Amygdala downregulation training using fMRI neurofeedback in post-traumatic stress disorder: a randomized, double-blind trial.

Hyperactivation of amygdala is a neural marker for post-traumatic stress disorder (PTSD) and improvement in control over amygdala activity has been associated with treatment success in PTSD. In this randomized, double-blind clinical trial we evaluated the efficacy of a real-time fMRI neurofeedback intervention designed to train control over amygdala activity following trauma recall. Twenty-five patients with PTSD completed three sessions of neurofeedback training in which they attempted to downregulate the feedback signal after exposure to personalized trauma scripts. For subjects in the active experimental group (N = 14), the feedback signal was from a functionally localized region of their amygdala associated with trauma recall. For subjects in the control group (N = 11), yoked-sham feedback was provided. Changes in control over the amygdala and PTSD symptoms served as the primary and secondary outcome measurements, respectively. We found significantly greater improvements in control over amygdala activity in the active group than in the control group 30-days following the intervention. Both groups showed improvements in symptom scores, however the symptom reduction in the active group was not significantly greater than in the control group. Our finding of greater improvement in amygdala control suggests potential clinical application of neurofeedback in PTSD treatment. Thus, further development of amygdala neurofeedback training in PTSD treatment, including evaluation in larger samples, is warranted.

Real-Time fMRI Neurofeedback with War Veterans with Chronic PTSD: A Feasibility Study.

Many patients with post-traumatic stress disorder (PTSD), especially war veterans, do not respond to available treatments. Here, we describe a novel neurofeedback (NF) intervention using real-time functional magnetic resonance imaging for treating and studying PTSD. The intervention involves training participants to control amygdala activity after exposure to personalized trauma scripts. Three combat veterans with chronic PTSD participated in this feasibility study. All three participants tolerated well the NF training. Moreover, two participants, despite the chronicity of their symptoms, showed clinically meaningful improvements, while one participant showed a smaller symptom reduction. Examination of changes in resting-state functional connectivity patterns revealed a normalization of brain connectivity consistent with clinical improvement. These preliminary results support feasibility of this novel intervention for PTSD and indicate that larger, well-controlled studies of efficacy are warranted.

An examination of the roles of trauma exposure and posttraumatic stress disorder on emotion regulation strategies of Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn veterans.

Theories of posttraumatic stress disorder (PTSD) implicate emotional processes, including difficulties utilizing adaptive emotion regulation strategies, as critical to the etiology and maintenance of PTSD. Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn (OIF/OEF/OND) veterans report high levels of combat exposure and PTSD. We aimed to extend findings suggesting that emotion regulation difficulties are a function of PTSD, rather than combat trauma exposure or common comorbidities, to OIF/OEF/OND veterans, in order to inform models of PTSD risk and recovery that can be applied to returning veterans. We tested differences in emotion regulation, measured with the Difficulties in Emotion Regulation Scale and Emotion Regulation Questionnaire, among trauma-exposed veterans with (n = 24) or without PTSD (n = 22) and healthy civilian comparison participants (n = 27) using multivariate analyses of covariance, adjusting for major depressive disorder, anxiety disorders, and demographic variables (age, sex, and ethnicity). Veterans with PTSD reported more use of expressive suppression and more difficulties with emotion regulation than veterans without PTSD and healthy comparison participants. Groups did not differ on cognitive reappraisal. Findings suggest the key role of PTSD above and beyond trauma exposure, depression, and anxiety in specific aspects of emotion dysregulation among OIF/OEF/OND veterans. Interventions that help veterans expand and diversify their emotion regulation skills may serve as helpful adjunctive treatments for PTSD among OIF/OEF/OND veterans.

Electrophysiological correlates of processing faces of younger and older individuals.

The 'own-age bias' in face processing suggests that the age of a face constitutes one important factor that influences attention to and memory for faces. The present experiment investigated electrophysiological correlates of processing faces of younger and older individuals. Younger participants were presented with pictures of unfamiliar younger and older faces in the context of a gender categorization task. A comparison of event-related potentials showed that early components are sensitive to faces of different ages: (i) larger positive potential peaking at 160 ms (P200) for older than younger faces at fronto-central electrodes; (ii) larger negative potential peaking at 252 ms (N200) for younger than older faces at fronto-central electrodes; (iii) larger negative-going deflection peaking at 320 ms (N250) for younger than older faces at occipito-temporal electrodes; and (iv) larger late positive potential peaking at 420 ms (LPP 420) for older than younger faces at parietal and other electrodes. We discuss similarities between the present study and a previously published study of faces of different races as suggesting involvement of comparable electrophysiological responses when differentiating between stimulus categories.

Event-related potentials reveal temporal staging of dynamic facial expression and gaze shift effects on attentional orienting.

