The Claustrum in Relation to Seizures and Electrical Stimulation

Abstract

The neural mechanisms of altered consciousness that accompanies most epileptic seizures are not known. We have reported alteration of consciousness resulting from electrical stimulation of the claustrum via a depth electrode in a woman with refractory focal epilepsy. Additionally, there are reports that suggest possible claustral involvement in focal epilepsy, including MRI findings of bilaterally increased T2 signal intensity in patients with status epilepticus (SE). Although its cytoarchitecture and connectivity have been studied extensively, the precise role of the claustrum in consciousness processing, and, thus, its contribution to the semiology of dyscognitive seizures are still elusive. To investigate the role of the claustrum in rats, we studied the effect of high-frequency stimulation (HFS) of the claustrum on performance in the operant chamber. We also studied the inter-claustral and the claustro-hippocampal connectivity through cerebro-cerebral evoked potentials (CCEPs), and investigated the involvement of the claustrum in kainate (KA)-induced seizures. We found that HFS of the claustrum decreased the performance in the operant task in a manner that was proportional to the current intensity used. In this article, we present previously unpublished data about the effect of stimulating extra-claustral regions in the operant chamber task as a control experiment. In these animals, stimulation of the corpus callosum, the largest interhemispheric commissure, as well as the orbitofrontal cortex in the vicinity of the claustrum did not produce that same effect as with claustral stimulation. Additionally, CCEPs established the presence of effective connectivity between both claustra, as well as between the claustrum and bilateral hippocampi indicating that these connections may be part of the circuitry involved in alteration of consciousness in limbic seizures. Lastly, some seizures induced by KA injections showed an early involvement of the claustrum with later propagation to the hippocampi. Further work is needed to clarify the exact role of the claustrum in mediating alteration of consciousness during epileptic seizures.

Keywords: attention; connectivity; dyscognitive seizures; electrical stimulation; kainic acid.

Figure 1

Cerebro-cerebral evoked potentials (CCEPs) obtained by stimulating the left claustrum at 800 μA (0.1 Hz, 500 μs). (A) The right claustral CCEP with first negative (N1) peak latency of 12 ms and amplitude of 328 μA. (B) Left hippocampal response with a smaller amplitude of N1 (91 μA), though with same N1 latency at 12 ms. (C) Right hippocampal response (N1 peak: 85 μA; latency: 16 ms). From Bayat et al. (2018)—with permission.

Figure 2

Electrical stimulation of the left claustrum in a patient with intractable epilepsy. (A) AI4 contact represented as a red circle, when stimulated elicited impairment of consciousness. (B) Representation of 15 selected bipolar channels. Z-scores are used for estimating the variations of h2 coefficients relative to the prestimulation period. Blue circle: two randomly chosen AI4 stimulations. One causes disruption of consciousness. Red cross: two randomly chosen AI4 stimulations that did not interfere with consciousness at lower current intensities. Significant variations are shown in medial parietal (MP) channels and posterior frontal (PF) channels. AF, anterior frontal; MF, medial frontal. From Koubeissi et al. (2014)—with permission.

Figure 3

Claustrum as the seizure onset zone: representative electroencephalography (EEG) indicating the onset of seizure in the right claustrum and propagating to the bilateral hippocampi. From Connell et al. (2017)—with permission.

Figure 4

Effects of claustrum stimulation on rat performance in the operant chamber: in the above plot x- and y-axes represent the stimulation current intensity and percentage points of effect size, respectively. In experimental group the electrodes were installed in bilateral claustra. In control group the electrodes were placed in corpus callosum, orbital cortex and frontal cortex (unpublished). GEE analysis in experimental group showed that there was significant decline in the performance score in unilateral and bilateral stimulation at 600–1,000 μA compared with the rest sessions score (p < 0.001). In the control group (unpublished) there was not any significant decline in performance at these current intensities in comparison to the rest session (p > 0.05). Modified from (Bayat et al., 2018)—with permission.