Infants' sex affects neural responses to affective touch in early infancy.

Social touch is closely related to the establishment and maintenance of social bonds in humans, and the sensory brain circuit for gentle brushing is already active soon after birth. Brain development is known to be sexually dimorphic, but the potential effect of sex on brain activation to gentle touch remains unknown. Here, we examined brain activation to gentle skin stroking, a tactile stimulation that resembles affective or social touch, in term-born neonates. Eighteen infants aged 11-36 days, recruited from the FinnBrain Birth Cohort Study, were included in the study. During natural sleep, soft brush strokes were applied to the skin of the right leg during functional magnetic resonance imaging (fMRI) at 3 cm/s velocity. We examined potential differences in brain activation between males (n = 10) and females (n = 8) and found that females had larger blood oxygenation level dependent (BOLD) responses (brushing vs. rest) in bilateral orbitofrontal cortex (OFC), right ventral striatum and bilateral inferior striatum, pons, and cerebellum compared to males. Moreover, the psychophysiological interactions (PPI) analysis, setting the left and right OFC as seed regions, revealed significant differences between males and females. Females exhibited stronger PPI connectivity between the left OFC and posterior cingulate or cuneus. Our work suggests that social touch neural responses are different in male and female neonates, which may have major ramifications for later brain, cognitive, and social development. Finally, many of the sexually dimorphic brain responses were subcortical, not captured by surface-based neuroimaging, indicating that fMRI will be a relevant technique for future studies.

Feasibility of using fNIRS to explore motor-related regional haemodynamic signal changes in patients with sensorimotor impairment and healthy controls: A pilot study.

BACKGROUND: While functional near-infrared spectroscopy (fNIRS) can provide insight into cortical brain activity during motor tasks in healthy and diseased populations, the feasibility of using fNIRS to assess haemoglobin-evoked responses to reanimated upper limb motor function in patients with tetraplegia remains unknown. OBJECTIVE: The primary objective of this pilot study is to determine the feasibility of using fNIRS to assess cortical signal intensity changes during upper limb motor tasks in individuals with surgically restored grip functions. The secondary objectives are: 1) to collect pilot data on individuals with tetraplegia to determine any trends in the cortical signal intensity changes as measured by fNIRS and 2) to compare cortical signal intensity changes in affected individuals versus age-appropriate healthy volunteers. Specifically, patients presented with tetraplegia, a type of paralysis resulting from a cervical spinal cord injury causing loss of movement and sensation in both lower and upper limbs. All patients have their grip functions restored by surgical tendon transfer, a procedure which constitutes a unique, focused stimulus for brain plasticity. METHOD: fNIRS is used to assess changes in cortical signal intensity during the performance of two motor tasks (isometric elbow and thumb flexion). Six individuals with tetraplegia and six healthy controls participate in the study. A block paradigm is utilized to assess contralateral and ipsilateral haemodynamic responses in the premotor cortex (PMC) and primary motor cortex (M1). We assess the amplitude of the optical signal and spatial features during the paradigms. The accuracy of channel locations is maximized through 3D digitizations of channel locations and co-registering these locations to template atlas brains. A general linear model approach, with short-separation regression, is used to extract haemodynamic response functions at the individual and group levels. RESULTS: Peak oxyhaemoglobin (oxy-Hb) changes in PMC appear to be particularly bilateral in nature in the tetraplegia group during both pinch and elbow trials whereas for controls, a bilateral PMC response is not especially evident. In M1 / primary sensory cortex (S1), the oxy-Hb responses to the pinch task are mainly contralateral in both groups, while for the elbow flexion task, lateralization is not particularly clear. CONCLUSIONS: This pilot study shows that the experimental setup is feasible for assessing brain activation using fNIRS during volitional upper limb motor tasks in individuals with surgically restored grip functions. Cortical signal changes in brain regions associated with upper extremity sensorimotor processing appear to be larger and more bilateral in nature in the tetraplegia group than in the control group. The bilateral hemispheric response in the tetraplegia group may reflect a signature of adaptive brain plasticity mechanisms. Larger studies than this one are needed to confirm these findings and draw reliable conclusions.

