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Difficulties in social interactions characterize both autism and schizophrenia and are correlated in the neurotypical population. It is unknown whether this represents a shared etiology or superficial phenotypic overlap. Both conditions exhibit atypical neural activity in response to the perception of social stimuli and decreased neural synchronization between individuals. This study investigated if neural activity and neural synchronization associated with biological motion perception are differentially associated with autistic and schizotypal traits in the neurotypical population. Participants viewed naturalistic social interactions while hemodynamic brain activity was measured with fMRI, which was modeled against a continuous measure of the extent of biological motion. General linear model analysis revealed that biological motion perception was associated with neural activity across the action observation network. However, intersubject phase synchronization analysis revealed neural activity to be synchronized between individuals in occipital and parietal areas but desynchronized in temporal and frontal regions. Autistic traits were associated with decreased neural activity (precuneus and middle cingulate gyrus), and schizotypal traits were associated with decreased neural synchronization (middle and inferior frontal gyri). Biological motion perception elicits divergent patterns of neural activity and synchronization, which dissociate autistic and schizotypal traits in the general population, suggesting that they originate from different neural mechanisms.

Emotions modulate behavioral priorities via central and peripheral nervous systems. Understanding emotions from the perspective of specific neurotransmitter systems is critical, because of the central role of affect in multiple psychopathologies and the role of specific neuroreceptor systems as corresponding drug targets. Here, we provide an integrative overview of molecular imaging studies that have targeted the human emotion circuit at the level of specific neuroreceptors and transmitters. We focus specifically on opioid, dopamine, and serotonin systems, given their key role in modulating motivation and emotions, and discuss how they contribute to both healthy and pathological emotions.

Laughter and crying are universal signals of prosociality and distress, respectively. Here we investigated the functional brain basis of perceiving laughter and crying using naturalistic functional magnetic resonance imaging (fMRI) approach. We measured haemodynamic brain activity evoked by laughter and crying in three experiments with 100 subjects in each. The subjects i) viewed a 20-minute medley of short video clips, and ii) 30 minutes of a full-length feature film, and iii) listened to 15 minutes of a radio play that all contained bursts of laughter and crying. Intensity of laughing and crying in the videos and radio play was annotated by independent observes, and the resulting time series were used to predict hemodynamic activity to laughter and crying episodes. Multivariate pattern analysis (MVPA) was used to test for regional selectivity in laughter and crying evoked activations. Laughter induced widespread activity in ventral visual cortex and superior and middle temporal and motor cortices. Crying activated thalamus, cingulate cortex along the anterior-posterior axis, insula and orbitofrontal cortex. Both laughter and crying could be decoded accurately (66-77% depending on the experiment) from the BOLD signal, and the voxels contributing most significantly to classification were in superior temporal cortex. These results suggest that perceiving laughter and crying engage distinct neural networks, whose activity suppresses each other to manage appropriate behavioral responses to others’ bonding and distress signals.Significance statementLaughter and crying are universal signals of prosociality and distress, respectively. They occur in complex, dynamic social settings with variable and dynamically evolving time courses. Here we used functional magnetic resonance imaging experiments and statistical pattern recognition for disentangling the neural systems that encode laughter and crying signals from dynamic and highly naturalistic scenes. These results show that separable neural circuits are engaged in processing distinct types of social attachment cues, and that pattern recognition during dynamic scene perception allows reliable separation of laughter and crying evoked activation patterns. Coordinated activity of these networks allows managing appropriate behavioral responses to others’ bonding and distress signals.

