VLPFC Activation Research Articles

I Like Them…Will They Like Me? Evidence for the Role of the Ventrolateral Prefrontal Cortex During Mismatched Social Appraisals in Anxious Youth.

Socially anxious adolescents report distress during social decision-making, wherein their favorable view of peers directly conflicts with their expectation to be viewed negatively by peers; a phenomenon we refer to as "mismatch bias." The present study utilizes a novel paradigm with dynamic social stimuli to explore the correlates of mismatch biases in anxious and healthy youth. The behavioral and neural correlates of mismatch biases were assessed in healthy (N = 17) and anxious (N = 14) youth during functional MRI. Participants completed a novel task where they viewed silent videos of unknown peers. After viewing each video, participants appraised the social desirability of the peer ("How much do you think you would like them [if you met them]") or predicted how socially desirable the peer would find them ("How much do you think they would like you [if you met them]"). Each participant's mismatch bias was calculated as the difference between their appraisal of peers and their prediction of peers' appraisal of them. We found that anxious youth exhibited mismatch bias: they rated unknown peers as more desirable than they predicted peers would rate them. This effect was not present in the healthy group. Mismatch biases were associated with increased engagement of the ventrolateral prefrontal cortex (vlPFC), a region broadly involved in flexible cognitions and behavioral selection. In addition, greater mismatch biases and vlPFC activation during mismatch biases were associated with more severe anxiety symptoms. The findings highlight the importance of understanding mismatch biases to inform treatments that target distress elicited by discrepant social appraisals in anxious youth.

Are ventrolateral and dorsolateral prefrontal cortices involved in the computerized Corsi block-tapping test execution? An fNIRS study.

The Corsi block-tapping test (CBT) is an old neuropsychological test that, requiring the storage and the reproduction of spatial locations, assesses spatial working memory (WM). Despite its wide use in clinical practice, the specific contribution of prefrontal cortex (PFC) subregions during CBT execution has not been clarified yet. Considering the importance of spatial WM in daily life and the well-known role of ventrolateral-PFC/dorsolateral-PFC (VLPFC/DLPFC) in WM processes, the present study was aimed at investigating, by a 20-channel functional near-infrared spectroscopy (fNIRS) system (including four short-separation channels), the hemodynamic response of the VLPFC/DLPFC during a computerized version of the CBT. Thirty-nine university students were asked to perform CBT standard version (CBTs), block-suppression CBT (CBTb), and control task (CBTc). A VLPFC activation during CBTs and a DLPFC activation during CBTb were hypothesized. The results of the Bayesian analysis have not shown a delineated specific activation of VLPFC/DLPFC during either CBTs or CBTb. These results together with the related ones obtained by others using fMRI are not sufficient to definitively state the role of the PFC subregions during CBT execution. The adoption of high-density diffuse optical tomography would be helpful in further exploration of the PFC involvement in spatial WM tasks.

Mediation by anxiety of the relationship between amygdala activity during emotion processing and poor quality of life in young adults

Young adults often experience psychological distress and poor quality of life (QoL). Yet, there are no objective neural markers to accurately guide interventions to help improve these measures. We thus aimed to identify directional relationships between frontoamygdala emotional regulation circuitry activity during emotion processing, personality traits, and symptoms associated with psychological distress, and QoL. One hundred twenty 18–25-year olds, n=51 psychologically distressed and n=69 healthy individuals, completed a face emotion-processing task during functional magnetic resonance imaging, clinical and behavioral measures, and QoL assessment. Penalized regression, accounting for large numbers of independent variables, showed that increased state and trait anxiety, cohort and measures of general and anhedonic depression severity predicted poorer QoL (all exponents>0.87). Only state and trait anxiety predicted emotion processing-related frontoamygdala activity (all exponents=1.00). State and trait anxiety fully mediated the relationship between amygdala activity and QoL (P-value increased from 0.001 to 0.29: left amygdala, and from 0.003 to 0.94: right amygdala). State anxiety fully mediated the relationship between left ventrolateral prefrontal cortical (vlPFC) activity and QoL (P-value increased from 0.01 to 0.18). Testing an alternative mediational pathway showed that the relationship between state and trait anxiety and QoL was not mediated by amygdala or left vlPFC activity. We thereby identify specific, directional relationships linking amygdala and left vlPFC activity, state and trait anxiety, and poor QoL across different diagnoses. Our findings highlight roles of amygdala and left vlPFC activity as neural predictors of anxiety and poor QoL, and as potentially important targets for novel interventions to reduce anxiety and, in turn, improve QoL in young adults.

