Deep Brain Stimulation

CHAPTER I

INTRODUCTION

One of the well established surgical treatment for medication-refractory movement disorders is Deep brain stimulation (DBS), DBS enabling people to regain control of their motor function (Perlmutter and Mink, 2006) and now being explored for a variety of neurological and psychiatric disorders (Tierney et al., 2011), providing new possibilities to manage conditions that become refractory to conventional medical therapy.

In this chapter, we cover the physiological mechanisms underlying DBS therapy, positing that, although general principles exist, DBS threating the disorder and the therapeutic mechanism(s) of action may depend on the site of stimulation

The use of electrical stimulation to modulate brain function has been around for some time, evolving from a predictive tool for ablative outcomes to its modernday therapeutic application. Through the 1950s, Hassler and colleagues were one of the first groups to use intraoperative electrical stimulation to alleviate or exacerbate contralateral tremor when applied to the globus pallidus (GP) at what was considered at that time high (25–100 Hz) and low (<25 Hz) frequency, respectively (Hassler et al., 1960). They suggested that high-frequency electrical stimulation could be used as a tool to identify brain regions that would reduce motor symptoms when lesioned.In the following years numerous studies reported the use of high-frequency electrical stimulation to treat movement disorders ranging from dyskinesia (Alberts et al., 1966) to cerebral palsy (Bergstrom et al., 1966), psychiatricdisorders(Heath1954),autonomicdisorders(SemJacobsen 1968), convulsive disorders (Cooper 1973), and pain syndromes (Hosobuchi et al., 1977). Yet, it was not until the 1980s, with the development of fully implantable pulse generators and the pioneering work of Benabid and colleagues (1987), that DBS was introduced as a feasible alternative to lesioning procedures, with the added benefit of reversibility and titration to maximize therapeutic effects while minimizing sideeffects. Since then, DBS systems have been implanted in nearly 100 000 patients with medication-refractory neurological and psychiatric disorders.

We also cover electrophysiological experiments, biochemical analyses, computer modeling, and imaging studies related to DBS to support the hypothesis that the mechanism(s) of action depend on both the site of stimulation and the neurological disorder being treated. Specifically, we address the questions of (1) how DBS affects neuronal tissue surrounding the electrode through an overview of experimental studies related to DBS for Parkinson’s disease, and (2) how these neurophysiological effects translate into clinical benefit for a range of neural targets and disorders.

CHAPTER II

CONTENT

2.1.            Definition

Deep Brain Stimulation (DBS) is a surgical procedure that use a high frequency electrical stimulation through chronically implanted electrodes into a specific target in the subcortical structures (Chiken and Nambu, 2016). Nowadays it’s been widely used as an effective treatment for movement disorders, such as Parkinson’s Disease (PD), essential tremor, and dystonia, and it is now under investigation as for it to be used for a wide variety of neurological and psychiatric conditions such as, epilepsy, Obsessive-Compulsive Disorder (OCD), and major depression (Herrington, Cheng and Eskandar, 2016).

2.2.            History of Deep Brain Stimulation

The account of DBS is an entrancing case of the transaction amongst fundamental and clinical science as a two-way process. A possibility clinical perceptions identified with tranquilize manhandle prompted the production of a monkey demonstrate for PD, and serious examination of this model drove inside four years to a handy approach in PD patients (Bergman H, 1990). Some the turning points in this specific improvement were:

a.       1983 The compound MPTP was found to be the wellspring of Parksinson-like manifestations in youthful architect tranquilize addicts

b.      1983 Injection of MPTP into monkeys caused a Parkinson-like state.

c.       1983-1990 Recordings in the basal ganglia of both ordinary and MPTP-treated monkeys characterized the operational standards of basal ganglia-thalamocortical circles, and appeared interestingly articulated over-movement in a piece of the basal ganglia called the subthalamic core (STN). These papers have given the reasonable structure to quite a bit of work on the basal ganglia and development issue over the previous decade or something like that. They depended on the two chronicles from single neurons in alert, carrying on monkeys, yet additionally utilized metabolic markers to delineate of over-and under-action (Bergman H,1990).

d.      1990 Lesions of STN in monkeys were appeared to totally and forever turn around the impacts of MPTP

e.       1993 The principal report from Benabid's facility of the utilization of DBS in the STN to treat Parkinson's Disease. Benabid's gathering had first utilized DBS in the thalamus as ahead of schedule as 1987. This was completed in three patients, with DBS anodes embedded on the two sides of the cerebrum, which is currently the standard approach in PD patients (Svjetlana Miocinovic, MD, PhD, 2013)

f.       1997 FDA endorsement given for DBS in the thalamus.

g.      2001 FDA endorsement given for DBS in the STN.

