Biology subjects

Hirvonen, J.

Publications and source records attributed to Hirvonen, J..

At least 19 recordsLinked to original sources

bioRxiv2025

Physical exercise and brain network dynamics: reduction of frontoparietal-striatal connectivity following 1 hour of aerobic cycling

Physical exercise is beneficial for metabolic health and cognitive performance. In addition, exercise can be highly pleasurable and and serves as an effective stress reliever. Extant studies have highlighted frontal, parietal, and subcortical brain changes following acute bouts of exercise. However, slower, slightly delayed brain correlates after exercise at the network level have not been studied. Therefore, this studys objective was to investigate the changes in dynamic functional connectivity after 60 minutes of exercise in healthy males. Here we measured a 6-minute resting state fMRI in 24 young males at baseline and after a 60-minute cycling exercise challenge. Apart from routine preprocessing, the data were denoised with FSL-FIX and modeled with i) leading eigenvector dynamics analysis (LEiDA) to probe whole brain network dynamics and ii) with group independent component analysis (ICA) and dual regression to quantify static brain connectivity. The within subject statistical tests compared baseline to post-exercise conditions. We found that a striato-fronto-parietal network is destabilized after exercise, as indicated by a lower probability of occurrence in dynamic analysis through LEiDA. The brain areas in the network include the bilateral caudate, putamen and pallidum as well as middle orbitofrontal, frontal operculum, frontal trigonum and inferior parietal cortices. No differences between baseline and post exercise conditions were found in the dual regression of the group ICA components. We conclude that 60 minutes of cycling causes a prolonged effect in brain network dynamics, reducing synchronization between the striatum and frontoparietal networks with respect to baseline. This provides insights into the network-level neural correlates of aerobic exercise, which may be directly linked with the stress relieving effects of physical exercise.

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bioRxiv2025

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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bioRxiv2025

Exposure to bullying engages social distress circuits in the adolescent and adult brain

Despite advances in understanding the psychological and social consequences of peer victimization, the immediate effects of bullying on the central nervous system remain elusive. Here we mapped the neural responses to simulated bullying in adolescents and adults and tested whether these responses are associated with real-life victimization experiences. Fifty-one adolescents aged 11-14 years, and 47 adults underwent a functional MRI (fMRI) while watching first-person videos of bullying (victimization) in the school environment, as well as neutral and positive social interactions in a similar setting. Exposure to bullying versus positive social interaction engaged the socio-emotional and threat response systems, as well as regions related to social cognition, sensory and interoceptive processing, and motor control. These responses were consistent across adolescents and adults and dependent on the current and past victimization experiences of the participants. This large-scale activation of neural systems subserving socioemotional, somatosensory, and interoceptive processing highlights how peer victimization evokes a severe stress and alarm state in the central nervous system.

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bioRxiv2024

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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bioRxiv2024

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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bioRxiv2024

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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bioRxiv2024

Dopamine D2R and opioid MOR availability in autism spectrum disorder

Opioid and dopamine receptor systems are implicated in the pathoetiology of autism, but in vivo human brain imaging evidence for their role remains elusive. Here, we investigated regional type 2 dopamine and mu-opioid receptor (D2R and MOR, respectively) availabilities and regional interactions between the two neuromodulatory systems associated with autism spectrum disorder (ASD). In vivo positron emission tomography (PET) with radioligands [11C]raclopride (D2R) and [11C]carfentanil (MOR) was carried out in 16 adult males with high functioning ASD and 19 age and sex matched controls. Regional group differences in D2R and MOR receptor availabilities were tested with linear mixed models and associations between regional receptor availabilities were examined with correlations. There were no group differences in whole-brain voxel-wise analysis of DR2 but ROI analysis presented a lower overall mean D2R availability in striatum of the ASD versus control group. Post hoc regional analysis revealed reduced D2R availability in nucleus accumbens of the ASD group. The whole-brain voxel-wise analysis of MOR revealed precuneal up-regulation in the ASD group, but there was no overall group difference in the ROI analysis for MOR. MOR down-regulation was observed in the hippocampi of the ASD group in a post hoc analysis. Regional correlations between D2R and MOR availabilities were weaker in the ASD group versus control group in the amygdala and nucleus accumbens. These alterations may translate to disrupted modulation of social motivation and reward in ASD.