Activation in Context: Differential Conclusions Drawn from Cross-Sectional and Longitudinal Analyses of Adolescents' Cognitive Control-Related Neural Activity.

Although immature cognitive control, subserved by late-developing prefrontal regions, has been proposed to underlie increased risk taking during adolescence, it remains unclear what patterns of PFC activation represent mature brain states: more or less activation? One challenge to drawing cogent conclusions from extant work stems from its reliance on single-time point neuroimaging and cross-sectional comparisons, which are ill-suited for assessing the complex changes that characterize adolescence. This necessitates longitudinal fMRI work to track within-subject changes in PFC function and links to risk-taking behavior, which can serve as an external marker for maturation of neural systems involved in cognitive control. In the current study, 20 healthy adolescents (13 males) completed a go/nogo task during two fMRI scans, once at age 14 years and again at age 15 years. We found that the association between cognitive control-related VLPFC activation and risk-taking behavior reversed when examining wave 1 (W1) versus longitudinal change (W2 > W1) and wave 2 (W2) in neural activation, such that increased VLPFC activation at W1 was associated with lower risk taking, whereas longitudinal increases in cognitive control-related VLPFC activation as well as heightened VLPFC activation at W2 were associated with greater risk taking. Several steps were taken to disentangle potential alternative accounts that might explain these disparate results across time. Findings highlight the necessity of considering brain-behavior relationships in the context of ongoing developmental changes and suggests that using neuroimaging data at a single time point to predict behavioral changes can introduce interpretation errors when failing to account for changes in neural trajectories.

Prefrontal Cortex Activation Upon a Demanding Virtual Hand-Controlled Task: A New Frontier for Neuroergonomics.

Functional near-infrared spectroscopy (fNIRS) is a non-invasive vascular-based functional neuroimaging technology that can assess, simultaneously from multiple cortical areas, concentration changes in oxygenated-deoxygenated hemoglobin at the level of the cortical microcirculation blood vessels. fNIRS, with its high degree of ecological validity and its very limited requirement of physical constraints to subjects, could represent a valid tool for monitoring cortical responses in the research field of neuroergonomics. In virtual reality (VR) real situations can be replicated with greater control than those obtainable in the real world. Therefore, VR is the ideal setting where studies about neuroergonomics applications can be performed. The aim of the present study was to investigate, by a 20-channel fNIRS system, the dorsolateral/ventrolateral prefrontal cortex (DLPFC/VLPFC) in subjects while performing a demanding VR hand-controlled task (HCT). Considering the complexity of the HCT, its execution should require the attentional resources allocation and the integration of different executive functions. The HCT simulates the interaction with a real, remotely-driven, system operating in a critical environment. The hand movements were captured by a high spatial and temporal resolution 3-dimensional (3D) hand-sensing device, the LEAP motion controller, a gesture-based control interface that could be used in VR for tele-operated applications. Fifteen University students were asked to guide, with their right hand/forearm, a virtual ball (VB) over a virtual route (VROU) reproducing a 42 m narrow road including some critical points. The subjects tried to travel as long as possible without making VB fall. The distance traveled by the guided VB was 70.2 ± 37.2 m. The less skilled subjects failed several times in guiding the VB over the VROU. Nevertheless, a bilateral VLPFC activation, in response to the HCT execution, was observed in all the subjects. No correlation was found between the distance traveled by the guided VB and the corresponding cortical activation. These results confirm the suitability of fNIRS technology to objectively evaluate cortical hemodynamic changes occurring in VR environments. Future studies could give a contribution to a better understanding of the cognitive mechanisms underlying human performance either in expert or non-expert operators during the simulation of different demanding/fatiguing activities.

Adolescent neurodevelopment of cognitive control and risk-taking in negative family contexts

Adolescents have an increased need to regulate their behavior as they gain access to opportunities for risky behavior; however, cognitive control systems necessary for this regulation remain relatively immature. Parents can impact their adolescent child's abilities to regulate their behavior and engagement in risk taking. Since adolescents undergo significant neural change, negative parent–child relationship quality may impede or alter development in prefrontal regions subserving cognitive control. To test this hypothesis, 20 adolescents completed a Go/NoGo task during two fMRI scans occurring 1year apart. Adolescents reporting greater family conflict and lower family cohesion showed longitudinal increases in risk-taking behavior, which was mediated by longitudinal increases in left VLPFC activation during cognitive control. These results underscore the importance of parent–child relationships during early adolescence, and the neural processes by which cognitive control may be derailed and may lead to increased risk taking.

