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

Westmead Hospital, Sydney, New South Wales, Australia
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 10/2006; 26(36):9264-71. DOI: 10.1523/JNEUROSCI.1016-06.2006
Source: PubMed


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.

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Available from: Leanne M Williams, Feb 08, 2015
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    • "Hyper-activation of the amygdala has also been observed during the supraliminal and subliminal processing of facial expressions of sadness (Surguladze et al, 2005; Fu et al, 2004; Victor et al, 2010; Arnone et al, 2012). The advantage of subliminal conditions is that they help to isolate the automatic processes that underpin amygdala activation from more elaborative supraliminal processes (Williams et al, 2006; Costafreda et al, 2008). Yet other studies have observed no differences between MDD patients and controls in amygdala reactivity for sad expressions (Almeida et al, 2010; Townsend et al, 2010). "
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    ABSTRACT: Although the cost of poor treatment outcomes of depression is staggering we do not yet have clinically useful methods for selecting the most effective antidepressant for each depressed person. Emotional brain activation is altered in MDD and implicated in treatment response. Identifying which aspects of emotional brain activation are predictive of general and specific responses to antidepressants may help clinicians and patients when making treatment decisions. We examined whether amygdala activation probed by emotion stimuli is a general or differential predictor of response to three commonly prescribed antidepressants, using functional magnetic resonance imaging (fMRI). A test-retest design was used to assess patients with major depressive disorder (MDD) in an academic setting as part of the International Study to Predict Optimized Treatment in Depression. 80 MDD outpatients were scanned pre-treatment and 8 weeks after randomization to the selective serotonin reuptake inhibitors escitalopram and sertraline and the serotonin-norepinephrine reuptake inhibitor, venlafaxine-extended release (XR). 34 matched controls were scanned at the same timepoints. We quantified the blood oxygen level-dependent signal of the amygdala during subliminal and supraliminal viewing of facial expressions of emotion. Response to treatment was defined by >=50% symptom improvement on the 17-item Hamilton Depression Rating Scale. Pre-treatment amygdala hypo-reactivity to subliminal happy and threat was a general predictor of treatment response, regardless of medication type (cohen's d effect size.63 to.77; classification accuracy, 75%). Responders showed hypo-reactivity compared to controls at baseline, and an increase toward "normalization" post-treatment. Pre-treatment amygdala reactivity to subliminal sadness was a differential moderator of non-response to venlafaxine-XR (cohen's d effect size 1.5; classification accuracy, 81%). Non-responders to venlafaxine-XR showed pre-treatment hyper-reactivity which progressed to hypo-reactivity rather than normalization post-treatment and hypo-reactivity post-treatment was abnormal compared to controls. Impaired amygdala activation has not previously been highlighted in the general versus differential prediction of antidepressant outcomes. Amygdala hypo-reactivity to emotions signaling reward and threat predicts the general capacity to respond to antidepressants. Amygdala hyper-reactivity to sad emotion is involved in a specific non-response to a serotonin-norepinephrine reuptake inhibitor. The findings suggest amygdala probes may help inform the personal selection of antidepressant treatments.Neuropsychopharmacology accepted article preview online, 31 March 2015. doi:10.1038/npp.2015.89.
    Full-text · Article · Mar 2015 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
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    • "With regard to the processing of emotional aspects of scenes, there is some evidence suggesting that the pulvinar and superior colliculus act as a pathway to amygdala during the preattentive processing of fearful faces (Morris et al., 1998, 2001; Tamietto and de Gelder, 2010; Williams et al., 2006), however the meaning of these effects are controversial (Cowey, 2004; Pessoa and Adolphs, 2010; Pessoa and Ungerleider, 2004), and intracranial studies in the primate (Nakamura et al., 1994; Nishijo et al., 2007; Sugase et al.,1999) and human (Oya et al., 2002; Krolak-Salmon et al., 2004; Pourtois et al., 2010) report emotional discrimination in the amygdala much later than would be expected via a purely subcortical route. Other evidence in humans suggests that while the pulvinar is unlikely to contain the processing power necessary to discriminate complex visual information (Grieve et al., 2000; Petersen et al., 1985), it may be involved indirectly in the emotional evaluation process (Ward et al., 2005; Padmala et al., 2010) perhaps reflecting the enhanced visual attention to motivationally relevant features of visual stimuli. "