Maternal psychological distress associates with alterations in resting-state low-frequency fluctuations and distal functional connectivity of the neonate medial prefrontal cortex.

Prenatal stress exposure (PSE) has been observed to exert a programming effect on the developing infant brain, possibly with long-lasting consequences on temperament, cognitive functions and the risk for developing psychiatric disorders. Several prior studies have revealed that PSE associates with alterations in neonate functional connectivity in the prefrontal regions and amygdala. In this study, we explored whether maternal psychological symptoms measured during the 24th gestational week had associations with neonate resting-state network metrics. Twenty-one neonates (nine female) underwent resting-state fMRI scanning (mean gestation-corrected age at scan 26.95 days) to assess fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). The ReHo/fALFF maps were used in multiple regression analysis to investigate whether maternal self-reported anxiety and/or depressive symptoms associate with neonate functional brain features. Maternal psychological distress (composite score of depressive and anxiety symptoms) was positively associated with fALFF in the neonate medial prefrontal cortex (mPFC). Anxiety and depressive symptoms, assessed separately, exhibited similar but weaker associations. Post hoc seed-based connectivity analyses further showed that distal connectivity of mPFC covaried with PSE. No associations were found between neonate ReHo and PSE. These results offer preliminary evidence that PSE may affect functional features of the developing brain during gestation.

Lateral prefrontal cortex thickness is associated with stress but not cognitive fatigue in exhaustion disorder.

Introduction: Impaired executive functioning, including cognitive fatigue, is a core feature of the long-term stress-related condition exhaustion disorder (ED). Recent research suggests that a key area for executive control, the lateral prefrontal cortex (LPFC), may be mechanistically linked to cognitive fatigue due to stress. Here, we therefore asked if and how stress, the LPFC and cognitive fatigue may be related in ED. Methods: We used a multimodal cross-sectional study design with high-resolution structural magnetic resonance imaging (MRI), self-reported measures, and path analysis modeling in 300 participants with ED. Results: We found positive associations between stress and cognitive fatigue, and stress and LPFC thickness,but no association between LPFC thickness and cognitive fatigue. Furthermore, LPFC thickness did not mediate or moderate the association between stress and cognitive fatigue. Discussion: These findings suggest that LPFC brain morphology is related to perceived stress levels but not cognitive fatigue, expanding previous research on the role of the LPFC in executive functioning. Moreover, the results support the notion that the LPFC may be mechanistically involved in stress-related executive function impairment but prompt further research into if and how this may be related to cognitive symptoms in ED.

Enhanced Instructed Fear Learning in Delusion-Proneness.

Psychosis is associated with distorted perceptions and deficient bottom-up learning such as classical fear conditioning. This has been interpreted as reflecting imprecise priors in low-level predictive coding systems. Paradoxically, overly strong beliefs, such as overvalued beliefs and delusions, are also present in psychosis-associated states. In line with this, research has suggested that patients with psychosis and associated phenotypes rely more on high-order priors to interpret perceptual input. In this behavioural and fMRI study we studied two types of fear learning, i.e., instructed fear learning mediated by verbal suggestions about fear contingencies and classical fear conditioning mediated by low level associative learning, in delusion proneness-a trait in healthy individuals linked to psychotic disorders. Subjects were shown four faces out of which two were coupled with an aversive stimulation (CS+) while two were not (CS-) in a fear conditioning procedure. Before the conditioning, subjects were informed about the contingencies for two of the faces of each type, while no information was given for the two other faces. We could thereby study the effect of both classical fear conditioning and instructed fear learning. Our main outcome variable was evaluative rating of the faces. Simultaneously, fMRI-measurements were performed to study underlying mechanisms. We postulated that instructed fear learning, measured with evaluative ratings, is stronger in psychosis-related phenotypes, in contrast to classical fear conditioning that has repeatedly been shown to be weaker in these groups. In line with our hypothesis, we observed significantly larger instructed fear learning on a behavioural level in delusion-prone individuals (n = 20) compared to non-delusion-prone subjects (n = 23; n = 20 in fMRI study). Instructed fear learning was associated with a bilateral activation of lateral orbitofrontal cortex that did not differ significantly between groups. However, delusion-prone subjects showed a stronger functional connectivity between right lateral orbitofrontal cortex and regions processing fear and pain. Our results suggest that psychosis-related states are associated with a strong instructed fear learning in addition to previously reported weak classical fear conditioning. Given the similarity between nocebo paradigms and instructed fear learning, our results also have an impact on understanding why nocebo effects differ between individuals.

