Note: Descriptions are shown in the official language in which they were submitted.
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DEVICE, SYSTEM, AND METHOD FOR MECHANOSENSORY NERvE ENDING
STIMULATION
to
=
BACKGROUND OF THE INV8NTION
Adaptation is a dynamic process reflected by a decrease in neuronal
sensitivity due to
repeated sensory stimulation, which can span a wide range of temporal scales
ranging from
milliseconds to lifetime of an organism. Attenuation of sensory responses due
to adaptation
is a common mechanism in sensory systems (visual, auditory, olfactory and
sornatosen..soiy),
which is stimulus specific (since it dopends on factors like stimulus strength
and frequency),
and generally rnpre pronounced at cortical rather than subcortical levels
(Chung et at., 2002).
Since sensory systems have a distinct number of outputs to represent a wide
range of
environmental stimuli, adaptation is considered essential to dynamically
reassign the limited
set of outputs to encode varying ranges of stimuli. As such, devices and
systems for
implementing studies to monitory adaptation in sensory systems have been
researched and
developed.
The delivery of electrical currents through the skin to activate sensory nerve
terminals
was studied, but electrical currents are an unnatural form of stimulation, and
may bypass
peripheral mechanoreceptors while activating fibers from deep and superficial
receptors
(Willis & Coggcshall, 1991). This approach to stimulation potentially reSults
in an altered
pattern of afferent recruitment due to differences in the electrical impedance
of nerve fibers
based on spectra, and collateral activation of efferent nerve fibers proximal
to the stimulus
site. Moreover, if biornagnetic techniques such as magnetoencephalography
scanning
(MEC:7) are used to study the cortical response adaptation, electrical
stimulation presents a
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source of interference in the neuromagnetic recordings. Also, piezoelectric
transducers to
provide vibratory stimulation were studied, and have an excellent frequency
response.
However, the piezeoelectric transducers have limited displacement amplitudes,
and require
large source currents to operate the piezoelectric crystal. Proximity of these
transducers to
the MEG sensor array produces substantial electrical interference. Disk
vibrators (Kawahira
et al., 2004; Shirahashi et al., 2007) can provide vibratory stimulation, but
operate at a single
frequency and are incompatible with MRI and MEG due to multiple noise sources
(electric,
magnetic, acoustic). Recently, pneumatic manifolds were used to generate
tactile stimuli
using air-puffs (Huang et al., 2007) and Von Frey filaments (Dresel et al.,
2008) in the MRT
scanner. However, the time required to instrument the participant can limit
protocol
application, and the movement of face or limbs during a stimulation session
may alter the site
of stimulation.
Therefore there is a continued need for improved devices and systems for
implementing studies to monitory adaptation in sensory systems have been
researched and
developed
BRIEF SUMMARY OF THE INVENTION
In one embodiment, a device for stimulating mechanosensory nerve endings can
include: a housing having an internal chamber and first and second openings; a
membrane
covering the first opening of housing, said membrane being sufficient
flexibility to vibrate
upon receiving vibratory stimulation from a vibratory mechanism; and a
coupling mechanism
at the second opening configured for being fluidly coupled to the vibratory
mechanism,
wherein the entire device consists of magnetically unresponsive materials. The
housing can
be cylindrical, or any polygon shape. The membrane can be integrated with the
housing or
coupled thereto, such as with adhesive. Optionally, the membrane can be
removably coupled
to the housing.
In one embodiment, the device can include a lid having an aperture
therethrough.
The lid can be configured to couple the membrane to the housing. The lid and
housing can
include corresponding fasteners so that the lid can fasten to the housing. The
corresponding
fasteners can include one or more of the following: a snap coupling, a tongue
and groove,
corresponding threads, adhesive, or a clip.
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In one embodiment, the coupling mechanism for receiving the vibratory
stimulation
can include a fluid coupling mechanism that fluidly couples the internal
chamber to the
vibratory mechanism. For example, the coupling mechanism can include a luer
lock.
Optionally, the coupling mechanism can be located in a wall of the housing. In
another
option, the coupling mechanism can be located opposite of the membrane with
respect to the
to internal chamber.
In one embodiment, the device can include a tube coupled to the coupling
mechanism
and capable of being coupled to the vibratory mechanism. The tube can have a
length
sufficient to extend out of a magnetic field of an MRI or MEG so that an
opposite end of the
tube is capable of being coupled to a component having magnetically responsive
components, and where the magnetically responsive components do not react to
the magnetic
field.
In one embodiment, the membrane has a cross-sectional profile corresponding to
a
cross-sectional profile of the housing. In one aspect, the membrane is
flexibly resilient
and/or elastic. In one aspect, the membrane is less than about 0.5 mm thick.
In another
aspect, the membrane is less than about 0.127 mm or about 0.0005 inches. The
thickness of
the membrane can vary greatly. The membrane is configured to vibrate
sufficiently to
activate cutaneous mcchanoreceptors which then convey neural impulses along
primary
somatosensory pathways and are encoded in the brain. . The membrane can have a
positive
vibration displacement of at least 1 mm. Preferably, the vibration
displacement is at least
about 4 mm.
