Deep brain stimulation for movement and other neurologic disorders

Abstract

Deep brain stimulation was introduced as a treatment for patients with Parkinsonism and other movement disorders in the early 1990s. The technique rapidly became the treatment of choice for these conditions, and is now also being explored for other diseases, including Tourette syndrome, gait disorders, epilepsy, obsessive-compulsive disorder, and depression. Although the mechanism of action of DBS remains unclear, it is recognized that DBS works through focal modulation of functionally specific circuits. The fact that that the same DBS parameters and targets can be used in multiple diseases suggests that DBS does not counteract the pathophysiology of any specific disorder, but acts to replace pathologic activities in disease-affected brain circuits with activity that is more easily tolerated. Despite the progress made in the use of DBS, much remains to be done to fully realize the potential of this therapy. We describe some of the most active areas of research in this field, both in terms of exploration of new targets and stimulation parameters, and in terms of new electrode or stimulator designs.

Deep Brain Stimulation of the Subthalamic Nucleus Regulates Postabsorptive Glucose Metabolism in Patients With Parkinson's Disease

“…It also suggests that severe neurodegenerative disorders like PD may be associated with impaired glucose homeostasis that may be induced by specific alterations of the circuits between the brain and peripheral tissues. It is recognized that deep brain stimulation works through the focal modulation of functionally specific brain circuits including inhibition of glutamatergic cells belonging to the subthalamic nucleus (6). From the results of our study, we can hypothesize that the direct effect of STN-DBS on the thalamus may modulate peripheral glucose homeostasis.…”

“…In particular, hypoglycemia is able to induce synaptic activation in the dorsal midline thalamus. Also, a stimulation of afferents or efferents within the stimulated nucleus itself may prominently involve passing fibers within the range of stimulation (6).…”

Glial activation is associated with l-DOPA induced dyskinesia and blocked by a nitric oxide synthase inhibitor in a rat model of Parkinson's disease

“…5A and B) in rats chronically treated with L-DOPA. In both structures, the statistical analysis revealed highly significant effects of brain side [Str,F (1,19) = 69.244, P b 0.001; Pallidum, The substantia nigra, striatum, pallidal complex (VP, LGP, EP), and subthalamic nucleus are primary substrates of PD pathophysiology (Duke et al, 2007;DeLong and Wichmann, 2012). The cerebral cortex was examined due to its involvement in PD even at early stages of the neurodegenerative process (Ferrer, 2009;Ferrer et al, 2012).…”

Computational modeling of neurostimulation in brain diseases

“…DBS in PD is one of the most common treatment options when patients develop disabling motor symptoms, with the subthalamic nucleus (STN) and globus pallidus interna (GPi) being the primary stimulation targets (Miocinovic et al, 2013). However, following its incidental discovery in 1987 (Benabid et al, 1987), the mechanism of action of the DBS therapy is still debated (Da Cunha et al, 2015;DeLong and Wichmann, 2012;Dostrovsky and Lozano, 2002;Lobb, 2014;McIntyre and Hahn, 2010) and its effects are not consistent for all patients. Proposals range from DBS introducing antidromic action potentials stimulating the motor cortex (Li et al, 2012) to DBS changing the large-scale structural connectivity of the brain (van Hartevelt et al, 2014).…”