High-Density Intraoperative ECoG-A Pilot Study

With advancing analytical capabilities in mathematics and ever increasing
computing power, measurements of electrical activity of the human brain are
becoming increasingly valuable. An expanding number of papers are published on
the neurophysiological underpinnings of human cognition and behaviour, using
electrode grids (silicon sheets with embedded platinum discs) positioned under
the dura in surgery patients. Many of these aim to elucidate mechanisms in
order to improve treatment of neurological and psychiatric brain disorders.
Evidence from electrophysiological studies suggests that brain functions are
subserved by small collections of neurons performing the same specific tasks,
so-called neural ensembles or functional units. Optimal investigation of human
brain functions would be at that level of detail. Electrocorticography is
already clinically used during epilepsy surgery and sometimes tumor surgery to
find the epileptogenic brain tissue. Newly found electrical biomarkers for
epilepsy, called high frequency oscillations, typically occur in small cortical
areas and can be missed by large-scale recordings.

At the UMC Utrecht, research is conducted with high-density grids in epilepsy
patients, as part of a larger ethics protocol (approved protocol 14-420).
However, the duration of projects within that protocol is quite long due to a
low volume of intracranially monitored eligible (ie adult) patients (6-8/year),
with quite variable grid positions. Hence research questions with high-density
grids are projected to last 3-6 years. This obviously is prohibitive. In the
current protocol we want to explore the feasibility of obtaining high density
electrocorticography (HD-ECoG) data in patients who undergo awake surgery,
which takes place every week.

The UMC Utrecht has an excellent reputation in research on brain function and
epillepsy involving implanted and/or intra-operative electrode grids (routine
ECoG) in the epilepsy surgery program. Patients who undergo brain surgery for
tumor or other (epileptogenic) laesion removal, undergo either an awake of
sedated surgery, which can also include clinical registrations of epilepsy with
routine low-density ECoG. Recent developments create the opportunity to address
questions regarding the spatial detail of epileptogenic tissue and brain
function in a more expedited fashion, with a different patient population. In
2013 the number of surgeons at the UMC who are skilled in awake surgery
performed on patients with early stages of brain tumours, has doubled (now 4),
and the number of performed awake surgeries has increased dramatically, to 50+
per year. Awake surgery offers a unique window of opportunity for research on
epileptogenesis and brain function. During surgery, after removal of the tumour
there is a period of 15-20 minutes in which the surgeon waits for bleeding to
stop (haemostasis) while the patient is wide awake. In this period, an high
density electrode grid can be placed on healthy cortex to collect ECoG data
while the patient performs one or two specific tasks. Moreover, during this
type of surgery often routine intra-operative ECoG recordings are performed
using standard clinical grids to localize the lesion*s associated epileptogenic
tissue and tailor the resection. A HD-ECoG grid can be placed next to this
routine ECoG grid to record in parallel high-resolution data of sick tissue
(e.g. epileptogenic).

We will address two primary objectives related to performing HD-ECoG
recordings, targeting the same patient population: patients with a tumor and/or
epileptogenic laesion who will undergo brain surgery. There are two different
surgical strategies in which we want to add our HD-ECoG recordings:
1.) obtain functional data - from healthy tissue - in people undergoing awake
brain surgery for removal of brain tumors or other anomalies
2.) obtain data from epileptogenic tissue in people undergoing awake or sedated
brain surgery in whom routine ECoG is recorded to delineate the epileptogenic
cortex.

We address two primary objectives: 1.) To determine whether (awake) surgery on
patients with a brain tumor or epilepsy allows for HD-ECoG data collection of
adequate quality to address research questions on brain function. In other
words, we want to determine whether HD-ECoG studies on brain functions can be
conducted during (awake) surgery. 2.) to develop and test HD-ECoG for better
recognition of epileptogenic tissue and eventually replace the routinely used
low-density grids.

Subjects are included in an observational pilot study with intra-operative
functional ECoG recordings with a high-density grid on healthy (primary
objective 1) and/or epileptogenic brain tissue (primary objective 2). An fMRI
scan is performed to determine the grid position on the healthy cortex (primary
objective 1 only).

There are no known risks associated with presurgical fMRI acquisition and the
burden can be considered minimal (performing the fMRI localizer tasks may be
slightly tiring). During the surgery we will ask the neurosurgeon to
temporarily position a high-density electrode grid on exposed or accessible
brain surface, at a time that is convenient. Grids are frequently used during
epilepsy surgery and there are no known risks associated with their
intraoperative use. All the ECoG equipment is CE certified and is safe. The
ECoG measurements are not required for the surgery. There is no immediate
benefit to the participants. Including all procedures, the burden can be
considered minimal.
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