In one embodiment, the present invention can include a system for stimulating
mechanosensory nerve endings. Such a system can include: a device as described
herein; a
vibratory mechanism configured for being fluidly coupled with the coupling
mechanism of
the device; and a magnetically unresponsive tube configured to fluidly couple
the device to
the vibratory mechanism.
In one embodiment, the vibratory mechanism is configured to oscillate fluid
into
and/or from the chamber so as to vibrate the membrane or to cause pressure
changes in the
fluid. Optionally, the vibratory mechanism can include a servo motor. In one
aspect, the
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vibratory mechanism is fluidly coupled with the magnetically unresponsive tube
which is
fluidly coupled to the coupling mechanism.
In one embodiment, the system can include a computing system capable of being
operably coupled with the vibratory mechanism. In one aspect, the computing
system is
operably coupled with the vibratory mechanism.
In one embodiment, the system includes an MM system.
In one embodiment, the system includes a MEG system.
In one embodiment, the present invention can include a method for stimulating
mechanosensory nerve endings. Such a method can include: providing a device or
system as
described herein; placing the membrane on skin of a subject; and oscillating
the membrane
on the skin.
In one embodiment, the mechanosensory nerve endings are stimulated in an MRI.
In one embodiment, the mechanosensory nerve endings are stimulated in an MEG.
In one embodiment, the mechanosensory nerve endings are stimulated as part of
physical therapy.
In one embodiment, the simulation is for motor rehabilitation in patients with
developmental sensorimotor disorders or injury.
During any of the testing, the method can include monitoring the brain of the
subject
during the nerve ending stimulation.
These and other embodiments and features of the present invention will become
more
fully apparent from the following description and appended claims, or may be
learned by the
practice of the invention as set forth hereinafter.
BRIEF DESCRIPTION OF THE DRAWINGS
To further clarify the above and other advantages and features of the present
invention, a more particular description of the invention will be rendered by
reference to
specific embodiments thereof which are illustrated in the appended drawings.
It is
appreciated that these drawings depict only illustrated embodiments of the
invention and are
therefore not to be considered limiting of its scope. The invention will be
described and
explained with additional specificity and detail through the use of the
accompanying
drawings in which:
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Figures 1A-1B include brain MRI images (Figure IA panels A and B) and the
tactile
stimulation response to frequency (Figure 1B panels A-F). These figures show
source
reconstruction results for one subject. Dipoles are localized bilaterally in
response to lip
stimulation (Figure lA panel A), and contralaterally for right hand
stimulation (Figure lA
panel B). Dipoles locations and orientations are shown in orthogonal (axial
and coronal)
MRI slices. The Si dipole strength across time is illustrated for each
stimulation rate in the
panels on the right (Figure 1B panels A-F)
Figures 2A-2B include graphs that illustrate a comparison of primary
somatosensory
cortex (Si) peak dipole strengths at 2, 4, and 8 Hz for lip and hand
stimulation.
Figures 3A-3C include graphs that illustrate a comparison of SI peak dipole
strength
latency for lip and hand stimulation at 2 (Figure 3A), 4 (Figure 3B), and 8 Hz
(Figure 3C).
Figures 4A-4B illustrate an embodiment of a TAC-Cell device showing a
polyethylene cylinder, 0.005" thick silicone membrane, and Luer tube fitting
which links the
cell to the servo-controlled pneumatic pump.
Figure 5 includes a schematic diagram of the TAC-Cell stimulus control system.
Figure 6 includes a graph that illustrates sample stimulus voltage pulse and
the
corresponding TAC-Cell displacement response. The mechanical response time
(MRT) of
the TAC-Cell is 17 ms.
Figure 7 is an image illustrating a TAC-Cell device secured on the midline of
the
upper and lower lip vermilion using double-adhesive tape prior to the MEG
recording
session. The TAC-Cell device can also be secured on other body portions, such
as on the
glabrous surface of the right hand (index and middle digits), and the oral
angle on the face.
Figure 8 illustrates patterned stimulus trains used as input to the TAC-Cell
pneumatic
servo controller for MEG sessions. 125 pulse trains at 2, 4, and 8 Hz were
applied in
separate runs to the glabrous skin of the hand and lower face. Each pulse
train consists of six
50 ms pulses regardless of train rate.
Figures 9A-9C include graphs that show the TAC-Cell displacement in
millimeters
versus time in seconds for 2 Hz, 4 Hz, and 8 Hz.
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Figure 10 includes a graph that shows the facial stimulation at 2 Hz, 4 Hz,
and 8 Hz
and the corresponding decrease in the mean global field potential cortical MEG
response
which shows adaptation to the stimulation.
