Luca Passamonti

A key role for similarity in vicarious reward

A functional magnetic resonance imaging study reveals the interactions within the brain that modulate feelings of reward on seeing a similar person win a contest. Humans appear to have an inherent prosocial tendency toward one another in that we often take pleasure in seeing others succeed. This fact is almost certainly exploited by game shows, yet why watching others win elicits a pleasurable vicarious rewarding feeling in the absence of personal economic gain is unclear. One explanation is that game shows use contestants who have similarities to the viewing population, thereby kindling kin-motivated responses (for example, prosocial behavior). Using a game show–inspired paradigm, we show that the interactions between the ventral striatum and anterior cingulate cortex subserve the modulation of vicarious reward by similarity, respectively. Our results support studies showing that similarity acts as a proximate neurobiological mechanism where prosocial behavior extends to unrelated strangers.

Brain structure abnormalities in early-onset and adolescent-onset conduct disorder

OBJECTIVE The developmental taxonomic theory proposes that neurodevelopmental factors play a critical role in the etiology of early-onset conduct disorder, whereas adolescent-onset conduct disorder arises as a result of social mimicry of deviant peers. Recent studies have challenged this theory by demonstrating that adolescents with both early- and adolescent-onset forms of conduct disorder show impaired emotional learning and abnormal neural activation during facial expression processing. The present study extends this work by investigating brain structure in both subtypes of conduct disorder. METHOD Voxel-based morphometry was used to compare gray matter volumes in four regions of interest (amygdala, insula, anterior cingulate, and orbitofrontal cortex) in male adolescents with early-onset (N=36) or adolescent-onset (N=27) conduct disorder and in healthy comparison subjects (N=27). Whole-brain structural analyses were also performed. RESULTS The combined conduct disorder group displayed gray matter volume reductions in the bilateral amygdala, extending into the insula, relative to healthy comparison subjects. Separate comparisons between healthy subjects and each conduct disorder subgroup revealed lower amygdala volume in both subgroups and reduced right insula volume in the adolescent-onset subgroup. Regression analyses within the conduct disorder subjects alone demonstrated a negative correlation between conduct disorder symptoms and right insula volume. CONCLUSIONS The results demonstrate that gray matter volume reductions in brain regions involved in processing socioemotional stimuli are associated with conduct disorder, regardless of age of onset. Brain structural abnormalities may contribute to the emergence of adolescent-onset as well as early-onset conduct disorder.

Monoamine Oxidase-A Genetic Variations Influence Brain Activity Associated with Inhibitory Control: New Insight into the Neural Correlates of Impulsivity

BACKGROUND Previous evidence has shown that genetic variations in the serotonergic system contribute to individual differences in personality traits germane to impulse control. The monoamine oxidase-A (MAO-A) gene, coding for an enzyme primarily involved in serotonin and noradrenaline catabolism, presents a well-characterized functional polymorphism consisting of a variable number of tandem repeats in the promoter region, with high-activity and low-activity variants. High-activity allele carriers have higher enzyme expression, lower amine concentration, and present higher scores on behavioral measures of impulsivity than low-activity allele carriers. METHODS We studied the relationship of this polymorphism to brain activity elicited by a response inhibition task (Go/NoGo task), using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging in 24 healthy men. RESULTS Direct comparison between groups revealed a greater BOLD response in the right ventrolateral prefrontal cortex (Brodmanns area [BA] 45/47) in high-activity allele carriers, whereas a greater response in the right superior parietal cortex (BA 7) and bilateral extrastriate cortex (BA 18) was found in low-activity allele carriers. CONCLUSIONS These data suggest that a specific genetic variation involving serotonergic catabolism can modulate BOLD response associated with human impulsivity.

Neural Abnormalities in Early-Onset and Adolescence-Onset Conduct Disorder

CONTEXT Conduct disorder (CD) is characterized by severe antisocial behavior that emerges in childhood (early-onset CD [EO-CD]) or adolescence (adolescence-onset CD [AO-CD]). Early-onset CD is proposed to have a neurodevelopmental basis, whereas AO-CD is thought to emerge owing to social mimicry of deviant peers. However, this developmental taxonomic theory is debated after reports of neuropsychological impairments in both CD subtypes. A critical, although unaddressed, issue is whether these subtypes present similar or distinct neurophysiological profiles. Hence, we investigated neurophysiological responses to emotional and neutral faces in regions associated with antisocial behavior (ie, the amygdala, ventromedial prefrontal cortex, insula, and orbitofrontal cortex) in individuals with EO-CD and AO-CD and in healthy control subjects. OBJECTIVE To investigate whether EO-CD and AO-CD subjects show neurophysiological abnormalities. DESIGN Case-control study. SETTING Government research institute, university department. PARTICIPANTS Seventy-five male adolescents and young adults aged 16 to 21 years, including 27 with EO-CD, 25 with AO-CD, and 23 healthy controls. Main Outcome Measure Neural activations measured by functional magnetic resonance imaging while participants viewed angry, sad, and neutral faces. RESULTS Comparing angry vs neutral faces, participants with both CD subtypes displayed reduced responses in regions associated with antisocial behavior compared with controls; differences between the CD subtypes were not significant. Comparing each expression with fixation baseline revealed an abnormal (increased) amygdala response to neutral but not angry faces in both groups of CD relative to controls. For sad vs neutral faces, reduced amygdala activation was observed in EO-CD relative to AO-CD and control participants. Comparing each expression with fixation revealed hypoactive amygdala responses to sadness in individuals with EO-CD relative to AO-CD participants and controls. These findings were not accounted for by attention-deficit/hyperactivity disorder symptoms. CONCLUSIONS Neurophysiological abnormalities are observed in both CD subtypes, contrary to the developmental taxonomic theory of CD. Additional amygdala hypofunction in relation to sad expressions might indicate why EO-CD is more severe and persistent than AO-CD.

