The path from trigeminal asymmetry to cognitive impairment: a behavioral and molecular study.

Trigeminal input exerts acute and chronic effects on the brain, modulating cognitive functions. Here, new data from humans and animals suggest that these effects are caused by trigeminal influences on the Locus Coeruleus (LC). In humans subjects clenching with masseter asymmetric activity, occlusal correction improved cognition, alongside with reductions in pupil size and anisocoria, proxies of LC activity and asymmetry, respectively. Notably, reductions in pupil size at rest on the hypertonic side predicted cognitive improvements. In adult rats, a distal unilateral section of the trigeminal mandibular branch reduced, on the contralateral side, the expression of c-Fos (brainstem) and BDNF (brainstem, hippocampus, frontal cortex). This counterintuitive finding can be explained by the following model: teeth contact perception loss on the lesioned side results in an increased occlusal effort, which enhances afferent inputs from muscle spindles and posterior periodontal receptors, spared by the distal lesion. Such effort leads to a reduced engagement of the intact side, with a corresponding reduction in the afferent inputs to the LC and in c-Fos and BDNF gene expression. In conclusion, acute effects of malocclusion on performance seem mediated by the LC, which could also contribute to the chronic trophic dysfunction induced by loss of trigeminal input.

Trigeminal input, pupil size and cognitive performance: From oral to brain matter.

It has been observed that, in patients affected by temporomandibular disorders (TMDs) and edentulism, a left-right asymmetry in electromyographic (EMG) activity of masseter muscles during clenching and in pupil size at rest (anisocoria) is present. Both are greatly reduced by an orthotic-prosthetic correction. In parallel, the correction significantly improves cognitive performance. These effects are possibly due to the recovery of a cortical balance, via Locus Coeruleus (LC) modulation, whose activity is powerfully affected by the sensorimotor trigeminal input. The role of this functional axis was further investigated in subjects without overt occlusal or dental problems. In these individuals, the EMG asymmetry was significantly correlated to anisocoria at rest, with the dental arches open or in contact. Also in normal subjects, both the EMG and the pupil asymmetry during clenching could be significantly reduced by an orthotic (bite) correction. Closing the arches without bite increased anisocoria and reduced performance in the Spinnler-Tognoni matrices test, as well as the mydriasis induced by a haptic task. When the bite was interposed, anisocoria was reduced, while both performance and task-related mydriasis were enhanced. Since pupil size is considered a proxy of the LC activity, these results suggest that asymmetric occlusion biases the LC discharge and the hemispheric excitability, possibly via a sensorimotor trigeminal imbalance. Removing the anisocoria through bite correction re-establishes a symmetric LC discharge, improving performance and enhancing task-related mydriasis. Therefore, occlusal balancing may represent a tool for improving subjective performance and may be exploited for training and rehabilitative purposes.