Dennis J.L.G. Schutter

Testosterone shifts the balance between sensitivity for punishment and reward in healthy young women

Animal research has demonstrated reductions in punishment sensitivity and enhanced reward dependency after testosterone administration. In humans, elevated levels of testosterone have been associated with violent and antisocial behavior. Interestingly, extreme forms of violent and antisocial behavior can be observed in the psychopath. Moreover, it has been argued that reduced punishment sensitivity and heightened reward dependency are crucially involved in the etiology and maintenance of psychopathy. A task that has been proven to be capable of simulating punishment-reward contingencies is the IOWA gambling task. Decisions to choose from decks of cards become motivated by punishment and reward schedules inherent in the task. Importantly, clinical and subclinical psychopaths demonstrate a risky, disadvantageous pattern of decision-making in the task, indicating motivational imbalance (insensitivity for punishment and enhanced reward dependency). Here, in a double-blind placebo-controlled crossover design (n = 12), whether a single administration of testosterone would shift the motivational balance between the sensitivity for punishment and reward towards this tendency to choose disadvantageously was investigated. As hypothesized, subjects showed a more disadvantageous pattern of decision-making after testosterone compared to placebo administration. These findings not only provide the first direct evidence for the effects of testosterone on punishment-reward contingencies in humans, but they also give further insights into the hypothetical link between testosterone and psychopathy.

Testosterone administration impairs cognitive empathy in women depending on second-to-fourth digit ratio

During social interactions we automatically infer motives, intentions, and feelings from bodily cues of others, especially from the eye region of their faces. This cognitive empathic ability is one of the most important components of social intelligence, and is essential for effective social interaction. Females on average outperform males in this cognitive empathy, and the male sex hormone testosterone is thought to be involved. Testosterone may not only down-regulate social intelligence organizationally, by affecting fetal brain development, but also activationally, by its current effects on the brain. Here, we show that administration of testosterone in 16 young women led to a significant impairment in their cognitive empathy, and that this effect is powerfully predicted by a proxy of fetal testosterone: the right-hand second digit-to-fourth digit ratio. Our data thus not only demonstrate down-regulatory effects of current testosterone on cognitive empathy, but also suggest these are preprogrammed by the very same hormone prenatally. These findings have importance for our understanding of the psychobiology of human social intelligence.

Testosterone Reduces Unconscious Fear but Not Consciously Experienced Anxiety: Implications for the Disorders of Fear and Anxiety

BACKGROUND The fear-reducing properties of testosterone have been firmly established in animals but not in humans. However, human data on the relation between testosterone, fear, and anxiety have predominantly involved questionnaires that index cortically executed conscious appraisal of anxious mood. Animal studies, on the other hand, indicate that the effects of testosterone on motivation and emotion are of subcortical origin and of unconscious nature. Presently, it was hypothesized that a single testosterone administration to humans would reduce unconscious fear but not consciously experienced anxiety. METHODS In a placebo-controlled, double-blind crossover design, a single dose of testosterone (.5 mg) or placebo was administered to 16 healthy female volunteers. Afterward, a masked emotional Stroop task measured unconscious emotional responses to fearful faces, while multiple self-reports of mood indexed consciously experienced anxiety. RESULTS As hypothesized, the habitual vigilant emotional response to the masked fearful face observed in the placebo condition was significantly reduced after testosterone was administered, while the self-reported measures of anxiety remained unaffected. CONCLUSIONS These data provide the first direct evidence for fear-reducing properties of testosterone in humans. Furthermore, by dissociating specific aspects of fear and anxiety in humans, this outcome highlights that testosterones effects on motivation and emotion concern the subcortical affective pathways of the brain.

The cerebellum on the rise in human emotion

For decennia the cerebellum has largely been excluded from scientific enquiry beyond motor function. However, the intimate afferent and efferent connections to the midbrain and limbic system provide for the neuroanatomical foundation of cerebellar involvement in emotion and emotional disorders. Moreover, an increasing body of empirical evidence indicates that the cerebellum may be involved in emotion regulation. Both functional and structural abnormalities of the cerebellum have been demonstrated in emotional disorders, including depression and schizophrenia. Research shows that the functional repertoire of the cerebellum is broader than previously thought and its involvement in emotion is noteworthy.

Defective somatic markers in sub-clinical psychopathy

Damasios somatic marker hypothesis is argued to be specifically applicable to psychopathy, though evidence has been meager until now. The principal evidence for the somatic marker hypothesis is based on findings in patients with orbitofrontal lesions, showing absent punishment learning on the Iowa gambling task. Interestingly, neuroimaging studies indicate orbitofrontal dysfunction in psychopathy also. Here we investigated the somatic marker hypothesis in subjects selected on low and high psychopathic behavioral characteristics from the outer extreme ranges of a large subject pool (n  = 525). The low psychopathic subject group (n  = 16) showed intact punishment learning, suggesting somatic markers came to guide their decisions in the course of the game. In contrast, such punishment learning was not observed in the high psychopathic subject group (n  = 16), who mimicked the gambling behavior of orbitofrontal patients. These findings provide further evidence for the hypothesized link between psychopathy and orbitofrontal dysfunction.

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.

