CyberBrain

A Preliminary Experience on Non Human Primate

M. Piangerelli

, A. Paris

and P. Romanelli

Computer Science Division, University of Camerino, Via del Bastione 1, 62032, Camerino, Italy

AB Medica s.p.a., via Nerviano 31, 20020, Lainate, Milano, Italy

Keywords:

Epilespy, Wireless EcoG device, Closed-loop Device, Abnormal Brain Activity.

Abstract:

The study of abnormal electrical activity of the brain, such as epilepsy, is attracting more and more interest for

its wide impact on the population. Intracranial EEG recording (electrocorticogaphy; EcoG) and direct cortical

stimulation (DCS) are, nowadays, the most accurate and reliable techniques to map cortical function and to

identify the boundaries of an epileptic focus. In this work we present the preliminary testing of intra-operative

ECoG and DCS performed in a non-human primate using a new custom-made fully-implantable wireless 16-

channels device (Patent Number: WO2012143850), called ECOGW-16E. This fully-integrated device, housed

in a compact hermetically sealed Polyetheretherketone (PEEK) enclosure, exploits the newly available Med-

ical Implant Communication Service band (MICS: 402-405 MHz). ECOGW-16E is wirelessly rechargeable

using a special designed cage for recharge, developed in accordance with guidelines for accommodation of

animals by Council of Europe.

1 INTRODUCTION

Multichannel electrophysiological measurements of

neural activity are a fundamental method in neu-

ral research and in medical applications. Nowa-

days Intracranial EEG recording (electrocorticogra-

phy, EcoG) and direct cortical stimulation (DCS) are

the gold standard techniques to map the cortical func-

tions and to identify the epileptogenic foci (Spena

et al., 2010; Borchers et al., 2012) but provide also an

exquisite tool to assess the function and interactions

of neuronal ensembles. For example, observing the

activity in a great number of simultaneously measured

channels is necessary for understanding the functions

of the visual cortex, where the signals from many mil-

lions of neurons represent the ﬁrst stages of creating

our visual perceptions. Electrode arrays are essential

tools to localize the source of epileptic seizures and

later remove these parts from the brain during a sur-

gical intervention (Crone et al., 1998): the higher the

spatial resolution of the array, the less healthy tissue

needs to be removed from the brain. Finally in a not

so distant future, integrated devices provided with ap-

propriate algorithms, can deliver performant closed-

loop stimulation modulating brain function. Closed-

loop stimulation can be used to abort seizures or to

provide countless potential intervention opportunities

to counteract brain disorders such as pain, tremor and

Parkinsons disease (Warren and Durand, 1998; Moro

et al., 2002; Johnson et al., 2013). Todays elec-

trode arrays are mostly connected via cables through

the skull which always brings the risk of infections,

limiting the observation window to short-term only.

There is therefore a strong need to develop wireless

systems able to extend substantially the monitoring

window, up to a chronic use. Our group developed

a highly innovative wireless externally-rechargeable

multi-channel EcoG device. Preliminary results of ex-

perimental tests on a monkey will be presented here.

2 MATERIALS & METHODS

2.1 Surgical Process

One male macaque monkey was used in this study

(Macaca fascicularis, 6.95 kg). Experimental proto-

col was approved by the regional committee (Cometh

Grenoble) and registered to the national commit-

tee under the number 12/136

Clinatec-NTM-01 and

complied with the EU directive 22th September 2010

(2010/63/EU ) on the care and use of laboratory an-

imals. MRI was performed prior to surgical explo-

Piangerelli M., Paris A. and Romanelli P..

CyberBrain - A Preliminary Experience on Non Human Primate.

DOI: 10.5220/0005089700940098

In Proceedings of the 2nd International Congress on Neurotechnology, Electronics and Informatics (NEUROTECHNIX-2014), pages 94-98

ISBN: 978-989-758-056-7

 2014 SCITEPRESS (Science and Technology Publications, Lda.)

Figure 1: Post-op radiographic image of the device.

ration to deﬁne surgical management. The animal was

anesthetized using a loading dose Xylazine 5 mg/kg,

and Ketamine hydrochloride 20 mg/kg, IM and then

a maintenance dose of 1.25 mg/kg, 5mg/kg Xylazine

/Ketamine respectively. Heart rate, blood pressure,

respiratory depth, and body temperature were con-

stantly monitored by veterinary staff. Surgical proce-

dures took place in standard aseptic conditions. When

deep anesthesia was achieved, the animal was secured

to a stereotaxic frame, and a craniotomy was per-

formed over the left motor cortex (M1), in Brodmann

area 4. The dura mater was cut in a Y fashion and

the leafs were retracted and sutured on the sides in

order to expose the central sulcus and the surfaces

of the primary motor(M1) and sensory (S1) cortex.

Radiographic images (Fig.1) during surgery were ac-

quired to guide device placement. The device was po-

sitioned orthogonally and the grid was centered above

the hand knob of the left motor cortex (Fig.2).

