Gloria Olivieri

Trauma modulates amygdala and medial prefrontal responses to consciously attended fear.

Effective fear processing relies on the amygdala and medial prefrontal cortex (MPFC). Post-trauma reactions provide a compelling model for examining how the heightened experience of fear impacts these systems. Post-traumatic stress disorder (PTSD) has been associated with excessive amygdala and a lack of MPFC activity in response to nonconscious facial signals of fear, but responses to consciously processed facial fear stimuli have not been examined. We used functional MRI to elucidate the effect of trauma reactions on amygdala-MPFC function during an overt fear perception task. Subjects with PTSD (n = 13) and matched non-traumatized healthy subjects (n = 13) viewed 15 blocks of eight fearful face stimuli alternating pseudorandomly with 15 blocks of neutral faces (stimulus duration 500 ms; ISI 767 ms). We used random effects analyses in SPM2 to examine within- and between-group differences in the MPFC and amygdala search regions of interest. Time series data were used to examine amygdala-MPFC associations and changes across the first (Early) versus second (Late) phases of the experiment. Relative to non-traumatized subjects, PTSD subjects showed a marked bilateral reduction in MPFC activity (in particular, right anterior cingulate cortex, ACC), which showed a different Early-Late pattern to non-traumatized subjects and was more pronounced with greater trauma impact and symptomatology. PTSD subjects also showed a small but significant enhancement in left amygdala activity, most apparent during the Late phase, but reduction in Early right amygdala response. Over the time course, trauma was related to a distinct pattern of ACC and amygdala connections. The findings suggest that major life trauma may disrupt the normal pattern of medial prefrontal and amygdala regulation.

Arousal dissociates amygdala and hippocampal fear responses: evidence from simultaneous fMRI and skin conductance recording.

The experience and appraisal of threat is essential to human and animal survival. Lesion evidence suggests that the subjective experience of fear relies upon amygdala-medial frontal activity (as well as autonomic arousal), whereas the factual context of threat stimuli depends upon hippocampal-lateral frontal activity. This amygdala-hippocampus dissociation has not previously been demonstrated in vivo. To explore this differentiation, we employed functional magnetic resonance imaging (fMRI) and simultaneous skin conductance response (SCR) measures of phasic arousal, while subjects viewed fearful versus neutral faces. fMRI activity was subaveraged according to whether or not the subject evoked an arousal SCR to each discrete face stimulus. The fMRI-with arousal and fMRI-without arousal data provided a distinct differentiation of amygdala and hippocampal networks. Amygdala-medial frontal activity was observed only with SCRs, whereas hippocampus-lateral frontal activity occurred only in the absence of SCRs. The findings provide direct evidence for a dissociation between human amygdala and hippocampus networks in the visceral experience versus declarative fact processing of fear.

The Mellow Years?: Neural Basis of Improving Emotional Stability over Age

Contrary to the pervasive negative stereotypes of human aging, emotional functions may improve with advancing age. However, the brain mechanisms underlying changes in emotional function over age remain unknown. Here, we demonstrate that emotional stability improves linearly over seven decades (12–79 years) of the human lifespan. We used both functional magnetic resonance imaging and event-related potential recording to examine the neural basis of this improvement. With these multimodal techniques, we show that better stability is predicted by a shift toward greater medial prefrontal control over negative emotional input associated with increased activity later in the processing sequence (beyond 200 ms after stimulus) and less control over positive input, related to a decrease in early activity (within 150 ms). This shift was independent from gray matter loss, indexed by structural magnetic resonance data. We propose an integrative model in which accumulated life experience and the motivation for meaning over acquisition in older age contribute to plasticity of medial prefrontal systems, achieving a greater selective control over emotional functions.

