In a recent study we investigated the acute effects of cortisol administration in healthy male vo... more In a recent study we investigated the acute effects of cortisol administration in healthy male volunteers on free recall of pleasant, unpleasant, and neutral nouns using a between-subjects double-blind placebo-controlled design. The volunteers were administered 10 mg of hydrocortisone or placebo between 9:00 and 10:30. Two hours after administration of cortisol a decline in recall of neutral and pleasant words was found, while recall of unpleasant words did not change. These results are consistent with a possible inhibitory influence of cortisol on a prefrontal dopaminergic mechanism involved in approach and positivity bias. In this paper we first explain why this interpretation would predict recall of pleasant words from recency positions to be especially sensitive to cortisol administration. Comparing primacy and recency recall of pleasant and unpleasant words, there proved to be a selective decline in recall of pleasant recency words. These results did not appear to stem from differences in recall strategies between our groups of volunteers.
Reduced emotional expression has been consistently related to susceptibility or fast progression ... more Reduced emotional expression has been consistently related to susceptibility or fast progression of breast cancer. Breast cancer development and reduced emotional expression have both been related to rejection- and separation-related conditions. The neuropeptide oxytocin is low in response to rejection or separation. Recent results suggest that oxytocin may protect against the development of breast cancer and slow its progression. In the present study, we investigated if individual differences in emotional expressivity relate to basal or cortisol-stimulated plasma oxytocin. Healthy female subjects were treated with placebo or 35mg of cortisol orally in a double-blind within-subject study. Seventy minutes later, blood was sampled for determination of oxytocin and cortisol levels. We found an interaction between treatment condition and Emotional Expression-out scores: after cortisol treatment, oxytocin levels increased proportional to Emotion Expression-out score. These preliminary findings provide a potential mechanism for associations in the literature between emotional expressive behavior and breast cancer.
Medial prefrontal cortical (mPFC) functions may be aspects of ventral or dorsal control pathways,... more Medial prefrontal cortical (mPFC) functions may be aspects of ventral or dorsal control pathways, depending on the position along a rostral-ventral to caudal-dorsal gradient within medial cortex that may mirror the pattern of interconnections between cortex and striatum. Rostral-ventral mPFC is connected to ventral striatum and posterior cingulate cortex/precuneus are connected with dorsal striatum. Reentrant ventral (limbic), central (associative), and dorsal (motor) corticostriatal loops pass information from ventral-to-dorsal striatum, shifting hedonic processing toward habitual action. Splitting up unexpected occurrences (positive surprise) from non-occurrences (negative surprise) instead of splitting according to valence mirrors the importance of negative surprise in dorsal habitual control which is insensitive to the valence of outcomes. The importance of positive surprise and valence increases toward the rostral-ventral end of the gradient in mPFC and ventrolateral prefrontal cortex. We discuss paradigms that may help to disentangle positive from negative surprise. Moreover, we think that the framework of the functional gradient may help giving various functions in mPFC their place in a larger scheme.
Treatment with cortisol has been found to decrease fatigue and increase feelings of vigor in both... more Treatment with cortisol has been found to decrease fatigue and increase feelings of vigor in both patients and healthy male subjects. We obtained self-reports of mood before 35 mg cortisol or placebo ingestion, 70 min later, and after the healthy female subjects performed cognitive tasks for 1 h in a double-blind within-subject study. Cortisol decreased fatigue, increased vigor, and tended to decrease tension. Effects on fatigue were largest after task performance, when fatigue had increased, suggesting that improvement of fatigue by cortisol is observed when subjects are fatigued. This is the first study to demonstrate improvements in fatigue in healthy female subjects; this is particularly relevant because of the high prevalence of hypocortisolimic fatigue syndromes in women and recent evidence that many psychiatric disorders may involve stress-induced hypocortisolemia that is responsive to cortisol replacement.
A framework for mental fatigue is proposed, that involves an integrated evaluation of both expect... more A framework for mental fatigue is proposed, that involves an integrated evaluation of both expected rewards and energetical costs associated with continued performance. Adequate evaluation of predicted rewards and potential risks of actions is essential for successful adaptive behaviour. However, while both rewards and punishments can motivate to engage in activities, both types of motivated behaviour are associated with energetical costs. We will review findings that suggest that the nucleus accumbens, orbitofrontal cortex, amygdala, insula and anterior cingulate cortex are involved evaluating both the potential rewards associated with performing a task, as well as assessing the energetical demands involved in task performance. Behaviour will only proceed if this evaluation turns out favourably towards spending (additional) energy. We propose that this evaluation of predicted rewards and energetical costs is central to the phenomenon of mental fatigue: people will no longer be motivated to engage in task performance when energetical costs are perceived to outweigh predicted rewards.