h.      (387 references from 2001-2003)  It is observable that in this illustration, both the calculated system and the exploratory confirmation to help clinical trials in PD patients originated from the creature display . Quite a bit of this exploratory work was done in the UK (Buckner RL, 2005)

2.3.            Components and placing

The Deep Brain Stimulation system consists of three major components, the first being the lead, which is also called the electrode, is essentially a coiled wire insulated in polyurethane with four platinum-iridium electrodes and is placed in one or two different nuclei of the brain (Drew S. Kern, 2017).  This component is inserted through a small opening in the skull and implanted in the brain. The tip of the electrode is positioned within the targeted brain area. The second component is the extensions, an insulated wire that is passed under the skin of the head, neck, and shoulder, connecting the lead to the third component, which is the neurostimulator or sometimes also called the “battery pack” or the implanted pulse generator (IPG) – the equivalent of a pacemaker. The IPG is a battery-powered neurostimulator encased in a titanium housing, which sends electrical pulses to the brain that interferes with neural activity at the target site. This component is usually implanted under the skin near the collarbone, and in some cases it may be implanted lower in the chest or under the skin over the abdomen (J.S. Perlmutterand, 2006).

2.4.            Method

Since 1997, a lot of Parkinson’s Disease patients have been treated with DBS, as surgical technique as I already said before that involves the implantation of ultra-hin wire electrodes. The Implanted device, sometimes referred to as a ‘brain pacemaker’, delivers electrical pulses to a structure called the subthalamic nucleus, located near the center of the brain, and effectively alleviates many of the physical symptoms nof the disease, such as tremor, muscle rigidity, and slowed movements. The most common use DBS system uses a four contact stimulating electrode stereo tactically implanted in the target and connected via a subcutaneous wire to pacemaker-like unit called an Implantable Pulse Generator (IPG) that is placed on the chest wall underneath the collarbone. Electrodes are typically placed bilaterally, although clinical needs sometimes dictate unilateral stimulation. Most targets are deep brain structures (include deep white matter tracts) rather than cortical areas. A clinician uses a handheld device to wirelessly communicate with with the IPG to adjust the parameters of stimulation, tuning stimulation to maximize symptom relief and minimize side effects (Umemura A,, 2017).

DBS is actually safe, but still like any other surgical procedure, comes with some risks. First of all, it is highly invasive, it requires small holes to be drilled in the patient’s skull, through which the electrodes are inserted. Potential complications of this include infection, stroke, and bleeding on the brain. The electrodes which are implanted for long periods of times also sometimes move out of place ; they can also cause swelling at the implantation side and the wire connecting them to the battery, typically placed  under the skin of the chest, can erode , all of which require additional surgical procedures (C. C. McIntyre, 2004)

Now, researchers at the Massachusetts Institute of Technology have a developed a new method that can stimulate cells deep inside the brain non-invasively, using multiple electric fields applied from outside the organ. In a study published today in the journal Cell, they show that the method can selectively stimulate deep brain structures in live mice, without affecting the activity of cells in the overlying regions, and also that it can be easily adjusted to evoke movements by stimulation of the motor cortex (T.M. Choiand, 2009).

The new method, called “temporal interference”, exploits the fact that neurons do not respond to electric fields with frequencies of around 1,000 Hertz (Hz, or cycles per second) or more. Thus, high frequency electric fields applied to the brain pass through it without affecting neuronal activity. If, however, two fields are applied to the brain, at high frequencies that differ by small amounts corresponding to the frequencies to which neurons can respond, they interfere with each other to produce an ‘envelope’ electric field that excites the cells within it (Grossman et al., 2017).

2.5.            Neurophysiology of Deep Brain Stimulations

Electrical stimulation of the brain has been shown to influence a variety of mechanisms involved in neuronal function and signaling. The effect of DBS on neurons in different nuclei may be quite different. Different types of central nervous system (CNS) neurons possess different types of ion channels that may have different voltage-sensitive activation and inactivation properties. Nonetheless, the net effect resulting from different mechanisms may be comparable (Christine CW, 2009).

There are many primary principles of CNS elements affected by DBS under the usual clinical conditions; one of the most important principles is the relationship between stimulus amplitude and duration. As current amplitude decreases, duration must increase to produce a constant effect. Similarly, as duration decreases, amplitude must increase to produce the same effect. The form of the amplitude-duration curve is usually an exponential decay. The amplitude asymptote (threshold) at very long durations is called the rheobase. The chronaxie distinguishes different types of neural tissues or elements. The larger the chronaxie, the higher the current or pulse width (duration) must be to activate the neuronal element (Vesper Fe Marie L Ramos, 2015).

The chronaxie is substantially different, large myelinated CNS fibers have chronaxies of 30–200 μs, whereas the chronaxie of dendrites and cell bodies may be in the 1–10-ms range. In rat visual cortex, the chronaxie was 271 μs for subcortical white matter, 380 μs for cortical gray matter, and 15 ms for cortical cell bodies. With usual stimulation parameters, postsynaptic responses from electrical stimulation of the cortical gray matter result primarily from the activation of efferent axons (initial segments or branches) rather than from cell bodies.

