Neural correlates of self-focused attention in social anxiety

Socially anxious individuals tend to shift their attention away from external socially threatening cues and instead become highly self-focused. Such heightened self-focused attention has been suggested to be involved in the development and maintenance of social anxiety disorder. This study used functional magnetic resonance imaging to investigate the neural correlates of self-focused attention in 16 high socially anxious (HSA) and 16 low socially anxious (LSA) individuals. Participants were instructed to focus their attention either inwardly or outwardly during a simulated social situation. Results indicate hyperactivation of medial prefrontal cortex (mPFC), temporo-parietal junction (TPJ) and temporal pole during inward vs outward attention in HSA compared with LSA participants. Furthermore, activation of mPFC, right anterior insula, TPJ and posterior cingulate cortex was positively correlated with the trait of self-focused attention in HSA subjects. Results highlight the prominent role of the mPFC and other cortical structures in abnormal self-focused attention in social anxiety. Finally, findings for the insula suggest increased processing of bodily states that is related to the amount of habitual self-focused attention in social anxiety.     

Tools of the trade: theory and method in mindfulness neuroscience

Mindfulness neuroscience is an emerging research field that investigates the underlying mechanisms of different mindfulness practices, different stages and different states of practice as well as different effects of practice over the lifespan. Mindfulness neuroscience research integrates theory and methods from eastern contemplative traditions, western psychology and neuroscience, and from neuroimaging techniques, physiological measures and behavioral tests. We here review several key theoretical and methodological challenges in the empirical study of mindfulness neuroscience and provide suggestions for overcoming these challenges.     

Investigation of mindfulness meditation practitioners with voxel-based morphometry

Mindfulness meditators practice the non-judgmental observationof the ongoing stream of internal experiences as they arise.Using voxel-based morphometry, this study investigated MRI brainimages of 20 mindfulness (Vipassana) meditators (mean practice8.6 years; 2 h daily) and compared the regional gray matterconcentration to that of non-meditators matched for sex, age,education and handedness. Meditators were predicted to showgreater gray matter concentration in regions that are typicallyactivated during meditation. Results confirmed greater graymatter concentration for meditators in the right anterior insula,which is involved in interoceptive awareness. This group differencepresumably reflects the training of bodily awareness duringmindfulness meditation. Furthermore, meditators had greatergray matter concentration in the left inferior temporal gyrusand right hippocampus. Both regions have previously been foundto be involved in meditation. The mean value of gray matterconcentration in the left inferior temporal gyrus was predictableby the amount of meditation training, corroborating the assumptionof a causal impact of meditation training on gray matter concentrationin this region. Results suggest that meditation practice isassociated with structural differences in regions that are typicallyactivated during meditation and in regions that are relevantfor the task of meditation.     

γ-Aminobutyric acid (GABA) concentration inversely correlates with basal perfusion in human occipital lobe

Commonly used neuroimaging approaches in humans exploit hemodynamic or metabolic indicators of brain function. However, fundamental gaps remain in our ability to relate such hemo-metabolic reactivity to neurotransmission, with recent reports providing paradoxical information regarding the relationship among basal perfusion, functional imaging contrast, and neurotransmission in awake humans. Here, sequential magnetic resonance spectroscopy (MRS) measurements of the primary inhibitory neurotransmitter, γ-aminobutyric acid (GABA+macromolecules normalized by the complex N-acetyl aspartate-N-acetyl aspartyl glutamic acid: [GABA⁺]/[NAA–NAAG]), and magnetic resonance imaging (MRI) measurements of perfusion, fractional gray-matter volume, and arterial arrival time (AAT) are recorded in human visual cortex from a controlled cohort of young adult male volunteers with neurocognitive battery-confirmed comparable cognitive capacity (3 T; n=16; age=23±3 years). Regression analyses reveal an inverse correlation between [GABA⁺]/[NAA–NAAG] and perfusion (R=−0.46; P=0.037), yet no relationship between AAT and [GABA⁺]/[NAA–NAAG] (R=−0.12; P=0.33). Perfusion measurements that do not control for AAT variations reveal reduced correlations between [GABA⁺]/[NAA–NAAG] and perfusion (R=−0.13; P=0.32). These findings largely reconcile contradictory reports between perfusion and inhibitory tone, and underscore the physiologic origins of the growing literature relating functional imaging signals, hemodynamics, and neurotransmission.     

