Don't you want me, baby? Cardiac and electrocortical concomitants of romantic interest and rejection.

Online dating has become a very popular way to find a romantic partner. In the present study, we examined whether romantic interest and rejection in such a setting would evoke differential electrocortical and cardiac responses. For this purpose a database was created, similar to a dating website, where the participants' personal information and photos were placed. Heterosexual, single participants (N = 61) evaluated the profiles of opposite-sex potential romantic partners and decided whether they would like to date this person or not. Subsequently, participants passively viewed (34 analyzable volunteers participated in the EEG session; 10 male; mean age = 20) the pictures of the potential partners together with their own judgment about the "dateability" of the potential partner, and the potential partner's judgment of the "dateability" of the participant. After viewing the pictures participants received the email addresses to contact their matches. Electrocortical and cardiac responses to these "match" or "non-match" judgments were measured. A significantly larger P3 response was found when participants received a positive evaluation as compared to negative evaluations. This is in line with an explanation in terms of reward. A significantly larger cardiac deceleration was found when participants received a negative evaluation as compared to positive evaluations, which is in line with an explanation in terms of social pain. Findings are discussed in terms of activation of different parts of the anterior cingulate cortex.

Why don't you like me? Midfrontal theta power in response to unexpected peer rejection feedback.

Social connectedness theory posits that the brain processes social rejection as a threat to survival. Recent electrophysiological evidence suggests that midfrontal theta (4-8Hz) oscillations in the EEG provide a window on the processing of social rejection. Here we examined midfrontal theta dynamics (power and inter-trial phase synchrony) during the processing of social evaluative feedback. We employed the Social Judgment paradigm in which 56 undergraduate women (mean age=19.67 years) were asked to communicate their expectancies about being liked vs. disliked by unknown peers. Expectancies were followed by feedback indicating social acceptance vs. rejection. Results revealed a significant increase in EEG theta power to unexpected social rejection feedback. This EEG theta response could be source-localized to brain regions typically reported during activation of the saliency network (i.e., dorsal anterior cingulate cortex, insula, inferior frontal gyrus, frontal pole, and the supplementary motor area). Theta phase dynamics mimicked the behavior of the time-domain averaged feedback-related negativity (FRN) by showing stronger phase synchrony for feedback that was unexpected vs. expected. Theta phase, however, differed from the FRN by also displaying stronger phase synchrony in response to rejection vs. acceptance feedback. Together, this study highlights distinct roles for midfrontal theta power and phase synchrony in response to social evaluative feedback. Our findings contribute to the literature by showing that midfrontal theta oscillatory power is sensitive to social rejection but only when peer rejection is unexpected, and this theta response is governed by a widely distributed neural network implicated in saliency detection and conflict monitoring.

Thumbs up or thumbs down? Effects of neuroticism and depressive symptoms on psychophysiological responses to social evaluation in healthy students.

The effects of neuroticism and depressive symptoms on psychophysiological responses in a social judgment task were examined in a sample of 101 healthy young adults. Participants performed a social judgment task in which they had to predict whether or not a virtual peer presented on a computer screen liked them. After the prediction, the actual judgment was shown, and behavioral, electrocortical, and cardiac responses to this judgment were measured. The feedback-related negativity (FRN) was largest after unexpected feedback. The largest P3 was found after the expected "like" judgments, and cardiac deceleration was largest following unexpected "do not like" judgments. Both the P3 and cardiac deceleration were affected by gender-that is, only males showed differential P3 responses to social judgments, and males showed stronger cardiac decelerations. Time-frequency analyses were performed to explore theta and delta oscillations. Theta oscillations were largest following unexpected outcomes and correlated with FRN amplitudes. Delta oscillations were largest following expected "like" judgments and correlated with P3 amplitudes. Self-reported trait neuroticism was significantly related to social evaluative predictions and cardiac reactivity to social feedback, but not to the electrocortical responses. That is, higher neuroticism scores were associated with a more negative prediction bias and with smaller cardiac responses to judgments for which a positive outcome was predicted. Depressive symptoms did not affect the behavioral and psychophysiological responses in this study. The results confirmed the differential sensitivities of various outcome measures to different psychological processes, but the found individual differences could only partly be ascribed to the collected subjective measures.

