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ABSTRACT: This study investigates the stimulation strength and focality of electroconvulsive therapy (ECT) with individualized current amplitude in a nonhuman primate (NHP) model. We generated an anatomically realistic finite element model of a NHP head incorporating tissue heterogeneity and white matter conductivity anisotropy based on structural magnetic resonance imaging (MRI) and diffusion tensor MRI data. The electric field spatial distributions of three conventional ECT electrode placements (bilateral, bifrontal, and right unilateral) and an experimental frontomedial electrode configuration were simulated. We calibrated the electric field maps relative to an empirical neural activation threshold and evaluated the stimulation strength and focality of the various ECT electrode configurations with individualized current amplitudes corresponding to the motor threshold and seizure threshold assessed in the anesthetized NHP. Understanding the stimulation strength and focality of various forms of ECT could provide insight into the mechanisms of therapeutic seizure induction, and could provide support for the clinical investigation of ECT with individualized current amplitude as an intervention with potentially improved risk/benefit ratio.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2012; 2012:6430-3.
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ABSTRACT: BACKGROUND: Various transcranial magnetic stimulation (TMS) coil designs are available or have been proposed. However, key coil characteristics such as electric field focality and attenuation in depth have not been adequately compared. Knowledge of the coil focality and depth characteristics can help TMS researchers and clinicians with coil selection and interpretation of TMS studies. OBJECTIVE: To quantify the electric field focality and depth of penetration of various TMS coils. METHODS: The electric field distributions induced by 50 TMS coils were simulated in a spherical human head model using the finite element method. For each coil design, we quantified the electric field penetration by the half-value depth, d(1/2), and focality by the tangential spread, S(1/2), defined as the half-value volume (V(1/2)) divided by the half-value depth, S(1/2) = V(1/2)/d(1/2). RESULTS: The 50 TMS coils exhibit a wide range of electric field focality and depth, but all followed a depth-focality tradeoff: coils with larger half-value depth cannot be as focal as more superficial coils. The ranges of achievable d(1/2) are similar between coils producing circular and figure-8 electric field patterns, ranging 1.0-3.5 cm and 0.9-3.4 cm, respectively. However, figure-8 field coils are more focal, having S(1/2) as low as 5 cm(2) compared to 34 cm(2) for circular field coils. CONCLUSIONS: For any coil design, the ability to directly stimulate deeper brain structures is obtained at the expense of inducing wider electrical field spread. Novel coil designs should be benchmarked against comparison coils with consistent metrics such as d(1/2) and S(1/2).
Brain Stimulation 03/2012; · 3.76 Impact Factor
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ABSTRACT: We present the first computational study investigating the electric field (E-field) strength generated by various electroconvulsive therapy (ECT) electrode configurations in specific brain regions of interest (ROIs) that have putative roles in the therapeutic action and/or adverse side effects of ECT. This study also characterizes the impact of the white matter (WM) conductivity anisotropy on the E-field distribution. A finite element head model incorporating tissue heterogeneity and WM anisotropic conductivity was constructed based on structural magnetic resonance imaging (MRI) and diffusion tensor MRI data. We computed the spatial E-field distributions generated by three standard ECT electrode placements including bilateral (BL), bifrontal (BF), and right unilateral (RUL) and an investigational electrode configuration for focal electrically administered seizure therapy (FEAST). The key results are that (1) the median E-field strength over the whole brain is 3.9, 1.5, 2.3, and 2.6 V/cm for the BL, BF, RUL, and FEAST electrode configurations, respectively, which coupled with the broad spread of the BL E-field suggests a biophysical basis for observations of superior efficacy of BL ECT compared to BF and RUL ECT; (2) in the hippocampi, BL ECT produces a median E-field of 4.8 V/cm that is 1.5-2.8 times stronger than that for the other electrode configurations, consistent with the more pronounced amnestic effects of BL ECT; and (3) neglecting the WM conductivity anisotropy results in E-field strength error up to 18% overall and up to 39% in specific ROIs, motivating the inclusion of the WM conductivity anisotropy in accurate head models. This computational study demonstrates how the realistic finite element head model incorporating tissue conductivity anisotropy provides quantitative insight into the biophysics of ECT, which may shed light on the differential clinical outcomes seen with various forms of ECT, and may guide the development of novel stimulation paradigms with improved risk/benefit ratio.
