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Background Depression is associated with altered functional connectivity and altered cortisol sensitivity, but the effects of cortisol on functional connectivity in depression are unknown. Previous research shows that brief cortisol augmentation (CORT) has beneficial neurocognitive effects in depression. Methods We investigated the effects of CORT (20mg oral cortisol) on functional connectivity during emotion processing in women with depression. Participants included 75 women with no depression or a depressive disorder. In a double-blind, crossover study, we used functional magnetic resonance imaging to measure effects of CORT vs. placebo on task-based functional connectivity during presentation of emotionally-laden images. We performed psychophysiological interaction (PPI) to test interactions among depression severity, cortisol administration, and task-dependent functional connectivity using the hippocampus and amygdala as seeds. Results During the presentation of negative images, CORT (vs. placebo) increased functional connectivity between the hippocampus and putamen in association with depression severity. During the presentation of positive pictures CORT increased functional connectivity between the hippocampus and middle frontal gyrus as well as superior temporal gyrus in association with depression. Limitations Because cortisol was pharmacologically manipulated, results cannot be extrapolated to endogenous increases in cortisol levels. The sample did not permit investigation of differences due to race, ethnicity, or sex. Co-morbidities such as anxiety or PTSD were not accounted for. Conclusions The results suggest that CORT has normalizing effects on task-dependent functional connectivity in women with depression during emotion processing. Increasing cortisol availability or signaling may have therapeutic benefits within affective disorders.

Background: Theory of Mind (ToM) is an ability to infer the mental state of others, which plays an important role during social events. Previous studies have shown that ToM deficits exist frequently in schizophrenia, which may result from abnormal activity in brain regions related to sociality. However, the interactions between brain regions during ToM processing in schizophrenia are still unclear. Therefore, in this study, we investigated functional connectivity during ToM processing in patients with schizophrenia, using functional magnetic resonance imaging (fMRI). Methods: A total of 36 patients with schizophrenia and 33 healthy controls were recruited to complete a ToM task from the Human Connectome Project (HCP) during fMRI scanning. Psychophysiological interaction (PPI) analysis was applied to explore functional connectivity. Results: Patients with schizophrenia were less accurate than healthy controls in judging social stimuli from non-social stimuli (Z = 2.31, p = 0.021), and displayed increased activity in the right inferior frontal gyrus and increased functional connectivity between the bilateral middle temporal gyrus and the ipsilateral parahippocampal gyrus during ToM processing (AlphaSim corrected p < 0.05). Conclusions: Here, we showed that the brain regions related to sociality interact more with the parahippocampal gyrus in patients with schizophrenia during ToM processing, which may reflect a possible compensatory pathway of ToM deficits in schizophrenia. Our study provides a new idea for ToM deficits in schizophrenia, which could be helpful to better understand social cognition of schizophrenia.

Protracted abstinence (PA) and Methadone maintenance treatment (MMT) are two main types of heroin addiction treatment, however, the effects of both measures on the functional connectivity (FC) of the brain in heroin dependents in the drug cue event-related response are unclear. Functional magnetic resonance imaging (fMRI) based drug cue-reactivity task has been widely used in addiction research, which may provide a new way to understand the change of brain function during a certain period of treatment. The default function network (DMN) with posterior cingulate cortex (PCC) as the core is generally involved in the process of addiction. The aim of the present study was to explore the brain response of FC in patients with heroin-dependent during PA, MMT treatment under task-fMRI. Twenty-two heroin-dependent patients during PA, 18 heroin-dependent patients during MMT and 16 healthy control (HC) individuals were included to conduct the heroin cue-reactivity task during fMRI. The MMT and PA patients' subjective craving for heroin was evaluated. The psychophysiological interaction (PPI) analysis of SPM12 was used to get FC during the task state. There was a significant difference on FC between PCC and the right medial Prefrontal Cortex (mPFC) in three groups. The post-hoc analysis showed that there was a significant difference of brain regions between the MMT and the PA group. The FC of PCC-mPFC in the MMT group was significantly stronger than that in the PA group. Compared with the PA group, the FC of the DMN in the MMT group was significantly increased under drug cue response. Therefore, PA is more beneficial for the heroin-dependent patients to lower the salience value of drug related cues, in turn to reduce relapse risks. It also reflected the important role of PCC-mPFC pathway in heroin dependents induced by heroin cues.

