Matthias Gamer

Different amygdala subregions mediate valence-related and attentional effects of oxytocin in humans.

The neuropeptide oxytocin enhances the processing of positive social stimuli and improves the capacity to effectively attend the eye region of conspecifics. To investigate the neural basis of these effects, we combined intranasal oxytocin administration with high-resolution functional magnetic resonance imaging in a unique emotion classification task. Emotional faces were briefly presented while controlling for the initial fixation, and measuring subsequent eye movements. Oxytocin had differential effects on the activity of specific amygdala subregions. On the one hand, it attenuated activation in lateral and dorsal regions of the anterior amygdala for fearful faces but enhanced activity for happy expressions, thus indicating a shift of the processing focus toward positive social stimuli. On the other hand, oxytocin increased the likelihood of reflexive gaze shifts toward the eye region irrespective of the depicted emotional expression. This gazing pattern was related to an increase of activity in the posterior amygdala and an enhanced functional coupling of this region to the superior colliculi. Thus, different behavioral effects of oxytocin seem to be closely related its specific modulatory influence on subregions within the human amygdala.

Amygdala Activation Predicts Gaze toward Fearful Eyes

The human amygdala can be robustly activated by presenting fearful faces, and it has been speculated that this activation has functional relevance for redirecting the gaze toward the eye region. To clarify this relationship between amygdala activation and gaze-orienting behavior, functional magnetic resonance imaging data and eye movements were simultaneously acquired in the current study during the evaluation of facial expressions. Fearful, angry, happy, and neutral faces were briefly presented to healthy volunteers in an event-related manner. We controlled for the initial fixation by unpredictably shifting the faces downward or upward on each trial, such that the eyes or the mouth were presented at fixation. Across emotional expressions, participants showed a bias to shift their gaze toward the eyes, but the magnitude of this effect followed the distribution of diagnostically relevant regions in the face. Amygdala activity was specifically enhanced for fearful faces with the mouth aligned to fixation, and this differential activation predicted gazing behavior preferentially targeting the eye region. These results reveal a direct role of the amygdala in reflexive gaze initiation toward fearfully widened eyes. They mirror deficits observed in patients with amygdala lesions and open a window for future studies on patients with autism spectrum disorder, in which deficits in emotion recognition, probably related to atypical gaze patterns and abnormal amygdala activation, have been observed.

Covariations Among fMRI, Skin Conductance, and Behavioral Data During Processing of Concealed Information

Imaging techniques have been used to elucidate the neural correlates that underlie deception. The scientifically best understood paradigm for the detection of deception, however, the guilty knowledge test (GKT), was rarely used in imaging studies. By transferring a GKT‐paradigm to a functional magnetic resonance imaging (fMRI) study, while additionally quantifying reaction times and skin conductance responses (SCRs), this study aimed at identifying the neural correlates of the behavioral and electrodermal response pattern typically found in GKT examinations. Prior to MR scanning, subjects viewed two specific items (probes) and were instructed to hide their knowledge of these. Two other specific items were designated as targets and required a different behavioral response during the experiment and eight items served as irrelevant stimuli. Reaction times and SCR amplitudes differed significantly between all three item types. The neuroimaging data revealed that right inferior frontal and mid‐cingulate regions were more active for probe and target trials compared to irrelevants. Moreover, the differential activation in the right inferior frontal region was modulated by stimulus conflicts. These results were interpreted as an increased top‐down influence on the stimulus‐response‐mapping for concealed and task‐relevant items. Additionally, the influence of working memory and retrieval processes on this activation pattern is discussed. Using parametric analyses, reaction times and SCR amplitudes were found to be linearly related to activity in the cerebellum, the right inferior frontal cortex, and the supplementary motor area. This result provides a first link between behavioral measures, sympathetic arousal, and neural activation patterns during a GKT examination. Hum Brain Mapp 2007.

