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

Abstract

Influential models of emotion have proposed multiple direct subcortical pathways, often referred to as “low roads,” linking the thalamus to the amygdala and implicated in fear processing. While such pathways are anatomically well characterized in non-human animals, they have not yet been mapped in the human brain. Here, building on converging evidence from animal models, we provide a comprehensive anatomical characterization of distinct thalamo-amygdala pathways in 113 human participants. Using an advanced high-resolution tractography protocol, we reconstructed pathways originating from posterior, medial, and intralaminar thalamic nuclei and projecting to the basolateral amygdala (BLA). To evaluate their anatomical plausibility, we assessed test-retest reproducibility across sessions. Within the posterior thalamus, projections from the medial geniculate nucleus and the medial and inferior pulvinar to the BLA emerged as the strongest and most robust pathways. Within the medial thalamus, the mediodorsal nucleus showed a prominent connection to the BLA, characterized by a high number of streamlines and moderate-to-high reproducibility. Finally, projections from intralaminar thalamic nuclei were consistently identified but exhibited greater intersession variability and lower reproducibility. Together, these findings provide a unifying anatomical framework for multiple direct thalamo-amygdala pathways in the human brain contributing to the characterization of evolutionarily conserved systems potentially underlying affective processing.