Studies comparing neural correlates of reward processing across development yield inconsistent findings. This challenges theories characterizing adolescents as globally hypo- or hypersensitive to rewards. Developmental differences in reward sensitivity may fluctuate based on reward magnitude, and on whether rewards require decision-making. We examined whether these factors modulate developmental differences in neural response during reward anticipation and/or receipt in 26 adolescents (14.05±2.37yrs) and 26 adults (31.25±8.23yrs). Brain activity was assessed with fMRI during reward anticipation, when subjects made responses with-vs.-without decision-making, to obtain large–vs.–small rewards, and during reward receipt. When reward-receipt required decision-making, neural activity did not differ by age. However, when reward receipt did not require decision-making, neural activity varied by development, reward magnitude, and stage of the reward task. During anticipation, adolescents, but not adults, exhibited greater activity in the insula, extending into putamen, and cingulate gyrus for large-vs.-small incentives. During feedback, adults, but not adolescents, exhibited greater activity in the precuneus for large-vs.-small incentives. These data indicate that age-related differences in reward sensitivity cannot be characterized by global hypo- or hyper-responsivity. Instead, neural responding in striatum, prefrontal cortex and precuneus is influenced by both situational demands and developmental factors. This suggests nuanced maturational effects in adolescent reward sensitivity.
reward; incentive; brain; fMRI; development; adolescents; decision-making
Generalized Social Phobia (GSP) and Generalized Anxiety Disorder (GAD) are both associated with emotion dysregulation. In healthy subjects, research implicates dorsal anterior cingulate (dACC) in both explicit emotion regulation and top-down attentional control. While studies have examined these processes in GSP or GAD, no work compares findings across the two disorders. Moreover, no work examines functioning in cases comorbid for both disorders (GSP/GAD). Here we compare the neural correlates of explicit emotion regulation (EER) and top-down attentional control (TAC) in GSP, GAD, and GSP/GAD.
Medication-free adults with GSP (EER n=19; TAC n=18), GAD (EER n=17; TAC n =17), GSP/GAD (EER n=17; TAC=15), or no psychopathology (EER n=18; TAC n=18). During EER, individuals alternatively viewed, up-regulated, and down-regulated responses to emotional pictures. During TAC, they performed an emotional Stroop task.
For both tasks, significant group-by-condition interactions emerged in dACC and parietal cortices. Healthy adults showed significantly increased recruitment during emotion regulation, relative to emotion-picture viewing. GAD, GSP, and GSP/GAD subjects showed no such increases, with all three groups differing from healthy adults but not from each other. Evidence of emotion-related disorder-specificity emerged in medial prefrontal cortex (MPFC) and amygdala. This disorder-specific responding varied as a function of stimulus emotion content but not emotion-regulatory demands.
GSP and GAD both involve reduced capacity for engaging emotion-regulation brain networks, whether explicitly or via top-down attentional control. A reduced ability to recruit regions implicated in top-down attention might represent a general risk factor for anxiety disorders.
imaging; social anxiety; generalized anxiety; emotion regulation; anterior cingulate cortex; top-down attentional control
The current study examined the relations between individual differences in sustained attention in infancy, the temperamental trait behavioral inhibition in childhood, and social behavior in adolescence. The authors assessed 9-month-old infants using an interrupted-stimulus attention paradigm. Behavioral inhibition was subsequently assessed in the laboratory at 14 months, 24 months, 4 years, and 7 years. At age 14 years, adolescents acted out social scenarios in the presence of an unfamiliar peer as observers rated levels of social discomfort. Relative to infants with high levels of sustained attention, infants with low levels of sustained attention showed increasing behavioral inhibition throughout early childhood. Sustained attention also moderated the relation between childhood behavioral inhibition and adolescent social discomfort, such that initial levels of inhibition at 14 months predicted later adolescent social difficulties only for participants with low levels of sustained attention in infancy. These findings suggest that early individual differences in attention shape how children respond to their social environments, potentially via attention’s gate-keeping role in framing a child’s environment for processing.
sustained attention; temperament; social behavior; infancy; childhood and adolescence
Behaviorally inhibited children display a temperamental profile characterized by social withdrawal and anxious behaviors. Previous research, focused largely on adolescents, suggests that attention biases to threat may sustain high levels of behavioral inhibition (BI) over time, helping link early temperament to social outcomes. However, no prior studies examine the association between attention bias and BI before adolescence. The current study examined the interrelations among BI, attention biases to threat, and social withdrawal already manifest in early childhood. Children (N=187, 83 Male, Mage=61.96 months) were characterized for BI in toddlerhood (24 & 36 months). At 5 years, they completed an attention bias task and concurrent social withdrawal was measured. As expected, BI in toddlerhood predicted high levels of social withdrawal in early childhood. However, this relation was moderated by attention bias. The BI-withdrawal association was only evident for children who displayed an attention bias toward threat. The data provide further support for models associating attention with socioemotional development and the later emergence of clinical anxiety.
