Deep Brain Stimulation

Deep brain stimulation (DBS) is a well-established functional neurosurgical

technique that is used to treat a variety of neurological disorders
It is a medical procedure that involves a mild electrical current delivered to a
specific part of the brain.
The electricity in that current stimulates the brain cells in that area, which
can help several conditions. The current reaches the brain through one or
more wires attached to a small device implanted underneath the skin.
DBS treats conditions that affect how the neurons, a key type of brain cell,
do their job. When neurons aren't working properly, that affects the abilities
those neurons control. Depending on how severe the problem is, they can
either partly or completely lose those abilities.
DBS implantation procedure

There are two steps:

• Lead placement
• Pulse generator placement
• Lead placement

The number of leads and their placement depend on the

patient‘s case. Some people may only have one lead, while
others may have multiple leads on one or both sides of their
heads.
Once the electrodes are secure, the ends of the electrodes are
protected with a plastic cap and tunneled under your skin to the
back of your head. The incisions are then cleaned and closed.
• Pulse generator placement

The surgeon will make a small incision in your skin just below your clavicle
bone during this procedure, then create a small pouch-like space under your
skin to hold the pulse generator.
They will insert an extension wire that travels between the outside of the
skull and the underside of the skin.
They'll make the wire travel downward until the far end is underneath the
skin near clavicle at the pocket for the battery. They'll then connect the
extension wires to the DBS electrodes and the other end of the extension
wire to the pulse generator. It's then placed into the pouch-like space under
the skin before sewing it shut.
Transcranial Magnetic Stimulation (TMS)

is a noninvasive form of brain stimulator in which a changing magnetic field is

used to induce an electric current at a specific area of the brain
through electromagnetic induction. An electric pulse generator, or stimulator,
is connected to a magnatic coil connected to the scalp. The stimulator
generates a changing electric current within the coil which creates a varying
magnetic field, inducing a current within a region in the brain itself .

TMS has shown diagnostic and therapeutic potential in the CNS with a wide
variety of diseases.
There are different ways to perform TMS. They have to do with the
magnet’s strength or various ways to apply the magnetic field.

• Magnet strength. The unit for measuring the strength of a magnet is

the tesla (T). Most TMS magnets generate a magnetic field with a
strength of 1.5T to 2T, similar to a magnetic resonance imaging (MRI)
scanner. However, the area of the magnetic field is much smaller than it
is for an MRI because the TMS magnet is so much smaller.

• Pulse frequency. Each time the magnetic field turns on and off is a
pulse. The number of pulses per second is the frequency (which is
measured in hertz, abbreviated Hz). TMS can involve low-frequency
pulses at 1 Hz (1 pulse per second) or high-frequency pulses at 5 Hz to
10 Hz (5 pulses per second to 10 pulses per second). TMS that uses
repetitive pulses is known as repetitive TMS (rTMS).
• Pulse patterns. TMS can also use different patterns of pulses for
treatment. An example of this is theta-burst stimulation (TBS). During
TBS, a triplet of 5 Hz bursts happens, for a total of 15 pulses in a
second. Using these burst patterns speeds up treatment, making it
about five or six times faster than other methods.

• Magnetic coil type and stimulation target. Different kinds of

magnetic coils can target different brain structures. Deep TMS
(dTMS), which involves an H-shaped helmed coil, targets deeper brain
structures than rTMS and TBS. Research shows dTMS is effective in
treating conditions such as obsessive-compulsive disorder (OCD).
TMS has several advantages that make it a useful treatment.

• It’s noninvasive. You don’t need surgery for this procedure, and you
can go about your day once a session ends. It also doesn’t involve
anesthesia of any kind.

• It’s safe. Seizures are the most common serious side effect of TMS, but
these are very rare. Your risk of having a seizure from TMS is less than
0.01% for each session. Other side effects are usually mild and only last
a few minutes.

• It’s effective. The success rates of TMS vary by condition, but the
available research clearly shows that it works.
• It can save lives. One of the key conditions that TMS treats, major
depressive disorder, can be so severe that it leads to death by suicide.
TMS can save lives when it brings improvements to depression
symptoms or causes depression to go into remission entirely.

