0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Article |

Correlation of Olfactory Function With Changes in the Volume of the Human Olfactory Bulb FREE

Antje Haehner, MD; Antje Rodewald, MD; Johannes C. Gerber, MD; Thomas Hummel, MD
[+] Author Affiliations

Author Affiliations: Departments of Neurology (Dr Haehner), Otorhinolaryngology (Drs Haehner and Hummel), and Neuroradiology (Drs Rodewald and Gerber), University of Dresden Medical School, Dresden, Germany.


Arch Otolaryngol Head Neck Surg. 2008;134(6):621-624. doi:10.1001/archotol.134.6.621.
Text Size: A A A
Published online

Objective  To investigate changes of olfactory bulb (OB) volume over time in relation to olfactory function.

Design  Prospective, before-after trial.

Setting  Outpatient clinic of a university clinic for otorhinolaryngology.

Patients  A total of 20 patients with olfactory loss participated in the study. The duration of olfactory deficits ranged from 3 months to 6 years.

Main Outcome Measures  Olfactory function was assessed for phenyl ethyl alcohol odor threshold, odor discrimination, and odor identification. Olfactory bulb volume was determined using magnetic resonance imaging.

Results  In initially hyposmic patients (n = 13), changes in OB volume were found to correlate with odor threshold changes (r = 0.82; P = .001); no such correlation was found for odor discrimination or odor identification.

Conclusion  As demonstrated in a longitudinal study for the first time to our knowledge, the human OB is a highly plastic structure that responds to individual changes in olfactory status.

Figures in this Article

Magnetic resonance imaging (MRI) offers an ideal means to reliably evaluate the volume of the olfactory bulb (OB), which appears to be of interest in olfactory loss. Olfactory bulb size has been studied in patients with posttraumatic14 and postinfectious olfactory deficits,3,5 congenital anosmia,1,6 and neurodegenerative diseases7,8 and in subjects with a normal sense of smell.7 These cross-sectional studies indicate that (1) OB volume seems to change in parallel to smell function, (2) OB volume decreases with duration of olfactory loss, and (3) patients with parosmia present with smaller OBs compared with those without.35

Experimental animal studies show that the OB remains highly plastic throughout adult life. Bulbar neurogenesis relates to the activity level of sensory input from the olfactory epithelium,9 leading to a reduction in OB size or to an improvement of sensory abilities.10 In addition, contributing to the plasticity of this structure in humans, neuroblasts migrate to the OB via a lateral ventricular extension OB volume.11

The question arises whether changes of OB volume may reflect changes in olfactory function. This would support the idea of OB volumetry as a prognostic tool in assessing the course of postinfectious and posttraumatic olfactory loss. For the first time to our knowledge, the present study aimed to longitudinally investigate possible differences of OB volume over a period in patients with peripheral olfactory deficits (ie, postinfectious and posttraumatic olfactory dysfunction) in relation to changes in olfactory function. It was hypothesized that OB volume should increase in patients exhibiting recovery of olfactory function and vice versa.

Investigations were performed according to the Declaration of Helsinki on Biomedical Studies Involving Human Subjects.12 The study design was approved by the ethics committee of the Medical Faculty of the University of Dresden Medical School, Dresden, Germany. All subjects attended our Smell and Taste Clinic for detailed diagnostic evaluation. They received an otorhinolaryngological investigation including nasal endoscopy, olfactory testing, and a MRI of the brain between October 2003 and March 2004 (time 1) and again after 13 to 19 months (time 2) (mean interval, 15 months).

PARTICIPANTS

A total of 20 randomly selected patients participated. Fourteen of the patients had postinfectious olfactory deficits (mean [range] age, 65 years [50-76 years]; 10 women and 4 men), 6 had posttraumatic olfactory loss (mean [range] age, 59 years [23-72 years]; 2 women and 4 men). Duration of olfactory deficits at the time of the first examination ranged from 3 months to 6 years. Ten patients with postinfectious smell deficits, and 1 patient with posttraumatic olfactory dysfunction reported parosmia (mean [range] age, 63 years [50-76 years]; 8 women and 3 men; mean [range] duration of olfactory deficits, 10 months [3 months to 3 years]).

