Sex differences in orienting to pictures with and without humans: evidence from the cardiac evoked response (ECR) and the cortical long latency parietal positivity (LPP).

OBJECTIVE: This study investigated the effect of social relevance in affective pictures on two orienting responses, i.e. the evoked cardiac response (ECR), and a long latency cortical evoked potential (LPP) and whether this effect would differ between males and females. Assuming that orienting to affective social information is fundamental to experiencing affective empathy, associations between self-report measures of empathy and the two orienting responses were investigated. METHOD: ECRs were obtained from 34 female and 30 male students, and LPPs from 25 female and 27 male students viewing 414 pictures from the International Affective Picture System. Pictures portrayed pleasant, unpleasant and neutral scenes with and without humans. RESULTS: Both the ECR and LPP showed the largest response to pictures with humans in unpleasant situations. For both measures, the responses to pictures with humans correlated with self-report measures of empathy. While we found a greater male than female responsiveness to the pictures without humans in the ECR, a greater female than male responsiveness was observed in the LPP response to pictures with humans. CONCLUSION AND SIGNIFICANCE: The sensitivity of these orienting responses to social relevance and their differential contribution to the prediction of individual differences underline the validity of their combined use in clinical studies investigating individuals with social disabilities.

Processing of continuously provided punishment and reward in children with ADHD and the modulating effects of stimulant medication: an ERP study.

OBJECTIVES: Current models of ADHD suggest abnormal reward and punishment sensitivity, but the exact mechanisms are unclear. This study aims to investigate effects of continuous reward and punishment on the processing of performance feedback in children with ADHD and the modulating effects of stimulant medication. METHODS: 15 Methylphenidate (Mph)-treated and 15 Mph-free children of the ADHD-combined type and 17 control children performed a selective attention task with three feedback conditions: no-feedback, gain and loss. Event Related Potentials (ERPs) time-locked to feedback and errors were computed. RESULTS: All groups performed more accurately with gain and loss than without feedback. Feedback-related ERPs demonstrated no group differences in the feedback P2, but an enhanced late positive potential (LPP) to feedback stimuli (both gains and losses) for Mph-free children with ADHD compared to controls. Feedback-related ERPs in Mph-treated children with ADHD were similar to controls. Correlational analyses in the ADHD groups revealed that the severity of inattention problems correlated negatively with the feedback P2 amplitude and positively with the LPP to losses and omitted gains. CONCLUSIONS: The early selective attention for rewarding and punishing feedback was relatively intact in children with ADHD, but the late feedback processing was deviant (increased feedback LPP). This may explain the often observed positive effects of continuous reinforcement on performance and behaviour in children with ADHD. However, these group findings cannot be generalised to all individuals with the ADHD, because the feedback-related ERPs were associated with the severity of the inattention problems. Children with ADHD-combined type with more inattention problems showed both deviant early attentional selection of feedback stimuli, and deviant late processing of non-reward and punishment.

Cortisol-induced increases of plasma oxytocin levels predict decreased immediate free recall of unpleasant words.

Cortisol and oxytocin have been shown to interact in both the regulation of stress responses and in memory function. In the present study we administered cortisol to 35 healthy female subjects in a within-subject double-blind placebo-controlled design, while measuring oxytocin levels, adrenocorticotropic hormone (ACTH) levels, and free recall of pleasant and of unpleasant words. We found that cortisol administration suppressed ACTH levels and (1) induced a decrease in oxytocin associated with ACTH suppression and (2) an increase in oxytocin that was independent from ACTH suppression. This cortisol-induced increase in plasma oxytocin was associated with a selective decrease in immediate free recall of unpleasant words from primacy positions. The present results add to evidence that cortisol-induced increases in oxytocin could mediate some of the effects of stress and cortisol on memory, and possibly play a role in the regulation of the hypothalamo-pituitary-adrenal stress response. This mechanism could significantly impact affective and social behaviors, in particular during times of stress.