Grapheme-color synesthesia interferes with color perception in a standard Stroop task.

This study examined the proposed automatic and involuntary nature of synesthetic experiences in grapheme-color synesthetes by comparing behavioral and blood-oxygen level dependent (BOLD) responses in a synesthetic and a standard version of the Stroop task. Clear interference effects in terms of slower reaction times and stronger BOLD responses in the rostral cingulate zone (RCZ) were found in synesthetes performing the synesthetic version of the Stroop task. Surprisingly, less interference was found in synesthetes compared with controls performing the standard Stroop task. This smaller interference effect, expressed as the difference in reaction time between incongruent and neutral stimuli, was explained in terms of experienced interference during the neutral condition of the Stroop task in synesthetes. This was confirmed by stronger BOLD responses in the RCZ for synesthetes specifically in the neutral condition. To the best of our knowledge, this is the first study to show different performance of synesthetes in a standard Stroop task and the presented data can be seen as strong evidence for the automatic and involuntary nature of synesthetic experiences.

Systematic review of the influence of antipsychotics on the blood oxygenation level-dependent signal of functional magnetic resonance imaging.

Functional Magnetic Resonance Imaging (FMRI) is a non-invasive technique for brain mapping and mostly performed using changes of the blood-oxygen-level-dependent (BOLD)-signal. It has been widely used to investigate patients with schizophrenia. Most of the studies examine patients treated with antipsychotic drugs, although little is known about the effects of these drugs on the BOLDsignal. Here we examined studies of patients with schizophrenia treated with different antipsychotics to address the question whether and to what extent antipsychotic drugs in themselves produce BOLD-signal changes. We performed a PubMed-search for the period from 1999 until January 2012 with the search items "schizophrenia" and "Magnetic Resonance Imaging" and "Antipsychotic Agents; or "Magnetic Resonance Imaging" and "Antipsychotic Agents"; or "schizophrenia" and "Antipsychotic Agents" and "FMRI". We extracted articles that examined at least two patient groups with different treatments, or patients examined on different medications at different times and that provided information about drug effects. No common effect of antipsychotics on BOLD-signal was found. However, based on the results for different antipsychotics (haloperidol, olanzapine, quetiapine and risperidone) we found evidence that the affinity to the dopamine (DA) D(2)-receptor may influence BOLD-signal.

Drug-free patients with major depression show an increased electrophysiological response to valid and invalid feedback.

BACKGROUND: Depressed patients are biased in their response to negative information. They have been found to show a maladaptive behavioral and aberrant electrophysiological response to negative feedback. The aim of this study was to investigate the behavioral and electrophysiological response to feedback validity in drug-free depressed patients. METHOD: Fifteen drug-free in-patients with unipolar major depression disorder (MDD) and 30 demographically matched controls performed a time-estimation task in which they received valid and invalid (i.e. related and unrelated to performance) positive and negative feedback. The number of behavioral adjustments to the feedback and the feedback-related negativity (FRN) were measured. RESULTS: Patients made fewer correct adjustments after valid negative feedback than controls, and their FRNs were larger. Neither patients nor controls adjusted their time estimates following invalid negative feedback. CONCLUSIONS: The FRN results suggest that depressed drug-free in-patients have an atypical rostral anterior cingulate response to feedback that is independent of feedback validity. Their behavioral response to invalid negative feedback, however, is not impaired. This study confirms the notion that the behavioral responses of depressed individuals to negative feedback are context dependent.

The effects of acute tryptophan depletion on brain activation during cognition and emotional processing in healthy volunteers.

