The specific neural systems underlying the subjective feeling of fear are debated in affective neuroscience. Here, we combine functional MRI with machine learning to identify and evaluate a sensitive and generalizable neural signature predictive of the momentary self-reported subjective fear experience across discovery (n = 67), validation (n = 20) and generalization (n = 31) cohorts. We systematically demonstrate that accurate fear prediction crucially requires distributed brain systems, with important contributions from cortical (e.g., prefrontal, midcingulate and insular cortices) and subcortical (e.g., thalamus, periaqueductal gray, basal forebrain and amygdala) regions. We further demonstrate that the neural representation of subjective fear is distinguishable from the representation of conditioned threat and general negative affect. Overall, our findings suggest that subjective fear, which exhibits distinct neural representation with some other aversive states, is encoded in distributed systems rather than isolated ‘fear centers’.

Pain empathy can be evoked by multiple cues, particularly observation of acute pain inflictions or facial expressions of pain. Previous studies suggest that these cues commonly activate the insula and anterior cingulate, yet vicarious pain encompass pain-specific responses as well as unspecific processes (e.g., arousal) and overlapping activations are not sufficient to determine process-specific shared neural representations. We employed multivariate pattern analyses to fMRI data acquired during observation of noxious stimulation of body limbs (NS) and painful facial expressions (FE) and found spatially and functionally similar cross-modality (NS versus FE) whole-brain vicarious pain-predictive patterns. Further analyses consistently identified shared neural representations in the bilateral mid-insula. The vicarious pain patterns were not sensitive to respond to non-painful high-arousal negative stimuli but predicted self-experienced thermal pain. Finally, a domain-general vicarious pain pattern predictive of self-experienced pain but not arousal was developed. Our findings demonstrate shared pain-associated neural representations of vicarious pain.

Facilitation of social attraction and bonding by the evolutionarily conserved neuropeptide oxytocin is well-established in female mammals. However, accumulating behavioral evidence suggests that oxytocin may have evolved sex-specific functional roles in the domain of human social cognition. A critical question is how oxytocin differentially modulates neural processing of social information in men and women, leading to divergent behavioral responses. Here we show that intranasal oxytocin treatment produces sex-and valence-dependent increases in amygdala activation when women view individuals identified as praising others but in men those who criticize them. Women subsequently show increased liking for the faces of these individuals, whereas in men it is reduced. Thus, oxytocin may act differentially via the amygdala to enhance the salience of positive social attributes in women but negative ones in men. We hypothesize that oxytocin may have evolved different but complementary roles to help ensure successful reproduction by encouraging mothers to promote a prosocial rearing environment for offspring and fathers to protect against antisocial influences.T he hypothalamic neuropeptide oxytocin (OXT) plays a key role in promoting maternal behavior and mother-infant bonding in mammals (1) as well as pair bonds with males in monogamous species (2). Recent studies in both monkeys and humans have suggested that it has not only evolved a more extensive role in social cognition in female primates but also become progressively used by males in this domain (3). Although OXT appears to facilitate both salience and motivational aspects of social cues in both sexes (3, 4), there is increasing evidence that it may often produce opposite effects in these domains in men and women (5-7), raising the intriguing possibility that it has evolved some sex-specific functions at both neural and behavioral levels. In particular, behavioral studies have reported that whereas OXT tends to facilitate positive social judgments (7), social approach (8), kinship recognition (5), and altruism (9) in women, in men it can facilitate negative social judgments (7), social avoidance (10), competitor recognition (5), and selfishness (9). Similarly, in response to couple conflict, OXT decreased sympathetic activity and arousal in women but increased them in men (6). The neural basis of these opposing sex-dependent behavioral effects of OXT has not, however, been established.Previous research has shown that the amygdala has different responses to positive and negative valence social information in men and women (11) and also may be a critical target for sex-specific functional effects of OXT. The amygdala has a sexually dimorphic distribution and expression of OXT receptors in nonprimate mammals (12, 13), and separate OXT-application studies in humans have indicated that there may be differential amygdala reactivity to fearful faces and fearful/threatening scenes in men (14, 15) and women (16,17). Importantly, this region plays a key role in processing so...

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Background Animal models of addiction suggest that the transition from incentive-driven to habitual and ultimately compulsive drug use is mediated by a shift from ventral to dorsal striatal cue-control over drug seeking. Previous studies in human cannabis users reported elevated trait impulsivity and cue-reactivity in striatal circuits, however, these studies were not able to separate addiction-related from exposure-related adaptations.Methods To differentiate the adaptive changes, the present functional magnetic resonance imaging study examined behavioral and neural cue-reactivity in dependent (n = 18) and nondependent (n = 20) heavy cannabis users and a non-using reference group (n = 44). ResultsIrrespective of dependence status, cannabis users demonstrated elevated trait impulsivity as well as increased ventral striatal reactivity and striato-frontal coupling in response to drug cues. Dependent users selectively exhibited dorsal-striatal reactivity and decreased striato-limbic coupling during cue-exposure. An exploratory analysis revealed that higher ventral caudate cue-reactivity was associated with stronger cue-induced arousal and craving in dependent users, whereas this pattern was reversed in non-dependent users.Conclusions Together the present findings suggest that an incentive sensitization of the ventral striatal reward system may promote excessive drug use in humans, whereas adaptations in dorsal striatal systems engaged in habit formation may promote the transition to addictive use.