OLFACTORY TESTING

Following a physical examination by an experienced ear, nose, and throat specialist, olfactory function was assessed in all individuals by means of the validated “Sniffin’ Sticks” test kit,13,14 which comprises 3 individual tests of olfactory function (phenyl ethyl alcohol odor threshold, odor discrimination, and odor identification). The scores of the individual tests were summarized to the so-called TDI (threshold, discrimination, and identification) score, which is a reliable means to estimate the degree of olfactory function.1316

MAGNETIC RESONANCE IMAGING

The volume of the OB was determined using MRI (Figure 1). All examinations were performed on a 1.5-T system (Magnetom Vision; Siemens, Erlangen, Germany) using the circularly polarized head coil. To visualize the OB, a 3-dimensional CISS (constructive interference in steady state) sequence was applied, with slice selection gradients oriented coronally and perpendicularly to the frontal skull base or the cribriform plate. Depending on the size of the head, a slice thickness of 0.5 to 0.7 mm was used. The in-plane resolution varied between 0.5 × 0.2 mm and 1.0 × 0.2 mm. As previously described,6 volumetric measurements were performed by an experienced radiologist (A.R.) who was blind to the olfactory test data by manual segmentation of the coronal slices through the OBs on both sides separately. The change of diameter at the beginning of the olfactory tract was used as the proximal demarcation of the OB.

Place holder to copy figure label and caption
Figure 1.

Coronal T2-weighted magnetic resonance image of the olfactory bulbs (arrowheads).

Graphic Jump Location
STATISTICAL ANALYSIS

Data were analyzed using SPSS 12.0 (SPSS Inc, Chicago, Illinois) statistical software for Windows. For analyses, the “best” volume was used, meaning the larger of the left- or right-side OB volume. This approach was chosen because results from birhinal olfactory tests typically reflect function of the better of the 2 sides of the nose,17,18 and thus, the OB with the largest volume was assumed to reflect the function of the best nostril. Comparisons were performed using t tests for paired samples. Correlation analyses were performed controlling for the patients' age. The α level was .05.

In general, change of OB volume in this study was not significantly related to age and sex of the individuals or to the occurrence of parosmia.

At time 1, 7 of the 20 patients presented with anosmia and 13 were hyposmic. When testing individuals for the second time, 6 of them had anosmia and 14 presented with hyposmia (for total results, see Table). Correlation analyses between the change in olfactory sensitivity and in OB volume during the testing interval were made separately for hyposmic and anosmic patients. In initially hyposmic patients (3 with posttraumatic and 10 with postinfectious smell loss), changes in OB volume were found to correlate significantly with odor threshold changes (r = 0.82; P = .001) (Figure 2), indicating that subjects with improving olfactory function also exhibited an increase of OB volume. However, no such correlations were found for odor discrimination or odor identification. In addition, the length of the intertest interval showed a negative correlation with OB volume (r = −0.57; P = .05), which, however, missed the criterion for significance.

Place holder to copy figure label and caption
Figure 2.

Changes of best olfactory bulb (OB) volumes plotted against changes of phenyl ethyl alcohol (PEA) odor threshold testing in 13 hyposmic subjects indicating that subjects with improving olfactory function (higher threshold score) also exhibit an increase of OB volume.

Graphic Jump Location
Table Graphic Jump LocationTable. Olfactory Bulb (OB) Volumes and Results From Olfactory Testing in 20 Patientsa at the Time 1 and Time 2 Measurementsb

The main outcome of the present longitudinal study was that in hyposmic patients, changes in OB volume correlated with changes in odor threshold. Thus, the results from the present study demonstrate that OB volumes reflect olfactory function in patients with olfactory loss.

The present findings also support research in experimental animals on changes of OB volume in relation to input from the olfactory epithelium. This correlation between structure and function is most likely due to the high plasticity found in the synaptogenesis of the OB.19 In addition, there is a continuous stream of neurons to the OB, which is a unique phenomenon in the central nervous system.11

The present investigation revealed correlations between OB volume and odor thresholds, but not between OB volume and suprathreshold measures of olfactory function (ie, smell discrimination and identification abilities). Provided that odor thresholds are more closely related to peripheral function,2022 these results support the idea that OB volume is more directly related to peripheral input than to higher central nervous processing of olfactory information. It is also possible that the relatively small sample size investigated in this study accounts, at least in part, for the missing correlations between changes of suprathreshold functions and changes of OB volume. Nevertheless, the present data argue that the correlation between changes of OB volume and changes of odor thresholds may be stronger than that the correlation between changes of odor identification scores and changes of OB volume. The present results also are in line with previous research,4 exhibiting significant correlations between odor thresholds and OB volume but not between OB volume and odor identification or odor discrimination scores for orthonasal testing.

