The mandibular branch of the trigeminal nerve controls muscles of mastication through an area of the pontine brainstem called the trigeminal motor nucleus (5M). In rodents, 5M motor neurons have been shown to be involved in various circuits that contribute to jaw functions. Mapping these circuits in humans has been challenging because of the complex structure of the brainstem, the prevalence of crossing fibers, and the need for high-resolution technology to unravel these circuits.

Written by:
Vaidhehi Veena Sanmugananthan

Edited by:
Georgia Hadjis

UTCSP scientists Dr. Massieh Moayedi and Dr. Iacopo Cioffi and their team used Human Connectome Project (HCP) data to probe white matter pathways in the human brainstem to see if they could resolve a similar circuit in humans. Their main focus was on the pathway between 5M and the central nucleus of the amygdala (CeA), as the CeA has connections to autonomic centers in the brainstem and cortex, and plays an important role in modulating responses (physiological and behavioural) to various stimuli. To resolve this pathway, they performed probabilistic tractography on both 7T and 3T diffusion weighted imaging (DWI) scans. As a negative control, the authors performed a tractography analysis between 5M and the basolateral amygdala (BLAT), an amygdalar subregion that projects to the cortex but not to the brainstem. The connectivity strength between the BLAT-5M and CeA-5M circuits was then compared, expecting much lower connectivity strength in the BLAT-5M circuit than the CeA-5M circuit. The analysis was performed on 30 healthy individuals (17 females, mean age ± SD: 30.6 ± 2.6 years; 13 males, mean age ± SD: 27.5 ± 3.0 years).

An adaptive exponential integrate-and-fire computational model was first adjusted to match the properties of S1 pyramidal neurons. To simulate physiological electrical “noise” due to random opening and closing of ion channels or background synaptic input, the model was tested in the presence or absence of uncorrelated noise. Using this model, the authors found that without the inclusion of noise, higher frequency inputs were coded in a nearly identical pattern as lower frequency inputs due to limitations in neuronal firing rates. However, when noise approximating in vivo conditions was included in the model, cycles of stimulation were skipped irregularly, resulting in spiking intervals that correlated with the frequency of the input. By delivering and recording electrical signals from neurons directly, the authors also found that S1 neurons fire intermittently during high frequency inputs, which allowed population responses to be modulated in sync with input frequency.


Within each hemisphere, the authors found significantly greater connectivity strength in the CeA–5M circuit compared to the BLAT–5M circuit in both 7T and 3T scans. The authors conclude that their findings are the first to demonstrate an in vivo construction of the CeA-5M pathway in humans. This should encourage future studies to explore the role of this circuit in humans in more detail.