Dissociation of motor symptoms during deep brain stimulation of the subthalamic nucleus in the region of the internal capsule

Abstract

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can be an effective treatment for the motor symptoms of Parkinson’s disease. The therapeutic benefits are voltage dependent and, in many cases, limited by the appearance of side effects, including muscle contractions. We have observed a number of clinical cases where improvements in rigidity were accompanied by a worsening of bradykinesia. Considering the anatomic position of STN and current approaches to implantation of the DBS lead, we hypothesized that this dissociation of motor symptoms arises from activation of pyramidal tract fibers in the adjacent internal capsule. The objective of this study was to assess the physiological basis for this dissociation and to test our hypothesis that the underlying etiology of this paradox is activation of fibers of the internal capsule. The effect of STN DBS at 80% of motor threshold for each of the four contacts was evaluated for its effect on rigidity, bradykinesia and akinesia in a single primate made parkinsonian with MPTP. Consistent with our observations in humans, this near-threshold stimulation was found to improve rigidity while bradykinesia and akinesia worsened. Worsening bradykinesia in the face of improvement of other motor signs in PD patients is suggestive of activation of pyramidal tract fibers during stimulation. This phenomenon may occur without overt muscle contraction and in the face of improved rigidity.

Neural targets for relieving parkinsonian rigidity and bradykinesia with pallidal deep brain stimulation

“…These studies, along with a recent case study of STN-DBS in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated nonhuman primate (Xu et al 2011), support the mechanistic hypothesis that treating both bradykinesia and rigidity with DBS may require direct stimulation of more than one neuronal pathway within the brain. It remains unclear, however, which neuronal pathways to target for relieving parkinsonian bradykinesia and rigidity and to what extent those pathways are involved in the therapeutic mechanisms of DBS.…”

“…Indeed, transcranial stimulation, at levels thought to produce weak activation of the corticospinal tract pathway, has been reported to improve several parkinsonian motor symptoms, especially rigidity (Fregni et al 2006;Lefaucheur et al 2004). However, at higher levels of stimulation through electrodes near IC, strong muscle contractions can also appear (Ashby et al 1998;Butson et al 2007;Tommasi et al 2008) and thus worsen bradykinesia and rigidity outcome measures (Xu et al 2011).…”

Neural Circuit Modulation During Deep Brain Stimulation at the Subthalamic Nucleus for Parkinson's Disease: What Have We Learned from Neuroimaging Studies?

“…Compared with target lesioning, DBS therapy has several appealing qualities, including its reversibility and the capacity to modulate the extent of stimulated tissue by altering stimulation parameters and active lead configuration. The latter advantage is particularly useful for tailoring the electric field to reduce the effect on off-target areas (McIntyre et al, 2004a;Xu et al, 2011). Based on such considerations, DBS has rapidly supplanted target lesioning as the premier neurosurgical technique for advanced, treatment-refractory motor disorders.…”

Motor behaviors in the sheep evoked by electrical stimulation of the subthalamic nucleus

“…Motor side effects of clinical DBS are generally attributed to unintended spreading of the stimulation field to adjacent neuroanatomical structures. The traditional view that STN DBS side effects most commonly result from inadvertent stimulation of capsular fibers [55][56][57][58][59] is supported by the location of the IC immediately lateral to STN in both human and nonhuman primate brains [60,61]. However, capsular fibers in the sheep brain terminate ~10 mm lateral to the STN [41]; (see Figure 1A), suggesting instead that the stimulation-evoked Although the mechanisms of therapeutic DBS are not well understood, intraoperative macrorecordings from movement disorder patients support the hypothesis that the treatment works by suppressing exaggerated low-frequency oscillations detected within the basal ganglia [65].…”