J. van Honk

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.

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 brains threat vigilance system, which has important implications for the understanding of the amygdalas role in the disorders of fear and anxiety.

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.

The role of human basolateral amygdala in ambiguous social threat perception

Previous studies have shown that the amygdala (AMG) plays a role in how affective signals are processed. Animal research has allowed this role to be better understood and has assigned to the basolateral amygdala (BLA) an important role in threat perception. Here we show that, when passively exposed to bodily threat signals during a facial expressions recognition task, humans with bilateral BLA damage but with a functional central-medial amygdala (CMA) have a profound deficit in ignoring task-irrelevant bodily threat signals.

Testosterone and Dominance in Humans: Behavioral and Brain Mechanisms

Most people think that the hormone testosterone especially triggers aggression and antisocial behavior in humans. Mistakenly, the male sex steroid principally underlies each and every aspect of human social behavior but especially social dominance behavior. Testosterone by itself or by way of its metabolite, estradiol, the female sex steroid, is essential in the action of the social peptides oxytocin and vasopressin and regulates the turnover of the social monoamines, dopamine and serotonin. The hormone also has many other actions in the brain; thus the social brain’s main chemical, without exaggeration, is testosterone. Here we review a line of findings with placebo-controlled testosterone administration in the field of social neuroscience in which various techniques are used to investigate social dominance and trustworthiness behaviors. These findings give insights into how and by what biobehavioral mechanisms testosterone acts in humans to motivate them to establish and maintain a dominant status.

Gray's BIS/BAS dimensions in non-comorbid, non-medicated social anxiety disorder

Grays behavioural inhibition and behavioural activation (BIS/BAS) neural systems model has led to research on approach and withdrawal as the two most fundamental dimensions of affective behaviour, and their role in psychopathology. Although Gray proposed the BIS as the neurological basis of anxiety, there are no reports examining approach and withdrawal predispositions in social anxiety disorder. Here we report approach and withdrawal predispositions in a group of 23 non-medicated individuals with social anxiety disorder (SAD) without co-morbid depression and in 48 normal controls. Results show increased BIS and decreased BAS fun-seeking in SAD subjects thereby underscoring Grays dimensional model.

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.

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.

Principes en toepassingen van transcraniale magnetische stimulatie in de klinische neurowetenschappen

Naast de mogelijkheden om hersenprocessen indirect te visualiseren met behulp van technieken zoals functionele magnetische resonantie beeldvorming (fmri) en positron emissie tomografie (pet), is het nu ook mogelijk om actief dergelijke neuronale processen te beïnvloeden door middel van transcraniale magnetische stimulatie (tms). tms is gebaseerd op het principe van elektromagnetische inductie.