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    ABSTRACT: Emotional scene perception is associated with enhanced activity in ventral occipitotemporal cortex and amygdala. While a growing body of research supports the perspective that emotional perception is organized via amygdala feedback to rostral ventral visual cortex, the contributions of high-order thalamic structures strongly associated with visual attention, specifically the mediodorsal nucleus and pulvinar, have not been well investigated. Here we sample the activity of amygdala, MDN, pulvinar, and extrastriate ventral visual regions with fMRI as a group of participants view a mixed series of pleasant, neutral, and unpleasant natural scenes, balanced for basic perceptual characteristics. The results demonstrate that all regions showed enhanced activity during emotionally arousing relative to neutral scene perception. Consistent with recent research, the latency of emotional discrimination across subcortical and visual cortical regions suggests a role for the amygdala in the early evaluation of scene emotion. These data support the perspective that higher order visual thalamic structures are sensitive to the emotional value of complex scene stimuli, and may serve in concert with amygdala and fusiform gyrus to modulate visual attention toward motivationally relevant cues.
    Full-text · Article · Aug 2014 · Brain Research
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    • "Previous work has also shown that both disgusted and fearful expressions can be perceived independently of awareness (e.g., Smith, in press). Using various methods to render stimuli invisible, neuroimaging studies demonstrated that the amygdala is involved in the non-conscious processing of emotional faces (e.g., Whalen et al., 1998; Morris et al., 1999; Pasley et al., 2004; Williams et al., 2004, 2006; Jiang and He, 2006; but see Phillips et al., 2004). Scarce studies found support for an involvement of the insula in the non-conscious processing of emotional stimuli (e.g., Sabatini et al., 2009; but see, Anderson et al., 2003, and Phillips et al., 2004, for results that speak against automatic facial expression processing in the insula). "
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    ABSTRACT: Previous studies have shown that complex visual stimuli, such as emotional facial expressions, can influence brain activity independently of the observers’ awareness. Little is known yet, however, about the “informational correlates” of consciousness—i.e., which low-level information correlates with brain activation during conscious vs. non-conscious perception. Here, we investigated this question in the spatial frequency (SF) domain. We examined which SFs in disgusted and fearful facial expressions modulate activation in the insula and amygdala over time and as a function of awareness, using a combination of intracranial event-related potentials (ERPs), SF Bubbles (Willenbockel et al., 2010a), and Continuous Flash Suppression (CFS; Tsuchiya and Koch, 2005). Patients implanted with electrodes for epilepsy monitoring viewed face photographs (13° x 7°) that were randomly SF filtered trial-by-trial. In the conscious condition, the faces were visible; in the non-conscious condition, they were rendered invisible using CFS. Data were analyzed by performing multiple linear regressions on the SF filters from each trial and the transformed ERP amplitudes across time. The resulting classification images suggest that many SFs are involved in the conscious and non-conscious perception of emotional expressions, with those between 6 and 10 cycles per face width being particularly important early on. The results also revealed qualitative differences between the awareness conditions for both regions. Non-conscious processing relied on low SFs more and was faster than conscious processing. Overall, our findings are consistent with the idea that different pathways are employed for the processing of emotional stimuli under different degrees of awareness. The present study represents a first step to mapping with a high temporal resolution how SF information “flows” through the emotion-processing network and to shedding light on the informational correlates of consciousness in general.
    Full-text · Article · Jul 2012 · Frontiers in Psychology
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