NeuroImage 218 (2020) 117005 Contents lists available at ScienceDirect NeuroImage journal homepage: www.elsevier.com/locate/neuroimage Morphological changes in secondary, but not primary, sensory cortex in individuals with life-long olfactory sensory deprivation Moa G. Peter a,*, Gustav Mårtensson b, Elbrich M. Postma c,d, Love Engstrom€ Nordin b,e, Eric Westman b,f, Sanne Boesveldt c, Johan N. Lundstrom€ a,g,h,i,** a Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden b Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden c Division of Human Nutrition and Health, Wageningen University, Wageningen, the Netherlands d Smell and Taste Centre, Hospital Gelderse Vallei, Ede, the Netherlands e Department of Diagnostic Medical Physics, Karolinska University Hospital Solna, Stockholm, Sweden f Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK g Monell Chemical Senses Center, Philadelphia, PA, USA h Department of Psychology, University of Pennsylvania, Philadelphia, USA i Stockholm University Brain Imaging Centre, Stockholm University, Stockholm, Sweden ARTICLE INFO ABSTRACT Keywords: Individuals with congenital sensory deprivation usually demonstrate altered brain morphology in areas associated Anosmia with early processing of the absent sense. Here, we aimed to establish whether this also applies to individuals born Cortical thickness without a sense of smell (congenital anosmia) by comparing cerebral morphology between 33 individuals with Curvature isolated congenital anosmia and matched controls. We detected no morphological alterations in the primary Area olfactory (piriform) cortex. However, individuals with anosmia demonstrated gray matter volume atrophy in Plasticity Voxel-based bilateral olfactory sulci, explained by decreased cortical area, curvature, and sulcus depth. They further Morphometry demonstrated increased gray matter volume and cortical thickness in the medial orbital gyri; regions closely associated with olfactory processing, sensory integration, and value-coding. Our results suggest that a lifelong absence of sensory input does not necessarily lead to morphological alterations in primary sensory cortex and extend previous findings with divergent morphological alterations in bilateral orbitofrontal cortex, indicating influences of different developmental processes. 1. Introduction potential plastic effects of complete olfactory sensory deprivation (anosmia, for a review see Reichert and Schopf,€ 2018) and reports on The notion that the human brain is plastic and undergoes morpho- cerebral reorganization in individuals with lifelong (congenital) anosmia logical as well as functional alterations in response to changes in expe- is particularly rare. rienced demands is widely accepted (Buonomano and Merzenich, 1998; Although the brain exhibits plasticity throughout life, it is strongest Lindenberger et al., 2017). One of the more drastic changes in demands early in life when even brief periods of sensory deprivation can make it on the brain is undoubtedly the loss of a sensory modality, comprising a difficult, if not impossible, to gain normal abilities even if the sensory loss complete lack of input from the lost sense combined with altered de- is reversed and normal sensory input established (Collignon et al., 2015; mands on the remaining senses. Indeed, visual sensory deprivation has Guerreiro et al., 2016; Hyvarinen€ et al., 1981; Wiesel and Hubel, 1965). repeatedly been linked to both structural and functional cerebral re- Thus, in comparison to individuals who have gone through normal sen- organizations with often profound changes in regions normally focused sory development, individuals with a congenital or very early acquired on the processing of the absent sense, often in primary sensory cortex (for complete sensory deprivation would be expected to demonstrate pro- reviews see Bavelier and Neville, 2002; Frasnelli et al., 2011; Merabet nounced patterns of cerebral reorganization. In addition, studying in- and Pascual-Leone, 2010). In contrast, few studies have investigated the dividuals with an isolated congenital sensory deprivation (i.e., a * Corresponding author. Dept. of Clinical Neuroscience, Karolinska Institutet, Nobels vag€ 9, 17177, Stockholm, Sweden. ** Corresponding author. Dept. of Clinical Neuroscience, Karolinska Institutet, Nobels vag€ 9, 17177, Stockholm, Sweden. E-mail addresses: [email protected] (M.G. Peter), [email protected] (J.N. Lundstrom).