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Putkinen, V. J.

Publications and source records attributed to Putkinen, V. J..

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Endogenous Opioid System Modulates Neural Activation During Emotion Regulation

Emotion regulation is critical for adaptive functioning and mental health. Functional neuroimaging studies have identified distributed frontal, parietal, and limbic networks involved in emotion regulation, particularly during cognitive reappraisal. However, the neurochemical mechanisms underlying individual differences in emotion regulation remain poorly understood. The endogenous opioid system is a promising candidate because -opioid receptor systems acts as a stress buffer and modulates emotional responses to both rewarding and aversive stimuli We used positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to examine whether baseline -opioid receptor (MOR) availability is associated with haemodynamic responses during emotion regulation through reappraisal. Participants underwent [11C]carfentanil PET imaging to quantify MOR availability and subsequently completed an fMRI task involving passive viewing of emotional images and cognitive reappraisal of their emotions during image viewing As expected, fMRI revealed engagement of the dorsolateral prefrontal cortex and inferior parietal lobule during cognitive reappraisal. Baseline MOR availability predicted blood oxygenation level-dependent (BOLD) responses in frontal, temporal, and parietal regions: individuals with higher MOR availability showed a larger difference between regulation and viewing trials in the temporal pole, angular gyrus, anterior insula, thalamus, and inferior frontal gyrus. These associations were driven primarily by stronger responses during passive viewing, although some regions also showed evidence of reduced responses during active reappraisal. These findings suggest that higher endogenous opioid tone is associated with stronger recruitment of distributed frontal, temporal, and parietal networks during emotional stimulus processing as well as attenuation of activity in some of these regions during cognitive reappraisal. Thus, while higher MOR availability is associated with enhanced neural responsiveness to emotional stimuli, these responses can nevertheless be effectively modulated through deliberate emotion regulation.

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Attentional reconfiguration during acute and sustained fear

BACKGROUNDFear is a fundamental survival mechanism that both enhances the chances of survival by rapid detection and adaptive responses to potential threat and by optimizing sensory input and cognitive processing. Here we used naturalistic design with eye tracking to map the spatiotemporal dynamics of attention and arousal during fearful events with slow and fast temporal dynamics. METHODS21 participants watched a full-length horror movie while their eye-movements were recoded with eye tracker. Moment-to-moment intensity of sustained fear as well as the onsets of the jump scares (acute fear) were annotated and used to predict gaze parameters (fixation duration & counts, blink frequency, saccade amplitude, pupil size and intersubject synchronization of gaze position). RESULTSAcute fear events led to shortening of fixation duration, suppression of blinking, as well as increase of fixation count, saccade amplitude, and pupil size. Sustained fear was in turn associated with increased pupil size and decrease in blinking and saccade amplitude. These effects remained significant when controlling for luminosity. CONCLUSIONSDuring natural vision both acute and sustained fear cause rapid reconfiguration, state dependent and individual changes in visual attention prioritizing that is accompanied by increased affective arousal.

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CEREBRAL GLUCOSE UTILISATION DURING MUSICAL EMOTIONS: A MULTIMODAL FUNCTIONAL PET/MRI STUDY.

Functional magnetic resonance imaging (fMRI) studies have demonstrated music-induced activation of the blood-oxygen-level-dependent (BOLD) signal across brain networks associated with auditory perception, motor control, and emotion. However, BOLD-fMRI reflects vascular responses that may not fully capture underlying neural activity. Here, we used simultaneous [18F]fluorodeoxyglucose (FDG) functional positron emission tomography (fPET) and fMRI to examine glucose metabolism closely linked to neural activity, alongside hemodynamic responses during pleasurable music listening. Thirty-five female participants listened to self-selected pleasurable music and control stimuli while undergoing 90-minute PET-MRI scans. fPET revealed music-evoked increase in glucose consumption in auditory and motor cortices, as well as reward-related regions, including the nucleus accumbens (NAcc), caudate, insula, and orbitofrontal cortex. The fPET and fMRI results showed substantial overlap though some discrepancies were also observed. Notably, the NAcc exhibited increased glucose consumption in fPET but showed no activation in fMRI. Conversely, deactivation of the default mode network during music processing was only observed with fMRI. These results highlight the complementary nature of neurometabolic and neurovascular processes and offer novel insights into their dynamics during the processing of aesthetic rewards.

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Four-dimensional neural space for moral inference

Intuitive moral inference enables us to evaluate moral situations and judge their rightness or wrongness. Although Moral Foundations Theory provides a framework for understanding moral inference, its underlying neural basis remains unclear. To capture spontaneous neural activity during moral inference, participants were instructed to watch a film rich in moral content without making explicit judgments while undergoing fMRI scanning. Independent participants evaluated the moment-to-moment presence of twenty moral dimensions in the film. Correlation and consensus cluster analyses revealed four independent main moral dimensions: virtue, vice, hierarchy, and rebellion. While each dimension exhibited unique neural activation patterns, the temporoparietal junction and inferior parietal lobe were activated across all types of moral inference. These findings establish the low-dimensional nature for the neural basis of intuitive moral inference in everyday settings.

