Oliver Tuescher

Differential Time Courses and Specificity of Amygdala Activity in Posttraumatic Stress Disorder Subjects and Normal Control Subjects

BACKGROUND Previous neuroimaging studies have demonstrated exaggerated amygdala responses to negative stimuli in posttraumatic stress disorder (PTSD). The time course of this amygdala response is largely unstudied and is relevant to questions of habituation and sensitization in PTSD exposure therapy. METHODS We applied blood oxygen level dependent functional magnetic resonance imaging and statistical parametric mapping to study amygdala responses to trauma-related and nontrauma-related emotional words in sexual/physical abuse PTSD and normal control subjects. We examined the time course of this response by separate analysis of early and late epochs. RESULTS PTSD versus normal control subjects have a relatively increased initial amygdala response to trauma-related negative, but not nontrauma-related negative, versus neutral stimuli. Patients also fail to show the normal patterns of sensitization and habituation to different categories of negative stimuli. These findings correlate with measured PTSD symptom severity. CONCLUSIONS Our results demonstrate differential time courses and specificity of amygdala response to emotional and control stimuli in PTSD and normal control subjects. This has implications for pathophysiologic models of PTSD and treatment response. The results also extend previous neuroimaging studies demonstrating relatively increased amygdala response in PTSD and expand these results to a largely female patient population probed with emotionally valenced words.

Neural substrates of the interaction of emotional stimulus processing and motor inhibitory control: An emotional linguistic go/no-go fMRI study

Neural substrates of behavioral inhibitory control have been probed in a variety of animal model, physiologic, behavioral, and imaging studies, many emphasizing the role of prefrontal circuits. Likewise, the neurocircuitry of emotion has been investigated from a variety of perspectives. Recently, neural mechanisms mediating the interaction of emotion and behavioral regulation have become the focus of intense study. To further define neurocircuitry specifically underlying the interaction between emotional processing and response inhibition, we developed an emotional linguistic go/no-go fMRI paradigm with a factorial block design which joins explicit inhibitory task demand (i.e., go or no-go) with task-unrelated incidental emotional stimulus valence manipulation, to probe the modulation of the former by the latter. In this study of normal subjects focusing on negative emotional processing, we hypothesized activity changes in specific frontal neocortical and limbic regions reflecting modulation of response inhibition by negative stimulus processing. We observed common fronto-limbic activations (including orbitofrontal cortical and amygdalar components) associated with the interaction of emotional stimulus processing and response suppression. Further, we found a distributed cortico-limbic network to be a candidate neural substrate for the interaction of negative valence-specific processing and inhibitory task demand. These findings have implications for elucidating neural mechanisms of emotional modulation of behavioral control, with relevance to a variety of neuropsychiatric disease states marked by behavioral dysregulation within the context of negative emotional processing.

Human fear-related motor neurocircuitry

Using functional magnetic resonance imaging and an experimental paradigm of instructed fear, we observed a striking pattern of decreased activity in primary motor cortex with increased activity in dorsal basal ganglia during anticipation of aversive electrodermal stimulation in 42 healthy participants. We interpret this pattern of activity in motor neurocircuitry in response to cognitively-induced fear in relation to evolutionarily-conserved responses to threat that may be relevant to understanding normal and pathological fear in humans.

Fear-related activity in subgenual anterior cingulate differs between men and women

Functional magnetic resonance imaging in association with an instructed fear/anticipatory anxiety paradigm was used to explore sex differences in the human fear response. During anticipation of mild electrodermal stimulation, women, as compared with men, demonstrated increased activity in the subgenual anterior cingulate cortex and functionally related regions of the insula and brainstem. The subgenual anterior cingulate cortex is a region critical for emotional control implicated in the pathogenesis of psychiatric disease. Present findings suggest a contributory neural substrate for the greater susceptibility of women to anxiety and affective disorders, and emphasize the importance of considering participant sex when designing and interpreting functional neuroimaging studies.

Differential activity of subgenual cingulate and brainstem in panic disorder and PTSD

Most functional neuroimaging studies of panic disorder (PD) have focused on the resting state, and have explored PD in relation to healthy controls rather than in relation to other anxiety disorders. Here, PD patients, posttraumatic stress disorder (PTSD) patients, and healthy control subjects were studied with functional magnetic resonance imaging utilizing an instructed fear conditioning paradigm incorporating both Threat and Safe conditions. Relative to PTSD and control subjects, PD patients demonstrated significantly less activation to the Threat condition and increased activity to the Safe condition in the subgenual cingulate, ventral striatum and extended amygdala, as well as in midbrain periaquaeductal grey, suggesting abnormal reactivity in this key region for fear expression. PTSD subjects failed to show the temporal pattern of activity decrease found in control subjects.