Response inhibition during emotional contexts in children with ADHD: Neural and behavioral data.

Event Abstract Back to Event Response inhibition during emotional contexts in children with ADHD: Neural and behavioral data. Sara López-Martín1*, Jacobo Albert2, Alberto Fernández-Jaén3 and Luis Carretié4 1 Universidad Autónoma de Madrid, Psicología Biológica y de la Salud, Spain 2 Universidad Complutense de Madrid, Spain 3 Hospital Quirón, Spain 4 Universidad Autónoma de Madrid, Spain Background: Although the deficit in response inhibition represents one of the most common alterations in attention deficit hyperactivity disorder (ADHD) and increasing evidence points to the presence of emotional problems in patients with this disorder, little is known about the neural and behavioral substrates underlying the interaction of emotion and response inhibition in ADHD. Methods: In an attempt to shed light on this issue, scalp event-related potentials (ERPs) were recorded while 24 children with ADHD and 24 healthy comparison subjects performed a modified version of the Go/Nogo task that required the inhibition of prepotent responses to neutral cues during three different contexts generated by pictorial backgrounds: negative, neutral, and positive. Temporal principal component analyses were employed to detect and quantify, in a reliable manner, those ERP components related to response inhibition (i.e., Nogo-N2 and Nogo-P3), and a source-localization technique (sLORETA) provided information on their neural origin. Results: Behavioral data showed no differences in performance on the emotional Go/Nogo task between ADHD and control groups. Scalp-ERP data revealed that, compared with control subjects, patients with ADHD showed larger frontocentral Nogo-P3 amplitudes and enhanced ventrolateral prefrontal cortex (vlPFC) activation during the successful inhibition of motor responses. These group differences were especially evident during positive (Nogo-P3 amplitude and vlPFC activation) and negative (Nogo-P3 amplitude) contexts. Conclusions: Results suggest that children with ADHD need to activate inhibitory processes more than control subjets to achieve a similar level of performance. The present study provides relevant data data on the neural substrates underlying the interaction of emotion and resposne inhibition in ADHD. Acknowledgements:this work was supported by the grant PSI2011-26314 from the Ministerio de Economía y Economía yCompetitividad of Spain (MINECO) Keywords: EEG, emotion, inhibition, ADHD, ERPs, sLORETA Conference: XII International Conference on Cognitive Neuroscience (ICON-XII), Brisbane, Queensland, Australia, 27 Jul - 31 Jul, 2014. Presentation Type: Poster Topic: Emotional and Social Processes Citation: López-Martín S, Albert J, Fernández-Jaén A and Carretié L (2015). Response inhibition during emotional contexts in children with ADHD: Neural and behavioral data.. Conference Abstract: XII International Conference on Cognitive Neuroscience (ICON-XII). doi: 10.3389/conf.fnhum.2015.217.00219 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Feb 2015; Published Online: 24 Apr 2015. * Correspondence: Mrs. Sara López-Martín, Universidad Autónoma de Madrid, Psicología Biológica y de la Salud, Madrid, Spain, sara.lopez@uam.es Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Sara López-Martín Jacobo Albert Alberto Fernández-Jaén Luis Carretié Google Sara López-Martín Jacobo Albert Alberto Fernández-Jaén Luis Carretié Google Scholar Sara López-Martín Jacobo Albert Alberto Fernández-Jaén Luis Carretié PubMed Sara López-Martín Jacobo Albert Alberto Fernández-Jaén Luis Carretié Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Poster #S107 DIMENSIONS OF DELUSIONS AND SELF-SERVING BIAS ALONG THE CONTINUUM OF PSYCHOSIS