The orientation of the cell body and axons in relation to current flow is an important determinant of responsiveness. For axons, the voltage gradient parallel to the axon is most important for eliciting a response. Gray matter and white matter have different resistivities as do myelinated and unmyelinated fibers. Thus the response to stimulation in a nucleus containing a mixture of elements is likely to be complex depending on the geometry of the neural elements, the stimulating electrode configuration, and the nucleus (Alexander GE, 1990).

A final factor in determining responsiveness is the distance of the neural element from the electrode. Rheobase and chronaxie rise in proportion to the distance from the electrode. Furthermore, currents from monopolar cathodes more than eight times threshold may block action potentials in axons. Thus, at high currents, nearby elements may be blocked, and distant elements may not receive sufficient stimulation, but elements in an intermediate “shell” will be activated.

The response to high-frequency stimulation in the context of therapeutic DBS has been studied mostly in the ventral tier nuclei of the thalamus, the STN, and the globus pallidus. Studies have suggested the physiologic response to high-frequency stimulation may differ across nuclei.

Ventral Thalamic Nuclei

The cerebellar afferent receiving zone of the thalamus (human VIM nucleus) has been the primary target for the treatment of tremor. These nuclei receive excitatory glutamatergic afferents from the deep cerebellar nuclei, excitatory glutamatergic afferents from the cerebral cortex, and inhibitory GABAergic inputs from the reticular nucleus of the thalamus. The output from these nuclei primarily targets motor areas of cerebral cortex but has also been shown to project to striatum. Thus, although it is common to view VIM as a simple relay for information from the cerebellum to cerebral cortex, the synaptic connections are complex and DBS likely influences multiple elements.

To investigate the cellular mechanism by which DBS might work, studies have used a slice preparation from rat thalamus. The rat homologues of human VIM are the ventrolateral and ventroposterior nuclei. Using simulated DBS (sDBS) with variables comparable with that used in human DBS, the effect of stimulation of ventral lateral ventral posterior thalamic nuclei (VL-VP) on neurons is both amplitude and frequency dependent. Response to stimulation was seen at frequencies above 20 Hz, it increased with increasing stimulation frequency, and it reached a maximum at 200 Hz. This is comparable with the frequency response characteristics of VIM DBS for ET. When rhythmic pulse trains were injected into VL-VP neurons to simulate tremor-like bursting, sDBS eliminated the rhythmic firing. At moderate currents, the rhythmic firing was replaced by nonrhythmic firing, but higher currents induced block and eliminated firing.

In addition to activating excitatory presynaptic terminals, sDBS in rat thalamic slice also produced increased excitability of thalamic neurons. The threshold for triggering Na+-dependent action potentials was decreased by sDBS, even in the presence of ionotropic glutamate blockade, causing a 30% increased probability of firing action potentials in response to injected depolarizing currents. The decreased threshold was not a result of changes in membrane resistance. These nonsynaptic effects were dependent on current and distance from the stimulating electrode. Thus, regardless of presynaptic effects, the increased excitability of cell bodies suggests there also may be increased excitability of efferent axons (Rosa M, 2012).

Subthalamic Nucleus

The STN has become the most commonly used target for DBS in the treatment of PD. The STN is an important node in basal ganglia circuits, serving as a major target for cortical afferents and also receiving multiple inputs from other basal ganglia components. DBS in the STN has the potential to influence a variety of afferent and efferent targets and may have different effects on different neurons (Limousin P, 1995).

The effect of high frequency stimulation has been studied in rat STN slices by several investigators. The two most frequently encountered neuron types were (a) tonically active neurons that had a round soma and extensive radial dendritic field (68%) and (b) bursting neurons with a triangular soma and less extensive dendritic field (25%). Tonically active cells followed 130 Hz stimulation for 5–15 s, then developed a bursting pattern, before ceasing to fire after 25 s of stimulation. Bursting cells responded to stimulation trains with a brief burst of action potentials followed by prolonged silence. However, the stimulation current was low and primarily affected presynaptic axons rather than cell bodies, suggesting that presynaptic driving of STN neurons may fail at sustained high frequencies.

A prolonged inactivation of STN neurons also has been reported. The post-stimulation silence was a result of changes in membrane properties and not synaptic effects. Prolonged post-stimulation silencing occurred only at frequencies higher than those that produce maximum benefit from STN DBS in PD patients (Aziz TZ, 1991).

The pattern of response varied among neurons but did not depend on the distance from the stimulating electrode. The blockade of ionotropic or metabotropic glutamate receptors or of GABA receptors had no effect on the stimulus-driven firing. The stimulation-driven firing appeared to be a result of the activation of voltage-sensitive Na⁺ and L-type Ca²⁺ channels. Combinations in the therapeutic range replaced baseline firing with stimulus-driven spikes in a stable oscillatory pattern time locked to the stimuli.

In the absence of STN stimulation, motor cortex stimulation typically elicits a triphasic response in SNr neurons with early excitation, inhibition, then late excitation. The early excitation is mediated by the activation of the excitatory projection from the STN to the SNr and the inhibition by the activation of inhibitory striatonigral neurons (“direct pathway”), and the late excitation is mediated by the disinhibition of subthalamonigral neurons (“indirect pathway”). High-frequency STN stimulation blocks the transmission of information through the STN. This implies that STN stimulation can activate multiple pathways but also that high-frequency STN stimulation activates excitatory projections from the STN to the SNr. Furthermore, STN stimulation blocks the flow of information through the STN, potentially preventing aberrant signals from being propogated in disease states (Mitchell IJ, 1989).

Globus Pallidus

The GPi is the second most commonly used DBS target for the treatment of PD and is increasingly targeted for DBS treatment of dystonia. The GPi is one of the primary output nuclei of the basal ganglia and is considered the main output representation of limb movements. The GPi receives excitatory glutamatergic afferents from the STN, inhibitory GABAergic afferents from striatum, inhibitory inputs from the GPe, and nigral dopamine afferents. The inhibitory GABAergic output of the GPi projects to the ventral anterior and ventral lateral thalamus, intralaminar thalamus, and the pedunculopontine area. Owing to its size and geometry, the effect of stimulation in the GPi is more likely to be restricted to the nucleus, but the potential remains for the possible spread to adjacent structures and pathways, especially the GPe and internal capsule.

In human subjects undergoing the implantation of GPi DBS electrodes, studies recorded the response of GPi neurons to low-frequency (5–50-Hz), that low-amplitude stimulation delivered 250–600 μm from the recording site. The response in 22 of 23 cells was inhibition lasting 15–25 ms after each pulse, consistent with the activation of presynaptic inhibitory terminals. At higher frequencies up to 300 Hz, stimulus trains produced decreased firing but did not completely block firing (Manuela Rosa, 2012).

Release of neurotransmitters by deep brain stimulation

An early study stated that high-frequency stimulation of the STN in rodents increases extracellular glutamate in the GPi and a downstream target of STN projections, and that release may be dependent upon stimulation frequency. Although a similar increase was not found in humans with PD, there was an increase in cyclic guanosine monophosphate (cGMP) in the GPi. Other studies also support the notion that STN DBS drives output neurons. A similar effect may be important for other sites of stimulation. For example, the effects of high-frequency stimulation of thalamic slices were blocked by glutamate receptor antagonists (Manuela Rosa, 2012).

Synthesis of Neurophysiologic data

Differences in techniques, anatomy, cell type, and experimental setting limit the ability to make direct comparisons across the studies reviewed above. However, several conclusions are possible. (a) High-frequency stimulation affects multiple elements, including afferent axons, cell bodies, efferent axons, and fibers of passage. (b) The stimulated elements may differ depending on the anatomy of the target (e.g., the VIM thalamus, STN, GPi, or others). (c) The effects may vary depending on the intrinsic physiologic properties of the targeted cells. (d) The effects vary with frequency, amplitude, pulse width, and duration of the spike trains. (e) Stimulation of the STN releases glutamate from excitatory efferent neurons. (f) The net effect on distant targets, whether monosynaptic or polysynaptic, may be independent of local effects. Thus local cells may be inhibited by the activation of inhibitory afferents or by the effects on intrinsic ion conductances, but the efferent axons may still be activated. The high-frequency stimulation effect on downstream targets is consistent with the activation of efferent axons either directly or through activation of local cell bodies to axon initial segments. This conclusion is also supported by computer models and by human functional imaging work (Vesper Fe Marie L Ramos, 2015).

DBS has the potential to provide substantial benefit for a variety of neuropsychiatric conditions. Physiologic and imaging studies support the notion that the net effect of DBS is to increase the firing of neurons projecting from the site of stimulation. This may be mediated primarily via the stimulation of axons rather than cell bodies.

DBS seems to mimic the effect of destructive lesions, suggesting that despite the activation of efferent axons, there is interruption of information flow or processing. Experiments using rats and monkeys indicate that high-frequency stimulation can prevent the normal pattern activity whether driven by electrical cortical stimulation or related to a limb-movement task. If normal circuits are disrupted in this way, it makes sense that abnormal circuit activity also would be disrupted. Indeed, STN DBS has been shown to eliminate abnormal rhythmic oscillation of GPi local field potentials, and impairing abnormal firing patterns may be more critical than changing net firing rates.

Future studies may continue to distinguish variations in the effects of DBS on different nuclei and different neuronal cell types. Furthermore, patients with implanted DBS electrodes afford an outstanding opportunity to investigate behavioral effects of functional circuits (Greenberg, B. D., 2010).

2.6.            Application of Deep Brain Stimulation

Deep brain stimulation (DBS) is a surgical treatment that effective for medication-refractory hypokinetic and hyperkinetic disorder. It’s also being explored for a variety of other psychiatric and neurological diseases. Deep brain stimulation has been Food and Drug Administration–approved for essential tremor and Parkinson disease and has a humanitarian device exemption for dystonia and obsessive-compulsive disorder.

There are some application of Deep Brain Stimulation. Deep brain stimulation can be an alternative to surgery for the management of tremor. Thalamic DBS has been shown to be efficacious in the treatment of essential and parkinsonian tremor, with excellent long-term outcomes and an acceptable adverse effect profile The main adverse effects of the stimulation are paresthesias, headache, dysarthria, paresis, gait disturbance, and ataxia. Adverse effects are usually mild and effectively managed by stimulation parameter adjustment (S.Y. Chen, 2017).

One of the primary clinical uses of DBS is for the treatment of Parkinson Disease. A robust motor response to levodopa is generally considered a prerequisite for successful DBS outcome in Parkinson Disease (except for tremor-predominant PD), and stimulation may be considered once patients develop disabling motor fluctuations and dyskinesias while receiving medical therapy (Michael S. Okun, M.D, 2012).  Studies of DBS for PD have reported significant improvement in cardinal motor signs, including tremor, bradykinesia, and rigidity, with variable response in medication-refractory gait freezing, postural instability, and gait mechanics. Adverse effects are typically transient and reversible (Langston JW, 1983).

Deep brain stimulation has also been useful for treatment of primary dystonia. Unlike tremor and PD, there is typically a gradually increasing clinical response to stimulation over weeks to months of therapy. The shorter disease duration has been reported to lead to better result Overall, DBS for essential and parkinsonian tremor has been successful, while treatment of other causes of tremor has been more limited (Burns RS, 1983).

This surgical procedure can be done to Anorexia Nervosa patient. After surgery, average follow-up period was 38months (range, 9 –50 months). Average BMI at last follow-up was 19.6 kg/m² (range, 18.4 –22.1 kg/m²), an average increase of 65% in body weight. All patients weighed greater than 85% of expected body weight and thus no longer met the diagnostic criteria of AN. Israel et al. reported a 52-year-old female patient suffering from severe refractory depression with concomitant recurrent AN (AN age of onset: 17 years of age) who underwent bilateral DBS at subgenual cingulate cortex in 2005. She was able to maintain her BMI at an average of 19.1 kg/m² for more than two years postoperatively. The nature of this procedure, however, remains investigational andshould not be viewed as a standard clinical treatment option. Further scientific investigation is essential to warrant the long-term efficacy and safety of DBS for AN (Hemmings Wu, 2013).

Deep brain stimulation (DBS) has emerged as a treatment for severe cases of therapy-refractory obsessive-compulsive disorder (OCD). The latest results from the procedure have shown a 50% reduction of OCD scores, depression, and anxiety. There is a clinical trial that using DBS as a treatment for Alzheimer Disease and Dementia. Evidence for the use of DBS to treat dementia is preliminary and limited. Further investigation into the potential clinical effects of DBS for dementia is warranted (Patric Blomstedt, 2012).

DBS can also used as a treatment for Resistant Major Depression. After the procedure was done. all patients showed strikingly similar intraoperative effects of increased appetitive motivation (Thomas E. Schlaepfer, 2013).

This study first reviews clinical outcomes and mechanisms of Deep Brain Stimulation (DBS) for OCD then discusses these results in an overview of current and future psychiatric applications which is including DBS for Parkinson's disease, mood disorders, Tourette's syndrome, addiction, anorexia nervosa, autism, schizophrenia and anxiety disorders. Deep brain stimulation, implantation surgery is an established treatment modality for a variety of medical refractory movement disorders such as Parkinson's disease and many more. Following the success of DBS in these movement disorders with a high rate of safety and efficacy, there is a resurgence of interest in the utility of this modality in other medical refractory disorders. Consequently, neuromodulation has been explored for a variety of refractory conditions such as neuropsychiatric disorders (major depressive disorders and obsessive-compulsive disorders), eating disorders including obesity, traumatic brain injury, post-traumatic stress disorders (PTSD), dementias and chronic pain. This review provides an overview of the emerging applications of DBS in these disorders. DBS does not cures Parkinson's but it can help to manage some of it's symptoms whose medications has severe side effects. It's the direct effect on the physiology of brain cells and neurotransmitters are currently debated but by sending high frequency of electrical impulses into specific areas of the brain, it can diminish the side effects produced by Parkinson's medications which allows a decrease in medications. Parkinson's disease is one of the example that application of DBS works on to reduce the side effects (Yamamoto T, 2010).

2.7.            Prognosis

Profound cerebrum incitement successfully eases engine side effects of therapeutically stubborn Parkinson's illness, and furthermore alleviates numerous other treatment-safe development and full of feeling issue. Regardless of its relative accomplishment as a treatment choice, the premise of its viability stays slippery. In Parkinson's infection, expanded practical availability and oscillatory movement happen inside the basal ganglia because of dopamine misfortune. A correlative connection between obsessive oscillatory action and the engine manifestations of the illness, specifically bradykinesia, inflexibility, and tremor, has been set up. Concealment of the motions by either dopamine supplanting or DBS likewise relates with a change in engine side effects. DBS parameters are at present picked experimentally utilizing an "experimentation" approach, which can be tedious and expensive. The work exhibited here amalgamates ideas from speculations of neural system displaying with nonlinear control building to portray and break down a model of synchronous neural action and connected incitement. A hypothetical articulation for the ideal incitement parameters important to smother motions is determined. The impact of changing stimulation parameters on incited motions is examined in the model. Expanding either incitement beat span or plentifulness improved the level of concealment. The anticipated parameters were found to concur well with clinical estimations detailed in the writing for singular patients. It is expected that the disentangled model portrayed may encourage the advancement of conventions to help ideal incitement parameter decision on a patient by quiet premise (Hamani C, 2008).

Deep brain stimulation (DBS) is a final resort treatment for neurological and mental disarranges that are recalcitrant to standard treatment. In the course of the most recent decades, the advance of DBS in psychiatry has been slower than in neurology, to some extent inferable from the heterogenic symptomatology and complex neuroanatomy of mental issue. In any case, for over the top urgent issue (OCD) DBS is presently an acknowledged treatment. This examination initially audits clinical results and instruments of DBS for OCD, and after that talks about these outcomes in a diagram of present and future mental applications, including DBS for disposition issue, Tourette's disorder, dependence, anorexia nervosa, extreme introvertedness, schizophrenia, and nervousness issue. Likewise, it will concentrate on novel procedures that may improve the utilization of DBS in psychiatry (C. R. Butson, 2006).

Deep brain stimulation (DBS) has created amid the previous 20 years as an exceptional treatment alternative for a few distinct issue. Advances in innovation and surgical methods have basically substituted ablative methodology for the greater part of these conditions. Incitement of the ventralis intermedius core of the thalamus has unmistakably been appeared to uniquely enhance tremor control in patients with basic tremor and tremor identified with Parkinson malady. Manifestations of bradykinesia, tremor, walk unsettling influence, and inflexibility can be fundamentally enhanced in patients with Parkinson malady. As a result of these upgrades, a lessening in prescription can be instrumental in diminishing the debilitating highlights of dyskinesias in such patients. Essential dystonia has been appeared to react well to DBS of the globus pallidus internus. The accomplishment of these methods has prompted use of these systems to various other crippling conditions, for example, neuropsychiatric clutters, recalcitrant agony, epilepsy, camptocormia, cerebral pain, fretful legs disorder, and Alzheimer ailment (Adrian W. Laxton, 2013).

Deep brain stimulation (DBS) has been found as a more highly effective and less morbidity-producing alternative to other surgeries in the treatment of medically intractable movement disorders , but the exact incidence of morbidity and mortality associated with the procedure is not well known.

A study was done  to assess the surgical morbidity  in 140 consecutive patients with various disease entities of movement disorders, epilepsy and obsessive-compulsive disorders that underwent deep brain stimulation (DBS) in a single DBS center of Taiwan. From Feb 2002 to Feb 2015, a total of 140 patients in the institute were included . All patients underwent standard DBS procedures with intra-operative microelectrode recordings, and were followed for at least 6 months.

The results shows that among surgical morbidity, symptomatic hemorrhage 2.8%(4/140), lead mal-positioned 3.6%(5/140) and hardware infection 1.4%(2/140). There had no surgical related mortality. Post-operative morbidity within 6 months was 40.7% (57/140), which included: weight gain (more than 5 kg) 28.6% (40/140), mania/hypophonia 8.6%(12/140), transient confusion 7.9% (11/140), depression 4.3%(6/140) and pulmonary edema 2.1%(3/140). Stimulation related morbidity was 47.8% (66/140), which included hypophonia 18.1%(n=25/138), dyskinesia 13.8%(19/138), dysarthria 13.8%(19/138), sialorrhea 12.3%(17/138) and decreased memory 11.6% (16/138). The comorbidity of these patients within the follow-up period up to 13 years was 73%(86/118, loss follow=20), which included patients who expired, demented, received bone/spine surgery and diagnosed as cancer (Sorin Breit, 2014).

The associated morbidity and comorbidity is significant in DBS patients. Stimulation related morbidity was high, nevertheless, most of these was transient, and could be improved after change in stimulation parameters. Though the incidence is low, intracranial hemorrhage remains as a high risk in DBS surgery.There is also a significant incidence of adverse events associated with the DBS procedure. Nevertheless, DBS is clinically effective in well-selected patients and should be seriously considered as a treatment option for patients with medically refractory movement disorders (Lancioni GE, 2010).

CHAPTER III

SUMMARY

Deep Brain Stimulation (DBS) is a surgical procedure that use a high frequency electrical stimulation through chronically implanted electrodes into a specific target in the subcortical structures. The Deep Brain Stimulation system consists of three major components, the first being the lead, which is also called the electrode, is essentially a coiled wire insulated in polyurethane with four platinum-iridium electrodes and is placed in one or two different nuclei of the brain. The second component is the extensions, an insulated wire that is passed under the skin of the head, neck, and shoulder, connecting the lead to the third component, which is the neurostimulator or sometimes also called the “battery pack” or the implanted pulse generator (IPG) – the equivalent of a pacemaker.

The most common use DBS system uses a four contact stimulating electrode stereo tactically implanted in the target and connected via a subcutaneous wire to pacemaker-like unit called an Implantable Pulse Generator (IPG) that is placed on the chest wall underneath the collarbone. Electrodes are typically placed bilaterally, although clinical needs sometimes dictate unilateral stimulation. Most targets are deep brain structures (include deep white matter tracts) rather than cortical areas. The effect of DBS on neurons in different nuclei may be quite different.

DBS can be an alternative to surgery for the management of tremor, Parkinson Disease (PD), primary dystonia, Anorexia Nervosa, treatment for OCD and aslo for Resistant Major Depression. Deep brain stimulation (DBS) has been found as a more highly effective and less morbidity-producing alternative to other surgeries in the treatment of medically intractable movement disorders , but the exact incidence of morbidity and mortality associated with the procedure is not well known.

REFERENCES

Adrian W. Laxton, Andres M. Lozano. Deep Brain Stimulation for the Treatment of Alzheimer Disease and Dementias. 2013. Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada

Alexander GE, Crutcher MD and DeLong MR. (1990) Basal ganglia-thalmocortical circuits: parallel substrates for engine, oculomotor, prefrontal and limbic capacities. Advance in Brain Research 85: 119-146

Aziz TZ, Peggs D, Sambrook MA and Crossman AR. (1991) Lesion of the subthalamic core for the mitigation of 1-methyl-4-phenyl1,2,3,6tetrahydropyridine (MPTP)- instigated parkinsonism in the primate. Development Disorders 6: 288-292

Bergman H, Wichmann T, DeLong M. (1990) Reversal of trial parkinsonism by sores of the subthalamic core. Science 249: 1436-1438.

Buckner RL, Snyder AZ, Shannon BJ, et al. Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci. 2005;25(34):7709-7017

Burns RS, Chieuh CC, Markey SP, Eberet MH, Jacobwitz DM and Kopin IJ (1983) A primate model of parkinsonism: particular decimation of dopaminergic neurons in the standards compacta of the substantia nigra by MPTP. PNAS 80, 4546-4550

Chiken, S. and Nambu, A. (2016) ‘Mechanism of Deep Brain Stimulation : Inhibition , Excitation , or Disruption ?’.

Christine CW, Langston JW, Turner RS, Starr PA. The neurophysiology and effect of deep brain stimulation in a patient with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism. J. Neurosurg. 2009 Feb;110(2):234-8. doi: 10.3171/2008.8.JNS08882

C. C. McIntyre, et al. “Uncovering the mechanism(s) of deep brain stimulation: activation, inhibition, or both” Clinical Neurophysiology, vol. 115, pp. 1239-1248, 2004

C. R. Butson, et al. “Sources and effects of electrode impedance during deep brain stimulation” Clinical Neurophysiology,vol. 117, no. 2, pp. 447-454, 2006

Drew S. Kern, MS, Rajeev Kumar, MD, FRCPC. Deep Brain Stimulation. The Neurologist • Volume 13, Number 5, (2017)

Greenberg, B. D.; Rauch S. L.; Haber, S. N.; “Invasive Circuitry-Based Neurotherapeutics: Stereotactic Ablation and Deep Brain Stimulation for OCD”Neuropsychopharmacology(2010) 35,317–336; 16 September 2009

Grossman, N. et al. (2017) ‘Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields’, Cell. Elsevier Inc., 169(6), p. 1029–1041.e16.

Hamani C, McAndrews MP, Cohn M, et al. Memory enhancement induced by hypothalamic/fornix deep brain stimulation. Ann Neurol. 2008;63(1):119-123

Hemmings Wu, Pieter Jan Van Dyck-Lippens, Remco Santegoeds, Kris van Kuyck, Loes Gabriëls et all. Deep-Brain Stimulation for Anorexia Nervosa. World Neurosurg. (2013) 80, 3/4:S29.e1-S29.e10, alvaible http://dx.doi.org/10.1016/j.wneu.2012.06.039

Herrington, T. M., Cheng, J. J. and Eskandar, E. N. (2016) ‘Mechanisms of deep brain stimulation’, Journal of Neurophysiology, 115(1), pp. 19–38.

J.S. Perlmutterand J. W. Mink “Deep Brain Stimulation” Annual Review of Neuroscience, vol. 29, pp. 229-257, 2006

Lancioni GE, Bosco A, Belardinelli MO, Singh NN, O'Reilly MK, Sigafoos J. An overview of intervention options for promoting adaptive behavior of persons with acquired brain injury and minimally conscious state. Res Dev Disabil. 2010;31(6):1121-1134

Langston JW, Ballard P, Tetrud JW, Irwin I. (1983) Chronic Parkinsonism in people because of a result of meperidine-simple combination. Science, 219:979-80.

Limousin P, Pollak P, Benazzouz A, Hoffmann D, Le Bas JF, Broussolle E, Perret JE, Benabid AL (1995). Impact of parkinsonian signs and indications of two-sided subthalamic core incitement. Lancet, 345, 91-95

Manuela Rosa, Gaia Giannicola, Sara Marceglia, Manuela Fumagalli, Sergio Barbieri, Alberto Priori. Neurophysiology of Deep Brain Stimulation. International Review of Neurobiology, Vol. 107, Burlington: Academic Press, 2012, pp. 23-55.

Michael S. Okun, M.D. Deep-Brain Stimulation for Parkinson’s Disease. N Engl J Med 2012;367:1529-38.

Mitchell IJ, Jackson A, Sambrook MA and Crossman AR. (1989) The part of subthalamic core in trial chorea-prove from 2deoxyglucose metabolic mapping and horseradish-peroxidase following examinations. Mind 112: 1533-1548.

Patric Blomstedt, Rickard L. Sjo¨ berg, Maja Hansson, Owe Bodlund, and Marwan I. Hariz. Deep Brain Stimulation in the Treatment of Obsessive-Compulsive Disorder. World Neurosurg. (2012). Available http://dx.doi.org/10.1016/j.wneu.2012.10.006

Rosa M, Giannicola G, Marceglia S, Fumagalli M, Barbieri S, Priori A. Neurophysiology of deep brain stimulation. Int Rev Neurobiol. 2012;107:23-55. doi: 10.1016/B978-0-12-404706-8.00004-8

Sorin Breit, Jörg B. Schulz, Alim-Louis Benabid. Deep Brain Stimulation. Cell Tissue Res (2014) 318: 275–288

Svjetlana Miocinovic, MD, PhD; Suvarchala Somayajula, MD; Shilpa Chitnis, MD, PhD; Jerrold L. Vitek, MD, PhD. History, Applications, and Mechanisms of Deep Brain Stimulation. JAMA Neurol. 2013;70(2):163-171

S.Y. Chen, Y.H. Pan, S.H. Lin. Morbidity and comorbidity of deep brain stimulation for Parkinson’s disease – A thirteen-years retrospective cohort study [abstract]. Mov Disord.2016; 31 (suppl 2). http://www.mdsabstracts.org/abstract/morbidity-and-comorbidity-of-deep-brain-stimulation-for-parkinsons-disease-a-thirteen-years-retrospective-cohort-study/. Accessed September 14, 2017.

Thomas E. Schlaepfer, Bettina H. Bewernick, Sarah Kayser, Burkhard M¨adler, and Volker A. Coenen. Rapid Effects of Deep Brain Stimulation for Treatment-Resistant Major Depression. Biol psychiatry. 2013

T.M. Choiand Y.T. Lee, “Modeling Deep Brain Stimulation” IFMBE Proceedings, vol. 23, no. 1, pp. 619-621, 2009

Umemura A, e. (2017). Deep brain stimulation for movement disorders: morbidity and mortality in 109 patients. - PubMed - NCBI. [online] Ncbi.nlm.nih.gov. Available at: https://www.ncbi.nlm.nih.gov/pubmed/12691402 [Accessed 15 Sep. 2017].

Vesper Fe Marie L Ramos, Ajay S Pillai, Codrin Lungu,  Jill Ostrem, Philip Starr, and Mark Hallett. Intraoperative neurophysiology in deep brain surgery for psychogenic dystonia. Ann Clin Transl Neurol. 2015 Jun; 2(6): 707–710.

Yamamoto T, Katayama Y, Kobayashi K, Oshima H, Fukaya C, Tsubokawa T. Deep brain stimulation for the treatment of vegetative state. Eur J Neurosci. 2010;32(7):1145-1151