Maternal childhood maltreatment experiences (CMEs) may influence responses to infants and affect child outcomes. We examined associations between CME and mothers’ neural responses and functional connectivity to infant distress. We hypothesized that mothers with greater CME would exhibit higher amygdala reactivity and amygdala–supplementary motor area (SMA) functional connectivity to own infant’s cries. Postpartum mothers (N = 57) assessed for CME completed an functional magnetic resonance imaging task with cry and white-noise stimuli. Amygdala region-of-interest and psychophysiological interaction analyses were performed. Our models tested associations of CME with activation and connectivity during task conditions (own/other and cry/noise). Exploratory analyses with parenting behaviors were performed. Mothers with higher CME exhibited higher amygdala activation to own baby’s cries vs other stimuli (F1,392 = 6.9, P

Preclinical studies have implicated noradrenergic (NA) dysfunction in cocaine addiction. In particular, the NA system plays a central role in motivated behavior and may partake in the regulation of craving and drug use. Yet, human studies of the NA system are scarce, likely hampered by the difficulty in precisely localizing the locus coeruleus (LC). Here, we used neuromelanin imaging to localize the LC and quantified LC neuromelanin signal (NMS) intensity in 44 current cocaine users (CU; 37 men) and 59 nondrug users (NU; 44 men). We also employed fMRI to investigate cue-induced regional responses and LC functional connectivities, as quantified by generalized psychophysiological interaction (gPPI), in CU. Imaging data were processed by published routines and the findings were evaluated with a corrected threshold. We examined how these neural measures were associated with chronic cocaine craving, as assessed by the Cocaine Craving Questionnaire (CCQ). Compared to NU, CU demonstrated higher LC NMS for all probabilistic thresholds defined of 50–90% of the peak. In contrast, NMS of the ventral tegmental area/substantia nigra (VTA/SN) did not show significant group differences. Drug as compared to neutral cues elicited higher activations of many cortical and subcortical regions, none of which were significantly correlated with CCQ score. Drug vs. neutral cues also elicited “deactivation” of bilateral parahippocampal gyri (PHG) and PHG gPPI with a wide array of cortical and subcortical regions, including the ventral striatum and, with small volume correction, the LC. Less deactivation of the PHG (r = 0.40, p = 0.008) and higher PHG-LC gPPI (r = 0.44, p = 0.003) were positively correlated with the CCQ score. In contrast, PHG-VTA/SN connectivity did not correlate with the CCQ score. Together, chronic cocaine exposure may induce higher NMS intensity, suggesting neurotoxic effects on the LC. The correlation of cue-elicited PHG LC connectivity with CCQ score suggests a noradrenergic correlate of chronic cocaine craving. Potentially compensating for memory functions as in neurodegenerative conditions, cue-elicited PHG LC circuit connectivity plays an ill-adaptive role in supporting cocaine craving.

To clarify the involvement of the cerebellum in impaired sensory integration in patients with schizophrenia, 52 first-episode patients with schizophrenia and 52 age- and sex-matched healthy controls underwent a verified sensory integration imaging task to examine the whole-brain dysfunction underlying impaired sensory integration. The familiality of cerebellar activation when integrating sensory stimuli was investigated in 25 siblings of the patients with schizophrenia, while the heritability of cerebellar activation was estimated in 56 monozygotic twins and 56 dizygotic twins. In addition, the functional connectivity between the cerebellum and the remaining regions of the whole brain was explored with psychophysiological interaction analysis. Relative to healthy controls, patients with schizophrenia showed reduced cerebellar activation when performing the sensory integration task in the whole-brain analysis. This reduced cerebellar activation was also found in the siblings of patients with schizophrenia, but to a lesser extent compared with schizophrenia patients. Cerebellar activation during sensory integration was also found to be significantly heritable. Furthermore, dysconnectivity within the cerebellum was found in patients with schizophrenia when integrating auditory and visual stimuli. These findings highlight the role of cerebellar dysfunction in the pathophysiology of schizophrenia symptoms and its potential role as an endophenotype of schizophrenia spectrum disorders. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Smooth pursuit eye movements (SPEM) hold the image of a slowly moving stimulus on the fovea. The neural system underlying SPEM primarily includes visual, parietal, and frontal areas. In the present study, we investigated how these areas are functionally coupled and how these couplings are influenced by target motion frequency. To this end, healthy participants (n = 57) were instructed to follow a sinusoidal target stimulus moving horizontally at two different frequencies (0.2 Hz, 0.4 Hz). Eye movements and blood oxygen level-dependent (BOLD) activity were recorded simultaneously. Functional connectivity of the key areas of the SPEM network was investigated with a psychophysiological interaction (PPI) approach. How activity in five eye movement-related seed regions (lateral geniculate nucleus, V1, V5, posterior parietal cortex, frontal eye fields) relates to activity in other parts of the brain during SPEM was analyzed. The behavioral results showed clear deterioration of SPEM performance at higher target frequency. BOLD activity during SPEM versus fixation occurred in a geniculo-occipito-parieto-frontal network, replicating previous findings. PPI analysis yielded widespread, partially overlapping networks. In particular, frontal eye fields and posterior parietal cortex showed task-dependent connectivity to large parts of the entire cortex, whereas other seed regions demonstrated more regionally focused connectivity. Higher target frequency was associated with stronger activations in visual areas but had no effect on functional connectivity. In summary, the results confirm and extend previous knowledge regarding the neural mechanisms underlying SPEM and provide a valuable basis for further investigations such as in patients with SPEM impairments and known alterations in brain connectivity.NEW & NOTEWORTHY This study provides a comprehensive investigation of blood oxygen level-dependent (BOLD) functional connectivity during smooth pursuit eye movements. Results from a large sample of healthy participants suggest that key oculomotor regions interact closely with each other but also with regions not primarily associated with eye movements. Understanding functional connectivity during smooth pursuit is important, given its potential role as an endophenotype of psychoses.

