Microscale Cortical Activity Recorded for the First Time

In the past, the study of neural activity has concentrated on two ends of a spectrum detected with extracellular recordings: single-neuron activity or network-level activity of large populations of neurons. Neural electrical signals can also be captured intracellularly, but they are difficult to study on a large scale and much less is known about them.

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Angelique C. Paulk, PhD, instructor in Neurology, and Sydney Cash, MD, PhD, co-director of the Center for Neurotechnology and Neurorecovery (CNTR) of the Department of Neurology at Massachusetts General Hospital, and colleagues have performed intracranial recordings that detected three distinct classes of cortical activity, never described before, that are not locked to ongoing natural brain rhythmic activity. They report the findings and their implications in Cerebral Cortex.

Study Methods

The recordings were made at eight centers and with four types of microelectrodes:

• New ultra-high-density microelectrodes (PEDOT:PSS), which can be laid over the top of the cortex without penetrating the pial surface and covers large areas of the brain, were used in 15 patients undergoing tumor resection and 22 patients scheduled for surgical resection to treat intractable epilepsy
• Single-channel sharp electrodes were used in two patients undergoing placement of electrodes for deep brain stimulation
• Laminar arrays or two-dimensional arrays of microelectrodes were implanted for several days to two weeks in 17 additional patients scheduled for surgical treatment of epilepsy

PEDOT:PSS electrodes were also used in four mice and one rhesus macaque.

Results

Repeated, localized microscale waveforms were observed that could be divided into three distinct classes of events:

• Type 1—Faster (about 1 ms), similar to an extracellular single-unit activity
• Types 2 and 3—Slower (about 10–100 ms), found preferentially in upper cortical layers

The events had distinctive morphologic, temporal and spatial patterns and showed rare but statistically significant interactions, with type 1 events usually preceding type 2 and type 3 events. The rates of all three events changed with auditory and electrical stimulation, application of cold saline and application of pro-convulsant medications in patients with epilepsy.

Types 2 and 3 events were also recorded in the mice and macaque and with the long-term microelectrodes. Almost no type 2 or type 3 events were recorded by clinical electrodes.

Laying the Groundwork

This study captured neural activity that is "intermediate" between single-cell and network dynamics. Type 2 and type 3 events seem to be distinct from ongoing spontaneous oscillations, and because they occurred across multiple microelectrode types, species and experimental conditions, it can be concluded they are physiologically normal. It is hypothesized that these events may represent post-synaptic potentials, localized dendritic spikes or backpropagating action potentials.

Further study of these events are necessary to understand the underlying mechanism and could have substantial implications for understanding pathologies such as brain tumors and epilepsy, as well as the healthy brain.

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