• It can work cooperatively with other treatments. TMS often

happens along with other treatment techniques, such as medications,
mental health therapy and more.
 Neural Tissue Engineering

Tissue engineering is the use of engineering methods to replace, replicate, or

improve biological tissues. Tissue engineering evolved out of the field of
material science, as biologically mimicking or biologically supporting material
chemistries were discovered that could support and sustain cellular growth
at tissue scales.
Broadly speaking, a suitable material substrate can provide a scaffolding to
cells and tissues and be tailored to provide a wide variety of effects from
supporting specific multicellular structures, to coincident immune system
modulation, to supporting sustained release of growth of supportive
chemical agents.
Neural tissue engineering may be able to address challenges for which
there may be no other medical solution. These challenges fall into three
categories: injury, disease, and implant integration. In tissue engineering,
we often look at the resultant pathophysiology from these challenges as a
way to identify specific biological responses that can serve as therapeutic
targets that may be corrected, manipulated, or replaced, with the goal of
reducing or repairing the consequent tissue damage.
 Neural Device Integration

With the emergence of neural interfaces and neural implants such as deep
brain stimulators, vagal nerve stimulators, or implantable brain–computer
interfaces, tissue engineering approaches can help to reduce the
consequent foreign body inflammatory response, improve integration, or
even be used to support innervation and afferent/efferent nervous
connectivity of implantable organs or nonnervous tissues. Tissue
engineering the integration of devices with the nervous system has the
parallel goals of minimized tissue trauma, maximized efficiency of
transmission/signal propagation, and access to a more complex and precise
density of sense and control.
Many implantable systems can be considered a form of local, chronic injury
(e.g., small stab wounds for penetrating electrodes), and can incur mechanical
disruption of organized nervous tissues, breaches of the BBB, and an
undesired influx of inflammatory or immune cells.

Tissue engineering strategies have the potential to improve these situations,

either via enhancing acute or chronic tissue tolerance to an implanted foreign
body, directing immunomodulation to decrease the overall inflammatory
response, or by the design of tissue engineered electrode coatings that
facilitate improved tissue intergration and prolonged electrode function.
 Tissue Engineering Technologies

1. Material Infrastructure for Regeneration

2. Neurotrophic Factors
3. Cellular Engineering Approaches
4. Immunomodulation
5. Electrical Stimulation for Repair and Regeneration
1. Material Infrastructure for Regeneration

The primary approach to neural tissue engineering is to develop a post-

injury environment that can facilitate structural regeneration, as well as to
provide the necessary signaling cues to promote cellular tropism and
growth, and eventual regeneration of cells and tissues.
Schematic of spinal cord hemisection injury model and delivery of enzyme
to the lesion site. The 1% SeaPrep agarose gel-microtube scaffold is
implanted on top of the lesion and covered with stiffer 0.7% SeaKem
agarose gel to keep the scaffold in place. (Reprinted from Lee et al).
2. Neurotrophic Factors

Neurotrophic growth factors play important roles in regulating axonal

growth, survival, neurotransmission, and plasticity, and positively influence
nerve regeneration after injury to the nervous system.
An important family of neurotrophic factors are neurotrophins, a class of
neuron-supporting molecules including nerve growth factor (NGF), brain-
derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and
neurotrophin 4/5 (NT-4/5); ciliary neurotrophic factor (CNTF); and glial cell
line-derived growth factor (GDNF).
While a majority of these neurotrophic factors elicit favorable response on
axonal growth, the effect of individual growth factors on axonal elongation
after injury depends heavily on the severity of the injury, neuronal cell
type, and population of growth factor receptors.
Neurotrophic factors induce axonal elongation in a chemotactic manner
and hence need to be present in high enough concentrations at the
lesion site in order to facilitate nerve regeneration.

The potential for nerve regeneration after injury to the nervous system
was traditionally thought to be limited due to the absence of significant
neurogenesis.

However, it was only when neuronal precursor cells isolated from the
forebrain were shown to differentiate into neurons that the potential of
stem cell therapy for nerve regeneration was fully realized.
A number of stem cell types are currently being investigated to treat CNS
and PNS injuries. Stem cells are of interest in tissue engineering and repair
as they have the propensity to replace the lost or injured cells, have
immunomodulatory effects, and can induce neuroprotection and
remyelination cascades.
4. Immunomodulation

Another tissue engineering strategy is to target the endogenous immune

system as a means of diminishing or managing the immunemediated
effects on tissue degeneration.
 5. Electrical Stimulation for Repair and Regeneration
Electrical stimulation of the nervous system has been shown to accelerate
plasticity and promote recovery and rehabilitation after injury.
Electrical activity is known to stabilize the synapse, induce gene expression
changes, and facilitate neurogenesis. The mechanism by which electrical
activity induces these outcomes, however, is largely unclear.
It is believed that increased electrical activity of the neurons induces the
influx and accumulation of intracellular calcium which then triggers a
secondary cascade–mediated synthesis of “early genes.” Protein products
of these early genes are then responsible for activation of “late genes” that
control neurogenesis.
Therefore, a genetic neuroprosthesis can be developed by controlling the
electrical activity of the neuron.
Direct current (DC) is generally applied for electrical stimulation of nerves
due to the endogenous presence of DC voltage gradients within tissues.

In early studies, the application of DC electric fields (approx. 100 mV/mm)

from an electrode-containing, silicone conduit onto the dorsal half of guinea
pig spinal cords showed robust regeneration of axons into the conduit when
compared to control guidance channels.