Acute tryptophan depletion (ATD), a method to temporarily lower central serotonin levels, has been used to study the functioning of the serotonergic system. Relatively recent studies that examined the effects of ATD on brain activation associated with cognitive and emotional processing in healthy volunteers are reviewed. An overview of the findings in healthy volunteers is important for the interpretation of the effect of ATD on brain activation in patients with an affective disorder, such as major depression. These studies show that during response control and negative feedback processing ATD modulates the BOLD response in the inferior/orbitofrontal cortex, the anterior cingulate cortex and the dorsomedial prefrontal cortex. During emotional processing, it is consistently found that ATD modulates the BOLD response in the amygdala. These brain regions also show abnormal activation in depressed patients. However, at the moment it remains unclear if the changes induced by ATD are related to decreased basal serotonin (5-HT) release or the result of other biochemical changes that are mediated by ATD. Future studies should implement methodological improvements, explore the possibilities of new promising imaging techniques and expand investigations into the effects of ATD on basal 5-HT release and other biochemical mechanisms that might be modulated by ATD.

Acute tryptophan depletion selectively attenuates cardiac slowing in an Eriksen flanker task.

In the present study, the effects of transiently lowering central serotonin levels by means of acute tryptophan depletion on measures of cognitive flexibility were examined. Flexible behaviour was measured in an Eriksen flanker task, and cardiac and electro-cortical responses to errors and congruent and incongruent stimuli were measured. The depletion was successful in lowering tryptophan levels and, as expected, it did not affect subjective mood. Depletion did not affect performance and electro-cortical measures and selectively affected cardiac measures. Depletion attenuated cardiac slowing to incongruent flanker stimuli but did not affect cardiac responses to congruent stimuli and errors. The selective effect on cardiac responses as compared to performance and electro-cortical measures was in accordance with earlier findings, as well as the attenuation of cardiac slowing. The selective effect on the cardiac response to incongruent stimuli was unexpected. Detailed analyses showed a close connection to the earlier reported attenuation of the cardiac response to negative feedback, and the effect is explained in terms of reduced anticipation of the feedback stimulus due to enhanced punishment prediction.

Serotonin and cognitive flexibility: neuroimaging studies into the effect of acute tryptophan depletion in healthy volunteers.

Cognitive flexibility is the ability to adjust behavior to changes in the environment or task conditions. Previous research suggested that serotonin (5-HT) is involved in cognitive flexibility. Disturbed 5-HT functioning in animals, psychiatric patients and healthy volunteers leads to more rigid behavior. A well recognized method to manipulate levels of brain 5-HT is acute tryptophan depletion (ATD). This method induces a transient and reversible lowering of plasma tryptophan that has been shown to result in decreased brain 5-HT. Only recently has ATD research been combined with functional Magnetic Resonance Imaging (fMRI). In this review, we discuss recent investigations into the effect of ATD on the Blood Oxygen Level Dependent (BOLD) response during tasks that require cognitive flexibility, in healthy volunteers. Functional MRI studies have shown that ATD changes brain activation during tasks that require cognitive flexibility. It is hypothesized that ATD changes the processing of negative feedback, rather than impairing response inhibition, impairing the response to an error or the loss of cognitive control during response interference. Although the results of these studies are intriguing, they are sometimes contradictory. This could be the result of the different paradigms that have been used. Importantly, these studies strongly suggest that future multidisciplinary research should evaluate the mechanisms underlying individual differences and control for variables that have been shown to interact with the effect of ATD on cognitive flexibility and the related brain activation.

Acute tryptophan depletion improves performance and modulates the BOLD response during a Stroop task in healthy females.

