Pathways for fear perception: Modulation of amygdala activity by thalamo-cortical systems

Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), Darlinghurst, NSW, Australia.
NeuroImage (Impact Factor: 6.36). 06/2005; 26(1):141-8. DOI: 10.1016/j.neuroimage.2005.01.049
Source: PubMed


Effective perception of fear signals is crucial for human survival and the importance of the amygdala in this process is well documented. Animal, lesion and neuroimaging studies indicate that incoming sensory signals of fear travel from thalamus to amygdala via two neural pathways: a direct subcortical route and an indirect pathway via the sensory cortex. Other lines of research have demonstrated prefrontal modulation of the amygdala. However, no study to date has examined the prefrontal modulation of the thalamo-cortico-amygdala pathways in vivo. We used psychophysiological and physiophysiological interactions to examine the functional connectivity within thalamus, amygdala and sensory (inferior occipital, fusiform) cortices, and the modulation of these networks by the anterior cingulate cortex (ACC). Functional magnetic resonance imaging (fMRI) data were acquired for 28 healthy control subjects during a fear perception task, with neutral as the 'baseline' control condition. Main effect analysis, using a region of interest (ROI) approach, confirmed that these regions are part of a distributed neural system for fear perception. Psychophysiological interactions revealed an inverse functional connectivity between occipito-temporal visual regions and the left amygdala, but a positive connectivity between these visual region and the right amygdala, suggesting that there is a hemispheric specialization in the transfer of fear signals from sensory cortices to amygdala. Physiophysiological interactions revealed a dorsal-ventral division in ACC modulation of the thalamus-sensory cortex pathway. While the dorsal ACC showed a positive modulation of this pathway, the ventral ACC exhibited an inverse relationship. In addition, both the dorsal and ventral ACC showed an inverse interaction with the direct thalamus-amygdala pathway. These findings suggest that thalamo-amygdala and cortical regions are involved in a dynamic interplay, with functional differentiation in both lateralized and ventral/dorsal gradients. Breakdowns in these interactions may give rise to affect-related symptoms seen in a range of neuropsychiatric disorders.

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Available from: Leanne M Williams, Feb 24, 2015
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    • "We focus on amygdala connectivity due to the animal literature indicating an important role for the amygdala in the early development of fear (Barr et al., 2009; Bauman et al., 2004; Bliss-Moreau et al., 2010; Moriceau and Sullivan, 2006; Moriceau et al., 2006; Raper et al., 2013). In humans, the amygdala functions in a coordinated manner with multiple subcortical and cortical brain regions including sensorimotor, emotion, memory and higher order attention centers (Das et al., 2005; Gabard-Durnam et al., 2014; Gee et al., 2013a,b; Qin et al., 2014, 2012; Roy et al., 2009; Stein et al., 2007). Previous work in children and adults has highlighted coordinated functioning of the amygdala with several of these brain regions, including the anterior insula (aI) and medial prefrontal cortex (MPFC), as particularly important for understanding the neural basis of typical and pathological fear (Callaghan et al., 2014; Etkin et al., 2011; Etkin and Wager, 2007; Milad and Quirk, 2012; Qin et al., 2014; Rabinak et al., 2011; Sripada et al., 2012). "
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    ABSTRACT: The first year of life is an important period for emergence of fear in humans. While animal models have revealed developmental changes in amygdala circuitry accompanying emerging fear, human neural systems involved in early fear development remain poorly understood. To increase understanding of the neural foundations of human fear, it is important to consider parallel cognitive development, which may modulate associations between typical development of early fear and subsequent risk for fear-related psychopathology. We, therefore, examined amygdala functional connectivity with rs-fcMRI in 48 neonates (M=3.65 weeks, SD=1.72), and measured fear and cognitive development at 6-months-of-age. Stronger, positive neonatal amygdala connectivity to several regions, including bilateral anterior insula and ventral striatum, was prospectively associated with higher fear at 6-months. Stronger amygdala connectivity to ventral anterior cingulate/anterior medial prefrontal cortex predicted a specific phenotype of higher fear combined with more advanced cognitive development. Overall, findings demonstrate unique profiles of neonatal amygdala functional connectivity related to emerging fear and cognitive development, which may have implications for normative and pathological fear in later years. Consideration of infant fear in the context of cognitive development will likely contribute to a more nuanced understanding of fear, its neural bases, and its implications for future mental health.
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    • "Based on its putative role in fear conditioning, a seed was placed in right amygdala [MNI [22] [26] [212]; coordinates obtained from Das et al., 2005] to examine functional connectivity from and to this region. A set of regions was found to drive neural responses in amygdala across experimental phases for both CS1 and CS2 (habituation CS1: size 5 62, habituation CS2: size 5 24, conditioning CS1: 45, conditioning CS2: 136, extinction CS1: size 5 73, extinction CS2: size 5 84). "
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    ABSTRACT: Despite a strong focus on the role of the amygdala in fear conditioning, recent works point to a more distributed network supporting fear conditioning. We aimed to elucidate interactions between subcortical and cortical regions in fear conditioning in humans. To do this, we used two fearful faces as conditioned stimuli (CS) and an electrical stimulation at the left hand, paired with one of the CS, as unconditioned stimulus (US). The luminance of the CS was rhythmically modulated leading to "entrainment" of brain oscillations at a predefined modulation frequency. Steady-state responses (SSR) were recorded by MEG. In addition to occipital regions, spectral analysis of SSR revealed increased power during fear conditioning particularly for thalamus and cerebellum contralateral to the upcoming US. Using thalamus and amygdala as seed-regions, directed functional connectivity was calculated to capture the modulation of interactions that underlie fear conditioning. Importantly, this analysis showed that the thalamus drives the fusiform area during fear conditioning, while amygdala captures the more general effect of fearful faces perception. This study confirms ideas from the animal literature, and demonstrates for the first time the central role of the thalamus in fear conditioning in humans. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
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    • "Studies also found that the connectivity between different subregions of the MPFC and amygdala may make diverse effects on emotion function. For example, when people did a fear perception task, there was a dorsal-ventral division in ACC modulation of the thalamus-sensory cortex pathway, with a positive modulation of this pathway from dorsal ACC and a negative one from the ventral ACC (Das et al., 2005). In addition, Satterthwaite et al. (2011) demonstrated that the amygdala responded preferentially to threatening (fearful or angry) faces and had increased connectivity during threat trials with the OFC. "
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