Title: Miniaturized high-density multichannel electrode array for long-term neuronal recordings
Abstract: A high-density multichannel microwire electrode array is disclosed. The array can comprise a variable number of electrodes. A method of assembling the array is further disclosed. Additionally, a plurality of devices employing the array are disclosed, including an intelligent brain pacemaker and a closed loop brain machine interface.
Patent Number: 6,993,392 Issued on 01/31/2006 to Nicolelis, et al.
| Inventors:
|
Nicolelis; Miguel A. L. (Chapel Hill, NC);
Lehew; Gary C. (Durham, NC);
Krupa; David J. (Durham, NC)
|
| Assignee:
|
Duke University (Durham, NC)
|
| Appl. No.:
|
097312 |
| Filed:
|
March 14, 2002 |
| Current U.S. Class: |
607/45 |
| Current Intern'l Class: |
A61N 1/08 (20060101) |
| Field of Search: |
600/373,378,393,544,545
607/45,46,116
|
References Cited [Referenced By]
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|
Primary Examiner: Pezzuto; Robert E.
Assistant Examiner: Oropeza; Frances P.
Attorney, Agent or Firm: Jenkins, Wilson & Taylor, P.A.
Goverment Interests
GRANT STATEMENT
This work was supported by DARPA grant N00014-98-0676. Thus, the U.S. Government
has certain rights in the invention.
Claims
What is claimed is:
1. A real time closed loop brain-machine interface comprising:
(a) a multichannel microwire electrode array for acquiring neural signals from
a plurality of single neurons comprising:
(i) a plurality of microwire electrodes;
(ii) one or more printed circuit boards in electrical connection with the microwire
electrodes comprising:
(1) a plurality of conductive traces spaced apart about 0.015 inches (center
to center) or less; and
(2) a plurality of conductive pads in electrical connection with the one or more
conductive traces; and
(iii) one or more connectors in communication with conductive pads and having
contacts spaced apart about 0.030 inches (center to center) or less;
(b) a signal processing mechanism adapted to communicate with the multichannel
microwire electrode array and adapted to form extracted motor commands from the
extracellular electrical signals; and
(c) an actuator adapted to communicate with the signal processing mechanism and
to respond to the extracted motor commands by effecting a movement, and to provide
sensory feedback to the subject.
2. The real time closed loop brain-machine interface of claim 1, wherein the
microwire electrodes comprise a material selected from the group consisting of
stainless steel, tungsten, noble metals, conductive alloys and conductive polymers.
3. The real time closed loop brain-machine interface of claim 1, wherein the
microwire electrodes are substantially coated with a material selected from the
group consisting of TEFLON®, S-lsonel, polymers, plastics and non-conductive materials.
4. The real time closed loop brain-machine interface of claim 1, wherein the
one or more printed circuit boards are flexible and about 0.01 inch thick.
5. The real time closed loop brain-machine interface of claim 1, wherein the
one or more printed circuit boards are substantially rigid and about 0.08 inches thick.
6. The real time closed loop brain-machine interface of claim 1, wherein the
one or more printed circuit boards comprise a plurality of the circuit boards secured
together in a superimposed stacked relationship.
7. The real time closed loop brain-machine interface of claim 1, wherein the
one or more printed circuit boards each comprise one or more removable support tabs.
8. The real time closed loop brain-machine interface of claim 1, wherein the
conductive traces are substantially insulated.
9. The real time closed loop brain-machine interface of claim 1, wherein the
one or more connectors are zero insertion force (ZIF) connectors.
10. The real time closed loop brain-machine interface of claim 1, wherein the
one or more connectors are low insertion force (LIF) connectors.
11. The real time closed loop brain-machine interface of claim 1, wherein the
one or more connectors comprise a plurality of connectors soldered to the plurality
of conductive pads.
Description
TECHNICAL FIELD
The present invention relates generally to an apparatus for acquiring neural
signals and more particularly to an apparatus for acquiring neural signals from
a large number of single neurons. The apparatus of the present invention is adapted
for chronic implantation in the brain of subject and facilitates simultaneous acquisition
of an unlimited number of neural signals.