The correlation between OB volume and olfactory function may potentially be used in combination with other factors influencing olfaction such as remaining olfactory function, age, and duration of olfactory loss23 as a means to provide patients with individual information on the prognosis of their disease. Hypothetically, a multifactorial approach could be applied to eventually come up with a formula that would allow a more precise prognosis of olfactory function. Especially since therapeutic options in patients with olfactory loss are limited,24 at present, this type of information is of high clinical significance.

In conclusion, the present study emphasizes that OB volume correlates with olfactory function, and our data support the evidence that the human OB is a highly plastic structure.9,10

Correspondence: Thomas Hummel, MD, Department of Otorhinolaryngology, University of Dresden Medical School, Fetscherstrasse 74, 01307 Dresden, Germany (thummel@rcs.urz.tu-dresden.de).

Submitted for Publication: July 20, 2007; final revision received October 5, 2007; accepted October 10, 2007.

Author Contributions: All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Hummel. Acquisition of data: Haehner, Rodewald, Gerber, and Hummel. Analysis and interpretation of data: Haehner and Hummel. Drafting of the manuscript: Haehner and Hummel. Critical revision of the manuscript for important intellectual content: Haehner, Rodewald, and Gerber. Statistical analysis: Hummel. Administrative, technical, and material support: Rodewald, Gerber, and Hummel. Study supervision: Haehner and Hummel.

Financial Disclosure: None reported.

Additional Contributions: Katja Lill, MD, helped with some of the psychophysical olfactory tests and Rüdiger von Kummer, MD, provided suggestions with regard to earlier versions of the manuscript.