Temperament; Behavioral inhibition; Social withdrawal; Attention biases; Early childhood
A better understanding of the neural underpinnings of bipolar disorder (BD) can be obtained by examining brain activity in symptom-free individuals at risk for BD. This study examined the neural correlates of motor inhibition in a sample of symptom-free youths at familial risk for BD.
19 euthymic youths with BD, 13 asymptomatic youths with a first-degree relative with BD, and 21 healthy comparison children completed the stop signal task in a 3T scanner.
Children at familial risk for BD exhibited increased putamen activation during unsuccessful inhibition that distinguished them from both healthy and BD children. Youths with BD exhibited reduced activation of the right nucleus accumbens during unsuccessful inhibition as compared to the other participant groups.
Striatal activation patterns differ between youths at risk for BD and healthy comparison children during a motor inhibition task.
motor inhibition; bipolar disorder; population at risk; magnetic resonance imaging
Anxiety disorders are highly prevalent in children and adolescents, and are associated with aberrant emotion-related attention orienting and inhibitory control. While recent studies conducted with high-trait anxious adults have employed novel emotion-modified antisaccade tasks to examine the influence of emotional information on orienting and inhibition, similar studies have yet to be conducted in youths.
Participants were 22 children/adolescents diagnosed with an anxiety disorder, and 22 age-matched healthy comparison youths. Participants completed an emotion-modified antisaccade task that was similar to those used in studies of high-trait anxious adults. This task probed the influence of abruptly appearing neutral, happy, angry, or fear stimuli on orienting (prosaccade) or inhibitory (antisaccade) responses.
Anxious compared to healthy children showed facilitated orienting towards angry stimuli. With respect to inhibitory processes, threat-related information improved antisaccade accuracy in healthy but not anxious youth. These findings were not linked to individual levels of reported anxiety or specific anxiety disorders.
Findings suggest that anxious relative to healthy children manifest enhanced orienting towards threat-related stimuli. Additionally, the current findings suggest that threat may modulate inhibitory control during adolescent development.
Anxiety; Development; Children; Emotion; Orienting; Inhibition; Bias; Saccade
Youths with conduct disorder or oppositional defiant disorder and psychopathic traits (CD/ODD+PT) are at high risk of adult anti-social behaviour and psychopathy. Neuroimaging studies demonstrate functional abnormalities in orbitofrontal cortex and the amygdala in both youths and adults with psychopathic traits. Diffusion tensor imaging in psychopathic adults demonstrates disrupted structural connectivity between these regions (uncinate fasiculus). The current study examined whether functional neural abnormalities present in youths with CD/ODD+PT are associated with similar white matter abnormalities. Youths with CD/ODD+PT and comparison participants completed 3.0 T diffusion tensor scans and functional MRI scans. Diffusion tensor imaging did not reveal disruption in structural connections within the uncinate fasiculus or other white matter tracts in youths with CD/ODD+PT, despite the demonstration of disrupted amygdala-prefrontal functional connectivity in these youths. These results suggest that disrupted amygdala-frontal white matter connectivity as measured by fractional anisotropy is less sensitive than imaging measurements of functional perturbations in youths with psychopathic traits. If white matter tracts are intact in youths with this disorder, childhood may provide a critical window for intervention and treatment, before significant structural brain abnormalities solidify.
