Biology subjects

Nummenmaa, L.

Publications and source records attributed to Nummenmaa, L..

At least 55 records · Page 3Linked to original sources

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

The predictive power of mRNA mapping for Cannabinoid 1 receptor protein in the human brain

Type 1 cannabinoid (CB1) receptor is expressed in cortex, hippocampus, amygdala, basal ganglia, and cerebellum. With the help of the Allen Human Brain Atlas, genomic maps visualize not only the gene expression across whole brain regions, but also the functional profile of brain structures. Therefore, it is more timely than ever to integrate genomic mapping from brain mRNA atlas with the protein expression from positron emission tomography (PET) scans for better understanding of CB1 receptor of the human brain. F18-FMPEP-d2 PET scans were retrieved from the AIVO neuroinformatics project. Autoradiography data were based on the study with H3-CP55940. mRNA expressions of CNR1 gene (Cannabinoid receptor 1) were downloaded from the Allen Human Brain Atlas. Volume of distribution (VT) from F18-FMPEP-d2 PET scans, CNR1 gene expression, and H3-CP55940 binding were calculated and Spearman correlation analysis was performed. Also, a meta-analysis was done to investigate the association between protein expression from PET and mRNA expression from the Allen Human Brain Atlas. Between VT of F18-FMPEP-d2 PET scans and CNR1 mRNA expression, moderate strength of correlation was observed (rho = 0.5026, p = 0.0354). Strong positive correlation was also found between CNR1 mRNA expression and H3-CP55940 binding (rho = 0.6727, p = 0.0281), validating the finding between F18-FMPEP-d2 PET scans and CNR1 mRNA. From the meta-analysis, the correlation coefficient ranged from -0.46 to 0.99, with a pooled effect of 0.58. In conclusion, the moderate to strong associations between gene and protein expression for CB1 receptor in the human brain were observed that CNR1 mRNA mapping might have the predictive power for in vivo CB1 receptor protein expression. From the meta-analysis, the moderate to strong correlation was observed between mRNA expression and protein expressions across multiple genes, showing the predictive power of genes to estimate protein levels of human brains. HIGHLIGHTSO_LIWe investigated the association between CNR1 gene expression from the Allen Human Brain Atlas and type 1 cannabinoid (CB1) receptor expression from F18-FMPEP-d2 PET scans. C_LIO_LIThe moderate to strong associations between gene and protein expression for CB1 receptor in the human brain were observed that CNR1 mRNA mapping might have the predictive power for in vivo CB1 receptor protein expression. C_LIO_LIFrom the meta-analysis, the moderate to strong correlation was observed between mRNA expression and protein expressions across multiple genes, showing the predictive power of genes to estimate protein levels of human brains. C_LI

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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

Age and sex dependent variability of type 2 dopamine receptors in the human brain: A large-scale PET cohort

BACKGROUNDThe dopamine system contributes to a multitude of functions ranging from reward and motivation to learning and movement control, making it a key component in goal-directed behavior. Altered dopaminergic function is observed in neurological and psychiatric conditions. Numerous factors have been proposed to influence dopamine function, but due to small sample sizes and heterogeneous data analysis methods in previous studies their specific and joint contributions remain unresolved. METHODSIn this cross-sectional register-based study we investigated how age, sex, body mass index (BMI), as well as cerebral hemisphere and regional volume influence striatal type 2 dopamine receptor (D2R) availability in the human brain. We analyzed a large historical dataset (n=156, 120 males and 36 females) of [11C]raclopride PET scans performed between 2004 and 2018. RESULTSStriatal D2R availability decreased through age for both sexes and was higher in females versus males throughout age. BMI and striatal D2R availability were weakly associated. There was no consistent lateralization of striatal D2R. The observed effects were independent of regional volumes. These results were validated using two different spatial normalization methods, and the age and sex effects also replicated in an independent sample (n=135). CONCLUSIONSD2R density is dependent on age and sex, which may contribute to the vulnerability of neurological and psychiatric conditions involving altering D2R expression.