Enhanced amygdala and medial prefrontal activation during nonconscious processing of fear in posttraumatic stress disorder: An fMRI study

Biological models of posttraumatic stress disorder (PTSD) suggest that patients will display heightened amygdala but decreased medial prefrontal activity during processing of fear stimuli. However, a rapid and automatic alerting mechanism for responding to nonconscious signals of fear suggests that PTSD may display heightened rather than decreased MPFC under nonconscious processing of fear stimuli. This study used functional magnetic resonance imaging to examine blood oxygenation level‐dependent signal changes during nonconscious presentation (16.7 ms, masked) of fearful and neutral faces in 15 participants with PTSD and 15 age and sex‐matched healthy control participants. Results indicate that PTSD participants display increased amygdala and MPFC activity during nonconscious processing of fearful faces. These data extend existing models by suggesting that the impaired MPFC activation in PTSD may be limited to conscious fear processing. Hum Brain Mapp, 2008.

The neural correlates of orienting: an integration of fMRI and skin conductance orienting.

In fMRI studies, the averaging of neural activity across multiple trials might obscure important psychophysiological subprocesses. The orienting response (OR) is a distinctive subprocess signalling the active orientation of attention towards potentially significant events. We sought to elucidate fMRI activity associated with visual stimuli that did or did not evoke simultaneously recorded electrodermal ORs (using customised skin conductance recording). ‘With-OR’ stimuli were associated with significant activity in the hippocampus, anterior cingulate and ventromedial prefrontal cortex. Averaged analysis revealed activity only in the expected visual circuits. Our results suggest that potentially significant stimuli (with-OR) activate different functional networks to familiar (without-OR) stimuli, and that orienting may therefore be an informative subprocess to consider in cognitive fMRI studies.

Dissociative responses to conscious and non-conscious fear impact underlying brain function in post-traumatic stress disorder

BACKGROUND Dissociative reactions in post-traumatic stress disorder (PTSD) have been regarded as strategic responses that limit arousal. Neuroimaging studies suggest distinct prefrontal responses in individuals displaying dissociative and hyperarousal responses to threat in PTSD. Increased prefrontal activity may reflect enhanced regulation of limbic arousal networks in dissociation. If dissociation is a higher-order regulatory response to threat, there may be differential responses to conscious and automatic processing of threat stimuli. This study addresses this question by examining the impact of dissociation on fear processing at different levels of awareness. METHOD Functional magnetic resonance imaging (fMRI) with a 1.5-T scanner was used to examine activation to fearful (versus neutral) facial expressions during consciously attended and non-conscious (using backward masking) conditions in 23 individuals with PTSD. Activation in 11 individuals displaying non-dissociative reactions was compared to activation in 12 displaying dissociative reactions to consciously and non-consciously perceived fear stimuli. RESULTS Dissociative PTSD was associated with enhanced activation in the ventral prefrontal cortex for conscious fear, and in the bilateral amygdala, insula and left thalamus for non-conscious fear compared to non-dissociative PTSD. Comparatively reduced activation in the dissociative group was apparent in dorsomedial prefrontal regions for conscious fear faces. CONCLUSIONS These findings confirm our hypotheses of enhanced prefrontal activity to conscious fear and enhanced activity in limbic networks to non-conscious fear in dissociative PTSD. This supports the theory that dissociation is a regulatory strategy invoked to cope with extreme arousal in PTSD, but this strategy appears to function only during conscious processing of threat.

BOLD, sweat and fears: fMRI and skin conductance distinguish facial fear signals.

It is not known how the brain and autonomic systems interact during perception of facial signals of danger. We recorded blood-oxygen-level-dependent (BOLD) activity using fMRI and simultaneous skin conductance measures of autonomic arousal in healthy subjects. Distinct response profiles were elicited for fear (enhanced arousal with amygdala activity), anger (rapid onset, slow recovery arousal responses with anterior cingulate) and disgust (delayed arousal responses with insula and basal ganglia activity). The findings suggest that fear, anger and disgust perception involves specific interactions in the neural arousal systems for emotion and motivation.