**4. Brief chronicle of DBS**

### **4.1 Early history**

During the early 1900s' experiments, first stereotactic frame was designed that allowed stimulation of deeper regions of brain. In 1947, X-ray pneumoencephalography was developed that enabled surgeons to locate the target with the help of detailed stereotactic atlas that was developed later on. In 1950, stereotactic techniques were used for the tremor treatment. Later, in 1963, Albe Fessard reported high-frequency (~100–200 Hz) electrical stimulation for the first time in the ventral intermediate thalamic nucleus that could substantially alleviate Parkinsonian tremor [9].

**33**

*Deep Brain Stimulation Approach in Neurological Diseases*

In 1960, levodopa treatment development was highly effective for Parkinsonian symptoms with lesser risk and expense compared to DBS implantation and this led

Inspite of the drawbacks, the research for use of DBSnever stopped. DBS continued to observe restricted use in intractable chronic treatment, with Medtronic Inc. (Minneapolis, MN, USA) and released the first fully implanted DBS systems

Other study groups investigated the use of thalamic DBS to treat consciousness diseases and reported few benefits. By the end of 1980s, it was evident that using levodopa would not hold the promising effects, after years of therapy, and patients developed wearing off along with the side effects like dyskinesias. Meanwhile, the technology of implantable medical devices had improved to the stage that it was routinely used for chronically implanted devices like cardiac pacemakers and spinal cord stimulators. The animal model study eventually got translated into clinical practices, and the first subthalamic nucleus (STN) DBS study got published [11]. By the beginning of the century, clinical use of DBS in Parkinsonian disorders has begun

Although the exact mechanisms of action of DBS are still elusive in spite of extensive research, several theories have been put forward. These proposed mechanisms can be divided according to the latency of onset of the effects from the time of stimulation into acute (seconds to hours) and chronic (days to months). The two

1.Electrophysiological and neurotransmitter modulation 395 likely explain the

However, there is a considerable overlap among the proposed mechanisms and one group of mechanisms has effects over the other, as described in detail in the following sections. Furthermore, depending on the methods used to investigate the mechanisms of action, different aspects of stimulation effects are tested. With an integrative approach combining investigations employing different modalities, one

Different methods have been used to quantify the changes produced by the DBS at the cellular, tissue and system levels to study the mechanisms of action of DBS. These modalities can be broadly classified into electrophysiological, imaging, biochemical, and molecular methods. Imaging techniques such as positron emission tomography (PET) and functional MRI (fMRI) provide information on both localand system-level changes. These are complementary methods: functional imaging studies have high spatial resolution, whereas electrophysiological methods have high temporal resolution. Moreover, electrophysiological methods directly measure neuronal activities rather than indirect measures of neural activities using blood-

2.Plasticity and neurogenesis may explain the chronic effects [12].

*DOI: http://dx.doi.org/10.5772/intechopen.91756*

the curtailing of early forms of DBS research.

**5. Rationale and mechanisms of action**

major proposed mechanisms are as follows:

can understand the general effects of DBS.

**5.1 Modalities used to study the mechanisms of DBS**

flow changes measured by imaging methods [13].

commercially accessible for this purpose in the mid-1970s [10].

**4.2 The last 50 years**

to become common [8].

acute effects.

### **4.2 The last 50 years**

*Neurostimulation and Neuromodulation in Contemporary Therapeutic Practice*

magnetic induction or by changing magnetic field [6].

of intractable long-term neuropathic pain.

electrodes, but the exact mechanism is still unknown.

nonneuropathic chronic conditions.

and fibromyalgia [7].

**3. Deep brain stimulation (DBS)**

various other disorders.

spinal cord.

intensive antiepileptic drug treatment and suffers from their adverse effects. FDA has approved VNS in 1997 for the treatment of epilepsy, depression, and

3.Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation by producing electrical impulses at a specific area of the brain through electro-

4.Spinal cord stimulation (SCS) is useful in the treatment of long-lasting pain, which utilizes a stimulator that gives an electrical stimulus to the

5.Epidural motor cortex stimulation technique is highly useful in the treatment

6. rTMS is useful in the treatment of experimental pain, neuropathic pain, and

7.Transcranial direct current stimulation is a highly used noninvasive technique altering neuronal plasticity. It is moderately used in treating neuropathic pain

DBS is an electrode implantation method using stereotactic techniques into the deep regions of brain for modulating neuronal function. An implantable pulse generator (IPG) is attached below the clavicle region, with an intention to treat neurological and psychiatric conditions. This attached IPG works on battery and delivers electrical stimulation, which is regulated externally by patients with the help of the remote. The electronic components like frequency, pulse, voltage, and other parameters can be altered to attain maximum efficacy of the treatment. It is believed that it works on excitation and inhibition of neurons present nearby the

Low-frequency stimulation seems to excite nearby neurons, while high-frequency

During the early 1900s' experiments, first stereotactic frame was designed that allowed stimulation of deeper regions of brain. In 1947, X-ray pneumoencephalography was developed that enabled surgeons to locate the target with the help of detailed stereotactic atlas that was developed later on. In 1950, stereotactic techniques were used for the tremor treatment. Later, in 1963, Albe Fessard reported high-frequency (~100–200 Hz) electrical stimulation for the first time in the ventral intermediate thalamic nucleus that could substantially alleviate Parkinsonian

stimulation may decrease local activity leading to rescindable functional lesion. This simple-minded opinion for the mechanistic action has been a challenge in recent years, and more comprehensive knowledge may promote enhanced DBS

**32**

tremor [9].

treatments [8].

**4.1 Early history**

**4. Brief chronicle of DBS**

In 1960, levodopa treatment development was highly effective for Parkinsonian symptoms with lesser risk and expense compared to DBS implantation and this led the curtailing of early forms of DBS research.

Inspite of the drawbacks, the research for use of DBSnever stopped. DBS continued to observe restricted use in intractable chronic treatment, with Medtronic Inc. (Minneapolis, MN, USA) and released the first fully implanted DBS systems commercially accessible for this purpose in the mid-1970s [10].

Other study groups investigated the use of thalamic DBS to treat consciousness diseases and reported few benefits. By the end of 1980s, it was evident that using levodopa would not hold the promising effects, after years of therapy, and patients developed wearing off along with the side effects like dyskinesias. Meanwhile, the technology of implantable medical devices had improved to the stage that it was routinely used for chronically implanted devices like cardiac pacemakers and spinal cord stimulators. The animal model study eventually got translated into clinical practices, and the first subthalamic nucleus (STN) DBS study got published [11]. By the beginning of the century, clinical use of DBS in Parkinsonian disorders has begun to become common [8].