We hypothesized that interactions between traits and context predict task engagement, as measured... more We hypothesized that interactions between traits and context predict task engagement, as measured by the amplitude of the error-related negativity (ERN), performance, and relative frontal activity asymmetry (RFA). In Study 1, we found that drive for reward, absorption, and constraint independently predicted self-reported persistence. We hypothesized that, during a prolonged monotonous task, absorption would predict initial ERN amplitudes, constraint would delay declines in ERN amplitudes and deterioration of performance, and drive for reward would predict left RFA when a reward could be obtained. Study 2, employing EEG recordings, confirmed our predictions. The results showed that most traits that have in previous research been related to ERN amplitudes have a relationship with the motivational trait persistence in common. In addition, trait—context combinations that are likely associated with increased engagement predict larger ERN amplitudes and RFA. Together, these results support the hypothesis that engagement may be a common underlying factor predicting ERN amplitude.
Infant laughter is a rewarding experience. It activates neural reward circuits and promotes paren... more Infant laughter is a rewarding experience. It activates neural reward circuits and promotes parental proximity and care, thus facilitating parent-infant attachment. The neuropeptide oxytocin might enhance the incentive salience of infant laughter by modulating neural circuits related to the perception of infant cues. In a randomized controlled trial with functional magnetic resonance imaging we investigated the influence of intranasally administered oxytocin on functional brain connectivity in response to infant laughter. Blood oxygenation level-dependent responses to infant laughter were measured in 22 nulliparous women who were administered oxytocin and 20 nulliparous women who were administered a placebo. Elevated oxytocin levels reduced activation in the amygdala during infant laughter and enhanced functional connectivity between the amygdala and the orbitofrontal cortex, the anterior cingulate, the hippocampus, the precuneus, the supramarginal gyri, and the middle temporal gyrus. Increased functional connectivity between the amygdala and regions involved in emotion regulation may reduce negative emotional arousal while enhancing the incentive salience of the infant laughter.
Asymmetrical turning behavior is an established indicator of asymmetrical dopaminergic activity a... more Asymmetrical turning behavior is an established indicator of asymmetrical dopaminergic activity and thought to be a manifestation of hemispatial neglect. We set out to find converging support for the hypothesis that cortisol modulates frontal dopaminergic asymmetrical activity, and hence dopaminergically mediated approach behaviors, by studying the effect of cortisol administration on turning behavior in healthy subjects. Both when our subjects attempted to rotate through a target angle (twice 360 degrees) in a clockwise or anticlockwise direction with reduced sensory input, cortisol induced a relative clockwise turning bias. Furthermore, this effect interacted with scores on novelty seeking, a putative indicator of individual differences in dopaminergic function: subjects scoring higher on novelty seeking demonstrated a smaller or no increase after cortisol administration in their clockwise turning bias. The results provide converging support for the hypothesis that cortisol modulates frontal dopaminergic asymmetrical activity. As we discuss, they further point to the possible involvement of the insula in cortisol effects.
Oxytocin and attachment seem to interact in suppressing subjective anxiety and physiological stre... more Oxytocin and attachment seem to interact in suppressing subjective anxiety and physiological stress responses. In this study we investigated the relationships between individual differences in trait attachment scores, state and trait anxiety, plasma cortisol, and plasma oxytocin levels in healthy premenopausal women. Attachment proved to be a strong positive predictor of oxytocin levels, which were also positively predicted by cortisol levels and state and trait anxiety. The relationship between oxytocin and state anxiety was modulated by attachment scores. The present results may help interpreting seeming contradictions in the recent literature on oxytocin, attachment, and stress in humans, by suggesting that context effects determine which relationships are found in different studies: anxiolytic effects of oxytocin in a context of partner support versus stress- or cortisol-induced oxytocin responses in a context of distress or increased cortisol.
The acute effects of cortisol (35mg) administration in 11 healthy male volunteers on resting fron... more The acute effects of cortisol (35mg) administration in 11 healthy male volunteers on resting frontal EEG asymmetry measured in the alpha band were investigated, using a within-subjects double-blind design. Results were indicative of a relative increase of right frontal activity with cortisol. This pattern of activity is similar to the deviant pattern that has been reported in patients suffering from depression, a condition often accompanied by elevated plasma cortisol levels. The significant effect on frontal asymmetry provides convergent support for our hypothesis, based upon previous results, that sustained (>30 minutes after stress termination) relative high levels of cortisol inhibit approach motivation.
