Cortical and subcortical blood flow effects of subthalamic nucleus stimulation in PD

Hershey, Tamara; Revilla, Fredy J.; Wernle, Angie R.; McGee‐Minnich, Lori; Antenor, J.V.; Videen, Tom O.; Dowling, Joshua L.; Mink, Jonathan W.; Perlmutter, Joel S.

doi:10.1212/01.wnl.0000083991.81859.73

Cited by 185 publications

(156 citation statements)

References 21 publications

Supporting

Mentioning

132

Contrasting

Unclassified

Order By: Relevance

“…Discrete metabolic reductions in motor cortical and cerebellar areas distant from the stimulation site have been reported with STN DBS (Hershey et al, 2003;Hilker et al, 2004;Payoux et al, 2004). Our data are compatible with the notion of CSPTC hyperactivity in resting PD patients, which may be reduced by stimulation.…”

Section: Metabolic Changes With Stn Stimulationsupporting

confidence: 91%

Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease

et al. 2006

View full text Add to dashboard Cite

Deep brain stimulation of the subthalamic nucleus (STN DBS) has become an accepted tool for the treatment of Parkinson's disease (PD). Although the precise mechanism of action of this intervention is unknown, its effectiveness has been attributed to the modulation of pathological network activity. We examined this notion using positron emission tomography (PET) to quantify stimulation-induced changes in the expression of a PD-related covariance pattern (PDRP) of regional metabolism. These metabolic changes were also compared with those observed in a similar cohort of patients undergoing STN lesioning.We found that PDRP activity declined significantly (P < 0.02) with STN stimulation. The degree of network modulation with DBS did not differ from that measured following lesioning (P = 0.58). Statistical parametric mapping (SPM) revealed that metabolic reductions in the internal globus pallidus (GPi) and caudal midbrain were common to both STN interventions (P < 0.01), although declines in GPi were more pronounced with lesion. By contrast, elevations in posterior parietal metabolism were common to the two procedures, albeit more pronounced with stimulation.These findings indicate that suppression of abnormal network activity is a feature of both STN stimulation and lesioning. Nonetheless, these two interventions may differ metabolically at a regional level.

show abstract

Section: Metabolic Changes With Stn Stimulationsupporting

confidence: 91%

Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease

et al. 2006

View full text Add to dashboard Cite

show abstract

“…The relative importance of inhibitory GPe-GPi connections compared to excitatory STN-GPi connections in nonparkinsonian subjects (see the 1995 article by Calon et al, 42 for example) stimulated with small electrodes and long pulses may have contributed to the observed differences. Positron emission tomography (PET) experiments in humans have confirmed that blood flow in the region of GPi increases during STN HFS, 43 which is consistent with activation of output from the stimulated site. A functional MRI study also found an increase in blood oxygen level-dependent signal in GPi of patients undergoing STN HFS.…”

Section: Axonal Output Of the Stimulated Nucleusmentioning

confidence: 75%

Mechanisms and Targets of Deep Brain Stimulation in Movement Disorders

et al. 2008

View full text Add to dashboard Cite

Summary:Chronic electrical stimulation of the brain, known as deep brain stimulation (DBS), has become a preferred surgical treatment for medication-refractory movement disorders. Despite its remarkable clinical success, the therapeutic mechanisms of DBS are still not completely understood, limiting opportunities to improve treatment efficacy and simplify selection of stimulation parameters. This review addresses three questions essential to understanding the mechanisms of DBS. 1) How does DBS affect neuronal tissue in the vicinity of the active electrode or electrodes? 2) How do these changes translate into therapeutic benefit on motor symptoms? 3) How do these effects depend on the particular site of stimulation? Early hypotheses proposed that stimulation inhibited neuronal activity at the site of stimulation, mimicking the outcome of ablative surgeries. Recent studies have challenged that view, suggesting that although somatic activity near the DBS electrode may exhibit substantial inhibition or complex modulation patterns, the output from the stimulated nucleus follows the DBS pulse train by direct axonal excitation. The intrinsic activity is thus replaced by high-frequency activity that is time-locked to the stimulus and more regular in pattern. These changes in firing pattern are thought to prevent transmission of pathologic bursting and oscillatory activity, resulting in the reduction of disease symptoms through compensatory processing of sensorimotor information. Although promising, this theory does not entirely explain why DBS improves motor symptoms at different latencies. Understanding these processes on a physiological level will be critically important if we are to reach the full potential of this powerful tool.

show abstract

“…These studies have resulted in general guidelines on the selection of stimulation parameters, as well as clinical algorithms for programming the devices. Imaging studies have developed correlations between stimulation parameters and markers of brain activity (Hershey et al, 2003;Haslinger et al, 2005;Phillips et al, 2006;Trost et al, 2006), and identified the location of therapeutic DBS electrode contacts (Saint-Cyr et al, 2002;Voges and J, 2002;Herzog et al, 2004;Zonenshayn et al, 2004;Kitagawa et al, 2005;Nowinski et al, 2005;Plaha et al, 2006). Modeling studies have characterized the theoretical effects of DBS electric fields on the underlying neural tissue (McIntyre et al, 2004b;Miocinovic et al, 2006b).…”

Section: Discussionmentioning

confidence: 99%

Patient-specific analysis of the volume of tissue activated during deep brain stimulation

et al. 2007

View full text Add to dashboard Cite

Despite the clinical success of deep brain stimulation (DBS) for the treatment of movement disorders, many questions remain about its effects on the nervous system. We have developed a methodology to predict the volume of tissue activated (VTA) by DBS on a patient-specific basis. Our goals are to identify the intersection between the VTA and surrounding anatomical structures and to compare activation of these structures with clinical outcomes. The model system consists of three fundamental components: 1) a 3D anatomical model of the subcortical nuclei and DBS electrode position in the brain, each derived from magnetic resonance imaging (MRI); 2) a finite element model of the DBS electrode and electric field transmitted to the brain, with tissue conductivity properties derived from diffusion tensor MRI; 3) VTA prediction derived from the response of myelinated axons to the applied electric field, which is a function of the stimulation parameters (contact, impedance, voltage, pulse width, frequency). We used this model system to analyze the effects of subthalamic nucleus (STN) DBS in a patient with Parkinson's disease. Quantitative measurements of bradykinesia, rigidity, and corticospinal tract (CST) motor thresholds were evaluated over a range of stimulation parameter settings. Our model predictions showed good agreement with CST thresholds. Additionally, stimulation through electrode contacts that improved bradykinesia and rigidity generated VTAs that overlapped the zona incerta / fields of Forel (ZI/H2). Application of DBS technology to various neurological disorders has preceded scientific characterization of the volume of tissue directly affected by the stimulation. Synergistic integration of clinical analysis, neuroimaging, neuroanatomy, and neurostimulation modeling provides the opportunity to address wide ranging questions on the factors linked with the therapeutic benefits and side effects of DBS.

show abstract

Cortical and subcortical blood flow effects of subthalamic nucleus stimulation in PD

Abstract: These data suggest that STN stimulation increases firing of STN output neurons, which increases inhibition of thalamocortical projections, ultimately decreasing blood flow in cortical targets. STN stimulation appears to drive, rather than inhibit, STN output neurons.

Cited by 185 publications

References 21 publications

Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease

Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease

Mechanisms and Targets of Deep Brain Stimulation in Movement Disorders

Patient-specific analysis of the volume of tissue activated during deep brain stimulation

Contact Info

Product

Resources

About