Music can induce strong subjective experience of emotions, but it is debated whether these responses engage the same neural circuits as emotions elicited by biologically significant events. We examined the functional neural basis of music-induced emotions in a large sample (n = 102) of subjects who listened to emotionally engaging (happy, sad, fearful, and tender) pieces of instrumental music while their hemodynamic brain activity was measured with functional magnetic resonance imaging (fMRI). Ratings of the four categorical emotions and liking were used to predict hemodynamic responses in general linear model (GLM) analysis of the fMRI data. Multivariate pattern analysis (MVPA) was used to reveal discrete neural signatures of the four categories of music-induced emotions. To map neural circuits governing non-musical emotions, the subjects were scanned while viewing short emotionally evocative film clips. The GLM revealed that most emotions were associated with activity in the auditory, somatosensory, and motor cortices, cingulate gyrus, insula, and precuneus. Fear and liking also engaged the amygdala. In contrast, the film clips strongly activated limbic and cortical regions implicated in emotional processing. MVPA revealed that activity in the auditory cortex and primary motor cortices reliably discriminated the emotion categories. Our results indicate that different music-induced basic emotions have distinct representations in regions supporting auditory processing, motor control, and interoception but do not strongly rely on limbic and medial prefrontal regions critical for emotions with survival value.

Difficulties in social interactions are common to both autism and schizophrenia, and contribute to correlated autistic and schizotypal traits in the neurotypical population. It remains unresolved whether this represents a shared etiology or a superficial phenotypic overlap. Both conditions are associated with atypical neural activity in response to the perception of social stimuli, and also decreased neural synchronization between individuals that may prohibit establishing shared experiences. This study sought to establish if neural activity and neural synchronization associated with biological motion perception are differentially associated with autistic and schizotypal traits in the neurotypical population. Participants watched an audiovisual montage of naturalistic social interactions whilst hemodynamic brain activity was measured with fMRI. A separate sample of participants provided a continuous measure of the extent of biological motion, which was used to predict hemodynamic activity. General Linear Model analysis revealed that biological motion perception was associated with neural activity across the action-observation network. However, inter-subject phase synchronization analysis revealed that neural activity synchronized between individuals in occipital and parietal areas, but de-synchronized in temporal and frontal regions. Autistic traits were associated with a decrease in neural activity (precuneus, middle cingulate gyrus) and schizotypal traits were associated with a decrease in neural synchronization (middle and inferior frontal gyri). Biological motion perception elicits convergent and divergent patterns of neural activity and neural synchronization, and are differentially associated with shared traits related with autism and schizophrenia in the general population, suggesting that they originate from different neural mechanisms.

Sex differences in brain activity evoked by sexual stimuli remain elusive despite robust evidence for stronger enjoyment of and interest towards sexual stimuli in men than in women. To test whether visual sexual stimuli evoke different brain activity patterns in men and women, we measured haemodynamic brain activity induced by visual sexual stimuli in two experiments in 91 subjects (46 males). In one experiment, the subjects viewed sexual and non-sexual film clips and dynamic annotations for nudity in the clips was used to predict their hemodynamic activity. In the second experiment, the subjects viewed sexual and non-sexual pictures in an event-related design. Males showed stronger activation than females in the visual and prefrontal cortices and dorsal attention network in both experiments. Furthermore, using multivariate pattern classification we could accurately predict the sex of the subject on the basis of the brain activity elicited by the sexual stimuli. The classification generalized across the experiments indicating that the sex differences were consistent. Eye tracking data obtained from an independent sample of subjects (N = 110) showed that men looked longer than women at the chest area of the nude female actors in the film clips. These results indicate that visual sexual stimuli evoke discernible brain activity patterns in men and women which may reflect stronger attentional engagement with sexual stimuli in men than women.

