Rostral Anterior Cingulate Cortex Activation Research Articles

Differential role of fusiform gyrus coupling in depressive and anxiety symptoms during emotion perception.

Anxiety and depression co-occur; the neural substrates of shared and unique components of these symptoms are not understood. Given emotional alterations in internalizing disorders, we hypothesized that function of regions associated with emotion processing/regulation, including the anterior cingulate cortex (ACC), amygdala and fusiform gyrus (FG), would differentiate these symptoms. Forty-three adults with depression completed an emotional functional magnetic resonance imaging task and the Hamilton Depression and Anxiety Scales. We transformed these scales to examine two orthogonal components, one representing internalizing symptom severity and the other the type of internalizing symptoms (anxiety vs depression). We extracted blood oxygen level dependent signal from FG subregions, ACC, and amygdala and performed generalized psychophysiological interaction analyses to assess relationships between symptoms and brain function. Type of internalizing symptoms was associated with FG3-FG1 coupling (F = 8.14, P = 0.007). More coupling was associated with a higher concentration of depression, demonstrating that intra-fusiform coupling is differentially associated with internalizing symptom type (anxiety vs depression). We found an interaction between task condition and internalizing symptoms and dorsal (F = 4.51, P = 0.014) and rostral ACC activity (F = 4.27, P = 0.012). Post hoc comparisons revealed that less activity was associated with greater symptom severity during emotional regulation. Functional coupling differences during emotional processing are associated with depressive relative to anxiety symptoms and internalizing symptom severity. These findings could inform future treatments for depression.

Smoking cues impair monitoring but not stopping during response inhibition in abstinent male smokers

The attenuated inhibitory control of smokers is a stumbling block for treating nicotine dependence. Unfortunately, smokers are often exposed to cigarette-related salient cues, which may violate homeostasis, override self-control, and lead to relapse. To understand the mechanisms underlying these associations, we investigate the cognitive and neural processes of inhibitory control (including proactive and reactive inhibition) of smoking cues in abstinent smokers. Twenty-six smokers completed cue-reactivity and stop signal tasks during functional magnetic resonance imaging scans, on two separate sessions, 2–3 weeks apart: one involved a neutral cue reactivity task, and the other a smoking cue reactivity task. Findings pointed to no significant subjective craving changes, or behavioral influences of smoking cues on proactive and reactive inhibition. However, abstinent smokers exhibited hyperactive brain reactivity in response to smoking versus neutral stimuli, in regions including the insula, amygdala, anterior cingulate cortex (ACC), and putamen. They also had hypoactive bilateral rostral ACC (rACC) and hyperactive right pre-supplementary motor area during reactive inhibition in smoking versus neutral conditions. Support vector regression analysis showed that activation of these regions predicted and correlated with reactive inhibition index (i.e., SSRT), alluding to the possibility of their involvement in the reactive inhibition. Subjective craving scores were predicted by and correlated with activation of bilateral dorsal and rostral ACC, supporting the ideas of their possible involvement in subjective craving. These findings suggest that smoking cues evoke hyperactive brain reactivity; this may interfere with normal performance monitoring and rapid reactive inhibition. These findings have important implication for treating smoking dependence.

Amygdala activity to angry and fearful faces relates to bullying and victimization in adolescents.

Relational bullying and victimization are common social experiences during adolescence, but relatively little functional magnetic resonance imaging (fMRI) research has examined the neural correlates of bullying and victimization in adolescents. The aim of the present study was to address this gap by examining the association between amygdala activity to angry and fearful faces and peer relational bullying and victimization in a community-based sample of adolescents. Participants included 49 adolescents, 12–15 years old, who underwent fMRI scanning while completing an emotional face matching task. Results indicated that interactions between amygdala activity to angry and fearful faces predicted self-reported relational bullying and victimization. Specifically, a combination of higher amygdala activity to angry faces and lower amygdala activity to fearful faces predicted more bullying behavior, whereas a combination of lower amygdala activity to angry faces and lower amygdala activity to fearful faces predicted less relational victimization. Exploratory whole-brain analyses also suggested that increased rostral anterior cingulate cortex activity to fearful faces was associated with less bullying. These results suggest that relational bullying and victimization are related to different patterns of neural activity to angry and fearful faces, which may help in understanding how patterns of social information processing predict these experiences.