NeuroImage 02/2012; 59(3):2110-23. · 5.89 Impact Factor
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ABSTRACT: The goal of this study is to investigate the influence of white matter conductivity anisotropy on the electric field strength induced by electroconvulsive therapy (ECT). We created an anatomically-realistic finite element human head model incorporating tissue heterogeneity and white matter conductivity anisotropy using structural magnetic resonance imaging (MRI) and diffusion tensor MRI data. The electric field spatial distributions of three conventional ECT electrode placements (bilateral, bifrontal, and right unilateral) and an experimental electrode configuration, focal electrically administered seizure therapy (FEAST), were computed. A quantitative comparison of the electric field strength was subsequently performed in specific brain regions of interest thought to be associated with side effects of ECT (e.g., hippocampus and in-sula). The results show that neglecting white matter conductivity anisotropy yields a difference up to 19%, 25% and 34% in electric field strength in the whole brain, hippocampus, and insula, respectively. This study suggests that white matter conductivity anisotropy should be taken into account in ECT electric field models.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2011; 2011:5473-6.
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ABSTRACT: Blinded studies with transcranial magnetic stimulation (TMS) require a valid sham condition. A wide range of sham approaches have been implemented but they have various limitations including residual electric field in the brain, inadequate reproduction of auditory and cutaneous sensations, and/or need for electrical stimulation with scalp electrodes. We propose a quadrupole TMS coil configuration that can be electronically switched between active and sham modes. In active mode, the quadrupole coil has electric field characteristics similar to a conventional figure-8 coil. In sham mode, the quadrupole coil compared to the reverse-current sham figure-8 coil has 50% less electric field penetration depth, is 97% more focal, produces 35% less intense field in the brain, and induces scalp electric field characteristics closer to those of active TMS.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2011; 2011:1993-6.
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ABSTRACT: The characteristics of transcranial magnetic stimulation (TMS) pulses influence the physiological effect of TMS. However, available TMS devices allow very limited adjustment of the pulse parameters. We describe a novel TMS device that uses a circuit topology incorporating two energy storage capacitors and two insulated-gate bipolar transistor (IGBT) modules to generate near-rectangular electric field pulses with adjustable number, polarity, duration, and amplitude of the pulse phases. This controllable pulse parameter TMS (cTMS) device can induce electric field pulses with phase widths of 10-310 µs and positive/negative phase amplitude ratio of 1-56. Compared to conventional monophasic and biphasic TMS, cTMS reduces energy dissipation up to 82% and 57% and decreases coil heating up to 33% and 41%, respectively. We demonstrate repetitive TMS trains of 3000 pulses at frequencies up to 50 Hz with electric field pulse amplitude and width variability less than the measurement resolution (1.7% and 1%, respectively). Offering flexible pulse parameter adjustment and reduced power consumption and coil heating, cTMS enhances existing TMS paradigms, enables novel research applications and could lead to clinical applications with potentially enhanced potency.
Journal of Neural Engineering 06/2011; 8(3):036016. · 3.84 Impact Factor
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ABSTRACT: We present the first computational study comparing the electric field induced by various electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) paradigms. Four ECT electrode configurations (bilateral, bifrontal, right unilateral, and focal electrically administered seizure therapy) and three MST coil configurations (circular, cap, and double cone) were modeled. The model incorporated a modality-specific neural activation threshold. ECT (0.3 ms pulse width) and MST induced the maximum electric field of 2.1-2.5 V cm⁻¹ and 1.1-2.2 V cm⁻¹ in the brain, corresponding to 6.2-7.2 times and 1.2-2.3 times the neural activation threshold, respectively. The MST electric field is more confined to the superficial cortex compared to ECT. The brain volume stimulated was much larger with ECT (up to 100%) than with MST (up to 8.2%). MST with the double-cone coil was the most focal, and bilateral ECT was the least focal. Our results suggest a possible biophysical explanation of the reduced side effects of MST compared to ECT. Our results also indicate that the conventional ECT pulse amplitude (800-900 mA) is much higher than necessary for seizure induction. Reducing the ECT pulse amplitude should be explored as a potential means of diminishing side effects.
Journal of Neural Engineering 01/2011; 8(1):016007. · 3.84 Impact Factor
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ABSTRACT: In this article, we review the parameters that define the electroconvulsive therapy (ECT) electrical stimulus and discuss their biophysical roles. We also present the summary metrics of charge and energy that are conventionally used to describe the dose of ECT and the rules commonly deployed to individualize the dose for each patient. We then highlight the limitations of these summary metrics and dosing rules in that they do not adequately capture the roles of the distinct stimulus parameters. Specifically, there is strong theoretical and empirical evidence that stimulus parameters (pulse amplitude, shape, and width, and train frequency, directionality, polarity, and duration) exert unique neurobiological effects that are important for understanding ECT outcomes. Consideration of the distinct stimulus parameters, in conjunction with electrode placement, is central to further optimization of ECT dosing paradigms to improve the risk-benefit ratio. Indeed, manipulation of specific parameters, such as reduction of pulse width and increase in number of pulses, has already resulted in dramatic reduction of adverse effects, while maintaining efficacy. Furthermore, the manipulation of other parameters, such as current amplitude, which are commonly held at fixed, high values, might be productively examined as additional means of targeting and individualizing the stimulus, potentially reducing adverse effects. We recommend that ECT dose be defined using all stimulus parameters rather than a summary metric. All stimulus parameters should be noted in treatment records and published reports. To enable research on optimization of dosing paradigms, we suggest that ECT devices provide capabilities to adjust and display all stimulus parameters.