ABBREVIATIONS
- PCB printed circuit board
- FPC flexible printed circuit board
BACKGROUND ART
Over the past ten years, there has been an explosive growth in the use of multi-channel
neuronal recordings, for both basic neurobiology research as well as clinical applications
(see, e.g., Chicurel, (2001)
Nature, 412: 266-8; Nicolelis et al., (1997)
Neuron, 18: 529-37; and Nicolelis, (ed.),
Methods for Neural Ensemble
Recordings, CRC Press, Boca Raton, 1998). However, during this time, progress
in these fields has been limited by the design of the electrodes and electrode
arrays presently available for clinical and research applications. In particular,
the relatively large size and low electrode density of the presently available
electrode array designs has limited the density of implanted electrodes to about
32 channels (or electrodes) per square centimeter. In comparison, because of the
extremely high-density of neurons in the human (and other mammalian) brain, many
researchers and clinicians cite a density of about 100 more electrodes per square
millimeter as a theoretically ideal density of implanted electrodes. Therefore
any improvement in electrode density would greatly facilitate work in these fields.
Prior art brain research instrumentation includes movable single channel or
single electrode mechanisms that are limited to recording from a single location
in the brain. Early research tended to be concentrated in sensory portions of the
brain such as the visual cortex. For example, the research would seek to identify
what particular stimulus in the subject's visual field would cause an individual
neuron in the visual cortex to fire. The prior art single electrode mechanisms
were capable of being moved to different locations in the brain but were only capable
of recording from a single neuron or a small neuron cluster at a time.
The prior art also includes apparatuses with multiple electrodes whose position
in space is fixed relative to the other electrodes. These prior art electrodes
are capable of recording timing or firing patterns of multiple neurons or multiple
small clusters of neurons. The importance of being able to record timing patterns
is helpful to understanding higher order functions of the brain. However, the multi-channel
or multi-electrode prior art devices could only be employed in restrained subjects
and were not capable of being moved within the brain.
Thus, neurology research and the development of clinical applications were
limited by the number of electrodes and research was confined to only those patterns
that occurred between the individual neurons or small neuron clusters that happen
to be near the tips of the recording electrodes. Another disadvantage of the fixed
array of electrodes is that the research is inherently limited to those brain functions
performed by a non-moving subject.
Yet another limitation of prior art apparatuses is that they are unsuited to
long-term implantation. In order to accurately study neural processes and to treat
neural maladies, it is important to be able to acquire significant amounts of data
over a long period of time. This is not possible using prior art apparatuses that
cannot be implanted for long periods of time in the neural tissue of a subject.
Early efforts to implant electrodes in the brain tissue of a subject have met
with some success, but still encounter many problems. In many prior art devices
and methods, a wire, or wires, is implanted in the cortex, the wire is immobilized
on the skull in some manner, and is connected to an amplification and recording device(s).
These prior art methods and devices are deficient because movement of the electrode
within the skull can disrupt signal transmission or cause signal artifacts. Excessive
rigidity of the electrode can cause, in addition to signal disruption, irritation
and damage to the cortex. Additionally, there is the possibility of a local tissue
reaction to the presence of a foreign body or scar tissue formation over time,
which can decrease the usefulness of the electrode and the signal transmitted.
Infection due to electrode wires can cause deleterious effects. Current implant
electrodes have been used to record signals over a period of days or weeks, and
in few instances, for several months. An electrode array is needed, therefore,
that can transmit signals accurately over a longer period, since repeated operations
on a subject to repair or replace an electrode are clearly undesirable. Additionally,
freedom of movement is also often restricted by the bulky electrode arrays used
by present techniques. Thus, it is desirable to have access to small electrode
arrays that do not limit movement.
