Belinda J. Liddell

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.

Amygdala-Prefrontal Dissociation of Subliminal and Supraliminal Fear

Facial expressions of fear are universally recognized signals of potential threat. Humans may have evolved specialized neural systems for responding to fear in the absence of conscious stimulus detection. We used functional neuroimaging to establish whether the amygdala and the medial prefrontal regions to which it projects are engaged by subliminal fearful faces and whether responses to subliminal fear are distinguished from those to supraliminal fear. We also examined the time course of amygdala‐medial prefrontal responses to supraliminal and subliminal fear. Stimuli were fearful and neutral baseline faces, presented under subliminal (16.7 ms and masked) or supraliminal (500 ms) conditions. Skin conductance responses (SCRs) were recorded simultaneously as an objective index of fear perception. SPM2 was used to undertake search region‐of‐interest (ROI) analyses for the amygdala and medial prefrontal (including anterior cingulate) cortex, and complementary whole‐brain analyses. Time series data were extracted from ROIs to examine activity across early versus late phases of the experiment. SCRs and amygdala activity were enhanced in response to both subliminal and supraliminal fear perception. Time series analysis showed a trend toward greater right amygdala responses to subliminal fear, but left‐sided responses to supraliminal fear. Cortically, subliminal fear was distinguished by right ventral anterior cingulate activity and supraliminal fear by dorsal anterior cingulate and medial prefrontal activity. Although subcortical amygdala activity was relatively persistent for subliminal fear, supraliminal fear showed more sustained cortical activity. The findings suggest that preverbal processing of fear may occur via a direct rostral–ventral amygdala pathway without the need for conscious surveillance, whereas elaboration of consciously attended signals of fear may rely on higher‐order processing within a dorsal cortico–amygdala pathway. Hum Brain Mapp, 2005.

Mapping the time course of nonconscious and conscious perception of fear: An integration of central and peripheral measures

Neuroimaging studies using backward masking suggest that conscious and nonconscious responses to complex signals of fear (facial expressions) occur via parallel cortical and subcortical circuits. Little is known, however, about the temporal differentiation of these responses. Psychophysics procedures were first used to determine objective thresholds for both nonconscious detection (face vs. blank screen) and discrimination (fear vs. neutral face) in a backward masking paradigm. Event‐related potentials (ERPs) were then recorded (n = 20) using these thresholds. Ten blocks of masked fear and neutral faces were presented under each threshold condition. Simultaneously recorded skin conductance responses (SCRs) provided an independent index of stimulus perception. It was found that Fear stimuli evoked faster SCR rise times than did neutral stimuli across all conditions, indicating that emotional content influenced responses, regardless of awareness. In the first 400 msec of processing, ERPs dissociated the time course of conscious (enhanced N4 component) from nonconscious (enhanced N2 component) perception of fear, relative to neutral. Nonconscious detection of fear also elicited relatively faster P1 responses within 100 msec post‐stimulus. The N2 may provide a temporal correlate of the initial sensory processing of salient facial configurations, which is enhanced when top‐down cortical feedback is precluded. By contrast, the N4 may index the conscious integration of emotion stimuli in working memory, subserved by greater cortical engagement. Hum. Brain Mapping 21:64–74, 2004.

A Temporal Dissociation of Subliminal versus Supraliminal Fear Perception: An Event-related Potential Study

Current theories of emotion suggest that threat-related stimuli are first processed via an automatically engaged neural mechanism, which occurs outside conscious awareness. This mechanism operates in conjunction with a slower and more comprehensive process that allows a detailed evaluation of the potentially harmful stimulus (LeDoux, 1998). We drew on the Halgren and Marinkovic (1995) model to examine these processes using event-related potentials (ERPs) within a backward masking paradigm. Stimuli used were faces with fear and neutral (as baseline control) expressions, presented above (supraliminal) and below (subliminal) the threshold for conscious detection. ERP data revealed a double dissociation for the supraliminal versus subliminal perception of fear. In the subliminal condition, responses to the perception of fear stimuli were enhanced relative to neutral for the N2 excitatory component, which is thought to represent orienting and automatic aspects of face processing. By contrast, supraliminal perception of fear was associated with relatively enhanced responses for the late P3 inhibitory component, implicated in the integration of emotional processes. These findings provide evidence in support of Halgren and Marinkovics temporal model of emotion processing, and indicate that the neural mechanisms for appraising signals of threat may be initiated, not only automatically, but also without the need for conscious detection of these signals.