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bioRxiv2023

Endogenous opioid receptor system mediates costly altruism in the human brain

Functional neuroimaging studies suggest that a large-scale brain network transforms others pain into its vicarious representation in the observer, potentially modulating helping behaviour. The neuromolecular basis of individual differences in vicarious pain and helping, however, have remain poorly understood. Here we investigated the role of the endogenous -opioid receptor (MOR) system - known for its role in analgesia and sociability - in altruistic costly helping. MOR density was measured with high-affinity agonist radioligand [11C]carfentanil. In a separate fMRI experiment, participants could choose to donate money to reduce the pain of the confederate who was subjected to electric shocks of varying intensity. We found that subjects were in general willing to engage in costly helping, and haemodynamic activity in amydala, anterior insula, anterior cingulate cortex, striatum, primary motor cortex, primary somatosensory cortex, and thalamus increased when participants witnessed the pain of others. These haemodynamic responses were negatively associated with MORs availability in the striatolimbic and cortical emotion circuits. In turn, haemodynamic responses during helping were positively associated with MOR availability in the anterior cingulate cortex and hippocampus. Altogether these data suggest that the endogenous MOR system modulates the processing of altruistic behaviour and costly helping in the human brain.

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bioRxiv2023

Aberrant type 2 dopamine receptor availability in criminal psychopathy

BackgroundPsychopathy is characterized by antisocial behavior, poor behavioral control and lacking empathy, and structural alterations in the corresponding neural circuits. Molecular brain basis of psychopathy remains poorly characterized. MethodsHere we studied type 2 dopamine receptor (D2R) and mu-opioid receptor (MOR) availability in convicted violent offenders with high psychopathic traits (n=11) and healthy matched controls (n=19) using positron emission tomography (PET). D2R were measured with radioligand [11C]raclopride and MORs with radioligand [11C]carfentanil. ResultsPsychopathic subjects had lowered D2R availability in caudate and putamen, and D2R striatal availability was also associated with degree of psychopathic traits in this prisoner sample. No group differences were found in MOR availability, although in the prisoner sample, psychopathic traits were negatively correlated with MOR availability amygdala and nucleus accumbens. ConclusionsWe conclude that D2R signaling could be the putative neuromolecular pathway for psychopathy, whereas evidence for the aberrant MOR system is more limited.

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bioRxiv2022

Endogenous opioid release following orgasm in man: A combined PET-fMRI study

Sex is one of the most rewarding and motivating behaviours for humans. Endogenous mu-opioid receptor system (MORs) plays a key role in the mammalian reward circuit. Both human and animal experiments suggest the involvements of MORs in human sexual pleasure, yet this hypothesis currently lacks in vivo support. We used positron emission tomography (PET) with the radioligand [11C]carfentanil, which has high affinity for MORs to quantify endogenous opioid release following orgasm in man. Subjects were scanned twice: Once immediately after reaching an orgasm and once in a baseline state. Haemodynamic activity was measured with functional magnetic resonance imaging during penile stimulation from partner. The PET data revealed significant opioid release in hippocampus. Haemodynamic activity in somatosensory and motor cortices as well as hippocampus and thalamus increased during penile stimulation, and thalamic activation was linearly dependent on self-reported sexual arousal. Altogether these data show that endogenous opioidergic activation in the medial temporal lobe is centrally involved in sexual arousal.

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bioRxiv2022

Is mild ADHD beneficial: Brain criticality is maximal with moderate ADHD symptom scores

Attention-deficit/hyperactivity disorder (ADHD) is characterized by a continuum of symptoms including inattentiveness, hyperfocus, and hyperactivity, that are manifested, e.g., in increased reaction-time variability in continuous performance tasks (CPTs). Framework of brain criticality posits that brains operate in an extended regime of critical-like dynamics where neuronal and behavioral processes exhibit scale-free long-range temporal correlations (LRTCs) across hundreds of seconds. Whether shifts across critical-like brain states and parallel changes in LRTCs underlie ADHD symptoms has remained unexplored. We investigated whether brain-state shifts towards excitation-dominated dynamics and associated changes in LRTCs could explain ADHD symptoms and their continuum across individuals. We measured brain activity with magnetoencephalography (MEG) during resting and two CPTs from adult participants diagnosed with ADHD (N = 34) and neurotypical controls (NC) (N = 36) and characterized criticality with LRTCs of neuronal oscillations. ADHD patients exhibited stronger LRTCs than NC in low (5-20 Hz) and high (30-100 Hz) frequencies and dichotomous task effects. High-frequency LRTCs were positively correlated with ADHD symptoms, while beta-band (20-30 Hz) activity exhibited a quadratic correlation, peaking at moderate scores across the ADHD and NC cohorts being smaller for low and high scores. We demonstrate that ADHD is associated with shifts in brain criticality in resting-and task-state brain dynamics. Individuals with intermediate symptom scores across the NC and ADHD cohorts operated at peak criticality that is associated with a several functional benefits The progressive shift towards the supercritical side of the critical regime becomes detrimental only at moderate and severe symptoms.

