A new study maps several direct routes between the human thalamus and amygdala that may help the brain respond rapidly to threatening information. The research, published in NeuroImage, identifies the most reliable connections linking the posterior thalamus to the basolateral amygdala and highlights multiple pathways beyond a single route. The work is led by Emmanouela Kosteletou-Kassotaki of the University of Barcelona and draws on 113 healthy, right-handed volunteers with an average age of 24.5 and 65 women.
The team used high-resolution diffusion-weighted MRI to estimate the direction of nerve fibres by tracking water movement through brain tissue. They then applied tractography to reconstruct likely fibre pathways between several thalamic nuclei and the basolateral amygdala, a region central to fear learning. The approach was designed to cope with the dense, crisscrossing fibres around these deep brain structures. A smaller subset of 24 participants underwent a second MRI scan about 15 days later to assess the consistency of the pathways across sessions.
The most reliable connections linked the posterior thalamus to the basolateral amygdala. One pathway ran from the inferior colliculus, an auditory hub in the midbrain, through the medial geniculate nucleus, a key auditory relay in the thalamus, to the amygdala, mirroring an auditory fear pathway well documented in rodents. This pathway was found in nearly all participants.
Connections between the amygdala and the medial, inferior and lateral parts of the pulvinar, a thalamic structure involved in visual attention and multisensory integration, appeared in all 113 participants and were highly reproducible, particularly for the inferior pulvinar. By contrast, connections with the anterior pulvinar were sparse and inconsistent, and a direct route from the inferior colliculus to the amygdala that bypassed the medial geniculate nucleus could not be reliably reconstructed.
The mediodorsal nucleus, located in the medial thalamus, also showed a prominent connection with the basolateral amygdala, with a high number of reconstructed fibre paths and moderate-to-high reproducibility. The authors note, however, that this connection may mainly carry signals from the amygdala rather than to it.
Connections from intralaminar thalamic nuclei, a group of small nuclei near the centre of the thalamus, were also identified, particularly from the parafascicular and central medial nuclei. However, these pathways varied more between individuals and between the first and second scans. This suggests that some connections are robust across people, while others may be weaker, more difficult to detect or more variable in their anatomy.
Different thalamic regions tended to connect with different subregions of the basolateral amygdala, and several pathways showed more reconstructed fibre paths in the left hemisphere than in the right, though the authors caution that this asymmetry may partly reflect methodological factors. Overall, the findings support the idea that humans possess several direct thalamus–amygdala pathways rather than a single straightforward route, potentially enabling rapid sensory and emotional signalling to support flexible defensive responses.
Kosteletou-Kassotaki and colleagues described the study as providing “a unifying anatomical framework for multiple direct thalamo-amygdala pathways in the human brain.”
Diffusion tractography does have technical limitations. It can misidentify pathways that are not present or fail to detect those that are, particularly where nerve fibres cross, so the connections will need confirmation with studies of brain tissue. The method cannot determine the direction of signal flow and provides information about structure rather than real-time brain function, so the link to fear remains largely inferentially drawn from animal research.
The study, “Mapping the subcortical pathways associated with fear in the human brain: multiple thalamo-amygdala connections revealed by high-resolution tractography,” was authored by Emmanouela Kosteletou-Kassotaki, Liu Mengxing, Martina T. Cinca-Tomás, Pedro M. Paz-Alonso and Judith Domínguez-Borràs.
