Neural activity during the viewing of emotional pictures in veterans with pathological anger and aggression.

Anger and aggression are common mental health problems after military deployment. Anger and aggression have been associated with abnormalities in subcortical and cortical levels of the brain and their connectivity. Here, we tested brain activation during the processing of emotional stimuli in military veterans with and without anger and aggression problems. Thirty military veterans with anger and aggression problems and 29 veterans without a psychiatric diagnosis (all males) participated in this study. During an fMRI scan 32 negative, 32 positive and 32 neutral pictures from the International Affective Picture System were presented in intermixed order. The Aggression group showed heightened activity in brain areas including the supplementary motor area, the cingulum and the parietal cortex, in response to stimuli, regardless of category. Furthermore, the Aggression group showed stronger connectivity between the dorsal anterior cingulate cortex (dACC) and the amygdala during the viewing of negative stimuli, and weaker connectivity between dACC and medial prefrontal cortex during the viewing of positive stimuli. Veterans with anger and aggression problems showed enhanced brain response to all stimuli during the task, irrespective of valence and they rated the pictures more likely as negative. We take this to indicate enhanced preparation for action and attention to the presentation of stimuli that could prove to be threatening. Further, group differences in functional connectivity involving the dACC reveal abnormal processing of stimuli with negative and positive valence. In sum, the results point towards a bias towards an enhanced sensitivity to perceived or potential threat in aggression.

Translational neuroscience of basolateral amygdala lesions: Studies of Urbach-Wiethe disease.

Urbach-Wiethe disease (UWD) is an extremely rare autosomal recessive disorder characterized by mutations in the extracellular matrix protein 1 gene on chromosome 1. Typical clinical manifestations include voice hoarseness in early infancy and neuropsychiatric, laryngeal, and dermatological pathologies later in life. Neuroimaging studies have revealed a pattern of brain calcification often but not exclusively leading to selective bilateral amygdala damage. A large body of work on amygdala lesions in rodents exists, generally employing a subregion model focused on the basolateral amygdala (BLA) and the central-medial amygdala. However, human work usually considers the amygdala as a unified structure, not only complicating the translation of animal findings to humans but also providing a unique opportunity for further research. To compare data from rodent models with human cases and to complement existing data from Europe and North America, a series of investigations was undertaken on UWD subjects with selective BLA damage in the Namaqualand region, South Africa. This review presents key findings from this work, including fear processing, social-economic behavior, and emotional conflict processing. Our findings are broadly consistent with and support rodent models of selective BLA lesions and show that the BLA is integral to processing sensory stimuli and exhibits inhibitory regulation of responses to unconditioned innate fear stimuli. Furthermore, our findings suggest that the human BLA mediates calculative-instrumental economic behaviors and may compromise working memory via competition for attentional resources between the BLA salience detection system and the dorsolateral prefrontal cortex working memory system.

Hypervigilance for fear after basolateral amygdala damage in humans.

Recent rodent research has shown that the basolateral amygdala (BLA) inhibits unconditioned, or innate, fear. It is, however, unknown whether the BLA acts in similar ways in humans. In a group of five subjects with a rare genetic syndrome, that is, Urbach-Wiethe disease (UWD), we used a combination of structural and functional neuroimaging, and established focal, bilateral BLA damage, while other amygdala sub-regions are functionally intact. We tested the translational hypothesis that these BLA-damaged UWD-subjects are hypervigilant to facial expressions of fear, which are prototypical innate threat cues in humans. Our data indeed repeatedly confirm fear hypervigilance in these UWD subjects. They show hypervigilant responses to unconsciously presented fearful faces in a modified Stroop task. They attend longer to the eyes of dynamically displayed fearful faces in an eye-tracked emotion recognition task, and in that task recognize facial fear significantly better than control subjects. These findings provide the first direct evidence in humans in support of an inhibitory function of the BLA on the brain's threat vigilance system, which has important implications for the understanding of the amygdala's role in the disorders of fear and anxiety.

Sex steroids and brain structure in pubertal boys and girls: a mini-review of neuroimaging studies.