Background: Adolescence is a period of acting out and emotional instability. This may be due to an imbalance between the subcortical areas and the prefrontal cortex. Subcortical areas are thought to be more fully developed already early in adolescence, while cortical areas reach their mature state only at the very end of this period. Adolescence is also the time of onset of psychiatric disorders such as Schizophrenia (SZ) and Bipolar Disorder (BD). These disorders are characterized by impairments in networks involving subcortical and frontal brain regions. We hypothesize that these impairments are already present during adolescent development, prior to the overt manifestation of the disorder. Here, we investigate the development of limbic subcortical regions and the frontal cortex during emotion processing in offspring of SZ and BD patients compared to control subjects. These offspring have a ten-fold increased risk to develop a psychotic disorder themselves, and about 70% will develop non-specific psychopathology. Methods: Fourteen offspring of schizophrenia patients (mean age 12.9, 11 females), twenty nine offspring of bipolar patients (mean age 14.1, 12 females) and 31 control offspring (mean age 13.7, 17 females) viewed and rated neutral, negative, and positive pictures (IAPS), while being scanned with functional MRI (2D-EPI, TR = 1.6s, TE = 23ms). All pictures were presented for 2 seconds, with another 2 second period for subjects to respond. Only those trials in which there was a match between the subjects’ response and the IAPS rating were included. Activation during the presentation of negative pictures was contrasted against activity during the neutral pictures. Changes in activity levels with age were investigated using regression analyses in four a priori regions (amygdala, hippocampus, ventrolateral prefrontal cortex (vlPFC), and the orbitofrontal cortex (OFC)). In addition, psychophysiological interaction (PPI) analyses were performed to reveal changes in functional coupling with age between the areas involved in the emotion network. Results: There were no differences in task performance (reaction time, accuracy) between the groups. Compared to the control group, activation in the amygdala and hippocampus was decreased in the SZ offspring, but not in the BD offspring when processing emotional salient stimuli. In contrast, activation in the vlPFC activity increased with age. Moreover, and in line with previous research (Vink et al., submitted), activation in these limbic subcortical regions decreased with age in the controls but not in the offspring groups. These changes in activation were paralleled by an increase in functional connectivity between the amygdala and vlPFC in controls. No such increase was observed in the offspring groups. Discussion: In sum, we found, using a simple emotion task, that SZ offspring already show impaired brain development during adolescence compared to controls. These findings of reduced limbic subcortical and frontal functioning are consistent with findings in adult patients (Aleman & Kahn, 2005). Remarkably, these deficits occur before the manifestation of the illness. Surprisingly, we did not observed differences between BD offspring and controls. These data provide evidence in support of the notion that psychiatric illnesses have their origin in early adolescence. We plan to follow these groups longitudinally to We plan to follow these groups longitudinally, so that we can identify how the familial risk for SZ and BD impacts individual developmental trajectories.

Neural activity to positive expressions predicts daily experience of schizophrenia-spectrum symptoms in adults with high social anhedonia.

Social anhedonia (SA), the diminished pleasure from social relationships, is a prominent characteristic of the vulnerability and manifestation of schizophrenia disorder. However, SA can develop for multiple reasons and little is known about its neural basis; these 2 issues hinder the utility and sensitivity of SA as a marker of schizophrenia pathology. This study investigated whether lateral prefrontal cortex (LPFC) deficits in social reward processing are associated with both SA and other schizophrenia-spectrum symptoms. During functional MRI (fMRI), a community sample of healthy adults (N = 30) with high and low SA viewed positive, negative, and neutral facial expressions. Afterward, participants completed an online daily diary in which they rated schizophrenia-spectrum symptoms and occurrence of interpersonal conflict each day for 21 days. Compared with low SA, high SA participants had less ventral (V)LPFC activity to positive versus neutral expressions. In addition, participants with a combination of high SA and low VLPFC activity to positive versus neutral expressions had worse daily diary ratings of schizophrenia-spectrum symptoms, including worse cognition, paranoia, motivation/productivity, and vigor/positive affect (i.e., psychomotor activation). Finally, among high SA participants, VLPFC activity predicted the daily relationship between distress from interpersonal conflict and symptom-severity; specifically, high SA participants with low VLPFC activity had worse paranoia on days of high conflict distress. These findings indicate that VLPFC deficits in positive emotion are associated with both SA and other schizophrenia-spectrum symptoms and that understanding the interaction of SA, VLPFC function, and social stress could facilitate the use of SA in the prevention and treatment of schizophrenia.