Psychopathic traits; conduct disorder; oppositional defiant disorder; diffusion tensor imaging; functional connectivity
Social Anxiety Disorder (SAD) is a common and debilitating condition that typically manifests in adolescence. Here we describe cognitive factors engaged by brain-imaging tasks, which model the peer-based social interactions that evoke symptoms of SAD. We then present preliminary results from the Virtual School paradigm, a novel peer-based social interaction task. This paradigm is designed to investigate the neural mechanisms mediating individual differences in social response flexibility and in participants’ responses to uncertainty in social contexts. We discuss the utility of this new paradigm for research on brain function and developmental psychopathology.
fMRI; Development; Peers; Uncertainty; Social cognition; Affect; Behavioral inhibition; Response flexibility; Peer victimization; Bullying
Serotonin is strongly implicated in the mammalian stress response, but surprisingly little is known about its mode of action. Recent data suggest that serotonin can inhibit aversive responding in humans, but this remains underspecified. In particular, data in rodents suggest that global serotonin depletion may specifically increase long-duration bed nucleus of the stria terminalis (BNST)-mediated aversive responses (ie, anxiety), but not short-duration BNST-independent responses (ie, fear). Here, we extend these findings to humans. In a balanced, placebo-controlled crossover design, healthy volunteers (n=20) received a controlled diet with and without the serotonin precursor tryptophan (acute tryptophan depletion; ATD). Aversive states were indexed by translational acoustic startle measures. Fear and anxiety were operationally defined as the increase in startle reactivity during short- and long-duration threat periods evoked by predictable shock (fear-potentiated startle) and by the context in which the shocks were administered (anxiety-potentiated startle), respectively. ATD significantly increased long-duration anxiety-potentiated startle but had no effect on short-duration fear-potentiated startle. These results suggest that serotonin depletion in humans selectively increases anxiety but not fear. Current translational frameworks support the proposition that ATD thus disinhibits dorsal raphé-originating serotonergic control of corticotropin-releasing hormone-mediated excitation of the BNST. This generates a candidate neuropharmacological mechanism by which depleted serotonin may increase response to sustained threats, alongside clear implications for our understanding of the manifestation and treatment of mood and anxiety disorders.
ATD; serotonin; anxiety; startle; depression; biological psychiatry; serotonin; mood/anxiety/stress disorders; psychiatry & behavioral sciences; ATD; anxiety; startle
Attention biases towards threat are often detected in individuals with anxiety disorders. Threat biases can be measured experimentally through dot-probe paradigms, in which individuals detect a probe following a stimulus pair including a threat. On these tasks, individuals with anxiety tend to detect probes that occur in a location previously occupied by a threat (i.e., congruent) faster than when opposite threats (i.e., incongruent). In pediatric anxiety disorders, dot-probe paradigms detect abnormal attention biases towards threat and abnormal ventrolateral prefrontal cortex (vlPFC) function. However, it remains unclear if this aberrant vlPFC activation occurs while subjects process threats (e.g., angry faces) or, alternatively, while they process and respond to probes. This magnetoencephalography (MEG) study was designed to answer this question.
Adolescents with either generalized anxiety disorder (GAD, n=17) or no psychiatric diagnosis (n=25) performed a dot-probe task involving angry and neutral faces while MEG data were collected. Synthetic Aperture Magnetometry (SAM) beamformer technique was used to determine whether there were group differences in power ratios while subjects processed threats (i.e., angry vs. neutral faces) or when subjects responded to incongruent vs. congruent probes.
Group differences in vlPFC activation during the response period emerged with a 1-30 Hz frequency band. No group differences in vlPFC activation were detected in response to angry-face cues.
In the dot-probe task, anxiety-related perturbations in vlPFC activation reflect abnormal attention control when responding to behaviorally-relevant probes, but not to angry faces. Given that motor responses to these probes are used to calculate threat bias, this study provides insight into the pathophysiology reflected in this commonly-used marker of anxiety. In addition, this finding may inform the development of novel anxiety-disorder treatments targeting the vlPFC to enhance attention control to task-relevant demands.
magnetoencephalography; ventrolateral prefrontal cortex; attention
Bipolar disorder (BD) is highly debilitating in both children and adults. Child and adult BD patients show both behavioral deficits in face emotion processing and abnormal amygdala activation. However, amygdala function in pediatric vs. adult BD patients has never been compared directly.
This study compared amygdala responses to emotional facial expressions in 74 subjects [pediatric (N=18) and adult (N=17) patients with BD, healthy volunteer (HV) children (N=15) and adults (N=22)]. Subjects performed a gender identification task while viewing fearful, angry, and neutral faces.
In response to fearful faces, patients with BD across age-groups showed right amygdala hyperactivity relative to healthy volunteers. However, when responses to all facial expressions were combined, pediatric patients exhibited greater right amygdala activation than either adults with BD or HV children.
Amygdala hyperactivity in response to fearful faces is present in both youths and adults with BD. However, compared to adults with BD or healthy youths, youths with BD show amygdala hyperactivity in response to a broad array of emotional faces. Thus, abnormal amygdala activation during face processing appears to be more pervasive in children than adults with BD.
