Single-Neuron Recordings Research in Children: Ethical Considerations, Feasibility, Technical Aspects, and Scientific Opportunities

Abstract

Background: Human intracranial recordings and single-neuron recordings in particular have provided much knowledge on the mechanisms of human cognition and its impairment by disease. Improvements in recording technology, experimental design, and computational analysis methods have permitted an increasingly sophisticated understanding of uniquely human brain processes, including those underlying executive function, memory, and language. Despite the routine clinical use of intracranial recordings for invasive epilepsy monitoring in the pediatric population, there remains a significant gap between the associated research conducted in adult and pediatric neuroscientific investigation.

Summary: Single-neuron recordings in pediatric epilepsy patients are ethical, technically feasible, and safe. These data can provide mechanistic insights into the neurophysiology of the developing human brain.

Key messages: Routine use of invasive electrophysiological monitoring via stereoelectroencephalography studies in pediatric drug-resistant epilepsy offers opportunities to extend the utility of single-neuron recordings to the pediatric population and advance our knowledge of the neuronal basis of behaviors in children.

Keywords: Cognitive control; Human single neurons; Intracranial recordings; Neuroethics; Pediatrics.

Fig. 1.

Evolution of intracranial neurophysiological research in adult and pediatric populations (1950–2024). PubMed database was searched to survey the number of publications for each recording technique from 1950 – 2024. A). The number of publications involving stereoelectroencephalography (SEEG) was obtained from the PubMed database and is shown using bars, with pediatric-focused SEEG studies indicated as a subset of the total. To compare the evolution of intracranial research with non-invasive neurophysiology techniques, the number of publications using electroencephalography (EEG, excluding SEEG and ECoG studies) and functional MRI (fMRI) are displayed as line plots. B). The number of Electrocorticography (ECoG)-related publications was gathered from the PubMed database and is shown as bar plots, with pediatric-specific ECoG publications highlighted within the total. EEG (excluding SEEG and ECoG studies) and fMRI publication trends are plotted as lines to provide a comparison of the evolution of intracranial research vs non-invasive techniques.

Fig. 2.

Surgical workflow for patients with drug-resistant epilepsy (DRE). Phase 2 invasive monitoring for DRE is indicated in cases with either a lack of concordance between structural imaging (such as MRI) and noninvasive (scalp) electrophysiology, or when there is evidence of seizure onset laterality/focality on EEG, but no identifiable focus on structural or functional neuroimaging. These phase 2 patients undergo intracranial electrode implantation for high resolution sampling of parenchymal activity, providing opportunity for research investigation during the associated hospital stay (see text for details). Abbreviations: SEEG stereoelectroencephalography; SDG subdural grid electrodes; RXN resection; RNS responsive neurostimulation.

Fig. 3.. Behnke-Fried recording electrode.

(A) The Behnke-Fried electrode is a hybrid electrode consisting of a hollow outer probe with macro-contacts (top probe) through which a bundle of microwires can be inserted (bottom probe). (Inset) Magnified view of the assembled electrode with the micro-wires splaying out of the tip of the macro-electrode probe. (B) Illustration of the loaded Behnke-Fried electrode. (from left-to-right): splay of microwires that record single neuron activity, black bars denote macro-contacts in the brain, large gray bars denote output of the macro-signals which connect to the clinical and research systems, small gray bars denote output of the microwires which connect to the research system. (C) A Post-operative CT fused with a pre-operative MRI depicts two Behnke-Fried electrodes targeting the anterior cingulate. (D) Illustrative depiction of recording locations displayed on an Atlas brain in MNI152-space [114]. yellow=pre-Supplementary Motor Area, blue=dorsal Anterior Cingulate Cortex, purple=Orbitofrontal Cortex)