Activity In Left Anterior Insula Research Articles

Changes in neural responses during affective and non-affective tasks and improvement of posttraumatic stress disorder symptoms following trauma-focused psychotherapy

At least one-third posttraumatic stress disorder (PTSD) patients do not respond to trauma-focused psychotherapy (TF-psychotherapy), which is the treatment of choice for PTSD. To clarify the change mechanisms that may be associated with treatment response, this study examined changes in neural activations during affective and non-affective processing that occur with improvement of symptoms after TF-psychotherapy. This study assessed PTSD treatment-seeking patients (n = 27) prior to and after TF-psychotherapy using functional magnetic resonance imaging when they completed three tasks: (a) passive viewing of affective faces, (b) cognitive reappraisal of negative images, and (c) non-affective response inhibition. Patients then underwent 9 sessions of TF-psychotherapy, and were assessed on the Clinician-Administered PTSD Scale following treatment. Changes in neural responses in affect and cognitive processing regions-of-interest for each task were correlated with reduction of PTSD severity from pretreatment to posttreatment in the PTSD cohort. Data from 21 healthy controls was used for comparison. Improvement of symptoms in PTSD were associated with increased activation of left anterior insula, reductions in the left hippocampus and right posterior insula during viewing of supraliminally presented affective images, and reduced connectivity between the left hippocampus with the left amygdala and rostral anterior cingulate. Treatment response was also associated with reduced activation in the left dorsolateral prefrontal cortex during reappraisal of negative images. There were no associations between response and activation change during response inhibition. This pattern of findings indicates that improvement of PTSD symptoms following TF-psychotherapy is associated with changes in affective rather than non-affective processes. These findings accord with prevailing models that TF-psychotherapy promotes engagement and mastery of affective stimuli.Clinical Trials Registration: Trial Registration: Prospectively registered at Australian and New Zealand Clinical Trials Registry, ACTRN12612000185864 and ACTRN12609000324213. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83857

Precentral gyrus and insula responses to stress vary with duration to diagnosis in functional seizures.

This study was undertaken to determine whether undiagnosed illness duration (time between functional seizures [FS] onset and diagnosis) is linked to differences in neural response and functional connectivity during processing of stressful experiences. Forty-nine participants with traumatic brain injury preceding the onset of FS confirmed by video-electroencephalography were recruited prospectively. Participants completed psychiatric symptom assessments before undergoing functional magnetic resonance imaging (fMRI) with an acute psychosocial stress task. Linear mixed effects (LME) analyses identified significant interactions between the factors of group (early vs. delayed diagnosis) and time lag to diagnosis on neural responses to stressful math performance and auditory feedback (corrected α=.05). Functional connectivity analysis utilized clusters from initial LME analyses as seed regions to determine significant interactions between these factors on network functional connectivity. Demographic and psychiatric symptom measures were similar between early (n=25) and delayed (n=24) groups. Responses to stressful math performance within the left anterior insula and functional connectivity between the anterior insula seed region and a precentral gyrus cluster were significantly negatively correlated with time lag to diagnosis for the early but not the delayed FS diagnosis group. There was no correlation between fMRI findings and psychiatric symptoms. This study indicates that aberrant left anterior insula activation and its functional connectivity to the precentral gyrus underlie differences in processing of stressful experiences in patients with delayed FS diagnosis. Follow-up comparisons suggest changes are associated with undiagnosed illness duration rather than psychiatric comorbidities and indicate a potential mechanistic association between neuropathophysiology, response to stressful experiences, and functional neuroanatomy in FS.

Processing of emotionally ambiguous stimuli in eating disorders: an fMRI pilot study.