DETAILED DESCRIPTION
Generally, the present invention relates to the use of the relatively high
temporal
resolution of the MEG technique with skin stimulating vibration in
milliseconds to compare
and characterize the short-term adaptation patterns of the nervous system
(e.g., using human
hand and lip stimulating vibration) primary somatosensory cortex Si in
response to trains of
synthesized pneumatic cutaneous stimuli provided by the skin stimulating
vibrations. The
spatial resolution of MEG has proved sufficient to map the SI representation
of the human
body including the lips, tongue, fingers, and hand, but can be used on other
body part as welt
Although previous studies have shown that a vibrotactile adaptation mechanism
exists in
both hand and face, little is known about the short-term adaptation mechanisms
of either
hand or face Si to repeated punctate mechanical stimuli in humans. The
stimulating
vibration can be induced using a MRI/MEG compatible tactile stimulator cell
(TAC-Cell). It
is thought that repetitive cutaneous vibration stimuli can result in frequency-
dependent
patterns of short-term adaptation manifested in the evoked neuromagnetic S1
responses. It is
also thought that there may be a significant difference between spatiotemporal
characteristics
of the adaptation patterns of the face and hand because of fundamental
differences in
mechanoreceptor innervations and function in motor behavior.
The TAC-Cell device can non-invasively deliver patterned cutaneous stimulation
to
the face and hand in order to study the neuromagnetic response adaptation
patterns within the
primary somatosensory cortex (Si). Individual TAC-Cells can be positioned on
any
cutaneous body surface, such as the glabrous surface of the right hand, and
midline of the
upper and lower lip vermilion as described herein. A 151-channel
magnetocncephalography
(MEG) scanner can be used to record the cortical response to tactile stimulus
provided by the
TAC-Cell, which consisted of a repeating 6-pulse train delivered at three
different
frequencies through the active membrane surface of the TAC-Cell. The evoked
activity in
S1 (contralateral for hand stimulation, and bilateral for lip stimulation) can
be characterized
from the best-fit dipoles of the earliest prominent response component. The Si
responses
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manifested significant modulation and adaptation as a function of the
frequency of the
punctate pneumatic stimulus trains and stimulus site (glabrous lip versus
glabrous hand).
The TAC-Cell can be useful for activating the human somatosensory brain
pathways
using punctate, scalable stimuli in the MRI/MEG scanner environment. The TAC-
Cell is
non-invasive and efficient at nerve stimulation applications.
Accordingly, the present invention includes devices, systems, and method of
using
the TAC-Cell to stimulate mechanosensory nerve endings in the skin of the face
and hand.
The device is prepared from non-magnetic responsive materials (e.g., materials
that do not
respond to magnetic fields, such as non-ferromagnetic, non-antiferromagnetic,
non-
ferrimagnetic, non-diamagnetic, or other similar materials). Such stimulation
can be used in
Is brain imaging instruments, such as magnetic resonance imaging (MRI) and
magnetoencephalography (MEG) brain scanners. During use, the device stimulates
nerves,
which then allows imaging of the brain response during peripheral nerve
stimulation.
The device can include a container with one open end that is fitted with a
micro
membrane over the opening and having a cap with an aperture that fits over the
membrane
and fastens to the cylinder. The container also has another opening with a
fitting to receive
fluid ( e.g., hydraulic liquid or pneumatic gas, such as air) into and out
from the chamber
within the container, where the change in pressure in response to movement of
pressure
causes the micro membrane to vibrate similar to a drum. The opening and
fitting can be
configured to connect to a pressure source that can supply a fluid, such as
air or the like, to
cause the vibration by rapidly oscillating the fluid into and out from the
chamber. The TAC-
Cell can be used as a neurotherapeutic intervention device has considerable
potential in adult
and pediatric movement disorders. The TAC-Cell can have other configurations
to provide
the vibratory stimulation as described herein, and operate so as to be
compatible with MM
and/or MEG.
The TAC-Cell can be used to stimulate mechanosensory nerve endings in the skin
of
the face and hand or other body parts for brain imaging and potential motor
rehabilitation
applications in humans. The TAC-Cell can be used in a clinical research
setting for motor
rehabilitation in patients with (1) developmental sensorimotor disorders, and
(2) adults who
have sustained cerebral vascular stroke. Other uses of TAC-Cell are also
contemplated, such
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as in physical therapy, monitoring brain activity during a brain scan, or
combined with
electroencephalography.
The TAC-Cell can be configured as a small-bore pneumatic actuator that has a
membrane configured to vibrate in response to pneumatic changes provided from
a
pneumatic device. The TAC-Cell can be configured to be MR1/MEG compatible, non-
invasive and suitable for both adults and children, with and without
neurologic insult/disease.
In one example, the TAC-Cell can be prepared from a cylindrical (e.g., 19.3 mm
diameter)
chamber prepared from a material that is not magnetically responsive (e.g., a
polyethylene
vial), and includes a vibratory membrane (e.g., 0.005" silicone membrane
sheet) attached to
an opening of the cylindrical chamber such that the vibratory membrane can
vibrate in
response to fluid pressure changes within the cylindrical chamber. For
example, the vibratory
membrane can be placed between the lip of the cylindrical chamber and a
retaining ring.
