Marieke Jepma

Pupil diameter tracks changes in control state predicted by the adaptive gain theory of locus coeruleus function

An important dimension of cognitive control is the adaptive regulation of the balance between exploitation (pursuing known sources of reward) and exploration (seeking new ones) in response to changes in task utility. Recent studies have suggested that the locus coeruleus-norepinephrine system may play an important role in this function and that pupil diameter can be used to index locus coeruleus activity. On the basis of this, we reasoned that pupil diameter may correlate closely with control state and associated changes in behavior. Specifically, we predicted that increases in baseline pupil diameter would be associated with decreases in task utility and disengagement from the task (exploration), whereas reduced baseline diameter (but increases in task-evoked dilations) would be associated with task engagement (exploitation). Findings in three experiments were consistent with these predictions, suggesting that pupillometry may be useful as an index of both control state and, indirectly, locus coeruleus function.

Representation of aversive prediction errors in the human periaqueductal gray

Pain is a primary driver of learning and motivated action. It is also a target of learning, as nociceptive brain responses are shaped by learning processes. We combined an instrumental pain avoidance task with an axiomatic approach to assessing fMRI signals related to prediction errors (PEs), which drive reinforcement-based learning. We found that pain PEs were encoded in the periaqueductal gray (PAG), a structure important for pain control and learning in animal models. Axiomatic tests combined with dynamic causal modeling suggested that ventromedial prefrontal cortex, supported by putamen, provides an expected value–related input to the PAG, which then conveys PE signals to prefrontal regions important for behavioral regulation, including orbitofrontal, anterior mid-cingulate and dorsomedial prefrontal cortices. Thus, pain-related learning involves distinct neural circuitry, with implications for behavior and pain dynamics.

The effects of accessory stimuli on information processing: Evidence from electrophysiology and a diffusion model analysis

People typically respond faster to a stimulus when it is accompanied by a task-irrelevant accessory stimulus presented in another perceptual modality. However, the mechanisms responsible for this accessory-stimulus effect are still poorly understood. We examined the effects of auditory accessory stimulation on the processing of visual stimuli using scalp electrophysiology (Experiment 1) and a diffusion model analysis (Experiment 2). In accordance with previous studies, lateralized readiness potentials indicated that accessory stimuli do not speed motor execution. Surface Laplacians over the motor cortex, however, revealed a bihemispheric increase in motor activation—an effect predicted by nonspecific arousal models. The diffusion model analysis suggested that accessory stimuli do not affect parameters of the decision process, but expedite only the nondecision component of information processing. Consequently, we conclude that accessory stimuli facilitate stimulus encoding. The visual P1 and N1 amplitudes on accessory-stimulus trials were modulated in a way that is consistent with multisensory energy integration, a possible mechanism for this facilitation.

Neural mechanisms underlying the induction and relief of perceptual curiosity

Curiosity is one of the most basic biological drives in both animals and humans, and has been identified as a key motive for learning and discovery. Despite the importance of curiosity and related behaviors, the topic has been largely neglected in human neuroscience; hence little is known about the neurobiological mechanisms underlying curiosity. We used functional magnetic resonance imaging (fMRI) to investigate what happens in our brain during the induction and subsequent relief of perceptual curiosity. Our core findings were that (1) the induction of perceptual curiosity, through the presentation of ambiguous visual input, activated the anterior insula and anterior cingulate cortex (ACC), brain regions sensitive to conflict and arousal; (2) the relief of perceptual curiosity, through visual disambiguation, activated regions of the striatum that have been related to reward processing; and (3) the relief of perceptual curiosity was associated with hippocampal activation and enhanced incidental memory. These findings provide the first demonstration of the neural basis of human perceptual curiosity. Our results provide neurobiological support for a classic psychological theory of curiosity, which holds that curiosity is an aversive condition of increased arousal whose termination is rewarding and facilitates memory.

