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Chronic, Multi-Contact, Neural Interface for Deep Brain
Stimulation
Angela Tooker, Teresa E. Madsen, Andrea Crowell, Kedar G. Shah, Sarah Felix, Helen S. Mayberg,
Satinderpall Pannu, Donald G. Rainnie, Vanessa TolosaAbstract- Recent clinical studies show deep brain
stimulation (DBS) as a promising therapy for the chronic
treatment of major depression. Although an increasing
number of studies have shown the clinical benefits of DBS in
patients with major depressive disorder, little is known about
the underlying mechanisms by which the treatment works. The
neural interface described here consists of two multi-contact,
polymer-based, microelectrode arrays that were specially-
designed and fabricated. The first is for stimulation of the
medial prefrontal cortex (mPFC) and the second is for
recording local field potentials (LFPs) and event related
potentials (ERPs) in the basolateral amygdala (BLA). Unlike
conventional metal wire stimulating arrays, this stimulating
array offers 144 spatial configurations, both monopolar and
bipolar. We present here preliminary results involving
stimulation of various contact points spanning the mPFC, with
simultaneous recording from multiple contacts across the
temporal lobe.
I. INTRODUCTION
Deep brain stimulation (DBS) as a therapeutic option has
been FDA-approved for the treatment of essential tremor, and
Parkinson's disease. With promising clinical trials for
diseases such as obsessive-compulsive disorder, Alzheimer's,
dystonia, and epilepsy, the patient population treated with
DBS is expected to grow [1-3]. Major depressive disorder
has also emerged as another neuropsychiatric disorder to
benefit from DBS [4-5]. Despite the clinical successes,
however, the biological mechanisms of DBS are still
unknown. As the mechanisms are likely specific to both the
disease and the stimulation parameters/location, investigating
the mechanisms of DBS treatment for different disorders will
likely require a flexible platform with a variety of different
sensing/stimulating modalities.
Investigations into the neurobiology and brain circuitry
underlying the mechanisms of DBS treatment for depression
have been limited, partly by the neuro-technologies available.
Standard metal wire stimulating electrodes only allow a
single stimulation site per animal, with no control over
position or current spread after implantation. A commitment
to either monopolar or bipolar stimulation is made even
*Research supported by Lawrence Livermore National Laboratory.
A. Tooker is with Lawrence Livermore National Laboratory, Livermore,
CA 94550 USA (phone: 925-422-2326; e-mail: tooker1@llnl.gov).
K. Shah, S. Felix, S. Pannu, and V. Tolosa are with Lawrence Livermore
National Laboratory, Livermore, CA 94550 USA (e-mail: shah22@llnl.gov,
felix5@llnl.gov, pannul@llnl.gov, tolosal@llnl.gov).
T.E. Madsen, A. Crowell, and D.G. Rainnie are with Emory University
School of Medicine, Atlanta, GA (email: tmadsen@emory.edu,
andrea.crowell@emory.edu, drainni@emory.edu)
H.S. Mayberg is with Department of Psychiatry, Emory University,
Atlanta, GA (email: hmayber(aemory.edu)earlier, as they require different electrode structures (a ground
wire wrapped around a skull screw, as opposed to a bipolar
concentric stimulating electrode). Therefore, only one
configuration per animal is possible, and all comparisons of
different conditions must be made between animals
introducing high variability. The development of neuro-
technologies with larger numbers of electrodes, capable of a
wide range of stimulus parameters, will further contribute
towards an understanding of the mechanisms underlying
DBS and may result in more effective stimulation.
Micro-fabricated, multi-contact, polymer-based electrode
arrays are well-suited to overcome these challenges [6-10].
These arrays can be fabricated with large numbers of
variously-sized electrodes, suitable for recording or
stimulating at very specific locations in the brain. They can
be easily interfaced with commercially-available stimulating
and recording equipment. Further, a single microelectrode
array can be used with a wide variety of stimulus options,
both bipolar and monopolar.
Multiple studies have now demonstrated the effectiveness
of stimulation of subcallosal cingulate region, specifically
adjacent to the Brodmann area (BA) 25, for treatment of
depression. In the rat, the ventromedial prefrontal cortex
(vmPFC) has been suggested to be homologous to the human
BA 25, and stimulation of the vmPFC has been tested in rat
models of depression [11]. However, the rat vmPFC can be
further divided into the infralimbic and prelimbic cortex,
each of which has distinct patterns of anatomic connectivity,
including different projections to the amygdala [12]. They
also have dissociable, sometimes opposing, effects on fear
conditioning [13] and on response to the forced swim test, an
animal model of depression [14]. Independent stimulation of
these areas, while recording the electrophysiological response
from an anatomical target involved in emotion regulation and
expression, together with simultaneous behavioral
observation provides a powerful way to further investigate
the therapeutic mechanism of DBS.
We present here results from an investigation of electrical
stimulation and electrophysiological recording in a freely
moving rat using a microfabricated polymer-based neural
interface. The neural interface is customized to stimulate
across 12 different contacts within the mPFC and
simultaneously record LFPs and single units (spikes) across
the temporal lobe. Preliminary analysis show marked
differences in response across the temporal lobe depending
on stimulation contacts and other factors, providing support
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Tooker, A. C.; Madsen, T. E.; Crowell, A.; Shah, K. G.; Felix, S. H.; Mayberg, H. S. et al. Neural Interface for Deep Brain Stimulation, article, June 6, 2013; Livermore, California. (https://digital.library.unt.edu/ark:/67531/metadc862928/m1/3/: accessed April 19, 2024), University of North Texas Libraries, UNT Digital Library, https://digital.library.unt.edu; crediting UNT Libraries Government Documents Department.