Oxytocin and Reduction of Social Threat Hypersensitivity in Women With Borderline Personality Disorder

OBJECTIVE Patients with borderline personality disorder are characterized by emotional hyperarousal with increased stress levels, anger proneness, and hostile, impulsive behaviors. They tend to ascribe anger to ambiguous facial expressions and exhibit enhanced and prolonged reactions in response to threatening social cues, associated with enhanced and prolonged amygdala responses. Because the intranasal administration of the neuropeptide oxytocin has been shown to improve facial recognition and to shift attention away from negative social information, the authors investigated whether borderline patients would benefit from oxytocin administration. METHOD In a randomized placebo-controlled double-blind group design, 40 nonmedicated, adult female patients with a current DSM-IV diagnosis of borderline personality disorder (two patients were excluded based on hormonal analyses) and 41 healthy women, matched on age, education, and IQ, took part in an emotion classification task 45 minutes after intranasal administration of 26 IU of oxytocin or placebo. Dependent variables were latencies and number or initial reflexive eye movements measured by eye tracking, manual response latencies, and blood-oxygen-level-dependent responses of the amygdala to angry and fearful compared with happy facial expressions. RESULTS Borderline patients exhibited more and faster initial fixation changes to the eyes of angry faces combined with increased amygdala activation in response to angry faces compared with the control group. These abnormal behavioral and neural patterns were normalized after oxytocin administration. CONCLUSIONS Borderline patients exhibit a hypersensitivity to social threat in early, reflexive stages of information processing. Oxytocin may decrease social threat hypersensitivity and thus reduce anger and aggressive behavior in borderline personality disorder or other psychiatric disorders with enhanced threat-driven reactive aggression.

Combining physiological measures in the detection of concealed information

Meta-analytic research has confirmed that skin conductance response (SCR) measures have high validity for the detection of concealed information. Furthermore, cumulating research has provided evidence for the validity of two other autonomic measures: Heart rate (HR) and Respiration Line Length (RLL). In the present report, we compared SCR detection efficiency with HR and RLL, and investigated whether HR and RLL provide incremental validity to electrodermal responses. Analyses were based on data from 7 different samples covering 275 guilty and 53 innocent examinees. Results revealed that the area under the ROC curve was significantly higher for SCR than for HR and RLL. A weighted combination of these measures using a logistic regression model yielded slightly larger validity coefficients than the best single measure. These results proved to be stable across different protocols and various samples.

Oxytocin specifically enhances valence-dependent parasympathetic responses.

The evolutionarily highly conserved neuropeptide oxytocin seems to be involved in the regulation of complex forms of social behavior. It enhances the processing of positive social stimuli, reduces behavioral and neuroendocrine stress responses and modulates amygdala activity in humans. Moreover, it has been proposed that oxytocin dampens sympathetic nervous system activity. This hypothesis was tested in a double-blind, placebo-controlled study with 38 men either receiving 24 IU oxytocin intranasally or a placebo spray. While accomplishing an emotion classification task, electrodermal responses were measured as an index of sympathetic activity. Moreover, heart rate changes were recorded that are additionally mediated by the parasympathetic nervous system. Oxytocin enhanced differential heart rate responses to facial expressions as a function of the emotional valence, but had no effect on electrodermal activity or tonic measures of physiological arousal. These results indicate that oxytocin specifically modulates phasic activity of the parasympathetic nervous system which potentially reflects an increased motivational value of facial expressions following oxytocin treatment. Findings suggest that anxiolytic effects of oxytocin are not reflected in short-term sympathetic responses and may even be a consequence of rather than a prerequisite for improved social information processing.

fMRI-activation patterns in the detection of concealed information rely on memory-related effects

Recent research on potential applications of fMRI in the detection of concealed knowledge primarily ascribed the reported differences in hemodynamic response patterns to deception. This interpretation is challenged by the results of the present study. Participants were required to memorize probe and target items (a banknote and a playing card, each). Subsequently, these items were repeatedly presented along with eight irrelevant items in a modified Guilty Knowledge Test design and participants were instructed to simply acknowledge item presentation by pressing one button after each stimulus. Despite the absence of response monitoring demands and thus overt response conflicts, the experiment revealed a differential physiological response pattern as a function of item type. First, probes elicited the largest skin conductance responses. Second, differential hemodynamic responses were observed in bilateral inferior frontal regions, the right supramarginal gyrus and the supplementary motor area as a function of item type. Probes and targets were accompanied by a larger signal increase than irrelevant items in these regions. Moreover, the responses to probes differed substantially from targets. The observed neural response pattern seems to rely on retrieval processes that depend on the depth of processing in the encoding situation.

