Biology subjects

Kosteletou-Kassotaki, E.

Publications and source records attributed to Kosteletou-Kassotaki, E..

3 recordsLinked to original sources

bioRxiv2026

Distinct associations between thalamo-amygdala pathways and state anxiety

Neurobiological models of emotion have proposed the existence of multiple direct subcortical pathways in humans, often referred to as "low roads", linking the thalamus to the amygdala and implicated in affective function. Among these, pulvinar-amygdala structural connectivity has been associated with individual differences in anxiety and anxiety-related conditions. However, whether distinct thalamo-amygdala pathways across thalamic subnuclei differentially relate to anxiety remains unknown. Using diffusion MRI in 34 healthy participants, we reconstructed four candidate subcortical "low roads" bilaterally from the medial geniculate body (MGB), as well as the medial, inferior and lateral pulvinar to the basolateral amygdala (BLA). We then tested whether their structural connectivity strength was associated with individual differences in state and trait anxiety. Linear regression analyses revealed that fiber density in three left thalamo-amygdala pathways predicted state, but not trait, anxiety. Importantly, our results showed a functional dissociation across pathways. While fiber density in MGB-BLA and medial pulvinar-BLA pathways was negatively related to state anxiety, the inferior pulvinar-BLA tract showed the opposite association. These findings support differentiated contributions across thalamo-amygdala pathways in humans to state anxiety. The results highlight these subcortical pathways as potentially relevant neurobiological substrates for understanding anxiety and affective function. Key pointsO_LIFiber density of three left thalamo-amygdala pathways explained 24.1% of the variance in state anxiety across 34 healthy individuals C_LIO_LIFiber density in the left medial geniculate body and left medial pulvinar-amygdala pathways was negatively associated with state anxiety C_LIO_LIFiber density in the left inferior pulvinar-amygdala pathway was positively associated with state anxiety C_LI

neuroscience↗

bioRxiv2026

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

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.

neuroscience↗

bioRxiv2025

An auditory "low road" for threat in humans sensitive to fast temporal cues

Rapid threat processing is crucial for survival. In vision, neural models of emotion propose the existence of direct pathways, or "low roads", from visual thalamus to the amygdala, which may rely on magnocellular inputs and thereby enable rapid processing of threat signals. In audition, evidence from non-human animals points to the existence of a similar fast direct pathway, but its presence in humans remains unknown. Building on animal evidence that high-rate amplitude-modulated (highAM) sounds preferentially engage magnocellular processing, we used behavioral, physiological, and neuroimaging measures to search for an auditory "low road" for threat in humans responsive to magnocellular-associated features. Specifically, we tested whether highAM threat cues elicit rapid affective responses, and whether highAM threat processing aligns with structural thalamo-amygdala connectivity. We recorded electroencephalography and pupillometry from participants while they detected voices during fear conditioning. Emotional voices presented at highAM rates, as opposed to lowAM, elicited threat-related responses during the earliest post-stimulus window. A further study combining functional and diffusion-weighted imaging revealed that selective amygdala responses to highAM threatening voices were functionally associated with individual fiber density of an auditory thalamo-amygdala pathway. These results provide convergent functional and anatomical evidence supporting a subcortical pathway for auditory threat processing, consistent with evolutionarily conserved emotional systems.

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