The electrode arrays in use today can either sample broad regions of the brain (~80mm × ~80mm) at low spatial resolution (~10mm spacing), or small regions of brain (~4mm × ~4mm) at high spatial resolution (~400μm spacing)11
, with both requiring N wires for N electrodes. Here we have shown a 360-channel active electrode array capable of sampling a 5-fold larger region of brain (10mm × 9mm) than prior work11
, with high spatial resolution (500μm spacing) and high temporal resolution (>10kS/s) while reducing the number of wires 9-fold. This technology offers spatial resolution approaching that of voltage sensitive dyes, with greatly improved temporal resolution and signal to noise ratio, with the ability to record from non-planar and non-optically accessible areas and in a potentially fully implantable, non-toxic, clinical-scale system. This technology can be rapidly scaled to clinical sizes (~80mm × ~80mm) with 25,600 channels, while maintaining high temporal resolution (>1.2kS/s), enabling elucidation of micro-scale brain dynamics in human normal brain activity and disease.
Spiral activity has been described by mathematical models of 2-dimensional excitable media46
and has been documented in brain and heart39–42
but until now a tool did not exist to record exhaustive spatiotemporal patterns of brain activity in a large mammalian brain, as we demonstrate here. Our results suggested that spiral waves are present during seizures, though the seizures produced in this case were induced by acute disinhibition and may not accurately represent activity characterizing spontaneous seizures in chronic epilepsy. Perhaps more importantly, our technology offers a method to record this kind of activity chronically, in awake, behaving animals and humans with unprecedented detail.
The significance of high density, active array technology is evident in the neural dynamics which emerge at a spatial scale 400 times finer than used clinically. This technology demonstrated complex spatial patterns, such as spiral waves, clustering of spatiotemporal patterns, and heterogeneity and anisotropy of sleep oscillations, all of which occurred within the space occupied by one current clinical ECoG electrode. Whereas coarse spatial undersampling prevents current technology from resolving the micro-scale spatial patterns that occur in the brain, the high resolution of this active array technology enabled us to distinguish intrinsic from pathologic signals efficiently, even within the same frequency bands.
Our observations suggested that spindles are spatially punctate, stationary, and temporally coherent, whereas epileptiform activity in this model propagates as planar and spiral waves. Further research is needed to fully characterize these preliminary results and their significance. Prior investigations using voltage-sensitive dyes have found spiral waves in rodents during EEG epochs dominated by sleep-like delta frequencies42
, in contrast, we demonstrate activity which was spatially inhomogeneous and did not spiral, yet was present during delta-dominant states, and which appeared as sleep spindles electrographically. While optical imaging has demonstrated spatial patterns such as planar waves and spirals in disinhibited rat cortex41
, high-density, active array technology enabled us to show that these spiral dynamics in disinhibited cat cortex are electrographic seizures at the clinical scale.
Ultimately, the question of clinical relevance is whether there are spiral waves in human cortex, yet voltage sensitive dye recordings are infeasible for use in humans due to the requirement that the brain be optically exposed and subjected to toxic dyes. Our results suggested that technology incorporating flexible, high-density, active arrays of electrodes can provide equal or superior recordings in a fully implantable system. If spiral waves are demonstrated in human cortex, the clinical implications are profound. Seizure control may be analogous to the control of cardiac arrhythmias, which are also known to manifest as reentrant spiral waves of excitation39
. Further, as learning tasks increase spindle activity47
, which may be due to consolidation and integration of memories48
, understanding the fine structure of spindles has implications for learning and memory efficiency, as well as thalamocortical networks involved in sleep and primary generalized epilepsy.
Finally, flexible devices such as those shown here hold the promise to enable neuroprosthetic devices that have been limited until now by the lack of resolution of the brain-machine interface and by the irregular topography of the brain. Utilizing the extreme flexibility of active electrode arrays, devices can be folded and implanted into currently inaccessible brain regions, such as sulci and fissures, that can be simultaneously recorded and stimulated, along with surface regions to enable devices to facilitate movement, sensation, vision, hearing and cognition. These devices can also be powered remotely through wireless power transmission techniques49
Our work also has implications for treating disease. Disorders such as epilepsy, dementia, affective disorders, movement disorders and schizophrenia are all conditions that affect dispersed brain networks, rather than a single locus of brain function. Investigations of major depression, parkinsonism, and chronic pain with magnetoencephalography have identified “thalamocortical dysrhythmia,” but increases of spatial and temporal resolution as with the recording method presented here would allow a more detailed characterization of these diseased networks50
. Only with new approaches that can resolve micro-scale activity over large areas of cortex will we be able to begin to understand how the brain functions in both disease and health, and to develop better diagnostic and therapeutic options for those affected.