Yousem  DMGeckle  RJBilker  W McKeown  DADoty  RL MR evaluation of patients with congenital hyposmia or anosmia. AJR Am J Roentgenol 1996;166 (2) 439- 443
PubMed Link to Article
Yousem  DMGeckle  RJBilker  WBKroger  HDoty  RL Posttraumatic smell loss: relationship of psychophysical tests and volumes of the olfactory bulbs and tracts and the temporal lobes. Acad Radiol 1999;6 (5) 264- 272
PubMed Link to Article
Mueller  ARodewald  AReden  JGerber  Jvon Kummer  RHummel  T Reduced olfactory bulb volume in post-traumatic and post-infectious olfactory dysfunction. Neuroreport 2005;16 (5) 475- 478
PubMed Link to Article
Rombaux  P Mouraux  ABertrand  BNicolas  GDuprez  THummel  T Retronasal and orthonasal olfactory function in relation to olfactory bulb volume in patients with posttraumatic loss of smell. Laryngoscope 2006;116 (6) 901- 905
PubMed Link to Article
Rombaux  PMouraux  ABertrand  BNicolas  GDuprez  THummel  T Olfactory function and olfactory bulb volume in patients with postinfectious olfactory loss. Laryngoscope 2006;116 (3) 436- 439
PubMed Link to Article
Abolmaali  NDHietschold  VVogl  TJHuttenbrink  KBHummel  T MR evaluation in patients with isolated anosmia since birth or early childhood. AJNR Am J Neuroradiol 2002;23 (1) 157- 164
PubMed
Yousem  DMGeckle  RJBilker  WBDoty  RL Olfactory bulb and tract and temporal lobe volumes: normative data across decades. Ann N Y Acad Sci 1998;855546- 555
PubMed Link to Article
Mueller  AAbolmaali  NDHakimi  AR  et al.  Olfactory bulb volumes in patients with idiopathic Parkinson's disease—a pilot study. J Neural Transm 2005;112 (10) 1363- 1370
PubMed Link to Article
Lledo  PMGheusi  G Olfactory processing in a changing brain. Neuroreport 2003;14 (13) 1655- 1663
PubMed Link to Article
Lledo  PMGheusi  GVincent  JD Information processing in the mammalian olfactory system. Physiol Rev 2005;85 (1) 281- 317
PubMed Link to Article
Curtis  MAKam  MNannmark  U  et al.  Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 2007;315 (5816) 1243- 1249
PubMed Link to Article
World Medical Association, World Medical Association declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. JAMA 1997;277 (11) 925- 926
PubMed Link to Article
Hummel  TSekinger  BWolf  SPauli  EKobal  G “Sniffin' Sticks”: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses 1997;22 (1) 39- 52
PubMed Link to Article
Kobal  GKlimek  LWolfensberger  M  et al.  Multicenter investigation of 1,036 subjects using a standardized method for the assessment of olfactory function combining tests of odor identification, odor discrimination, and olfactory thresholds. Eur Arch Otorhinolaryngol 2000;257 (4) 205- 211
PubMed Link to Article
Wolfensberger  MSchnieper  IWelge-Lussen  A “Sniffin' Sticks”: a new olfactory test battery. Acta Otolaryngol 2000;120 (2) 303- 306
PubMed Link to Article
Hummel  THeilmann  SHüttenbrink  KB Lipoic acid in the treatment of smell dysfunction following viral infection of the upper respiratory tract. Laryngoscope 2002;112 (11) 2076- 2080
PubMed Link to Article
Betchen  SADoty  RL Bilateral detection thresholds in dextrals and sinistrals reflect the more sensitive side of the nose, which is not lateralized. Chem Senses 1998;23 (4) 453- 457
PubMed Link to Article
Frasnelli  JLivermore  ASoiffer  AHummel  T Comparison of lateralized and binasal olfactory thresholds. Rhinology 2002;40 (3) 129- 134
PubMed
Cummings  DMKnab  BRBrunjes  PC Effects of unilateral olfactory deprivation in the developing opossum, Monodelphis domesticaJ Neurobiol 1997;33 (4) 429- 438
PubMed Link to Article
Hornung  DEKurtz  DBBradshaw  CB  et al.  The olfactory loss that accompanies an HIV infection. Physiol Behav 1998;64 (4) 549- 556
PubMed Link to Article
Jones-Gotman  MZatorre  RJ Contribution of the right temporal lobe to odor memory [abstract]. Epilepsia 1988;29 (5) 661
Moberg  PJAgrin  RGur  REGur  RCTuretsky  BIDoty  RL Olfactory dysfunction in schizophrenia: a qualitative and quantitative review. Neuropsychopharmacology 1999;21 (3) 325- 340
PubMed Link to Article
Reden  JMueller  AMueller  C  et al.  Recovery of olfactory function following closed head injury or infections of the upper respiratory tract. Arch Otolaryngol Head Neck Surg 2006;132 (3) 265- 269
PubMed Link to Article
Landis  BNHummel  TLacroix  JS Basic and clinical aspects of olfaction. Pickard  JDAdvances and Technical Standards in Neurosurgery. Vol 30 Wien, Austria Springer2005;69- 105

Figures

Place holder to copy figure label and caption
Figure 1.

Coronal T2-weighted magnetic resonance image of the olfactory bulbs (arrowheads).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Changes of best olfactory bulb (OB) volumes plotted against changes of phenyl ethyl alcohol (PEA) odor threshold testing in 13 hyposmic subjects indicating that subjects with improving olfactory function (higher threshold score) also exhibit an increase of OB volume.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable. Olfactory Bulb (OB) Volumes and Results From Olfactory Testing in 20 Patientsa at the Time 1 and Time 2 Measurementsb