Testosterone Reduces Conscious Detection of Signals Serving Social Correction: Implications for Antisocial Behavior

Elevated levels of testosterone have repeatedly been associated with antisocial behavior, but the psychobiological mechanisms underlying this effect are unknown. However, testosterone is evidently capable of altering the processing of facial threat, and facial signals of fear and anger serve sociality through their higher-level empathy-provoking and socially corrective properties. We investigated the hypothesis that testosterone predisposes people to antisocial behavior by reducing conscious recognition of facial threat. In a within-subjects design, testosterone (0.5 mg) or placebo was administered to 16 female volunteers. Afterward, a task with morphed stimuli indexed their sensitivity for consciously recognizing the facial expressions of threat (disgust, fear, and anger) and nonthreat (surprise, sadness, and happiness). Testosterone induced a significant reduction in the conscious recognition of facial threat overall. Separate analyses for the three categories of threat faces indicated that this effect was reliable for angry facial expressions exclusively. This testosterone-induced impairment in the conscious detection of the socially corrective facial signal of anger may predispose individuals to antisocial behavior.

Is this hand for real? attenuation of the rubber hand illusion by transcranial magnetic stimulation over the inferior parietal lobule

In the rubber hand illusion (RHI), participants incorporate a rubber hand into a mental representation of ones body. This deceptive feeling of ownership is accompanied by recalibration of the perceived position of the participants real hand toward the rubber hand. Neuroimaging data suggest involvement of the posterior parietal lobule during induction of the RHI, when recalibration of the real hand toward the rubber hand takes place. Here, we used off-line low-frequency repetitive transcranial magnetic stimulation (rTMS) in a double-blind, sham-controlled within-subjects design to investigate the role of the inferior posterior parietal lobule (IPL) in establishing the RHI directly. Results showed that rTMS over the IPL attenuated the strength of the RHI for immediate perceptual body judgments only. In contrast, delayed perceptual responses were unaffected. Furthermore, ballistic action responses as well as subjective self-reports of feeling of ownership over the rubber hand remained unaffected by rTMS over the IPL. These findings are in line with previous research showing that the RHI can be broken down into dissociable bodily sensations. The illusion does not merely affect the embodiment of the rubber hand but also influences the experience and localization of ones own hand in an independent manner. Finally, the present findings concur with a multicomponent model of somatosensory body representations, wherein the IPL plays a pivotal role in subserving perceptual body judgments, but not actions or higher-order affective bodily judgments.

The neurobiology of oppositional defiant disorder and conduct disorder: Altered functioning in three mental domains

This review discusses neurobiological studies of oppositional defiant disorder and conduct disorder within the conceptual framework of three interrelated mental domains: punishment processing, reward processing, and cognitive control. First, impaired fear conditioning, reduced cortisol reactivity to stress, amygdala hyporeactivity to negative stimuli, and altered serotonin and noradrenaline neurotransmission suggest low punishment sensitivity, which may compromise the ability of children and adolescents to make associations between inappropriate behaviors and forthcoming punishments. Second, sympathetic nervous system hyporeactivity to incentives, low basal heart rate associated with sensation seeking, orbitofrontal cortex hyporeactiviy to reward, and altered dopamine functioning suggest a hyposensitivity to reward. The associated unpleasant emotional state may make children and adolescents prone to sensation-seeking behavior such as rule breaking, delinquency, and substance abuse. Third, impairments in executive functions, especially when motivational factors are involved, as well as structural deficits and impaired functioning of the paralimbic system encompassing the orbitofrontal and cingulate cortex, suggest impaired cognitive control over emotional behavior. In the discussion we argue that more insight into the neurobiology of oppositional defiance disorder and conduct disorder may be obtained by studying these disorders separately and by paying attention to the heterogeneity of symptoms within each disorder.

Socially Explosive Minds: The Triple Imbalance Hypothesis of Reactive Aggression

The psychobiological basis of reactive aggression, a condition characterized by uncontrolled outbursts of socially violent behavior, is unclear. Nonetheless, several theoretical models have been proposed that may have complementary views about the psychobiological mechanisms involved. In this review, we attempt to unite these models and theorize further on the basis of recent data from psychological and neuroscientific research to propose a comprehensive neuro-evolutionary framework: The Triple Imbalance Hypothesis (TIH) of reactive aggression. According to this model, reactive aggression is essentially subcortically motivated by an imbalance in the levels of the steroid hormones cortisol and testosterone (Subcortical Imbalance Hypothesis). This imbalance not only sets a primal predisposition for social aggression, but also down-regulates cortical-subcortical communication (Cortical-Subcortical Imbalance Hypothesis), hence diminishing control by cortical regions that regulate socially aggressive inclinations. However, these bottom-up hormonally mediated imbalances can drive both instrumental and reactive social aggression. The TIH suggests that reactive aggression is differentiated from proactive aggression by low brain serotonergic function and that reactive aggression is associated with left-sided frontal brain asymmetry (Cortical Imbalance Hypothesis), especially observed when the individual is socially threatened or provoked. This triple biobehavioral imbalance mirrors an evolutionary relapse into violently aggressive motivational drives that are adaptive among many reptilian and mammalian species, but may have become socially maladaptive in modern humans.