Personality Predicts the Brain's Response to Viewing Appetizing Foods: The Neural Basis of a Risk Factor for Overeating

Eating is not only triggered by hunger but also by the sight of foods. Viewing appetizing foods alone can induce food craving and eating, although there is considerable variation in this “external food sensitivity” (EFS). Because increased EFS is associated with overeating, identifying its neural correlates is important for understanding the current epidemic of obesity. Animal research has identified the ventral striatum, amygdala, hypothalamus, medial prefrontal and premotor cortices as key interacting structures for feeding. However, it is unclear whether a similar network exists in humans and how it is affected by EFS. Using functional magnetic resonance imaging, we showed that viewing appetizing compared with bland foods produced changes in connectivity among the human ventral striatum, amygdala, anterior cingulate and premotor cortex that were strongly correlated with EFS. Differences in the dynamic interactions within the human appetitive network in response to pictures of appetizing foods may determine an individuals risk of obesity.

Brain structure abnormalities in adolescent girls with conduct disorder

Background Conduct disorder (CD) in female adolescents is associated with a range of negative outcomes, including teenage pregnancy and antisocial personality disorder. Although recent studies have documented changes in brain structure and function in male adolescents with CD, there have been no neuroimaging studies of female adolescents with CD. Our primary objective was to investigate whether female adolescents with CD show changes in grey matter volume. Our secondary aim was to assess for sex differences in the relationship between CD and brain structure. Methods Female adolescents with CD (n = 22) and healthy control participants matched in age, performance IQ and handedness (n = 20) underwent structural magnetic resonance imaging. Group comparisons of grey matter volume were performed using voxel-based morphometry. We also tested for sex differences using archive data obtained from male CD and control participants. Results Female adolescents with CD showed reduced bilateral anterior insula and right striatal grey matter volumes compared with healthy controls. Aggressive CD symptoms were negatively correlated with right dorsolateral prefrontal cortex volume, whereas callous-unemotional traits were positively correlated with bilateral orbitofrontal cortex volume. The sex differences analyses revealed a main effect of diagnosis on right amygdala volume (reflecting reduced amygdala volume in the combined CD group relative to controls) and sex-by-diagnosis interactions in bilateral anterior insula. Conclusions We observed structural abnormalities in brain regions involved in emotion processing, reward and empathy in female adolescents with CD, which broadly overlap with those reported in previous studies of CD in male adolescents.

Appetitive Motivation Predicts the Neural Response to Facial Signals of Aggression

The “behavioral approach system” (BAS) (Gray, 1990) has been primarily associated with reward processing and positive affect. However, additional research has demonstrated that the BAS plays a role in aggressive behavior, heightened experience of anger, and increased attention to facial signals of aggression. Using functional magnetic resonance imaging, we show that variation in the BAS trait in healthy participants predicts activation in neural regions implicated in aggression when participants view facial signals of aggression in others. Increased BAS drive (appetitive motivation) was associated with increased amygdala activation and decreased ventral anterior cingulate and ventral striatal activation to facial signals of aggression, relative to sad and neutral expressions. In contrast, increased behavioral inhibition was associated with increased activation in the dorsal anterior cingulate, a region involved in the perception of fear and threat. Our results provide the first demonstration that appetitive motivation constitutes a significant factor governing the function of neural regions implicated in aggression, and have implications for understanding clinical disorders of aggression.

Effects of acute tryptophan depletion on prefrontal-amygdala connectivity while viewing facial signals of aggression.