Separating brain processing of pain fromthat of stimulus intensity.

Regions of the brain network activated by painful stimuli are also activated by nonpainful and even nonsomatosensory stimuli. We therefore analyzed where the qualitative change from nonpainful to painful perception at the pain thresholds is coded. Noxious stimuli of gaseous carbon dioxide (n = 50) were applied to the nasal mucosa of 24 healthy volunteers at various concentrations from 10% below to 10% above the individual pain threshold. Functional magnetic resonance images showed that these trigeminal stimuli activated brain regions regarded as the “pain matrix.” However, most of these activations, including the posterior insula, the primary and secondary somatosensory cortex, the amygdala, and the middle cingulate cortex, were associated with quantitative changes in stimulus intensity and did not exclusively reflect the qualitative change from nonpainful to pain. After subtracting brain activations associated with quantitative changes in the stimuli, the qualitative change, reflecting pain‐exclusive activations, could be localized mainly in the posterior insular cortex. This shows that cerebral processing of noxious stimuli focuses predominately on the quantitative properties of stimulus intensity in both their sensory and affective dimensions, whereas the integration of this information into the perception of pain is restricted to a small part of the pain matrix. Hum Brain Mapp, 2012.

Don’t Look Back in Anger! Responsiveness to Missed Chances in Successful and Nonsuccessful Aging

Emotionally healthy older adults show a reduced responsiveness to regret when performing a sequential decision task. No Regrets As people grow older, the possibility to think about “missed chances” increases. When we are young, thinking about missed opportunities may help to optimize future behavior. However, the older we get the probability of “second chances” decreases and thus the benefit of ruminating upon them disappears. Brassen et al. (p. 612, published online 19 April) studied the behavioral and neural response to missed chances in young adults, the healthy elderly subjects and late-life depressed volunteers. Compared with young and depressed subjects, the healthy elderly subjects showed a reduced sensitivity to missed opportunities. The findings suggest a potential mechanism for preserved emotional health in older age. Life-span theories explain successful aging with an adaptive management of emotional experiences like regret. As opportunities to undo regrettable situations decline with age, a reduced engagement into these situations represents a potentially protective strategy to maintain well-being in older age. Yet, little is known about the underlying neurobiological mechanisms supporting this claim. We used a multimodal psychophysiological approach in combination with a sequential risk-taking task that induces the feeling of regret and investigated young as well as emotionally successfully and unsuccessfully (i.e., late-life depressed) aged participants. Responsiveness to regret was specifically reduced in successful aging paralleled by autonomic and frontostriatal characteristics indicating adaptive shifts in emotion regulation. Our results suggest that disengagement from regret reflects a critical resilience factor for emotional health in older age.

Anterior Cingulate Activation Is Related to a Positivity Bias and Emotional Stability in Successful Aging

BACKGROUND Behavioral studies consistently reported an increased preference for positive experiences in older adults. The socio-emotional selectivity theory explains this positivity effect with a motivated goal shift in emotion regulation, which probably depends on available cognitive resources. The present study investigates the neurobiological mechanism underlying this hypothesis. METHODS Functional magnetic resonance imaging data were acquired in 21 older and 22 young subjects while performing a spatial-cueing paradigm that manipulates attentional load on emotional face distracters. We focused our analyses on the anterior cingulate cortex as a key structure of cognitive control of emotion. RESULTS Elderly subjects showed a specifically increased distractibility by happy faces when more attentional resources were available for face processing. This effect was paralleled by an increased engagement of the rostral anterior cingulate cortex, and this frontal engagement was significantly correlated with emotional stability. CONCLUSIONS The current study highlights how the brain might mediate the tendency to preferentially engage in positive information processing in healthy aging. The finding of a resource-dependency of this positivity effect suggests demanding self-regulating processes that are related to emotional well-being. These findings are of particular relevance regarding implications for the understanding, treatment, and prevention of nonsuccessful aging like highly prevalent late-life depression.