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A multi-pathway hypothesis for human visual fear signaling.

Silverstein DN, Ingvar M - Front Syst Neurosci (2015)

Bottom Line: Using the anatomical path lengths and latency estimates for each of these five pathways, predictions are made for the relative processing times at selective ROIs and arrival at the amygdala, based on the presentation of a fear-relevant visual stimulus.Partial verification of the temporal dynamics of this hypothesis might be accomplished using experimental MEG analysis.Possible experimental protocols are suggested.

View Article: PubMed Central - PubMed

Affiliation: PDC Center for High Performance Computing and Department of Computational Biology, KTH Royal Institute of Technology Stockholm, Sweden ; Stockholm Brain Institute, Karolinska Institutet Solna, Sweden.

ABSTRACT
A hypothesis is proposed for five visual fear signaling pathways in humans, based on an analysis of anatomical connectivity from primate studies and human functional connectvity and tractography from brain imaging studies. Earlier work has identified possible subcortical and cortical fear pathways known as the "low road" and "high road," which arrive at the amygdala independently. In addition to a subcortical pathway, we propose four cortical signaling pathways in humans along the visual ventral stream. All four of these traverse through the LGN to the visual cortex (VC) and branching off at the inferior temporal area, with one projection directly to the amygdala; another traversing the orbitofrontal cortex; and two others passing through the parietal and then prefrontal cortex, one excitatory pathway via the ventral-medial area and one regulatory pathway via the ventral-lateral area. These pathways have progressively longer propagation latencies and may have progressively evolved with brain development to take advantage of higher-level processing. Using the anatomical path lengths and latency estimates for each of these five pathways, predictions are made for the relative processing times at selective ROIs and arrival at the amygdala, based on the presentation of a fear-relevant visual stimulus. Partial verification of the temporal dynamics of this hypothesis might be accomplished using experimental MEG analysis. Possible experimental protocols are suggested.

No MeSH data available.


Primate network diagram showing a subset of relevant brain areas and projections for visual fear signaling. Anatomical abbreviations are described in Table 1. The proposed fear signaling pathways are labeled p1–p5. Projection preferences 1–39 are listed in Table 2, which are not exhaustive. Hippocampus and most ACC circuits are excluded. The amygdala superficial cortical nuclei are also excluded. For clarity, PFC and ITC groups appear more than once. Projections may connect a nested group when there are multiple internal sources/destinations or the source/destination is uncertain.
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Figure 2: Primate network diagram showing a subset of relevant brain areas and projections for visual fear signaling. Anatomical abbreviations are described in Table 1. The proposed fear signaling pathways are labeled p1–p5. Projection preferences 1–39 are listed in Table 2, which are not exhaustive. Hippocampus and most ACC circuits are excluded. The amygdala superficial cortical nuclei are also excluded. For clarity, PFC and ITC groups appear more than once. Projections may connect a nested group when there are multiple internal sources/destinations or the source/destination is uncertain.

Mentions: Figure 2 shows a detailed subset of known connectivity between brain regions involved in fear processing, as well as the hypothesized fear signaling pathways for vision, all of which exhibited experimental evidence for both functional and direct anatomical connectivity. However, in addition to the pathways illustrated in Figure 2, others likely exist. Connections with the adjacent hippocampus (Saunders et al., 1988) were not considered, which are known to play a role in fear conditioning, based on spatial cues and memory (LeDoux, 2000; Phelps and LeDoux, 2005; Alvarez et al., 2008). A fearful place for example, might trigger a visual signal via the posterior parietal to the hippocampus and on to the amygdala, but there is not yet functional evidence for this in primates. The FEF is bidirectionally connected to the VC, IT and parietal cortex, and projects to the PFC as well. In addition to saccade control, the FEF is known to modulate attention (Chica et al., 2014), but does not project to the amygdala directly. Hypothesized magnocellular projections to the mOFC have been suggested to preferably transfer low spatial frequency features before IT might see it (Bar et al., 2006; Kveraga et al., 2007; Chaumon et al., 2014), but the anatomical evidence is still uncertain. While IT and particularly TE strongly projects to OFC, weak projections were found from the IPS area of the posterior parietal to the lOFC in monkeys (Morecraft et al., 1992), along with projections to the FEF from the superior temporal sulcus (Schall et al., 1995). Still, in humans, the inferior fronto-occipital fasiculus (IFOF) appears to project from the parietal dorsal stream to the lateral and basal OFC (Martino et al., 2010; Sarubbo et al., 2013). A sub-cortical route to OFC is possible through the amygdala or pulvinar, although the amygdala is not likely to transfer details in low spatial frequency features. It is also possible for the signal to arrive at the mOFC rapidly via IT, which can be activated in 80–110 ms (Rolls et al., 2005), possibly along the inferior longitudinal fasciculus (ILF) or even directly via the LGN (Webster et al., 1993), followed by traversing the UF to the OFC. A pathway to the amygdala through the insula is also possible, since both the OFC and PFC project to it directly. Movement can induce fear as well. Visual-vestibular input can induce fear when falling, for example (Coelho and Balaban, 2015). There also exists evidence of a vestibular pathway to the amygdala. The vestibular nuclei have been found to project to the parabrachial nucleus in primates (Balaban et al., 2002), which in turn have direct bi-directional connections to the amygdala Ce, as well as indirect connections via the hypothalamus and OFC (Balaban and Thayer, 2001).


