Normal Olfactory Functional Connectivity Despite Lifelong Absence of Olfactory Experiences

Abstract

Congenital blindness is associated with atypical morphology and functional connectivity within and from visual cortical regions; changes that are hypothesized to originate from a lifelong absence of visual input and could be regarded as a general (re) organization principle of sensory cortices. Challenging this is the fact that individuals with congenital anosmia (lifelong olfactory sensory loss) display little to no morphological changes in the primary olfactory cortex. To determine whether olfactory input from birth is essential to establish and maintain normal functional connectivity in olfactory processing regions, akin to the visual system, we assessed differences in functional connectivity within the olfactory cortex between individuals with congenital anosmia (n = 33) and matched controls (n = 33). Specifically, we assessed differences in connectivity between core olfactory processing regions as well as differences in regional homogeneity and homotopic connectivity within the primary olfactory cortex. In contrast to congenital blindness, none of the analyses indicated atypical connectivity in individuals with congenital anosmia. In fact, post-hoc Bayesian analysis provided support for an absence of group differences. These results suggest that a lifelong absence of olfactory experience has a limited impact on the functional connectivity in the olfactory cortex, a finding that indicates a clear difference between sensory modalities in how sensory cortical regions develop.

Acquired olfactory loss alters functional connectivity and morphology

“…Nonetheless, on the other extreme of the time-spectra lie individuals who are born without a sense of smell and who can serve as a theoretical contrast to assess potential effects of time. In line with this assumption, and in contradiction with the present results, we recently showed that the piriform cortex in individuals with congenital anosmia did not differ from healthy controls in either gray matter volume, cortical thickness, or functional connectivity to olfactory-associated areas (Peter et al, 2021(Peter et al, , 2020; but see Frasnelli et al, 2013). Why there is more evidence of reorganization in primary olfactory regions in individuals with shorter olfactory sensory loss, here with an average of 14 months without olfactory inputs, than in individual with long-term sensory loss is not known.…”

“…Most evidence of sensory loss-related neuroplasticity originates from the visual and auditory systems where significant effects are demonstrated in primary sensory processing areas (Fine and Park, 2018;Röder and Rösler, 2004). Studies assessing impact on primary olfactory cortex (piriform cortex) due to loss of the sense of smell (anosmia) have, in contrast, reported either minor (Frasnelli et al, 2013;Karstensen et al, 2018;Peng et al, 2013;Reichert and Schöpf, 2018) or indiscernible functional or morphological changes (Han et al, 2018(Han et al, , 2017Peter et al, 2021Peter et al, , 2020Yao et al, 2018). The vast majority of studies exploring neural impact of acquired visual and auditory sensory loss have focused on adult individuals that experienced their sensory loss early, often before their second year of life, and with many years without sensory function.…”

“…In contrast, few studies have explored effects of olfactory sensory loss on functional connectivity from the primary olfactory cortex, the piriform cortex, or functional processing within. Whereas lifelong absence of olfactory input, so-called congenital anosmia, does not seem to alter functional connectivity either within or from piriform cortex during rest (Peter et al, 2021), acquired anosmia has been linked to decreased connectivity within the piriform cortex odor- and sniff-induced network (Kollndorfer et al, 2015; Reichert et al, 2018). Moreover, artificially induced shortterm olfactory loss by naris occlusion alters odor-related processing in both the posterior piriform cortex and the orbitofrontal cortex (Wu et al, 2012); areas linked to the formation of odor representation as well as, among other skills, odor attention (Lundström et al, 2011).…”

Post-traumatic olfactory loss and brain response beyond olfactory cortex

“…Functional neuroimaging studies on patients with isolated congenital olfactory impairment, which to our knowledge do not exist at this time, may lend substance to this explanation. Interestingly, very recently a report on intact resting-state networks in olfactory areas were confirmed in congenital anosmia 61 . The current results suggest that the post-traumatic damage causing olfactory dysfunction is central and in other brain areas than the primary olfactory cortex, however, it is also possible that this network reflects regions that have adapted to cope with olfactory loss.…”

Beyond olfactory cortex – severity of post-traumatic olfactory loss is associated with response to odors in frontal-parietal-insular networks

“…Functional neuroimaging studies on patients with isolated congenital olfactory impairment, which to our knowledge do not exist at this time, may lend substance to this explanation. Interestingly, very recently a report on intact resting-state networks in olfactory areas were confirmed in congenital anosmia (69). The current results suggest that the post-traumatic damage causing olfactory dysfunction is central and in other brain areas than the primary olfactory cortex, however, it is also possible that this network reflects regions that have adapted to cope with olfactory loss.…”