Congenital olfactory impairment is linked to cortical changes in prefrontal and limbic brain regions

Abstract

The human sense of smell is closely associated with morphological differences of the fronto-limbic system, specifically the piriform cortex and medial orbitofrontal cortex (mOFC). Still it is unclear whether cortical volume in the core olfactory areas and connected brain regions are shaped differently in individuals who suffer from lifelong olfactory deprivation relative to healthy normosmic individuals. To address this question, we examined if regional variations in gray matter volume were associated with smell ability in seventeen individuals with isolated congenital olfactory impairment (COI) matched with sixteen normosmic controls. All subjects underwent whole-brain magnetic resonance imaging, and voxel-based morphometry was used to estimate regional variations in grey matter volume. The analyses showed that relative to controls, COI subjects had significantly larger grey matter volumes in left middle frontal gyrus and right superior frontal sulcus (SFS). COI subjects with severe olfactory impairment (anosmia) had reduced grey matter volume in the left mOFC and increased volume in right piriform cortex and SFS. Within the COI group olfactory ability, measured with the "Sniffin' Sticks" test, was positively associated with larger grey matter volume in right posterior cingulate and parahippocampal cortices whereas the opposite relationship was observed in controls. Across COI subjects and controls, better olfactory detection threshold was associated with smaller volume in right piriform cortex, while olfactory identification was negatively associated with right SFS volume. Our findings suggest that lifelong olfactory deprivation trigger changes in the cortical volume of prefrontal and limbic brain regions previously linked to olfactory memory.

Structural changes in secondary, but not primary, sensory cortex in individuals with congenital olfactory sensory loss

“…In line with previous studies, we could demonstrate that individuals with ICA have a significantly decreased olfactory sulcus depth, as compared to matched normosmic individuals (Yousem et al 1996;Abolmaali et al 2002;Huart et al 2011;Levy et al 2013;Karstensen et al 2018). The shallow olfactory sulcus depth in individuals with ICA is thought to be related to the complete lack of, or hypoplasia of, olfactory bulbs, often accompanied by small or absent olfactory tracts (Yousem et al 1996;Abolmaali et al 2002); structures located in the olfactory sulci.…”

“…The cortical structural reorganization demonstrated by individuals with ICA were restricted to higher order olfactory (medial orbitofrontal) cortex, without indications of structural alterations in the primary olfactory (piriform) cortex. This lack of reorganization in primary sensory cortex is in disagreement with the literature on congenital visual sensory loss (Bridge et al 2009;Jiang et al 2009;Park et al 2009;Hasson et al 2016), as well as previous studies on individuals with congenital anosmia Karstensen et al 2018). Although the two previous studies investigating cortical morphology in individuals with congenital anosmia indicate increased cortical thickness and increased gray matter volume within the piriform cortex, their results are, however, unilateral and in opposite hemispheres.…”

“…The olfactory bulbs and tracts reside in the olfactory sulci and the projection of the olfactory tracts is suggested to play an important role in the formation and deepening of the olfactory sulci during early development (Abolmaali et al 2002;Turetsky et al 2009;Huart et al 2011). A congenital abnormal cortical folding explains not only the decreased olfactory sulcus depth and decreased curvature in olfactory sulci and medial orbital gyri, but also the decreased gray matter volume in the olfactory sulci, as a natural consequence of the decreased surface (Karstensen et al 2018). However, a decrease in cortical surface in the pericalcarine sulci (visual cortex) in congenitally blind individuals has been described by Park and colleagues (Park et al 2009).…”

Normal Olfactory Functional Connectivity Despite Life-Long Absence of Olfactory Experiences

“…That olfactory loss is poorly studied is not surprising given that many think, erroneously, that the human sense of smell is a residual sense; however, humans have a better sense of smell than most animals (McGann 2017) and olfactory information is of importance for our wellbeing (Croy et al 2014). Congenital anosmia has been linked to morphological reorganization within the orbitofrontal cortex (Frasnelli et al 2013;Karstensen et al 2018;Peter et al 2019) including areas commonly referred to as secondary olfactory cortex (Lundström et al 2011), but, surprisingly, it has been suggested that no morphological alterations occur within primary olfactory cortex despite a life-long absence of olfactory input (Peter et al 2019). As of today, it is not known whether these morphological deviations (and suggested lack thereof) are reflected in functional neuroimaging data.…”

Neural processing of olfactory-related words in subjects with congenital and acquired olfactory dysfunction

“…To date only a few studies have investigated the structural and functional alterations in CA. While reduced gray matter volume in olfactory related brain regions are found in acquired anosmia, CA is associated with increased gray matter volume in the primary olfactory area and the orbitofrontal cortex 14,15 . One recent study showed that CA exhibited audio-visual multisensory enhancement, which suggested a compensation for complete lack of olfactory input 16 .…”