The Insula: A Stimulating Island of the Brain

Epilepsia, 2010

Purpose: Different lines of evidence suggest that the insular cortex has many important functional roles. Direct electrical stimulation (ES) of the human insular cortex during surgical procedures for epilepsy, functional imaging techniques, and lesion studies also occasionally induces clinical responses. Methods: In this study, we evaluated 25 patients with drug-refractory focal epilepsy by stereotactically implanting at least one electrode into the insular cortex using an oblique approach (transfrontal or transparietal). One hundred twenty-eight insular sites (each situated between two contiguous contacts within the same electrode) were examined within the gyral substructures. We located each stimulation site by fusing preimplantation threedimensional (3D) magnetic resonance imaging (MRI) images with the postimplantation 3D computed tomography (CT) scans that revealed the electrode contacts.

Journal of Neurology Neurosurgery and Psychiatry, 1994

The hypothesis that focal scalp EEG and MEG interictal epileptiform activity can be modelled by single dipoles or by a limited number of dipoles was examined. The time course and spatial distribution of interictal activity recorded simultaneously by surface electrodes and by electrodes next to mesial temporal structures in 12 patients being assessed for epilepsy surgery have been studied to estimate the degree of confinement of neural activity present during interictal paroxysms, and the degree to which volume conduction and neural propagation take part in the diffusion of interictal activity. Also, intrapatient topographical correlations of ictal onset zone and deep interictal activity have been studied. Correlations between the amplitudes of deep and surface recordings, together with previous reports on the amplitude of scalp signals produced by artificially implanted dipoles suggest that the ratio of deep to surface activity recorded during interictal epileptiform activity on the scalp is around 1:2000. This implies that most such activity recorded on the scalp does not arise from volume conduction from deep structures but is generated in the underlying neocortex. Also, time delays of up to 220 ms recorded between interictal paroxysms at different recording sites show that interictal epileptiform activity can propagate neuronally within several milliseconds to relatively remote cortex. Large areas of archicortex and neocortex can then be simultaneously or sequentially active via three possible mechanisms: (1) by fast association fibres directly, (2) by fast association fibres that trigger local phenomena which in turn give rise to sharp/slow waves or spikes, and propagation along the neocortex. The low ratio of deep-to-surface signal on the scalp and the simultaneous activation of large neocortical areas can yield spurious equivalent dipoles localised in deeper structures. Frequent interictal spike activities can also take place independently in areas other than the ictal onset zone and their interictal propagation to the surface is independent of their capacity to trigger seizures. It is concluded that: (1) the deep-to-surface ratios of electromagnetic fields from deep sources are extremely low on the scalp; (2) single dipoles or a limited number of dipoles are not adequate models for interictal activity for surgical assessment; (3) the correct localisation of the onset of interictal activity does not necessarily imply the onset of seizures in the region or in the same hemisphere. It is suggested that, until volume conduction and neurophysiological propagation can be distinguished, semiempirical correlations between symptomatology, surgical outcome, and detailed presurgical modelling of the neocortical projection patterns by combined MEG, EEG, and MRI could be more fruitfil than source localisation with unrealistic source models. (JNeurolNeurosurg Psychiatry 1994;57:435-449)

Revue Neurologique, 2019

Electrical stimulations of the insula performed during stereo-electroencephalography (SEEG) reproduce the ictal symptoms observed during the development of insular seizures and are also a unique opportunity to provide a functional mapping of the insular cortex. We provide here a functional mapping of the insular cortex obtained by electrical stimulation, based on our previous work and a review of literature. The most frequent responses to insula stimulation were somatosensory sensations followed by visceral responses. Then, in decreasing order of frequency, auditory sensations, vestibular illusions, speech impairment, gustato-olfactory sensations and motor reactions were evoked. A bipolar organization could be evidenced with a posterior part assigned to somatosensory functions and notably to pain perception; and an anterior part assigned to visceral functions. Although some degree of spatial segregation could be evidenced, there was a clear spatial overlap between the representations of the different types of responses. These data provide a better understanding of physiological insular functions, insula seizures semiology and a prediction of post-surgical deficits. Insula is the only cortical region where stimulations demonstrate such a multi-modal representation, perhaps supporting its integrative functions of polymodal inputs.

Annals of Neurology, 2000

The role of the insular cortex in the genesis of temporal lobe epileptic (TLE) seizures has been investigated in 21 patients with drug-refractory TLE using chronic depth stereotactic recordings of the insular cortex activity and video recordings of ictal symptoms during 81 spontaneous electroclinical seizures. All of the recorded seizures were found to invade the insula, most often after a relay in the ipsilateral hippocampus (19/21 patients). However, 2 patients had seizures that originated in the insular cortex itself. Ictal symptoms associated with the insular discharges were similar to those usually attributed to mesial temporal lobe seizures, so that scalp video-electroencephalographic monitoring does not permit making any difference between ictal symptoms of temporo-mesial and insular discharges. A favorable outcome was obtained after a temporal cortectomy sparing the insular cortex in 15 of 17 operated patients. Seizures propagating to the insular cortex were found to be fully controlled by surgery, whereas those originating in the insular cortex persisted after temporal cortectomy. The fact that seizures originating in the insular cortex are not influenced by temporal lobectomy is likely to explain some of the failures of this surgical procedure in TLE.