EPA-1674 – Effects of dialectic behavior therapy on the neuronal correlates of emotion regulation in borderline personality disorder

A fundamental aspect of Borderline Personality Disorder (BPD) is emotional dysregulation. Dialectic Behavior Therapy (DBT) is a widely used therapy program developed specifically for improving emotion regulation in BPD. To date little is known about the neural mechanisms associated with the amelioration of BPD symptoms after DBT. In the present study we investigated pre-post therapy changes in a) brain activity during cognitive reappraisal, one commonly acquired skill during DBT and b) brain gray matter volume attributable to successful participation in a DBT skills training. Before and after a 12-week in-patient DBT treatment program 22 female BPD patients and 22 healthy control subjects participated in two fMRI sessions of a well-established emotion reappraisal paradigm. Using voxel-based morphometry (VBM) changes in gray matter volume were analysed. Pre-post therapy changes were compared between the group of DBT-Responders (n=12) and DBT-Non-Responders (n=10). After participating in a DBT skills training, DBT responders exhibited a reduced activity in vlPFC compared to the first scanning session and to DBT non-responders during reappraisal of aversive stimuli. The reduction in vlPFC activity correlated significantly with symptom improvement after therapy. After therapy DBT-Responders showed a significant higher gray matter volume in an extended cluster comprising anterior insula, caudate nucleus, and putamen. In the current study, we provide evidence that a successful participation in DBT is associated with altered activity in the vlPFC and changes in gray matter concentration in anterior insula and striatum.

Anomalous Use of Context During Task Preparation in Schizophrenia: A Magnetoencephalography Study

Impaired ability to use contextual information to optimally prepare for tasks contributes to performance deficits in schizophrenia. We used magnetoencephalography and an antisaccade task to investigate the neural basis of this deficit. In schizophrenia patients and healthy control participants, we examined the difference in preparatory activation to cues indicating an impending antisaccade or prosaccade. We analyzed activation for correct trials only and focused on the network for volitional ocular motor control-frontal eye field (FEF), dorsal anterior cingulate cortex (dACC), and the ventrolateral and dorsolateral prefrontal cortex (VLPFC, DLPFC). Compared with control subjects, patients made more antisaccade errors and showed reduced differential preparatory activation in the dACC and increased differential preparatory activation in the VLPFC. In patients only, antisaccade error rates correlated with preparatory activation in the FEF, DLPFC, and VLPFC. In schizophrenia, reduced differential preparatory activation of the dACC may reflect reduced signaling of the need for control. Greater preparatory activation in the VLPFC and the correlations of error rate with FEF, DLPFC, and VLPFC activation may reflect that patients who are more error prone require stronger activation in these regions for correct performance. These findings provide the first evidence of abnormal task preparation, distinct from response generation, during volitional saccades in schizophrenia. We conclude that schizophrenia patients are impaired in using task cues to modulate cognitive control and that this contributes to deficits inhibiting prepotent but contextually inappropriate responses and to behavior that is stimulus bound and error prone rather than flexibly guided by context.

Neural mechanisms of symptom improvements in generalized anxiety disorder following mindfulness training

Mindfulness training aims to impact emotion regulation. Generalized anxiety disorder (GAD) symptoms can be successfully addressed through mindfulness-based interventions. This preliminary study is the first to investigate neural mechanisms of symptom improvements in GAD following mindfulness training. Furthermore, we compared brain activation between GAD patients and healthy participants at baseline. 26 patients with a current DSM-IV GAD diagnosis were randomized to an 8-week Mindfulness Based Stress Reduction (MBSR, N = 15) or a stress management education (SME, N = 11) active control program. 26 healthy participants were included for baseline comparisons. BOLD response was assessed with fMRI during affect labeling of angry and neutral facial expressions. At baseline, GAD patients showed higher amygdala activation than healthy participants in response to neutral, but not angry faces, suggesting that ambiguous stimuli reveal stronger reactivity in GAD patients. In patients, amygdala activation in response to neutral faces decreased following both interventions. BOLD response in ventrolateral prefrontal regions (VLPFC) showed greater increase in MBSR than SME participants. Functional connectivity between amygdala and PFC regions increased significantly pre- to post-intervention within the MBSR, but not SME group. Both, change in VLPFC activation and amygdala–prefrontal connectivity were correlated with change in Beck Anxiety Inventory (BAI) scores, suggesting clinical relevance of these changes. Amygdala–prefrontal connectivity turned from negative coupling (typically seen in down-regulation of emotions), to positive coupling; potentially suggesting a unique mechanism of mindfulness. Findings suggest that in GAD, mindfulness training leads to changes in fronto-limbic areas crucial for the regulation of emotion; these changes correspond with reported symptom improvements.

