Review ArticleAnatomical imaging of the piriform cortex in 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.
References (128)
- et al.
Voxel-based morphometry—the methods
NeuroImage
(2000) - et al.
Review: neurons and circuits for odor processing in the piriform cortex
Trends Neurosci.
(2013) - et al.
Structural changes in the temporal lobe and piriform cortex in frontal lobe epilepsy
Epilepsy Res.
(2014) - et al.
Afferent projections to the dorsal thalamus of the rat as shown by retrograde lectin transport—I
The mediodorsal nucleus. Neuroscience
(1988) - et al.
Invited review: the pilocarpine model of temporal lobe epilepsy
J. Neurosci. Methods
(2008) - et al.
Retrograde and anterograde tracing combined with transmitter identification and electron microscopy
J. Neurosci. Methods
(2000) Chapter 2 - the structure and connections of the claustrum
- et al.
Report: recurrent circuitry dynamically shapes the activation of piriform cortex
Neuron
(2011) - et al.
Review: on the scent of human olfactory orbitofrontal cortex: meta-analysis and comparison to non-human primates
Brain Res. Rev.
(2005) - et al.
Automated 3-D extraction and evaluation of the inner and outer cortical surfaces using a Laplacian map and partial volume effect classification
Neuroimage
(2005)
Earlier seizure onset and longer epilepsy duration correlate with the degree of temporal hypometabolism in patients with mesial temporal lobe sclerosis
Epilepsy Res.
The role of the piriform cortex in kindling
Prog. Neurobiol.
Insular interconnections with the amygdala in the rhesus monkey
Neuroscience
Brain Mechanisms for Extracting Spatial Information from Smell
Three-dimensional neuron tracing by voxel scooping
J. Neurosci. Methods
The central piriform cortex: anatomical connections and anticonvulsant effect of gaba elevation in the kindling model
Neuroscience
Olfactory Cortex
Serotonin modulation of cortical neurons and networks
Frontiers in Integrative Neuroscience, Vol
Olfactory information converges in the amygdaloid cortex via the piriform and entorhinal cortices: observations in the guinea pig isolated whole-brain preparation
European Journal of Neuroscience
Olfactory epileptic auras
Neurology
The secondary olfactory areas in the human brain
J. Anat.
In vivo high angular resolution diffusion-weighted imaging of mouse brain at 16.4 Tesla
PLoS One
Multiple Sources of Conscious Odor Integration and Propagation in Olfactory Cortex
Comparative organization of the claustrum: what does structure tell us about function?
Front. Syst. Neurosci.
Olfactory perceptual stability and discrimination
Nat. Neurosci.
Regional Connections of the Mediodorsal Thalamic Nucleus in the Rat
Intrinsic and efferent connections of the endopiriform nucleus in rat
J. Comp. Neurol.
Mesial temporal damage in temporal lobe epilepsy: a volumetric MRI study of the hippocampus, amygdala and parahippocampal region
Brain
Locus Coeruleus Activation Modulates Firing Rate and Temporal Organization of Odour-Induced Single-Cell Responses in Rat Piriform Cortex
The claustrum in review
Frontiers in Systems Neuroscience, Vol
Men may be more vulnerable to seizure-associated brain damage
Neurology
Effect of stage 2 kindling on local cerebral blood flow rates in rats with genetic absence epilepsy
Epilepsia
Geodesic information flows: spatially-variant graphs and their application to segmentation and fusion
IEEE Trans. Med. Imaging
Central Olfactory Connections in the Macaque Monkey
Temporal lobe epilepsy caused by domoic acid intoxication: evidence for glutamate receptor-mediated excitotoxicity in humans
Ann. Neurol.
Olfactory auras in patients with temporal lobe epilepsy
Epilepsia
Proust nose best: odors are better cues of autobiographical memory
Mem. Cogn.
Dynamic cortical lateralization during olfactory discrimination learning
J. Physiol.
The olfactory thalamus: unanswered questions about the role of the mediodorsal thalamic nucleus in olfaction
Frontiers In Neural Circuits
Neural Circuit Mechanisms for Pattern Detection and Feature Combination in Olfactory Cortex
Visualization of the amygdalo-hippocampal border and its structural variability by 7T and 3T magnetic resonance imaging
Hum. Brain Mapp.
The claustrum: considerations regarding its anatomy, functions and a programme for research
Brain and Neuroscience Advances
Functional brain mapping at 9.4T using a new MRI-compatible electrode chronically implanted in rats
Magn. Reson. Med.
Neuronal and glial cell populations in the piriform cortex distinguished by using an approximation of q-space imaging after status epilepticus
Am. J. Neuroradiol.
A new subdivision of anterior piriform cortex and associated deep nucleus with novel features of interest for olfaction and epilepsy
J. Comp. Neurol.
Status epilepticus–induced neuronal loss in humans without systemic complications or epilepsy
Epilepsia
Progression and generalization of seizure discharge: anatomical and neurochemical substrates
Epilepsia
Association of Piriform Cortex Resection With Surgical Outcomes in Patients With Temporal Lobe Epilepsy
Pre- and postsynaptic activation of GABAB receptors modulates principal cell excitation in the piriform cortex
Front. Cell. Neurosci.
Sensory maps in the olfactory cortex defined by long-range viral tracing of single neurons
Nature
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This manuscript is part of a special issue “The Piriform Cortex in Epilepsy”.