Puberty is an important period during development hallmarked by increases in sex steroid levels. Human neuroimaging studies have consistently reported that in typically developing pubertal children, cortical and subcortical gray matter is decreasing, whereas white matter increases well into adulthood. From animal studies it has become clear that sex steroids are capable of influencing brain organization, both during the prenatal period as well as during other periods characterized by massive sex steroid changes such as puberty. Here we review structural neuroimaging studies and show that the changes in sex steroids availability during puberty and adolescence might trigger a period of structural reorganization of grey and white matter in the developing human brain. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

Cortisol, depression and reduced cortico-cortical cross-talk in Cushing's syndrome.

In the present report assumed relationships between hypercortisolism, depression and cortico-cortical cross-talk in Cushing's syndrome were investigated. Electroencephalographic (EEG) recordings and depression ratings from three patients diagnosed with mild, moderate and severe hypercortisolism were obtained. Reductions in cortico-cortical cross-talk as quantified by EEG coherence together with increases in depression were observed in the moderate and severe as compared to the mild hypercorticolism state. These findings provide preliminary evidence for the hypothesis that loss of cortico-cortical cross-talk might be linked to hypercortisolism and the severity of depressive symptoms.

Attentionally modulated effects of cortisol and mood on memory for emotional faces in healthy young males.

Heightened cortisol levels due to stress or acute administration seem to enhance memory for emotional material, independently of emotional valence. An arousal-driven neurobiological mechanism involving the amygdala has been proposed. The relation between pre-task salivary measures of cortisol (by convention named 'basal levels') and emotionally modulated memory has not been investigated yet. Given the association between higher basal levels of cortisol and indices of low mood, valence-specific effects on emotionally modulated memory could be expected (e.g. mood-congruent or stimulus-specific forms of processing). This study was designed to investigate the relationship between basal levels of salivary cortisol, self-reported mood and spatial memory for neutral, happy and angry facial expressions in healthy young volunteers (N=31). Memory performance was indexed using a modified version of a computerized object-relocation task, using emotional facial expressions as stimuli. Results showed a significant relation between cortisol and depressive mood. More importantly, both the levels of cortisol and depressive mood were inversely related to the memory performance for the happy facial expressions, while a similar relationship between cortisol and memory performance on angry faces neared significance. An explanation in terms of the down-regulation of social behavior by elevated basal cortisol levels is postulated.

Spatial and temporal characteristics of visual motion perception involving V5 visual cortex.

The anatomical substrates of the perception of motion have not yet been established in a detailed way on an individual level. The aim of this study was to develop a systematic procedure for mapping the visual cortex using Transcranial Magnetic Stimulation (TMS). The results showed that such an individual and detailed map of the spatial and temporal characteristics of motion perception can be constructed using TMS.

Parietal electroencephalogram beta asymmetry and selective attention to angry facial expressions in healthy human subjects.

Research on cerebral affective processing in humans has concentrated on the lateralization of the prefrontal cortex. However, the parietal cortex also seems to play a role in motivation and emotion. In the present study the lateralized role of the parietal cortex in motivated attention was investigated, using an electrophysiological correlate of brain activity (electroencephalogram (EEG)) and a modified Dot probe task, which indexes selective, i.e. avoidant or vigilant attention for angry faces in a spatial display. Twenty-two participants underwent an EEG baseline recording from the F3, F4, P3 and P4 electrode positions, which was followed by the modified Dot probe task. Spectral power in 1 Hz frequency bins were derived for each electrode site and transformed to power density values in the 8-12 Hz (alpha) and 13-30 Hz (beta) frequency range. Log-transformed prefrontal and parietal asymmetries and bias scores for selective attention to angry and happy faces were calculated. Results showed a highly significant relationship between the asymmetry in parietal EEG beta activity and the attentional response to the angry face. Relative more right-sided parietal EEG activity in the beta frequency domain was predictive of a more avoidant response to angry facial expression. This finding suggests that asymmetrical parietal beta activity might be linked to the behavioural dimensions of approach and withdrawal.

Effects of slow rTMS at the right dorsolateral prefrontal cortex on EEG asymmetry and mood.