The journal of ECT 09/2010; 26(3):159-74. · 1.19 Impact Factor
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ABSTRACT: The safety of transcranial magnetic stimulation (TMS) in patients with an implanted deep brain stimulation (DBS) systems has not been thoroughly investigated. One potential safety hazard is the induction of significant voltages in the subcutaneous leads in the scalp that could result in unintended electrical currents in the DBS electrode contacts. We measured ex-vivo the TMS-induced voltages and currents in DBS electrodes with the implantable pulse generator (IPG) set in various modes of operation. We show that voltages as high as 100 V resulting in currents as high as 83 mA can be induced in the DBS leads by a TMS pulse in all IPG modes. These currents are an order of magnitude higher than the normal DBS pulses, and could result in tissue damage. When the IPG is turned off, electrode currents flow only if the TMS-induced voltage exceeds 5 V.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2010; 2010:6821-4.
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ABSTRACT: We describe a novel transcranial magnetic stimulation (TMS) device that uses a circuit topology incorporating two energy-storage capacitors and two insulated-gate bipolar transistors (IGBTs) to generate near-rectangular electric field E-field) pulses with adjustable number, polarity, duration, and amplitude of the pulse phases. This controllable-pulse-parameter TMS (cTMS) device can induce E-field pulses with phase widths of 5-200 µs and positive/negative phase amplitude ratio of 1-10. Compared to conventional monophasic and biphasic TMS, cTMS reduces energy dissipation by 78-82% and 55-57% and decreases coil heating by 15-33% and 31-41%, respectively. We demonstrate repetitive TMS (rTMS) trains of 3,000 pulses at frequencies up to 50 Hz with E-field pulse amplitude and width variability of less than 1.7% and 1%, respectively. The reduced power consumption and coil heating, and the flexible pulse parameter adjustment offered by cTMS could enhance existing TMS paradigms and could enable novel research and clinical applications with potentially enhanced potency.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2010; 2010:2922-6.
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ABSTRACT: The goal of this study is to investigate the regional distribution of the electric field (E-field) strength induced by electroconvulsive therapy (ECT), and to contrast clinically relevant electrode configurations through finite element (FE) analysis. An FE human head model incorporating tissue heterogeneity and white matter anisotropy was generated based on structural magnetic resonance imaging (MRI) and diffusion tensor MRI (DT-MRI) data. We simulated the E-field spatial distributions of three standard ECT electrode placements [bilateral (BL), bifrontal (BF), and right unilateral (RUL)] and an investigational electrode configuration [focal electrically administered seizure therapy (FEAST)]. A quantitative comparison of the E-field strength was subsequently carried out in various brain regions of interests (ROIs) that have putative role in the therapeutic action and/or adverse side effects of ECT. This study illustrates how the realistic FE head model provides quantitative insight in the biophysics of ECT, which may shed light on the differential clinical outcomes seen with various forms of ECT, and may guide the development of novel stimulation paradigms with improved risk/benefit ratio.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2010; 2010:2045-8.
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ABSTRACT: The safety of electroconvulsive therapy (ECT) in patients who have deep brain stimulation (DBS) implants represents a significant clinical issue. A major safety concern is the presence of burr holes and electrode anchoring devices in the skull, which may alter the induced electric field distribution in the brain. We simulated the electric field using finite-element method in a five-shell spherical head model. Three DBS electrode anchoring techniques were modeled, including ring/cap, microplate, and burr-hole cover. ECT was modeled with bilateral (BL), right unilateral (RUL), and bifrontal (BF) electrode placements and with clinically-used stimulus current amplitude. We compared electric field strength and focality among the DBS implantation techniques and ECT electrode configurations. The simulation results show an increase in the electric field strength in the brain due to conduction through the burr holes, especially when the burr holes are not fitted with nonconductive caps. For typical burr hole placement for subthalamic nucleus DBS, the effect on the electric field strength and focality is strongest for BF ECT, which runs contrary to the belief that more anterior ECT electrode placements are safer in patients with DBS implants.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2010; 2010:2049-52.
