The piriform cortex and human focal epilepsy

Abstract

It is surprising that the piriform cortex, when compared to the hippocampus, has been given relatively little significance in human epilepsy. Like the hippocampus, it has a phylogenetically preserved three-layered cortex that is vulnerable to excitotoxic injury, has broad connections to both limbic and cortical areas, and is highly epileptogenic - being critical to the kindling process. The well-known phenomenon of early olfactory auras in temporal lobe epilepsy highlights its clinical relevance in human beings. Perhaps because it is anatomically indistinct and difficult to approach surgically, as it clasps the middle cerebral artery, it has, until now, been understandably neglected. In this review, we emphasize how its unique anatomical and functional properties, as primary olfactory cortex, predispose it to involvement in focal epilepsy. From recent convergent findings in human neuroimaging, clinical epileptology, and experimental animal models, we make the case that the piriform cortex is likely to play a facilitating and amplifying role in human focal epileptogenesis, and may influence progression to epileptic intractability.

Keywords: EEG-fMRI; area tempestas; claustrum; intracranial electrodes; olfaction; olfactory aura; pyriform; temporal lobe epilepsy.

Figure 1

Anatomical location of the piriform cortex. Nissl stained coronal brain slice at the level of the anterior commissure of a 65-year-old woman, from the BigBrain dataset (9). Labels were placed with reference to Mai et al. (7): ac, anterior commissure; PirF, frontal piriform cortex; PirT, temporal piriform cortex; Cl, claustrum; Unc, uncus; Ent, entorhinal cortex.

Figure 2

The “piriform axis”. T1-weighted MPRAGE image of a 37-year-old man, displayed in a (A) para-sagittal and (B) oblique-axial orientation, approximately +20° relative to the anterior commissure-posterior commissure axis. This orientation allows the relationship between the piriform cortex (Pir), amygdala (Am), and hippocampus (Hip) to be seen. The arrow indicates the position of the middle cerebral artery within the endorhinal sulcus.

Figure 3

Comparison of piriform cortex activation in EEG-fMRI studies of focal epilepsy. (A) Group EEG-fMRI analysis for a mixed cohort of focal epilepsy at threshold p < 0.001 (n = 19). (B) Group EEG-fMRI random effects analysis for a mixed epilepsy cohort (n = 27) showing p-values <0.05 FWE corrected. Reproduced from Flanagan et al. (153) with permission from Elsevier. (C) Group EEG-fMRI analysis of a purely TLE cohort (n = 32), with hemodynamic response function peaking at 5 s (p < 0.05 cluster corrected). Reproduced from Fahoum et al. (154) with permission from Wiley Periodicals, Inc. ©2012 International League against Epilepsy.

Figure 4

Clinical imaging of a patient with possible piriform epilepsy. (A) Lateral skull X-ray showing positions of intracranial electrodes. RF, right frontal subdural electrodes; RT, right temporal subdural electrode strip; RHip, right hippocampal depth electrode; RAm, right amygdala depth electrodes; RPir, right piriform electrodes; ROF, right orbitofrontal subdural electrodes; LT, left temporal subdural electrode strip. (B) CT performed in the piriform axis showing the position of the most inferomesial RPir electrode contact, in orbitofrontal cortex adjacent to frontal piriform cortex. (C) Coronal T1-weighted MRI, showing posterior extent of surgical resection, with removal of right frontal piriform cortex. (D) EEG recorded from most inferomesial RPir electrode, showing trains of inter-ictal spiking, and (E) a seizure from sleep, with progressively building discharges, then gamma activity and attenuation, followed 7 s later by an evolving ictal rhythm. At the “clinical onset,” there was explosive onset of screaming and flailing movements of the limbs.