Yoan Mihov

Fear processing and social networking in the absence of a functional amygdala

BACKGROUND The human amygdala plays a crucial role in processing social signals, such as face expressions, particularly fearful ones, and facilitates responses to them in face-sensitive cortical regions. This contributes to social competence and individual amygdala size correlates with that of social networks. While rare patients with focal bilateral amygdala lesion typically show impaired recognition of fearful faces, this deficit is variable, and an intriguing possibility is that other brain regions can compensate to support fear and social signal processing. METHODS To investigate the brains functional compensation of selective bilateral amygdala damage, we performed a series of behavioral, psychophysiological, and functional magnetic resonance imaging experiments in two adult female monozygotic twins (patient 1 and patient 2) with equivalent, extensive bilateral amygdala pathology as a sequela of lipoid proteinosis due to Urbach-Wiethe disease. RESULTS Patient 1, but not patient 2, showed preserved recognition of fearful faces, intact modulation of acoustic startle responses by fear-eliciting scenes, and a normal-sized social network. Functional magnetic resonance imaging revealed that patient 1 showed potentiated responses to fearful faces in her left premotor cortex face area and bilaterally in the inferior parietal lobule. CONCLUSIONS The premotor cortex face area and inferior parietal lobule are both implicated in the cortical mirror-neuron system, which mediates learning of observed actions and may thereby promote both imitation and empathy. Taken together, our findings suggest that despite the pre-eminent role of the amygdala in processing social information, the cortical mirror-neuron system may sometimes adaptively compensate for its pathology.

Oxytocin enhances attractiveness of unfamiliar female faces independent of the dopamine reward system.

Evidence from animal studies suggests that the social attraction and bonding effects of the neuropeptide oxytocin (OXT) are mediated by its modulation of dopamine (DA) release in brain reward centers, but this has not yet been demonstrated in humans. DA release can be measured by positron emission tomography (PET) using the radioligand [11C]raclopride. Its binding to DA D2 receptors (D2R) is sensitive and reciprocally related to endogenous DA, especially in the striatum. In a randomized double-blind placebo-controlled within-subjects trial on 18 adult male volunteers we combined [11C]raclopride PET and a facial attractiveness rating task to establish whether intranasal OXT (24 IU) increased both the perceived attractiveness of unfamiliar female faces and striatal DA release compared with placebo administration. While our behavioral data confirmed that subjects rated unfamiliar female faces as more attractive following OXT treatment, and this correlated with an increased perfusion rate in the striatum, there was no evidence for altered [11C]raclopride binding in the striatum or pallidum. Instead under OXT we rather observed an increased [11C]raclopride binding and reduced perfusion rate in subregions of the right dorsomedial prefrontal gyrus and superior parietal gyrus. The absence of OXT effects on dopamine release and D2 receptors in brain reward centers, despite increased striatal activity, implies that the peptide may facilitate perceived attraction via non-dopaminergic actions.

Genetic variation in dopaminergic activity is associated with the risk for psychiatric side effects of levetiracetam

Purpose:  Levetiracetam (LEV) is a highly effective antiepileptic agent. A clinically relevant psychiatric complication of LEV treatment, however, is the provocation of irritability and aggression. Recent behavioral research indicates that personality traits may predispose to these side effects. To assess the genetic basis of the adverse psychotropic profile of LEV, a candidate gene‐based two‐stage association study was conducted.

A negative emotional and economic judgment bias in major depression

Although major depression is projected to be among the top three causes of disability-adjusted life years lost in 2030, relatively little is known concerning the extent to which depressed mood states can bias social–economic decision making away from optimal outcomes. One experimental framework to study the interaction between negative emotion and social–economic decisions is the ultimatum game (UG), where the fair, cooperative player altruistically punishes the unfair, non-cooperative player. To assess a potential susceptibility of altruistic punishment to depressed mood, we repeatedly administered the UG task to a cohort of 20 currently depressed patients with a diagnosis of recurrent major depressive disorder and 20 healthy controls. Furthermore, valence and arousal ratings of emotionally laden pictures were obtained from all participants in order to assess a depressed mood-related distortion of emotion judgments. Compared to healthy controls, depressed patients over-sanctioned unfair proposals in the UG and judged emotional stimuli too negatively. Thus, major depression is associated with a negative emotional bias that hampers social–economic decision making and produces large personal costs.

Altered amygdala function in nicotine addiction: insights from human neuroimaging studies.

