Taru Flagan

Dorsolateral Prefrontal Cortex Activation During Emotional Anticipation and Neuropsychological Performance in Posttraumatic Stress Disorder

CONTEXT Posttraumatic stress disorder (PTSD) has been associated with executive or attentional dysfunction and problems in emotion processing. However, it is unclear whether these two domains of dysfunction are related to common or distinct neurophysiological substrates. OBJECTIVE To examine the hypothesis that greater neuropsychological impairment in PTSD relates to greater disruption in prefrontal-subcortical networks during emotional anticipation. DESIGN Case-control, cross-sectional study. SETTING General community and hospital and community psychiatric clinics. PARTICIPANTS Volunteer sample of 37 women with PTSD related to intimate partner violence and 34 age-comparable healthy control women. MAIN OUTCOME MEASURES We used functional magnetic resonance imaging (fMRI) to examine neural responses during anticipation of negative and positive emotional images. The Clinician-Administered PTSD Scale was used to characterize PTSD symptom severity. The Wechsler Adult Intelligence Scale, Third Edition, Digit Symbol Test, Delis-Kaplan Executive Function System Color-Word Interference Test, and Wisconsin Card Sorting Test were used to characterize neuropsychological performance. RESULTS Women with PTSD performed worse on complex visuomotor processing speed (Digit Symbol Test) and executive function (Color-Word Interference Inhibition/Switching subtest) measures compared with control subjects. Posttraumatic stress disorder was associated with greater anterior insula and attenuated lateral prefrontal cortex (PFC) activation during emotional anticipation. Greater dorsolateral PFC activation (anticipation of negative images minus anticipation of positive images) was associated with lower PTSD symptom severity and better visuomotor processing speed and executive functioning. Greater medial PFC and amygdala activation related to slower visuomotor processing speed. CONCLUSIONS During emotional anticipation, women with PTSD show exaggerated activation in the anterior insula, a region important for monitoring internal bodily state. Greater dorsolateral PFC response in PTSD patients during emotional anticipation may reflect engagement of cognitive control networks that are beneficial for emotional and cognitive functioning. Novel treatments could be aimed at strengthening the balance between cognitive control (dorsolateral PFC) and affective processing (medial PFC and amygdala) networks to improve overall functioning for PTSD patients.

Red Brain, Blue Brain: Evaluative Processes Differ in Democrats and Republicans

Liberals and conservatives exhibit different cognitive styles and converging lines of evidence suggest that biology influences differences in their political attitudes and beliefs. In particular, a recent study of young adults suggests that liberals and conservatives have significantly different brain structure, with liberals showing increased gray matter volume in the anterior cingulate cortex, and conservatives showing increased gray matter volume in the in the amygdala. Here, we explore differences in brain function in liberals and conservatives by matching publicly-available voter records to 82 subjects who performed a risk-taking task during functional imaging. Although the risk-taking behavior of Democrats (liberals) and Republicans (conservatives) did not differ, their brain activity did. Democrats showed significantly greater activity in the left insula, while Republicans showed significantly greater activity in the right amygdala. In fact, a two parameter model of partisanship based on amygdala and insula activations yields a better fitting model of partisanship than a well-established model based on parental socialization of party identification long thought to be one of the core findings of political science. These results suggest that liberals and conservatives engage different cognitive processes when they think about risk, and they support recent evidence that conservatives show greater sensitivity to threatening stimuli.

Neural basis of egalitarian behavior

Individuals are willing to sacrifice their own resources to promote equality in groups. These costly choices promote equality and are associated with behavior that supports cooperation in humans, but little is known about the brain processes involved. We use functional MRI to study egalitarian preferences based on behavior observed in the “random income game.” In this game, subjects decide whether to pay a cost to alter group members’ randomly allocated incomes. We specifically examine whether egalitarian behavior is associated with neural activity in the ventromedial prefrontal cortex and the insular cortex, two regions that have been shown to be related to social preferences. Consistent with previous studies, we find significant activation in both regions; however, only the insular cortex activations are significantly associated with measures of revealed and expressed egalitarian preferences elicited outside the scanner. These results are consistent with the notion that brain mechanisms involved in experiencing the emotional states of others underlie egalitarian behavior in humans.

Subjecting elite athletes to inspiratory breathing load reveals behavioral and neural signatures of optimal performers in extreme environments.