However, other coupling configurations can be used to couple the vibratory
membrane to the
cylindrical chamber, such as by adhering the membrane to the chamber. These
size
parameters can be varied to a diameter (or cross-sectional dimension of the
sheet) at about
0.5 nun, 1 mm, 1.5 mm, 2 mm, 3 mm, 5 mm, or even larger up to 2 cm, 5 cm, and
possibly
even bigger. Also, the materials of the TAC-Cell chamber and/or membrane can
vary as
long as being magnetically unresponsive. That is, the materials of TAC-Cell
arc not
magnetically responsive. As such, the chamber can be prepared from various
polymers and
ceramics, where the membrane is prepared from polymers and some rubbers. The
variation
of the materials while maintaining the magnetically unresponsive
characteristic can be
achieved with a myriad of materials.
The TAC-Cell can be included in a TAC-Cell system that includes other
components,
such as a pneumatic device that provides the vibratory fluid that vibrates the
membrane.
Also, the TAC-Cell system can include an MM and/or MEG or other scanner. An
example
includes a 151-channel CTF MEG scanner that is configured to record the
cortical
neuromagnetic response to a pneumatic tactile stimulus produced by the TAC-
Cell. The
pneumatic device can be configured to provide the TAC-Cell with a vibratory
stimulus that
includes a repeating 6-pulse train (50-ms pulse width, intertrain interval = 5
s, 125 reps/train
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rate, train rates [2, 4, & 8 Hz, see Figure 8]); however, other variations and
patterns of
pneumatic tactile stimulation can be performed.
The TAC-Cell device/system can also include a fastener that secures the TAC-
Cell to
a subject on the skin. An example of such a fastener includes adhesive,
strapping, a clamp,
an adhesive collar, a double-adhesive tape collar, or other types of non-
ferrous attachment,
such as adhesives, clips, wrappings, bandages, and the like can be used for
attachment of the
TAC-Cell to a subject. The fastener can be configured to secure the TAC-Cell
at various
locations across the skin, such as on the face, hands, fingers, finger tips,
palms, feet, feet
bottoms, arms, legs, torso, or any other location. For example, some skin
locations that a
fastener can be configured for holding a TAC-Cell thereto can include: a
glabrous surface of
the right hand (index/middle finger), and midline of the upper and lower lip
vermillion.
A single TAC-Cell can be attached to any portion of the skin of a subject.
Alternatively, an array of TAC-Cell devices can be attached to one or more
portions of skin
of a subject.
Additionally, the present invention can include a multichannel TAC-Cell array
(e.g.,
multiple TAC-Cell devices) that can be used to simulate the sensory
experiences associated
with apparent motion and direction in the face and hand or other parts of the
body. The
TAC-Cell array may include several TAC-Cells placed in a spatial pattern that
can be
activated in a sequence (e.g., w/small time delays such as 10 ms from one
adjacent TAC-Cell
to another). Alternatively, the placement and activation can be random or
predesigned. The
TAC-Cell array can be used as a new form of neurotherapeutic stimulation
(intervention) to
induce and accelerate mechanisms of brain plasticity and recovery in patients
suffering from
acute cerebrovascular stroke affecting movements of the face (speech,
swallowing, gesture)
and hand (manipulation).
The TAC-Cell can be in other variations and embodiments. For example, the TAC-
Cell can have: a 'dome' membrane; textured membrane; membrane integrated to
the TAG-
Cell body (e.g., without retainer collar); miniaturization of the pneumatic
servo controllers
and high-speed pneumatic switches (valves) is feasible when available;
integrated oscillating
feature to move membrane, such as micro servo or pumps; other various features
can be
modified. The TAC-Cell could potentially be driven by the servo electronics.
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Also, the TAC-Cell can be driven by a magnetically responsive pneumatic
device,
which is installed distally from the TAC-Cell device and a magnetically
unresponsive tube
can fluidly couple the TAC-Cell with the pneumatic device.
The TAC-Cell membrane can be oscillated by pneumatic servo control of a
pneumatic device so as to provide vibratory stimulus generation at the skin. A
fluid conduit
prepared from a magnetically unresponsive material can pipe the vibratory
fluid to the TAC-
Cell so as to vibrate the membrane. The active 'pulsating' surface of the TAC-
Cell can be
used to generate a punctate mechanical input to the skin (e.g., vibration can
be 4.25 ram
displacement with 25 ms rise/fall time), where the rise and oscillation can
vary depending on
fluid oscillation and the cross-section profile and size of the membrane.
However, all of the
dimensional, oscillatory, material or other parameters can be varied within
reason.
