Mapping subcortical fear pathways in the human brain: thalamo-amygdala connections revealed by high-resolution tractography

Abstract

Influential models of emotion have postulated the existence of several direct subcortical pathways, or low roads, that convey fast sensory thalamic inputs to the amygdala for affective processing. In rodents and non-human primates, specific thalamo-amygdala connections have been identified and linked to fear responses. These connections mainly originate in three thalamic nuclear groups (posterior, intralaminar, and medial) and project to the basolateral amygdala (BLA). However, the existence of similar thalamo-amygdala pathways in humans remains uncertain. Here, aiming to reproduce subcortical amygdala connections previously described in the non-human animal literature, we mapped those tracts in 113 human participants of either sex. We implemented an advanced high-resolution tractography protocol optimized for reliably tracing axonal pathways through regions with complex white-matter architecture. We reconstructed white matter tracts connecting thalamic nuclei to the BLA, and assessed their test-retest reproducibility to evaluate their anatomical plausibility. Among posterior thalamic nuclei, projections from the medial geniculate nucleus and the medial and inferior pulvinar to the BLA emerged as the strongest and most robust thalamo-amygdala pathways. In turn, the mediodorsal nucleus within the medial group exhibited a prominent connection to the BLA, with a high number of streamlines and moderate-to-high reliability across sessions. Finally, intralaminar thalamic nuclei (parafascicular, central medial, and centromedian) showed consistent connections to the BLA, albeit with higher intrasubject variability and moderate-to-low reproducibility. Together, these findings provide a unifying anatomical framework for multiple direct thalamo-amygdala pathways in the human brain, and suggest the existence of distinct evolutionarily conserved routes for subcortical affective processing. Significance statementAnimal studies have identified several subcortical "low road" pathways that may convey direct sensory inputs from the thalamus to the amygdala. Here, we analyzed human diffusion magnetic resonance imaging data to reconstruct thalamo-amygdala pathways previously reported in non-human species and assessed their test-retest reproducibility. White matter tracts linking the medial geniculate nucleus, as well as the medial and inferior pulvinar, to the basolateral amygdala appeared to be the most robust and reliable. Additional connections were found between the mediodorsal and intralaminar nuclei of the thalamus and the basolateral amygdala. These findings reveal the presence of multiple conserved direct pathways to the amygdala in humans, likely supporting rapid affective processing across modalities.