In both human and nonhuman primates the eyes are a highly salient feature of the face, conveying identity, emotion and attentional direction of conspecifics. Studies have indicated that the amygdala plays an important role in eye contact, and amygdala dysfunction may underlie social deficits in disorders such as autism through effects on eye contact. In the present study we compared the volume of the amygdala in 32 juvenile rhesus monkeys to visual fixation patterns in a social memory paradigm. Amygdala volume was determined from manual traces of structural MRIs and fixation patterns were assessed using eyetracking methodology. A significant positive relationship was found between amygdala volume and fixation on both the face and the eye region. Amygdala volume was also found to relate to habituation across multiple presentations of different photographs of the same individual monkeys indicating a role in social memory. These data provide an important linkage between structural variation of amygdala and previous demonstrations of function in a nonhuman primate model.
Face Recognition; MRI; Social; Affiliative; Gaze
Similar patterns of vulnerability to CO2 inhalation have been reported in adults with panic disorder (PD) and children with separation anxiety disorder (SAD), suggesting a link between the adult and child conditions. This study examines the influence of familial risk for PD on CO2 responses in children with SAD. We hypothesized that offspring with SAD of parents with PD would have distinct CO2 responses.
Two hundred twelve nine-to-20 year-old offspring of parents with or without PD exposed to maintained 5% CO2 inhalation in the participants' homes. Anxiety symptoms, panic attacks, and respiratory physiology (respiratory frequency and tidal volume) were monitored during baseline and 15 minutes maintained CO2 breathing.
As hypothesized, significant offspring SAD by parent PD interactions were obtained for anxiety symptoms, respiratory frequency, tidal volume, and an panting index during CO2 inhalation. Offspring with both SAD and parental PD exhibited more anxiety symptoms at termination of 5% CO2 breathing than the other offspring groups, and had the most extreme values on measures of respiratory physiology.
Youth with both SAD and parental PD have respiratory responses to CO2 similar to adult PD. They may be a subtype of SAD at particularly high risk for adult PD.
Separation Anxiety Disorder; Panic Disorder; At Risk; Carbon Dioxide Hypersensitivity; Respiratory Frequency; Tidal Volume
Behavioral inhibition (BI) is a temperament characterized in young children by a heightened sensitivity to novelty, social withdrawal, and anxious behaviors. For many children, these social difficulties dissipate over time. For others, patterns of social withdrawal continue into adolescence. Over time, attention biases to threat may influence the stability of behavioral inhibition and its association with social withdrawal, ultimately modulating the risk for anxiety disorders in BI children. However, we know relatively little about the cognitive processes that accompany BI and shape later socio-emotional functioning. We examined the relations among BI in childhood, attention biases to threat in adolescence, and adolescent social withdrawal in a longitudinal study (N=126, Mean age=15 years). As has been reported in anxious adults, adolescents who were behaviorally inhibited as toddlers and young children showed heightened attention bias to threat. In addition, attention bias to threat moderated the relation between childhood BI and adolescent social withdrawal.
Temperament; Behavioral Inhibition; Social Withdrawal; Attention Biases
Research on attention provides a promising framework for studying anxiety pathophysiology and treatment. The study of attention biases appears particularly pertinent to developmental research, as attention affects learning and has down-stream effects on behavior. This review summarizes recent findings about attention orienting in anxiety, drawing on findings in recent developmental psychopathology and affective neuroscience research. These findings generate specific insights about both development and therapeutics. The review goes beyond a traditional focus on biased processing of threats and considers biased processing of rewards. Building on this work, we then turn to treatment of pediatric anxiety, where manipulation of attention to threat and/or reward may serve a therapeutic role as a component of Attention Bias Modification Therapy.
Early-life stress (ES) such as adoption, change of caregiver, or experience of emotional neglect may influence the way in which affected individuals respond to emotional stimuli of positive or negative valence. These modified responses may stem from a direct alteration of how emotional stimuli are coded, and/or the cognitive function implicated in emotion modulation, such as self-regulation or inhibition. These ES effects have been probed on tasks either targeting reward and inhibitory function. Findings revealed deficits in both reward processing and inhibitory control in ES youths. However, no work has yet examined whether incentives can improve automatic response or inhibitory control in ES youths.