BackgroundInternet gaming disorder (IGD) is a type of behavioural addictions. One of the key features of addiction is the excessive exposure to addictive objectives (e.g. drugs) reduces the sensitivity of the brain reward system to daily rewards (e.g. money). This is thought to be mediated via the signals expressed as dopaminergic reward prediction error (RPE). Emerging evidence highlights blunted RPE signals in drug addictions. However, no study has examined whether IGD also involves alterations in RPE signals that are observed in other types of addictions.MethodsTo fill this gap, we used functional magnetic resonance imaging data from 45 IGD and 42 healthy controls (HCs) during a reward-related prediction-error task and utilised a psychophysiological interaction (PPI) analysis to characterise the underlying neural correlates of RPE and related functional connectivity.ResultsRelative to HCs, IGD individuals showed impaired reinforcement learning, blunted RPE signals in multiple regions of the brain reward system, including the right caudate, left orbitofrontal cortex (OFC), and right dorsolateral prefrontal cortex (DLPFC). Moreover, the PPI analysis revealed a pattern of hyperconnectivity between the right caudate, right putamen, bilateral DLPFC, and right dorsal anterior cingulate cortex (dACC) in the IGD group. Finally, linear regression suggested that the connection between the right DLPFC and right dACC could significantly predict the variation of RPE signals in the left OFC.ConclusionsThese results highlight disrupted RPE signalling and hyperconnectivity between regions of the brain reward system in IGD. Reinforcement learning deficits may be crucial underlying characteristics of IGD pathophysiology.

Background Few previous studies explored negative emotion processing in autistic-like traits people using task-based fMRI. In this study, we applied task fMRI to determine the relationship between negative emotion processing and social skill within autistic-like traits people. aimed to find which brain areas specificity play a key role in emotional processing. Methods 106 of Chinese individuals measured with AQ. Then applied emotion regulation task to explore the difference in brain activation and functional connectivity in individuals with autistic traits. Results The results showed increased activation in the right middle temporal gyrus (MTG). The mediation analysis showed the right MTG mediates the relationship between autistic-like traits and negative emotion. Generalized psychophysiological interaction (gPPI) analysis also suggested that the right MTG shows significant functional connectivity with the left parahippocampal gyrus (PHG) and left precuneus cortex. Limitations Our sample are university students, there may have a bias in the sample compared to sub-average and have no differences between the gender, we will broaden the sample size and take the gender into account. We use two conditions as our focused theme, we want to use a more specific task to explore negative emotion in autistic-like traits people. Conclusions The results showed that the right MTG was an important brain region in individuals with autistic-like traits, and our study provides a wider discussion about autism brain activation and functional connectivity patterns and the use the MTG as a hallmark in individuals with autistic-like traits.

Language comprehension depends on tight functional interactions between distributed brain regions. While these interactions are established for semantic and syntactic processes, the functional network of speech intonation – the linguistic variation of pitch – has been scarcely defined. Particularly little is known about intonation in tonal languages, in which pitch not only serves intonation but also expresses meaning via lexical tones. The present study used psychophysiological interaction analyses of functional magnetic resonance imaging data to characterise the neural networks underlying intonation and tone processing in native Mandarin Chinese speakers. Participants categorised either intonation or tone of monosyllabic Mandarin words that gradually varied between statement and question and between Tone 2 and Tone 4. Intonation processing induced bilateral fronto‐temporal activity and increased functional connectivity between left inferior frontal gyrus and bilateral temporal regions, likely linking auditory perception and labelling of intonation categories in a phonological network. Tone processing induced bilateral temporal activity, associated with the auditory representation of tonal (phonemic) categories. Together, the present data demonstrate the breadth of the functional intonation network in a tonal language including higher‐level phonological processes in addition to auditory representations common to both intonation and tone., The present functional magnetic resonance imaging study investigated task‐specific functional connectivity in intonation and tone processing in Mandarin speakers.Intonation processing increased functional interactions between left inferior frontal and bilateral temporal regions and between lateral‐medial frontal regions, likely reflecting higher‐level phonological processes and verbal response preparation.Tone processing only induced bilateral temporal activity, likely associated with auditory representation of tone (phonemic) categories.