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bioRxiv2022

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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bioRxiv2022

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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bioRxiv2022

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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bioRxiv2021

Functional organization of social perception in the human brain

Humans rapidly extract diverse and complex information from ongoing social interactions, but the perceptual and neural organization of the different aspects of social perception remains unresolved. We showed short film clips with rich social content to 97 healthy participants while their haemodynamic brain activity was measured with fMRI. The clips were annotated moment-to-moment for 112 social features. Cluster analysis revealed that 13 dimensions were sufficient for describing the social perceptual space. Regression analysis was used to map regional neural response profiles to different social features. Multivariate pattern analysis was then utilized to establish the spatial specificity of these responses. The results revealed a gradient in the processing of social information in the brain. Posterior temporal and occipital regions were broadly tuned to most social dimensions and the classifier revealed that these responses showed spatial specificity for social dimensions; in contrast Heschl gyri and parietal areas were also broadly associated with different social signals, yet the spatial patterns of responses did not differentiate social dimensions. Frontal and subcortical regions responded only to a limited number of social dimensions and the spatial response patterns did not differentiate social dimension. Altogether these results highlight the distributed nature of social processing in the brain.

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bioRxiv2021

Mu-opioid receptor system modulates responses to vocal bonding and distress signals in humans

Laughter is a contagious prosocial signal that conveys bonding motivation; adult crying conversely communicates desire for social proximity by signalling distress. Endogenous mu-opioid receptors (MORs) modulate sociability in humans and non-human primates. In this combined PET-fMRI study (n=17) we tested whether central MOR tone is associated with regional brain responses to social signals of laughter and crying sounds. MOR availability was measured with positron emission tomography using high-affinity agonist radioligand [11C]carfentanil. Haemodynamic responses to social laughter and crying sounds were measured using functional magnetic resonance imaging (fMRI). Social laughter evoked activation in the auditory cortex, insula, cingulate cortex, amygdala, primary and secondary somatosensory cortex, primary and secondary motor cortex; crying sounds led to more restricted activation in auditory cortex and nearby areas. MOR availability was negatively correlated with the haemodynamic responses to social laughter in primary and secondary somatosensory cortex, primary and secondary motor cortex, posterior insula, posterior cingulate cortex, precuneus, cuneus, temporal gyri, and lingual gyrus. For crying-evoked activations, MOR availability was negatively correlated with medial and lateral prefrontal haemodynamic responses. Altogether our findings highlight the role of MOR system in modulating acute brain responses to both positive and negative social signals.

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bioRxiv2021

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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bioRxiv2020

Cerebral μ-opioid and CB1-receptor systems have distinct roles in human feeding behavior

Eating behavior varies greatly between healthy individuals, but the neurobiological basis of these trait-like differences in feeding remains unknown. Central {micro}-opioid receptors (MOR) and cannabinoid CB1-receptors (CB1R) regulate energy balance via multiple neural pathways, promoting food intake and reward. Because obesity and eating disorders have been associated with alterations in the brains opioid and endocannabinoid signaling, the variation in MOR and CB1R system function could potentially underlie distinct eating behavior phenotypes. In this retrospective positron emission tomography (PET) study, we analyzed [11C]carfentanil PET scans of MORs from 92 healthy subjects (70 males and 22 females), and [18F]FMPEP-d2 scans of CB1Rs from 35 subjects (all males, all also included in the [11C]carfentanil sample). Eating styles were measured with the Dutch Eating Behavior Questionnaire (DEBQ). We found that lower cerebral MOR availability was associated with increased external eating - individuals with low MORs reported being more likely to eat in response to environments palatable food cues. CB1R availability was associated with multiple eating behavior traits. We conclude that although MORs and CB1Rs overlap anatomically and functionally in the brain, they have distinct roles in mediating individual feeding patterns.

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