Further, it is desirable to simultaneously record data from large numbers
of single neurons in comparatively small areas of a subject's brain. This can greatly
enhance the quality and quantity of data recorded from a subject and can offer
insight into neural processes and afflictions. However, to meet this desire, an
apparatus preferably provides a high-density of implantable electrodes. By increasing
the density of electrodes, a greater volume of data can be acquired, and thus a
deeper understanding of neural processes can be obtained. Prior art apparatuses,
however, are unsuited to this goal, due to their limited electrode density.
Yet another significant advantage in recording data from a large number of single
neurons is that a wealth of basic neurophysiological data would become available,
data that is not accessible through prior art electrode arrays. Questions regarding
the functional organization of adjacent neurons, their relative activities during
sensory perception, and their relative coordinated activities during motor output
could be determined. Relative activity during conditioning and during learning
of new tasks could be studied. Furthermore, implanting electrodes over different
cortical areas could demonstrate functional interactions in a manner unavailable
by any other means.
Summarily, prior art apparatuses do not disclose a high-density multichannel
electrode array for long-term intra-cranial neuronal recordings. A high-density
electrode array would be a great asset to researchers in the field of neurobiology
and to researchers in related fields. The problem, then, is to develop a high-density
multi-channel electrode array that can improve the density of implanted electrodes
by a significant degree. The present invention solves this and other problems.
DISCLOSURE OF THE INVENTION
A multichannel microwire electrode array for acquiring neural signals from large
numbers of single neurons is disclosed. In a preferred embodiment, the array comprises:
(a) one or more microwire electrodes; (b) one or more printed circuit boards in
electrical connection with the one or more microwire electrodes, the one or more
printed circuit boards comprising: (i) one or more conductive traces spaced apart
about 0.015 inches (center to center) or less; and (ii) one or more conductive
pads in electrical connection with the one or more conductive traces; and (c) one
or more connectors in electrical connection with the one or more conductive pads
and having contacts spaced apart about 0.030 inches or less.
A method of assembling a multichannel microwire electrode array for acquiring
neural
signals from large numbers of single neurons is also disclosed. In a preferred
embodiment, the method comprises: (a) associating one or more microwire electrodes
with a printed circuit board comprising conductive traces spaced about 0.015 inches
(center to center) or less and conductive pads in electrical connection with the
conductive traces to form a PCB-electrode assembly; (b) applying a conductive paint
to the PCB-electrode assembly to form a coated PCB-electrode assembly; and (c)
associating the coated PCB-electrode assembly with at least one connector via the
conductive pads, the connector comprising: (i) a contact adapted to electrically
connect with each of the conductive pads; and (ii) a ground contact in order to
form a multichannel microwire electrode array for acquiring neural signals from
large numbers of single neurons.
Additionally, a multichannel microwire electrode array kit is disclosed.
In a preferred embodiment, the kit comprises: (a) one or more microwire electrodes;
(b) one or more printed circuit boards comprising: (i) one or more conductive traces
spaced apart about 0.015 inches (center to center) or less; and (ii) one or more
conductive pads in electrical connection with the one or more conductive traces;
and (c) one or more connectors having contacts spaced apart about 0.030 inches
(center to center) or less.
Further, a real time closed loop brain-machine interface is disclosed. In
a preferred embodiment, the interface comprises: (a) a multichannel microwire electrode
array for acquiring neural signals from large numbers of single neurons comprising:
(i) one or more microwire electrodes; (ii) one or more printed circuit boards in
electrical connection with the one or more microwire electrodes comprising: (1)
one or more conductive traces spaced apart about 0.015 inches (center to center)
or less; and (2) one or more conductive pads in electrical connection with the
one or more conductive traces; and (iii) one or more connectors in communication
with the one or more conductive pads and having contacts spaced apart about 0.030
inches (center to center) or less; (b) a signal processing mechanism adapted to
communicate with the multichannel microwire electrode array and adapted to form
extracted motor commands from the extracellular electrical signals; and (c) an
actuator adapted to communicate with the signal processing mechanism and to respond
to the extracted motor commands by effecting a movement, and to provide sensory
feedback to the subject.