Background Reduced levels of serotonin (5-HT) within prefrontal cortex (PFC)–amygdala circuits have long been implicated in impulsive aggression. However, whether lowering 5-HT alters the dynamic interplay between the PFC and the amygdala has not been directly tested in humans. It is known that manipulating 5-HT via acute tryptophan depletion (ATD) causes variable effects on brain responses to a variety of emotional stimuli, but it remains unclear whether ATD affects functional connectivity in neural networks involved in processing social signals of aggression (e.g., angry faces). Methods Thirty healthy individuals were enrolled in a randomized, double-blind, placebo-controlled ATD study. On each treatment, brain responses to angry, sad, and neutral faces were measured with functional magnetic resonance imaging. Two methods (psycho-physiological-interaction in a general linear model and dynamic causal modeling) were used to assess the impact of ATD on the functional connectivity between PFC and amygdala. Results Data from 19 subjects were available for the final analyses. A whole-brain psycho-physiological-interaction in a general linear model showed that ATD significantly modulated the connectivity between the amygdala and two PFC regions (ventral anterior cingulate cortex and ventrolateral PFC) when processing angry vs. neutral and angry vs. sad but not sad vs. neutral faces. Dynamic causal modeling corroborated and extended these findings by showing that 5-HT depletion reduced the influence of processing angry vs. neutral faces on circuits within PFC and on PFC–amygdala pathways. Conclusions We provide strong support for neurobiological accounts positing that 5-HT significantly influences PFC–amygdala circuits implicated in aggression and other affective behaviors.

Connectivity from the ventral anterior cingulate to the amygdala is modulated by appetitive motivation in response to facial signals of aggression

For some people facial expressions of aggression are intimidating, for others they are perceived as provocative, evoking an aggressive response. Identifying the key neurobiological factors that underlie this variation is fundamental to our understanding of aggressive behaviour. The amygdala and the ventral anterior cingulate cortex (ACC) have been implicated in aggression. Using functional magnetic resonance imaging (fMRI), we studied how the interaction between these regions is influenced by the drive to obtain reward (reward–drive or appetitive motivation), a personality trait consistently associated with aggression. Two distinct techniques showed that the connectivity between the ventral ACC and the amygdala was strongly correlated with personality, with high reward–drive participants displaying reduced negative connectivity. Furthermore, the direction of this effect was restricted from ventral ACC to the amygdala but not vice versa. The personality-mediated variation in the pathway from the ventral anterior cingulate cortex to the amygdala provides an account of why signals of aggression are interpreted as provocative by some individuals more than others.

Altered cortical-cerebellar circuits during verbal working memory in essential tremor

Essential tremor is a common neurological disorder characterized by motor and cognitive symptoms including working memory deficits. Epidemiological research has shown that patients with essential tremor are at a higher risk to develop dementia relative to age-matched individuals; this demonstrates that cognitive impairments reflect specific, although poorly understood, disease mechanisms. Neurodegeneration of the cerebellum has been implicated in the pathophysiology of essential tremor itself; however, whether cerebellar dysfunctions relate to cognitive abnormalities is unclear. We addressed this issue using functional neuroimaging in 15 patients with essential tremor compared to 15 sex-, education- and age-matched healthy controls while executing a verbal working memory task. To remove confounding effects, patients with integrity of the nigrostriatal terminals, no dementia and abstinent from medications altering cognition were enrolled. We tested whether patients displayed abnormal activations of the cerebellum (posterior lobules) and other areas typically engaged in working memory (dorsolateral prefrontal cortex, parietal lobules). Between-groups differences in the interactions of these regions were also assessed with functional connectivity methods. Finally, we determined whether individual differences in neuropsychological and clinical measures modulated the magnitude of regional brain responses and functional connectivity data in patients with essential tremor. Despite similar behavioural performances, patients showed greater cerebellar response (crus I/lobule VI) compared to controls during attentional-demanding working memory trials (F = 8.8; P < 0.05, corrected). They also displayed altered functional connectivity between crus I/lobule VI and regions implicated in focusing attention (executive control circuit including dorsolateral prefrontal cortex, inferior parietal lobule, thalamus) and in generating distracting self-related thoughts (default mode network including precuneus, ventromedial prefrontal cortex and hippocampus) (T-values > 3.2; P < 0.05, corrected). These findings were modulated by the variability in neuropsychological measures: patients with low cognitive scores displayed reduced connectivity between crus I/lobule VI and the dorsolateral prefrontal cortex and enhanced connectivity between crus I/lobule VI and the precuneus (T-values > 3.7; P < 0.05, corrected). It is likely that cerebellar neurodegeneration underlying essential tremor is reflected in abnormal communications between key regions responsible for working memory and that adaptive mechanisms (enhanced response of crus I/lobule VI) occur to limit the expression of cognitive symptoms. The connectivity imbalance between the executive control circuit and the default mode network in patients with essential tremor with low cognitive scores may represent a dysfunction, driven by the cerebellum, in suppressing task irrelevant thoughts via focused attention. Overall, our results offer new insights into pathophysiological mechanisms of cognition in essential tremor and suggest a primary role of the cerebellum in mediating abnormal interactions between the executive control circuit and the default mode network.