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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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bioRxiv2021

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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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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bioRxiv2020

Mesolimbic opioid-dopamine interaction is disrupted in obesity but recovered by weight loss following bariatric surgery

BackgroundObesity is a growing burden to health and economy worldwide. Obesity is associated with central -opioid receptor (MOR) downregulation, and the interaction between MOR and dopamine D2 receptor (D2R) system in the ventral striatum is disrupted among obese subjects. Weight loss recovers MOR function, but it remains unknown whether it also recovers aberrant opioid-dopamine interaction. Here we addressed this issue by studying subjects undergoing surgical weight loss (bariatric surgery) procedure. MethodsWe recruited 20 healthy non-obese (mean BMI 22) and 25 morbidly obese women (mean BMI 41) eligible for bariatric surgery. Brain MOR and D2R availability was measured using positron emission tomography (PET) with [11C]carfentanil and [11C]raclopride, respectively. Either Roux-en-Y gastric bypass or sleeve gastrectomy was performed to obese subjects according to standard clinical treatment. 21 obese subjects participated in the postoperative PET scanning six months after bariatric surgery. ResultsIn the control subjects, MOR and D2R availabilities were associated in the ventral striatum (r = .62) and dorsal caudate (r = .61). Preoperatively, the obese subjects had disrupted association in the ventral striatum (r = .12) but unaltered association in dorsal caudate (r = .43). The association between MOR and D2R availabilities in the ventral striatum was recovered (r = .62) among obese subjects following the surgery-induced weight loss (mean total weight loss 22 %). ConclusionsBariatric surgery and concomitant weight loss recovers the interaction between MOR and D2R in the ventral striatum in the morbidly obese. Consequently, the dysfunctional opioid-dopamine interaction in the ventral striatum is likely associated with an obese phenotype and may mediate excessive energy uptake. Striatal opioid-dopamine interaction provides a feasible target for pharmacological and behavioural interventions for treating obesity. Clinical Trials RegistrationSleevePET2, NCT01373892, http://www.clinicaltrials.gov

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bioRxiv2020

Decoding music-evoked emotions in the auditory and motor cortex

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.

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bioRxiv2020

Seasonal variation in brain mu-opioid receptor availability

Seasonal rhythms influence mood and sociability. The brain -opioid receptor (MOR) system modulates a multitude of seasonally varying socioemotional functions, but its seasonal variation remains elusive with no previously reported in vivo evidence. Here, we studied the seasonal effects on brain MOR availability via analysing a dataset (n=204) of [11C]carfentanil positron emission tomography (PET) scans of healthy volunteers. We found that seasonally varying daylength had an inverted U-shaped functional relationship with brain MOR availability. Brain regions sensitive to daylength spanned the socio-emotional brain circuits, where MOR availability formed a spring-like peak. Causal effect of daylength on brain MOR availability was further verified by a post hoc experiment with repeated PET imaging of rats (n=9) under seasonal photoperiodic simulation. Therefore, the in vivo brain MOR availability in normal humans shows significant seasonal variation, which aligns with expected seasonal variation in mood and suicidality.

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bioRxiv2020

Cerebral grey matter density is associated with neuroreceptor and neurotransporter availability: A combined PET and MRI study

Positron emission tomography (PET) can be used for in vivo measurement of specific neuroreceptors and transporters using radioligands, while voxel-based morphometric analysis of magnetic resonance images allows automated estimation of local grey matter densities. However, it is not known how regional neuroreceptor or transporter densities are reflected in grey matter densities. Here, we analyzed brain scans retrospectively from 325 subjects and compared grey matter density estimates with three different neuroreceptors and transporter availabilities. {micro}-opioid receptors (MORs) were measured with [11C]carfentanil (162 scans), dopamine D2 receptors with [11C]raclopride (91 scans) and serotonin transporters (SERT) with [11C]MADAM (72 scans). The PET data were modelled with simplified reference tissue model. Voxel-wise correlations between binding potential and grey matter density images were computed. Regional binding of all the used radiotracers was associated with grey matter density in region and ligand-specific manner independently of subjects age or sex. These data show that grey matter density and MOR and D2R neuroreceptor / SERT availability are correlated, with effect sizes (r2) ranging from 0.04 to 0.69. This suggests that future studies comparing PET outcome measure different groups (such as patients and controls) should take grey matter density differences between the groups into account.