Meditation,mindfulness and executive control: the importance of emotional acceptance and brain-based performance monitoring

Previous studies have documented the positive effects of mindfulness meditation on executive control. What has been lacking, however, is an understanding of the mechanism underlying this effect. Some theorists have described mindfulness as embodying two facets—present moment awareness and emotional acceptance. Here, we examine how the effect of meditation practice on executive control manifests in the brain, suggesting that emotional acceptance and performance monitoring play important roles. We investigated the effect of meditation practice on executive control and measured the neural correlates of performance monitoring, specifically, the error-related negativity (ERN), a neurophysiological response that occurs within 100 ms of error commission. Meditators and controls completed a Stroop task, during which we recorded ERN amplitudes with electroencephalography. Meditators showed greater executive control (i.e. fewer errors), a higher ERN and more emotional acceptance than controls. Finally, mediation pathway models further revealed that meditation practice relates to greater executive control and that this effect can be accounted for by heightened emotional acceptance, and to a lesser extent, increased brain-based performance monitoring.     

Psychological and neural mechanisms of trait mindfulness in reducing depression vulnerability

Mindfulness-based interventions are effective for reducing depressive symptoms. However, the psychological and neural mechanisms are unclear. This study examined which facets of trait mindfulness offer protection against negative bias and rumination, which are key risk factors for depression. Nineteen male volunteers completed a 2-day functional magnetic resonance imaging study. One day utilized a stress-induction task and the other day utilized a mindful breathing task. An emotional inhibition task was used to measure neural and behavioral changes related to state negative bias, defined by poorer performance in inhibiting negative relative to neutral stimuli. Associations among trait mindfulness [measured by the Five Facet Mindfulness Questionnaire (FFMQ)], trait rumination, and negative bias were examined. Non-reactivity scores on the FFMQ correlated negatively with rumination and negative bias following the stress induction. Non-reactivity was inversely correlated with insula activation during inhibition to negative stimuli after the mindful breathing task. Our results suggest non-reactivity to inner experience is the key facet of mindfulness that protects individuals from psychological risk for depression. Based on these results, mindfulness could reduce vulnerability to depression in at least two ways: (i) by buffering against trait rumination and negative bias and (ii) by reducing automatic emotional responding via the insula.     

Neural correlates of attributing causes to the self,another person and the situation

This study compares brain activation during causal attribution to three different loci, the self, another person and the situation; and further explores correlations with clinical scales (i.e. depression, anxiety and autism) in a typical population. While they underwent functional magnetic resonance imaging, 20 participants read short sentences about another person (‘someone’) who engaged in behaviors with the participant or made comments about the participant. The participants then attributed these behaviors to three attribution loci: themselves, the other person or the situation. The results revealed common activation across the three attribution loci in the bilateral temporo-parietal junction (TPJ), left posterior superior temporal sulcus, precuneus and right temporal pole (TP). Comparisons between the attribution loci revealed very little differences, except for increased activation of the right TP while making attributions to the situation compared with the self. In addition, when making attributions to the situation or other persons for negative events, there were reliable correlations between low activity in the left TPJ and high levels of anxiety and problematic social interaction in autism. The results indicate that attributions to different loci are based on the same underlying brain process, which might be atypical among persons with anxiety or autism symptoms.     

Neural correlates of anticipation and processing of performance feedback in social anxiety

Fear of negative evaluation, such as negative social performance feedback, is the core symptom of social anxiety. The present study investigated the neural correlates of anticipation and perception of social performance feedback in social anxiety. High (HSA) and low (LSA) socially anxious individuals were asked to give a speech on a personally relevant topic and received standardized but appropriate expert performance feedback in a succeeding experimental session in which neural activity was measured during anticipation and presentation of negative and positive performance feedback concerning the speech performance, or a neutral feedback‐unrelated control condition. HSA compared to LSA subjects reported greater anxiety during anticipation of negative feedback. Functional magnetic resonance imaging results showed deactivation of medial prefrontal brain areas during anticipation of negative feedback relative to the control and the positive condition, and medial prefrontal and insular hyperactivation during presentation of negative as well as positive feedback in HSA compared to LSA subjects. The results indicate distinct processes underlying feedback processing during anticipation and presentation of feedback in HSA as compared to LSA individuals. In line with the role of the medial prefrontal cortex in self‐referential information processing and the insula in interoception, social anxiety seems to be associated with lower self‐monitoring during feedback anticipation, and an increased self‐focus and interoception during feedback presentation, regardless of feedback valence. Hum Brain Mapp 35:6023–6031, 2014. © 2014 Wiley Periodicals, Inc.     