Anterior cingulate activation to implicit threat before and after treatment for pediatric anxiety disorders

BackgroundResearch suggests that individuals with anxiety have difficulty ignoring threat distractors when completing tasks with competing stimuli. Studies examining the neural correlates of these emotional processing difficulties in youth anxiety highlight reduced recruitment of regions associated with goal-directed attention, such as the anterior cingulate cortex (ACC). In the current study, we examined neural activation during an emotional conflict task in youth with anxiety disorders before and after treatment. MethodsTwenty-five youth (ages 9–19 years) with generalized, separation, and/or social anxiety disorder and 25 healthy controls underwent 2 functional magnetic resonance imaging scans approximately 13 weeks apart. At each scan, participants completed a task in which they matched shapes in the context of emotional distractors (happy and threatening faces). Between scans, anxious youth were treated with the selective serotonin reuptake inhibitor (SSRI) sertraline or cognitive behavior therapy (CBT). ResultsPrior to treatment, anxious youth exhibited reduced activation of the medial prefrontal cortex, encompassing the rostral ACC, when matching shapes in the context of threat distractors relative to healthy controls. Activation in this region increased in anxious youth after treatment, but remained unchanged in the healthy control group. Increases in rostral ACC activation were related to greater reductions in social anxiety and avoidance symptoms following treatment. ConclusionsEffective treatments for pediatric anxiety may enhance rostral ACC response during attempts to filter out threat-relevant stimuli. Enhanced recruitment of this region may constitute one manner in which CBT and SSRI treatment reduce youth anxiety symptoms, particularly social anxiety and avoidance.

Fronto-Limbic Alterations in Negatively Biased Attention in Young Adults with Subthreshold Depression.

Attentional bias toward negative stimuli has been observed in major depression disorders (MDDs). Imaging studies suggest the engagement of fronto-limbic regions like amygdala, anterior cingulate cortex (ACC), and lateral prefrontal cortex, is related to negatively biased attention. However, neural correlates of attentional bias for negative stimuli in individuals with subthreshold depression (SubD), that is individuals who have clinically relevant depressive symptoms but do not fulfill the criteria for MDD, remain unclear. Here, we used functional neuroimaging and the dot-probe task to elucidate the neural substrates of negatively biased attention among individuals with SubD. Behavioral results found that individuals with SubD allocated more attention toward negative stimuli relative to neutral stimuli, which were not observed among non-depressed controls (NCs). Imaging results found greater amygdala and rostral ACC activity in attentional bias toward negative stimuli among participants with SubD compared to NCs; Additionally, participants with SubD showed reduced engagement of bilateral inferior frontal gyrus compared with NCs in the attentional processing of negative stimuli. Together, these results suggest that alteration of fronto-limbic systems relative to controls, known to be related to negative detection and attentional control, is associated with negatively biased attention in individuals with SubD.

Neural correlates of an attentional bias to health-threatening stimuli in individuals with pathological health anxiety.

An attentional bias to health-threat stimuli is assumed to represent the primary pathogenetic factor for the development and maintenance of pathological health anxiety (PHA; formerly termed "hypochondriasis"). However, little is known about the neural basis of this attentional bias in individuals with PHA. A group of patients with PHA, a group of depressed patients and a healthy control group completed an emotional Stroop task with health-threat (body symptom and illness) words and neutral control words while undergoing functional MRI. We included 33 patients with PHA, 28 depressed patients and 31 controls in our analyses. As reflected in reaction times, patients with PHA showed a significantly stronger attentional bias to health-threat words than both control groups. In addition, patients with PHA showed increased amygdala and rostral anterior cingulate cortex activation for body symptom, but not for illness words. Moreover, only in patients with PHA amygdala activation in response to symptom words was positively associated with higher arousal and more negative valence ratings of the body symptom word material. A control group of patients with an anxiety disorder but without PHA would have helped to define the specificity of the results for PHA. The attentional bias observed in patients with PHA is associated with hyperactivation in response to body symptom words in brain regions that are crucial for an arousal-related fear response (e.g., the amygdala) and for resolving emotional interference (e.g., the rostral anterior cingulate cortex). The findings have important implications for the nosological classification of PHA and suggest the application of innovative exposure-based interventions for the treatment of PHA.