As shown in Figures 4A-4B, one embodiment of the TAC-Cell device 400 has a
housing 402 with an internal chamber 402a and a membrane 403 over one opening
404 of the
chamber 402a, where the membrane 403 is configured to vibrate in response to a
vibratory
mechanism. As shown, an optional annular ring 405 is used to couple the
membrane 403 to
the housing 402 so as to cover the opening 404. The TAC-Cell device 400 can
include a
neck 406 coupled to the housing 402, and the neck 406 can have an internal
lumen 408 that
extends from the chamber 402a to an opening 412. The neck 406 can also have a
coupling
component 410 at the opening 412 that can be coupled to a pneumatic device,
such as
through a tube. The coupling component 410, for example, can be configured as
a luer
fitting.
In one embodiment, the housing 402, membrane 403, ring lid 404 (with aperture
if
membrane is not integrated with housing), neck 406, and coupling component can
be plastic,
polymeric, rubber, silicone, polyethylene, polypropylene, ceramic, or the like
as long as not
magnetically responsive.
Figure 5 shows an embodiment of a TAC-Cell system. As shown, the TAG-Cell is
fluidly coupled to a servo motor through a pneumatic line. The servo motor can
include a
position sensor that is operably coupled to a servo motor controller. Also,
the servo motor
controller can receive input from a central processing unit (CPU), such as
with a 16 bit
ADC/DAC. Additionally, the servo motor controller can be operably coupled to
an amplifier
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that can amplify the signal from the servo motor controller before being
provided to the servo
motor. As such, the TAC-Cell can be controlled and receive fluid pneumatic
vibrations from
a remote servo motor through a magnetically unresponsive pneumatic line.
Accordingly, the TAC-Cell 402 can have a fluid coupling between the chamber
402a
that can be connected to an external vibratory mechanism (e.g., servo motor)
to generate an
oscillatory action. The servo can be a sophisticated servo system that
regulates and generates
the pressure to drive the membrane 403. The servo or other vibratory mechanism
can be
located a large distance from the housing 402 and membrane 403 so that there
are no metallic
or other magnetically responsive components associated with the housing 402
and membrane
403, which allows for use in brain scanners.
In one embodiment, the housing can be similar to a standard vile, such as a
sample
vile one or chemistry vial. The vial lid can be machined so that an opening
(aperture) is
formed in the lid, and a membrane (e.g., 5,000th of an inch thick silicone
membrane) can
cover the opening of the vial and vibrate through the opening of the cap. The
housing can be
configured to include a fluid coupling mechanism, such as a Luer fitting. The
fluid coupling
mechanism can be located at the bottom of the housing, or at any other
location in the
housing. The fluid coupling (e.g., Luer-loc fitting) can accept a silicon tube
or other
magnetically unresponsive tube that is fluidly coupled to the vibratory
mechanism at the
other end.
The vibratory mechanism can be computer controlled (e.g., CPU) so that the
pressure
inside the TAC-Cell is controlled and very precisely regulated. The vibratory
mechanism
can drive the TAC-Cells, a membrane is displaced very rapidly so it bulges up
or is sucked
into the cylinder and the 10-90% rise/fall time can be on the scale of 25 ms.
In a 25,000th of
a second the membrane can travel over 3.6 mm or other dimension depending on
the
dimension of the membrane, and that produces a very robust stimulus to the
surface of the
skin which in turn drives the somato sensory nerves in the skin.
Previously, providing stimulus in an MRI or MEG has been difficult because of
the
problems associated with stimulating somatosensory systems in a magnetic
environment like
the MRI or the MEG. The magnetically unresponsive TAC-Cell can provide
cutaneous or
tactile stimulus without being compromised by a magnetic field. This allows
for feeling the
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pressure change on the skin, and allowing a medical professional to be able to
see what is
happening inside the brain of the subject having the pressure change on their
skin. The TAC-
Cell can provide a way to objectively test an entire pathway in the human
nervous system
using the two scanner technologies the MM and MEG. The sensation of the TAC-
Cell is
like tapping on skin because the stimulus comes on and off so fast. The
membrane
stimulator has a good frequency response of up to about 30 Hz. Examples herein
show 2, 4,
and 8 Hz. The TAC-Cell can vibrate the skin surface and activate thousands
sensory nerve
terminals in the skin, which sends a nerve volley (signal) through the spinal
cord or brain
stem, and then finally to the thalamus and relayed to the somatosensory
cortex.
Accordingly, TAC-Cell provides a pneumatic tactile stimulation cell membrane
for
somatosensory stimulator that is MM compatible and MEG compatible, and can be
used in
human neuromagnetic cutaneous stimulation. It could also be used with any
animal, such as
fish, birds, reptiles, mammals, and the like.
The TAC-Cell could be used for basic neurologic assessment of brain function
using
MM and MEG scanning technologies, specifically to map the integrity of
trigemino-thalamo-
cortical (face) and medial lemniscal-thalamo-cortical (hand-forelimb/foot-hind
limb)
somatosensory pathways in human brain, and properties of neural adaptation.