Also disclosed is a real time closed loop brain-machine interface for restoring
voluntary motor control and sensory feedback to a subject that has lost a degree
of voluntary motor control and sensory feedback. In a preferred embodiment, the
interface comprises: (a) a multichannel microwire electrode array for acquiring
neural signals from large numbers of single neurons comprising: (i) one or more
microwire electrodes; (ii) one or more printed circuit boards in electrical connection
with the one or more microwire electrodes comprising: (1) one or more conductive
traces spaced part about 0.015 inches (center to center) or less; and (2) one or
more conductive pads in electrical connection with the one or more conductive traces;
and (iii) one or more connectors in electrical connection with the one or more
conductive pads and having contacts spaced about 0.030 inches (center to center)
or less; (b) an implantable neurochip adapted to communicate with the multichannel
microwire electrode array and to filter and amplify the one or more neural signals;
(c) a motor command extraction microchip adapted to communicate with the implantable
neurochip and embodying one or more motor command extraction algorithms, the microchip
and the algorithms adapted to extract motor commands from the brain-derived neural
signals; (d) an actuator adapted to communicate with the motor command extraction
microchip and to move in response to the motor commands and to acquire sensory
feedback information during and subsequent to a movement; (e) a sensory feedback
microchip embodying one or more sensory feedback information interpretation algorithms
adapted to communicate with the actuator, the sensory feedback microchip adapted
to form interpreted sensory feedback information; (f) a structure adapted to communicate
with the sensory feedback microchip and to deliver interpreted sensory feedback
information to the subject; and (g) one or more power sources adapted to provide
power, as necessary, to one or more of the group comprising: the implantable neurochip;
the motor command extraction microchip; the actuator; the sensory feedback microchip;
and the structure adapted to relay interpreted sensory feedback information to
the subject.
Furthermore, an intelligent brain pacemaker for a mammal having a cranial
nerve not associated with an autonomic function is disclosed. In a preferred embodiment,
the intelligent brain pacemaker comprises: (a) a multichannel microwire electrode
array for acquiring neural signals from large numbers of single neurons comprising:
(i) one or more microwire electrodes; (ii) one or more printed circuit boards in
electrical connection with the one or more microwire electrodes comprising: (1)
one or more conductive traces spaced apart about 0.015 inches (center to center)
or less; and (2) one or more conductive pads in communication with the one or more
conductive traces; and (iii) one or more connectors in electrical connection with
the one or more conductive pads and having contacts spaced about apart 0.030 inches
(center to center) or less; (b) a seizure detector adapted to detect seizure-related
brain activity of a mammal in real-time, the seizure detector being electrically
connected to the multichannel microwire electrode array; (c) one or more nerve
stimulators adapted to provide electrical stimulation to a mammal's cranial nerve
not associated with an autonomic function, to terminate or ameliorate the seizure,
the one or more nerve simulators being electrically connected to the seizure detector;
and (d) a power source for providing power to the intelligent brain pacemaker.
It is thus an object of the present invention to provide a high-density multichannel
microwire electrode array. It is another object of the present invention to provide
a method for assembling a high-density multichannel microwire electrode array.
These and other objects are achieved in whole or in part by the present invention.
Some of the objects of the invention having been stated hereinabove, other objects
will become evident as the description proceeds, when taken in connection with
the accompanying Drawings and Examples as best described hereinbelow.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1A is a photograph depicting one embodiment of a high-density multichannel
microelectrode array of the present invention.
FIG. 1B is a photograph depicting another embodiment of a high-density multichannel
microelectrode array of the present invention.
FIG. 2 is a photograph depicting a rigid printed circuit board showing the components
of the board.
FIG. 3 is a schematic diagram of a flexible printed circuit board showing the
components of the board.
FIG. 4A is a schematic diagram of a high-density connector that can be employed
to connect one or more electrode arrays with an external device.
FIG. 4B is a schematic diagram of a high-density connector that can be employed
to connect one or more electrode arrays with an external device.
FIG. 5A is a photograph depicting an array of 6 rows of 8 electrodes per row
for a total of 48 electrodes.