In a recent study we investigated the acute effects of cortisol administration in healthy male vo... more In a recent study we investigated the acute effects of cortisol administration in healthy male volunteers on free recall of pleasant, unpleasant, and neutral nouns using a between-subjects double-blind placebo-controlled design. The volunteers were administered 10 mg of hydrocortisone or placebo between 9:00 and 10:30. Two hours after administration of cortisol a decline in recall of neutral and pleasant words was found, while recall of unpleasant words did not change. These results are consistent with a possible inhibitory influence of cortisol on a prefrontal dopaminergic mechanism involved in approach and positivity bias. In this paper we first explain why this interpretation would predict recall of pleasant words from recency positions to be especially sensitive to cortisol administration. Comparing primacy and recency recall of pleasant and unpleasant words, there proved to be a selective decline in recall of pleasant recency words. These results did not appear to stem from differences in recall strategies between our groups of volunteers.
Reduced emotional expression has been consistently related to susceptibility or fast progression ... more Reduced emotional expression has been consistently related to susceptibility or fast progression of breast cancer. Breast cancer development and reduced emotional expression have both been related to rejection- and separation-related conditions. The neuropeptide oxytocin is low in response to rejection or separation. Recent results suggest that oxytocin may protect against the development of breast cancer and slow its progression. In the present study, we investigated if individual differences in emotional expressivity relate to basal or cortisol-stimulated plasma oxytocin. Healthy female subjects were treated with placebo or 35mg of cortisol orally in a double-blind within-subject study. Seventy minutes later, blood was sampled for determination of oxytocin and cortisol levels. We found an interaction between treatment condition and Emotional Expression-out scores: after cortisol treatment, oxytocin levels increased proportional to Emotion Expression-out score. These preliminary findings provide a potential mechanism for associations in the literature between emotional expressive behavior and breast cancer.
Medial prefrontal cortical (mPFC) functions may be aspects of ventral or dorsal control pathways,... more Medial prefrontal cortical (mPFC) functions may be aspects of ventral or dorsal control pathways, depending on the position along a rostral-ventral to caudal-dorsal gradient within medial cortex that may mirror the pattern of interconnections between cortex and striatum. Rostral-ventral mPFC is connected to ventral striatum and posterior cingulate cortex/precuneus are connected with dorsal striatum. Reentrant ventral (limbic), central (associative), and dorsal (motor) corticostriatal loops pass information from ventral-to-dorsal striatum, shifting hedonic processing toward habitual action. Splitting up unexpected occurrences (positive surprise) from non-occurrences (negative surprise) instead of splitting according to valence mirrors the importance of negative surprise in dorsal habitual control which is insensitive to the valence of outcomes. The importance of positive surprise and valence increases toward the rostral-ventral end of the gradient in mPFC and ventrolateral prefrontal cortex. We discuss paradigms that may help to disentangle positive from negative surprise. Moreover, we think that the framework of the functional gradient may help giving various functions in mPFC their place in a larger scheme.
Treatment with cortisol has been found to decrease fatigue and increase feelings of vigor in both... more Treatment with cortisol has been found to decrease fatigue and increase feelings of vigor in both patients and healthy male subjects. We obtained self-reports of mood before 35 mg cortisol or placebo ingestion, 70 min later, and after the healthy female subjects performed cognitive tasks for 1 h in a double-blind within-subject study. Cortisol decreased fatigue, increased vigor, and tended to decrease tension. Effects on fatigue were largest after task performance, when fatigue had increased, suggesting that improvement of fatigue by cortisol is observed when subjects are fatigued. This is the first study to demonstrate improvements in fatigue in healthy female subjects; this is particularly relevant because of the high prevalence of hypocortisolimic fatigue syndromes in women and recent evidence that many psychiatric disorders may involve stress-induced hypocortisolemia that is responsive to cortisol replacement.
A framework for mental fatigue is proposed, that involves an integrated evaluation of both expect... more A framework for mental fatigue is proposed, that involves an integrated evaluation of both expected rewards and energetical costs associated with continued performance. Adequate evaluation of predicted rewards and potential risks of actions is essential for successful adaptive behaviour. However, while both rewards and punishments can motivate to engage in activities, both types of motivated behaviour are associated with energetical costs. We will review findings that suggest that the nucleus accumbens, orbitofrontal cortex, amygdala, insula and anterior cingulate cortex are involved evaluating both the potential rewards associated with performing a task, as well as assessing the energetical demands involved in task performance. Behaviour will only proceed if this evaluation turns out favourably towards spending (additional) energy. We propose that this evaluation of predicted rewards and energetical costs is central to the phenomenon of mental fatigue: people will no longer be motivated to engage in task performance when energetical costs are perceived to outweigh predicted rewards.