Doubts about actions and flanker incongruity-related potentials and performance.

The brain networks that are involved in flanker incongruity and error processing are also consistently implicated in mental disorders such as obsessive compulsive disorder (OCD) that feature increased "Doubts about Actions" (DaA) scores. In the present study we investigated whether DaA scores, similar to what has been found for its positive correlate, OCD symptom severity scores, predict less interference from incompatible flankers during an Eriksen flanker task. Sixteen healthy right-handed female participants performed the flanker task and event-related potentials to the stimuli were recorded. DaA, but not other trait measures such as concern over mistakes and punishment sensitivity, related to less interference from incompatible flankers on performance and a smaller increase in N2 amplitude on incongruent compared to congruent flanker trials. This seems to point to a strategy or focused attention capacity to minimize flanker interference effects. The present results suggest that specific attentional capacities or strategies that appear to characterize disorders such as OCD, are related to disorder-associated traits in healthy populations as well.

Foveal and parafoveal spatial attention and its impact on the processing of facial expression: an ERP study.

OBJECTIVE: The aim was to investigate the effects of spatial attention, stimulus location, and emotional expression on the processing of face stimuli. METHODS: Healthy volunteers performed two sustained attention tasks, focusing their attention on either fixation (foveal location) or on a location several degrees above fixation (parafoveal location). Photographs of faces with either a neutral or a fearful expression were presented randomly at one of these locations. Event-related potentials were recorded in response to the face stimuli. RESULTS: Spatial attention modulated the early P1 and N1 components for both foveally and parafoveally presented stimuli. Emotional expression effects already occurred at the P1 stage in response to attended foveal stimuli, but only arose from 220ms post-stimulus onwards in response to attended parafoveal stimuli. When faces were unattended, emotional expression effects were still present for parafoveal stimuli, whereas they were completely absent for foveal stimuli. CONCLUSIONS: The modulations of the P1/N1 components by fearful faces are due to an early sensory modulation of extrastriate generators, and reflect an enhanced allocation of attention to threat-related stimuli. SIGNIFICANCE: Future studies should take into account the possibility that spatial attention effects and effects of emotional expression processing are different for different positions in the visual field.

Variants of the SLC6A3 (DAT1) polymorphism affect performance monitoring-related cortical evoked potentials that are associated with ADHD.

Although the 10-repeat (10R) variant of the dopamine transporter gene (DAT1 or SLC6A3) is suggested to be a risk allele for Attention Deficit Hyperactivity Disorder (ADHD) no relationships between DAT1 and measures of cognition in children with ADHD have yet been demonstrated. We studied neurophysiological correlates of performance monitoring during a feedback-based learning task by measuring cortical event-related potentials (ERPs) in a group of 65 10-13-year-old children half of whom were diagnosed as ADHD. The first part of the study investigates correlations between parent-reported behaviour problems and several performance monitoring components, while the second part investigates the relationship between DAT1 and these components. Specifically ADHD problems correlated significantly with an error-related positivity (Pe) and a feedback-anticipatory negativity (the SPN). Only these two components discriminated between the DAT1 10/10R and 9R carriers. The 10/10R carriers showed a smaller Pe to errors and a smaller SPN in anticipation of negative feedback, particularly with learning.

Methylphenidate improves diminished error and feedback sensitivity in ADHD: An evoked heart rate analysis.

Attention Deficit Hyperactivity Disorder (ADHD) is a developmental disorder that has previously been related to a decreased sensitivity to errors and feedback. Supplementary to the traditional performance measures, this study uses autonomic measures to study this decreased sensitivity in ADHD and the modulating effects of medication. Children with ADHD, on and off Methylphenidate (Mph), and typically developing (TD) children performed a selective attention task with three feedback conditions: reward, punishment and no feedback. Evoked Heart Rate (EHR) responses were computed for correct and error trials. All groups performed more efficiently with performance feedback than without. EHR analyses, however, showed that enhanced EHR decelerations on error trials seen in TD children, were absent in the medication-free ADHD group for all feedback conditions. The Mph-treated ADHD group showed 'normalised' EHR decelerations to errors and error feedback, depending on the feedback condition. This study provides further evidence for a decreased physiological responsiveness to errors and error feedback in children with ADHD and for a modulating effect of Mph.