Background It is unclear whether and how elite athletes process physiological or psychological challenges differently than healthy comparison subjects. In general, individuals optimize exercise level as it relates to differences between expected and experienced exertion, which can be conceptualized as a body prediction error. The process of computing a body prediction error involves the insular cortex, which is important for interoception, i.e. the sense of the physiological condition of the body. Thus, optimal performance may be related to efficient minimization of the body prediction error. We examined the hypothesis that elite athletes, compared to control subjects, show attenuated insular cortex activation during an aversive interoceptive challenge. Methodology/Principal Findings Elite adventure racers (n = 10) and healthy volunteers (n = 11) performed a continuous performance task with varying degrees of a non-hypercapnic breathing load while undergoing functional magnetic resonance imaging. The results indicate that (1) non-hypercapnic inspiratory breathing load is an aversive experience associated with a profound activation of a distributed set of brain areas including bilateral insula, dorsolateral prefrontal cortex and anterior cingulated; (2) adventure racers relative to comparison subjects show greater accuracy on the continuous performance task during the aversive interoceptive condition; and (3) adventure racers show an attenuated right insula cortex response during and following the aversive interoceptive condition of non-hypercapnic inspiratory breathing load. Conclusions/Significance These findings support the hypothesis that elite athletes during an aversive interoceptive condition show better performance and an attenuated insular cortex activation during the aversive experience. Interestingly, differential modulation of the right insular cortex has been found previously in elite military personnel and appears to be emerging as an important brain system for optimal performance in extreme environments.

Selective effects of social anxiety, anxiety sensitivity, and negative affectivity on the neural bases of emotional face processing.

Individuals with high anxiety show heightened neural activation in affective processing regions, including the amygdala and insula. Activations have been shown to be correlated with anxiety severity, but although anxiety is a heterogeneous state, prior studies have not systematically disentangled whether neural activity in affective processing circuitry is uniquely related to specific domains of anxiety. Forty-five young adults were tested on an emotional face processing task during functional magnetic resonance imaging. Participants completed the Social Interactional Anxiety Scale, Anxiety Sensitivity Index, and Spielberger Trait Anxiety Inventory. Using a robust multiple regression approach, we examined the effects of social anxiety, anxiety sensitivity, and trait anxiety (which overlapped with depressive symptoms, and can therefore be considered a measure of negative affectivity) on activation in insula, amygdala, and medial prefrontal cortex, in response to emotional faces. Adjusting for negative affectivity and anxiety sensitivity, social anxiety was associated with activity in left amygdala, right insula, and subgenual anterior cingulate across all emotional faces. When comparing negative and positive faces directly, greater negative affectivity was uniquely associated with less activity to positive faces in left amygdala, left anterior insula, and dorsal anterior cingulate. The current findings support the hypothesis that hyperactivity in brain areas during general emotional face processing is predominantly a function of social anxiety. In comparison, hypoactivity to positively valenced faces was predominantly associated with negative affectivity. Implications for the understanding of emotion processing in anxiety are discussed.

Pregabalin Influences Insula and Amygdala Activation During Anticipation of Emotional Images

Pregabalin (PGB) has shown potential as an anxiolytic for treatment of generalized and social anxiety disorder. PGB binds to voltage-dependent calcium channels, leading to upregulation of GABA inhibitory activity and reduction in the release of various neurotransmitters. Previous functional magnetic resonance imaging (fMRI) studies indicate that selective serotonin reuptake inhibitors and benzodiazepines attenuate amygdala, insula, and medial prefrontal cortex activation during anticipation and emotional processing in healthy controls. The aim of this study was to examine whether acute PGB administration would attenuate activation in these regions during emotional anticipation. In this double-blind, placebo-controlled, randomized crossover study, 16 healthy controls completed a paradigm involving anticipation of negative and positive affective images during fMRI approximately 1 h after administration of placebo, 50, or 200 mg PGB. Linear mixed model analysis revealed that PGB was associated with (1) decreases in left amygdala and anterior insula activation and (2) increases in anterior cingulate (ACC) activation, during anticipation of positive and negative stimuli. There was also a region of the anterior amygdala in which PGB dose was associated with increased activation during anticipation of negative and decreased activation during anticipation of positive stimuli. Attenuation of amygdala and insula activation during anticipatory or emotional processing may represent a common regional brain mechanism for anxiolytics across drug classes. PGB induced increases in ACC activation could be a unique effect related to top–down modulation of affective processing. These results provide further support for the viability of using pharmaco-fMRI to determine the anxiolytic potential of pharmacologic agents.