Prolonged NoGo P3 latency as a possible neurobehavioral correlate of aggressive and antisocial behaviors: A Go/NoGo ERP study.

Aggressive and antisocial behaviors are detrimental to society and constitute major challenges in forensic mental health settings, yet the associated neural circuitry remains poorly understood. Here, we investigated differences in aggressive and antisocial behaviors between healthy controls (n = 20) and violent mentally disordered offenders (MDOs; n = 26), and examined associations between aggressive and antisocial behaviors, behavioral inhibitory control, and neurophysiological activity across the whole sample (n = 46). Event-related potentials were obtained using EEG while participants completed a Go/NoGo response inhibition task, and aggressive and antisocial behaviors were assessed with the Life History of Aggression (LHA) instrument. Using a robust Bayesian linear regression approach, we found that MDOs scored substantially higher than healthy controls on LHA Aggression and Antisocial subscales. Using the whole sample and after adjusting for age, we found that scores on the LHA Aggression and Antisocial subscales were robustly associated with longer NoGo P3 latency, and less robustly with longer NoGo N2 latency. Post-hoc analyzes suggested that healthy controls and MDOs exhibited similar associations. With several limitations in mind, we suggest that prolonged NoGo P3 latency, reflecting decreased neural efficiency during the later stages of conflict monitoring or outcome evaluation, is a potential neurobehavioral correlate of aggressive and antisocial behaviors.

Maternal pre-pregnancy BMI associates with neonate local and distal functional connectivity of the left superior frontal gyrus.

Maternal obesity/overweight during pregnancy has reached epidemic proportions and has been linked with adverse outcomes for the offspring, including cognitive impairment and increased risk for neuropsychiatric disorders. Prior neuroimaging investigations have reported widespread aberrant functional connectivity and white matter tract abnormalities in neonates born to obese mothers. Here we explored whether maternal pre-pregnancy adiposity is associated with alterations in local neuronal synchrony and distal connectivity in the neonate brain. 21 healthy mother-neonate dyads from uncomplicated pregnancies were included in this study (age at scanning 26.14 ± 6.28 days, 12 male). The neonates were scanned with a 6-min resting-state functional magnetic resonance imaging (rs-fMRI) during natural sleep. Regional homogeneity (ReHo) maps were computed from obtained rs-fMRI data. Multiple regression analysis was performed to assess the association of pre-pregnancy maternal body-mass-index (BMI) and ReHo. Seed-based connectivity analysis with multiple regression was subsequently performed with seed-ROI derived from ReHo analysis. Maternal adiposity measured by pre-pregnancy BMI was positively associated with neonate ReHo values within the left superior frontal gyrus (SFG) (FWE-corrected p < 0.005). Additionally, we found both positive and negative associations (p < 0.05, FWE-corrected) for maternal pre-pregnancy BMI and seed-based connectivity between left SFG and prefrontal, amygdalae, basal ganglia and insular regions. Our results imply that maternal pre-pregnancy BMI associates with local and distal functional connectivity within the neonate left superior frontal gyrus. These findings add to the evidence that increased maternal pre-pregnancy BMI has a programming influence on the developing neonate brain functional networks.

Structural Brain Correlates of the Externalizing Spectrum in Young Adults.