Neurophysiological correlates of age-related changes in working memory updating

Normal aging is associated with a gradual decline in executive functions such as set-shifting, inhibition, and updating, along with a progressive decline of neurotransmitter systems including the dopamine system. Modulation from the dopamine system is thought to be critical for the gating of information during working memory. Given the known relationships between executive aging, cognition, and dopamine, this study aims to explore the neurobiology underlying age-related changes in working memory updating using fMRI with healthy subjects from across the adult age spectrum. Our results indicate that older age is associated with poorer performance, reduced meso-cortico-striatal activation, and reduced functional coupling between the caudate and the VLPFC during the updating task. Additionally, caudate activation is associated with improved accuracy and VLPFC activation with faster reaction times in the full sample. Thus, older subjects' under-recruitment of and reduced functional coupling between these regions may specifically underlie age-related changes in working memory updating. These results are consistent with computational models of executive cognition and dopamine-mediated age-related cognitive decline.

Neural correlates of attention bias to threat in post-traumatic stress disorder

Attentional biases have been proposed to contribute to symptom maintenance in posttraumatic stress disorder (PTSD), although the neural correlates of these processes have not been well defined; this was the goal of the present study. We administered an attention bias task, the dot probe, to a sample of 37 (19 control, 18 PTSD+) traumatized African-American adults during fMRI. Compared to controls, PTSD+ participants demonstrated increased activation in the dorsolateral prefrontal cortex (dlPFC) in response to threat cue trials. In addition, attentional avoidance of threat corresponded with increased ventrolateral prefrontal cortex (vlPFC) and dorsal anterior cingulate cortex (dACC) activation in the PTSD group, a pattern that was not observed in controls. These data provide evidence to suggest that relative increases in dlPFC, dACC and vlPFC activation represent neural markers of attentional bias for threat in individuals with PTSD, reflecting selective disruptions in attentional control and emotion processing networks in this disorder.

Isolating neural components of threat bias in pediatric anxiety

Attention biases toward 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 toward 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 versus. 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.

Altered age-related trajectories of amygdala-prefrontal circuitry in adolescents at clinical high risk for psychosis: A preliminary study

Emotion processing deficits are prominent in schizophrenia and exist prior to the onset of overt psychosis. However, developmental trajectories of neural circuitry subserving emotion regulation and the role that they may play in illness onset have not yet been examined in patients at risk for psychosis. The present study employed a cross-sectional analysis to examine age-related functional activation in amygdala and prefrontal cortex, as well as functional connectivity between these regions, in adolescents at clinical high risk (CHR) for psychosis relative to typically developing adolescents. Participants (n=34) performed an emotion processing fMRI task, including emotion labeling, emotion matching, and non-emotional control conditions. Regression analyses were used to predict activation in the amygdala and ventrolateral prefrontal cortex (vlPFC) based on age, group, sex, and the interaction of age by group. CHR adolescents exhibited altered age-related variation in amygdala and vlPFC activation, relative to controls. Controls displayed decreased amygdala and increased vlPFC activation with age, while patients exhibited the opposite pattern (increased amygdala and decreased vlPFC activation), suggesting a failure of prefrontal cortex to regulate amygdala reactivity. Moreover, a psychophysiological interaction analysis revealed decreased amygdala-prefrontal functional connectivity among CHR adolescents, consistent with disrupted brain connectivity as a vulnerability factor in schizophrenia. These results suggest that the at-risk syndrome is marked by abnormal development and functional connectivity of neural systems subserving emotion regulation. Longitudinal data are needed to confirm aberrant developmental trajectories intra-individually and to examine whether these abnormalities are predictive of conversion to psychosis, and of later deficits in socioemotional functioning.

Ventrolateral prefrontal cortex and self-initiated semantic elaboration during memory retrieval

Left ventrolateral prefrontal cortex (LVPFC) is often implicated in neuroimaging studies of context memory retrieval. This activation has been argued to reflect proactive semantic processing that facilitates recollection of past events, or instead to reflect a reactive response to experienced episodic interference. We investigated these characterizations in an fMRI study that manipulated the relative distinctiveness of encoding across subsequent targets and lures by varying encoding task manipulations. Critically, during later testing, retrieval queries and prior target processing where held constant across the distinctive and non-distinctive testing conditions, and therefore any differences in cortical activity would be linked to subject-initiated retrieval strategies. We found that LVPFC activity was specific to context retrieval under distinctive conditions even though this condition demonstrated the least interference. The results suggest that this region is critical for self-initiated semantic elaboration during retrieval, and this conclusion was bolstered by finding that LVPFC activity predicted individual differences in context memory discrimination. In line with Tulving's Encoding Specificity Principle, we suggest that subjects actively construct semantic retrieval cues, reflected in increased VLPFC activation, in an attempt to isolate the distinctive semantic features of hypothetical experiences when possible. If successful, this improves the match between retrieval cue and engram and facilitates performance.