We hypothesized that interactions between traits and context predict task engagement, as measured... more We hypothesized that interactions between traits and context predict task engagement, as measured by the amplitude of the error-related negativity (ERN), performance, and relative frontal activity asymmetry (RFA). In Study 1, we found that drive for reward, absorption, and constraint independently predicted self-reported persistence. We hypothesized that, during a prolonged monotonous task, absorption would predict initial ERN amplitudes, constraint would delay declines in ERN amplitudes and deterioration of performance, and drive for reward would predict left RFA when a reward could be obtained. Study 2, employing EEG recordings, confirmed our predictions. The results showed that most traits that have in previous research been related to ERN amplitudes have a relationship with the motivational trait persistence in common. In addition, trait—context combinations that are likely associated with increased engagement predict larger ERN amplitudes and RFA. Together, these results support the hypothesis that engagement may be a common underlying factor predicting ERN amplitude.
Infant laughter is a rewarding experience. It activates neural reward circuits and promotes paren... more Infant laughter is a rewarding experience. It activates neural reward circuits and promotes parental proximity and care, thus facilitating parent-infant attachment. The neuropeptide oxytocin might enhance the incentive salience of infant laughter by modulating neural circuits related to the perception of infant cues. In a randomized controlled trial with functional magnetic resonance imaging we investigated the influence of intranasally administered oxytocin on functional brain connectivity in response to infant laughter. Blood oxygenation level-dependent responses to infant laughter were measured in 22 nulliparous women who were administered oxytocin and 20 nulliparous women who were administered a placebo. Elevated oxytocin levels reduced activation in the amygdala during infant laughter and enhanced functional connectivity between the amygdala and the orbitofrontal cortex, the anterior cingulate, the hippocampus, the precuneus, the supramarginal gyri, and the middle temporal gyrus. Increased functional connectivity between the amygdala and regions involved in emotion regulation may reduce negative emotional arousal while enhancing the incentive salience of the infant laughter.
Asymmetrical turning behavior is an established indicator of asymmetrical dopaminergic activity a... more Asymmetrical turning behavior is an established indicator of asymmetrical dopaminergic activity and thought to be a manifestation of hemispatial neglect. We set out to find converging support for the hypothesis that cortisol modulates frontal dopaminergic asymmetrical activity, and hence dopaminergically mediated approach behaviors, by studying the effect of cortisol administration on turning behavior in healthy subjects. Both when our subjects attempted to rotate through a target angle (twice 360 degrees) in a clockwise or anticlockwise direction with reduced sensory input, cortisol induced a relative clockwise turning bias. Furthermore, this effect interacted with scores on novelty seeking, a putative indicator of individual differences in dopaminergic function: subjects scoring higher on novelty seeking demonstrated a smaller or no increase after cortisol administration in their clockwise turning bias. The results provide converging support for the hypothesis that cortisol modulates frontal dopaminergic asymmetrical activity. As we discuss, they further point to the possible involvement of the insula in cortisol effects.
Oxytocin and attachment seem to interact in suppressing subjective anxiety and physiological stre... more Oxytocin and attachment seem to interact in suppressing subjective anxiety and physiological stress responses. In this study we investigated the relationships between individual differences in trait attachment scores, state and trait anxiety, plasma cortisol, and plasma oxytocin levels in healthy premenopausal women. Attachment proved to be a strong positive predictor of oxytocin levels, which were also positively predicted by cortisol levels and state and trait anxiety. The relationship between oxytocin and state anxiety was modulated by attachment scores. The present results may help interpreting seeming contradictions in the recent literature on oxytocin, attachment, and stress in humans, by suggesting that context effects determine which relationships are found in different studies: anxiolytic effects of oxytocin in a context of partner support versus stress- or cortisol-induced oxytocin responses in a context of distress or increased cortisol.
The acute effects of cortisol (35mg) administration in 11 healthy male volunteers on resting fron... more The acute effects of cortisol (35mg) administration in 11 healthy male volunteers on resting frontal EEG asymmetry measured in the alpha band were investigated, using a within-subjects double-blind design. Results were indicative of a relative increase of right frontal activity with cortisol. This pattern of activity is similar to the deviant pattern that has been reported in patients suffering from depression, a condition often accompanied by elevated plasma cortisol levels. The significant effect on frontal asymmetry provides convergent support for our hypothesis, based upon previous results, that sustained (>30 minutes after stress termination) relative high levels of cortisol inhibit approach motivation.
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