Electric Field Modeling for Transcranial Magnetic Stimulation and Electroconvulsive Therapy

Deng, Zhi‐De; Liston, Conor; Gunning, Faith M.; Dubin, Marc G.; Friðgeirsson, Egill A.; Lilien, Joseph; Wingen, Guido van; Waarde, Jeroen van

doi:10.1007/978-3-030-21293-3_4

Cited by 13 publications

(17 citation statements)

References 20 publications

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“…Guiding treatment by the induced electric field has not yet been systematically studied, and it is unknown whether clinical efficacy does indeed depend on it. One small study with 26 depressed patients treated with F3-guided rTMS of the lDLPFC found no correlation between the e-field strength and clinical outcomes [35].…”

Section: Discussionmentioning

confidence: 99%

A direct comparison of neuronavigated and non-neuronavigated intermittent theta burst stimulation in the treatment of depression

et al. 2021

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Objective: To investigate whether a four-week course of neuronavigated intermittent theta burst stimulation (iTBS) of the left dorsolateral prefrontal cortex is superior to the non-neuronavigated F3-EEG method of positioning. Methods: We conducted a single-center, two-arm, randomized and double-blinded study (clinicaltrials. gov NCT03953521). 37 inpatients with an at least moderate depressive episode were randomized to receive either neuronavigated or 10-20-EEG-system based F3 guided iTBS. Both groups received twenty week daily sessions of iTBS while continuing to receive standard-of-care treatment by their ward physicians. For navigated iTBS, we used magnetic resonance imaging to target the border between the anterior and middle third of the middle frontal gyrus considered to represent the left dorsolateral prefrontal cortex (lDLPFC). Differences in the treatment arms were blinded by completely mimicking the procedures of the respective other treatment group. Rating physicians were not involved in the treatment procedure. Primary outcome was defined as the change of the 21-item version of the Hamilton Depression Score (HAMD) from baseline to end of treatment at week 4. Secondary outcomes included HAMD score during the treatment, Patient Health Questionnaire-9, WHO Quality of Life-BREF and Clinical Global Impression. For primary outcome, we used a planned group comparison for the absolute change in the HAMD. For secondary outcome measures we calculated analyses of variance (ANOVAs) with the within-subjects factor time (primary: baseline vs. week 4; secondary: all visits) and the between-subjects factor group (navigated vs. F3 guided group). We also did planned contrasts between both groups for all variables and all treatment and follow-up visits with the aim not to oversee any group differences. For group contrasts we used Student T-tests for metric and chi-square tests for categorial variables. Significance threshold was set to 5% uncorrected for multiple comparisons. Results: Enrolment of 80 patients with interim analysis was planned. Interim analysis was performed after 37 patients (intention to treat). 6 patients dropped out, leaving 31 for analysis. With respect to primary outcome criteria, absolute change in the HAMD did not differ significantly between groups. In accordance, relative change and number of responders and remitters were not significantly different. Overall number of responders was 53% and of remitters was 60%. On a descriptive level, the results favor the clinical effects of the F3 group for the absolute and relative change in the HAMD and the number of responders. Number of remitters were exactly the same for both groups. Therefore, we decided to stop the trial due to the added burden of magnetic resonance imaging and neuronavigated treatment in relation to the effect. Secondary outcomes did also not differ significantly between groups. Patients did not differ in their baseline characteristics nor with respect to intake of medication during the trial period and all had access to the same the...

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Section: Discussionmentioning

confidence: 99%

A direct comparison of neuronavigated and non-neuronavigated intermittent theta burst stimulation in the treatment of depression

et al. 2021

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“…Similarly, Lee et al ( 83 ) determined that subthreshold iTBS caused greater reductions in depressive symptoms than suprathreshold iTBS, again pointing to an optimal middle stimulation intensity. In retrospective E-field analyses of clinical rTMS for depression and smoking cessation, the prefrontal E-field magnitude from 120% MT stimulation did not linearly correlate with the percentage of symptom change ( 84 , 85 ), possibly suggesting a non-linear dose-response relationship and perhaps peak efficacy with an optimized middle amount of stimulation. A remaining question is whether there is an optimal E-field dosing intensity, which itself could be prone to interindividual differences due to varied distributions of particular neuron types or different neurotransmitter concentrations between patients.…”

Section: Introductionmentioning

confidence: 91%

The Problem and Potential of TMS' Infinite Parameter Space: A Targeted Review and Road Map Forward