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Reward responses to vicarious feeding depend on BMI

Eating is inherently social for humans. Yet, most neuroimaging studies of appetite and food-induced reward have focused on studying brain responses to food intake or viewing pictures of food alone. Here we used functional magnetic resonance imaging (fMRI) to measure haemodynamic responses to "vicarious" feeding. The subjects (n=97) viewed series of short videos representing naturalistic episodes of social eating intermixed with videos without feeding / appetite related content. Viewing the vicarious feeding (versus control) videos activated motor and premotor cortices, thalamus, and dorsolateral prefrontal cortices, consistent with somatomotor and affective engagement. Responses to the feeding videos were also downregulated as a function of the participants BMI. Altogether these results suggest that seeing others eating engages the corresponding motor and affective programs in the viewers brain, potentially increasing appetite and promoting mutual feeding.

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Endogenous opioid system modulates proximal and distal threat signals in the human brain

BACKGROUNDFear promotes rapid detection of threats and appropriate fight-or-flight responses. The endogenous opioid system modulates responses to pain and psychological stressors. Opioid agonists also have also anxiolytic effects. Fear and anxiety constitute major psychological stressors for humans, yet the contribution of the opioid system to acute human fear remains poorly characterized. METHODSWe induced intense unconditioned fear in the subjects by gradually exposing them to a living constrictor snake (threat trials) versus an indoor plant (safety trials). Brain haemodynamic responses were recorded from 33 subjects during functional magnetic resonance imaging (fMRI). In addition, 15 subjects underwent brain positron emission tomography (PET) imaging using [11C]carfentanil, a high affinity agonist radioligand for -opioid receptors (MORs). PET studies under threat or safety exposure were performed on separate days. Pupillary arousal responses to snake and plant exposure were recorded in 36 subjects. Subjective fear ratings were measured throughout the experiments. RESULTSSelf-reports and pupillometric responses confirmed significant experience of fear and autonomic activation during the threat trials. fMRI data revealed that proximity with the snake robustly engaged brainstem defense circuits as well as thalamus, dorsal attention network, and motor and premotor cortices. These effects were diminished during repeated exposures. PET data revealed that [11C]carfentanil binding to MORs was significantly higher during the fear versus safety condition, and the acute haemodynamic responses to threat were dependent on baseline MOR binding in the cingulate gyrus and thalamus. Finally, baseline MOR tone predicted dampening of the haemodynamic threat responses during the experiment. CONCLUSIONSPreparatory response during acute fear episodes involves a strong motor component in addition to the brainstem responses. These haemodynamic changes are coupled with a deactivation of the opioidergic circuit, highlighting the role of MORs in modulating the human fear response.

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Pleasurable music activates cerebral μ-opioid receptors: A combined PET-fMRI study

The -opioid receptor (MOR) system mediates incentive motivation and the hedonic component of primary rewards such as food and sex. However, there is no direct in vivo evidence for the involvement of the MOR system in pleasure derived from aesthetic rewards such as music. We measured MOR activation with positron emission tomography (PET) and the agonist radioligand [11C] carfentanil with high affinity for MORs during the listening of pleasurable music and neutral baseline condition. Haemodynamic responses to pleasurable music were measured using functional magnetic resonance imaging (fMRI). The PET results revealed that pleasurable music increased [11C]carfentanil binding in several cortical and subcortical regions, including ventral striatum and orbitofrontal cortex, known to contain "hedonic hotspots". Individual variation in baseline MOR tone influenced pleasure-dependent haemodynamic responses during music listening in regions associated with interoceptive, sensorimotor, and reward processing. Our results provide the first-ever neuroimaging evidence that listening to pleasurable music modulates MOR system activation and indicate that the -opioid system governs complex aesthetic rewards in addition to biologically salient primary rewards.

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Decoding brain basis of laughter and crying in natural scenes.

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.

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Neural responses to biological motion distinguish autistic and schizotypal traits in the general population

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.

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Accurate sex classification from neural responses to sexual stimuli

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.

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Aberrant motor contagion of emotions in psychopathy and high-functioning autism

Psychopathy and autism are both associated with aberrant social interaction and communication, yet only psychopaths are markedly antisocial and violent. Here we compared the functional neural alterations underlying these two different phenotypes with distinct patterns of socioemotional difficulties. We studied 19 incarcerated male offenders with high psychopathic traits, 20 males with high-functioning autism and 19 age-matched healthy controls. All groups underwent functional magnetic resonance imaging while they viewed dynamic happy, angry and disgust facial expressions or listened to laughter and crying sounds. Psychopathy was associated with reduced somatomotor responses to almost all expressions, while subjects with autism demonstrated less marked and emotion-specific alterations in the somatomotor area. These data suggest that psychopathy and autism involve both common and distinct functional alterations in the brain networks involved in socioemotional processing.

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Endogenous μ-opioid receptor system modulates sex drive in human males

The endogenous mu-opioid receptor (MOR) system modulates a multitude of social and reward-related functions, and exogenous opiates also influence sex drive in humans and animals. Sex drive shows substantial variation across humans, and it is possible that individual differences in MOR availability underlie interindividual of variation in human sex drive. Here we measured healthy male subjects (n=52) brains MOR availability with positron emission tomography (PET) using an agonist radioligand, [11C]carfentanil, that has high affinity for MORs. Sex drive was measured using self-reports of engaging in sexual behaviour (sex with partner and masturbating). Bayesian hierarchical regression analysis revealed that sex drive was positively associated with MOR availability in cortical and subcortical areas, notably in caudate nucleus, hippocampus, and cingulate cortices. These results were replicated in full-volume GLM analysis. These widespread effects are in line with high spatial autocorrelation in MOR expression in human brain. Complementary voxel-based morphometry analysis (n=108) provided limited evidence for association between sex drive and cortical density in the midcingulate cortex. We conclude that endogenous MOR tone is associated with individual differences in sex drive in human males.

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