Neural changes with attention bias modification for anxiety: a randomized trial

Attention bias modification (ABM) procedures typically reduce anxiety symptoms, yet little is known about the neural changes associated with this behavioral treatment. Healthy adults with high social anxiety symptoms (n = 53) were randomized to receive either active or placebo ABM. Unlike placebo ABM, active ABM aimed to train individuals’ attention away from threat. Using the dot-probe task, threat-related attention bias was measured during magnetic resonance imaging before and after acute and extended training over 4 weeks. A subset of participants completed all procedures (n = 30, 15 per group). Group differences in neural activation were identified using standard analyses. Linear regression tested predictive factors of symptom reduction (i.e., training group, baseline indices of threat bias). The active and placebo groups exhibited different patterns of right and left amygdala activation with training. Across all participants irrespective of group, individuals with greater left amygdala activation in the threat-bias contrast prior to training exhibited greater symptom reduction. After accounting for baseline amygdala activation, greater symptom reduction was associated with assignment to the active training group. Greater left amygdala activation at baseline predicted reductions in social anxiety symptoms following ABM. Further research is needed to clarify brain-behavior mechanisms associated with ABM training.     

Imaging mesial temporal lobe activation during scene encoding: comparison of fMRI using BOLD and arterial spin labeling

Memory encoding is a critical brain function subserved by the hippocampus (HP) and mesial temporal lobe (mTL) structures. Visualization of mTL memory activation with BOLD fMRI is complicated by the presence of static susceptibility gradients in this region. Arterial spin labeled (ASL) perfusion fMRI offers an alternative approach not dependent on susceptibility contrast that instead suffers from lower intrinsic signal-to-noise ratio. An improved ASL perfusion fMRI approach combining pseudo-continuous ASL and a T(2)*-insensitive sequence (GRASE) with background suppression was compared to BOLD fMRI at 3 T during a scene encoding task known to activate the HP. Overall, an approximate sixfold sensitivity increase of ASL fMRI was achieved, with improved coverage in the anterior mTL, while suppression of the static tissue enhanced the stability of the ASL series by a factor of 2.4. Perfusion fMRI using this approach with 4 mm isotropic resolution yielded better localized and stronger group activation maps than BOLD fMRI at a standard resolution of 3 mm isotropic voxels. Increasing the resolution for BOLD to 2.5 mm isotropic produced stronger mTL and hippocampal activation in the group and individual subjects than the ASL technique, due to superior temporal resolution and reduced partial volume effects. Future improvements in ASL spatial and temporal resolution would allow the benefits of both approaches to be combined to further enhance the sensitivity for detecting mTL activation during memory encoding.     

Neural correlates of anxiety sensitivity during masked presentation of affective faces

Background: Anxiety Sensitivity (AS), the tendency to fear the thoughts, symptoms, and social consequences associated with the experience of anxiety, is associated with increased risk for developing anxiety disorders. Some evidence suggests that higher scores on the Anxiety Sensitivity Index (ASI), a measure of the AS construct, are associated with activation of the anterior insular cortex during overt emotion perception. Although the ASI provides subscale scores measuring Physical, Mental Incapacitation, and Social Concerns of AS, no study has examined the relationship between these factors and regional brain activation during affect processing. We hypothesized that insular responses to fear‐related stimuli would be primarily related to the Physical Concerns subscale of the ASI, particularly for a sample of subjects with specific phobias. Methods: Adult healthy controls (HC; n = 22) and individuals with specific phobia, small animal subtype (SAP; n = 17), completed the ASI and underwent functional magnetic resonance imaging while engaged in a backward‐masked affect perception task that presents emotional facial stimuli below the threshold of conscious perception. Results: Groups did not differ in ASI, state or trait anxiety scores, or insula activation. Total ASI scores were positively correlated with activation in the right middle/anterior insula for the combined sample and for the HC and SAP groups separately. Multiple regression analysis revealed that the relationship between AS and insular activation was primarily accounted for by Physical Concerns only. Conclusions: Findings support the hypothesized role of the right anterior insula in the visceral/interoceptive aspects of AS, even in response to masked affective stimuli. Depression and Anxiety 28:243–249, 2011. © 2011 Wiley‐Liss, Inc.     