173. The Incremental Predictive Validity of Rostral Anterior Cingulate Cortex Activity in Relation to Treatment Response in Depression: Evidence from the EMBARC Study

173. The Incremental Predictive Validity of Rostral Anterior Cingulate Cortex Activity in Relation to Treatment Response in Depression: Evidence from the EMBARC Study

Neural responses to social exclusion in adolescents: Effects of peer status

We examined whether adolescents' neural responses to social exclusion and inclusion are influenced by their own popularity and acceptance and by the popularity of their excluders and includers. Accepted adolescents are highly prosocial. In contrast, popular adolescents, who are central and influential, show prosocial as well as antisocial behaviors, such as peer exclusion. Fifty-two 12–16 year-old adolescents underwent an functional magnetic resonance imaging (fMRI) scan while playing the ball-tossing game Cyberball in which they received or did not receive the ball from other virtual players. The other virtual players were described as either highly popular or average in popularity. Participants' own popularity and acceptance were assessed with peer nominations at school (n = 31). Participants' acceptance was positively correlated with activity of the dorsal anterior cingulate cortex (ACC) during exclusion. Participants' popularity was positively associated with ventral striatum and medial prefrontal cortex activity during exclusion, but only when the excluders were popular virtual players. Participants showed increased rostral ACC activation to inclusion by players who were average in popularity. These findings indicate that peer status plays an important role in adolescents' neural processing of social exclusion and inclusion. Moreover, these findings underscore that popularity and acceptance are distinct types of high peer status in adolescence, with not only distinct behavioral correlates, but also distinct neural correlates.

Degrading traumatic memories with eye movements: a pilot functional MRI study in PTSD

BackgroundEye movement desensitization and reprocessing (EMDR) is an effective treatment for posttraumatic stress disorder (PTSD). During EMDR, the patient recalls traumatic memories while making eye movements (EMs). Making EMs during recall is associated with decreased vividness and emotionality of traumatic memories, but the underlying mechanism has been unclear. Recent studies support a “working-memory” (WM) theory, which states that the two tasks (recall and EMs) compete for limited capacity of WM resources. However, prior research has mainly relied on self-report measures.MethodsUsing functional magnetic resonance imaging, we tested whether “recall with EMs,” relative to a “recall-only” control condition, was associated with reduced activity of primary visual and emotional processing brain regions, associated with vividness and emotionality respectively, and increased activity of the dorsolateral prefrontal cortex (DLPFC), associated with working memory. We used a randomized, controlled, crossover experimental design in eight adult patients with a primary diagnosis of PTSD. A script-driven imagery (SDI) procedure was used to measure responsiveness to an audio-script depicting the participant's traumatic memory before and after conditions.ResultsSDI activated mainly emotional processing-related brain regions (anterior insula, rostral anterior cingulate cortex (ACC), and dorsomedial prefrontal cortex), WM-related (DLPFC), and visual (association) brain regions before both conditions. Although predicted pre- to post-test decrease in amygdala activation after “recall with EMs” was not significant, SDI activated less right amygdala and rostral ACC activity after “recall with EMs” compared to post-“recall-only.” Furthermore, functional connectivity from the right amygdala to the rostral ACC was decreased after “recall with EMs” compared with after “recall-only.”ConclusionsThese preliminary results in a small sample suggest that making EMs during recall, which is part of the regular EMDR treatment protocol, might reduce activity and connectivity in emotional processing-related areas. This study warrants replication in a larger sample.Highlights of the articleScript driven imagery (SDI) before and after recall of traumatic memories is feasible to investigate working mechanisms of degrading of traumatic memories with eye movements (EMs) in PTSD.Right amygdala and rostral ACC activity was significantly lower after “recall with EMs” than after “recall-only”.Functional connectivity from amygdala to rostral ACC was decreased after “recall with EMs” vs. “recall-only”.This study warrants replication in a larger sample.