The externalizing spectrum, including traits and behaviors such as aggression, reduced inhibitiory control and substance abuse, is associated with altered prefrontal brain morphology. However, the degree to which different manifestations of the externalizing spectrum are associated with distinct or overlapping variations in individual brain morphology is unclear. Here, we therefore used structural magnetic resonance imaging, self-report assessment, and a response inhibition task in a sample of 59 young adults to examine how cortical thickness in the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and dorsolateral prefrontal cortex (DLPFC) relate to four different manifestations of the externalizing spectrum: disinhibition, callous aggression, substance abuse, and behavioral inhibitory control. Using Bayesian linear regression models controlling for age, gender, and years of education, we found that the different manifestations of the externalizing spectrum were associated with both distinct and overlapping morphology variations. Specifically, both callous aggression and inhibitory control was associated with increased cortical thickness of the OFC, a region involved in reward processing, decision-making, and regulation of anxiety and fear. Both disinhibition and substance abuse were associated with DLPFC thickness, although with opposite association patterns, possibly reflecting processes related to inhibitory control, working memory and attention. Moreover, disinhibition, but not callous aggression or substance abuse, was associated with behavioral inhibitory control. Our results provide further support for the link between externalizing behaviors and prefrontal brain morphology, while identifying distinct prefrontal areas associated with different clinically relevant manifestations. These findings may help guide further research aimed at developing novel treatment and intervention strategies for externalizing behaviors and disorders.

Trait Disinhibition and NoGo Event-Related Potentials in Violent Mentally Disordered Offenders and Healthy Controls.

Trait disinhibition may function as a dispositional liability toward maladaptive behaviors relevant in the treatment of mentally disordered offenders (MDOs). Reduced amplitude and prolonged latency of the NoGo N2 and P3 event-related potentials have emerged as promising candidates for transdiagnostic, biobehavioral markers of trait disinhibition, yet no study has specifically investigated these two components in violent, inpatient MDOs. Here, we examined self-reported trait disinhibition, experimentally assessed response inhibition, and NoGo N2 and P3 amplitude and latency in male, violent MDOs (N = 27) and healthy controls (N = 20). MDOs had a higher degree of trait disinhibition, reduced NoGo P3 amplitude, and delayed NoGo P3 latency compared to controls. The reduced NoGo P3 amplitude and delayed NoGo P3 latency in MDOs may stem from deficits during monitoring or evaluation of behavior. NoGo P3 latency was associated with increased trait disinhibition in the whole sample, suggesting that trait disinhibition may be associated with reduced neural efficiency during later stages of outcome monitoring or evaluation. Findings for NoGo N2 amplitude and latency were small and non-robust. With several limitations in mind, this is the first study to demonstrate attenuated NoGo P3 amplitude and delayed NoGo P3 latency in violent, inpatient MDOs compared to healthy controls.

Resting-state networks of the neonate brain identified using independent component analysis.

Resting-state functional magnetic resonance imaging (rs-fMRI) has been successfully used to probe the intrinsic functional organization of the brain and to study brain development. Here, we implemented a combination of individual and group independent component analysis (ICA) of FSL on a 6-min resting-state data set acquired from 21 naturally sleeping term-born (age 26 ± 6.7 d), healthy neonates to investigate the emerging functional resting-state networks (RSNs). In line with the previous literature, we found evidence of sensorimotor, auditory/language, visual, cerebellar, thalmic, parietal, prefrontal, anterior cingulate as well as dorsal and ventral aspects of the default-mode-network. Additionally, we identified RSNs in frontal, parietal, and temporal regions that have not been previously described in this age group and correspond to the canonical RSNs established in adults. Importantly, we found that careful ICA-based denoising of fMRI data increased the number of networks identified with group-ICA, whereas the degree of spatial smoothing did not change the number of identified networks. Our results show that the infant brain has an established set of RSNs soon after birth.

Regional estimates of cortical thickness in brain areas involved in control of surgically restored limb movement in patients with tetraplegia.

Context/Objective: Spinal cord injury (SCI) causes atrophy of brain regions linked to motor function. We aimed to estimate cortical thickness in brain regions that control surgically restored limb movement in individuals with tetraplegia. Design: Cross-sectional study. Setting: Sahlgrenska University hospital, Gothenburg, Sweden. Participants: Six individuals with tetraplegia who had undergone surgical restoration of grip function by surgical transfer of one elbow flexor (brachioradialis), to the paralyzed thumb flexor (flexor pollicis longus). All subjects were males, with a SCI at the C6 or C7 level, and a mean age of 40 years (range = 31-48). The average number of years elapsed since the SCI was 13 (range = 6-26). Outcome measures: We used structural magnetic resonance imaging (MRI) to estimate the thickness of selected motor cortices and compared these measurements to those of six matched control subjects. The pinch grip control area was defined in a previous functional MRI study. Results: Compared to controls, the cortical thickness in the functionally defined pinch grip control area was not significantly reduced (P = 0.591), and thickness showed a non-significant but positive correlation with years since surgery in the individuals with tetraplegia. In contrast, the anatomically defined primary motor cortex as a whole exhibited substantial atrophy (P = 0.013), with a weak negative correlation with years since surgery. Conclusion: Individuals with tetraplegia do not seem to have reduced cortical thickness in brain regions involved in control of surgically restored limb movement. However, the studied sample is very small and further studies with larger samples are required to establish these findings.