Neural correlates of anxiety associated with obsessive-compulsive symptom dimensions in normal volunteers.

BACKGROUND: The neural correlates of anxiety associated with obsessive-compulsive symptomlike provocation in normal volunteers are unknown. METHODS: Ten healthy volunteers participated in four functional magnetic resonance experiments. Subjects were scanned while viewing alternating blocks of emotional (normally aversive, washing-relevant, checking-relevant, or hoarding-relevant pictures) and neutral pictures, and imagining scenarios related to the content of each picture type. Nonparametric brain mapping analyses were used. RESULTS: In response to the provocative pictures in all experiments, increases in subjective anxiety and activation in bilateral ventral prefrontal, limbic, dorsal prefrontal, and visual regions were demonstrated. Anxiety related to different symptom dimensions was associated with different patterns of activation: provocation of washing-relevant anxiety predominantly activated dorsal and ventral prefrontal regions; checking-relevant anxiety predominantly activated dorsal prefrontal regions; and hoarding-relevant anxiety predominantly activated ventral prefrontal regions and the left amygdala. CONCLUSIONS: Our findings support a dimensional model of obsessive-compulsive disorder (OCD) whereby 1) the brain systems implicated in the mediation of anxiety in response to symptom-related material in normal subjects are similar to those identified in OCD patients during symptom provocation, and 2) anxiety associated with different symptom dimensions is associated with differential patterns of activation of these neural systems. Further investigation of the neural basis of OCD symptom dimensions is required.     

Altered cerebral blood flow patterns associated with pathologic worry in the elderly

Background: Generalized anxiety disorder (GAD) is the most prevalent anxiety disorder among the elderly and has high functional and cognitive morbidity. However, late‐life GAD is relatively understudied and its functional neuroanatomy is uncharted. Several imaging studies have suggested abnormalities in the cognitive control systems of emotion regulation in anxiety disorders in young adults. The aim of this study was to examine the neural correlates of emotion regulation in late‐life GAD. Method: We compared 7 elderly GAD subjects and 10 elderly nonanxious comparison subjects using functional MRI. Regional cerebral blood flow (rCBF) was measured using pulsed arterial spin labeling perfusion MRI at rest and during an emotion regulation paradigm. Results: Relative to the rest condition, elderly nonanxious comparison subjects had increased rCBF during worry induction (WI) in the right insula, bilateral amygdala, and associative temporooccipital areas. Elderly GAD subjects had increased rCBF during WI in the associative temporooccipital areas, but not in the insula or the amygdala. During worry suppression (WS), elderly nonanxious comparison subjects had increased rCBF in the prefrontal cortex (PFC) and dorsal ACC. Elderly GAD subjects had no changes in rCBF during WS in the PFC. Conclusions: When attempting to regulate their emotional responses, elderly anxious subjects failed to activate prefrontal regions involved in the downregulation of negative emotions. These results, showing that elderly anxious subjects are not effectively engaging the PFC in suppressing worry, may be clinically relevant for developing personalized therapeutic strategies for the treatment of late‐life GAD. Depression and Anxiety 28:202–209, 2011. © 2011 Wiley‐Liss, Inc.     

Neural correlates of locative prepositions

Locative prepositions might be special linguistic modifiers because they form a natural link between verbal and visual-spatial information. In the present fMRI study we found evidence that understanding categorical spatial relations expressed in language with locative prepositions such as “to the left of” and “to the right of” were reliably associated with cerebral activity in the supramarginal gyrus (SMG) located in the left inferior parietal lobe. The higher activity associated with spatial as compared to non-spatial sentences in this region was not dependent on the context (verbal or visual-spatial) in which the sentence was read. Therefore, the function of this activity appears to be to create a general, amodal representation of locative prepositions that allow for flexible comparisons to either verbal or visual-spatial material.