Do children with ADHD and/or PDD-NOS differ in reactivity of alpha/theta ERD/ERS to manipulations of cognitive load and stimulus relevance?

OBJECTIVE: We examined whether the method of event-related (de-)synchronization (ERD/ERS) revealed differential effects of selective attention and working memory load in children (8-11 years) with pervasive developmental disorder - not otherwise specified (PDD-NOS) or attention-deficit/hyperactivity disorder (ADHD). METHODS: Fifteen healthy controls and three equally large groups of children with symptoms of PDD-NOS, ADHD or both (PDD/HD) performed a visual selective memory search task. The EEG was recorded from which occipital alpha and frontal theta were derived. RESULTS: The effects of the overall task manipulations of task load, relevance and target/nontarget were clearly present in the overall analyses of alpha and theta ERD/ERS. However, no significant differences with respect to these manipulations existed between any of the subject groups. CONCLUSIONS: The results supply no evidence for a distinction in information processing abilities of selective attention and working memory as reflected by alpha and theta ERD/ERS between children diagnosed with either ADHD, PDD-NOS or healthy controls. SIGNIFICANCE: Alpha and theta ERD/ERS are sensitive to manipulations of task load, relevance and target/nontarget, but supply no additional information on possible group differences in comparison to the more frequently used method of event-related potentials.

Differential effects of 5-HTTLPR and DRD2/ANKK1 polymorphisms on electrocortical measures of error and feedback processing in children.

OBJECTIVE: Applying a probabilistic learning task we examined the influence of functional polymorphisms of the serotonin transporter gene (5-HTTLPR) and the D2 dopamine receptor gene (DRD2/ANKK1) on error and feedback processing by measuring electrocortical event-related potentials (ERPs) in 10- to 12-year-old children. METHODS: Three pairwise group comparisons were conducted on four distinguishable ERP components, two of which were response-related, the other two feedback-related. RESULTS: Our ERP data revealed that children carrying the short (S) variant of the 5-HTTLPR gene process their errors more intensively while exhibiting less habituation to negative feedback with task progression compared to children who are homozygous for the 5-HTTLPR long (L) variant. Children possessing the Taq1 A variant of the DRD2 gene showed greater sensitivity to negative feedback and, as opposed to Taq1 A non-carriers, a diminishing sensitivity to positive feedback with task progression. Regarding error processing, children possessing both the S variant of the 5-HTTLPR and the Taq1 A allele of the DRD2 gene showed a picture quite similar to that of the 5-HTTLPR S carriers and regarding feedback processing quite similar to that of the DRD2 Taq1 A carriers. CONCLUSIONS: Our findings support the hypotheses that the 5-HTTLPR S allele may predispose to (performance) anxiety, while DRD2 Taq1 A allele may predispose to the reward deficiency syndrome. SIGNIFICANCE: The results may further enhance our understanding of known associations between these polymorphisms and psychopathology.

ERP correlates of selective attention and working memory capacities in children with ADHD and/or PDD-NOS.

OBJECTIVE: We examined whether children (8-11 years) diagnosed with Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) or Attention-Deficit/Hyperactivity Disorder (ADHD) showing primarily hyperactive behavior, differed in selective attention and working memory (WM) abilities. METHODS: Healthy controls and children with ADHD, PDD-NOS or symptoms of both disorders (PDD/HD) (n=15 in each group) carried out a visual selective memory search task while their EEG was recorded from which event-related potentials were derived. RESULTS: Compared to the control group, all patient groups made more omissions while hyperactive children also exhibited more false alarms. Regarding the process of WM-controlled search, significant group differences in ERP data were found between the control group and each of the clinical groups. CONCLUSIONS: The results point to less efficient WM-functioning in all patient groups. Whereas the clinical groups differed from each other at the behavioral level as measured by questionnaires, no distinction between the clinical groups could be made with respect to performance or ERP measures of WM capacity and selective attention. SIGNIFICANCE: The results suggest that a possible differentiation in selectivity and working memory capacities between PDD-NOS and ADHD is hard to find. This may agree with clinical practice, where differential diagnosis is a subject of discussion.