The TAC-Cell can be used to study animals using a MEG scanner to map the brain
response to the TAC-Cell vibration stimulation. The TAC-Cell can be used for
activation of
the somatosensory pathways in the human brain.
Figure 10 herein shows a servo-controlled stimulus waveform, which serves to
drive
the pneumatic pump, which in turn modulates pressure within the TAC-Cell. They
are
discrete, quick pulses, which are just a few milliseconds in duration. The
waveform in the
lower trace shows the brain neuromagnetic response. As shown for face
stimulation, the
brain is firing within about 50 ms after each stimulus pulse.
The TAC-Cell can stimulate the brain so that it is highly visible stimulation
in brain
scans (see Figure 1A). The TAC-Cell device is useful for diagnostics in
mapping out a
lesion, and can be used to determine if a neural signal pathway is
interrupted. Also, the
TAC-Cell device can identify whether a patient sustained damage during a
stroke. The TAC-
Cell can also be used in the rehabilitation of a damaged brain. As such, the
TAC-Cell can be
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used for activating the nervous system, and as therapeutic stimulus to help
the brain re-wire
after it's been injured.
In physical therapy, the TAC-Cell can be used to replace the electrical
stimulators.
One shortcoming with electrical stimulators is that it reverses the order in
which nerve cells
are recruited. Another shortcoming is that electrical stimulation does not
distinguish between
sensory and motor fiber activation. When you introduce electrical current to
the skin, the
neurons with the lowest threshold to current stimulation will fire first and
may involve a
mixed activation of sensory and/or motor neurons. The TAC-Cell eliminates this
problem
and selectively activates mechanoreceptive afferent neurons and does not
directly stimulate
motor neurons. Under natural forms of cutaneous stimulation (i.e., touch,
pressure, vibration
as opposed to the use of electrical currents), normal recruitment order and
neuron type is
preserved. The TAC-Cell is particularly well suited to selectively simulate
the A13 primary
afferents associated with the fast adapting type I (FA I) and type II (FA II),
and the slow
adapting (SA I and SA Ipsensory nerve fibers found in skin which encode touch,
vibration,
texture, and skin stretch. Thus, the TAC-Cell is superior to
electrostimulation in these
regards.
The single or TAC-Cell array can be used in all different types of ways for
different
stimulation studies. This can include right body studies, left body studies,
bilateral
stimulation, and hemispheric lateralization.
In an example of an array, five TAC-Cells can be placed at predetermined
locations,
and each TAC-Cell is individually controlled by an individual fluid line. When
the TAG-
Cells are arranged in a straight line, and then turning the individual cells
on with a time
delay, such as a 10 ms time delay between each TAC-Cell, the brain interprets
this
perception as apparent motion or movement This can provide a virtual
experience of motion
for the healing brain, and the perception and the experience of motion that
will actually help
damaged neurons and cortex re-wire and form connections. This is part of brain
plasticity.
The TAC-Cell device can be used for stimulation of either the lip or hand with
the
same patterned stimulus, and can be effective to induce short-term adaptation
of S1 .
Difference in short-term adaptation patterns of the hand and lip may be a
function of the
difference in mechanoreceptor typing in cutaneous and subcutaneous regions and
also due to
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the difference in facial and limbic musculature. There may also be difference
with other
parts of the body. The magnitude of attenuation of S1 response depends on the
stimulus
frequency and pulse index with attenuation being most prominent at 8 Hz for
both hand and
lip stimulation and less prominent at 2 Hz. The significant difference between
the latencies
of peak dipole strengths of hand and lip Si is attributable to the difference
in axon length and
distance from the mechanosensory nerve terminals in the lip and hand to their
central targets
in Si.
The TAC-Cell can be used for basic neurologic assessment of brain function
using
MRI and MEG scanning technologies, specifically to map the integrity of
trigemino-thalamo-
cortical (face) and dorsal column-medial lemniscal-thalamo-cortical (hand-
forelimb/foot-
hindlimb) somatosensory pathways in human brain. Comparison of the
spatiotemporal
adaptation patterns between normal healthy adults and different clinical
populations such as
children with autism, adults with a traumatic brain injury or a
cerebrovascular stroke may
shed new insight on fundamental sensory processes.
For example, repeated tactile stimulation in autistic children resulted in
hypersensitivity, and an enhanced but slower adaptation response. A suppressed
GABAergic
inhibition mechanism due to the reduction in the proteins utilized for
synthesizing GABA is
believed to be responsible for these abnormal response characteristics.
Another embodiment can include patterned somatosensory stimulation for motor
rehabilitation using TAC-Cell or TAC-Cell arrays. Sustained somatosensory
stimulation can
increase motor cortex excitability and has implications in motor learning and
recovery of
function after a cortical lesion. Thus, in addition to functional mapping of
somatosensory
pathways, the TAC-Cell may find application as a new neurotherapeutic
intervention device
for the rehabilitation of adult and pediatric movement disorders.