To gain more insight into the effect of low brain serotonin (5-HT) on brain activation related to conflict, the present study examined the effect of acute tryptophan depletion (ATD) on performance and the blood oxygen level dependent (BOLD) response during a combined cognitive and emotional Stroop task. Fifteen healthy female volunteers were tested during a placebo and tryptophan depletion session in an event-related fMRI design. ATD improved performance during Stroop interference. Two effects of ATD on the BOLD response were found. Firstly, ATD increased the BOLD response in the anterior cingulate cortex (ACC) (BA 32) when incongruent color words were compared with congruent color words in the first Stroop block the participants performed. Secondly, ATD increased the BOLD response in the left precuneus (BA 31) and cuneus (BA 18) during congruent color words. ATD did not affect the BOLD response accompanying emotional stimuli. However, we showed that ATD increased the interference of negative words on color naming. This finding was explained in terms of an emotional processing bias in favor of negative words, which leads to stronger interference of these words. In line with previous studies, the present study showed that a temporary reduction of 5-HT improved Stroop performance and changed the underlying brain activation pattern in healthy female participants. Moreover, we replicated our previous finding that ATD modulated the BOLD response in the dorsomedial prefrontal cortex during tasks that require cognitive control.

Reduced cerebral blood flow response and compensation among patients with untreated hypertension.

OBJECTIVE: To determine whether memory performance in hypertensive subjects induces diminished parietal and prefrontal blood flow activation relative to normotensive subjects but compensatory amygdala/hippocampal activation. METHODS: Thirty-seven untreated hypertensive subjects and 59 normotensive control subjects performed in two memory and one sensorimotor task while global and regional cerebral blood flow (rCBF) was assessed with [15O]water and PET. Neuropsychological, carotid artery ultrasound, and MRI assessments were obtained. RESULTS: When they were engaged in memory tasks, increases of CBF in hypertensive subjects were less than in normotensive subjects in the posterior parietal area, as expected; blunted responses were also shown within the middle posterior arterial watershed and thalamus. Relative to all other participants, hypertensive subjects that performed relatively well on verbal memory showed an enhanced rCBF response in the right amygdala/hippocampus. Furthermore, hypertensive, but not normotensive, subjects showed task-induced rCBF in the amygdala/hippocampal area that was significantly correlated with task-induced prefrontal rCBF. No confounding influences were identified from carotid artery or MRI measures. CONCLUSIONS: Memory performance in hypertensive individuals is related to a blunted regional cerebral blood flow (rCBF) response, particularly in parietal cortex. Potentially compensatory rCBF responses appear to occur in midbrain and correlate with prefrontal rCBF.

Effects of a novel method of acute tryptophan depletion on plasma tryptophan and cognitive performance in healthy volunteers.

RATIONALE: Disorders associated with low levels of serotonin (5-HT) are characterized by mood and cognitive disturbances. Acute tryptophan depletion (ATD) is an established method for lowering 5-HT levels and an important tool to study the effects of reduced 5-HT on mood and cognition in human subjects. The traditional ATD method, i.e., administration of separate amino acids (AAs), has several disadvantages. The AA mixture is costly, unpalatable and associated with gastrointestinal discomfort. OBJECTIVES: The University of Maastricht developed a new and inexpensive method for ATD: a natural collagen protein (CP) mixture with low tryptophan (TRP) content. The reductions in plasma TRP after taking this CP mixture were compared with the reductions achieved taking the traditional AA mixture, and effects on memory and reversal learning were studied. METHODS: Fifteen healthy young volunteers participated in a double-blind, counterbalanced within-subject study. Reversal learning, verbal memory and pattern recognition were assessed at baseline and 3-4 h after taking the CP mixture. RESULTS: The new ATD method significantly reduced plasma TRP by 74% and the ratio between TRP and the other large AAs (TRP/LNAA) by 82%. The placebo mixture did not change these measures. Delayed recognition reaction time on the verbal learning task was increased following ATD. No other cognitive effects were found. CONCLUSIONS: The CP mixture was shown to be an efficient tool for lowering plasma TRP in humans. The validity of this method with regard to behavioral changes remains to be established in healthy, vulnerable and clinical populations.

Selective attention and response inhibition alter phase-dependent cardiac slowing.

