Elsevier

NeuroImage

Volume 59, Issue 2, 16 January 2012, Pages 1052-1057
NeuroImage

Is there a correlation between hippocampus and amygdala volume and olfactory function in healthy subjects?

https://doi.org/10.1016/j.neuroimage.2011.09.024Get rights and content

Abstract

Both amygdala (AG) and hippocampus (HC) are integral parts of the olfactory system. The present study, including a large number of healthy subjects, was performed to compare HC and AG volumes, measured by manual tracing, in relation to specific olfactory functions, including odor threshold, discrimination, identification, and odor memory tasks. It also aimed to provide age-related normative data about the volume of the HC and AG.

A total of 117 healthy volunteers participated (age range 19–77 years, mean age 37 years; 62 women, 55 men). Using the “Sniffin' Sticks”, subjects received lateralized tests for odor threshold, and odor discrimination. In addition, an odor memory and an odor identification task were performed bilaterally. A Mini-Mental-State test excluded dementia. MR scans were performed using a 1.5 T scanner for later manual volumetric measurements.

Volumetric measurements exhibited a good reproducibility. The average volume for the right HC was 3.29 cm3 (SD 0.47), for the left HC it was 3.15 cm3 (SD 0.47). The average right AG had a volume of 1.60 cm3 (SD 0.31), left 1.59 cm3 (SD 0.3). Increasing age was accompanied by a decrease of HC and AG volumes, which were much more pronounced for the right compared to the left side. Only the volume of the right HC showed a small but significant correlation with odor threshold (r117 = 0.21; p = 0.02). Importantly, this correlation was not mediated by age as indicated by the significant partial correlation when controlling for age (r114 = 0.18; p = 0.049).

In conclusion, the present data obtained in a relatively large group of subjects demonstrates a small correlation between the volume of the HC, as an integral part of the olfactory system, and smell function. In addition, these data can be used as the basis for normative values of HC and AG volumes, separately for men, women and different age groups. This is of potential interest in diseases with acute or chronic impairment of olfactory function, in metabolic or neurodegenerative diseases or in disorders with damage of areas involved in adult neurogenesis.

Highlights

► We investigated amygdala and hippocampus volume in relation to olfactory functions. ► The study was performed in 117 healthy volunteers (age 19-77 years, 62 w, 55 m). ► Only the right hippocampus correlated with odor threshold (r117 = 0.21; p = 0.02).

Introduction

In the adult mammal brain production of new neurons is almost limited to two particular regions, the hippocampus (HC) and the subventricular zone (Amrein and Lipp, 2009, Eriksson et al., 1998, Lee and Son, 2009). Concerning the latter, neurons derive from the walls of the lateral ventricles and migrate to the olfactory bulb (OB) (for a schematic representation of the olfactory system see Fig. 1). This has been shown in animals and in humans (Curtis et al., 2007). The OB, which is the first relay station in the olfactory pathway, remains highly plastic throughout adult life. This has been shown by animal studies with olfactory deprivation. These animals had a reduction in OB volume due to the decreased number of cells (Cummings et al., 1997, Korol and Brunjes, 1992). In humans a significant correlation between OB volumes in relation to olfactory function was observed. This was shown to be independent of the subjects' age, although OB volumes decreased with age (Buschhüter et al., 2008, Yousem et al., 1997).

Other neurons proliferate in the subgranular layer and differentiate into dentate gyrus cells of the HC. The hippocampal formation plays a prominent role in learning and memory, in spatial navigation and control of attention (Sahay and Hen, 2007). It is not an integral part of the primary olfactory cortex, but it receives strong afferent input from the entorhinal cortex. In contrast, the neighboring amygdalae (AG) are part of the primary olfactory cortex (Gottfried et al., 2002).

The size and structural plasticity of HC and AG have been previously studied in patients with Alzheimer dementia (Barnes et al., 2009, Horínek et al., 2007, Teipel et al., 2008), in temporal lobe epilepsy (Akhondi-Asl et al., 2011, Mechanic-Hamilton et al., 2009, Pardoe et al., 2009, Scorzin et al., 2008), in multiple sclerosis (Anderson et al., 2010), in schizophrenia (Klaer et al., 2010, Teipel et al., 2010), in aphasia after middle cerebral artery stroke (Meinzer et al., 2010), in autism spectrum disorder (Zeegers et al., 2009), in depression (Tae et al., 2008, van Eijndhoven et al., 2009), in acute psychosis (Velakoulis et al., 2006), in patients with bipolar disorder (Doty et al., 2008), and also in subjects with olfactory loss (Yousem et al., 1996a, Yousem et al., 1996b). However, these studies included either only a small control group or no controls at all. Most studies use automated volumetric measurements (e.g. FreeSurfer, Individual Brain Atlases using Statistical Parametric Mapping) or auto-assisted manual tracings. The results in these studies displayed significant variations in terms of volume. For example AG volumes were published ranging from 1.15 cm3 on the left side and 1.16 cm3 on the right side (Pruessner et al., 2000) to 3.34 cm3 on the left side and 3.44 cm3 on the right side (Watson et al., 1992). Studies showing smaller volumes of the AG (between 1 and 2 cm3) are supported by an anatomical study which showed an average size of the classic AG of 1.24 cm3 and in the AG with another definition of the anterior pole boundaries of 1.63 cm3. The volume was measured using planimetry based on Nissl-stained serial sections (Brabec et al., 2010).

The present study, including a large number of healthy subjects, was performed to compare HC and AG volumes, measured by manual tracing, in relation to specific olfactory functions. It also aimed to provide age-related normative data about the volumes of the HC and AG. These normative data for different decades of life would be necessary to realize the idea of volumetry of the HC and the AG as a tool which may help to assess stage and course of diseases associated with olfactory loss.

Section snippets

Volunteers and study design

A total of 117 randomly selected, subjectively normosmic individuals (55 men and 62 women), aged 19 to 79 years (mean ± standard deviation = 37 ± 17 years), participated in this study. The investigations were performed in accordance to the Declaration of Helsinki on Biomedical Studies Involving Human Subjects (World Medical Association, 1997). The study design was approved by the University of Dresden Medical Faculty Ethics Review Board (number EK 239112006). All subjects provided written informed

Volumetric measures of HC and AG

Interindividual variations in AG and HC volumes were relatively large, ranging from 2.09 cm3 to 4.49 cm3 for right HC volumes and from 1.8 cm3 to 4.45 cm3 for left HC volumes. The volumes for the right AG ranged from 0.21 cm3 to 2.67 cm3 and for the left AG from 0.97 to 2.75 cm3. Mean volumes for the entire brain were 1270 cm3 for women (SD 113.44) and 1445 cm3 for men (SD 122.26). In contrast, intraindividual variation was relatively small (correlation between left-sided and right-sided HC volumes: r117

Discussion

In agreement with previous research the data in the present study confirmed the range of HC and AG volumes measured by volumetric MRI-analysis from other groups and by anatomical studies (Brabec et al., 2010, Pruessner et al., 2000). The volume of the HC was in excellent accordance with other authors (Pruessner et al., 2000). Local adaptations of the proposed protocol had no major influence on the overall results. This is strong support for applying the protocol as guideline for measurements of

Acknowledgments

Supported by the DDELTAS (Dijon-Dresden European Laboratories for Taste and Smell — LEA 549), underwritten by the Centre National de la Recherche Scientifique-Paris and the Technische Universität Dresden, and awarded to BS and TH.

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