Microelectrode recordings in human epilepsy: a case for clinical translation

Abstract

With their 'all-or-none' action potential responses, single neurons (or units) are accepted as the basic computational unit of the brain. There is extensive animal literature to support the mechanistic importance of studying neuronal firing as a way to understand neuronal microcircuits and brain function. Although most studies have emphasized physiology, there is increasing recognition that studying single units provides novel insight into system-level mechanisms of disease. Microelectrode recordings are becoming more common in humans, paralleling the increasing use of intracranial electroencephalography recordings in the context of presurgical evaluation in focal epilepsy. In addition to single-unit data, microelectrode recordings also record local field potentials and high-frequency oscillations, some of which may be different to that recorded by clinical macroelectrodes. However, microelectrodes are being used almost exclusively in research contexts and there are currently no indications for incorporating microelectrode recordings into routine clinical care. In this review, we summarize the lessons learnt from 65 years of microelectrode recordings in human epilepsy patients. We cover the electrode constructs that can be utilized, principles of how to record and process microelectrode data and insights into ictal dynamics, interictal dynamics and cognition. We end with a critique on the possibilities of incorporating single-unit recordings into clinical care, with a focus on potential clinical indications, each with their specific evidence base and challenges.

Keywords: extracellular action potential; microelectrode; single units; stereoelectroencephalography; subdural grid.

Graphical Abstract

Figure 1

Concepts of the ictal ‘core’ and ‘penumbra’. Schematic representation illustrating the concepts of the ictal ‘core’ and ‘penumbra’, both areas of ictal activity on macroelectrode LFP recordings that lie within the clinically defined SOZ. The ictal onset zone has not been convincingly recorded on MEA recordings but propagation from that onset area to the core territory is facilitated by the ‘ictal wavefront’. The core is characterized by intense unit activity as it becomes recruited, whilst the penumbra may display the same LFP activity but corresponding intense unit activity is not present. Phase-locked high-gamma oscillations have been shown to be a marker of the ‘core’, with the resection of this region correlated with outcome. Adapted from Weiss et al. (2013) with permission (Schevon et al., 2012; Smith et al., 2016).

Figure 2

Current understanding of network concepts in focal epilepsy. Schematic representation of our current understanding of network concepts in focal epilepsy, which has largely been informed by network analyses of imaging and intracranial EEG recordings. The schema breaks down the brain regions (nodes) into groups based on a hierarchical classification of epileptogenicity into the SOZ networks (areas involved in seizure generation), propagation networks (less epileptogenic areas involved in seizure spread) and not involved networks. Adapted from Bartolomei et al. (2017) with permission.

Figure 3

Paradigms of network concepts in epilepsy surgery. Schematic representation of current paradigms of network concepts of epilepsy surgery, illustrating a normal network (A), an epileptogenic network (B) as in Fig. 2 that results in both seizures and associated comorbidities including cognitive, psychological and social problems. In terms of treatments, current surgical treatments (C) are focused heavily on addressing the seizures, which may have some impact on the cognitive and developmental aspects but we envisage a future where surgical and non-surgical treatments are individually tailored to push the network towards normal dynamics (D), concurrently addressing all facets of the disease. Adapted from Bartolomei et al. (2017) with permission (Lenck-Santini and Scott, 2015; Scott, 2016).