Diurnal cortisol amplitude and fronto-limbic activity in response to stressful stimuli

The development and exacerbation of many psychiatric and neurologic conditions are associated with dysregulation of the hypothalamic pituitary adrenal (HPA) axis as measured by aberrant levels of cortisol secretion. Here we report on the relationship between the amplitude of diurnal cortisol secretion, measured across 3 typical days in 18 healthy individuals, and blood oxygen level dependant (BOLD) response in limbic fear/stress circuits, elicited by in-scanner presentation of emotionally negative stimuli, specifically, images of the World Trade Center (WTC) attack. Results indicate that subjects who secrete a greater amplitude of cortisol diurnally demonstrate less brain activation in limbic regions, including the amygdala and hippocampus/parahippocampus, and hypothalamus during exposure to traumatic WTC-related images. Such initial findings can begin to link our understanding, in humans, of the relationship between the diurnal amplitude of a hormone integral to the stress response, and those neuroanatomical regions that are implicated as both modulating and being modulated by that response.

Frontolimbic function and cortisol reactivity in response to emotional stimuli

Frontolimbic structures involved in fear conditioning have also been associated with hypothalamic–pituitary–adrenal (HPA)-axis modulation, including amygdaloid, hippocampal, and ventromedial prefrontal cortex regions. Although HPA-axis function and endocrine changes have been investigated in the context of stress provocation, much research has not been conducted using functional neuroimaging in the study of the HPA axis and frontolimbic function in response to emotional stimuli. Using functional magnetic resonance imaging, the association of blood-oxygen-level dependent signal with salivary cortisol in response to an emotional visual scene paradigm was investigated, with prescan and postscan salivary cortisol analyzed as a covariate of interest during specific conditions. Cortisol reactivity to the paradigm was positively associated with amygdalar and hippocampal activity and negatively associated with ventromedial prefrontal cortex activity in conditions involving emotional imagery.

Small amygdala – high aggression? The role of the amygdala in modulating aggression in healthy subjects

Objective. Several lines of evidence suggest an association between the amygdala and the modulation of aggressive behaviour. Previous morphometric brain imaging studies have focused on the role of the amygdala in the context of pathologic neuropsychiatric conditions like depression, personality disorders, and dysphoric and aggressive behaviour in epilepsy. In order to better understand the physiological role of the amygdala in modulating aggressive behaviour we investigated the relationship between amygdala volumes and lifetime aggression in healthy subjects. Methods. Morphometric brain scans were obtained in 20 healthy volunteers. Amygdala volumes were measured by manually outlining the boundaries of the structure following a well established and validated protocol. Careful psychiatric and psychometric assessment was done to exclude any psychiatric disorder and to assess lifetime aggressiveness with an established and validated psychometric instrument (i.e. Life History of Aggression Assessment (LHA)). Results. All volunteers scored in the normal range of lifetime aggression. Volunteers with higher aggression scores displayed a 16–18% reduction of amygdala volumes. There was a highly significant negative correlation between amygdala volumes and trait aggression. Conclusion. The extent of volumetric differences in this study is remarkable and suggests that amygdala volumes might be a surrogate marker for the personality property of aggressiveness in healthy human beings.

Frontolimbic neural circuit changes in emotional processing and inhibitory control associated with clinical improvement following transference‐focused psychotherapy in borderline personality disorder

Borderline personality disorder (BPD) is characterized by self‐regulation deficits, including impulsivity and affective lability. Transference‐focused psychotherapy (TFP) is an evidence‐based treatment proven to reduce symptoms across multiple cognitive–emotional domains in BPD. This pilot study aimed to investigate neural activation associated with, and predictive of, clinical improvement in emotional and behavioral regulation in BPD following TFP.

Effects of Shame Induction in Borderline Personality Disorder

Shame is a powerful emotion with a strong link to borderline personality disorder. This study investigates shame levels in borderline personality disorder, compared to major depressive disorder and healthy women. A total of 25 women with borderline personality disorder, 25 women with major depression and 23 healthy women underwent a shame induction exercise. The self-reported intensity of shame, anger, anxiety, sadness, joy, annoyance, and boredom, was measured five times. Compared to participants with major depression and healthy women, patients with borderline personality disorder had higher baseline levels of shame, but there was no evidence of greater emotional intensity or a prolonged return to baseline after shame induction. They were the only group to express increased anger following the exercise. These findings strengthen the view of stronger emotional negativity in borderline personality disorder. The differences in the impact of shame on anger may contribute toward understanding emotion regulation difficulties in borderline personality disorder.