Cultural influences on neural basis of inhibitory control

Research on neural basis of inhibitory control has been extensively conducted in various parts of the world. It is often implicitly assumed that neural basis of inhibitory control is universally similar across cultures. Here, we investigated the extent to which culture modulated inhibitory-control brain activity at both cultural-group and cultural-value levels of analysis. During fMRI scanning, participants from different cultural groups (including Caucasian-Americans and Japanese-Americans living in the United States and native Japanese living in Japan) performed a Go/No-Go task. They also completed behavioral surveys assessing cultural values of behavioral consistency, or the extent to which one's behaviors in daily life are consistent across situations. Across participants, the Go/No-Go task elicited stronger neural activity in several inhibitory-control areas, such as the inferior frontal gyrus (IFG) and anterior cingulate cortex (ACC). Importantly, at the cultural-group level, we found variation in left IFG (L-IFG) activity that was explained by a cultural region where participants lived in (as opposed to race). Specifically, L-IFG activity was stronger for native Japanese compared to Caucasian- and Japanese-Americans, while there was no systematic difference in L-IFG activity between Japanese- and Caucasian-Americans. At the cultural-value level, we found that participants who valued being “themselves” across situations (i.e., having high endorsement of behavioral consistency) elicited stronger rostral ACC activity during the Go/No-Go task. Altogether, our findings provide novel insight into how culture modulates the neural basis of inhibitory control.

Look who's judging—Feedback source modulates brain activation to performance feedback in social anxiety

It is as yet unknown if behavioral and neural correlates of performance monitoring in socially anxious individuals are affected by whether feedback is provided by a person or a computer. This fMRI study investigated modulation of feedback processing by feedback source (person vs. computer) in participants with high (HSA) (N=16) and low social anxiety (LSA) (N=16). Subjects performed a choice task in which they were informed that they would receive positive or negative feedback from a person or the computer. Subjective ratings indicated increased arousal and anxiety in HSA versus LSA, most pronounced for social and negative feedback. FMRI analyses yielded hyperactivation in ventral medial prefrontal cortex (vmPFC)/anterior cingulate cortex (ACC) and insula for social relative to computer feedback, and in mPFC/ventral ACC for positive relative to negative feedback in HSA as compared to LSA. These activation patterns are consistent with increased interoception and self-referential processing in social anxiety, especially during processing of positive feedback. Increased ACC activation in HSA to positive feedback may link to unexpectedness of (social) praise as posited in social anxiety disorder (SAD) psychopathology. Activation in rostral ACC showed a reversed pattern, with decreased activation to positive feedback in HSA, possibly indicating altered action values depending on feedback source and valence. The present findings corroborate a crucial role of mPFC for performance monitoring in social anxiety.

Nocebo context modulates long-term habituation to heat pain and influences functional connectivity of the operculum.

In the past, nocebo manipulations have been found to modulate pain perception and influence long-term habituation to pain. Recently, neural correlates accompanying this finding have been identified: habituation over days is mirrored by decreased activity in pain-processing brain areas, whereas nocebo-specific modulation specifically involves the opercular cortex. Focusing on duration and central network characteristics of nocebo information in a longitudinal heat pain paradigm, we investigated 40 healthy participants over a period of 21 consecutive days, whereof sessions on days 1, 8, 14, and 21 were performed during functional magnetic resonance imaging scanning. Negative context information was given to half of the participants, inducing a nocebo manipulation through verbal suggestions. The analysis was focused on brain areas associated with habituation and nocebo effects and identified coupled brain regions using functional connectivity analysis. Decreased pain perception over days was reflected in reduced blood oxygenation level dependent signal in pain-processing areas, such as the insula and somatosensory cortices, whereas increased rostral anterior cingulate cortex activation reflected the central correlate for habituation over time. Habituation was significantly less pronounced in the nocebo group. Consistent with previous results, the nocebo manipulation not only modulated pain perception but also was accompanied by the activation of the operculum over an extended period of time. Importantly, the operculum exhibited changes in coupling during nociceptive input over time, as demonstrated by decreased connectivity with the basal ganglia and pinpoints differences, depending on whether a nocebo context was given. These data suggest that negative verbal suggestions prognosticating increasing pain may prevail by modulating basal ganglia-thalamocortical loops.

CHANGES IN REGIONAL BRAIN ACTIVATION RELATED TO DEPRESSIVE STATE: A 2-YEAR LONGITUDINAL FUNCTIONAL MRI STUDY.

Abnormal brain activations during processing of emotional facial expressions in depressed patients have been demonstrated. We investigated the natural course of brain activation in response to emotional faces in depression, indexed by functional magnetic resonance imaging (fMRI) scans preceding and following change in depressive state. We hypothesized a decrease in activation in the amygdala, anterior cingulate cortex (ACC), and insula with a decrease in depressive pathology. A 2-year longitudinal fMRI study was conducted as part of the Netherlands Study of Depression and Anxiety. We included 32 healthy controls and 49 depressed patients. During the second scan, 27 patients were in remission (remitters), the other 22 were not (nonremitters). All participants viewed faces with emotional expressions during scanning. Rostral ACC activation during processing of happy faces was predictive of a decrease in depressive state (PFWE = .003). In addition, remitters showed decreased activation of the insula over time (PFWE = .016), specifically during happy faces. Nonremitters displayed increased abnormalities in emotion recognition circuitry during the second scan compared to the first. No effect of selective serotonin reuptake inhibitor use was observed. Our results demonstrate that rostral ACC activation may predict changes in depressive state even at 2-year outcome. The association between change in depressed state and change in insula activation provides further evidence for the role of the insula in a network maintaining emotional and motivational states.

Effects of childhood maltreatment on the neural correlates of stress- and drug cue-induced cocaine craving.

Childhood adversity negatively influences all stages of the addiction process and is associated with persistent alterations in neuroendocrine, autonomic and brain responses to stress. We sought to characterize the impact of childhood abuse and neglect on the neural correlates of stress- and drug cue-induced drug craving associated with cocaine addiction. Cocaine-dependent men with (n = 20) and without (n = 18) moderate to severe childhood maltreatment histories underwent functional magnetic resonance imaging during script-guided mental imagery of personalized stress, drug use and neutral experiences. Compared to the neutral script, the stress and drug use scripts activated striatal, prefrontal, posterior cingulate, temporal and cerebellar regions consistent with prior studies of induced states of stress and drug craving. For the stress script, maltreated men exhibited reduced activation of the anterior precuneus and supplementary motor area (SMA); the interaction of maltreatment severity and stress-induced craving responses predicted lesser rostral anterior cingulate cortex activation. For the drug use script, maltreated men exhibited greater left dorsolateral prefrontal cortex activation. The interaction of maltreatment severity and craving responses was associated with greater activation of the visual cortex and SMA, whereas a maltreatment-by-anxiety interaction effect included lesser ventromedial prefrontal cortex activation. The outcomes indicate an association of childhood maltreatment with a heightened appetitive anticipatory response to drug cues and a diminished engagement of regulatory and controlled action selection processes in response to stress- or drug cue-induced drug craving and anxiety responses for cocaine-dependent men. These findings provide novel insights into possible brain mechanisms by which childhood maltreatment heightens risk for relapse in drug-dependent individuals.

