EEG Synchronized Left Prefrontal Transcranial Magnetic Stimulation (TMS) for Treatment Resistant Depression is Feasible and Produces an Entrainment Dependent Clinical Response: A Randomized Controlled Double Blind Clinical Trial

George, Mark S.; Huffman, Sarah; Doose, Jayce; Sun, Xiaoxiao; Dancy, Morgan; Faller, Josef; Li, Xingbao; Han, Yu; Goldman, Robin I.; Sajda, Paul; Brown, Truman R.

doi:10.2139/ssrn.4334289

Cited by 3 publications

(6 citation statements)

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“…1. Before recruitment, all patients were screened for all inclusion and exclusion criteria described in [27], [25], and [28]. Then the pre-treatment scan (scan#1) was done with our integrated fMRI-EEG-TMS (fET) system to determine the pre-treatment preferred phase ϕ pre of each subject [19, 25].…”

Section: Methodsmentioning

confidence: 99%

“…This trial and a partial analysis of the effects of the magnitude of entrainment have been detailed elsewhere [25, 28]. In this paper, we consider the consistency of the entrainment effects with respect to phase and how both magnitude and phase consistency interact with cortical excitability to form a set of biomarkers that directly predict treatment efficacy.…”

Section: Introductionmentioning

confidence: 99%

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Increased entrainment and decreased excitability predict efficacious treatment of closed-loop phase-locked rTMS for treatment-resistant depression

Sun,

Doose,

Faller

et al. 2023

Preprint

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Transcranial magnetic stimulation (TMS) is an FDA-approved therapy for major depressive disorder (MDD), specifically for patients who have treatment-resistant depression (TRD). However, TMS produces response or remission in about 50% of patients but is ineffective for the other 50%. Limits on efficacy may be due to individual patient variability, but to date, there are no good biomarkers or measures of target engagement. In addition, TMS efficacy is typically not assessed until a six-week treatment ends, precluding the evaluation of intermediate improvements during the treatment duration. Here, we report on results using a closed-loop phase-locked repetitive TMS (rTMS) treatment that synchronizes the delivery of rTMS based on the timing of the pulses relative to a patient’s individual electroencephalographic (EEG) prefrontal alpha oscillation informed by functional magnetic resonance imaging (fMRI). We find that, in responders, synchronized delivery of rTMS produces two systematic changes in brain dynamics. The first change is a decrease in global cortical excitability, and the second is an increase in the phase entrainment of cortical dynamics. These two effects predict clinical outcomes in the synchronized treatment group but not in an active-treatment unsynchronized control group. The systematic decrease in excitability and increase in entrainment correlated with treatment efficacy at the endpoint and intermediate weeks during the synchronized treatment. Specifically, we show that weekly tracking of these biomarkers allows for efficacy prediction and potential of dynamic adjustments through a treatment course, improving the overall response rates.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased entrainment and decreased excitability predict efficacious treatment of closed-loop phase-locked rTMS for treatment-resistant depression

Sun,

Doose,

Faller

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Experiments Designmentioning

confidence: 99%

“…This trial and a partial analysis of the effects of the magnitude of entrainment have been detailed elsewhere [25,28]. In this paper, we consider the consistency of the entrainment effects with respect to phase and how both magnitude-consistency and phase-consistency interact with cortical excitability to form a set of biomarkers that directly predict treatment efficacy.…”

Section: Introductionmentioning

confidence: 99%

Biomarkers predict the efficacy of closed-loop rTMS treatment for refractory depression

Sajda,

Sun,

Doose

et al. 2023

Preprint

Self Cite

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Transcranial magnetic stimulation (TMS) is a non-invasive FDA-approved therapy for major depressive disorder (MDD), specifically for treatment-resistant depression (TRD). Though offering promise for those with TRD, its effectiveness is less than one in two patients (i.e., less than 50%). Limits on efficacy may be due to individual patient variability, but to date, there are no established biomarkers or measures of target engagement that can predict efficacy. Additionally, TMS efficacy is typically not assessed until a six-week treatment ends, precluding interim re-evaluations of the treatment. Here, we report results using a closed-loop phase-locked repetitive TMS (rTMS) treatment that synchronizes the delivery of rTMS based on the timing of the pulses relative to a patient's individual electroencephalographic (EEG) prefrontal alpha oscillation indexed by functional magnetic resonance imaging (fMRI). Among responders, synchronized rTMS produces two systematic changes in brain dynamics: a reduction in global cortical excitability and enhanced phase entrainment of cortical dynamics. These effects predict clinical outcomes in the synchronized treatment group but not in an active-treatment unsynchronized control group. The systematic decrease in excitability and increase in entrainment correlated with treatment efficacy at the endpoint and intermediate weeks during the synchronized treatment. Specifically, we show that weekly biomarker tracking enables efficacy prediction and dynamic adjustments through a treatment course, improving the overall response rates. This innovative approach advances the prospects of individualized medicine in MDD and holds potential for application in other neuropsychiatric disorders.

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“…Although there are some circular clustering tools, they either only emphasize a polar angle difference (ignore the amplitude) or are designed with loss of generality -i.e., they are designed to work on datasets that obey specific assumptions [2,3,14]. Due to the absence of suitable tools, certain studies may resort to sub-optimal approaches [20] or concentrate exclusively on the angle difference, disregarding the radius aspect [21,22].…”

Section: Introductionmentioning

confidence: 99%

Circular Clustering With Polar Coordinate Reconstruction

Sun,

Sajda

2024

IEEE/ACM Trans. Comput. Biol. and Bioinf.

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There is a growing interest in characterizing circular data found in biological systems. Such data are wide-ranging and varied, from the signal phase in neural recordings to nucleotide sequences in round genomes. Traditional clustering algorithms are often inadequate due to their limited ability to distinguish differences in the periodic component θ. Current clustering schemes for polar coordinate systems have limitations, such as being only angle-focused or lacking generality. To overcome these limitations, we propose a new analysis framework that utilizes projections onto a cylindrical coordinate system to represent objects in a polar coordinate system optimally. Using the mathematical properties of circular data, we show that our approach always finds the correct clustering result within the reconstructed dataset, given sufficient periodic repetitions of the data. This framework is generally applicable and adaptable to most state-of-the-art clustering algorithms. We demonstrate on synthetic and real data that our method generates more appropriate and consistent clustering results than standard methods. In summary, our proposed analysis framework overcomes the limitations of existing polar coordinate-based clustering methods and provides an accurate and efficient way to cluster circular data. We provide the code as open-source on GitHub.

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EEG Synchronized Left Prefrontal Transcranial Magnetic Stimulation (TMS) for Treatment Resistant Depression is Feasible and Produces an Entrainment Dependent Clinical Response: A Randomized Controlled Double Blind Clinical Trial

Cited by 3 publications

References 0 publications

Increased entrainment and decreased excitability predict efficacious treatment of closed-loop phase-locked rTMS for treatment-resistant depression

Increased entrainment and decreased excitability predict efficacious treatment of closed-loop phase-locked rTMS for treatment-resistant depression

Biomarkers predict the efficacy of closed-loop rTMS treatment for refractory depression

Circular Clustering With Polar Coordinate Reconstruction

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