References

Yousem  DMGeckle  RJBilker  W McKeown  DADoty  RL MR evaluation of patients with congenital hyposmia or anosmia. AJR Am J Roentgenol 1996;166 (2) 439- 443
PubMed Link to Article
Yousem  DMGeckle  RJBilker  WBKroger  HDoty  RL Posttraumatic smell loss: relationship of psychophysical tests and volumes of the olfactory bulbs and tracts and the temporal lobes. Acad Radiol 1999;6 (5) 264- 272
PubMed Link to Article
Mueller  ARodewald  AReden  JGerber  Jvon Kummer  RHummel  T Reduced olfactory bulb volume in post-traumatic and post-infectious olfactory dysfunction. Neuroreport 2005;16 (5) 475- 478
PubMed Link to Article
Rombaux  P Mouraux  ABertrand  BNicolas  GDuprez  THummel  T Retronasal and orthonasal olfactory function in relation to olfactory bulb volume in patients with posttraumatic loss of smell. Laryngoscope 2006;116 (6) 901- 905
PubMed Link to Article
Rombaux  PMouraux  ABertrand  BNicolas  GDuprez  THummel  T Olfactory function and olfactory bulb volume in patients with postinfectious olfactory loss. Laryngoscope 2006;116 (3) 436- 439
PubMed Link to Article
Abolmaali  NDHietschold  VVogl  TJHuttenbrink  KBHummel  T MR evaluation in patients with isolated anosmia since birth or early childhood. AJNR Am J Neuroradiol 2002;23 (1) 157- 164
PubMed
Yousem  DMGeckle  RJBilker  WBDoty  RL Olfactory bulb and tract and temporal lobe volumes: normative data across decades. Ann N Y Acad Sci 1998;855546- 555
PubMed Link to Article
Mueller  AAbolmaali  NDHakimi  AR  et al.  Olfactory bulb volumes in patients with idiopathic Parkinson's disease—a pilot study. J Neural Transm 2005;112 (10) 1363- 1370
PubMed Link to Article
Lledo  PMGheusi  G Olfactory processing in a changing brain. Neuroreport 2003;14 (13) 1655- 1663
PubMed Link to Article
Lledo  PMGheusi  GVincent  JD Information processing in the mammalian olfactory system. Physiol Rev 2005;85 (1) 281- 317
PubMed Link to Article
Curtis  MAKam  MNannmark  U  et al.  Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 2007;315 (5816) 1243- 1249
PubMed Link to Article
World Medical Association, World Medical Association declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. JAMA 1997;277 (11) 925- 926
PubMed Link to Article
Hummel  TSekinger  BWolf  SPauli  EKobal  G “Sniffin' Sticks”: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses 1997;22 (1) 39- 52
PubMed Link to Article
Kobal  GKlimek  LWolfensberger  M  et al.  Multicenter investigation of 1,036 subjects using a standardized method for the assessment of olfactory function combining tests of odor identification, odor discrimination, and olfactory thresholds. Eur Arch Otorhinolaryngol 2000;257 (4) 205- 211
PubMed Link to Article
Wolfensberger  MSchnieper  IWelge-Lussen  A “Sniffin' Sticks”: a new olfactory test battery. Acta Otolaryngol 2000;120 (2) 303- 306
PubMed Link to Article
Hummel  THeilmann  SHüttenbrink  KB Lipoic acid in the treatment of smell dysfunction following viral infection of the upper respiratory tract. Laryngoscope 2002;112 (11) 2076- 2080
PubMed Link to Article
Betchen  SADoty  RL Bilateral detection thresholds in dextrals and sinistrals reflect the more sensitive side of the nose, which is not lateralized. Chem Senses 1998;23 (4) 453- 457
PubMed Link to Article
Frasnelli  JLivermore  ASoiffer  AHummel  T Comparison of lateralized and binasal olfactory thresholds. Rhinology 2002;40 (3) 129- 134
PubMed
Cummings  DMKnab  BRBrunjes  PC Effects of unilateral olfactory deprivation in the developing opossum, Monodelphis domesticaJ Neurobiol 1997;33 (4) 429- 438
PubMed Link to Article
Hornung  DEKurtz  DBBradshaw  CB  et al.  The olfactory loss that accompanies an HIV infection. Physiol Behav 1998;64 (4) 549- 556
PubMed Link to Article
Jones-Gotman  MZatorre  RJ Contribution of the right temporal lobe to odor memory [abstract]. Epilepsia 1988;29 (5) 661
Moberg  PJAgrin  RGur  REGur  RCTuretsky  BIDoty  RL Olfactory dysfunction in schizophrenia: a qualitative and quantitative review. Neuropsychopharmacology 1999;21 (3) 325- 340
PubMed Link to Article
Reden  JMueller  AMueller  C  et al.  Recovery of olfactory function following closed head injury or infections of the upper respiratory tract. Arch Otolaryngol Head Neck Surg 2006;132 (3) 265- 269
PubMed Link to Article
Landis  BNHummel  TLacroix  JS Basic and clinical aspects of olfaction. Pickard  JDAdvances and Technical Standards in Neurosurgery. Vol 30 Wien, Austria Springer2005;69- 105

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 29

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles