Deep brain stimulation

Abstract

During the last decade deep brain stimulation (DBS) has become a routine method for the treatment of advanced Parkinson's disease (PD), leading to striking improvements in motor function and quality of life of PD patients. It is associated with minimal morbidity. The rationale of targeting specific structures within basal ganglia such as the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) is strongly supported by the current knowledge of the basal ganglia pathophysiology, which is derived from extensive experimental work and which provides the theoretical basis for surgical therapy in PD. In particular, the STN has advanced to the worldwide most used target for DBS in the treatment of PD, due to the marked improvement of all cardinal symptoms of the disease. Moreover on-period dyskinesias are reduced in parallel with a marked reduction of the equivalent daily levodopa dose following STN-DBS. The success of the therapy largely depends on the selection of the appropriate candidate patients and on the precise implantation of the stimulation electrode, which necessitates careful imaging-based pre-targeting and extensive electrophysiological exploration of the target area. Despite the clinical success of the therapy, the fundamental mechanisms of high-frequency stimulation are still not fully elucidated. There is a large amount of evidence from experimental and clinical data that stimulation frequency represents a key factor with respect to clinical effect of DBS. Interestingly, high-frequency stimulation mimics the functional effects of ablation in various brain structures. The main hypotheses for the mechanism of high-frequency stimulation are: (1) depolarization blocking of neuronal transmission through inactivation of voltage dependent ion-channels, (2) jamming of information by imposing an efferent stimulation-driven high-frequency pattern, (3) synaptic inhibition by stimulation of inhibitory afferents to the target nucleus, (4) synaptic failure by stimulation-induced neurotransmitter depletion. As the hyperactivity of the STN is considered a functional hallmark of PD and as there is experimental evidence for STN-mediated glutamatergic excitotoxicity on neurons of the substantia nigra pars compacta (SNc), STN-DBS might reduce glutamatergic drive, leading to neuroprotection. Further studies will be needed to elucidate if STN-DBS indeed provides a slow-down of disease progression.

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

“…In general, both GPi-and STN-DBS are more effective than medical management alone to alleviate motor deficits in patients with advanced PD (Just and Ostergaard, 2002;Martinez-Martin et al, 2002;Troster et al, 2003;Lezcano et al, 2004;Diamond and Jankovic, 2005;Erola et al, 2005;Halbig et al, 2005;Lyons and Pahwa, 2005;Deuschl et al, 2006;Rodrigues et al, 2007a, b;Montel and Bungener, 2009;Weaver et al, 2009b;Zahodne et al, 2009). In contrast to patients with GPi-DBS, those with STN-DBS are often able to substantially reduce the medication doses (Breit et al, 2004; …”

Subcortical processes of motor response inhibition during a stop signal task

“…Dysfunction in the circuitry involving these subcortical structures has been implicated in a number of neurological conditions, including Parkinson's disease and attention deficit hyperactivity disorder (Bevan et al, 2006;DeLong and Wichmann, 2007;Mehler-Wex et al, 2006;Robbins et al, 2007). Among the subcortical structures, the subthalamic nucleus (STN) has received much attention because of its role in the pathogenesis and treatment of Parkinson's disease (Benabid, 2003;Bevan et al, 2006;Breit et al, 2004;Grafton et al, 2006;Hamani et al, 2005;Perlmutter and Mink, 2006). Deep brain stimulation (DBS) of the STN appeared to alleviate dyskinesia and other motor symptoms in patients with Parkinson's disease (Breit et al, 2004;Grafton et al, 2006;Hamani et al, 2005;Perlmutter and Mink, 2006).…”

“…Among the subcortical structures, the subthalamic nucleus (STN) has received much attention because of its role in the pathogenesis and treatment of Parkinson's disease (Benabid, 2003;Bevan et al, 2006;Breit et al, 2004;Grafton et al, 2006;Hamani et al, 2005;Perlmutter and Mink, 2006). Deep brain stimulation (DBS) of the STN appeared to alleviate dyskinesia and other motor symptoms in patients with Parkinson's disease (Breit et al, 2004;Grafton et al, 2006;Hamani et al, 2005;Perlmutter and Mink, 2006). Although a reduction of excessive inhibitory activity in the STN may mediate the treatment effects, the therapeutic mechanisms of DBS remain to be elucidated.…”

Transcranial Electrical Stimulation: Methodology and Applications

“…It has been used primarily for the improvement of motor function in patients with movement disorders, such as Parkinson's Disease (PD; Breit, Schulz, & Benabid, 2004), and more recently dystonia (Ostrem & Starr, 2008;Sakas et al, 2010), pain (Owen et al, 2007), obsessive-compulsive disorder (Greenberg et al, 2006), epilepsy (Handforth, DeSalles, & Krahl, 2006), depression (Mayberg et al, 2005), and Tourette's syndrome (Neuner et al, 2008). Although the original rationale for DBS was to replace neurosurgical lesions by inducing a reversible functional lesion in overactivated subcortical structures, such as the globus pallidus interna or the subthalamic nucleus, more recent insights hypothesize that the mechanisms of action of DBS are more complex, including depolarization blockade, synaptic inhibition, synaptic depression, and stimulation-induced modulation of pathological network activity (McIntyre, Savasta, KerkerianLe Goff, & Vitek, 2004).…”