The dynamics of pain: Evidence for simultaneous site-specific habituation and site-nonspecific sensitization in thermal pain

UNLABELLED Repeated exposure to noxious stimuli changes their painfulness, due to multiple adaptive processes in the peripheral and central nervous systems. Somewhat paradoxically, repeated stimulation can produce an increase (sensitization) or a decrease (habituation) in pain. Adaptation processes may also be body-site-specific or operate across body sites, and considering this distinction may help explain the conditions under which habituation versus sensitization occurs. To dissociate the effects of site-specific and site-nonspecific adaptation processes, we examined reported pain in 100 participants during counterbalanced sequences of noxious thermal stimulation on multiple skin sites. Analysis of pain ratings revealed 2 opposing sequential effects: repeated stimulations of the same skin site produced temperature-dependent habituation, whereas repeated stimulations across different sites produced sensitization. Stimulation trials were separated by ∼20 seconds, and sensitization was unrelated to the distance between successively stimulated sites, suggesting that neither temporal nor spatial summation occurred. To explain these effects, we propose a dynamic model with 2 adaptation processes, one site-specific and the other site-nonspecific. The model explains 93% of the variance in the group-mean pain ratings after controlling for current stimulation temperature, with its estimated parameters showing evidence for habituation for the site-specific process and sensitization for the site-nonspecific process. The 2 pain adaptation processes revealed in this study, and the ability to disentangle them, may hold keys to understanding multiple pain-regulatory mechanisms and their disturbance in chronic pain syndromes. PERSPECTIVE This article presents novel evidence for simultaneous site-specific habituation and site-nonspecific sensitization in thermal pain, which can be disentangled (and the direction and strength of each process estimated) by a dynamic model. The dissociation of site-specific and site-nonspecific adaptation processes may hold keys to understanding multiple pain-regulatory mechanisms in both healthy and patient populations.

Temporal expectation and information processing: A model-based analysis

People are able to use temporal cues to anticipate the timing of an event, enabling them to process that event more efficiently. We conducted two experiments, using the fixed-foreperiod paradigm (Experiment 1) and the temporal-cueing paradigm (Experiment 2), to assess which components of information processing are speeded when subjects use such temporal cues to predict the onset of a target stimulus. We analyzed the observed temporal expectation effects on task performance using sequential-sampling models of decision making: the Ratcliff diffusion model and the shifted-Wald model. The results from the two experiments were consistent: temporal expectation affected the duration of nondecision processes (target encoding and/or response preparation) but had little effect on the two main components of the decision process: response-threshold setting and the rate of evidence accumulation. Our findings provide novel evidence about the psychological processes underlying temporal-expectation effects on reaction time.

The role of the magnocellular and parvocellular pathways in the attentional blink

The attentional blink refers to the transient impairment in perceiving the 2nd of two targets presented in close temporal proximity in a rapid serial visual presentation (RSVP) stream. The purpose of this study was to examine the effect on human attentional-blink performance of disrupting the function of the magnocellular pathway--a major visual-processing pathway specialized in temporal segregation. The study was motivated by recent theories that relate the attentional blink to the limited temporal resolution of attentional responses, and by a number of poorly understood empirical findings, including the effects on the attentional blink of luminance adaptation and distraction. The attentional blink was assessed for stimuli on a red background (Experiment 1), stimuli on an equiluminant background (Experiment 2), and following flicker or motion adaptation (Experiment 3), three psychophysical manipulations known to disrupt magnocellular function. Contrary to our expectations, the attentional blink was not affected by these manipulations, suggesting no specific relationship between the attentional blink and magnocellular and/or parvocellular processing.