FIG. 5B is a photograph depicting an array of 8 rows of 16 electrodes per row
for a total of 128 electrodes wherein the array is about to be implanted into the
cerebral cortex of a Rhesus monkey.
DETAILED DESCRIPTION OF THE INVENTION
I. Definitions
Following long-standing patent law convention, the terms "a" and "an" mean
"one or more" when used in this application, including the claims.
As used herein, the terms "actuator", "external device" and "prosthetic limb"
are used interchangeably and mean any kind of device adapted to perform a movement.
Although an actuator preferably performs a movement in three dimensions, an actuator
can also be limited to performing movements in two dimensions. Thus, an actuator
can be a manipulandum confined to two-dimensional motion. A preferred actuator
comprises a prosthetic limb, which can be fitted on, or integrated into, the body
of a subject. An actuator can also be associated with machinery and/or circuitry
that allow the actuator to respond to one or more forms of input with one or more
movements. It is also preferable that the range of motion of an actuator designated
as a substitute for a patient's lost or paralyzed limb be limited to the range
of motion of the limb for which the actuator is substituting.
As used herein, the term "conductive paint" means a material that can be applied
to a surface and exhibits the property of conductivity when a current is applied
thereto. Preferred conductive paints include those comprising noble metals, such
as colloidal silver.
As used herein, the term "conductive pad" means a structure comprising a conductive
material, such as copper. A conductive pad is also preferably adapted for conductive
association (e.g. via soldering) with another structure, such as a contact of a conductor.
As used herein, the term "conductive trace" means a pattern of conductive material
disposed on a support. In a preferred embodiment, a conductive trace comprises
a pattern of copper disposed and is disposed on a circuit board or a flex circuit.
As used herein, the term "contact" means any structure adapted to transmit a
signal
therethrough. For example, a contact can comprise a pin or a socket disposed on
a connector. Preferred contacts comprise a conductive material and are preferably,
but not necessarily, insulated to prevent signal loss.
As used herein, the term "electrode" means an electric conductor through which
a voltage potential can be measured. An electrode can also be a collector and/or
emitter of an electric current. Preferably, an electrode is a solid and comprises
a conducting metal. Preferable conducting metals include noble metals, alloys and
particularly stainless steel and tungsten. An electrode can also be a microwire,
or the term "electrode" can describe a collection of microwires. Thus, particularly
preferred electrodes comprise TEFLON® coated stainless steel or tungsten microwires.
As used herein, the terms "field potential data" and "field potentials" are used
interchangeably and typically mean voltage low frequency measurements collected
from one or more locations in a subject's brain or nervous system.
As used herein, the term "microwire" means an insulated conductive wire having
a diameter of between about 10 and about 75 μm. Preferably, a microwire is
insulated, and is more preferably TEFLON® coated.
As used herein, the term "microwire array" means a collection of two or more
microwires,
the microwires having a first and a second end. The first end of a microwire is
preferably, but not required to be, adapted to interact with neural tissue and
the second end is preferably disposed in electrical communication with a printed
circuit board or flex circuit adapted to coalesce signals acquired by each microwire
of a microwire array. Preferably the second end of the each microwire is maintained
in a fixed spatial relationship with other microwires of the microwire array.
As used herein, the term "motor command" means one or more neural signals associated
with the control of one or more muscles or muscle groups of a subject. Motor commands
are generally formed in the brain or nervous system of a subject and these commands
control movements executed by the muscles of the subject. Movements preferably
comprise voluntary movements, however movements can also comprise involuntary movements.
As used herein, the term "nerve stimulator" means any device or means adapted
to stimulate one or more nerves. Stimulation imparted by a nerve stimulator can
be of an electrical, optical or physical nature, however electrical stimulation
is preferred.
As used herein, the term "neural signal" means a signal, which can take any form,
originating in the nervous system of an organism.
As used herein, the term "neurochip" means any microchip adapted for implantation
in the body of an organism. Preferably, a neurochip is adapted to be implanted
in the nervous system of an organism.