Purpose The three positron emission tomography (PET) imaging compounds: (2S,4R)-4-[18F]Fluoroglutamine ([18F]FGln), L-[methyl-11C]Methionine ([11C]Met), and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) were investigated to contrast their ability to image orthotopic BT4C gliomas in BDIX rats. Two separate small animal imaging systems were compared for their tumor detection potential. Dynamic acquisition of [18F]FGln was evaluated with multiple pharmacokinetic models for future quantitative comparison. Procedures Up to four imaging studies were performed on each orthotopically grafted BT4C glioma-bearing BDIX rat subject (n = 16) on four consecutive days. First, a DOTAREM® contrast enhanced MRI followed by attenuation correction CT and dynamic PET imaging with each radiopharmaceutical (20 min [11C]Met, 60 min [18F]FDG, and 60 min [18F]FGln with either the Molecubes PET/CT (n = 5) or Inveon PET/CT cameras (n = 11). Ex vivo brain autoradiography was completed for each radiopharmaceutical and [18F]FGln pharmacokinetics were studied by injecting 40 MBq into healthy BDIX rats (n = 10) and collecting blood samples between 5 and 60 min. Erythrocyte uptake, plasma protein binding and plasma parent-fraction were combined to estimate the total blood bioavailability of [18F]FGln over time. The corrected PET-image blood data was then applied to multiple pharmacokinetic models. Results Average BT4C tumor-to-healthy brain tissue uptake ratios (TBR) for PET images reached maxima of: [18F]FGln TBR: 1.99 ± 0.19 (n = 13), [18F]FDG TBR: 1.41 ± 0.11 (n = 6), and [11C]Met TBR: 1.08 ± 0.08, (n = 12) for the dynamic PET images. Pharmacokinetic modeling in dynamic [18F]FGln studies suggested both reversible and irreversible uptake play a similar role. Imaging with Inveon and Molecubes yielded similar end-result ratios with insignificant differences (p > 0.25). Conclusions In orthotopic BT4C gliomas, [18F]FGln may offer improved imaging versus [11C]Met and [18F]FDG. No significant difference in normalized end-result data was found between the Inveon and Molecubes camera systems. Kinetic modelling of [18F]FGln uptake suggests that both reversible and irreversible uptake play an important role in BDIX rat pharmacokinetics.

Psychopathy is characterized by persistent antisocial behavior, impaired empathy, and egotistical traits. These traits vary also in normally functioning individuals. Here, we tested whether such antisocial personalities are associated with similar structural and neural alterations as those observed in criminal psychopathy. Subjects were 100 non-convicted well-functioning individuals, 19 violent male offenders, and 19 matched controls. Subjects underwent T1-weighted magnetic resonance imaging and viewed movie clips with varying violent content during functional magnetic resonance imaging. Psychopathic traits were evaluated with Levenson Self-Report Psychopathy Scale (controls) and Psychopathy Checklist-Revised (offenders). Psychopathic offenders had lower gray matter density (GMD) in orbitofrontal cortex and anterior insula. In the community sample, affective psychopathy traits were associated with lower GMD in the same areas. Viewing violence increased brain activity in periaqueductal grey matter, thalamus, somatosensory, premotor, and temporal cortices. Psychopathic offenders had increased responses to violence in thalamus and orbitofrontal, insular, and cingulate cortices. In the community sample, impulsivity-related psychopathy traits were positively associated with violence-elicited responses in similar areas. We conclude that brain characteristics underlying psychopathic spectrum in violent psychopathy are related to those observed in well-functioning individuals with asocial personality features.

Music can induce strong subjective experience of emotions, but it is debated whether these responses engage the same neural circuits as emotions elicited by biologically significant events. We examined the functional neural basis of music-induced emotions in a large sample (n=102) of subjects who listened to emotionally engaging (happy, sad, fearful, and tender) pieces of instrumental music while their haemodynamic brain activity was measured with functional magnetic resonance imaging (fMRI). Ratings of the four categorical emotions and liking were used to predict haemodynamic responses in general linear model (GLM) analysis of the fMRI data. Multivariate pattern analysis (MVPA) was used to reveal discrete neural signatures of the four categories of music-induced emotions. To map neural circuits governing non-musical emotions, the subjects were scanned while viewing short emotionally evocative film clips. The GLM revealed that most emotions were associated with activity in the auditory, somatosensory and motor cortices, cingulate gyrus, insula, and precuneus. Fear and liking also engaged the amygdala. In contrast, the film clips strongly activated limbic and cortical regions implicated in emotional processing. MVPA revealed that activity in the auditory cortex in particular as well as in the primary motor cortices reliably discriminated the emotion categories. Our results indicate that different music-induced basic emotions have distinct representations in regions supporting auditory processing, motor control, somatosensation and interoception but do not strongly rely on limbic and medial prefrontal regions critical for emotions with survival value.

Emotions modulate behavioural priorities at the central and peripheral nervous system. Understanding emotions from the perspective of specific neurotransmitter systems is critical, because the central role of affect in multiple psychopathologies, and the role of specific neuroreceptor systems as corresponding drug targets. Here we provide an integrative overview of molecular imaging studies that have targeted the human emotion circuit at the level of specific neuroreceptors and transmitters. We focus specifically on opioid, dopamine and serotonin system given their key role in modulating motivation and emotions, and discuss how they contribute to both healthy and pathological emotions.

Fear protects organisms by increasing vigilance and preparedness, and by coordinating survival responses during life-threatening encounters. The fear circuit must thus operate on multiple timescales ranging from preparatory sustained alertness to acute fight-or-flight responses. Here we studied the brain basis of sustained and acute fear using naturalistic functional magnetic resonance imaging (fMRI) enabling analysis of different time-scales of fear responses. Subjects (N ​= ​37) watched feature-length horror movies while their hemodynamic brain activity was measured with fMRI. Time-variable intersubject correlation (ISC) was used to quantify the reliability of brain activity across participants, and seed-based phase synchronization was used for characterizing dynamic connectivity. Subjective ratings of fear were used to assess how synchronization and functional connectivity varied with emotional intensity. These data suggest that acute and sustained fear are supported by distinct neural pathways, with sustained fear amplifying mainly sensory responses, and acute fear increasing activity in brainstem, thalamus, amygdala and cingulate cortices. Sustained fear increased ISC in regions associated with acute fear, and also amplified functional connectivity within this network. The results were replicated in an independent experiment with a different subject sample and stimulus movie. The functional interplay between cortical networks involved in sustained anticipation of, and acute response to, threat involves a complex and dynamic interaction that depends on the proximity of threat, and the need to employ threat appraisals and vigilance for decision making and response selection.

Fear protects organisms by increasing vigilance and preparedness, and by coordinating survival responses during life-threatening encounters. The fear circuit must thus operate on multiple timescales ranging from preparatory sustained alertness to acute fight-or-flight responses. Here we studied the brain basis of sustained (“looming”) and acute fear using naturalistic functional magnetic resonance imaging (fMRI) enabling analysis of different time-scales of fear responses. Subjects (N = 51) watched feature-length horror movies while their hemodynamic brain activity was measured with fMRI. Time-variable intersubject correlation (ISC) was used to quantify the reliability of brain activity across participants, and seed-based phase synchronization was used for characterizing dynamic connectivity. Subjective ratings of fear were obtained from a separate sample, and were used to assess how synchronization and functional connectivity varied with emotional intensity. These data suggest that acute and sustained fear are supported by distinct neural pathways, with sustained fear amplifying mainly sensory responses, and acute fear increasing activity in brainstem, thalamus, amygdala and cingulate cortices. Sustained fear increased ISC in regions associated with acute fear, and also amplified functional connectivity within this network. The results were replicated in two independent experiments with different subject samples. The functional interplay between cortical networks involved in sustained anticipation of, and acute response to, threat involves a complex and dynamic interaction that depends on the proximity of threat, and the need to employ threat appraisals and vigilance for decision making and response selection.

Emotions can be characterized by dimensions of arousal and valence (pleasantness). While the functional brain bases of emotional arousal and valence have been actively investigated, the neuromolecular underpinnings remain poorly understood. We tested whether the opioid and dopamine systems involved in reward and motivational processes would be associated with emotional arousal and valence. We used in vivo positron emission tomography to quantify μ-opioid receptor and type 2 dopamine receptor (MOR and D2R, respectively) availability in brains of 35 healthy adult females. During subsequent functional magnetic resonance imaging carried out to monitor hemodynamic activity, the subjects viewed movie scenes of varying emotional content. Arousal and valence were associated with hemodynamic activity in brain regions involved in emotional processing, including amygdala, thalamus, and superior temporal sulcus. Cerebral MOR availability correlated negatively with the hemodynamic responses to arousing scenes in amygdala, hippocampus, thalamus, and hypothalamus, whereas no positive correlations were observed in any brain region. D2R availability—here reliably quantified only in striatum—was not associated with either arousal or valence. These results suggest that emotional arousal is regulated by the MOR system, and that cerebral MOR availability influences brain activity elicited by arousing stimuli.