Previous studies have identified a collection of brain areas that show neural selectivity for the distinction between human-to-human and human-to-object interactions, including regions implicated in sensory and social processing. It remains largely unknown, however, how the functional communication between these areas changes with the type of interaction. Combining a generalized psychophysiological interaction (gPPI) analysis and independent component analysis (ICA), the current study sought to identify the context-sensitive modulation of the functional network architecture during touch observation. Thirty-seven participants watched 75 video clips displaying social and non-social touch events during a functional imaging scan. A gPPI analysis of pre-defined regions of interest revealed that social-cognitive brain regions show enhanced interregional coupling during social touch observation, both among social-cognitive brain regions and between social-cognitive regions and sensory regions. Conversely, during non-social touch observation, a significantly stronger coupling among brain areas within the system that processes the unimodal sensory information was observed. At the level of large-scale brain networks extracted with ICA, stronger connectivity between 11 pairs of networks, including default mode networks, was observed during social touch observation, while only three pairs of networks showed stronger connectivity during non-social touch observation. The current study identifies the presence of context-dependent changes in functional brain architecture based on whether the touch recipient is a person or an object, highlighting an increased exchange of neural information for social processing. ispartof: Cortex vol:125 pages:73-89 ispartof: location:Italy status: published

BACKGROUND: In treating major depressive disorder (MDD), we lack tests anchored in neurobiology that predict antidepressant efficacy. Cognitive impairments are a particularly disabling MDD feature. We tested whether functional connectivity during a response-inhibition task can predict response to antidepressants and whether its changes over time are correlated to symptom changes. METHODS: We analyzed data from MDD outpatients (N=124) randomized to receive escitalopram, sertraline or venlafaxine (8 weeks) and healthy controls (N=59) (ages 18–65). At pre-and post-treatment, participants were interviewed and scanned using functional MRI and functional connectivity was measured using generalized psychophysiological interaction during response inhibition (Go-NoGo task). We investigated the interaction between treatment type and response (≥50% reduction on self-reported symptoms), coupling differences between responders/non-responders at baseline, their correlation with symptom improvement and their changes in time. RESULTS: During response inhibition, connectivity between the dorsolateral prefrontal cortex/supramarginal gyrus and supramarginal gyrus/middle temporal gyrus was associated with response to sertraline and venlafaxine, but not escitalopram. Sertraline responders had higher functional connectivity between these regions than non-responders, whereas venlafaxine responders had lower functional connectivity. For sertraline, attenuation of connectivity in the precentral and superior temporal gyri correlated with post-treatment symptom improvement. For venlafaxine, enhancement of connectivity between the orbitofrontal cortex and subcortical regions correlated with symptom improvement. CONCLUSIONS: Connectivity of the cognitive control circuit during response inhibition selectively and differentially predicts antidepressant treatment response and correlates with symptom improvement. These quantitative markers tied to the neurobiology of cognitive features of depression could be used translationally to predict and evaluate treatment response. CLINICAL TRIALS REGISTRATION: Registry Name: ClinicalTrials.gov URL: https://clinicaltrials.gov/ct2/show/NCT00693849 Registration Number: NCT00693849

The 7.5% CO2inhalational model (‘CO2challenge’) can be used to explore potential treatments for generalized anxiety disorder. However, it remains unknown how inter-individual variability in the functional architecture of negative affective valence systems might relate to the anxiogenic response to CO2challenge. In this pilot study, we explored how connectivity in systems associated with processing potential threat (“anxiety”) correlated with behavioural measures of anxiety following prolonged CO2inhalation.The negative affective valence system was identified using a passive emotional face perception task. Spherical regions of interest were created from peak voxels of significant brain activation when 100 young adult participants viewed emotional faces compared with black and white concentric circles during a functional MRI scan. Using these regions of interest, generalized psychophysiological interaction (gPPI) analysis was undertaken to explore task-evoked functional connectivity in a separate group of 13 healthy volunteers. Within 7 days of the scan, these participants underwent CO2challenge and results from the gPPI analysis were correlated with CO2outcome measures.Exposure to CO2challenge significantly increased subjective anxiety, negative affect, systolic blood pressure and heart rate. Functional connectivity between the ventromedial prefrontal cortex and right amygdala was positively correlated with heart rate. Increased connectivity between the vmPFC and the right amygdala, and decreased connectivity between the midcingulate cortex (MCC) and the left amygdala, correlated with subjective anxiety during CO2challenge.Response to CO2challenge was related to task-evoked functional connectivity between regions known to be important in processing potential threat. Further studies are required to assess whether this translates into clinical populations. Measures of functional connectivity within emotional processing networks could be potential biomarkers to enable stratification of healthy volunteers, and to examine correlates of response, in trials using experimental medicine models.

Background Abundant clinical studies have suggested that emotion dysregulation seems to be the essential pathogenesis for Internet gaming disorder (IGD). However, the neural mechanism of emotion regulation for IGD is still unclear. Methods Subjective evaluation and fMRI data were collected from 50 subjects (IGD: 24; recreational game user (RGU): 26) while they were performing an emotion reappraisal task. We collected and compared their brain features during emotion processing of different visual stimuli. Results Higher activation in the left dorsal anterior cingulate cortex (dACC), right ventral ACC, left claustrum and bilateral insula was observed in participants with IGD during emotion reappraisal relative to that of the RGU participants. In addition, generalized psychophysiological interaction analysis also showed that IGD participants had stronger functional connectivity between the right insula and bilateral dorsolateral prefrontal cortex (DLPFC) than the RGU participants. Conclusions The results suggest that IGD participants could not down-regulate their negative emotional experiences as efficiently as the RGU participants, although they engaged more cognitive resources. These results reveal the special neural circuits of emotion dysregulation in IGD individuals and provide new neural perspective for the intervention of IGD.