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bioRxiv2020

Classification of emotions based on functional connectivity patterns of the human brain

Neurophysiological and psychological models posit that emotions depend on connections across wide-spread corticolimbic circuits. While previous studies using pattern recognition on neuroimaging data have shown differences between various discrete emotions in brain activity patterns, less is known about the differences in functional connectivity. Thus, we employed multivariate pattern analysis on functional magnetic resonance imaging data (i) to develop a pipeline for applying pattern recognition in functional connectivity data, and (ii) to test whether connectivity signatures differ across emotions. Six emotions (anger, fear, disgust, happiness, sadness, and surprise) and a neutral state were induced in 16 participants using one-minute-long emotional narratives with natural prosody while brain activity was measured with functional magnetic resonance imaging (fMRI). We computed emotion-wise connectivity matrices both for whole-brain connections and for 10 previously defined functionally connected brain subnetworks, and trained an across-participant classifier to categorize the emotional states based on whole-brain data and for each subnetwork separately. The whole-brain classifier performed above chance level with all emotions except sadness, suggesting that different emotions are characterized by differences in large-scale connectivity patterns. When focusing on the connectivity within the 10 subnetworks, classification was successful within the default mode system and for all emotions. We conclude that functional connectivity patterns consistently differ across different emotions particularly within the default mode system.

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bioRxiv2019

Statistical Pattern Recognition Reveals Shared Neural Signatures for Displaying and Recognizing Specific Facial Expressions

Human neuroimaging and behavioural studies suggest that somatomotor "mirroring" of seen facial expressions may support their recognition. Here we show that viewing specific facial expressions triggers the representation corresponding to that expression in the observers brain. Twelve healthy female volunteers underwent two separate fMRI sessions: one where they observed and another where they displayed three types of basic facial expressions (joy, anger and disgust). Pattern classifier based on Bayesian logistic regression was trained to classify facial expressions i) within modality (trained and tested with data recorded while observing or displaying expressions) and ii) between modalities (trained with data recorded while displaying expressions and tested with data recorded while observing the expressions). Cross-modal classification was performed in two ways: with and without functional realignment of the data across observing / displaying conditions. All expressions could be accurately classified within and also across modalities. Brain regions contributing most to cross-modal classification accuracy included primary motor and somatosensory cortices. Functional realignment led to only minor increases in cross-modal classification accuracy for most of the examined ROIs. Substantial improvement was observed in the occipito-ventral components of the core system for facial expression recognition. Altogether these results support the embodied emotion recognition model and show that expression-specific somatomotor neural signatures could support facial expression recognition.

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bioRxiv2019

Imaging real-time tactile interaction with two-person dual-coil fMRI

Studies of brain mechanisms supporting social interaction are demanding because real interaction only occurs when the persons are in contact. Instead, most brain imaging studies scan subjects individually. Here we present a proof-of-concept demonstration of two-person blood oxygenation dependent (BOLD) imaging of brain activity from two individuals interacting inside the bore of a single MRI scanner. We developed a custom 16-channel (8 + 8 channels) two-helmet coil with two separate receiving elements providing whole-brain coverage, while bringing participants into a shared physical space and realistic face-to-face contact. Ten subject pairs were scanned with the setup. During the experiment, subjects took turns in tapping each others lip versus observing and feeling the taps timed by auditory instructions. Networks of sensorimotor brain areas were engaged alternatingly in the subjects during executing motor actions as well as observing and feeling them; these responses were clearly distinguishable from the auditory responses occurring similarly in both participants. Even though the signal-to-noise ratio of our coil system was compromised compared with standard 32-channel head coils, our results show that the two-person fMRI scanning is a feasible in studying the brain basis of social interaction.

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bioRxiv2019

Interindividual variability and lateralization of μ-opioid receptors in the human brain

The brains {micro}-opioid receptors (MORs) are involved in analgesia, reward and mood regulation. Several neuropsychiatric diseases have been associated with dysfunctional MOR system, and there is also considerable variation in receptor density among healthy individuals. Sex, age, body mass and smoking have been proposed to influence the MOR system, but due to small sample sizes the magnitude of their influence remains inconclusive. Here we quantified in vivo MOR availability in the brains of 204 individuals with no neurologic or psychiatric disorders using positron emission tomography (PET) with tracer [11C]carfentanil. We then used Bayesian hierarchical modeling to estimate the effects of sex, age, body mass index (BMI) and smoking on [11C]carfentanil binding potential. We also examined hemispheric lateralization of MOR availability. Age had regionally specific effects on MOR availability, with age-dependent increase in frontotemporal areas but decrease in amygdala, thalamus, and nucleus accumbens. The age-dependent increase was stronger in males. MOR availability was globally lowered in smokers but independent of BMI. Finally, MOR availability was higher in the right versus the left hemisphere. The presently observed variation in MOR availability may explain why some individuals are prone to develop MOR-linked pathological states, such as chronic pain or psychiatric disorders.

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bioRxiv2019

Dissociable neural systems for unconditioned acute and sustained fear

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.

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