Brain Imaging and Behavior

, Volume 12, Issue 6, pp 1569–1582 | Cite as

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

  • Helena Gásdal KarstensenEmail author
  • Martin Vestergaard
  • William F. C. Baaré
  • Arnold Skimminge
  • Bjarki Djurhuus
  • Bjarki Ellefsen
  • Norbert Brüggemann
  • Camilla Klausen
  • Anne-Mette Leffers
  • Niels Tommerup
  • Hartwig R. Siebner


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.


Anosmia Hyposmia Congenital Voxel based morphometry Olfactory Orbitofrontal cortex 



The authors thank the participants for their invaluable contribution. The authors wish to acknowledge the important contribution made by Léa Gagnon, PhD, Maurice Ptito, Professor, PhD and Ron Kupers, Professor, PhD in the assessment of olfaction and taste.


The study was supported by the Lundbeck Foundation (R32-A2947), Chevron Texaco, the Faroese Research Council (0313) and the Danish National Research Foundation (02-512-48), Gangstedfonden, Ville Heises Legat and Hvidovre Hospital’s Research Fund.

Compliance with ethical standards

Conflict of interest

Hartwig R. Siebner (HRS) has served on a scientific advisory board for Lundbeck A/S, Valby Denmark. HRS has received honoraria as speaker from Biogen Idec, Denmark A/S, Genzyme, Denmark and MerckSerono, Denmark. HRS has received honoraria as editor from Elsevier Publishers, Amsterdam, The Netherlands and Springer Publishing, Stuttgart, Germany. HRS has received travel support from MagVenture, Denmark, and a research fund from Biogen-idec. All other authors have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11682_2017_9817_MOESM1_ESM.jpg (3 mb)
Supplementary material 1 (JPG 3078 KB)
11682_2017_9817_MOESM2_ESM.docx (47 kb)
Supplementary material 2 (DOCX 46 KB)


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Helena Gásdal Karstensen
    • 1
    Email author
  • Martin Vestergaard
    • 2
  • William F. C. Baaré
    • 2
  • Arnold Skimminge
    • 2
  • Bjarki Djurhuus
    • 3
  • Bjarki Ellefsen
    • 3
  • Norbert Brüggemann
    • 2
  • Camilla Klausen
    • 2
  • Anne-Mette Leffers
    • 2
  • Niels Tommerup
    • 1
  • Hartwig R. Siebner
    • 2
    • 4
  1. 1.Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, Faculty of Health SciencesUniversity of CopenhagenCopenhagenDenmark
  2. 2.Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and ResearchCopenhagen University Hospital HvidovreHvidovreDenmark
  3. 3.Department of ENT Head and Neck SurgeryThe National Hospital of the Faroe IslandsTórshavnFaroe Islands
  4. 4.Department of NeurologyCopenhagen University Hospital BispebjergCopenhagenDenmark

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