Previous studies have identified the ventral and dorsal brain regions that respectively support semantic and non-semantic phonological access. Nevertheless, the specific role of the left occipitotemporal cortex (lOTC) in the two pathways of phonological access is ambiguous. To address that question, the present study compared word reading in Chinese (presumably relying on the semantic pathway) with that in English (presumably relying on the non-semantic pathway). Results revealed a clear dissociation in the involvement of the anterior and posterior lOTC in semantic and non-semantic phonological access. Specifically, the anterior lOTC showed greater activation for Chinese than for English, whereas the posterior lOTC showed greater activation for English than for Chinese. More importantly, both psychophysiological interaction analysis and resting-state functional connectivity analysis showed that the anterior lOTC was functionally connected to the ventral brain regions (e.g., left anterior fusiform gyrus, anterior temporal lobe, and ventral inferior frontal gyrus), whereas the posterior lOTC was functionally connected to the dorsal brain regions (e.g., left posterior superior temporal gyrus, supramarginal gyrus, and dorsal inferior frontal gyrus). These results suggest that the anterior and posterior lOTC are involved in semantic and non-semantic phonological access, respectively.

Naming individual objects is accompanied with semantic recognition. Previous studies examined brain‐networks responsible for these operations individually. However, it remains unclear how these brain‐networks are related. To address this problem, we examined the brain‐networks during a novel object‐naming task, requiring participants to name animals in photographs at a specific‐level (e.g., “pigeon”). When the participants could not remember specific names, they answered basic names (e.g., “bird”). After fMRI scanning during the object‐naming task, the participants rated familiarity of the animals based on their sense of knowing. Since participants tend to remember specific names for familiar objects compared with unfamiliar objects, a typical issue in an object‐naming task is an internal covariance between the naming and familiarity levels. We removed this confounding factor by adjusting the familiarity/naming level of stimuli, and demonstrated distinct brain regions related to the two operations. Among them, the left inferior frontal gyrus triangularis (IFGtri) contained object‐naming and semantic‐recognition related areas in its anterior‐ventral and posterior‐dorsal parts, respectively. Psychophysiological interaction analyses suggested that both parts show connectivity with the brain regions related to object‐naming. By examining the connectivity under control tasks requiring nonlexical semantic retrieval (e.g., animal's body color), we found that both IFGtri parts altered their targeting brain areas according to the required memory attributes, while only the posterior‐dorsal part connected the brain regions related to semantic recognition. Together, the semantic recognition may be processed by distinct brain network from those for voluntary semantic retrievals including object‐naming although all these networks are mediated by the posterior‐dorsal IFGtri.

In everyday conversation, we usually process the talker's face as well as the sound of the talker's voice. Access to visual speech information is particularly useful when the auditory signal is degraded. Here, we used fMRI to monitor brain activity while adult humans (n= 60) were presented with visual-only, auditory-only, and audiovisual words. The audiovisual words were presented in quiet and in several signal-to-noise ratios. As expected, audiovisual speech perception recruited both auditory and visual cortex, with some evidence for increased recruitment of premotor cortex in some conditions (including in substantial background noise). We then investigated neural connectivity using psychophysiological interaction analysis with seed regions in both primary auditory cortex and primary visual cortex. Connectivity between auditory and visual cortices was stronger in audiovisual conditions than in unimodal conditions, including a wide network of regions in posterior temporal cortex and prefrontal cortex. In addition to whole-brain analyses, we also conducted a region-of-interest analysis on the left posterior superior temporal sulcus (pSTS), implicated in many previous studies of audiovisual speech perception. We found evidence for both activity and effective connectivity in pSTS for visual-only and audiovisual speech, although these were not significant in whole-brain analyses. Together, our results suggest a prominent role for cross-region synchronization in understanding both visual-only and audiovisual speech that complements activity in integrative brain regions like pSTS.SIGNIFICANCE STATEMENTIn everyday conversation, we usually process the talker's face as well as the sound of the talker's voice. Access to visual speech information is particularly useful when the auditory signal is hard to understand (e.g., background noise). Prior work has suggested that specialized regions of the brain may play a critical role in integrating information from visual and auditory speech. Here, we show a complementary mechanism relying on synchronized brain activity among sensory and motor regions may also play a critical role. These findings encourage reconceptualizing audiovisual integration in the context of coordinated network activity.

