Synopsis
There
is intense interest in strategies for enhancing olfaction capabilities of dogs
for various applications such as bomb detection. Prior fMRI studies showed
increased neural activation when zinc nanoparticles were added to the odorants.
In this study, we obtained fMRI data from awake and unrestrained dogs when they
were exposed to odorants with and without zinc nanoparticles and zinc nanoparticles
alone. We observed that zinc nanoparticles up-regulated directional brain
connectivity in parts of the canine olfactory network. This provides a
mechanistic explanation for previously reported enhancement in the odor detection
capability of the dogs in the presence of zinc nanoparticles.Introduction
Olfactory
capability in canines is far superior to many other mammals including human
beings. Utilization of dogs for detecting different materials in the environment
either for detecting explosives
1 or tracking people
2 is
owed to this long established fact.However one should note that odor detection
in general is restricted by the concentration
3 of the odorant
present in that environment. In many real scenarios, target odor concentrations
can be below even for the dog’s detection threshold. Therefore other possible ways
of enhancing odor-related response in the dogs are being actively investigated.
Recently studies have shown how presence of zinc nanoparticles might enhance
odorant responses of olfactory receptor neurons in vitro
4,5,6 as well as enhance fMRI-based activation in
the dog brain in vivo
7. Given
that the odorants initiate a response cascade in the olfactory network, we
hypothesized that a mechanistic explanation for previously reported increased
brain activation may be provided by brain connectivity enhancement in the
olfactory network of dog brains in the presence of zinc nanoparticles.
Method
Functional
magnetic resonance imaging (fMRI) data was obtained from eight dogs trained to
stay awake, still and unrestrained in the MRI scanner while being exposed to
the stimulus of odorants via a computer controlled device as described in Jia et
al
7. Functional data were obtained from a MAGNETOM Verio 3T scanner( Siemens Healthcare, Erlangen, Germany) and a TX/RX 15 channel knee coil(
QED, Ohio, USA) using an EPI sequence with the following parameters: repetition time (TR) = 1000 ms, echo time
(TE) = 29 ms, field of view (FOV) = 192×192 mm
2, flip angle (FA) = 90 degree, in-plane
resolution 3×3 mm, in-plane matrix 64×64, and whole brain coverage.
Anatomical data was obtained for registration purposes using an MPRAGE sequence
with the following parameters: TR = 1550
ms, TE = 2.64 ms, voxel size: 0.792×0.792×1 mm
3, FA = 9°, and in-plane matrix 192×192,
FOV = 152×152 mm
2, number of slices: 104. As noted in Jia et al
7,
odorants were delivered using a custom built computer controlled device and an
external infra-red camera was used to track head motion in dogs and
retrospectively correct for motion artifacts in the data. The odorant used in
the study was a mixture of ethyl butyrate, eugenol, and (+) and (−) carvone in
water at a concentration of 0.016 mM
7. The block design paradigm
consisted of alternating blocks of odor conditions and rest
7. We
obtained different runs with each of the following odor conditions: Odorants+zinc
nanoparticles, odorants alone, water+ zinc nanoparticles, water vapor alone. After
standard pre-processing and a custom registration procedure for aligning data
from all dogs in a common space as reported before in Jia et al
8,
activation analysis was performed in SPM8
9. Mean time series from
activated regions (reported in Jia et al
7) were extracted and subjected
to blind hemodynamic de-convolution using a cubature Kalman filter and smoother
10 to
obtain the underlying latent neural variables. Directional brain connectivity
between the ROIs was then obtained for each condition using Dynamic Granger
causality(DGC) by using the analyses framework reported before
11,12.
Using two sample t-tests, connectivity was compared for the condition of
Odor+zinc(OZ) against the conditions of odor(O) ,water+zinc(WZ) and water(W).
Results
and Discussion
The paths with
corrected p<0.05 for the condition of OZ > (O,WZ,W) were obtained as
shown in the Table.1 and Fig.1. The olfaction process starts with triggering of
an action potential in the olfactory receptor neurons
13 that projects
onto the olfactory bulb (OB)
14. Then the signal is transmitted to
the piriform lobe, andentorhinal cortex via olfactory stria. The signal then
travels to various other structures such as the thalamus, frontal cortex,
caudate and hippocampus for further interpretation
15 and recognition
16,
17. It is noteworthy that the paths are not strictly unidirectional and
various feedback loops exist for top-down modulation. We observed that many of
these paths were significantly strengthened in the presence of zinc
nanoparticles compared to other control conditions. This demonstrates that when
zinc nanoparticles are added to the odorants, they up-regulate directional brain
connectivity in parts of the canine olfactory network, thereby enhancing odor
detection capability in dogs.
Acknowledgements
The authors acknowledge financial support for this work from Auburn University Intramural Level-3 research grant from the Office of the Vice President for Research, Auburn University. This work was also supported by the Defense Advanced Research Projects Agency (government grant/contract number W911QX-13-C-0123). The views, opinions, and/or findings contained in this article are those of the authors and should not be interpreted as representing the official views or policies, either expressed or implied, of the Defense Advanced Research Projects Agency, US Department of Defense or the federal Government of the United States of America. References
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