People with eating disorders (EDs) have difficulties understanding their own emotions and recognizing the emotions of others, especially in ambiguous settings. We examined the neuronal mechanisms underlying the emotion processing of ambiguous interpersonal stimuli in EDs and healthy controls (HCs). The fMRI data were acquired by a blocked experimental design with 28 women (14 EDs) during the visual presentation of a modified Thematic Apperception Test. EDs showed very strong associations between experienced and inferred emotions evoked by the stimuli; no such relationship was found in HCs. HCs displayed elevated left anterior insula activity during the mentalizing condition; EDs showed increased activity in the right supramarginal gyrus and medial prefrontal cortex. The two groups seem to apply different strategies for judging emotionally ambiguous stimuli, albeit resulting in equivalent judgments. We assume that activity in the supramarginal gyrus and insula in EDs is linked with suppressing their own perspective while considering emotional states, probably due to alexithymia and the lack of awareness of their own mental states. We hypothesize that the strong correlation between experienced and inferred emotions in EDs could reflect their tendency to use others as a reference point for perceiving themselves and gaining information about their affective state. No level of evidence, this is a basic science study.

Modifications in fMRI Representation of Mental Rotation Following a 6 Week Graded Motor Imagery Training in Chronic CRPS Patients

Complex regional pain syndrome (CRPS) is a neuropathic pain condition that is difficult to treat. For behavioral interventions, graded motor imagery (GMI) showed relevant effects, but underlying neural substrates in patient groups have not been investigated yet. A previous study investigating differences in the representation of a left/right hand judgment task demonstrated less recruitment of subcortical structures, such as the putamen, in CRPS patients than in healthy controls. In healthy volunteers, the putamen activity increased after a hand judgment task training. In order to test for longitudinal effects of GMI training, we investigated 20 CRPS patients in a wait-list crossover design with 3 evaluation time points. Patients underwent a 6 week GMI treatment and a 6 week waiting period in a randomized group assignment and treatment groups were evaluated by a blinded rater. When compared to healthy matched controls at baseline, CRPS patients showed less functional activation in areas processing visual input, left sensorimotor cortex, and right putamen. Only GMI treatment, but not the waiting period showed an effect on movement pain and hand judgment task performance. Regression analyses revealed positive associations of movement pain with left anterior insula activation at baseline. Right intraparietal sulcus activation change during GMI was associated with a gain in performance of the hand judgment task. The design used here is reliable for investigating the functional representation of the hand judgment task in an intervention study. PerspectiveTwenty chronic CRPS patients underwent a 6 week GMI intervention in a randomized wait-list crossover design. functional MRI was tested pre and post for the hand lateralization task which improved over GMI but not over WAITING. Performance gain was positively related to right parietal functional MRI activation.

The cognitive and neural mechanisms underlying norm-enforcement behaviors under social observation.

Abundant evidence has revealed that social observation could enhance people's norm-enforcement behaviors to norm violators. However, whether such enhancement is strategically reputation-based without changes on awareness of social norms or it is accompanied with strengthened perception of norm violations remains unclear. We aimed to test these two hypotheses using a modified Ultimatum Game (UG). Participants played the UG as responders in the fMRI scanner after being instructed the rules of the game and how the observers monitored their performances during the task. Behavioral results showed that unfair offers were perceived more unfair (decreased fairness ratings) and rejected more often under the condition with social observation than that without observation (the control condition). The changes in fairness ratings predicted the increase of rejection rates between two conditions, which provided more evidence for the latter hypothesis. Neural results demonstrated that right insula and anterior cingulate cortex associated with processing norm violations and/or negative emotions were more activated in response to unfair treatments under social observation relative to the control condition. Furthermore, bilateral anterior insula, anterior cingulate cortex, and right amygdala (an emotional processing structure) showed increased activations with the reduction of fairness ratings under social observation. Besides, compared to the control condition, rejecting unfair trials under social observation induced more left anterior insula activation. These findings indicated that the increase of norm-enforcement behaviors in the UG under social observation was more than a behavioral strategy for social desirability, but a result of enhanced sensitivity to fairness norm violations and unfairness-related negative feelings.