Dispositional cognitive reappraisal modulates the neural correlates of fear acquisition and extinction

Adverse learning experiences play a significant role in the etiology of anxiety disorders. However, not all individuals experiencing negative events develop heightened anxiety. This is possibly due to individual differences in the regulation of negative emotions associated with these negative events. Cognitive reappraisal is defined as reinterpreting an emotion-eliciting situation in a way that changes its emotional impact. A more frequent use of cognitive reappraisal in daily life has been shown to be more adaptive. However, no study to date examined the association of dispositional cognitive reappraisal with emotional learning, in order to elucidate individual differences in negative emotional responses towards aversive events.The goal of this functional magnetic resonance imaging (fMRI) study was to investigate the association of dispositional cognitive reappraisal with subjective, electrodermal and neural correlates of fear acquisition and extinction. Data of 41 healthy individuals, who participated in a socially relevant differential conditioning paradigm (acquisition and extinction learning: day 1, extinction recall: day 2), were acquired.Dispositional cognitive reappraisal was negatively associated with right insula, and hippocampus activation during acquisition. Furthermore, the reduction of self-reported conditioned fear during extinction learning as well as reduced insula and enhanced rostral anterior cingulate cortex activation during extinction learning was related to cognitive reappraisal. In addition, reduced recovery of conditioned arousal, reduced anterior cingulate and dorsomedial prefrontal cortex activation and enhanced ventromedial prefrontal cortex activation during extinction recall was observed in individuals with higher cognitive reappraisal scores.The results indicate that dispositional cognitive reappraisal modulates subjective and neural correlates of fear conditioning, probably leading to reduced acquisition and stronger extinction learning and recall. These results point to the important role of dispositional cognitive reappraisal in the development and modification of conditioned emotional responses and might further improve our understanding of anxiety disorders.

Differential Effects of Single-Dose Escitalopram on Cognitive and Affective Interference during Stroop Task

Background and objective: Our aim was to study the regulatory role of serotonin [(5-hydroxytryptamine (5-HT)] on two key nodes in the cognitive control networks – the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC). We hypothesized that increasing the levels of 5-HT would preferentially modulate the activity in ACC during cognitive control during interference by negative affects compared to cognitive control during interference by a superimposed cognitive task.Methods: We performed a functional magnetic resonance imaging investigation on 11 healthy individuals, comparing the effects of the selective 5-HT reuptake inhibitor escitalopram on brain oxygenation level dependent signals in the ACC and the DLPFC using affective and cognitive counting Stroop paradigms (aStroop and cStroop).Results: Escitalopram significantly decreased the activity in rostral ACC during aStroop compared to cStroop (p < 0.05). In the absence of escitalopram, both aStroop and cStroop significantly activated ACC and DLPFC (Z ≥ 2.3, p < 0.05).Conclusion: We conclude that escitalopram in a region and task specific manner modified the cognitive control networks and preferentially decreased activity induced by affective interference in the ACC.

Altered cingulate and insular cortex activation during risk‐taking in methamphetamine dependence: losses lose impact

To determine if methamphetamine-dependent (MD) individuals exhibit behavioral or neural processing differences in risk-taking relative to healthy comparison participants (CTL). This was a cross-sectional study comparing two groups' behavior on a risk-taking task and neural processing as assessed using functional magnetic resonance imaging (fMRI). The study was conducted in an in-patient treatment center and a research fMRI facility in the United States. Sixty-eight recently abstinent MD individuals recruited from a treatment program and 40 CTL recruited from the community completed the study. The study assessed risk-taking behavior (overall and post-loss) using the Risky Gains Task (RGT), sensation-seeking, impulsivity and blood-oxygenation-level-dependent activation in the brain during the decision phase of the RGT. Relative to CTL, MD displayed decreased activation in the bilateral rostral anterior cingulate cortex (ACC) and greater activation in the left insula across risky and safe decisions (P < 0.05). Right mid-insula activation among CTL did not vary between risky and safe decisions, but among MD it was higher during risky relative to safe decisions (P < 0.05). Among MD, lower activation in the right rostral ACC (r = -0.39, P < 0.01) and higher activation in the right mid-insula (r = 0.35, P < 0.01) during risky decisions were linked to a higher likelihood of choosing a risky option following a loss. Methamphetamine-dependent individuals show disrupted risk-related processing in both anterior cingulate and insula, brain areas that have been implicated in cognitive control and interoceptive processing. Attenuated neural processing of risky options may lead to risk-taking despite experiencing negative consequences.