Error and feedback processing in children with ADHD and children with Autistic Spectrum Disorder: an EEG event-related potential study.

OBJECTIVE: Performance monitoring was investigated in typically developing (TD) children, children with Autistic Spectrum Disorder (ASD), and Methylphenidate (Mph)-treated and medication-free children with Attention Deficit Hyperactivity Disorder (ADHD). METHODS: Subjects performed a feedback-based learning task. Event-related Potentials (ERPs) time locked to responses and feedback were derived from the EEG. RESULTS: Compared to the TD and ASD groups, the medication-free ADHD group showed a decreased response-locked Error Related Negativity (ERN) and error Positivity (Pe), particularly as learning progressed throughout the task. Compared to the medication-free ADHD group, the Methylphenidate-treated group showed a normalised Pe. All clinical groups showed or tended to show a decreased feedback-locked late positive potential to negative feedback. CONCLUSIONS: The ERPs suggest that medication-free children with ADHD, but not with ASD, have a diminished capacity to monitor their error responses when they are learning by performance feedback. This capacity partially 'normalises' in Mph-treated children with ADHD. Both children with ADHD and children with ASD are suggested being compromised in affective feedback processing. SIGNIFICANCE: This study shows that measuring ERPs of error and feedback processing is a useful method for (1) dissociating ADHD from ASD and (2) elucidating medication effects in ADHD on component processes of performance monitoring.

Physiological correlates of learning by performance feedback in children: a study of EEG event-related potentials and evoked heart rate.

In this study we measured event-related potentials (ERPs) and evoked heart rate (EHR) to investigate performance monitoring in 10-12-year-old children. The children received feedback on their performance while conducting a probabilistic learning task. Error-related ERP components time-locked to the response increased in amplitude when the children had learned the task, whereas the feedback-locked components decreased. Concerning EHR, there was a general reduction in feedback-related heart rate deceleration when the children had learned. Moreover, a prolonged heart rate deceleration was observed at negative feedback onset in comparison to positive feedback, which shifted in timing when the task progressed. Together, the ERP and EHR-measures suggest a shift from external to internal monitoring when the children are learning by performance feedback. The data suggest that error- and feedback-related EHR deceleration is a reflection of the same error monitoring system that is responsible for the emergence of the error-related negativity (ERN).

The psychobiology of burnout: are there two different syndromes?

BACKGROUND: Plasma prolactin levels are sensitive to dopamine and serotonin function, and fatigue. Low cortisol, dopamine and/or serotonin may be involved in burnout and detachment. METHODS: In this double-blind within-subject study, we treated 9 female burnout subjects and 9 controls with 35 mg cortisol and placebo orally. We measured state affect and plasma prolactin, oxytocin, cortisol and adrenocorticotropic hormone levels, and administered an attachment questionnaire. RESULTS: The burnout subjects displayed an extreme distribution of basal prolactin levels, displaying higher or lower levels compared to the controls. The low prolactin burnouts had profoundly low attachment scores and tended to have low oxytocin levels. The high prolactin burnout subjects tended to show cortisol-induced decreased prolactin and fatigue, and increased vigor. CONCLUSION: Results are consistent with the hypothesis that burnout subjects are either characterized by low serotonergic function or by low dopaminergic function, and that the latter group benefits from cortisol replacement. These preliminary results suggest that differentiating between two syndromes may resolve inconsistencies in research on burnout, and be necessary for selecting the right treatment strategy.

