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

Abstract

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.

Coupling between Trigeminal-Induced Asymmetries in Locus Coeruleus Activity and Cognitive Performance

“…In these subjects, when the dental arches were closed (without effort), the cognitive performance was impaired and task-related mydriasis was reduced. In contrast, the former improved and the latter increased by a bite application [12,13]. These modifications were negatively correlated to changes in anisocoria and average pupil size at rest [12,13].…”

“…In contrast, the former improved and the latter increased by a bite application [12,13]. These modifications were negatively correlated to changes in anisocoria and average pupil size at rest [12,13].…”

“…Subtle cognitive deficits associated with asymmetry in pupil size (anisocoria) at rest have been observed in subjects (either normal, bearing masticatory deficits or showing unilateral molar loss) characterized by an asymmetry in masseter electromyographic (EMG) activity during clenching [10][11][12][13]. Both the EMG asymmetry during clenching and the pupil asymmetry at rest disappeared when the occlusion was corrected by an appropriate orthotic device (bite) [10,12,13] or when the edentulism was corrected by artificial crowns [11]. In these subjects, when the dental arches were closed (without effort), the cognitive performance was impaired and task-related mydriasis was reduced.…”

“…Regarding the relation between changes in performance and average pupil size, readout of the average LC activity, it has to be reminded that, according to the "adaptive gain theory" of Aston-Jones and Cohen [31], performance is related to the tonic LC activity by an inverted-U shaped relation. Thus, a negative correlation between performance/mydriasis and pupil size should be expected when the basal level of noradrenergic activity is high [13].…”

Health-Related Quality of Life in Oral Cancer Patients: Scoping Review and Critical Appraisal of Investigated Determinants

“…The dental prosthetic restoration (supported or not by implants) could be a deeply influencing factor in patients' everyday life and HRQOL. The recovery of dental occlusion and a balanced mastication has been demonstrated to influence aesthetic outcomes, social parameters, swallowing and cognitive functions [102][103][104][105][106][107][108][109][110][111][112]. The published literature expressed highly significantly better results in patients undergoing micro-vascular mandibular reconstruction (mostly by using free fibula flap) with following implant-supported dental prosthetic rehabilitation compared to non-rehabilitated patients [108][109][110][111][112].…”