This study examined the effects of visual selective attention and stimulus discriminability on phasic heart rate changes. Grating stimuli consisting of four vertical bars were presented left or right from fixation. Participants attended to one side of the screen and responded with a button press to attended target stimuli that were defined by shorter middle bars. Stimulus discriminability was manipulated by increasing the length of the middle bars of targets. To examine the time course of response inhibition, participants had to respond to auditory probe stimuli that were presented occasionally and unpredictably at varying intervals following the visual stimulus. Responses to targets and probes following attended nontargets were slower in the difficult condition. Heart rate slowed in anticipation of a target and accelerated back to baseline afterwards. Phase-dependent cardiac slowing was larger for attended nontargets compared to unattended nontargets and was more pronounced in the difficult condition. These findings were interpreted vis-à-vis inhibition accounts of phase-dependent cardiac slowing.

Selective inhibition is indexed by heart rate slowing.

This study examined the hypothesis that global and selective inhibition are mediated by distinct mechanisms: respectively, a peripheral mechanism, indexed by heart rate slowing, and a central mechanism, indexed by cortical but not autonomic measures. Three varieties of a Go-NoGo task were presented in which the Go signal required an index finger response rapidly followed by a middle finger response. The NoGo signal required the inhibition of (a) both responses (global inhibition), (b) the middle finger response (simple selective inhibition), or (c) the index finger response of one hand and the middle finger response of the other hand (complex selective inhibition). As anticipated, global inhibition was indexed by heart rate slowing. Most importantly, heart rate slowing was also elicited by selective inhibition and was more pronounced for complex than simple selective inhibition. These findings suggest that global and selective inhibition are mediated by one rather than two mechanisms and that heart rate is sensitive to the demands placed on this inhibition mechanism.

Event-related brain potential and heart rate manifestations of visual selective attention.

Twenty-eight volunteers were instructed to attend stimuli presented at one side of the computer screen and to ignore stimuli presented at the other side. Both attended and unattended stimulus series consisted of targets (25%) and nontargets (75%) defined on the basis of stimulus shape. Attended targets required a binary choice based on stimulus color. Selective attention led to the expected increase in both midlatency (N2b) and late (P3) brain potential components. Furthermore, selective attention led to increased anticipatory cardiac slowing preceding the target stimulus and to increased primary bradycardia. Correlational analyses revealed a positive relation between the effects of selective attention on N2b amplitude and primary bradycardia suggestive of cortical involvement in the chronotropic control of heart rate.

Covariation of phasic cortical and cardiovascular responses in a detection task.

The relationship between cardiovascular and cortical responses was examined in an experiment in which subjects performed a detection task and a simple reference task. The detection task was developed according to Skinner et al., (1987). Cortical activity was examined with event related brain potentials (ERPs). ERPs revealed more cortical activation during detection task blocks. Both tonic and phasic measures of cardiovascular activity were derived. Tonic measures were heart rate (HR), systolic blood pressure (SBP). T-wave amplitude (TWA), respiration linked HR-variability and a measure for baroreflex sensitivity. These measures revealed no important differences between the reference task and detection task blocks. Phasic cardiovascular measures were evoked HR, SBP and TWA. Evoked HR showed a larger deceleration and evoked SBP showed a smaller decrease on detection task blocks. Evoked TWA did not differentiate between both types of task. It is concluded that an adjusted version of the fronto-cortical control hypothesis of Skinner could best account for the data.

Requirement of H-2-subregion differences for graft-versus-host autoimmunity in mice: superiority of the differences at class-II H-2 antigens (I-A/I-E).

The effect of various H-2-subregion differences on graft-versus-host (GVH) autoimmunity in mice was investigated by testing a variety of GVH combinations in which non-irradiated adult F1 hybrid mice were injected with parental strain lymphoid cells. As with previous results, the superiority of Class-II H-2 antigen (I-A/I-E) differences to other kinds of H-2 incompatibilities, such as Class-I H-2 antigen (H-2K/H-2D) differences, was largely confirmed. Anti-nuclear antibodies were produced significantly across Class-I as well as Class-II H-2 differences. However, the productions of anti-erythrocyte and anti-thymocyte autoantibodies were mainly confined to GVH reactions induced across Class-II H-2 antigens. Elevated proteinuria was elicited only in the GVH combinations that included the differences at Class-II H-2 antigens. GVH autoimmunity, however, did not always result in the significant occurrence of elevated proteinuria. The level of in-vitro IgG production by GVH spleen cells correlated closely with the degree of autoimmunity.