Brown

2022

Front. Psychiatry

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BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a non-invasive, effective, and FDA-approved brain stimulation method. However, rTMS parameter selection remains largely unexplored, with great potential for optimization. In this review, we highlight key studies underlying next generation rTMS therapies, particularly focusing on: (1) rTMS Parameters, (2) rTMS Target Engagement, (3) rTMS Interactions with Endogenous Brain Activity, and (4) Heritable Predisposition to Brain Stimulation Treatments.MethodsWe performed a targeted review of pre-clinical and clinical rTMS studies.ResultsCurrent evidence suggests that rTMS pattern, intensity, frequency, train duration, intertrain interval, intersession interval, pulse and session number, pulse width, and pulse shape can alter motor excitability, long term potentiation (LTP)-like facilitation, and clinical antidepressant response. Additionally, an emerging theme is how endogenous brain state impacts rTMS response. Researchers have used resting state functional magnetic resonance imaging (rsfMRI) analyses to identify personalized rTMS targets. Electroencephalography (EEG) may measure endogenous alpha rhythms that preferentially respond to personalized stimulation frequencies, or in closed-loop EEG, may be synchronized with endogenous oscillations and even phase to optimize response. Lastly, neuroimaging and genotyping have identified individual predispositions that may underlie rTMS efficacy.ConclusionsWe envision next generation rTMS will be delivered using optimized stimulation parameters to rsfMRI-determined targets at intensities determined by energy delivered to the cortex, and frequency personalized and synchronized to endogenous alpha-rhythms. Further research is needed to define the dose-response curve of each parameter on plasticity and clinical response at the group level, to determine how these parameters interact, and to ultimately personalize these parameters.

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“…These values were used to calculate a representative BBB space constant (λ BBB ) for each brain region. Typical brain electric field produced by each stimulation modality were also derived from literature [63][64][65][66][67][68][69][70][71][72][73]. Finally, using the analytical method for predicting maximal BBB polarization length and BBB electric field amplification factor (Fig.…”

Section: Electric Fields Amplification At the Bbb Across Neuromodulatmentioning

confidence: 99%

“…However, it is the macroscopic changes that are conventionally assumed to drive neuronal stimulation for many modalities. We thus, contrasted Activating Functions generated by conventional macroscopic tissue changes (values derived from literature; [35,61,67,68,70,73,[81][82][83][84][85]) with the BBB ultra-structure generated Activating Function derived here. This comparison is subject to a range of assumptions (e.g.…”

Section: Theoretical Basis For Neuron Polarization Amplification By Vmentioning

confidence: 99%

Neurovascular-modulation

Khadka

Bikson²

2020

Preprint

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Neurovascular-modulation is based on two principles that derive directly from brain vascular ultra-structure, namely an exceptionally dense capillary bed (BBB length density: 972 mm/mm3) and a blood-brain-barrier (BBB) resistivity (ρ ~ 1×105 Ω.m) much higher than brain parenchyma/interstitial space (ρ ~ 4 Ω.m) or blood (ρ ~ 1 Ω.m). Principle 1: Electrical current crosses between the brain parenchyma (interstitial space) and vasculature, producing BBB electric fields (EBBB) that are > 400x of the average parenchyma electric field (ĒBRAIN), which in turn modulates transport across the BBB. Specifically, for a BBB space constant (λBBB) and wall thickness (dth-BBB): analytical solution for maximum BBB electric field (EABBB) is given as: (ĒBRAIN × λBBB) / dth-BBB. Direct vascular stimulation suggests novel therapeutic strategies such as boosting metabolic capacity or interstitial fluid clearance. Boosting metabolic capacity impacts all forms of neuromodulation, including those applying intensive stimulation or driving neuroplasticity. Boosting interstitial fluid clearance has broad implications as a treatment for neurodegenerative disease including Alzheimer’s disease. Principle 2: Electrical current in the brain parenchyma is distorted around brain vasculature, amplifying neuronal polarization. Specifically, vascular ultra-structure produces ~50% modulation of the average parenchyma electric field (ĒBRAIN) over the ~40 μm inter-capillary distance. The divergence of EBRAIN (activating function) is thus ~100 kV/m2 per unit average parenchyma electric field (ĒBRAIN). This impacts all forms of neuromodulation, including Deep Brain Stimulation (DBS), Spinal Cord Stimulation (SCS), Transcranial Magnetic Stimulation (TMS), Electroconvulsive Therapy (ECT), and transcranial electrical stimulation (tES) techniques such a transcranial Direct Current Stimulation (tDCS). Specifically, whereas spatial profile of EBRAIN along neurons is traditionally assumed to depend on macroscopic anatomy, it instead depends on local vascular ultra-structure.

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Electric Field Modeling for Transcranial Magnetic Stimulation and Electroconvulsive Therapy

Abstract: Major depressive disorder (MDD) is a highly prevalent condition with a lifetime prevalence of nearly 20% [1]. MDD is currently the second leading cause of disability worldwide, and the World Health Organization (WHO) has predicted that, by

Cited by 13 publications

References 20 publications

A direct comparison of neuronavigated and non-neuronavigated intermittent theta burst stimulation in the treatment of depression

A direct comparison of neuronavigated and non-neuronavigated intermittent theta burst stimulation in the treatment of depression

The Problem and Potential of TMS' Infinite Parameter Space: A Targeted Review and Road Map Forward

Neurovascular-modulation

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