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.

Mode of Functional Connectivity in Amygdala Pathways Dissociates Level of Awareness for Signals of Fear

Many of the same regions of the human brain are activated during conscious attention to signals of fear and in the absence of awareness for these signals. The neural mechanisms that dissociate level of awareness from activation in these regions remain unknown. Using functional magnetic resonance imaging with connectivity analysis in healthy human subjects, we demonstrate that level of awareness for signals of fear depends on mode of functional connectivity in amygdala pathways rather than discrete patterns of activation in these pathways. Awareness for fear relied on negative connectivity within both cortical and subcortical pathways to the amygdala, suggesting that reentrant feedback may be necessary to afford such awareness. In contrast, responses to fear in the absence of awareness were supported by positive connections in a direct subcortical pathway to the amygdala, consistent with the view that excitatory feedforward connections along this pathway may be sufficient for automatic responses to “unseen” fear.

Functional disconnections in the direct and indirect amygdala pathways for fear processing in schizophrenia

BACKGROUND Schizophrenia patients show reduced neural activity, relative to controls, in the amygdala and its projection to the medial prefrontal cortex (MPFC) in response to fear perception. In this study we tested the hypothesis that schizophrenia is characterized by abnormal functional connectivity in the amygdala network underlying fear perception. METHODS Functional MRI images were acquired from 14 schizophrenia patients and 14 matched healthy control subjects during an emotion perception task, in which fearful and neutral facial expression stimuli were presented pseudorandomly under nonconscious (using masking) and conscious conditions. Both subtraction and functional connectivity analyses were undertaken using a region of interest approach. RESULTS In response to fearful facial expressions, schizophrenia patients displayed reduced amygdala activity, compared to controls, in both the conscious and nonconscious conditions. The amygdala displayed a reversal of the normal pattern of connectivity with the brainstem, visual cortex, and also with the dorsal and ventral divisions of the MPFC in the schizophrenia patients. CONCLUSIONS The presence of functional disconnections in amygdala pathways suggests that schizophrenia patients have a failure in coordinating their automatic orienting to salient signals and the associated prefrontal monitoring of these signals.

Distinct amygdala-autonomic arousal profiles in response to fear signals in healthy males and females.

The amygdala has a key role in regulating arousal and vigilance, and responds to both visual and vocal signals of fear, including facial expressions of fear. In this study, we used functional MRI to examine sex differences in the magnitude, extent, lateralization and time course of amygdala responses to facial signals of fear, in a relatively large sample of males and females. Skin conductance was recorded simultaneously with functional imaging to examine concomitant changes in emotional arousal, and to provide an independent index of response attenuation. Scanning and skin conductance recording was undertaken during perception of facial fear stimuli. Sex differences were apparent in the laterality and time course of fear perception. In males, the right amygdala and autonomic arousal attenuated over the late half of the experiment. By contrast, females showed persistent bilateral amygdala responses, with a tendency towards greater left amygdala engagement during the late phase. Females also showed a greater general extent of amygdala response. We suggest that distinct evolutionary pressures might contribute to a lower threshold for vigilance to signals of danger in females, reflected in a profile of sustained amygdala-arousal interaction.

Neural Responses to Masked Fear Faces: Sex Differences and Trauma Exposure in Posttraumatic Stress Disorder

Although women have a greater propensity than men to develop posttraumatic stress disorder (PTSD) following trauma, sex differences in neural activations to threat have received little investigation. This study tested the prediction that trauma would heighten activity in automatic fear-processing networks to a greater extent in women than in men. Functional magnetic resonance imaging (fMRI) data were recorded in 23 participants with PTSD (13 women, 10 men), 21 trauma-exposed controls (9 women, 12 men), and 42 non-trauma-exposed controls (22 women, 20 men) while they viewed masked facial expressions of fear. Exposure to trauma was associated with enhanced brainstem activity to fear in women, regardless of the presence of PTSD, but in men, it was associated only with the development of PTSD. Men with PTSD displayed greater hippocampal activity to fear than did women. Both men and women with PTSD showed enhanced amygdala activity to fear relative to controls. The authors conclude that greater brainstem activation to threat stimuli may contribute to the greater prevalence of PTSD in women, and greater hippocampal activation in men may subserve an enhanced capacity for contextualizing fear-related stimuli.

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.