Focal Electrically Administered Seizure Therapy Research Articles

Brain-Computer Interface Based Neuromodulation on Treatment of Depression

Major Depressive Disorder (MDD) represents a significant societal burden, with traditional first-line treatments often falling short. This pressing issue has spurred the exploration of neuromodulation therapies, demonstrating superior efficacy compared to conventional pharmaceutical interventions. The present review provides a rigorous evaluation of four advanced neuromodulation techniques: Focal Electrically Administered Seizure Therapy (FEAST), Transcranial Magnetic Stimulation (TMS), Intermittent Theta-Burst Stimulation (iTBS), and Magnetic Seizure Therapy (MST). A comprehensive analytical comparison is offered, focusing on their efficacy, feasibility, economic considerations, and underlying mechanisms. Among these therapies, iTBS, integrated with Brain-Computer Interface (BCI) systems, has emerged as notably effective, with clinical trials indicating an average 80% efficacy at a reduced economic cost. FEAST and MST, supported by recent research, also exhibit strong efficacy, around 60%, although with more pronounced side effects. TMS, in contrast, exhibits a slightly reduced efficacy but is promising due to its minimal side effects. The review further delves into the transformative role of increasingly sophisticated BCI technologies in addressing previously identified challenges of neuromodulation therapy, such as adverse side effects, time-consuming procedures, and high costs. These technological advancements are elucidated, emphasizing their contribution to more precise therapy delivery and an enhanced patient experience. The review culminates in illuminating a pathway for the harmonious integration of neuromodulation therapies with traditional psychopharmacological treatments, positioning this integrative approach as a groundbreaking paradigm poised to redefine the landscape of depression treatment.

What’s new with the oldest form of brain stimulation: Innovations in ECT

Abstract The practice of electroconvulsive therapy (ECT) continues to evolve. Changes in the nature of electrical stimulation and in intracerebral current paths have markedly reduced or eliminated ECT’s adverse cognitive side effects, while maintaining its effectiveness. Further improvements in the nature of electrical stimulation will likely involve titrating in the current domain to minimize individual differences in intracranial current density. Improvements in spatial targeting, using magnetic seizure therapy (MST) or focal electrically administered seizure therapy (FEAST), promise to further dissociate therapeutic and adverse effects, and are presently undergoing pivotal trials. The key clinical challenges facing ECT pertain to two issues: when and how to change ECT treatment technique in patients who show inadequate or slow benefit, and optimal methods for enhancing durability of benefit and reducing relapse risk. New research suggests that ECT is routinely terminated prematurely in many depressed patients resulting in unnecessarily reduced remission rates. It will be suggested that there has been a secular shift in ECT practice, where the modal patient currently receives considerably more treatments than in the past. In recent years, it has been demonstrated that ECT results acutely in widespread increases in grey matter volume. The implications of these findings will be briefly discussed. Keywords: electroconvulsive therapy, FEAST, MST, depression

A two-site, open-label, non-randomized trial comparing Focal Electrically-Administered Seizure Therapy (FEAST) and right unilateral ultrabrief pulse electroconvulsive therapy (RUL-UBP ECT)

BackgroundFocal Electrically-Administered Seizure Therapy (FEAST) is a form of electroconvulsive therapy (ECT) that spatially focuses the electrical stimulus to initiate seizure activity in right prefrontal cortex. Two open-label non-comparative studies suggested that FEAST has reduced cognitive side effects when compared to historical data from other forms of ECT. In two different ECT clinics, we compared the efficacy and cognitive side effects of FEAST and Right Unilateral Ultrabrief Pulse (RUL-UBP) ECT. MethodsUsing a non-randomized, open-label design, 39 depressed adults were recruited after referral for ECT. Twenty patients received FEAST (14 women; age 45.2 ± 12.7), and 19 received RUL-UBP ECT (16 women; age 43.2 ± 16.4). Key cognitive outcome measures were the postictal time to reorientation and the Columbia University Autobiographical Memory Interview: Short-Form (CUAMI-SF). Antidepressant effects were assessed using the Hamilton Rating Scale for Depression (HRSD24). ResultsIn the Intent-to-treat sample, a repeated measures mixed model suggested no between group difference in HRSD24 score over time (F1,35 = 0.82, p = 0.37), while the response rate favored FEAST (FEAST: 65%; RUL-UBP ECT: 57.9%), and the remission rate favored RUL-UBP ECT (FEAST: 35%; RUL-UBP ECT: 47.4%). The FEAST group had numeric superiority in average time to reorientation (FEAST: 6.6 ± 5.0 min; RUL-UBP ECT: 8.8 ± 5.8 min; Cohens d = 0.41), and CUAMI-SF consistency score (FEAST: 69.2 ± 14.2%; RUL-UBP ECT: 63.9 ± 9.9%; Cohens d = 0.43); findings that failed to meet statistical significance. ConclusionsFEAST exerts similar efficacy relative to an optimal form of conventional ECT and may have milder cognitive side effects. A blinded, randomized, non-inferiority trial is needed.

