It is usually considered that the sense of smell is poorly developed in humans, in comparison, for example, to lower vertebrates, such as rats and mice. However, in view of its evolutionary significance, it seems very unlikely that the sense of smell is trivial in guiding human behavior.

The fragility of the fibers in the olfactory mucosa of the nose, their delicate passage through the cribriform plate, and the course of the olfactory tract along the orbital surface of the brain underly the vulnerability of this sensory modality to external trauma—for example, from head injury. This is compounded by the locations of structures receiving the central representations of smell, such as, for example, the primary olfactory cortex and olfactory tubercle, which lie vulnerable on the undersurface of the brain overlying the anterior perforated space.

Smell sensations may occur as part of an aura in temporal lobe epilepsy. Traditionally referred to as uncinate seizures (simple partial seizures in today’s terminology), the seizure focus was thought to be in the uncus, overlying the amygdala. However, olfactory inputs also end in the anterior insula, which thus may be associated with the experience. These aurae therefore have some localizing value, but they are not of lateralizing significance.

The olfactory system is involved in several neuropsychiatric disorders. In depression, for example, the sense of smell can be diminished, as may be other sensory modalities, such as taste or touch. Diminished smell sensation also has been reported in Alzheimer’s disease and Parkinson’s disease, especially the Lewy body variant but not sufficiently reliably to be used in any diagnostic way (Hawkes, 2003). Diminished smell also may be observed early in the course of schizophrenia and may be associated with smaller perirhinal cortices as measured with MRI (Turetsky et al., 2003). Thus, disturbances of smell in such disorders may be associated with underlying neuroanatomical deficits, rather than being simply a manifestation of a psychosis or deteriorating intellect.