Background: Although higher cardiorespiratory fitness (CRF) has been linked to better executive function, the mechanisms by which this occurs remain a matter of speculation. One hypothesis is that higher CRF is associated with elevated top-down control in which brain regions processing task-relevant information are up-regulated and brain regions processing task-irrelevant information are down-regulated. Methods: We tested this top-down hypothesis in 50 young adults (μ age = 25.22 ± 5.17 years) by measuring CRF via a graded maximal exercise test and performing functional Magnetic Resonance Imaging (fMRI) during a color-word Stroop task. We used task-evoked functional connectivity, quantified from a psychophysiological interaction analysis (PPI), to test our hypotheses that (a) higher CRF would be associated with greater connectivity between control centers (i.e., prefrontal and parietal areas) and visual feature centers (i.e., occipital areas) that are involved with processing task-relevant stimulus dimensions (i.e., color), and (b) higher CRF would be associated with lower connectivity between control centers and visual feature centers that are involved with processing task-irrelevant dimensions of the stimuli (i.e., word processing areas). Results: Controlling for sex and BMI, we found, consistent with our second hypothesis, that higher CRF was associated with reduced functional connectivity between parietal and occipital areas involved in the task-irrelevant dimension of the task (i.e., word form areas). There were no associations between CRF and functional connectivity with the prefrontal cortex or evidence of heightened connectivity between attentional control and visual feature centers. Conclusions: These results suggest that CRF associations with executive functioning might be explained by CRF-mediated differences between brain regions involved with attentional control (parietal regions) and the down-regulation of regions involved with processing task-irrelevant stimulus features (occipital regions).

Background Deficient extinction learning and threat adaptation in the ventromedial prefrontal cortex (vmPFC)-amygdala circuitry strongly impede the efficacy of exposure-based interventions in anxiety disorders. Recent animal models suggest a regulatory role of the renin-angiotensin system in both these processes. Against this background, the present randomized placebo-controlled pharmacologic functional magnetic resonance imaging experiment aimed at determining the extinction enhancing potential of the angiotensin II type 1 receptor antagonist losartan (LT) in humans. Methods Seventy healthy male subjects underwent Pavlovian threat conditioning and received single-dose LT (50 mg) or placebo administration before extinction. Psychophysiological threat reactivity (skin conductance response) and neural activity during extinction served as primary outcomes. Psychophysiological interaction, voxelwise mediation, and novel multivariate pattern classification analyses were used to determine the underlying neural mechanisms. Results LT significantly accelerated the decline of the psychophysiological threat response during within-session extinction learning. On the neural level, the acceleration was accompanied and critically mediated by threat-specific enhancement of vmPFC activation. Furthermore, LT enhanced vmPFC-basolateral amygdala coupling and attenuated the neural threat expression, particularly in the vmPFC, during early extinction. Conclusions Overall the results indicate that LT facilitates within-session threat memory extinction by augmenting threat-specific encoding in the vmPFC and its regulatory control over the amygdala. The findings document a pivotal role of angiotensin regulation of extinction learning in humans and suggest that adjunct LT administration has the potential to facilitate the efficacy of exposure-based interventions in anxiety disorders.

Embodied theories of semantic cognition predict that brain regions involved in motion perception are engaged when people comprehend motion concepts expressed in language. Left lateral occipitotemporal cortex (LOTC) is implicated in both motion perception and motion concept processing but prior studies have produced mixed findings on which parts of this region are engaged by motion language. We scanned participants performing semantic judgements about sentences describing motion events and static events. We performed univariate analyses, multivariate pattern analyses (MVPA) and psychophysiological interaction (PPI) analyses to investigate the effect of motion on activity and connectivity in different parts of LOTC. In multivariate analyses that decoded whether a sentence described motion or not, the middle and posterior parts of LOTC showed above-chance level performance, with performance exceeding that of other brain regions. Univariate ROI analyses found the middle part of LOTC was more active for motion events than static ones. Finally, PPI analyses found that when processing motion events, the middle and posterior parts of LOTC (overlapping with motion perception regions), increased their connectivity with cognitive control regions. Taken together, these results indicate that the more posterior parts of LOTC, including motion perception cortex, respond differently to motion vs. static events. These findings are consistent with embodiment accounts of semantic processing, and suggest that understanding verbal descriptions of motion engages areas of the occipitotemporal cortex involved in perceiving motion.

Visual self-body recognition is one of the fundamental cognitive functions, and a major contributor to social development. Previous studies have shown that body identity judgement becomes difficult when subjects viewed their hand from a third-person perspective, and that this perspective effect was not observed when viewing the hand of another person, indicating that there are brain regions which are more strongly influenced by the perspective of one's own body than the body of another person. In this study, we aimed to depict the brain network contributing to the integration of perspective and identity of human bodies. We conducted a functional magnetic resonance imaging experiment where 29 participants observed their own or someone else's hand from first- and third-person perspectives. In the univariate analysis, none of the brain regions showed an interaction between perspective and body identity. However, in the searchlight and region-of-interest multivoxel pattern analysis (MVPA), decoding accuracies of self-hand from a first-person vs. those from a third-person perspective were higher than the decoding accuracies of other-hand from a first-person perspective vs. those from a third-person perspective in the early visual cortex. In addition, psychophysiological interaction analysis revealed a stronger effect of perspective of the self-hand than the other-hand condition in connectivity between the lateral occipito-temporal cortex and the early visual cortex, overlapped with the region depicted by MVPA. Our results suggest that the specific link between self-hand and first-person perspective is associated with identity-dependent perspective representations of the early visual cortex and functional connectivity between the early visual cortex and lateral occipito-temporal cortex, elucidating the nature of self-body recognition.