Anxiety, cortisol, and attachment predict plasma oxytocin.

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.

Acute cortisol administration reduces subjective fatigue in healthy women.

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.

State-dependent regulation of cortical activity by cortisol: an EEG study.

In the present study we investigated the effects of cortisol administration on EEG activity in eight healthy volunteers. We administered 35 mg of cortisol in a within-subjects double-blind placebo-controlled design. Cortisol administration caused a global decrease in cortical activity except for an increase frontally at the left, resulting in a significant change in frontal asymmetry. This pattern of results is almost the exact mirror image of one of our previous studies. Comparing subjective activation measures from the present and previous study showed that activation was substantially higher in the present study that was performed in formal testing conditions involving venipuncture, compared to the previous EEG study that was performed in non-formal testing conditions. However, the direction of the present cortisolinduced change in frontal activity asymmetry is consistent with the cortisolinduced change in asymmetric rotation behavior that we recently reported in similar testing conditions. We also found indications that, in contrast to the effects on the EEG measures, effects of cortisol administration on subjective anxiety and plasma oxytocin levels may be sex-dependent. These results are preliminary because of the post-hoc nature and the small number of subjects in the present study. However, they are in line with recent findings by others, suggesting that the effects of cortisol on cortical activity and subjective activation are state dependent and are influenced by testing conditions.

The effects of memory load and stimulus relevance on the EEG during a visual selective memory search task: an ERP and ERD/ERS study.

OBJECTIVE: Psychophysiological correlates of selective attention and working memory were investigated in a group of 18 healthy children using a visually presented selective memory search task. METHODS: Subjects had to memorize one (load1) or 3 (load3) letters (memory set) and search for these among a recognition set consisting of 4 letters only if the letters appeared in the correct (relevant) color. Event-related potentials (ERPs) as well as alpha and theta event-related synchronization and desynchronization (ERD/ERS) were derived from the EEG that was recorded during the task. RESULTS: In the ERP to the memory set, a prolonged load-related positivity was found. In response to the recognition set, effects of relevance were manifested in an early frontal positivity and a later frontal negativity. Effects of load were found in a search-related negativity within the attended category and a suppression of the P3-amplitude. Theta ERS was most pronounced for the most difficult task condition during the recognition set, whereas alpha ERD showed a load-effect only during memorization. CONCLUSIONS: The manipulation of stimulus relevance and memory load affected both ERP components and ERD/ERS. SIGNIFICANCE: The present paradigm may supply a useful method for studying processes of selective attention and working memory and can be used to examine group differences between healthy controls and children showing psychopathology.

Modulation of rotational behavior in healthy volunteers by cortisol administration.

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.

Acute cortisol administration modulates EEG alpha asymmetry in volunteers: relevance to depression.

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.

Dyslexics show a deviant lateralization of attentional control: a brain potential study.

The present study compared performance and event-related brain potentials between dyslexic subjects and control subjects while they performed a spatial selective attention-shifting task. The subjects received a prestimulus cue on each trial, which indicated whether the subjects should attend to a position to the left of fixation or to the position at the opposite right of fixation. Thereafter a stimulus was presented either at the cued position or at the other position. In this paper we report on the brain activity in the cue-stimulus interval, which is supposed to reflect processes involved in controlling spatial attention shifting. The dyslexics performed much poorer on this task than the control subjects. The ERP-effects of cue direction closely resembled earlier reports, and consisted of an early (onset at about 200 ms) posterior contralateral negativity, a later (onset at about 350 ms) posterior contralateral positivity, and a later (onset at about 350 ms) frontal positivity. Dyslexics and controls differed with respect to the frontal attention effect. Whereas the controls showed this effect almost exclusively over the right hemisphere, the dyslexics showed both left and right hemispheric effects. We propose that this might support the idea that in dyslexia the development of interhemispheric asymmetry is disregulated.