Brain scans map multiple “low road” fear pathways between the human thalamus and amygdala

Researchers have mapped several direct routes between the human thalamus and amygdala that may help the brain respond rapidly to threatening information, according to a study published in NeuroImage. Connections involving the back of the thalamus were the most consistent, while others were weaker or harder to detect reliably.

Fear responses can begin quickly. When a person hears a sudden noise or sees a possible threat, the brain must evaluate the information and prepare the body to respond. Animal studies have identified short pathways that carry sensory information from the thalamus, a central relay station for incoming sensory signals, to the amygdala, a region involved in emotional learning and defensive responses.

These pathways have sometimes been described as “low roads” because they may transmit basic sensory information without first passing through the cerebral cortex, where more detailed analysis takes place. Although animal studies have characterized them, they had not been comprehensively mapped in the human brain.

Led by Emmanouela Kosteletou-Kassotaki of the University of Barcelona, the researchers studied 113 healthy right-handed volunteers (average age 24.5 years; 65 women).

The team used high-resolution diffusion-weighted MRI, a scanning method that estimates the direction of nerve fibers by tracking the movement of water through brain tissue. They then used tractography, a technique that reconstructs likely fiber pathways from these data, to map connections between several thalamic nuclei and the basolateral amygdala, a part of the amygdala central to fear learning. Their approach was designed to cope with the dense, crisscrossing fibers around these deep brain structures.

A smaller group of 24 participants underwent a second MRI scan about 15 days later on average. This allowed the researchers to examine whether the pathways could be reconstructed consistently 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 portions of the pulvinar, a thalamic structure involved in visual attention and combining information across the senses, 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 fiber 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 center of the thalamus, were also identified, particularly from the parafascicular and central medial nuclei. However, these pathways varied more between people 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 also tended to connect with different subregions of the basolateral amygdala, and several pathways showed more reconstructed fiber paths in the left hemisphere than in the right, although the authors caution that this asymmetry may partly reflect methodological factors. Overall, the results support the idea that humans possess several direct thalamus–amygdala pathways rather than one simple route. These pathways could help transmit sensory and emotional signals quickly, potentially supporting 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 has technical limitations that should be noted. It can mistakenly identify pathways that are not present or fail to detect pathways that are present, particularly where nerve fibers cross, so the connections will need to be confirmed with studies of brain tissue. The method also cannot show which direction signals travel and provides information about structure rather than real-time brain function, so the link to fear is inferred largely 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.