Further evidence against random polyclonal antibody formation in mice with lupus-like graft-vs-host disease.

The pathologic symptoms in F1 mice with chronic graft-vs-host disease (GVHD) (GVH F1) strongly resemble those of systemic lupus erythematosus (SLE). Mice with SLE-like GVHD do not produce antibodies to a number of non-self and self antigens. This finding is inconsistent with the widely accepted view that the (auto)-antibody formation in SLE is polyclonal in the sense that B cells are triggered at random, i.e., irrespective of their specificity. In the present study, therefore, we performed a systematic study of the kinetics of total IgM- and IgG-secreting splenic B cells and tested their specificities. The total IgM-secreting B cell population was increased only in the first week after the initiation of SLE-like GVHD; it seemed to reflect a random, but self-limited, polyclonal B cell stimulation. In contrast, the total number of IgG-secreting cells in the GVH F1 mice was increased to a much higher extent than that of the IgM-secreting cells and remained increased. At no time during GVHD was there an increase in the number of plaque-forming cells (PFC) spontaneously secreting IgG antibodies to non-self antigens. The GVH reaction (GVHR) did, however, lead to the appearance of PFC that secreted IgG antibodies to DNA. Similarly, the GVH F1 mice showed high serum titers of antibodies to self antigens characteristic of SLE and to endogenous viruses, but during the entire observation period they failed to develop serum antibodies to non-self antigens and insulin. Hence, the enhanced production of Ig, especially that of IgG, that occurs in SLE-like GVHD is not a random process, because it requires the presence of antigen, or signal 1. The data support our hypothesis that only certain kinds of self antigen, such as DNA and cell membrane epitopes, can cross-link the Ig receptors on the corresponding B cells and thus provide an adequate signal 1. Given the increase in help, or signal 2, in chronic GVHD, only the B cell clones that simultaneously receive an adequate signal 1 seem to be driven into clonal proliferation and IgG secretion.

Injection of mouse thyroglobulin and/or adult thymectomy do not break tolerance to thyroglobulin during the lupus like graft versus host disease in mice.

In a previous paper (Gleichmann, van Elven & van der Veen, 1982), it had been reported that, in contrast to lupus like autoantibodies such as anti-DNA, autoantibodies to mouse thyroglobulin (MTg) were not detectable in serum of F1 mice suffering from a lupus like graft versus host disease (GVHD) (GVH F1). In the present paper, possible explanations for this restricted autoantibody formation during the potent allogeneic stimulation were investigated. The main question was whether the natural level of circulating MTg was too low to induce the formation of anti-MTg antibodies in GVH F1 mice. Existence, in the F1 mice studied, of B cells capable of producing anti-MTg antibodies was demonstrated by injection of lipopolysaccharide (LPS) and exogeneous MTg. However, MTg injected into various F1 mice at the onset of the GVH reaction (GVHR) failed to overcome the lack of antibody formation to MTg even though the GVHR led to a severe lupus like disease. Furthermore, adult thymectomy (ATx) of either the recipients, the donors, or both also did not break tolerance to MTg during the GVHR, irrespective of administration of exogeneous MTg. Thus, neither intravenous injection of MTg nor ATx, designed to remove T suppressor (TS) cells, is adequate to enable an autoantibody response to MTg during lupus like GVHD. Hence, the non-specific T cell help that causes lupus like GVHD seems to be intrinsically insufficient to trigger the Tg reactive B cells. We suggest that globular proteins, such as Tg, require specific T cell help. In the presence of only non-specific T help, self-antigens such as DNA seem to be more apt than globular proteins to provide an effective signal 1 to the corresponding autoreactive B cells.