Neural correlates of gentle skin stroking in early infancy.

Physical expressions of affection play a foundational role in early brain development, but the neural correlates of affective touch processing in infancy remain unclear. We examined brain responses to gentle skin stroking, a type of tactile stimulus associated with affectionate touch, in young infants. Thirteen term-born infants aged 11-36days, recruited through the FinnBrain Birth Cohort Study, were included in the study. Soft brush strokes, which activate brain regions linked to somatosensory as well as socio-affective processing in children and adults, were applied to the skin of the right leg during functional magnetic resonance imaging. We examined infant brain responses in two regions-of-interest (ROIs) known to process gentle skin stroking - the postcentral gyrus and posterior insular cortex - and found significant responses in both ROIs. These results suggest that the neonate brain is responsive to gentle skin stroking within the first weeks of age, and that regions linked to primary somatosensory as well as socio-affective processing are activated. Our findings support the notion that social touch may play an important role in early life sensory processing. Future research will elucidate the significance of these findings for human brain development.

Abnormal brain processing of gentle touch in anorexia nervosa.

Body image disturbance is a core symptom in anorexia nervosa (AN). Recent research suggests that abnormalities in touch perception may contribute to the disease mechanisms in AN. Here, we used functional magnetic resonance imaging (fMRI) to study possible abnormalities in cortical processing of affective touch in AN. Gentle skin strokes were applied to the right forearm during fMRI scanning in women diagnosed with AN (n = 25) and in matched healthy controls (HC; n = 25). Blocks of skin stroking were alternated with blocks of static skin indentation. Participants provided ratings of the pleasantness of skin stroking stimulation. AN participants perceived skin stroking as significantly less pleasant than HC. We observed no group differences for the contrast between skin stroking and skin indentation in primary tactile regions. We did find, however, significantly less activity in the AN group in areas including left caudate nucleus. Also, we found less activity in the AN group in bilateral lateral occipital cortex for the main effect of skin stroking. Our results suggest that abnormal functioning of the dorsal striatum could affect evaluation of pleasant tactile stimuli, and that abnormal functioning of the lateral occipital cortex might be related to disturbed body image perception.

Grey matter correlates of autistic traits in women with anorexia nervosa.

BACKGROUND: Patients with anorexia nervosa exhibit higher levels of behaviours typically associated with autism-spectrum disorder (ASD), but the neural basis is unclear. We sought to determine whether elevated autistic traits in women with anorexia nervosa may be reflected in cortical morphology. METHODS: We used voxel-based morphometry (VBM) to examine regional grey matter volumes in high-resolution MRI structural brain scans in women with anorexia nervosa and matched healthy controls. The Autism-spectrum Quotient (AQ) scale was used to assess autistic traits. RESULTS: Women with anorexia nervosa (n = 25) had higher AQ scores and lower bilateral superior temporal sulcus (STS) grey matter volumes than the control group (n = 25). The AQ scores correlated negatively with average left STS grey matter volume in women with anorexia nervosa. LIMITATIONS: We did not control for cognitive ability and examined only women with ongoing anorexia nervosa. CONCLUSION: Elevated autistic traits in women with anorexia nervosa are associated with morphometric alterations of brain areas linked to social cognition. This finding provides neurobiological support for the behavioural link between anorexia nervosa and ASD and emphasizes the importance of recognizing autistic traits in preventing and treating anorexia nervosa.

Adaptive motor cortex plasticity following grip reconstruction in individuals with tetraplegia.