In a sham-controlled design (n = 12), slow repetitive transcranial magnetic stimulation (rTMS) was applied to the right dorsolateral prefrontal cortex for 20 min, and the subsequent effects on mood and the EEG spectrum were investigated, Analysis revealed a significant left hemisphere increase in EEG theta activity at 25-35 and 55-65 min after stimulation. In addition, participants reported significant decrease in anxiety immediately after stimulation, as well as 35 and 65 min after rTMS. These findings indicate that reductions in anxiety after slow rTMS at the right dorsolateral prefrontal cortex are associated with a contralateral increase in theta activity.

A single administration of testosterone induces cardiac accelerative responses to angry faces in healthy young women.

Recently, it was demonstrated how individuals with high levels of testosterone selectively attend toward angry faces. It was argued that this suggests that high levels of testosterone are associated with an aggressive, dominating personality style. In this study, the authors used a double-blind, placebo-controlled design to examine whether exogenous testosterone would induce cardiac acceleration in response to angry faces. Participants (healthy young women) were exposed to neutral, happy, or angry faces. Administration of a single dosage of testosterone (0.5 mg) induced an accelerative cardiac response to angry faces. It is argued that this effect is due to the encouragement of dominance behavior and the inclination toward aggression. Possible mechanisms behind testosterone-driven changes in behavior are discussed with relevance to steroid-responsive networks in the limbic system that drive and control motivational and physiological aspects of social behavior.

Effects of testosterone administration on selective aspects of object-location memory in healthy young women.

Previous work has indicated that object-location memory is sensitive to sex differences as well as variations in the menstrual cycle. The goal of the present study was to further examine the hormonal basis of human spatial memory by assessing the effects of a single dose of exogenous testosterone in healthy young women on three recall conditions: positional reconstruction; object-to-position-assignment; and the combined condition in which subjects both have to reconstruct the precise locations and to link the different objects to the correct places. In the latter condition, delayed recall (3 min delay) improved with testosterone. Although the effects were only small and need further substantiation, they support the idea that testosterone may have an activational effect on selective aspects of cognitive functioning.

Conscious and preconscious selective attention to social threat: different neuroendocrine response patterns.

This study was designed to investigate the relationship between selective attention to social threat and neuroendocrine activity. Selective attention to social threat was measured using a supraliminal (unmasked) and a subliminal (masked) version of a pictorial emotional Stroop task, comparing color-naming latencies of neutral and angry faces. Neuroendocrine activity was assessed as (pre-task to post-task) increases in salivary cortisol and testosterone. Forty subjects were randomly assigned to the unmasked or masked version of the task. Analyses for the unmasked task revealed that post-task cortisol levels were significantly increased in subjects showing selective attention to angry faces. Results for the masked task indicated that post-task cortisol and testosterone levels were significantly increased in subjects showing preconscious selective attention to angry faces. The difference in neuroendocrine activity between tasks is suggested to depend on cortical (i.e. prefrontal) control in the unmasked task. Thus, psychological affective regulatory processes were involved in the unmasked task, whereas the neuroendocrine response patterns in the masked task indicates a biologically prepared mechanism.

Laterality effects in selective attention to threat after repetitive transcranial magnetic stimulation at the prefrontal cortex in female subjects.

Recently, several experiments have indicated that the left and right prefrontal cortex (PFC) are differently involved in emotional processing. The aim of this study was to investigate the role of the left and right PFC in selective attention to angry faces by using a pictorial emotional Stroop task. Slow repetitive transcranial magnetic stimulation (rTMS) was applied to the left and right PFC of 10 female subjects for 15 min on separate days. Results showed a significant effect of stimulation position: right PFC rTMS resulted in selective attention towards angry faces, whereas left PFC rTMS resulted in selective attention away from angry faces. This finding is in accordance with theoretical accounts of the neural implementation of approach and withdrawal systems.

Time course of effects of testosterone administration on sexual arousal in women.

