized crossover study, 16 healthy male volunteers received typhoid vaccination or saline (placebo) injection in two experimental sessions. Profile of Mood State questionnaires were completed at baseline and at 2 and 3 hours. Two hours after injection, participants performed a high-demand color word Stroop task during functional magnetic resonance imaging. Blood samples were performed at baseline and immediately after scanning. Typhoid but not placebo injection produced a robust inflammatory response indexed by increased circulating interleukin-6 accompanied by a significant increase in fatigue, confusion, and impaired concentration at 3 hours. Performance of the Stroop task under inflammation activated brain regions encoding representations of internal bodily state. Spatial and temporal characteristics of this response are consistent with interoceptive information flow via afferent autonomic fibers. During performance of this task, activity within interoceptive brain regions also predicted individual differences in inflammation-associated but not placebo-associated fatigue and confusion. Maintenance of cognitive performance, despite inflammation-associated fatigue, led to recruitment of additional prefrontal cortical regions. These findings suggest that peripheral infection selectively influences central nervous system function to generate core symptoms of sickness and reorient basic motivational states.
Replay supports planning Learning from direct experience is easy—we can always use trial and error—but how do we learn from nondirect (nonlocal) experiences? For this, we need additional mechanisms that bridge time and space. In rodents, hippocampal replay is hypothesized to promote this function. Liu et al. measured high-temporal-resolution brain signals using human magnetoencephalography combined with a new model-based, visually oriented, multipath reinforcement memory task. This task was designed to differentiate local versus nonlocal learning episodes within the subject. They found that reverse sequential replay in the human medial temporal lobe supports nonlocal reinforcement learning and is the underlying mechanism for solving complex credit assignment problems such as value learning. Science , abf1357, this issue p. eabf1357
A standard view in health economics is that, although there is no market that determines the "prices" for health states, people can nonetheless associate health states with monetary values (or other scales, such as quality adjusted life year [QALYs] and disability adjusted life year [DALYs]). Such valuations can be used to shape health policy, and a major research challenge is to elicit such values from people; creating experimental "markets" for health states is a theoretically attractive way to address this. We explore the possibility that this framework may be fundamentally flawed-because there may not be any stable values to be revealed. Instead, perhaps people construct ad hoc values, influenced by contextual factors, such as the observed decisions of others.The participants bid to buy relief from equally painful electrical shocks to the leg and arm in an experimental health market based on an interactive second-price auction. Thirty subjects were randomly assigned to two experimental conditions where the bids by "others" were manipulated to follow increasing or decreasing price trends for one, but not the other, pain. After the auction, a preference test asked the participants to choose which pain they prefer to experience for a longer duration.Players remained indifferent between the two pain-types throughout the auction. However, their bids were differentially attracted toward what others bid for each pain, with overbidding during decreasing prices and underbidding during increasing prices.Health preferences are dissociated from market prices, which are strongly referenced to others' choices. This suggests that the price of health care in a free-market has the capacity to become critically detached from people's underlying preferences.
The effectiveness of distractor-filtering is a potentially important determinant of working memory capacity (WMC).However, a distinction between the contributions of distractor-filtering at WM encoding as opposed to filtering during maintenance has not been made and the assumption is that these rely on the same mechanism.Within 2 experiments, 1 conducted in the laboratory with 21 participants, and the other played as a game on smartphones (n ϭ 3,247) we measure WMC without distractors, and present distractors during encoding or during the delay period of a WM task to determine performance associated with distraction at encoding and during maintenance.Despite differences in experimental setting and paradigm design between the 2 studies, we show a unique contribution to WMC from both encoding and delay distractor performance in both experiments, while controlling for performance in the absence of distraction.Thus, within 2 separate experiments, 1 involving an extremely large cohort of 3,247 participants, we show a dissociation between encoding and delay distractor-filtering, indicating that separate mechanisms may contribute to WMC.
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