BACKGROUND: Tendon transfer is a surgical technique for restoring upper limb motor control in patients with cervical spinal cord injuries (SCI), and offers a rare window into cortical neuroplasticity following regained arm and hand function. OBJECTIVE: Here, we aimed to examine neuroplasticity mechanisms related to re-established voluntary motor control of thumb flexion following tendon transfer. METHODS: We used functional Magnetic Resonance Imaging (fMRI) to test the hypothesis that restored limb control following tendon transfer is mediated by activation of that limb's area of the primary motor cortex. We examined six individuals with tetraplegia who underwent right-sided surgical grip reconstruction at Sahlgrenska University Hospital, Sweden. All were right-handed males, with a SCI at the C6 or C7 level, and a mean age of 40 years (range = 31-48). The average number of years elapsed since the SCI was 13 (range = 6-26). Six right-handed gender- and age-matched control subjects were included (mean age 39 years, range = 29-46). Restoration of active thumb flexion in patients was achieved by surgical transfer of one of the functioning elbow flexors (brachioradialis), to the paralyzed thumb flexor (flexor pollicis longus). We studied fMRI responses to isometric right-sided elbow flexion and key pinch, and examined the cortical representations within the left hemisphere somatomotor cortex a minimum of one year after surgery. RESULTS: Cortical activations elicited by elbow flexion did not differ in topography between patients and control participants. However, in contrast to control participants, patients' cortical thumb flexion activations were not topographically distinct from their elbow flexion activations. CONCLUSION: This result speaks against a topographic reorganization in which the thumb region regains thumb control following surgical tendon transfer. Instead, our findings suggest a neuroplastic mechanism in which motor cortex resources previously dedicated to elbow flexion adapt to control the thumb.

Grey matter correlates of autistic traits in women with anorexia nervosa

Background: Patients with anorexia nervosa exhibit higher levels of behaviours typically associated with autism-spectrum disorder (ASD), but the neural basis is unclear. We sought to determine whether elevated autistic traits in women with anorexia nervosa may be reflected in cortical morphology. Methods: We used voxel-based morphometry (VBM) to examine regional grey matter volumes in high-resolution MRI structural brain scans in women with anorexia nervosa and matched healthy controls. The Autism-spectrum Quotient (AQ) scale was used to assess autistic traits. Results: Women with anorexia nervosa (n = 25) had higher AQ scores and lower bilateral superior temporal sulcus (STS) grey matter volumes than the control group (n = 25). The AQ scores correlated negatively with average left STS grey matter volume in women with anorexia nervosa. Limitations: We did not control for cognitive ability and examined only women with ongoing anorexia nervosa. Conclusion: Elevated autistic traits in women with anorexia nervosa are associated with morphometric alterations of brain areas linked to social cognition. This finding provides neurobiological support for the behavioural link between anorexia nervosa and ASD and emphasizes the importance of recognizing autistic traits in preventing and treating ­anorexia nervosa.

Posterior Superior Temporal Sulcus Responses Predict Perceived Pleasantness of Skin Stroking.

Love and affection is expressed through a range of physically intimate gestures, including caresses. Recent studies suggest that posterior temporal lobe areas typically associated with visual processing of social cues also respond to interpersonal touch. Here, we asked whether these areas are selective to caress-like skin stroking. We collected functional magnetic resonance imaging data from 23 healthy participants and compared brain responses to skin stroking and vibration. We did not find any significant differences between stroking and vibration in the posterior temporal lobe; however, right posterior superior temporal sulcus (pSTS) responses predicted healthy participant's perceived pleasantness of skin stroking, but not vibration. These findings link right pSTS responses to individual variability in perceived pleasantness of caress-like tactile stimuli. We speculate that the right pSTS may play a role in the translation of tactile stimuli into positively valenced, socially relevant interpersonal touch and that this system may be affected in disorders associated with impaired attachment.

Evaluation of Quantified Social Perception Circuit Activity as a Neurobiological Marker of Autism Spectrum Disorder.