As used herein, the terms "operator", "patient" and "subject" are used interchangeably
and mean any individual monitoring or employing the present invention, or an element
thereof. Operators can be, for example, researchers gathering data from an individual,
an individual who determines the parameters of operation of the present invention
or the individual in or on which a high-density multichannel microelectrode array
is disposed. Broadly, then, an "operator", "patient" or "subject" is one who is
employing the present invention for any purpose. As used herein, the terms "operator",
"patient" and "subject" need not refer exclusively to human beings, but rather
the terms encompass all organisms having neural tissue.
As used herein, the terms "printed circuit board" and "PCB" are used interchangeably
and broadly mean any structure comprising at least one conductive trace. A printed
circuit board (PCB) can comprise multiple layers, such as a conductive layer covered
with an insulating layer. A PCB can also comprise a third layer on top of the insulating
layer, creating a conductor-insulator-conductor sandwich structure.
A PCB need not be manufactured by an imprinting process. For example, a PCB can
be manufactured by an etching process and can still be a PCB. The term "printed
circuit board" is used in its broadest sense and refers to a structure, which is
preferably planar, that comprises one or more conductive structures. A PCB can
be flexible or rigid.
As used herein, the terms "sensory feedback", "sensory feedback information"
and
"sensory feedback data" are used interchangeably and mean any form of data relating
to the perception by, or interaction between, an actuator and an object. Sensory
feedback can take the form of tactile information such as shape, hardness and brittleness
or sensory feedback can take the form of temperature information, such as hot or
cold. Tactile information can also relate to the amount of force applied by an
actuator to an object.
II. General Considerations
In one aspect of the present invention, neural signal data are acquired from
large
numbers of single neurons. Neural signal data are measurements of the electrical
activity and other activity in an area or region of the brain or other organ. Collecting
data from large numbers of single neurons is a different process from collecting
field potentials from a region of a subject's brain or other neural tissue. However,
both types of data (field potential data and data from a large number of single
neurons) can be collected by employing an array of the present invention.
By way of example, when an individual monitors a field potential (i.e. the amplitude
of a field potential) at a point on the surface of the cerebral cortex, for example,
what is detected is the overlapping summation of electric fields generated by active
neurons in the depths of the cerebral cortex, which have spread through the tissues
and up to the surface. These nerve cells can be characterized as point dipoles
that are oriented perpendicular to the surface of the cerebral cortex. In other
words, each cell has a current source where positive charge moves outwardly across
its membrane and a current sink where the same amount of positive charge moves
inwardly at each instant. Thus, the flow of current across each cell establishes
an electric field potential that is equivalent to the electrostatic field potential
of a pair of point charges, one positive at the location of the current source
and one negative at the current sink. The amplitude of this field potential, i.e.,
the electric field strength, decreases inversely with distance in all directions
from each point charge, and is relatively low at the surface of the cerebral cortex.
When many nerve cells are generating field potentials in a given region, these
field potentials sum and overlap in the neural tissue, in the extracellular fluid,
and at the brain surface. This summation is a linear function in this volume conductor,
since the field strength of a given cell varies inversely as a function of the
distance from each current source or sink. Thus, if the electric potential of a
given region is measured at a sufficient number of points and depths, it is possible
to deduce the locations and amplitude of each dipole generator at any instant of time.
In contrast with recording field potential data, recording single neuron data
involves measuring, in relative isolation, the electric voltage potential of an
individual neuron that results when the electric charges flow into and out of the
cell. This is commonly achieved by positioning the exposed tip of a microwire recording
electrode into close proximity with an individual neuron. In this situation, the
electric signal that results when current flows into or out of the neuron closest
to the microwire is much greater in amplitude than the signal that is generated
by other neurons further from the microwire. The signals of differing amplitudes
can then be separated using various signal processing techniques. By positioning
many recording microwire electrodes into a region of neural tissue, it is possible
to isolate and record the electric activity of many individual neurons simultaneously.
Lower density electrode arrays are problematic because they are severely limited
in the amount of information they can gather.