2.2 ECOGW-16E

The device, called ECOG-16W (Cristiani et al., 2012)

(total length 58.3 mm), speciﬁcally designed for mon-

keys, consits of two parts (Fig.3 ): the grid (Fig.4),

consisting of a single sheet of ﬂexible polyimide

support that integrates 16 platinum electrodes (Neu-

ronexus, Ann Arbor, MI, USA) and the body, cas-

Figure 2: Device placement over the sensorimotor cortex:

the central sulcus is visible under the grid

ing in PEEK, includes a microcontroller handling lo-

cal processing and the transceiver module for im-

plantable medical applications within MICS band

with a 800/400/200 kbps raw data rate. In addition,

it includes a triaxial accelerometer, a stimulus gener-

ator, a sensor of temperature/load current and a Li-

Ion battery(3,6V 150mA/h ISO 13485). PEEK case

was chosen for its high and well documented biocom-

patibilty in prosthesis in different ﬁeld of medicine

(Rivard et al., 2002). Finally, we have adopted a

charging apparatus to provide an induction charger

(250mW, 70mA @ 3.7V) for a wireless recharge-

able battery. The interface consumes 58mA(16CH

@ 500SPS + TX RF), 30mA(16CH @ 500SPS) and

7mA in standby. The device was positioned orthogo-

nally and the grid was centered above the hand knob

of the left motor cortex (Fig.2) providing also cover-

age of the central sulcus and part of S1.

ECOGIW-16E is wirelessly rechargeable using a

special designed cage for recharge (Fig. 5).

Wired systems expose the cables to the risk of

damage induced by the monkey , which pulls them

away. To perform behavioral experiments, the mon-

key needs to seat in a special chair that does not allow

the arms of the animal to reach the cables. Our cable

free system opens therefore a new window of oppor-

tunities to observe the neural activities in unrestrained

animals. Using the smart wireless recharge cage it is

CyberBrain-APreliminaryExperienceonNonHumanPrimate

Figure 3: The scheme of the ECOG-16E.

Figure 4: The grid by NeuroNexus.

Figure 5: The recharge cage.

also possible to recharge the implanted device during

the physiological rest period.

3 DATA ANALYSIS AND RESULTS

In this study we used a commercial software for

ECoG recording (Micromed, Treviso; Italy) and we

tested software speciﬁcally developed for our hard-

ware (Aethra Communication company; Ancona,

Italy) for DCS and impedance measurement. The

procedure and post-operatory course was uneventful.

The monkey recovered immediately and was able to

Figure 6: Tipical Ecog traces: after the implant (top), after

three months (middle) and after six months (bottom).

resume all the normal motor activities within a few

hours. The ECoG signals of sixteen electrodes was

recorded with a 512 Hz sampling rate and a software-

imposed band-pass ﬁlter from 0.008-400 Hz. We ﬁrst

removed all frequencies below 0.5 Hz from the ECoG

signals using a high-pass ﬁlter. EcoG signal recording

was performed every day for 6 months and remained

excellent for all the time (Fig.6). In the ﬁgure 6 three

screenshots are shown: after few hours since the im-

plant, after three months and after six months. It is

possible to notice the high ﬁdelity of the signal with

no visible distortion and noise.

We measured, every day, the values of impedance

at different frequencies (from 16Hz to 2048Hz) in

all channel (Fig.7); in our experiment, impedance is

measured at different frequencies; as you can see in

ﬁgure 7, the values of the impedance for each elec-

NEUROTECHNIX2014-InternationalCongressonNeurotechnology,ElectronicsandInformatics

Figure 7: Impedance values over time

Figure 8: Impedance values over time.

trode is got @1kHz; in the inset the mean value for

each electrode is also reported. For all the days the

device has been implanted, impedance values has re-

mained under the horizontal pink line (@100 KHz),

representing the maximum limit of the impadance.

Our device has impedance values consistent to the

ones found in literature (Kellis et al., 2011). We

computer, also, the Fast Fourier Transform (FFT) of

the ECoG traces. The frequency spectrum shows

the characteristic decrease in amplitude at higher fre-

quencies and also that there are all the characteris-

tic frequency components of an ECoG signal (Fig.8).

Cortical stimulation was performed with a protocol

planning to stimulate the primate every seven days.

We performed bipolar stimulation by pulses of rectan-

gular shapes with anodal monophasic current pulses

CyberBrain-APreliminaryExperienceonNonHumanPrimate

of 0.5 ms duration. The stimulation technique con-

sists of a train of 5 pulses delivered at 1 Hz, which

is equivalent to an interstimulus interval of 100 ms.

Stimulus intensity was gradually increased in incre-

ments of 0.5 mA, starting at 1 mA, up to a maximum

of 3 mA. We testing all the contact with a reference

electrode positioned in the left of grid. During corti-

cal stimulation of the expected motor cortex, move-

ments of distinct portions of the right arm were ob-

served with a stimulation intensity of 2 mA.

4 CONCLUSIONS

The implantable wireless device, here presented, al-

low us to perform chronic EcoG recording and DCS.

research and clinical applications of this novel tech-

nology include brain mapping, seizure foci localiza-

tion and BCI. Wireless technology for transmitting

EcoG signal provides several advantages: risk and

limitation related to the presence of subcutaneous

connecting cables (Behrens et al., 1997) are removed

and the recording time can be substantially prolonged.

This fully-integrated system can also be used as a

closed loop system providing electrical stimulation

“on-demand” to abort promptly detected seizure ac-

tivity in drug-resistant epilepsy patients.

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