Amygdala and Ventrolateral Prefrontal Cortex Function During Anticipated Peer Evaluation in Pediatric Social Anxiety

Amygdala and ventrolateral prefrontal cortex (vlPFC) dysfunction manifests in adolescents with anxiety disorders when they view negatively valenced stimuli in threatening contexts. Such fear-circuitry dysfunction may also manifest when anticipated social evaluation leads socially anxious adolescents to misperceive peers as threatening. To determine whether photographs of negatively evaluated smiling peers viewed during anticipated social evaluation engage the amygdala and vlPFC differentially in adolescents with and without social anxiety. Case-control study. Government clinical research institute. Fourteen adolescents with anxiety disorders associated with marked concerns of social evaluation and 14 adolescents without a psychiatric diagnosis matched on sex, age, intelligence quotient, and socioeconomic status. Blood oxygenation level-dependent signal measured with event-related functional magnetic resonance imaging. Before and during neuroimaging scans, participants anticipating social evaluation completed peer- and self-appraisals. Event-related analyses were tailored to participants' ratings of specific peers. Participants classified 40 pictures of same-age peers as ones with whom they did or did not want to engage in a social interaction. Anxious adolescents showed greater amygdala activation than healthy adolescents when anticipating evaluation from peers previously rated as undesired for an interaction. Psychophysiological interaction connectivity analyses also revealed a significant positive association between amygdala and vlPFC activation in anxious vs healthy adolescents in response to these stimuli. Anticipating social evaluation from negatively perceived peers modulates amygdala and vlPFC engagement differentially in anxious and healthy adolescents. Amygdala and vlPFC dysfunction manifests in adolescent anxiety disorders in specific contexts of anticipated peer evaluation.

Prefrontal-Subcortical Pathways Mediating Successful Emotion Regulation

Although prefrontal cortex has been implicated in the cognitive regulation of emotion, the cortical-subcortical interactions that mediate this ability remain poorly understood. To address this issue, we identified a right ventrolateral prefrontal region (vlPFC) whose activity correlated with reduced negative emotional experience during cognitive reappraisal of aversive images. We then applied a pathway-mapping analysis on subcortical regions to locate mediators of the association between vlPFC activity and reappraisal success (i.e., reductions in reported emotion). Results identified two separable pathways that together explained approximately 50% of the reported variance in self-reported emotion: (1) a path through nucleus accumbens that predicted greater reappraisal success, and (2) a path through ventral amygdala that predicted reduced reappraisal success (i.e., more negative emotion). These results provide direct evidence that vlPFC is involved in both the generation and regulation of emotion through different subcortical pathways, suggesting a general role for this region in appraisal processes.

Prefrontal contributions to domain-general executive control processes during temporal context retrieval

Neuroimaging studies have reported increased prefrontal cortex (PFC) activity during temporal context retrieval versus recognition memory. However, it remains unclear if these activations reflect PFC contributions to domain-general executive control processes or domain-specific retrieval processes. To gain a better understanding of the functional roles of these various PFC regions during temporal context retrieval we propose it is necessary to examine PFC activity across tasks from different domains, in which parallel manipulations are included targeting specific cognitive processes. In the current fMRI study, we examined domain-general and domain-specific PFC contributions to temporal context retrieval by increasing stimulus (but maintaining response number) and increasing response number (but maintaining stimulus number) across temporal context memory and ordering control tasks, for faces. The control task required subjects to order faces from youngest to oldest. Our behavioral results indicate that the combination of increased stimulus and response numbers significantly increased task difficulty for temporal context retrieval and ordering tasks. Across domains, increasing stimulus number, while maintaining response numbers, caused greater right lateral premotor cortex (BA 6/8) activity; whereas increasing response number, while maintaining stimulus number, caused greater domain-general left DLPFC (BA 9) and VLPFC (BA 44/45) activity. In addition, we found domain-specific right DLPFC (BA 9) activity only during retrieval events. These results highlight the functional heterogeneity of frontal cortex, and suggest its involvement in temporal context retrieval is related to its role in various cognitive control processes.