To determine whether incentives would only improve self-regulated voluntary actions or generalize to automated motoric responses, participants were tested on a mixed eye movement task that included reflex-like prosaccades and voluntary controlled antisaccade eye movements. Seventeen adopted children (10 females, mean age 11.3 years) with a documented history of neglect and 29 typical healthy youths (16 females, mean age 11.9 years) performed the mixed prosaccade/antisaccade task during monetary incentive conditions or during no-incentive conditions.
Across both saccade types, ES adolescents responded more slowly than controls. As expected, control participants committed fewer errors on antisaccades during the monetary incentive condition relative to the no-incentive condition. By contrast, ES youths failed to show this incentive-related improvement on inhibitory control. No significant incentive effects were found with prepotent prosaccades trials in either group. Finally, co-morbid psychopathology did not modulate the findings.
These data suggest that youths with experience of early stress exhibit deficient modulation of inhibitory control by reward processes, in tandem with a reward-independent deficit in preparation for both automatic and controlled responses. These data may be relevant to interventions in ES youths.
reward; antisaccade; cognitive control; early adversity; stress
Youth at familial risk for bipolar disorder (BD) show deficits in face emotion processing, but the neural correlates of these deficits have not been examined. This preliminary study tests the hypothesis that, relative to healthy comparisons (HC), both BD subjects and youth at-risk for BD (i.e., those with a first-degree BD relative) will demonstrate amygdala hyperactivation when viewing fearful and happy faces. The at-risk youth were unaffected, in that they had no history of mood disorder.
Amygdala activity was examined in 101 unrelated participants, 8-18 years old. Age, gender, and IQ-matched groups included BD (N=32), unaffected at-risk (N=13), and HC (N=56). During fMRI scanning, participants attended to emotional and non-emotional aspects of fearful and happy faces.
While rating their fear of fearful faces, both BD and unaffected at-risk subjects exhibited amygdala hyperactivity vs. HC. There were no between-group differences in amygdala activity in response to happy faces. Post-hoc comparisons revealed that, in at-risk youth, familial risk status (offspring vs. sibling), presence of Axis I diagnosis (N=1 ADHD, 1 social phobia), and history of medication exposure (N=1) did not influence imaging findings.
We found amygdala hyperactivation in both unaffected at-risk and BD youth while rating their fear of fearful faces. These pilot data suggest that both face emotion labeling deficits and amygdala hyperactivity during face processing should receive further study as potential BD endophenotypes. Longitudinal studies should test whether amygdala hyperactivity to fearful faces predicts conversion to BD in at-risk youth.
bipolar; anxiety; endophenotype; fMRI; faces
This study examined relations among family environment, cortisol response, and behavior in the context of a randomized controlled trial with 92 children (M = 48 months) at risk for antisocial behavior. Previously, researchers reported an intervention effect on cortisol response in anticipation of a social challenge. The current study examined whether changes in cortisol response were related to later child aggression. Among lower warmth families, the intervention effect on aggression was largely mediated by the intervention effect on cortisol response. Although the intervention also resulted in significant benefits on child engaging behavior, cortisol response did not mediate this effect. These findings demonstrate meaningful associations between cortisol response and aggression among children at familial risk for antisocial behavior.
Previous studies demonstrate that anxiety is characterized by biased attention toward threats, typically measured by differences in motor reaction time to threat and neutral cues. Using eye-tracking methodology, the current study measured attention biases in anxious and nonanxious youth, using unrestricted free viewing of angry, happy, and neutral faces.
Eighteen anxious and 15 nonanxious youth (8–17 years old) passively viewed angry-neutral and happy-neutral face pairs for 10 s while their eye movements were recorded.
Anxious youth displayed a greater attention bias toward angry faces than nonanxious youth, and this bias occurred in the earliest phases of stimulus presentation. Specifically, anxious youth were more likely to direct their first fixation to angry faces, and they made faster fixations to angry than neutral faces.
Consistent with findings from earlier, reaction-time studies, the current study shows that anxious youth, like anxious adults, exhibit biased orienting to threat-related stimuli. This study adds to the existing literature by documenting that threat biases in eye-tracking patterns are manifest at initial attention orienting.
anxiety; threat-bias; orienting; eye tracking
Youth with bipolar disorder (BD) show behavioral and neural deficits in cognitive flexibility; however, whether such deficits exist among youths at risk for BD has not been explored.