A multi-pathway hypothesis for human visual fear signaling.

Silverstein DN, Ingvar M - Front Syst Neurosci (2015)

Primate network diagram showing a subset of relevant brain areas and projections for visual fear signaling. Anatomical abbreviations are described in Table 1. The proposed fear signaling pathways are labeled p1–p5. Projection preferences 1–39 are listed in Table 2, which are not exhaustive. Hippocampus and most ACC circuits are excluded. The amygdala superficial cortical nuclei are also excluded. For clarity, PFC and ITC groups appear more than once. Projections may connect a nested group when there are multiple internal sources/destinations or the source/destination is uncertain.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4547041&req=5

Figure 2: Primate network diagram showing a subset of relevant brain areas and projections for visual fear signaling. Anatomical abbreviations are described in Table 1. The proposed fear signaling pathways are labeled p1–p5. Projection preferences 1–39 are listed in Table 2, which are not exhaustive. Hippocampus and most ACC circuits are excluded. The amygdala superficial cortical nuclei are also excluded. For clarity, PFC and ITC groups appear more than once. Projections may connect a nested group when there are multiple internal sources/destinations or the source/destination is uncertain.
Mentions: Figure 2 shows a detailed subset of known connectivity between brain regions involved in fear processing, as well as the hypothesized fear signaling pathways for vision, all of which exhibited experimental evidence for both functional and direct anatomical connectivity. However, in addition to the pathways illustrated in Figure 2, others likely exist. Connections with the adjacent hippocampus (Saunders et al., 1988) were not considered, which are known to play a role in fear conditioning, based on spatial cues and memory (LeDoux, 2000; Phelps and LeDoux, 2005; Alvarez et al., 2008). A fearful place for example, might trigger a visual signal via the posterior parietal to the hippocampus and on to the amygdala, but there is not yet functional evidence for this in primates. The FEF is bidirectionally connected to the VC, IT and parietal cortex, and projects to the PFC as well. In addition to saccade control, the FEF is known to modulate attention (Chica et al., 2014), but does not project to the amygdala directly. Hypothesized magnocellular projections to the mOFC have been suggested to preferably transfer low spatial frequency features before IT might see it (Bar et al., 2006; Kveraga et al., 2007; Chaumon et al., 2014), but the anatomical evidence is still uncertain. While IT and particularly TE strongly projects to OFC, weak projections were found from the IPS area of the posterior parietal to the lOFC in monkeys (Morecraft et al., 1992), along with projections to the FEF from the superior temporal sulcus (Schall et al., 1995). Still, in humans, the inferior fronto-occipital fasiculus (IFOF) appears to project from the parietal dorsal stream to the lateral and basal OFC (Martino et al., 2010; Sarubbo et al., 2013). A sub-cortical route to OFC is possible through the amygdala or pulvinar, although the amygdala is not likely to transfer details in low spatial frequency features. It is also possible for the signal to arrive at the mOFC rapidly via IT, which can be activated in 80–110 ms (Rolls et al., 2005), possibly along the inferior longitudinal fasciculus (ILF) or even directly via the LGN (Webster et al., 1993), followed by traversing the UF to the OFC. A pathway to the amygdala through the insula is also possible, since both the OFC and PFC project to it directly. Movement can induce fear as well. Visual-vestibular input can induce fear when falling, for example (Coelho and Balaban, 2015). There also exists evidence of a vestibular pathway to the amygdala. The vestibular nuclei have been found to project to the parabrachial nucleus in primates (Balaban et al., 2002), which in turn have direct bi-directional connections to the amygdala Ce, as well as indirect connections via the hypothalamus and OFC (Balaban and Thayer, 2001).

Bottom Line: Using the anatomical path lengths and latency estimates for each of these five pathways, predictions are made for the relative processing times at selective ROIs and arrival at the amygdala, based on the presentation of a fear-relevant visual stimulus.Partial verification of the temporal dynamics of this hypothesis might be accomplished using experimental MEG analysis.Possible experimental protocols are suggested.

View Article: PubMed Central - PubMed

Affiliation: PDC Center for High Performance Computing and Department of Computational Biology, KTH Royal Institute of Technology Stockholm, Sweden ; Stockholm Brain Institute, Karolinska Institutet Solna, Sweden.

ABSTRACT
A hypothesis is proposed for five visual fear signaling pathways in humans, based on an analysis of anatomical connectivity from primate studies and human functional connectvity and tractography from brain imaging studies. Earlier work has identified possible subcortical and cortical fear pathways known as the "low road" and "high road," which arrive at the amygdala independently. In addition to a subcortical pathway, we propose four cortical signaling pathways in humans along the visual ventral stream. All four of these traverse through the LGN to the visual cortex (VC) and branching off at the inferior temporal area, with one projection directly to the amygdala; another traversing the orbitofrontal cortex; and two others passing through the parietal and then prefrontal cortex, one excitatory pathway via the ventral-medial area and one regulatory pathway via the ventral-lateral area. These pathways have progressively longer propagation latencies and may have progressively evolved with brain development to take advantage of higher-level processing. Using the anatomical path lengths and latency estimates for each of these five pathways, predictions are made for the relative processing times at selective ROIs and arrival at the amygdala, based on the presentation of a fear-relevant visual stimulus. Partial verification of the temporal dynamics of this hypothesis might be accomplished using experimental MEG analysis. Possible experimental protocols are suggested.

No MeSH data available.