STUDY OF THE INFLUENCE OF MALOCCLUSIONS ON COGNITIVE ACTIVITY DURING DEVELOPMENT

The thesis is grounded in a growing body of research linking the stomatognathic system to central nervous system function. Prior systematic reviews (Piancino et al., 2019, 2020) demonstrated that altered chewing whether from soft-food diets, molar extraction, or experimentally raised bites leads to reduced hippocampal neurons, decreased BDNF (brain-derived neurotrophic factor), impaired neurogenesis, and worse performance on memory and spatial orientation tests in animal models. Importantly, a raised bite condition was shown to activate the hypothalamic-pituitary-adrenal (HPA) axis, generating a chronic stress response with measurable effects on brain structures. Large-scale clinical studies in humans further support this link: tooth loss and reduced mastication are significantly associated with cognitive decline and higher risk of mild cognitive impairment and dementia, particularly when posterior teeth (those used for grinding) are lost. Studies have shown that masticatory asymmetry (e.g., from unilateral molar loss) produces asymmetric masseter activation and a corresponding pupillary asymmetry (anisocoria), pointing to an imbalance in LC activity. Pupillometry study (92 patients) Recognizing the complexity of neuropsychological testing in children, the protocol was refined to use pupillometry a non-invasive, rapid, objective measure of LC-NE activity via pupil diameter. Furthermore the orthodontic data, the NPi-200 pupillometer was used on each 92 children in mixed dentition undergoing FGB treatment (2023–2026), measuring pupil parameters at rest and after light stimulation, under three occlusal conditions: teeth in contact (maximal intercuspation), teeth not in contact, and with the FGB appliance in situ. Multiple linear regression models controlling for age, sex, laterality, and cephalometric variables were applied. Results: • Males had larger pupil diameters than females. • The right pupil was larger than the left. • Teeth-not-in-contact condition produced larger pupils than teeth-in-contact, suggesting dental occlusion influences ARAS/LC activity. • Hyperdivergent craniofacial morphology (greater vertical skeletal development) was significantly associated with smaller pupil diameters indicating lower LC arousal, consistent with the known lower EMG amplitude and greater occlusal instability in these patients. Discussion and Clinical Implications The results regarding sex and lateralization are in agreement with the neurologic data in literature. The most significant finding from the orthodontic point of view is the relationship between vertical craniofacial divergence and pupil size, suggesting that hyperdivergent patients have intrinsically lower central nervous system arousal. This means that the control of the facial divergence is an important therapeutic objective in orthodontics which is difficult to obtain with conventional fixed appliances while the FGB appliance through the posterior bite planes is able to reach. The thesis also establishes, for the first time in an orthodontic context, that pupillometry is a valid tool for monitoring CNS activity in developing patients. Conclusions Pupillary diameter is significantly associated with occlusal condition, a relationship that has never been previously considered or reported in the literature. Larger pupils occur in males and in the right eye, suggesting dental contact modulates Locus Coeruleus activity. These findings support an interaction between stomatognathic structures and the LC activity, opening new perspectives for integrated preventive and therapeutic approaches that consider oral function a component of brain health.