Neural responses during emotional processing before and after cognitive trauma therapy for battered women

Therapy for combat and accident-related posttraumatic stress disorder (PTSD) has been reported to influence amygdala and anterior cingulate cortex (ACC) response during emotional processing. It is not yet understood how therapy influences different phases of emotional processing, and whether previous findings generalize to other PTSD populations. We hypothesized that cognitive trauma therapy for battered women (CTT-BW) would alter insula, amygdala, and cingulate responses during anticipation and presentation of emotional images. Fourteen female patients with PTSD related to domestic violence completed the Clinician Administered PTSD Scale (CAPS) and functional magnetic resonance imaging (fMRI) before and after CTT-BW. The fMRI task involved cued anticipation followed by presentation of positive versus negative affective images. CTT-BW was associated with decreases in CAPS score, enhanced ACC and decreased anterior insula activation during anticipation, and decreased dorsolateral prefrontal cortex and amygdala response during image presentation (negative-positive). Pre-treatment ACC activation during anticipation and image presentation exhibited positive and negative relationships to treatment response, respectively. Results suggest that CTT-BW enhanced efficiency of neural responses during preparation for upcoming emotional events in a way that reduced the need to recruit prefrontal-amygdala responses during the occurrence of the event. Results also suggest that enhancing ACC function during anticipation may be beneficial for PTSD treatment.

Neural functional and structural correlates of childhood maltreatment in women with intimate-partner violence-related posttraumatic stress disorder

Childhood maltreatment (CM) is a strong risk factor for development of posttraumatic stress disorder (PTSD) upon adult exposure to extreme adverse events. However, the neural underpinnings of this relationship are not well understood. Here, we test the hypothesis that severity of CM history is positively correlated with emotion-processing limbic and prefrontal brain activation/connectivity and negatively correlated with prefrontal gray matter volumes in women with PTSD due to intimate-partner violence (IPV-PTSD). Thirty-three women with IPV-PTSD underwent structural and functional magnetic resonance imaging while completing a facial emotion processing task. Multivariate regressions examined the relationship of CM to patterns of activation, connectivity, and gray matter volumes. CM severity was: (a) positively correlated with ventral ACC activation while processing angry faces; (b) negatively correlated with dorsal ACC and insula activation while processing fear and angry faces, arising from positive correlations with the shape-matching baseline; (c) positively correlated with limbic-prefrontal connectivity while processing fear faces but negatively correlated with amygdalo-insular connectivity while processing fear and angry; and (d) negatively correlated with prefrontal gray matter volumes. These results suggest CM exposure may account for variability in limbic/prefrontal brain function and prefrontal structure in adulthood PTSD and offer one potential mechanism through which CM confers risk to future development of PTSD.

Three ways in which midline regions contribute to self-evaluation.

An integration of existing research and newly conducted psychophysiological interaction (PPI) connectivity analyses suggest a new framework for understanding the contribution of midline regions to social cognition. Recent meta-analyses suggest that there are no midline regions that are exclusively associated with self-processing. Whereas medial prefrontal cortex (MPFC) is broadly modulated by self-processing, subdivisions within MPFC are differentially modulated by the evaluation of close others (ventral MPFC: BA 10/32) and the evaluation of other social targets (dorsal MPFC: BA 9/32). The role of DMPFC in social cognition may also be less uniquely social than previously thought; it may be better characterized as a region that indexes certainty about evaluation rather than previously considered social mechanisms (i.e., correction of self-projection). VMPFC, a region often described as an important mediator of socioemotional significance, may instead perform a more cognitive role by reflecting the type of information brought to bear on evaluations of people we know well. Furthermore, the new framework moves beyond MPFC and hypothesizes that two other midline regions, ventral anterior cingulate cortex (VACC: BA 25) and medial orbitofrontal cortex (MOFC: BA 11), aid motivational influences on social cognition. Despite the central role of motivation in psychological models of self-perception, neural models have largely ignored the topic. Positive connectivity between VACC and MOFC may mediate bottom-up sensitivity to information based on its potential for helping us evaluate ourselves or others the way we want. As connectivity becomes more positive with striatum and less positive with middle frontal gyrus (BA 9/44), MOFC mediates top-down motivational influences by adjusting the standards we bring to bear on evaluations of ourselves and other people.

Neural correlates of a computerized attention modification program in anxious subjects

Computerized attention modification is a relatively new and empirically validated treatment approach for different types of anxiety disorders. However, its neural basis and processes involved are poorly understood. This study examined the effect of a one-time application of an attention modification program (AMP) on neural substrates underlying emotion processing in individuals with high social anxiety. Fourteen individuals with elevated social anxiety symptoms completed an emotional face processing task during functional magnetic resonance imaging before and after AMP, and were subsequently exposed to a laboratory stressor. Results revealed the following: First, there was attenuated activation from pre- to post-AMP in the bilateral amygdala, bilateral insula and subgenual anterior cingulate cortex. Second, post-AMP, individuals exhibited increased activation in several regions of the prefrontal cortex (PFC). Third, those individuals with greater enhancement of ventromedial PFC activation after AMP showed diminished attentional allocation for threat and attenuated anxiety reactivity to the stressor. We conclude that AMP exerts effects that are similar to those previously reported for standard anxiolytics; however, it also appears to foster deployment of top-down brain processes aimed to regulate anxiety.