Towards large-scale, human-based, mesoscopic neurotechnologies

Abstract

Direct human brain recordings have transformed the scope of neuroscience in the past decade. Progress has relied upon currently available neurophysiological approaches in the context of patients undergoing neurosurgical procedures for medical treatment. While this setting has provided precious opportunities for scientific research, it also has presented significant constraints on the development of new neurotechnologies. A major challenge now is how to achieve high-resolution spatiotemporal neural recordings at a large scale. By narrowing the gap between current approaches, new directions tailored to the mesoscopic (intermediate) scale of resolution may overcome the barriers towards safe and reliable human-based neurotechnology development, with major implications for advancing both basic research and clinical translation.

Figure 1. Dimensions of spatial and temporal resolution in human neurophysiology

Axes not drawn to scale. Large-scale ‘micro-ECoG’ may play an important role in advancing intermediate meso-scale, multi-scale neurophysiological recordings. Note that coverage (spatial extent) is just as important as spatial resolution. Adapted from Sejnowski et al., 2014.

Figure 2. Implanted intracranial electrodes superimposed on 3D reconstruction of the cerebrum

A. Electrode position and relative size in red. Standard 1 cm spaced array over frontal lobe (20 electrode), and ‘high-density’ 4mm array over the lateral cortex covering peri-Sylvian regions (256 electrodes). Subtemporal strip electrodes. Exposed area of electrodes are to scale. B. Speech sound stimulus acoustic waveform. C. Example neural response spectrograms from two neighboring electrodes (z-score) on the superior temporal gyrus. D. Single-trial, high gamma rasters at individual electrodes.

Figure 3. Population cortical responses to speech listening obtained with complete, higher-density coverage of human superior temporal gyrus

Hierarchical clustering of single-electrode and population responses to phonemes in continuous speech. Rows correspond to individual phonemes, and columns correspond to single electrodes. Clustering across both axes demonstrates phonetic feature selectivity and hierarchical organization. From Mesgarani et al., 2014.

Figure 4. Relationship between spatial distance and signal correlation across electrode pairs, stratified by frequency band

Derived from actual data (unpublished), human cortical recordings obtained on a 4mm spaced ECoG grid. Significant differences in spatial resolution, especially at less than 1 cm, can be observed depending upon the frequency band of interest. Note that correlations less than 4mm are extrapolated, as 4mm is the shortest distance assessed.

Figure 5. Examples of micro-fabricated ECoG array for human application

A microfabricated ECoG grid consisting of platinum metal conductors (silver) between two insulating polymer layers (translucent). The circular pads are exposed platinum electrodes designed to make contact with the brain. The platinum lines are insulated and form the routing wires that connect the electrodes to the recording instrumentation. Manufactured by Lawrence Livermore National Laboratories.