Intertemporal choice involves the evaluation of future rewards and reflects behavioral impulsivity. After choosing a delayed reward in an intertemporal choice, a behavioral agent waits for, receives, and then consumes the reward. The current study focused on the consumption of the delayed reward and examined the neural mechanisms of behavioral impulsivity. In humans consuming delayed real liquid rewards in an intertemporal choice, the ventral striatum (VS) showed differential activity between anterior (aVS) and posterior (pVS) regions depending on the degree of behavioral impulsivity. Additionally, impulsive individuals showed activity in the anterior prefrontal cortex (aPFC). An analysis of task-related effective connectivity based on psychophysiological interaction (PPI) revealed that PPI was robust from the aPFC to pVS, but not in the opposite direction. On the other hand, strong bidirectional PPIs were observed between the aVS and pVS, but PPIs from the pVS to aVS were enhanced in impulsive individuals. These results suggest that behavioral impulsivity is reflected in aPFC-VS mechanisms during the consumption of delayed real liquid rewards.

The amygdala and its connections with medial prefrontal cortex (mPFC) play central roles in the development of emotional processes. While several studies have suggested that this circuitry exhibits functional changes across the first two decades of life, findings have been mixed – perhaps resulting from differences in analytic choices across studies. Here we used multiverse analyses to examine the robustness of task-based amygdala–mPFC function findings to analytic choices within the context of an accelerated longitudinal design (4-22 years- old; N=98; 183 scans; 1-3 scans/participant). Participants, recruited from the greater Los Angeles area, completed an event-related emotional face (fear, neutral) task. Parallel analyses varying in preprocessing and modeling choices found that age-related change estimates for amygdala reactivity were more robust than task-evoked amygdala–mPFC functional connectivity to varied analytical choices. Specification curves indicated evidence for age-related decreases in amygdala reactivity to faces, though within-participant changes in amygdala reactivity could not be differentiated from between-participant differences. In contrast, amygdala—mPFC functional connectivity results varied across methods much more, and evidence for age-related change in amygdala–mPFC connectivity was not consistent. Generalized psychophysiological interaction (gPPI) measurements of connectivity were especially sensitive to whether a deconvolution step was applied. Our findings demonstrate the importance of assessing the robustness of findings to analysis choices, although the age-related changes in our current work cannot be overinterpreted given low test-retest reliability. Together, these findings highlight both the challenges in estimating developmental change in longitudinal cohorts and the value of multiverse approaches in developmental neuroimaging for assessing robustness of results. (Preprint: https://www.biorxiv.org/content/10.1101/2021.10.08.463601v1).Key PointsMultiverse analyses applied to fMRI data are valuable for determining the robustness of findings to varied analytical choicesIn the current study, age-related change estimates for amygdala reactivity were relatively robust to analytical decisions, though gPPI functional connectivity analyses were much more sensitive, leading some estimates to flip signBoth test-retest reliability and robustness to analytical choices are important considerations for developmental research

Introduction: Deceptive intentions may be realized by imparting false (simple deception) or true (manipulative truth) information. Both forms of deception require inferring others' thoughts and are underpinned by the theory of mind (TOM) neural system. Manipulative truth is thought to more strongly recruit these processes. However, the organization of functional interactions underlying simple deception and manipulative truth remains unclear. Materials and Methods: We performed psychophysiological interaction analysis for a key node in the TOM system, the right temporoparietal junction (rTPJ), using functional MRI data obtained from 23 volunteers (14 men and 9 women, age range 18-45 years) during the sender-receiver game. During the game, participants sent true, simple deceptive, or manipulative truthful messages to another player according to their own choice. A Bayesian approach to statistics was employed to perform statistical inference and define voxels with significant changes in functional interactions. Results: We observed functional interactions between nodes of the TOM system (bilateral TPJ, left precuneus, left dorsomedial prefrontal cortex, and right superior temporal sulcus) characterizing both forms of deception. We identified an increment in functional interactions of the rTPJ with the left TPJ (lTPJ) and right precuneus associated with manipulative truth. Furthermore, we demonstrated that a higher rate of manipulative truthful actions was associated with weaker functional interactions between the rTPJ and lTPJ, left precuneus, and left dorsomedial prefrontal cortex. Discussion: Compared with simple deception, manipulative truth is associated with a higher demand for socio-cognitive processes that contributes to the cognitive load of this form of deception.