Multiple sources of information from the face guide attention during social interaction. The present study modified the Posner cueing paradigm to investigate how dynamic changes in emotional expression and eye gaze in faces affect the neural processing of subsequent target stimuli. Event-related potentials (ERPs) were recorded while participants viewed centrally presented face displays in which gaze direction (left, direct, right) and facial expression (fearful, neutral) covaried in a fully crossed design. Gaze direction was not predictive of peripheral target location. ERP analysis revealed several sequential effects, including: (1) an early enhancement of target processing following fearful faces (P1); (2) an interaction between expression and gaze (N1), with enhanced target processing following fearful faces with rightward gaze; and (3) an interaction between gaze and target location (P3), with enhanced processing for invalidly cued left visual field targets. Behaviorally, participants responded faster to targets following fearful faces and targets presented in the right visual field, in concordance with the P1 and N1 effects, respectively. The findings indicate that two nonverbal social cues-facial expression and gaze direction-modulate attentional orienting across different temporal stages of processing. Results have implications for understanding the mental chronometry of shared attention and social referencing.

Happy and fearful emotion in cues and targets modulate event-related potential indices of gaze-directed attentional orienting.

The goal of the present study was to characterize the effects of valence in facial cues and object targets on event-related potential (ERPs) indices of gaze-directed orienting. Participants were shown faces at fixation that concurrently displayed dynamic gaze shifts and expression changes from neutral to fearful or happy emotions. Emotionally-salient target objects subsequently appeared in the periphery and were spatially congruent or incongruent with the gaze direction. ERPs were time-locked to target presentation. Three sequential ERP components were modulated by happy emotion, indicating a progression from an expression effect to a gaze-by-expression interaction to a target emotion effect. These effects included larger P1 amplitude over contralateral occipital sites for targets following happy faces, larger centrally distributed N1 amplitude for targets following happy faces with leftward gaze, and faster P3 latency for positive targets. In addition, parietally distributed P3 amplitude was reduced for validly cued targets following fearful expressions. Results are consistent with accounts of attentional broadening and motivational approach by happy emotion, and facilitation of spatially directed attention in the presence of fearful cues. The findings have implications for understanding how socioemotional signals in faces interact with each other and with emotional features of objects in the environment to alter attentional processes.

Emotion-attention network interactions during a visual oddball task.

Emotional and attentional functions are known to be distributed along ventral and dorsal networks in the brain, respectively. However, the interactions between these systems remain to be specified. The present study used event-related functional magnetic resonance imaging (fMRI) to investigate how attentional focus can modulate the neural activity elicited by scenes that vary in emotional content. In a visual oddball task, aversive and neutral scenes were presented intermittently among circles and squares. The squares were frequent standard events, whereas the other novel stimulus categories occurred rarely. One experimental group [N=10] was instructed to count the circles, whereas another group [N=12] counted the emotional scenes. A main effect of emotion was found in the amygdala (AMG) and ventral frontotemporal cortices. In these regions, activation was significantly greater for emotional than neutral stimuli but was invariant to attentional focus. A main effect of attentional focus was found in dorsal frontoparietal cortices, whose activity signaled task-relevant target events irrespective of emotional content. The only brain region that was sensitive to both emotion and attentional focus was the anterior cingulate gyrus (ACG). When circles were task-relevant, the ACG responded equally to circle targets and distracting emotional scenes. The ACG response to emotional scenes increased when they were task-relevant, and the response to circles concomitantly decreased. These findings support and extend prominent network theories of emotion-attention interactions that highlight the integrative role played by the anterior cingulate.

Functional parcellation of attentional control regions of the brain.

Recently, a number of investigators have examined the neural loci of psychological processes enabling the control of visual spatial attention using cued-attention paradigms in combination with event-related functional magnetic resonance imaging. Findings from these studies have provided strong evidence for the involvement of a fronto-parietal network in attentional control. In the present study, we build upon this previous work to further investigate these attentional control systems. In particular, we employed additional controls for nonattentional sensory and interpretative aspects of cue processing to determine whether distinct regions in the fronto-parietal network are involved in different aspects of cue processing, such as cue-symbol interpretation and attentional orienting. In addition, we used shorter cue-target intervals that were closer to those used in the behavioral and event-related potential cueing literatures. Twenty participants performed a cued spatial attention task while brain activity was recorded with functional magnetic resonance imaging. We found functional specialization for different aspects of cue processing in the lateral and medial subregions of the frontal and parietal cortex. In particular, the medial subregions were more specific to the orienting of visual spatial attention, while the lateral subregions were associated with more general aspects of cue processing, such as cue-symbol interpretation. Additional cue-related effects included differential activations in midline frontal regions and pretarget enhancements in the thalamus and early visual cortical areas.

BOLD signal compartmentalization based on the apparent diffusion coefficient.

Functional MRI (fMRI) can detect blood oxygenation level dependent (BOLD) hemodynamic responses secondary to neuronal activity. The most commonly used method for detecting fMRI signals is the gradient-echo echo-planar imaging (EPI) technique because of its sensitivity and speed. However, it is generally believed that a significant portion of these signals arises from large veins, with additional contribution from the capillaries and parenchyma. Early experiments using diffusion-weighted gradient-echo EPI have suggested that intra-voxel incoherent motion (IVIM) weighting inherent in the sequence can selectively attenuate contributions from different vessels based on the differences in the mobility of the blood within them. In the present study, we used similar approach to characterize the apparent diffusion coefficient (ADC) distribution within the activated areas of BOLD contrast. It is shown that the voxel values of the ADCs obtained from this technique can infer various vascular contributions to the BOLD signal.