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

Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA.
NeuroImage (Impact Factor: 6.13). 02/2007; 34(2):661-70. DOI: 10.1016/j.neuroimage.2006.09.034
Source: PubMed

ABSTRACT 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. This study presents a methodology to predict the volume of tissue activated (VTA) by DBS on a patient-specific basis. Our goals were to identify the intersection between the VTA and surrounding anatomical structures and to compare activation of these structures with clinical outcomes. The model system consisted 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 an opportunity to address wide ranging questions on the factors linked with the therapeutic benefits and side effects of DBS.

Download full-text


Available from: Jaimie M Henderson, Jul 06, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies in patients with treatment-resistant depression have shown similar results with the use of deep brain stimulation (DBS) in the subcallosal cingulate gyrus (SCG), ventral capsule/ventral striatum (VC/VS) and nucleus accumbens (Acb). As these brain regions are interconnected, one hypothesis is that by stimulating these targets one would just be influencing different relays in the same circuitry. We investigate behavioural, immediate early gene expression, and functional connectivity changes in rats given DBS in homologous regions, namely the ventromedial prefrontal cortex (vmPFC), white matter fibers of the frontal region (WMF) and nucleus accumbens. We found that DBS delivered to the vmPFC, Acb but not WMF induced significant antidepressant-like effects in the FST (31%, 44%, and 17% reduction in immobility compared to controls). Despite these findings, stimulation applied to these three targets induced distinct patterns of regional activity and functional connectivity. While animals given vmPFC DBS had increased cortical zif268 expression, changes after Acb stimulation were primarily observed in subcortical structures. In animals receiving WMF DBS, both cortical and subcortical structures at a distance from the target were influenced by stimulation. In regards to functional connectivity, DBS in all targets decreased intercorrelations among cortical areas. This is in contrast to the clear differences observed in subcortical connectivity, which was reduced after vmPFC DBS but increased in rats receiving Acb or WMF stimulation. In conclusion, results from our study suggest that, despite similar antidepressant-like effects, stimulation of the vmPFC, WMF and Acb induce distinct changes in regional brain activity and functional connectivity.
    Neurobiology of Disease 08/2014; 71. DOI:10.1016/j.nbd.2014.08.007 · 5.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: For accurate EEG/MEG source analysis it is necessary to model the head volume conductor as realistic as possible. This includes the distinction of the different conductive compartments in the human head. In this study, we investigated the influence of modeling/not modeling the conductive compartments skull spongiosa, skull compacta, cerebrospinal fluid (CSF), gray matter, and white matter and of the inclusion of white matter anisotropy on the EEG/MEG forward solution. Therefore, we created a highly realistic 6-compartment head model with white matter anisotropy and used a state-of-the-art finite element approach. Starting from a 3-compartment scenario (skin, skull, and brain), we subsequently refined our head model by distinguishing one further of the above-mentioned compartments. For each of the generated five head models, we measured the effect on the signal topography and signal magnitude both in relation to a highly resolved reference model and to the model generated in the previous refinement step. We evaluated the results of these simulations using a variety of visualization methods, allowing us to gain a general overview of effect strength, of the most important source parameters triggering these effects, and of the most affected brain regions. Thereby, starting from the 3-compartment approach, we identified the most important additional refinement steps in head volume conductor modeling. We were able to show that the inclusion of the highly conductive CSF compartment, whose conductivity value is well known, has the strongest influence on both signal topography and magnitude in both modalities. We found the effect of gray/white matter distinction to be nearly as big as that of the CSF inclusion, and for both of these steps we identified a clear pattern in the spatial distribution of effects. In comparison to these two steps, the introduction of white matter anisotropy led to a clearly weaker, but still strong, effect. Finally, the distinction between skull spongiosa and compacta caused the weakest effects in both modalities when using an optimized conductivity value for the homogenized compartment. We conclude that it is highly recommendable to include the CSF and distinguish between gray and white matter in head volume conductor modeling. Especially for the MEG, the modeling of skull spongiosa and compacta might be neglected due to the weak effects; the simplification of not modeling white matter anisotropy is admissible considering the complexity and current limitations of the underlying modeling approach.
    NeuroImage 06/2014; 100. DOI:10.1016/j.neuroimage.2014.06.040 · 6.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Clinical deep brain stimulation (DBS) is based on the use of cylindrical electrodes driven in monopolar or bipolar configurations. The simulation field spreads symmetri-cally around the electrode modulating both targeted and non-targeted neural structures. Recent advances have focused on novel stimulation techniques based on the use of high-density segmented electrodes, which allow current-steering and field-shaping capability. This paper presents the architecture of a multi-channel current-steering stimulator output stage that allows for monopolar, bipolar, tripolar and quadripolar multi-site stimulation. The core of the output stage comprises N independent high-compliance current drivers (HCCDs), capable of delivering up to 1.5 mA complementary currents in 10 different current ranges. Each of the N HCCDs can drive up to 8 adjacent electrode contacts thanks to a 2-32 multiplexer controlled by a 5-32 decoder. The HCCD was designed in a HV 0.18íµí¼‡m CMOS process. The circuits were simulated in Cadence Spectre and simulated results are presented in the paper.
    Biomedical Circuits and Systems Conference; 10/2013