The Efficacy and Safety of Neuromodulation Treatments in Late-Life Depression.

In this review, the efficacy and safety of FDA approved neuromodulation devices (electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) and vagus nerve stimulation (VNS)), as well as emerging neuromodulation treatments currently under investigation. ECT is the "gold standard" somatic therapy for treatment resistant depression (TRD). Although the clinical benefits are outweighed by potential cognitive and cardiovascular side effects in majority of cases, it remains unfairly stigmatized. TMS has few cognitive or somatic side effects but is not as effective the treatment of psychotic depression or more treatment resistant depression in elders. VNS has limited data in older patients but has been shown to be effective in chronic, treatment resistant adults. Several investigative neuromodulation treatments including magnetic seizure therapy (MST), focal electrically administered seizure therapy (FEAST), transcutaneous VNS (tVNS), transcranial direct current stimulation (tDCS), and deep brain simulation (DBS) shown promise in geriatric TRD. ECT, TMS and VNS are effective treatment for late-life depression, and research has continued to refine the techniques. Investigative neuromodulation techniques are promising, but evidence for the safety and efficacy of these devices in the geriatric population is needed.

A two-site, open-label, non-randomized update, suggests focal electrically administered seizure therapy (FEAST) may have a reduced time to re-orientation compared to right unilateral ultra-brief pulse electroconvulsive therapy (UBP-RUL ECT)

Background: Focal Electrically Administered Seizure Therapy (FEAST) is a form of ECT which maximally focuses the electrical stimulus to the frontal lobe. Recent open-label studies suggest that FEAST’s enhanced focality may lead to reduced cognitive side effects (1, 2), however there are no studies directly comparing FEAST to other forms of ECT (such as Right Unilateral Ultra-Brief Pulse Electroconvulsive therapy (UBP-RUL-ECT). We subsequently compared the efficacy, and cognitive side effect burden of FEAST and UBP-RUL-ECT.

Expanded Safety and Efficacy Data for a New Method of Performing Electroconvulsive Therapy: Focal Electrically Administered Seizure Therapy.

ObjectiveElectroconvulsive therapy (ECT) is the most rapid and effective antidepressant treatment but with concerns about cognitive adverse effects. A new form of ECT, focal electrically administered seizure therapy (FEAST), was designed to increase the focality of stimulation and better match stimulus parameters with neurophysiology. We recently reported on the safety and feasibility of FEAST in a cohort (n = 17) of depressed patients. We now report on the safety, feasibility, preliminary efficacy, and cognitive effects of FEAST in a new cohort.MethodsOpen-label FEAST was administered to 20 depressed adults (6 men; 3 with bipolar disorder; age 49.1 ± 10.6 years). Clinical and cognitive assessments were obtained at baseline and end of course. Time to orientation recovery was assessed at each treatment. Nonresponders switched to conventional ECT.ResultsParticipants tolerated the treatment well with no dropouts. Five patients (25%) transitioned from FEAST to conventional ECT due to inadequate response. After FEAST (mean, 9.3 ± 3.5 sessions; range, 4–14), there was a 58.1% ± 36.0% improvement in Hamilton Rating Scale for Depression scores compared with that in the baseline (P < 0.0001); 13 (65%) of 20 patients met response criteria, and 11 (55%) of 20 met remission criteria. Patients achieved reorientation (4 of 5 items) in 4.4 ± 3.0 minutes (median, 4.5 minutes), timed from eyes opening. There was no deterioration in neuropsychological measures.ConclusionsThese findings provide further support for the safety and efficacy of FEAST. The remission and response rates were in the range found using conventional ECT, and the time to reorientation may be quicker. However, without a randomized comparison group, conclusions are tentative.

Focal electrically administered seizure therapy (FEAST): Clinical and mechanistic updates

Electroconvulsive therapy (ECT) efficacy and cognitive side effects remain influenced by several parameters including electrodes position and configuration, the applied current intensity, duration, and polarity. We report on latest development in FEAST and its mechanisms of actions.

Effect of anatomical variability on electric field characteristics of electroconvulsive therapy and magnetic seizure therapy: a parametric modeling study.

Electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) are conventionally applied with a fixed stimulus current amplitude, which may result in differences in the neural stimulation strength and focality across patients due to interindividual anatomical variability. The objective of this study is to quantify the effect of head anatomical variability associated with age, sex, and individual differences on the induced electric field characteristics in ECT and MST. Six stimulation modalities were modeled including bilateral and right unilateral ECT, focal electrically administered seizure therapy (FEAST), and MST with circular, cap, and double-cone coils. The electric field was computed using the finite element method in a parameterized spherical head model representing the variability in the general population. Head tissue layer thicknesses and conductivities were varied to examine the impact of interindividual anatomical differences on the stimulation strength, depth, and focality. Skull conductivity most strongly affects the ECT electric field, whereas the MST electric field is independent of tissue conductivity variation in this model but is markedly affected by differences in head diameter. Focal ECT electrode configurations such as FEAST is more sensitive to anatomical variability than that of less focal paradigms such as BL ECT. In MST, anatomical variability has stronger influence on the electric field of the cap and circular coils compared to the double-cone coil, possibly due to the more superficial field of the former. The variability of the ECT and MST electric fields due to anatomical differences should be considered in the interpretation of existing studies and in efforts to improve dosing approaches for better control of stimulation strength and focality across patients, such as individualization of the current amplitude. The conventional approach to individualizing dosage by titrating the number of pulses cannot compensate for differences in the spatial extent of stimulation that result from anatomical variability.

A Feasibility Study of a New Method for Electrically Producing Seizures in Man: Focal Electrically Administered Seizure Therapy [FEAST

BackgroundElectroconvulsive therapy (ECT) remains the most effective acute treatment for severe major depression, but with significant risk of adverse cognitive effects. Unidirectional electrical stimulation with a novel electrode placement and geometry (Focal Electrically Administered Seizure Therapy (FEAST)) has been proposed as a means to initiate seizures in prefrontal cortex prior to secondary generalization. As such, it may have fewer cognitive side effects than traditional ECT. We report on its first human clinical application. MethodSeventeen unmedicated depressed adults (5 men; 3 bipolar disorder; age 53 ± 16 years) were recruited after being referred for ECT. Open-label FEAST was administered with a modified spECTrum 5000Q device and a traditional ECT dosing regimen until patients clinically responded. Clinical and cognitive assessments were obtained at baseline, and end of course. Time to orientation recovery, a predictor of long-term amnestic effects, was assessed at each treatment. Nonresponders to FEAST were transitioned to conventional ECT. ResultsOne patient withdrew from the study after a single titration session. After the course of FEAST (median 10 sessions), there was a 46.1 ± 35.5% improvement in Hamilton Rating Scale for Depression (HRSD24) scores compared to baseline (33.1 ± 6.8, 16.8 ± 10.9; P < 0.0001). Eight of 16 patients met response criteria (50% decrease in HRSD24) and 5/16 met remission criteria (HRSD24 ≤ 10). Patients achieved full re-orientation (4 of 5 items) in 5.5 ± 6.4 min (median = 3.6), timed from when their eyes first opened after treatment. ConclusionIn this feasibility study, FEAST produced clinically meaningful antidepressant improvement, with relatively short time to reorientation. Our preliminary work first in primates and now depressed adults demonstrates that FEAST is feasible, safe, well-tolerated and, if efficacy can be optimized, has potential to replace traditional ECT.

Convulsant and anticonvulsant properties of electroconvulsive therapy: towards a focal form of brain stimulation

Electroconvulsive therapy is the most rapidly acting and effective antidepressant treatment. For decades it was believed that the generalized seizure provided the necessary and sufficient conditions for efficacy, while the type and quantity of electricity determined the magnitude of cognitive effects. A series of randomized, double-masked trials at the New York State Psychiatric Institute has disproved this view. By systematically varying electrode placement, electrical dosage, and stimulus waveform, this work demonstrated that efficacy and cognitive effects are highly dependent on current paths and the current density within those paths. Specifically, antidepressant effects are contingent on the recruitment of a sufficiently large neuronal population in prefrontal cortex in seizure initiation. The anticonvulsant properties of ECT are reviewed and it is hypothesized that the magnitude of surround inhibition in a PFC network is the critical feature underlying these effects on efficacy. Given this localization, new forms of brain stimulation that elicit focal PFC seizures should have superior benefit/risk ratios. Magnetic seizure therapy has shown promise, but its development may be hindered by technical problems in delivering a sufficiently powerful stimulus. A new alternative, focal electrically administered seizure therapy (FEAST), is described and early work with non-human primates indicate that FEAST achieves a degree of focality in seizure expression that is not possible with traditional ECT.