Journal of Epileptology, 2015

SUMMARYThe seizure propagation phenomenon by inducing remote symptoms brings several difficulties in finding the seizure onset and delineating the epileptic network which should be taken into consideration in epilepsy surgery. By demonstrating a difficult (MRI negative) epilepsy surgery case explored with invasive presurgical evaluation we highlight the importance to recognise the secondary sensory area and to explore the the parieto-opercular-insular-medial frontal network in certain cases. A further conclusion is the consideration of the redistributory role of the insula as a special structure in the cerebral connectome, having a role in epileptic network organisation.To support the role of the insula in the organisation of an opercular – medial frontal epileptic network and to confirm Penfield’s the “second somatic sensory leg area” by way of a case report. We try to give an up to date exploration of our patient’s remote epileptic seizures by way of a connectome.The epileptic dis...

Epilepsy Currents, 2019

Insular seizures are great mimickers of seizures originating elsewhere in the brain. The insula is a highly connected brain structure. Seizures may only become clinically evident after ictal activity propagates out of the insula with semiology that reflects the propagation pattern. Insular seizures with perisylvian spread, for example, manifest first as throat constriction, followed next by perioral and hemisensory symptoms, and then by unilateral motor symptoms. On the other hand, insular seizures may spread instead to the temporal and frontal lobes and present like seizures originating from these regions. Due to the location of the insula deep in the brain, interictal and ictal scalp electroencephalogram (EEG) changes can be variable and misleading. Magnetic resonance imaging, magnetic resonance spectroscopy, magnetoencephalography, positron emission tomography, and single-photon computed tomography imaging may assist in establishing a diagnosis of insular epilepsy. Intracranial EEG recordings from within the insula, using stereo-EEG or depth electrode techniques, can prove insular seizure origin. Seizure onset, most commonly seen as low-voltage, fast gamma activity, however, can be highly localized and easily missed if the insula is only sparsely sampled. Moreover, seizure spread to the contralateral insula and other brain regions may occur rapidly. Extensive sampling of the insula with multiple electrode trajectories is necessary to avoid these pitfalls. Understanding the functional organization of the insula is helpful when interpreting the semiology produced by insular seizures. Electrical stimulation mapping around the central sulcus of the insula results in paresthesias, while stimulation of the posterior insula typically produces painful sensations. Visceral sensations are the next most common result of insular stimulation. Treatment of insular epilepsy is evolving, but poses challenges. Surgical resections of the insula are effective but risk significant morbidity if not carefully planned. Neurostimulation is an emerging option for treatment, especially for seizures with onset in the posterior insula. The close association of the insula with marked autonomic changes has led to interest in the role of the insula in sudden unexpected death in epilepsy and warrants additional study with larger patient cohorts.

Seizure, 1996

Background: Electric neurostimulation is being developed as an alternative treatment for drug-resistant epilepsy patients. A major challenge is to identify, among all possible combinations of stimulation parameters, the most effective stimulation protocol to achieve seizure control for each patient. Objective: To estimate the value of interictal intracranial EEG recordings in identifying the most effective stimulation protocol in order to decrease number of seizures during intracranial subacute cortical stimulation (SCS). Methods: Five patients undergoing SCS were included in this retrospective study. Bivariate correlation measures were applied to baseline interictal intracranial EEG recordings to infer functional correlation networks. The node strength of these networks was calculated for each recording electrode (indicating the overall correlation between activity from one electrode with the activity from all other electrodes). The relationship between node strength and the change...

Brain Sciences

Rationale: Deep brain stimulation (DBS) of several sites, such as the thalamus, has been shown to reduce seizure frequency and interictal epileptiform activity in patients with refractory epilepsy. Recent findings have demonstrated that the insula is part of the ‘rich club’ of highly connected brain regions. This pilot study investigated short-term effects of high-frequency (HF) insular DBS on interictal epileptiform discharge (IED) rate in patients with refractory epilepsy. Methods: Six patients with drug-resistant epilepsy undergoing an intracranial electroencephalographic study received two sets of 10 min continuous 150 Hz HF-DBS of the insula. For each patient, epileptiform activity was analyzed for a total of 80 min, starting 20 min prior to stimulation set 1 (S1), and ending 20 min after stimulation set 2 (S2). All IEDs were identified and classified according to their anatomic localization by a board-certified epileptologist. The IED rate during the 20 min preceding S1 served...

Brain, 2021

The identification of abnormal electrographic activity is important in a wide range of neurological disorders, including epilepsy for localizing epileptogenic tissue. However, this identification may be challenging during non-seizure (interictal) periods, especially if abnormalities are subtle compared to the repertoire of possible healthy brain dynamics. Here, we investigate if such interictal abnormalities become more salient by quantitatively accounting for the range of healthy brain dynamics in a location-specific manner. To this end, we constructed a normative map of brain dynamics, in terms of relative band power, from interictal intracranial recordings from 234 participants (21 598 electrode contacts). We then compared interictal recordings from 62 patients with epilepsy to the normative map to identify abnormal regions. We proposed that if the most abnormal regions were spared by surgery, then patients would be more likely to experience continued seizures postoperatively. We...