EXPERIMENTAL
Ten healthy females (Mean age = 24.8 years [SD = 2.9]) with no history of
neurological disease participated in this study. The TAC-Cell used is a c
custom, small-bore
pneumatic actuator based on a 5-ml round vial with a snap-type cap (Cole-
Parmer, Part no.
R-08936-00). The polyethylene cap was machined to create an internal lumen
with a
diameter of 19.3 mm. A 0.005" silicone membrane (AAA-ACME Rubber Company) was
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held securely between the vial rim and modified snap-type cap. When
pneumatically
charged, the active silicone membrane surface of the TAC-Cell generated a peak
displacement of 4.25 mm with a 27 ms rise/fall time (based on 10% to 90% slope
intercepts).
A custom non-commutated servo-motor (H2W Technologies, Inc., NCM 08-25-
100-2LB) coupled to a custom Airpel glass cylinder (Airpot Corporation,
2K4444P series)
operating under position feedback (Biocommunication Electronics, LLC, model
511 servo-
controller) and computer control was used to drive the TAC-Cell with pneumatic
pressure
pulses. The computer was equipped with a 16-bit multifunction card (PCI-6052E,
National
Instruments). The stimulus control signals were custom programmed with
LabVIEWO
software (version 8.0, National Instruments) in our laboratory. These signals
served as input
to the servo controller, and were also used to trigger data acquisition by the
MEG scanner.
This hardware configuration achieved synchronization between stimulus
generation and
MEG data acquisition. A 15-foot silicone tube (0.125" ID, 0.250" OD, 0.063"
wall
thickness) was used to conduct the pneumatic stimulus pulse from the servo
motor to the
TAC-Cell placed on the participant in the MEG seamier. Mechanical response
time (MRT),
defined as the delay between leading edge of the pulse train voltage waveform
and the
corresponding TAC-stimulus displacement onset, was constant at 17 ms for all
stimulus rates
(Figure 6). The reported peak dipole strength latency values reflect
correction for the MRT
of the TAC-C ell.
As shown in Figure 7, double-adhesive tape collars 450 were used to secure
separate
TAC-Cells 400 at two skin locations of a subject 460, including the glabrous
surface of the
right hand (index/middle finger) (not shown), and midline of the upper and
lower lip
vermilion (shown). Placement at each skin site was completed within 1 minute.
Pneumatic servo control was used to produce pulse trains [intertrain interval
of 5 s,
125 reps/train rate]. Each pulse train consisted of 6-monophasic pulses [50-ms
pulse width]
(Figure 8). Short-term adaptation of the cortical neuromagnetic response to
TAC-Cell
patterned input was assessed using a randomized block design of three pulse
train rates,
including 2, 4, and 8 Hz at each skin site. The 2, 4, and 8 Hz stimulus blocks
lasted for
approximately 16, 14, and 12 minutes respectively. The order of stimulation
frequency and
stimulation site condition was randomized among subjects.
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Figure 7 also shows the subject 460 being analyzed with a whole-head MEG
system
440 (CTF Omega) equipped with 151 axial-gradiometer sensors was used to record
the
cortical response to the TAC-Cell inputs. A magnetically unresponsive tube 420
is coupled to
the coupling mechanism 410. Localizing coils 430, 436 were placed at 3
positions including
the nasion, and left and right preauricular points to determine the head
position with respect
to the sensor coil. Two bipolar electrodes 432 were used to record
electrooculograms (EOG),
which were used to identify trials affected by ocular movement artifacts and
eye-blinks.
Registration landmarks were placed at the same 3 positions used for
positioning the
localizing coils. Following the MEG recording session, TAC-Cells were removed
from the
skin sites, and participants were immediately placed inside a MM scanner in an
adjacent
suite to image their brain anatomy.
The MEG data was digitally bandpass filtered between 1.5 Hz and 50 Hz using a
bidirectional 4th order Butterworth filter. Trials corresponding to is before
and after the
pulse train stimulus were visually inspected for artifacts and those
containing movement or
eye-blink artifacts were discarded. The remaining trials for each experimental
condition
were averaged and the DC was offset using the pre-stimulus period as baseline.
Not less than
90 trials per subject in each experimental condition were used in averaging.
CURRYTM (COMPUMEDICS NeuroScan) is a specialized signal processing
software used to analyze the data obtained from MEG recordings. CURRY TM can
also be
used to co-register anatomical MM images with MEG data to map the biomagnetic
dipole
sources. Thus, source reconstruction was performed in CURRYTM using a
spherically
symmetric volume conductor model fitted to each individual subject skull
segmented from
the MRI data. The source space was defined as a regular grid of points
throughout the brain
volume (averaged distance between points was 4 mm). Current density analysis
was
performed using Minimum Norm Least Squares (MNLS) applied for the first
responses in
the train (i.e. characterized by the best Signal-to-Noise Ratio (SNR)) to
identify the spatial
peaks of activity that correspond to the Si activity. Location constrained
dipole analysis
(with dipole positions set at the spatial maximum retrieved by MNLS) was
subsequently used
to estimate the dipole direction and peak strength ( Amm = microampere-
millimeter) for the
Si activity following each pulse in the trains.
