Fabiola Alonso

Investigation into Deep Brain Stimulation Lead Designs : A Patient-Specific Simulation Study

New deep brain stimulation (DBS) electrode designs offer operation in voltage and current mode and capability to steer the electric field (EF). The aim of the study was to compare the EF distributions of four DBS leads at equivalent amplitudes (3 V and 3.4 mA). Finite element method (FEM) simulations (n = 38) around cylindrical contacts (leads 3389, 6148) or equivalent contact configurations (leads 6180, SureStim1) were performed using homogeneous and patient-specific (heterogeneous) brain tissue models. Steering effects of 6180 and SureStim1 were compared with symmetric stimulation fields. To make relative comparisons between simulations, an EF isolevel of 0.2 V/mm was chosen based on neuron model simulations (n = 832) applied before EF visualization and comparisons. The simulations show that the EF distribution is largely influenced by the heterogeneity of the tissue, and the operating mode. Equivalent contact configurations result in similar EF distributions. In steering configurations, larger EF volumes were achieved in current mode using equivalent amplitudes. The methodology was demonstrated in a patient-specific simulation around the zona incerta and a “virtual” ventral intermediate nucleus target. In conclusion, lead design differences are enhanced when using patient-specific tissue models and current stimulation mode.

Patient-Specific Electric Field Simulations and Acceleration Measurements for Objective Analysis of Intraoperative Stimulation Tests in the Thalamus

Despite an increasing use of deep brain stimulation (DBS) the fundamental mechanisms of action remain largely unknown. Simulation of electric entities has previously been proposed for chronic DBS combined with subjective symptom evaluations, but not for intraoperative stimulation tests. The present paper introduces a method for an objective exploitation of intraoperative stimulation test data to identify the optimal implant position of the chronic DBS lead by relating the electric field (EF) simulations to the patient-specific anatomy and the clinical effects quantified by accelerometry. To illustrate the feasibility of this approach, it was applied to five patients with essential tremor bilaterally implanted in the ventral intermediate nucleus (VIM). The VIM and its neighborhood structures were preoperatively outlined in 3D on white matter attenuated inversion recovery MR images. Quantitative intraoperative clinical assessments were performed using accelerometry. EF simulations (n = 272) for intraoperative stimulation test data performed along two trajectories per side were set-up using the finite element method for 143 stimulation test positions. The resulting EF isosurface of 0.2 V/mm was superimposed to the outlined anatomical structures. The percentage of volume of each structure’s overlap was calculated and related to the corresponding clinical improvement. The proposed concept has been successfully applied to the five patients. For higher clinical improvements, not only the VIM but as well other neighboring structures were covered by the EF isosurfaces. The percentage of the volumes of the VIM, of the nucleus intermediate lateral of the thalamus and the prelemniscal radiations within the prerubral field of Forel increased for clinical improvements higher than 50% compared to improvements lower than 50%. The presented new concept allows a detailed and objective analysis of a high amount of intraoperative data to identify the optimal stimulation target. First results indicate agreement with published data hypothesizing that the stimulation of other structures than the VIM might be responsible for good clinical effects in essential tremor. (Clinical trial reference number: Ref: 2011-A00774-37/AU905)

Influence on Deep Brain Stimulation from Lead Design, Operating Modeand Tissue Impedance Changes â A Simulation Study

Background: Deep brain stimulation (DBS) systems in current mode and new lead designs are recently available. To switch between DBS-systems remains complicated as clinicians may lose their reference for programming. Simulations can help increase the understanding. Objective: To quantitatively investigate the electric field (EF) around two lead designs simulated to operate in voltage and current mode under two time points following implantation. Methods: The finite element method was used to model Lead 3389 (Medtronic) and 6148 (St Jude) with homogenous surrounding grey matter and a peri-electrode space (PES) of 250 μm. The PES-impedance mimicked the acute (extracellular fluid) and chronic (fibrous tissue) time-point. Simulations at different amplitudes of voltage and current (n=236) were performed using two different contacts. Equivalent current amplitudes were extracted by matching the shape and maximum EF of the 0.2 V/mm isolevel. Results: The maximum EF extension at 0.2 V/mm varied between 2-5 mm with a small difference between the leads. In voltage mode EF increased about 1 mm at acute compared to the chronic PES. Current mode presented the opposite relationship. Equivalent EFs for lead 3389 at 3 V were found for 7 mA (acute) and 2.2 mA (chronic). Conclusions: Simulations showed a major impact on the electric field extension between postoperative time points. This may explain the clinical decisions to reprogram the amplitude weeks after implantation. Neither the EF extension nor intensity is considerably influenced by the lead design. However, the EF distribution is affected by the larger contact of Lead 6148 generating an electric field below the tip.

Modelling Details for Electric Field Simulations of Deep Brain Stimulation

Deep brain stimulation is a well-established technique for symptomatic treatment of e.g. Parkinsons disease and essential tremor. Computer simulations using the finite element method (FEM) are wide ...

Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems : A Simulation Study

The success of deep brain stimulation (DBS) relies primarily on the localization of the implanted electrode. Its final position can be chosen based on the results of intraoperative microelectrode recording (MER) and stimulation tests. The optimal position often differs from the final one selected for chronic stimulation with the DBS electrode. The aim of the study was to investigate, using finite element method (FEM) modeling and simulations, whether lead design, electrical setup, and operating modes induce differences in electric field (EF) distribution and in consequence, the clinical outcome. Finite element models of a MER system and a chronic DBS lead were developed. Simulations of the EF were performed for homogenous and patient-specific brain models to evaluate the influence of grounding (guide tube vs. stimulator case), parallel MER leads, and non-active DBS contacts. Results showed that the EF is deformed depending on the distance between the guide tube and stimulating contact. Several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution. The DBS EF volume can cover the intraoperatively produced EF, but can also extend to other anatomical areas. In conclusion, EF deformations between stimulation tests and DBS should be taken into consideration as they can alter the clinical outcome.

Postoperative lead movement after deep brain stimulation surgery and changes of stimulation area

IntroductionLead movement after deep brain stimulation (DBS) may occur and influence the area of stimulation. The cause of the displacement is not fully understood. The aim of the study was to inve ...Objective: We here investigated the effect of bilateral 6-hydroxydopamine (6-OHDA) lesions, a rat model for Parkinsons disease (PD), on impulsivity and attention in an auditory oddball paradigm. In PD, the progressive loss of dopamine (DA) neurons in the substantia nigra leads to disturbed motor function, but cognitive disturbances, including attentional deficits and impulsivity, are increasingly recognized as disabling factors. Rats with 6-OHDA induced nigrostriatal lesions of dopamine neurons show significant motor impairment reminiscent of PD, and recent studies also indicate cognitive impairment in this model. Methods: Rats were trained in a 3-class auditory oddball paradigm, where they had to nose poke a hole after an infrequent correct tone, which was rewarded by a pellet, but to ignore a frequent standard tone and infrequent distractor tone. After reaching a criterion of 90% correct hits, retrograde degeneration of DA neurons in the substantia nigra were induced by bilateral striatal injection of 6-OHDA (10 μg in 1μl PBS; n=12), sham-lesioned rats (controls; n=8) received vehicle. Four weeks after surgery the rats were re-tested in the oddball paradigm. Results: After 6-OHDA lesions, rats show deteriorated attention, as indicated by a significant decrease in the hit rate to the correct tone. Additionally, the number of impulsive nose pokes was reduced compared to controls, which would indicate less impulsive behavior. Conclusion: We conclude that rats with bilateral 6-OHDA lesions may be used to investigate the biological basis of attentional deficits in PD, and to develop and test new therapeutic strategies for these symptoms ranging from pharmacological treatment to neurosurgical intervention.Introduction: Chronic electric deep brain stimulation (DBS) has been proposed to enable consciousness recovery, targeting mainly the central thalamus. Our aim was to study clinical effects of bilateral pallido-thalamic low frequency stimulation intended to overdrive neuronal activity in continuing disorders of consciousness. Methods: Five patients were included in a prospective, monocentric, 12-month clinical observational study, with blind crossover period (NCT01718249): P1 male, 32 y/o, 12 years after traumatic brain injury (TBI), vegetative status (VS); P2 female, 62 y/o, 14 months after intracerebral hemorrhage (ICH), minimally conscious state (MCS); P3 male, 24 y/o, 3 years after TBI, MCS; P4 female, 22 y/o, 4 years after TBI, MCS; P5 female, 47 y/o, 27 months after ICH, MCS. Four phases were individualized: (1) Baseline, at least 2 months; (2) DBS surgery and titration, 1 month; (3) blind, random, 3-month cross over (CO) period with 1.5month ON (CO-ON) and OFF (CO-OFF) conditions; (4) unblinded, at least 5 months, DBS period (DBS-ON). Electrodes (DBS 3389, Medtronic, USA) were placed within the right and left targets accounting for the lesions of patients. Two neuropacemakers (ACTIVA, Medtronic, USA) were implanted. Primary outcome was the analysis of scores of the Coma Recovery Scale Revised (CRS-R; 0-23): assessments 2 times per week; for the 5 patients, n=419, scores ranging from 1 to 18. Statistical analyses were conducted for a two-sided Type I error of 5% using random-effects models accounting between and within patient variability due to repeated measurements. Results: No mortality related to surgery and DBS. By individual we observed statistically significant improvement of CRS-R during DBS-ON versus baseline (P1, P3) and CO-On versus baseline (P3). For the 5 patients (group analysis) auditory, visual, motor, oromotor-verbal, communication subscores of CRS-R were significantly improved during DBS-ON versus baseline. Cross-over analysis did not show statistically significant improvement of CRS-R and subscores during CO-ON versus CO-OFF, except P2 and P3 motor sub scores. Conclusion: Bilateral low frequency DBS in severe continuing disorders of consciousness improved patients on the short term without irreversible adverse effects. Individual analysis seems preferable facing the complexity of clinical features and pathophysiology. Given the current state of knowledge, expectations of relatives, caregivers and physicians should be weighted.