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ABSTRACT: Electroconvulsive therapy (ECT) is a mainstay in the treatment of severe, medication-resistant depression. The antidepressant efficacy and cognitive side effects of ECT are influenced by the position of the electrodes on the head and by the degree to which the electrical stimulus exceeds the threshold for seizure induction. However, surprisingly little is known about the effects of other key electrical parameters such as current directionality, polarity, and electrode configuration. Understanding these relationships may inform the optimization of therapeutic interventions to improve their risk/benefit ratio. To elucidate these relationships, we evaluated a novel form of ECT (focal electrically administered seizure therapy, FEAST) that combines unidirectional stimulation, control of polarity, and an asymmetrical electrode configuration, and contrasted it with conventional ECT in a nonhuman primate model. Rhesus monkeys had their seizure thresholds determined on separate days with ECT conditions that crossed the factors of current directionality (unidirectional or bidirectional), electrode configuration (standard bilateral or FEAST (small anterior and large posterior electrode)), and polarity (assignment of anode and cathode in unidirectional stimulation). Ictal expression and post-ictal suppression were quantified through scalp EEG. Findings were replicated and extended in a second experiment with the same subjects. Seizures were induced in each of the 75 trials, including 42 FEAST procedures. Seizure thresholds were lower with unidirectional than with bidirectional stimulation (p<0.0001), and lower in FEAST than in bilateral ECS (p=0.0294). Ictal power was greatest in posterior-anode unidirectional FEAST, and post-ictal suppression was strongest in anterior-anode FEAST (p=0.0008 and p=0.0024, respectively). EEG power was higher in the stimulated hemisphere in posterior-anode FEAST (p=0.0246), consistent with the anode being the site of strongest activation. These findings suggest that current directionality, polarity, and electrode configuration influence the efficiency of seizure induction with ECT. Unidirectional stimulation and novel electrode configurations such as FEAST are two approaches to lowering seizure threshold. Furthermore, the impact of FEAST on ictal and post-ictal expression appeared to be polarity dependent. Future studies may examine whether these differences in seizure threshold and expression have clinical significance for patients receiving ECT.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 02/2009; 34(8):2002-10. · 6.99 Impact Factor
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ABSTRACT: We present a quantitative comparison of two metrics-neural stimulation strength and focality-in electrocon-vulsive therapy (ECT) and magnetic seizure therapy (MST) using finite-element method (FEM) simulation in a spherical head model. Five stimulation modalities were modeled, including bilateral ECT, unilateral ECT, focal electrically administered seizure therapy (FEAST), and MST with circular and double-cone coils, with stimulation parameters identical to those applied in clinical practice. We further examine the effect on the stimulation metrics of individual-, sex- and age-related variability in tissue layer thickness and conductivity. Neural stimulation by MST is shown to be more focal and superficial than ECT. This result suggests that it may be advantageous to reduce the current used in ECT. The stimulation strength in MST is also less sensitive to variations in head geometry and tissue conductivity than in ECT. Individualization of pulse amplitude in both ECT and MST could compensate for anatomical variability, which could lead to more consistent clinical outcomes.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2009; 2009:682-8.
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ABSTRACT: Deep-brain transcranial magnetic stimulation (dTMS) could provide new, non-invasive therapeutic options for various psychiatric and neurological disorders. Figures of merit (FoMs) are proposed to evaluate and compare dTMS coil designs. These FoMs characterize the depth of electric field penetration, scalp stimulation, focality, and energy. Two coil configurations potentially suitable for dTMS are analyzed: circular crown coil and C-core coil. These coils have significantly less attenuation of the electric field strength in depth, compared to conventional TMS coils. In the limiting case as the coil dimensions become large relative to the head, the electric field decay in depth becomes linear, which indicates that, at best, the electric field attenuation is directly proportional to the depth of the target. The charge density and heating induced in the brain are at safe levels, but the risk of unintended neuromodulation and seizures with dTMS has to be evaluated further. Preliminary simulation results suggest that the crown coil has the best overall performance for dTMS. Finally, synchronous firing of all TMS coil elements appears more effective at stimulating deep neurons than is sequential firing.
Engineering in Medicine and Biology Society, 2008. EMBS 2008. 30th Annual International Conference of the IEEE; 09/2008
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ABSTRACT: A novel transcranial magnetic stimulation (TMS) device with controllable pulse width (PW) and near-rectangular pulse shape (cTMS) is described. The cTMS device uses an insulated gate bipolar transistor (IGBT) with appropriate snubbers to switch coil currents up to 6 kA, enabling PW control from 5 micros to over 100 micros. The near-rectangular induced electric field pulses use 2%-34% less energy and generate 67%-72% less coil heating compared to matched conventional cosine pulses. CTMS is used to stimulate rhesus monkey motor cortex in vivo with PWs of 20 to 100 micros, demonstrating the expected decrease of threshold pulse amplitude with increasing PW. The technological solutions used in the cTMS prototype can expand functionality, and reduce power consumption and coil heating in TMS, enhancing its research and therapeutic applications.
IEEE Transactions on Biomedical Engineering 02/2008; 55(1):257-66. · 2.28 Impact Factor
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The Journal of Physiology 11/2007; 584(Pt 2):369-70. · 4.72 Impact Factor