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Peak dipole peak strengths and latencies were compared for significant
differences
between stimulation site (lip and hand), frequency (2, 4, and 8 Hz), and pulse
index within
the trains using a three-way ANOVA. Differences in the corresponding dipole
locations in
the left hemisphere for lip and hand stimulation, respectively, were tested
for statistical
significance using a one-way ANOVA. SPSS software (version 17, SPSS Inc.) was
used for
statistical analysis.
For the digits stimulation, the earliest prominent response component that was
consistently observed across subjects peaked at 74.3 6.7 ms following each
cutaneous
pulse. For the lips stimulation the earliest component peaked at 50.3 5.8 ms
across subjects.
For both stimulation sites, these early components were followed by several
late components
with different temporal morphologies and spatial patterns of magnetic field.
For the earliest components of the response, the distribution of the evoked
magnetic
field across the sensor array was consistent with the presence of a source in
the contralateral
Si for the hand stimulation condition, and bilateral Si for the lips
stimulation. This was
confirmed by results of the source reconstruction, exemplified in Figure 1A.
In Figure 1A,
the marked areas indicate the following: 100 (dipole activation of the face
representation in
the primary somatosensory cortex); 102 (dipole activation of the face
representation in the
primary somatosensory cortex); and 104 (dipole activation of the contralateral
hand
representation in the primary somatosensory cortex). Dipolar sources were
consistently
localized within the hand representation of the left Si (hand stimulation),
and bilaterally
within the face representation of the S1 (lip stimulation).
The mean dipole locations for the lip and hand Si responses are reported in
Table 1.
A comparison between the dipole locations in the left hemisphere for lip
versus hand
stimulation using a one-way ANOVA on each of the three Cartesian coordinates
showed a
significantly different Si source along all three directions: lateral (p <
0.001), anterior (p =
0.008), and inferior (p < 0.001). The results are in agreement with the
somatotopic
organization of the primary somatosensory cortex (Penfield and Rasmussen,
1968), with the
lip S1 represented more towards the base of the postcentral gyrus, i.e. more
laterally,
anteriorly, and inferiorly than the hand Si.
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The peak dipole strength was used to quantify the magnitude of cortical
response as a
function of stimulation rate and serial position within the trains. Latencies
of the S1
responses were determined from the peak dipole strength and corrected for
mechanical
response time (MRT). A three-way ANOVA of dipole strength peaks, with factors
of
stimulation site, stimulation frequency, and pulse index within trains of
stimuli, showed
statistically significant main effects of frequency (p < 0,001) and pulse
index (p < 0.001).
The interactions between the stimulation site and frequency (p = 0.016), and
frequency and
pulse index (p 0.003) were also statistically significant.
The peak dipole strength of the SI response (Figure 2A-2B) shows a progressive
attenuation with the serial position of the stimuli in the train. The sharp
attenuation of the
is neuromagnetic response that was apparent for the 8 Hz stimulation
condition prevented us
from analyzing the latencies beyond the 3rd dipole strength peak for both lip
and hand
stimulation conditions. The magnitude of the Si adaptation was slightly
greater for the lip
when compared to the hand among the 3 different test frequencies and this may
he explained
in part by differences in mechanoreeeptor representation and mechanisms of
central
integration along lemniscal and thalamocortical systems.
A three-way ANOVA of the Si peak latencies, with factors of stimulation site,
stimulation frequency, and pulse index of the stimulus in the trains, showed
that the main
factor of stimulation site (p < 0.001) was statistically significant. None of
the interactions
were significant in this case. This reveals that TAC-Cell evoked SI response
peak latencies
were significantly different between the hand and lip at all 3 stimulation
frequencies (Figure
3A-3C), which is consistent with a shorter conduction time of the trigeminal
pathway.
TABLES
Table I
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Right Eland stimulation Lip stimulation
Left hemisphere t Left hemisphere
Right hemisphere
x (mm) y (mm) z (nun) I x (sum) y (mm) z (nun) I x (mm) y (mm) (nun)
ne.1,10p., -432.9 10 8.-S.1 93. .s -5E.2=5. 0 145=7. S72 76 3=4
S:72 5.5. 18.4=9.6 76.35-4
- Dipole locations for lip (contralateral and ipsilateral hemispheres), and
hand (contralateral
hemisphere) Si associated with 2, 4, and, 8 Hz TAC-Cell stimulation. Mean
standard
deviations across subjects are expressed in a Cartesian system of coordinates
based on
external landmarks on the scalp, with the x-axis going from left to right
through pre-auricular
points, y-axis from the back of the head to nasion, and z-axis pointing
towards the vertex.