More than 5 million deaths a year are attributable to tobacco smoking, making it the largest single cause of preventable death worldwide. The primary addictive component in tobacco is nicotine. Its addictive power is exemplified by the fact that by far most attempts to quit smoking fail. It is therefore mandatory to understand the biological mechanisms by which nicotine leads to continued smoking despite its harmful consequences. While current research perspectives on nicotine addiction emphasize the contribution of reward-related mesocorticolimbic dopamine (DA) systems, the role of the amygdala remains less well characterized, although it is crucially engaged in the emotional and motivational modulation of cognition and behavior. Consequently, we here review brain imaging studies reporting altered neural responses of the amygdala in nicotine addiction. A major focus is placed upon resting-state and cue-induction studies documenting that nicotine addiction is associated with aberrant amygdala activity. Importantly, unprovoked abstinence-induced nicotine cravings have been shown to interfere with the amygdalas ability to detect and adequately respond to harm signals. In light of this empirical evidence, we propose that impaired amygdala-guided harm avoidance and executive functions may be instrumental in maintaining nicotine addiction despite serious health consequences.

Mirroring Fear in the Absence of a Functional Amygdala

F rom an evolutionary perspective, facial expressions of fear convey highly recognizable emotional signals that serve adaptive functions by promoting survival and reproductive success (1). Current theories of how the brain interprets facial expressions of fear implicate the mirror neuron network (MNN) in echoing the emotional states of others by internal simulation (2,3). Originally discovered in the ventral premotor cortex of macaque monkeys (4,5), mirror neurons are defined as being responsive to observation and execution of the same actions. Evidence that facial emotion recognition in humans is impaired by damage to MNN-associated cortical regions or the amygdala (6) has stimulated the hypothesis that the amygdala forms an integral component of an emotion MNN (7,8). An alternative view holds that the amygdala plays only a supporting role (9), for example, by directing attention to the informative eye region (10), suggesting the emotional MNN could operate independently, without a functional amygdala. To test these hypotheses directly, we studied two 38-year-old female monozygotic twins (patient 1 and patient 2) with equivalent, selective bilateral amygdala calcification damage because of congenital UrbachWiethe disease (synonyms hyalinosis cutis et mucosae or lipoid proteinosis; Online Mendelian Inheritance in Man 247100) (11–15) and 16 healthy female control subjects (mean age SD = 35.8 4.6 years). In previous experiments patient 1, but not patient 2, demonstrated preserved recognition of fearful faces and potentiated responses to them in MNN-associated regions suggesting that the MNN might functionally compensate her amygdala damage (14,15). We therefore predicted that patient 1, but not patient 2, would exhibit fear-specific supranormal MNN responses in a functional magnetic resonance imaging (fMRI) experiment (experiment 1) probing observation and imitation of

Facilitation of learning by social-emotional feedback in humans is beta-noradrenergic-dependent

Adaptive behavior in dynamic environments critically depends on the ability to learn rapidly and flexibly from the outcomes of prior choices. In social environments, facial expressions of emotion often serve as performance feedback and thereby guide declarative learning. Abundant evidence implicates beta-noradrenergic signaling in the modulatory influence of emotion on declarative learning. It is currently unclear whether a similar mechanism also mediates a guidance of declarative learning by social-emotional feedback administered in the form of facial expressions. We therefore conducted a double-blind randomized placebo-controlled trial to test the effects of a 40-mg single oral dose of the nonspecific beta-noradrenergic antagonist propranolol in a behavioral task that required gradual declarative learning of item-category associations from either social-emotional (happy vs. angry faces) or nonsocial (green vs. red color signals) trial-by-trial feedback. As predicted on the basis of our previous experiments, learning from social-emotional feedback was more effective than learning from nonsocial feedback in placebo-treated subjects. This advantage of social-emotional over nonsocial feedback was abolished by propranolol treatment. Propranolol had no effect on learning during the nonsocial feedback condition. Our findings suggest that a facilitation of declarative learning by social-emotional feedback critically involves signaling via beta-noradrenergic receptors.

Overnight Deprivation from Smoking Disrupts Amygdala Responses to Fear

Cigarette smoking, a major, yet avoidable, cause of disability and premature death, is the most prevalent form of nicotine addiction. An emerging theme in the neurobiology of nicotine addiction is the integrity of the amygdala. Using functional MRI, amygdala responses during a face perception task were compared between 28 chronic smokers [14 females, 14 males; age, 26.3 (2.8) years; age at onset of smoking, 15.8 (2.6) years; years smoked, 9.1 (2.1); cigarettes per day, 17.1 (3.7); Fagerström test for nicotine dependence score, 4.1 (1.9); exhaled carbon‐monoxide level, 17.8 (9.5) ppm] and 28 age‐ and education‐matched nonsmokers [14 females, 14 males; age, 26.9 (2.4) years]. Subjects underwent imaging on two separate occasions 1 week apart: smoking satiety versus overnight smoking deprivation, in a randomized counterbalanced order. Our results show no difference in amygdala responses to faces between nonsmokers and satiated smokers. However, overnight deprivation from smoking was associated with a significantly lowered amygdala response to fear, an effect that was probabilistically mapped to the basolateral amygdala. We suggest that aberrant amygdala reactivity in overnight‐deprived smokers may reflect a pre‐existing vulnerability to smoking and/or increase the risk of smoking relapse after a cessation attempt. Hum Brain Mapp, 2011.