Diminished rostral anterior cingulate cortex activation during trauma-unrelated emotional interference in PTSD

BackgroundPrevious research suggests that individuals with posttraumatic stress disorder (PTSD) preferentially attend to trauma-related emotional stimuli and have difficulty completing unrelated concurrent tasks. Compared to trauma-exposed control groups, individuals with PTSD also exhibit lower rostral anterior cingulate cortex (rACC) activation during tasks involving interference from trauma-related stimuli. However, it is not clear whether relatively diminished rACC activation in PTSD also occurs during interference tasks involving trauma-unrelated emotional stimuli. The present study employed functional magnetic resonance imaging (fMRI) and an interference task that involves emotional facial expressions and elicits rACC activation in healthy participants.FindingsWhile performing a trauma-unrelated emotional interference task, participants with PTSD (n=17) showed less rACC activation than trauma-exposed non-PTSD (TENP; n=18) participants. In the PTSD group, rACC activation was negatively correlated with the severity of re-experiencing symptoms. The two groups did not significantly differ on behavioral measures (i.e., response times and error rates).ConclusionsThese findings suggest that relatively diminished rACC activation in PTSD can be observed in interference tasks involving trauma-unrelated emotional stimuli, indicating a more general functional brain abnormality in this disorder. Future neuroimaging studies need not employ trauma-related stimuli in order to detect rACC abnormalities in PTSD.

Benzodiazepines Counteract Rostral Anterior Cingulate Cortex Activation Induced by Cholecystokinin-Tetrapeptide in Humans

Benzodiazepines modulate γ-aminobutyric acid type A (GABA(A)) receptors throughout the brain. However, it is not fully understood which brain regions within anxiety-related brain circuits are really responsible for their anxiolytic effects and how these regions interact. We investigated whether the benzodiazepine alprazolam affects activity in distinct brain regions within anxiety-related circuits during an experimental anxiety paradigm by means of functional magnetic resonance imaging (fMRI). Panic symptoms were elicited by a bolus injection of the neuropeptide cholecystokinin-tetrapeptide (CCK-4) in 16 healthy male subjects in a double-blind, placebo-controlled design. Functional brain activation patterns were determined before and during the CCK-4-challenge without pretreatment and after treatment with either placebo or 1 mg alprazolam. The CCK-4 induced anxiety and elicited widely distributed activation patterns in anxiety-related brain circuits, especially in the rostral anterior cingulate cortex (rACC), which was attenuated after alprazolam treatment. In contrast to placebo, alprazolam abolished the activation of the rACC after challenge with CCK-4 (p<.005, corrected for multiple comparisons) and increased functional connectivity between the rACC and other anxiety-related brain regions such as amygdala and prefrontal cortex. Moreover, the reduction in the CCK-4 induced activation of the rACC correlated with the anxiolytic effect of alprazolam (r(p) = .52; p = .04). These findings put forward the rACC as a target for benzodiazepines and suggest that the CCK-4/fMRI paradigm might represent a human translational model for the investigation of anxiolytic drugs.

Pain Attenuation through Mindfulness is Associated with Decreased Cognitive Control and Increased Sensory Processing in the Brain

Pain can be modulated by several cognitive techniques, typically involving increased cognitive control and decreased sensory processing. Recently, it has been demonstrated that pain can also be attenuated by mindfulness. Here, we investigate the underlying brain mechanisms by which the state of mindfulness reduces pain. Mindfulness practitioners and controls received unpleasant electric stimuli in the functional magnetic resonance imaging scanner during a mindfulness and a control condition. Mindfulness practitioners, but not controls, were able to reduce pain unpleasantness by 22% and anticipatory anxiety by 29% during a mindful state. In the brain, this reduction was associated with decreased activation in the lateral prefrontal cortex and increased activation in the right posterior insula during stimulation and increased rostral anterior cingulate cortex activation during the anticipation of pain. These findings reveal a unique mechanism of pain modulation, comprising increased sensory processing and decreased cognitive control, and are in sharp contrast to established pain modulation mechanisms.