IMPORTANCE: Autism spectrum disorder (ASD) is marked by social disability and is associated with dysfunction in brain circuits supporting social cue perception. The degree to which neural functioning reflects individual-level behavioral phenotype is unclear, slowing the search for functional neuroimaging biomarkers of ASD. OBJECTIVE: To examine whether quantified neural function in social perception circuits may serve as an individual-level marker of ASD in children and adolescents. DESIGN, SETTING, AND PARTICIPANTS: The cohort study was conducted at the Yale Child Study Center and involved children and adolescents diagnosed as having ASD and typically developing participants. Participants included a discovery cohort and a larger replication cohort. Individual-level social perception circuit functioning was assessed as functional magnetic resonance imaging brain responses to point-light displays of coherent vs scrambled human motion. MAIN OUTCOMES AND MEASURES: Outcome measures included performance of quantified brain responses in affected male and female participants in terms of area under the receiver operating characteristic curve (AUC), sensitivity and specificity, and correlations between brain responses and social behavior. RESULTS: Of the 39 participants in the discovery cohort aged 4 to 17 years, 22 had ASD and 30 were boys. Of the 75 participants in the replication cohort aged 7 to 20 years, 37 had ASD and 52 were boys. A relative reduction in social perception circuit responses was identified in discovery cohort boys with ASD at an AUC of 0.75 (95% CI, 0.52-0.89; P = .01); however, typically developing girls and girls with ASD could not be distinguished (P = .54). The results were confirmed in the replication cohort, where brain responses were identified in boys with ASD at an AUC of 0.79 (95% CI, 0.64-0.91; P < .001) and failed to distinguish affected and unaffected girls (P = .82). Across both cohorts, boys were identified at an AUC of 0.77 (95% CI, 0.64-0.86) with corresponding sensitivity and specificity of 76% each. Additionally, brain responses were associated with social behavior in boys but not in girls. CONCLUSIONS AND RELEVANCE: Quantified social perception circuit activity is a promising individual-level candidate neural marker of the male ASD behavioral phenotype. Our findings highlight the need to better understand effects of sex on social perception processing in relation to ASD phenotype manifestations.

Decoding illusory self-location from activity in the human hippocampus.

Decades of research have demonstrated a role for the hippocampus in spatial navigation and episodic and spatial memory. However, empirical evidence linking hippocampal activity to the perceptual experience of being physically located at a particular place in the environment is lacking. In this study, we used a multisensory out-of-body illusion to perceptually 'teleport' six healthy participants between two different locations in the scanner room during high-resolution functional magnetic resonance imaging (fMRI). The participants were fitted with MRI-compatible head-mounted displays that changed their first-person visual perspective to that of a pair of cameras placed in one of two corners of the scanner room. To elicit the illusion of being physically located in this position, we delivered synchronous visuo-tactile stimulation in the form of an object moving toward the cameras coupled with touches applied to the participant's chest. Asynchronous visuo-tactile stimulation did not induce the illusion and served as a control condition. We found that illusory self-location could be successfully decoded from patterns of activity in the hippocampus in all of the participants in the synchronous (P < 0.05) but not in the asynchronous condition (P > 0.05). At the group-level, the decoding accuracy was significantly higher in the synchronous than in the asynchronous condition (P = 0.012). These findings associate hippocampal activity with the perceived location of the bodily self in space, which suggests that the human hippocampus is involved not only in spatial navigation and memory but also in the construction of our sense of bodily self-location.

Posterior cingulate cortex integrates the senses of self-location and body ownership.

The senses of owning a body and being localized somewhere in space are two key components of human self-consciousness. Despite a wealth of neurophysiological and neuroimaging research on the representations of the spatial environment in the parietal and medial temporal cortices, the relationship between body ownership and self-location remains unexplored. To investigate this relationship, we used a multisensory out-of-body illusion to manipulate healthy participants' perceived self-location, head direction, and sense of body ownership during high-resolution fMRI. Activity patterns in the hippocampus and the posterior cingulate, retrosplenial, and intraparietal cortices reflected the sense of self-location, whereas the sense of body ownership was associated with premotor-intraparietal activity. The functional interplay between these two sets of areas was mediated by the posterior cingulate cortex. These results extend our understanding of the role of the posterior parietal and medial temporal cortices in spatial cognition by demonstrating that these areas not only are important for ecological behaviors, such as navigation and perspective taking, but also support the perceptual representation of the bodily self in space. Our results further suggest that the posterior cingulate cortex has a key role in integrating the neural representations of self-location and body ownership.