The current fMRI study examined the neural basis of cognitive flexibility in BD youth (n=28), unaffected youth at risk for BD (AR; n=13), and healthy volunteer youth (HV; n=21) by comparing brain activation patterns while participants performed the change task. On change trials, subjects must inhibit a prepotent response and execute an alternate one.
During successful change trials, both BD and AR youth had increased right ventrolateral prefrontal and inferior parietal activity, compared to HV youth. During failed change trials, both BD and AR youth exhibited increased caudate activation relative to HV youth, but BD youth showed increased activation in the subgenual anterior cingulate cortex (ACC) relative to the other two groups.
Abnormal activity in ventrolateral prefrontal cortex, inferior parietal cortex, and striatum during a cognitive flexibility task may represent a potential BD endophenotype, but subgenual ACC dysfunction may represent a marker of BD illness itself.
bipolar disorder; relatives; fMRI; cognitive flexibility; cognitive control
Controversy exists about whether non-episodic irritability (operationalized as severe mood dysregulation, SMD) should be considered a developmental presentation of pediatric bipolar disorder (BD). While assessments of brain function may address this controversy, only one fMRI study has compared BD versus SMD. We compared neural activation in BD, SMD, and controls during a motor inhibition task, since motor disinhibition is an important clinical feature in both BD and SMD. During failed inhibition, BD youths exhibited less activation in the right anterior cingulate cortex (ACC) and right nucleus accumbens relative to both SMD and healthy youths. Exploratory analyses indicate that, in BD youths, reduced activation in the right ACC may be independent of comorbid ADHD. These findings highlight neural distinctions between the phenotypically related BD and SMD populations.
Peer feedback affects adolescents’ behaviors, cognitions and emotions. We examined neural circuitry underlying adolescents’ emotional response to peer feedback using a functional neuroimaging paradigm whereby, 36 adolescents (aged 9–17 years) believed they would interact with unknown peers postscan. Neural activity was expected to vary based on adolescents’ perceptions of peers and feedback type. Ventrolateral prefrontal cortex (vlPFC) activity was found when adolescents indicated how they felt following feedback (acceptance or rejection) from peers of low vs high interest. Greater activation in both cortical (e.g. superior temporal gyrus, insula, anterior cingulate) and subcortical (e.g. striatum, thalamus) regions emerged in response to acceptance vs rejection feedback. Response to acceptance also varied by age and gender in similar regions (e.g. superior temporal gyrus, fusiform, insula), with greater age-related increases in activation to acceptance vs rejection for females than males. Affective response to rejection vs acceptance did not yield significantly greater neural activity in any region. vlPFC response suggests cognitive flexibility in reappraising initial perceptions of peers following feedback. Striatal response suggests that acceptance is a potent social reward for adolescents, an interpretation supported by more positive self-reported affective response to acceptance than rejection from high- but not low-interest peers.
adolescence; cognitive flexibility; peer feedback; social reward
Stressful experiences modulate neuro-circuitry function, and the temporal trajectory of these alterations, elapsing from early disturbances to late recovery, heavily influences resilience and vulnerability to stress. Such effects of stress may depend on processes that are engaged during resting-state, through active recollection of past experiences and anticipation of future events, all known to involve the default mode network (DMN). By inducing social stress and acquiring resting-state functional magnetic resonance imaging (fMRI) before stress, immediately following it, and 2 h later, we expanded the time-window for examining the trajectory of the stress response. Throughout the study repeated cortisol samplings and self-reports of stress levels were obtained from 51 healthy young males. Post-stress alterations were investigated by whole brain resting-state functional connectivity (rsFC) of two central hubs of the DMN: the posterior cingulate cortex (PCC) and hippocampus. Results indicate a ’recovery’ pattern of DMN connectivity, in which all alterations, ascribed to the intervening stress, returned to pre-stress levels. The only exception to this pattern was a stress-induced rise in amygdala-hippocampal connectivity, which was sustained for as long as 2 h following stress induction. Furthermore, this sustained enhancement of limbic connectivity was inversely correlated to individual stress-induced cortisol responsiveness (AUCi) and characterized only the group lacking such increased cortisol (i.e., non-responders). Our observations provide evidence of a prolonged post-stress response profile, characterized by both the comprehensive balance of most DMN functional connections and the distinct time and cortisol dependent ascent of intra-limbic connectivity. These novel insights into neuro-endocrine relations are another milestone in the ongoing search for individual markers in stress-related psychopathologies.
fMRI; resting-state functional connectivity; default-mode network; recovery; limbic connectivity