€ https://doi.org/10.1016/j.neuroimage.2020.117005 Received 10 January 2020; Received in revised form 26 May 2020; Accepted 27 May 2020 Available online 30 May 2020 1053-8119/© 2020 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). M.G. Peter et al. NeuroImage 218 (2020) 117005 congenital sensory deprivation not related to additional symptoms) has ICA (analyzed for 33, see methods) and 34 normosmic controls, matched the advantage of isolating plastic effects of the sensory deprivation, in terms of age, sex, and education. First, we determined potential group whereas individuals with an acquired sensory loss constitute a much differences in whole-brain gray matter volume using voxel-based more heterogeneous group where variability in the age at which the morphometry (VBM) for voxel-wise comparisons. Thereafter, to assess sense was lost, the duration of the sensory loss, the direct cause of sensory possible underlying mechanisms of the VBM results, we determined po- loss (as in the case of traumatic brain injury, which might in itself cause tential differences in cortical thickness, surface area, and curvature be- reorganization of the brain), and perceptual abilities before sensory loss tween individuals with ICA and controls. Based on past findings likely affect sensory loss-related cerebral reorganization (Jiang et al., indicating that both congenital blindness and ICA leads to alterations in 2015; Noppeney et al., 2005; Voss and Zatorre, 2012). Individuals with cortical thickness and/or gray matter volume within early processing isolated congenital sensory deprivation hence constitute a good model areas of the missing sense, we hypothesized that individuals with ICA for increasing our understanding of the adaptiveness the human brain would demonstrate an increase in gray matter volume within piriform possesses. cortex and OFC. Both congenital and acquired visual sensory deprivation have repeatedly been linked to atrophy in form of decreased gray matter 2. Materials and methods volume in areas related to visual processing, specifically within primary visual cortex (Bridge et al., 2009; Jiang et al., 2015; Noppeney et al., 2.1. Participants 2005; Pan et al., 2007; Ptito et al., 2008). The gray matter volume de- creases are, however, associated with divergent underlying morphology: A total of 68 participants were enrolled in the study: 34 individuals the atrophy in congenital blindness is accompanied by a thickening of the with isolated congenital anosmia (ICA, congenital anosmia unrelated to visual cortex (Bridge et al., 2009; Hasson et al., 2016; Jiang et al., 2009; specific genetic disorders, such as Kallmann syndrome) and 34 controls, Park et al., 2009), whereas the atrophy in individuals with acquired matched in terms of sex, age, and educational level (Table 1). Inclusion sensory loss has been linked to either a cortical thinning or a lack of criteria for the ICA group was a self-reported lifelong lack of olfactory cortical thickness alterations (Jiang et al., 2009; Park et al., 2009; Voss perception and thorough questioning failing to reveal any known un- and Zatorre, 2012). The fact that divergent underlying morphology may derlying condition causing the anosmia (such as head trauma), and for cause similar volumetric results emphasize the importance of not solely the control group a self-proclaimed functional sense of smell (subse- relying on one measure of morphological changes. quently tested). In addition, 24 out of the 34 individuals with ICA had Despite the established link between olfactory ability and the received a diagnosis from a physician. Of the 34 ICA individuals, 27 morphology of olfactory cortical structures such as the olfactory bulb, lacked bilateral olfactory bulbs, 3 individuals had identifiable (albeit piriform (commonly referred to as primary olfactory) cortex, and orbi- very small) bulbs, and the presence of bulbs in the remaining 4 was non- tofrontal cortex (OFC; commonly referred to as secondary olfactory determinable due to the limited spatial resolution of 1 mm3 (assessed by cortex; Lundstrom€ et al., 2011), which generally indicates a positive J. N. L.). Participants were recruited and tested at two different sites: 46 correlation between volume and ability (Frasnelli et al., 2010a; Hummel participants (23 ICA) in Stockholm, Sweden, and 22 (11 ICA) in Wage- et al., 2015; Seubert et al., 2013b), the only consistent finding in the ningen, the Netherlands; the matched control was always tested at the study of cerebral morphological reorganization in individuals with iso- same site as the individual with ICA. One individual from the ICA group lated congenital anosmia (ICA) is the absence, or hypoplasia, of the ol- was removed from analysis after visual inspection of the images due to factory bulbs and olfactory tracts, accompanied by a significant decrease abnormal