Surprising scenarios can have different behavioural and neuronal consequences depending on the violation of the expectation. On the one hand, previous research has shown that the omission of a visual stimulus results in a robust cortical response representing that missing stimulus, a so-called negative prediction error. On the other hand, a large amount of studies revealed positive prediction error signals, entailing an increased neural response that can be attributed to the experience of a surprising, unexpected stimulus. However, there has been no evidence, so far, regarding how and when these prediction error signals co-occur. Here, we argue that the omission of an expected stimulus can and often does coincide with the appearance of an unexpected one. Therefore, we investigated whether positive and negative prediction error signals evoked by unpredicted cross-category stimulus transitions would temporally coincide during a speeded forced-choice fMRI paradigm. Foremost, our findings provide evidence of a behavioural effect regarding the facilitation of responses linked to expected stimuli. In addition, we obtained evidence for negative prediction error signals as seen in differential activation of FFA and PPA during unexpected place and face trials, respectively. Lastly, a psychophysiological interaction analysis revealed evidence for positive prediction error signals represented by context-dependent functional coupling between the right IFG and FFA or PPA, respectively, implicating a network that updates the internal representation after the appearance of an unexpected stimulus through involvement of this frontal area. The current results are consistent with a predictive coding account of cognition and underline the importance of considering the potential dual nature of expectation violations. Furthermore, our results put forward that positive and negative prediction error signalling can be directly linked to regions associated with the processing of different stimulus categories.

One of the central topics in cognitive neuroscience revolves around understanding how responses in the default mode network (DMN) relate to cognitive process and disease states. While there has been many investigations of the intrinsic patterns of activation and connectivity of the DMN with other networks at rest, i.e. when an individual is not engaged in any particular behavior, to truly understand the influence and significance of the DMN activation and connectivity, we must study it in association with a particular process. Reward processing is an integral part of goal-directed behavior that has been shown to rely on the striatum, a subcortical brain region that is connected to multiple regions of the prefrontal cortex (PFC) that belong to the DMN. Yet, it remains unclear how the DMN interacts with the striatum during reward processing. To investigate this issue, we analyzed card-guessing task data of 453 subjects from the Human Connectome Project and applied a novel network-based psychophysiological interaction analysis (nPPI) that quantified reward-dependent connectivity of the DMN. We show that only the DMN exhibits increased connectivity with the ventral striatum (VS) during the receipt of reward. This result was specific to the DMN and the strength of connectivity was associated with the personality characteristic of openness. These findings point to a novel role of the DMN during reward processing, and to the nPPI approach being able to capture a unique contribution of a collection of regions to task performance.

Individuals with obesity (OB) prefer immediate rewards of food intake over the delayed reward of healthy well-being achieved through diet management and physical activity, compared with normal-weight controls (NW). This may reflect heightened impulsivity, an important factor contributing to the development and maintenance of obesity. However, the neural mechanisms underlying the greater impulsivity in OB remain unclear. Therefore, the current study employed functional magnetic resonance imaging with a delay discounting (DD) task to examine the association between impulsive choice and altered neural mechanisms in OB. During decision-making in the DD task, OB compared with NW had greater activation in the dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex, which was associated with greater discounting rate and weaker cognitive control as measured with the Three-Factor Eating Questionnaire (TFEQ). In addition, the association between DLPFC activation and cognitive control (TFEQ) was mediated by discounting rate. Psychophysiological interaction analysis showed decreased connectivity of DLPFC–inferior parietal cortex (within executive control network [ECN]) and angular gyrus–caudate (ECN–reward) in OB relative to NW. These findings reveal that the aberrant function and connectivity in core regions of ECN and striatal brain reward regions underpin the greater impulsivity in OB and contribute to abnormal eating behaviors.

Background: Oxytocin (OXT), shown to decrease food intake in animal models and men, is a promising novel treatment for obesity. We have shown that in men with overweight and obesity, intranasal (IN) OXT reduced the functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent signal in the ventral tegmental area (VTA), the origin of the mesolimbic dopaminergic reward system, in response to high-calorie food vs. non-food images. Here, we employed functional connectivity fMRI analysis, which measures the synchrony in activation between neural systems in a context-dependent manner. We hypothesized that OXT would attenuate the functional connectivity of the VTA with key food motivation brain areas only when participants viewed high-calorie food stimuli. Methods: This randomized, double-blind, placebo-controlled crossover study of 24 IU IN OXT included 10 men with overweight or obesity (mean±SEM BMI: 28.9±0.8 kg/m2). Following drug administration, subjects completed an fMRI food motivation paradigm including images of high and low-calorie foods, non-food objects, and fixation stimuli. A psychophysiological interaction analysis was performed with the VTA as seed region. Results: Following OXT administration, compared with placebo, participants exhibited significantly attenuated functional connectivity between the VTA and the insula, oral somatosensory cortex, amygdala, hippocampus, operculum, and middle temporal gyrus in response to viewing high-calorie foods (Z≥3.1, cluster-corrected, p