Elsevier

Experimental Neurology

Volume 320, October 2019, 113013
Experimental Neurology

Review Article
Anatomical imaging of the piriform cortex in epilepsy

https://doi.org/10.1016/j.expneurol.2019.113013Get rights and content

Highlights

  • The piriform cortex is critically involved in a variety of epilepsy networks

  • Studying the anatomy of the piriform cortex in animals compared to humans is crucial to understanding its role in epilepsy

  • Imaging reveals distinct anatomical changes in the piriform cortex in human epilepsies as well as animal models

Abstract

The piriform cortex is a distinct brain region that plays a key role in the sense of smell. The piriform cortex is the major part of primary olfactory cortex and has broad connections that extend beyond the olfactory regions into limbic and fronto-temporal cortical networks. Numerous studies have described these anatomical connections via microscopic imaging and tracer studies. More recently, macroscopic anatomical imaging studies have demonstrated changes in the piriform cortex in humans with focal epilepsy as well as in animal models, suggesting this brain region can play a critical role in epileptogenesis. This review examines the imaging methods and techniques that have been most informative, leading to our current understanding of the anatomy and subdivsions of the piriform cortex as well as its connections to other brain structures, and the abnormalities that can be detected in the setting of epilepsy.

Introduction

The piriform cortex is a phylogenetically old brain region that plays a key role in our sense of smell. Piriform cortex is the largest component of primary olfactory cortex (Haberly, 1985; Haberly and Price, 1978; Löscher and Ebert, 1996). Confusingly the terms “prepiriform” and “prepyriform” have also been used to refer to the entire piriform cortex (Allison, 1954) or just the anterior piriform cortex (Klockgether et al., 1989). Primary olfactory cortex is defined by receiving direct input from the lateral olfactory tract. In addition to the piriform cortex this comprises the anterior olfactory nucleus, olfactory tubercle, periamygdaloid cortex and the anterior part of the entorhinal cortex (Carmichael et al., 1994). Extending beyond the piriform cortex, the broader olfactory network includes orbitofrontal cortex, thalamus and insular cortex (Shipley and Reyes, 1991) as well as interactions with other major cognitive networks. It has unique anatomical and functional properties that enable this role, but these very features may also predispose the piriform cortex to critical involvement in focal epilepsy. In this review we provide an overview of the anatomical location and subdivisions of the piriform cortex, its histological structure observed via staining, and its anatomical connections revealed through microscopic anatomical imaging. We also describe the various macroscopic imaging methods implemented in the study of the piriform cortex in epilepsy including magnetic resonance imaging (MRI) and nuclear medicine. Finally we discuss the key findings of these macroscopic anatomical imaging studies of humans with epilepsy and epilepsy animal models involving the piriform cortex.

Section snippets

Overview of piriform cortex and subdivisions

In humans, the piriform cortex is situated at the intersection of the frontal and temporal lobes, medial to the temporal stem (Mai, 2008), where it lines the superior and inferior banks of the entorhinal sulcus. It has a U-shaped cross section in coronal sections curving around the middle cerebral artery. It is a relatively small structure in humans, but relatively larger in mammals, where it was named for its pear-shaped appearance (Löscher and Ebert, 1996).

Piriform cortex can be divided into

Microscopic anatomical imaging of the piriform cortex

Microscopic imaging of the piriform has informed us about its cellular structure and neuronal connectivity. The piriform cortex has a distinct trilaminar structure (Fig. 2) (Haberly, 1985) consisting of highly interconnected pyramidal cells, inhibitory GABAergic interneurons and a horizontal arrangement of fiber projections.

Photomicrographs were originally used to visualize the various neurons of the piriform cortex (Haberly, 1985) however modern techniques typically utilize confocal or

Anatomical methods to reveal piriform cortex connectivity

Neuronal tracing studies are the basis of our current understanding of the cellular connectivity of the piriform cortex. Anterograde tracing defines axonal projections from their source (soma) to their termination point (synapse) whilst retrograde tracing traces axonal projections from their synapse to their axon (Deller et al., 2000). Either molecular (e.g. Cholera toxin subunit B (CTB), Flurogold (FG), Horseradish Peroxidase (HRP)), genetic, viral or synthetic microspheres can be injected

Macroscopic anatomical imaging of the piriform cortex

There have been various imaging methods applied to analyse the macroscopic anatomical changes of the piriform cortex in epilepsy. These include magnetic resonance (MR) volumetric analysis, diffusion weighted MRI and nuclear medicine methods. The following section considers the approach and protocols for these imaging techniques and how they are best tailored to evaluate the piriform cortex.

Piriform cortex imaging findings associated with epilepsy

The various imaging studies conducted on the piriform cortex in epilepsy have provided insight into its morphological changes and potential early involvement in focal epilepsies as well as its possible contributions to absence epilepsy. The following section describes the current findings of direct anatomical changes to the piriform cortex in epilepsy, epileptic lesions of the piriform cortex and neurodegeneration of the piriform cortex following status epilepticus.

Future directions and conclusions

Macroscopic anatomical imaging findings demonstrate significant anatomical changes in the piriform cortex and neighbouring regions, specifically in focal epilepsy. Microscopic imaging methods, on the other hand, reveal the broad connections the piriform cortex displays to various limbic structures and cortical regions making it well-placed for seizure propagation. Whilst there have been recent improvements in volumetric analysis of the piriform cortex, future imaging studies should endeavour to

Declaration of Competing Interest

None.

Acknowledgments

The Florey Institute of Neuroscience and Mental Health acknowledges the strong support from the Victorian Government and in particular the funding from the Operational Infrastructure Support Grant. This study was supported by the National Health and Medical Research Council of Australia (NHMRC Project Grant 1091593). James C Young acknowledges that they have been supported through an Australian Government Research Training Program Scholarship.

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    This manuscript is part of a special issue “The Piriform Cortex in Epilepsy”.

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