Test-retest reliability of fMRI-measured brain activity during decision making under risk

Neural correlates of decision making under risk are being increasingly utilized as biomarkers of risk for substance abuse and other psychiatric disorders, treatment outcomes, and brain development. This research relies on the basic assumption that fMRI measures of decision making represent stable, trait-like individual differences. However, reliability needs to be established for each individual construct. Here we assessed long-term test-retest reliability (TRR) of regional brain activations related to decision making under risk using the Balloon Analogue Risk Taking task (BART) and identified regions with good TRRs and familial influences, an important prerequisite for the use of fMRI measures in genetic studies. A secondary goal was to examine the factors potentially affecting fMRI TRRs in one particular risk task, including the magnitude of neural activation, data analytical approaches, different methods of defining boundaries of a region, and participant motion. For the average BOLD response, reliabilities ranged across brain regions from poor to good (ICCs of 0 to 0.8, with a mean ICC of 0.17) and highest reliabilities were observed for parietal, occipital, and temporal regions. Among the regions that were of a priori theoretical importance due to their reported associations with decision making, the activation of left anterior insula and right caudate during the decision period showed the highest reliabilities (ICCs of 0.54 and 0.63, respectively). Among the regions with highest reliabilities, the right fusiform, right rostral anterior cingulate and left superior parietal regions also showed high familiality as indicated by intrapair monozygotic twin correlations (ranging from 0.66 to 0.69). Overall, regions identified by modeling the average BOLD response to a specific event type (rather than its modulation by a parametric regressor), regions including significantly activated vertices (compared to a whole parcel), and regions with greater magnitude of task-related activations showed greater reliabilities. Participant motion had a moderate negative effect on TRR. Regions activated during decision period rather than outcome period of risky decisions showed the greatest TRR and familiality. Regions with reliable activations can be utilized as neural markers of individual differences or endophenotypes in future clinical neuroscience and genetic studies of risk-taking.

Insula shows abnormal task-evoked and resting-state activity in first-episode drug-naïve generalized anxiety disorder.

Interoception is associated with neural activity in the insula of healthy humans. On the basis of the somatic symptoms in generalized anxiety disorder (GAD), especially abnormal heartbeat perception, we hypothesized that abnormal activity in the insula was associated with interoceptive awareness in patients with GAD. We investigated the psychological correlates of interoceptive awareness in a sample of 34 patients with first-onset, drug-naïve GAD and 30 healthy controls (HCs). Furthermore, we compared blood oxygenation level-dependent responses between the two groups during a heartbeat perception task to assess task-evoked activity and its relationship with psychological measures. We also examined between-group differences in insular subregions resting-state functional connectivity (rsFC), and its relationship with anxiety severity. Patients with GAD had significantly higher body perception scores than HCs. They also exhibited greater task-evoked activity in the left anterior insula, left posterior insula, and right anterior insula during interoceptive awareness than HCs. Left anterior insula activity was positively correlated with body awareness in patients with GAD, and rsFC between the left anterior insula and left medial prefrontal gyrus was negatively correlated with somatic anxiety severity. Investigating a sample of first-episode, drug-naïve patients, our study demonstrated abnormal interoceptive awareness in patients with GAD and that this was related to abnormal anterior insular activity during both rest and task. These results shed new light on the psychological and neural substrates of somatic symptoms in GAD, and they may serve to establish abnormal interoceptive awareness as a neural and psychological marker of GAD.

Low-dose augmentation with buprenorphine increases emotional reactivity but not reward activity in treatment resistant mid- and late-life depression.

Buprenorphine is currently being studied for treatment-resistant depression because of its rapid effect, relative safety, and unique pharmacodynamics. To understand the neural impact of buprenorphine in depression, we examined acute limbic and reward circuit changes during an intervention with low-dose buprenorphine augmentation pharmacotherapy. Mid and late-life adults with major depression (N = 31) who did not completely respond to an adequate trial of venlafaxine were randomized to augmentation with low-dose buprenorphine or matching placebo. We investigated early neural changes using functional magnetic resonance imaging (fMRI) from pre-randomization to 3 weeks using both an emotional reactivity task and a gambling task. We tested if: 1) there were significant neural changes acutely per intervention group, and 2) if acute neural changes were associated with depressive symptom change over 8 weeks using both the total score and the dysphoria subscale of the Montgomery Asberg Depression Rating Scale. Participants in both the buprenorphine and placebo groups showed similar changes in depressive symptoms. Neither the emotional reactivity nor gambling task resulted in significant neural activation changes from pre-randomization to 3-weeks. In both groups, increases in rostral anterior cingulate (rACC) and ventromedial prefrontal cortex (vmPFC) activation during the emotional reactivity task were associated with overall symptom improvement. In the buprenorphine but not the placebo group, increased activation in left anterior insula (aINS) and bilateral middle frontal gyrus (MFG) was associated with improvement on the dysphoria subscale. Activation changes in the reward task were not associated with buprenorphine. This is the first study to show an association between acute neural changes during emotion reactivity and changes in depression severity with buprenorphine treatment.

Neural correlates of sibling closeness and association with externalizing behavior in adolescence.

Sibling relationships have been linked to adolescent externalizing behaviors, but the neurobiological factors that underlie this association have not been identified. This study investigated sibling closeness and birth order as a predictor of adolescent externalizing behavior via differences in neural processes during safe decision-making. A total of 77 adolescents (range = 12–15 years, Mage = 13.45 years, 40 females) completed a computerized driving task during a functional MRI scan. Results showed that adolescents’ perceptions of sibling closeness were associated with greater neural activation in the anterior insula, ventral striatum and left ventrolateral prefrontal cortex when making safe decisions, suggesting that the quality of sibling relationships modulates adolescent neurocognition even without being present. Furthermore, moderated mediation analyses revealed that higher sibling closeness was associated with lower externalizing behavior via left anterior insula activation during safe decision-making, but only for adolescents without older siblings (i.e. eldest children) compared to adolescents who had multiple older siblings. Importantly, these findings persisted above and beyond parental and peer closeness and sibling characteristics (i.e. sex, relatedness, birth order), highlighting the significant influence of sibling relationships on adolescent externalizing behavior through the brain.

Extraordinary Altruists Exhibit Enhanced Self–Other Overlap in Neural Responses to Distress

Shared neural representations during experienced and observed distress are hypothesized to reflect empathic neural simulation, which may support altruism. But the correspondence between real-world altruism and shared neural representations has not been directly tested, and empathy’s role in promoting altruism toward strangers has been questioned. Here, we show that individuals who have performed costly altruism (donating a kidney to a stranger; n = 25) exhibit greater self–other overlap than matched control participants (n = 27) in neural representations of pain and threat (fearful anticipation) in anterior insula (AI) during an empathic-pain paradigm. Altruists exhibited greater self–other correspondence in pain-related activation in left AI, highlighting that group-level overlap was supported by individual-level associations between empathic pain and firsthand pain. Altruists exhibited enhanced functional coupling of left AI with left midinsula during empathic pain and threat. Results show that heightened neural instantiations of empathy correspond to real-world altruism and highlight limitations of self-report.

Mindfulness meditation regulates anterior insula activity during empathy for social pain.

Mindfulness has been shown to reduce stress, promote health, and well-being, as well as to increase compassionate behavior toward others. It reduces distress to one's own painful experiences, going along with altered neural responses, by enhancing self-regulatory processes and decreasing emotional reactivity. In order to investigate if mindfulness similarly reduces distress and neural activations associated with empathy for others' socially painful experiences, which might in the following more strongly motivate prosocial behavior, the present study compared trait, and state effects of long-term mindfulness meditation (LTM) practice. To do so we acquired behavioral data and neural activity measures using functional magnetic resonance imaging (fMRI) during an empathy for social pain task while manipulating the meditation state between two groups of LTM practitioners that were matched with a control group. The results show increased activations of the anterior insula (AI) and anterior cingulate cortex (ACC) as well as the medial prefrontal cortex and temporal pole when sharing others' social suffering, both in LTM practitioners and controls. However, in LTM practitioners, who practiced mindfulness meditation just prior to observing others' social pain, left AI activation was lower and the strength of AI activation following the mindfulness meditation was negatively associated with trait compassion in LTM practitioners. The findings suggest that current mindfulness meditation could provide an adaptive mechanism in coping with distress due to the empathic sharing of others' suffering, thereby possibly enabling compassionate behavior. Hum Brain Mapp 38:4034-4046, 2017. © 2017 Wiley Periodicals, Inc.

Altered olfactory processing and increased insula activity in patients with obsessive-compulsive disorder: An fMRI study

Obsessive-compulsive disorder (OCD) patients show increased insula activation to disgust-inducing images compared to healthy controls (HC). We explored whether this disgust reactivity was also present in the olfactory domain by conducting the first fMRI study of olfaction in OCD. Neural activation in response to pleasant and unpleasant odors (vs. unscented air) was investigated in 15 OCD and 15 HC participants using fMRI. OCD participants (vs. HC) had increased left anterior insula activation to unpleasant odors (vs. unscented air), which positively correlated with their disgust sensitivity and ratings of the unpleasantness and intensity of those odors. OCD participants (vs. HC) showed increased activation of caudate nucleus and left anterior and posterior insula to pleasant odors (vs. unscented air), which positively correlated with their OCD symptom severity, trait anxiety, frequency of feeling disgust, and odor intensity ratings. OCD participants had increased anterior insula activation to both pleasant and unpleasant odors, which correlated with their OCD symptoms, anxiety, disgust sensitivity, and frequency of feeling disgust. OCD patients might have a negative cognitive bias and experience all stimuli, regardless of valence, as being more unpleasant than healthy people. These findings further elucidate the neural underpinnings of OCD and may contribute to more effective treatments.

What do you feel? Adolescent drug and alcohol users show altered brain response to pleasant interoceptive stimuli

BackgroundAltered interoception, i.e., processing of stimuli from inside the body, has been considered an important component of drug-taking behavior. However, approaches to examine interoceptive sensitivity in humans have been limited. This study examined the hypothesis that adolescents with substance use disorder show altered interoceptive processing, measured by stimulating mechano-receptive C-fibers (MR-CF) via soft touch. MethodsAdolescents with substance use disorders (SUD, n=15) and comparison youth (CON, n=17) underwent functional magnetic resonance imaging (fMRI) during anticipation or reception of a positively valenced “Soft Touch” consisting of MR-CF stimulation to the palm or forearm. Visual analog scales (VAS) indexed subjective interoceptive experience (e.g., pleasantness, intensity). ResultsAcross all conditions, SUD displayed attenuated left posterior insula activation compared to CON. Greater left anterior insula and right lentiform nucleus activation was evident during the application of soft touch for SUD but not for CON. Whereas for CON, greater left anterior insula activation was associated with higher pleasantness ratings, pleasantness was linked to less anterior insula activation in SUD. Finally, within SUD, attenuated posterior insula activation was related to more recent cannabis use. ConclusionsSUD adolescents exhibit blunted somatovisceral processing of pleasant stimulation, heightened sensitivity in regions responsible for processing reward value, and altered relationships between interoceptive processing and subjective experience.

The neural correlates of incidental self-processing induced by handwritten negative words

Behavioral studies revealed that people were less likely to endorse negative information as self-descriptive. Neuroimaging studies have tapped on the neural mechanism underlying intentional self-processing of negative information using self-reflection tasks. Given that human self-processing occurring in our daily life is more likely to be captured by tasks involving incidental self-processing (automatic associations between the self- and external stimuli), rather than tasks involving intentional self-processing, it could be presumed that the relationship between self- and negative emotion might be better reflected during incidental self-processing. The present functional magnetic resonance imaging study aimed to explore incidental self-processing of negative information. To induce participants' incidental self-processing, we adopted negative and neutral words written by themselves or others as materials. They were scanned during judging whether the handwritten words were negative or neutral (additional non-self-task). Results revealed that incidental self-processing of negative information relied on the activation of left anterior insula, whereas medial prefrontal cortex activity was associated with incidental self-processing of neutral information.

Treatment effects on insular and anterior cingulate cortex activation during classic and emotional Stroop interference in child abuse-related complex post-traumatic stress disorder

Functional neuroimaging studies have shown increased Stroop interference coupled with altered anterior cingulate cortex (ACC) and insula activation in post-traumatic stress disorder (PTSD). These brain areas are associated with error detection and emotional arousal. There is some evidence that treatment can normalize these activation patterns. At baseline, we compared classic and emotional Stroop performance and blood oxygenation level-dependent responses (functional magnetic resonance imaging) of 29 child abuse-related complex PTSD patients with 22 non-trauma-exposed healthy controls. In 16 of these patients, we studied treatment effects of psycho-educational and cognitive behavioural stabilizing group treatment (experimental treatment; EXP) added to treatment as usual (TAU) versus TAU only, and correlations with clinical improvement. At baseline, complex PTSD patients showed a trend for increased left anterior insula and dorsal ACC activation in the classic Stroop task. Only EXP patients showed decreased dorsal ACC and left anterior insula activation after treatment. In the emotional Stroop contrasts, clinical improvement was associated with decreased dorsal ACC activation and decreased left anterior insula activation. We found further evidence that successful treatment in child abuse-related complex PTSD is associated with functional changes in the ACC and insula, which may be due to improved selective attention and lower emotional arousal, indicating greater cognitive control over PTSD symptoms.

Disgust trait modulates frontal-posterior coupling as a function of disgust domain

Following the two-stage model of disgust, 'core disgust' (e.g. elicited by rotten food) is extended to stimuli that remind us of our animal nature 'AR disgust' (e.g. mutilations, animalistic instincts). There is ample evidence that core and AR represent distinct domains of disgust elicitors. Moreover, people show large differences in their tendency to respond with disgust to potential disgust elicitors (propensity), as well as in their appraisal of experiencing disgust (sensitivity). Thus these traits may be important moderators of people's response patterns. Here, we aimed to find brain mechanisms associated with these distinct disgust domains and traits, as well as the interaction between them. The right ventrolateral occipitotemporal cortex, which preferentially responded to visual AR, was functionally coupled to the middle cingulate cortex (MCC), thalamus and prefrontal cortex (medial, dorsolateral), as a function of disgust domain. Coupling with the anterior part of MCC was modulated by disgust 'propensity', which was strongest during AR. Coupling with anterior insula and ventral premotor cortex was weaker, but relied fully on this domain-trait interaction. Disgust 'sensitivity' modulated left anterior insula activity irrespective of domain, and did not affect functional connectivity. Thus a frontal-posterior network that interacts with disgust 'propensity' dissects AR and core disgust.

Pregabalin effects on neural response to emotional faces

Pregabalin has shown promise in the treatment of anxiety disorders. Previous functional magnetic resonance imaging (fMRI) studies indicate agents used to treat anxiety, e.g., SSRIs and benzodiazepines, attenuate amygdala, insula, and medial prefrontal cortex (mPFC) activation during emotional processing. Our prior study has shown that during anticipation of an emotional stimulus, pregabalin attenuates amygdala and insula activation but increases medial PFC activation. In this study, we examined whether, similar to SSRIs and benzodiazepines, pregabalin attenuates amygdala, insula, and medial PFC during emotional face processing. Sixteen healthy volunteers underwent a double-blind within-subjects fMRI study investigating effects of placebo, 50 mg, and 200 mg pregabalin on neural activation during an emotional face-matching task. Linear mixed model analysis revealed that pregabalin dose-dependently attenuated left amygdala activation during fearful face-matching and left anterior insula activation during angry face-matching. The 50 mg dose exhibited more robust effects than the 200 mg dose in the right anterior insula and ventral ACC. Thus, pregabalin shares some similarity to SSRIs and benzodiazepines in attenuating anger and fear-related insula and amygdala activation during emotional face processing. However, there is evidence that a subclinical 50 mg dose of pregabalin produced more robust and widespread effects on neural responses in this paradigm than the more clinically relevant 200 mg dose. Taken together, pregabalin has a slightly different effect on brain activation as it relates to anticipation and emotional face processing, which may account for its unique characteristic as an agent for the treatment of anxiety disorders.

Using real-time fMRI to learn voluntary regulation of the anterior insula in the presence of threat-related stimuli

Previous studies have shown that healthy participants learn to control local brain activity with operant training by using real-time functional magnetic resonance imaging (rt-fMRI). Very little data exist, however, on the dynamics of interaction between critical brain regions during rt-fMRI-based training. Here, we examined self-regulation of stimulus-elicited insula activation and performed a psychophysiological interaction (PPI) analysis of real-time self-regulation data. During voluntary up-regulation of the left anterior insula in the presence of threat-related pictures, differential activations were observed in the ventrolateral prefrontal cortex, the frontal operculum, the middle cingulate cortex and the right insula. Down-regulation in comparison to no-regulation revealed additional activations in right superior temporal cortex, right inferior parietal cortex and right middle frontal cortex. There was a significant learning effect over sessions during up-regulation, documented by a significant improvement of anterior insula control over time. Connectivity analysis revealed that successful up-regulation of the activity in left anterior insula while viewing aversive pictures was directly modulated by dorsomedial and ventrolateral prefrontal cortex. Down-regulation of activity was more difficult to achieve and no learning effect was observed. More extensive training might be necessary for successful down-regulation. These findings illustrate the functional interactions between different brain areas during regulation of anterior insula activity in the presence of threat-related stimuli.

Volitional Control of Anterior Insula Activity Modulates the Response to Aversive Stimuli. A Real-Time Functional Magnetic Resonance Imaging Study

A promising new approach to cognitive neuroscience based on real-time functional magnetic resonance imaging (rtfMRI) demonstrated that the learned regulation of the neurophysiological activity in circumscribed brain regions can be used as an independent variable to observe its effects on behavior. Here, for the first time, we investigated the modulatory effect of learned regulation of blood oxygenation level-dependent (BOLD) response in the left anterior insula on the perception of visual emotional stimuli. Three groups of participants (n = 27) were tested: two underwent four rtfMRI training sessions receiving either specific (n = 9) or unspecific feedback (n = 9) of the insula's BOLD response, respectively, and one group used emotional imagery alone (n = 9) without rtfMRI feedback. During training, all groups were required to assess aversive and neutral pictures. Participants able to significantly increase BOLD signal in the target region rated the aversive pictures more negatively. We measured a significant correlation between enhanced left anterior insula activity and increased negative valence ratings of the aversive stimuli. Control groups performing either rtfMRI training with unspecific feedback or an emotional imagery training alone were not able to significantly enhance activity in the left anterior insula and did not show changes in subjective emotional responses. This study corroborates traditional neuroimaging studies demonstrating a critical role of the anterior insula in the explicit appraisal of emotional stimuli and indicates the adopted approach as a potential tool for clinical applications in emotional disorders.

Empathic brain responses in insula are modulated by levels of alexithymia but not autism

Difficulties in social cognition are well recognized in individuals with autism spectrum conditions (henceforth ‘autism’). Here we focus on one crucial aspect of social cognition: the ability to empathize with the feelings of another. In contrast to theory of mind, a capacity that has often been observed to be impaired in individuals with autism, much less is known about the capacity of individuals with autism for affect sharing. Based on previous data suggesting that empathy deficits in autism are a function of interoceptive deficits related to alexithymia, we aimed to investigate empathic brain responses in autistic and control participants with high and low degrees of alexithymia. Using functional magnetic resonance imaging, we measured empathic brain responses with an ‘empathy for pain’ paradigm assessing empathic brain responses in a real-life social setting that does not rely on attention to, or recognition of, facial affect cues. Confirming previous findings, empathic brain responses to the suffering of others were associated with increased activation in left anterior insula and the strength of this signal was predictive of the degree of alexithymia in both autistic and control groups but did not vary as a function of group. Importantly, there was no difference in the degree of empathy between autistic and control groups after accounting for alexithymia. These findings suggest that empathy deficits observed in autism may be due to the large comorbidity between alexithymic traits and autism, rather than representing a necessary feature of the social impairments in autism.