BACKGROUND: The assumption that testosterone is involved in human female sexual functioning is mainly based on results of studies of women with hypogonadotropic hypogonadism. This study sought to determine the effect of testosterone administration on physiological and subjective sexual arousal in sexually functional women. METHODS: In a double-masked, randomly assigned, placebo-controlled crossover design, we examined whether administration of a single dose of testosterone to sexually functional women increases vaginal and subjective sexual arousal when they are exposed to erotic visual stimuli. To search for a time lag in the effect of testosterone therapy, we exposed 8 healthy women to 6 erotic film excerpts depicting intercourse. The first and second excerpts were shown immediately before and 15 minutes after, respectively, intake of placebo or testosterone; the last 4 excerpts were then shown at 1(1/2)-hour intervals. RESULTS: Sublingual intake of testosterone caused a sharp increase in plasma testosterone levels within 15 minutes; these levels declined to baseline values within 90 minutes. Three to 4(1/2) hours after reaching peak testosterone level, we found a statistically significantly increase in genital responsiveness (P = .04). Furthermore, on the day of testosterone treatment, there also was a strong and statistically significant association between the increase in genital arousal and subjective reports of "genital sensations" (P = .02) and "sexual lust" (P = .01) after 4(1/2) hours. CONCLUSIONS: There is a time lag in the effect of sublingually administered testosterone on genital arousal in women. In addition, a consecutive increase in vaginal arousal might cause higher genital sensations and sexual lust.

Correlations among salivary testosterone, mood, and selective attention to threat in humans.

An experiment was designed to investigate the relation among salivary testosterone, mood, and selective attention to threat. The participant group consisted of 32 nonclinical subjects (16 men and 16 women). Individuals completed the Profile Of Mood States (POMS) and performed a pictorial emotional Stroop task measuring selective attention to angry faces. Anticipating a time lag between testosterone (as measured in saliva) and cognitive emotional behavior, multiple time-coursed saliva samples were taken preceding the assessment of questionnaire and task for every subject. In both sexes, salivary testosterone was significantly related to mood (i.e., anger and tension) and selective attention to angry faces when saliva samples were taken 6 h before questionnaire and task assessment. Research on the relation between testosterone and human behavior might benefit by taking into account time lags between the behavioral manifestations and the continuously changing levels of testosterone.

Sex differences and menstrual cycle effects in human spatial memory.

A typical test of spatial memory requires subjects to relocate a number of objects in their original, previously studied positions. It has been argued that this test includes multiple separate processing components (Postma, A., De Haan, E.H.F., 1996. Quarterly Journal of Experimental Psychology 48A (1), 178-199; Postma, A., Izendoorn, R., De Haan, E.H.F., 1998. Brain and Cognition 36, 334-345). One has to encode the precise positions occupied, assign the various objects to the correct (relative) locations, and achieve an integration of both types of spatial information. The present study examined the presence of sex differences and the role of hormonal factors for these selective components of spatial memory. A computerised, immediate (working) memory version of the test was used, comparing 23 males and 34 females on three experimental conditions: positions only, object-to-position-assignment, and the combined condition, requiring integration of the other two components. In line with previous research (Postma et al., 1998) males showed a selective advantage for fine-grained, metric positional reconstruction (i.e. positions-only). Interestingly, a within-subjects comparison in the females only revealed a menstrual cycle effect for exactly the same dimension of spatial memory. In the nonmenstrual phase, females were better than during menstruation. This clearly implies a role for sex hormones in spatial memory, even though a subsequent analysis of testosterone samples in saliva did not reveal a significant correlation with measures of spatial memory in both males and females.

Baseline salivary cortisol levels and preconscious selective attention for threat. A pilot study.

This study was conducted to examine the relationship between baseline salivary cortisol (CORT) levels and selective attention for displays of angry faces. Selective attention was investigated using a pictorial emotional Stroop task, comparing colournaming-speed of angry and neutral faces. The task was assessed in supraliminal (unmasked) and subliminal (masked) conditions to 28 non-clinical subjects (14 male and 14 female). Repeated measures analysis of variance revealed a significant interaction between median split CORT levels (low vs. high) and masked face valence (angry vs. neutral). The latter effect was mainly due to significant facilitation in the high CORT subject-group; these subjects seemed to allocate their attention away from the masked angry face. A relation between baseline CORT levels and fast withdrawal behavior is suggested.