The role of the noradrenergic system in the exploration-exploitation trade-off: a psychopharmacological study

Animal research and computational modeling have indicated an important role for the neuromodulatory locus coeruleus–norepinephrine (LC–NE) system in the control of behavior. According to the adaptive gain theory, the LC–NE system is critical for optimizing behavioral performance by regulating the balance between exploitative and exploratory control states. However, crucial direct empirical tests of this theory in human subjects have been lacking. We used a pharmacological manipulation of the LC–NE system to test predictions of this theory in humans. In a double-blind parallel-groups design (N = 52), participants received 4 mg reboxetine (a selective norepinephrine reuptake inhibitor), 30 mg citalopram (a selective serotonin reuptake inhibitor), or placebo. The adaptive gain theory predicted that the increased tonic NE levels induced by reboxetine would promote task disengagement and exploratory behavior. We assessed the effects of reboxetine on performance in two cognitive tasks designed to examine task (dis)engagement and exploitative versus exploratory behavior: a diminishing-utility task and a gambling task with a non-stationary pay-off structure. In contrast to predictions of the adaptive gain theory, we did not find differences in task (dis)engagement or exploratory behavior between the three experimental groups, despite demonstrable effects of the two drugs on non-specific central and autonomic nervous system parameters. Our findings suggest that the LC–NE system may not be involved in the regulation of the exploration–exploitation trade-off in humans, at least not within the context of a single task. It remains to be examined whether the LC–NE system is involved in random exploration exceeding the current task context.

Conceptual Conditioning Mechanisms Mediating Conditioning Effects on Pain

Classical conditioning can profoundly modify subsequent pain responses, but the mechanisms that drive this effect are unresolved. In pain-conditioning studies, cues are typically conditioned to primary aversive reinforcers; hence, subsequent pain modulation could reflect learned precognitive associations (i.e., those involving neural plasticity independent of expectations and other forms of conceptual thought) or conceptual expectancies. We isolated conceptual contributions using a thermal pain-conditioning procedure in which different conditioned stimulus (CS) cues were repeatedly paired with symbolic representations of high and low noxious heat. In a subsequent test phase, identical noxious stimuli evoked larger skin conductance responses (SCRs) and pain ratings when preceded by CS cues associated with high temperature than by those associated with low temperature. These effects were mediated by participants’ self-reported expectancies. CS cues associated with high temperature also evoked larger anticipatory SCRs than did CS cues associated with low temperature, but larger anticipatory SCRs predicted smaller subsequent heat-evoked SCRs. These results provide novel evidence that conditioned modulation of pain physiology can be acquired through purely conceptual processes, and that self-reported expectancies and physiological threat responses have opposing effects on pain.

Neurocognitive Function in Dopamine- β -Hydroxylase Deficiency

Dopamine-β-hydroxylase (DβH) deficiency is a rare genetic syndrome characterized by the complete absence of norepinephrine in the peripheral and the central nervous system. DβH-deficient patients suffer from several physical symptoms, which can be treated successfully with L-threo-3,4-dihydroxyphenylserine, a synthetic precursor of norepinephrine. Informal clinical observations suggest that DβH-deficient patients do not have obvious cognitive impairments, even when they are not medicated, which is remarkable given the important role of norepinephrine in normal neurocognitive function. This study provided the first systematic investigation of neurocognitive function in human DβH deficiency. We tested 5 DβH-deficient patients and 10 matched healthy control participants on a comprehensive cognitive task battery, and examined their pupil dynamics, brain structure, and the P3 component of the electroencephalogram. All participants were tested twice; the patients were tested once ON and once OFF medication. Magnetic resonance imaging scans of the brain revealed that the patients had a smaller total brain volume than the control group, which is in line with the recent hypothesis that norepinephrine has a neurotrophic effect. In addition, the patients showed an abnormally small or absent task-evoked pupil dilation. However, we found no substantial differences in cognitive performance or P3 amplitude between the patients and the control participants, with the exception of a temporal-attention deficit in the patients OFF medication. The largely spared neurocognitive function in DβH-deficient patients suggests that other neuromodulators have taken over the function of norepinephrine in the brains of these patients.