Poster No:
76
Submission Type:
Abstract Submission
Authors:
Kevin Kadak1, Davide Momi2, Sorenza Bastiaens1, Mohammad Oveisi1, Taha Morshedzadeh1, Minarose Ismail3, John Griffiths4
Institutions:
1Centre for Addiction and Mental Health, Toronto, Ontario, 2Stanford University, Stanford, CA, 3The Hospital for Sick Children, Toronto, Ontario, 4University of Toronto, Toronto, Ontario
First Author:
Kevin Kadak
Centre for Addiction and Mental Health
Toronto, Ontario
Co-Author(s):
Parsa Oveisi
Centre for Addiction and Mental Health
Toronto, Ontario
Introduction:
Repetitive Transcranial Magnetic Stimulation (rTMS) is a neuromodulatory tool for inducing neural plasticity and treating neuropsychiatric disorders, notably major depressive disorder (MDD). Intermittent theta-burst stimulation (iTBS), an rTMS protocol class, yields greater treatment efficiency and reduced dosage compared to high-frequency (10 Hz) rTMS (HF-rTMS). These enhancements emphasize the importance of protocol parameters for robustly inducing long-term potentiation (LTP) and depression (LTD). However, clinical responses to iTBS remain inconsistent, necessitating further research into the mechanisms underlying responsiveness and a basis upon which to personalize treatments. Resting-state EEG, particularly the individual alpha frequency (IAF), provides insights into resting-state corticothalamic circuitry dynamics and serves as a biomarker for MDD status and treatment responsiveness. Aligning rTMS frequencies with a person's IAF may enhance therapeutic effects by resonating with endogenous oscillations. The patterned 5 Hz iTBS pulse structure, a subharmonic of 10 Hz, offers a congruence between the two for frequency alignment. Although IAF-synchronized rTMS has shown promise in improving MDD outcomes, its efficacy in treatment-resistant depression (TRD) remains variable, prompting further investigation. Computational models of corticothalamic circuits simulate neural oscillations and rTMS-induced effects, addressing experimental challenges in subcortical dynamics. These models, incorporating calcium-dependent plasticity governed by NMDA receptor conductance and BCM theory, capture bidirectional plasticity and response variability. This study proposes an individualized iTBS paradigm using a computational framework to optimize stimulation protocols aligned with IAF, aiming to enhance neuromodulation efficacy.
Methods:
The present study used a computational model of corticothalamic circuitry to simulate resting-state EEG activity and the effects of rTMS-induced plasticity effects on spectral power, synaptic weights, and calcium levels, and to examine brain-stimulation interactions on iTBS responsiveness. A 4-population corticothalamic neural mass model composed of excitatory and inhibitory neurons of the cortex and thalamus was used. A physiological description of synaptic weight change was applied wherein post-synaptic calcium concentrations and NMDA receptor conductance rates adaptively mediate plasticity effects. iTBS was scaled across pulses-per-bursts and inter-burst frequency parameters, then assessed for pre-post changes in outcome item measures.
Results:
Model simulations captured resting-state EEG, including alpha oscillations, and demonstrated broadband power modulation induced by iTBS across parameter space, with the strongest extent of modulation occurring in protocols whose frequencies aligned with the IAF first subharmonic. These effects were underlied by enhanced modifications to synaptic weight and calcium release compared to non-aligned protocols, with treatment efficacy being predicted by stronger LTP of inhibitory-afferent connections and LTD of excitatory-afferent connections. These findings support the hypothesis that IAF alignment enhances iTBS efficacy and suggest that IAF subharmonics could be leveraged as a neurophysiological basis upon which to tailor treatments.
Conclusions:
The present work demonstrates a neurophysiological basis for iTBS responsiveness and provides a computational framework for optimizing patient-specific protocols. By aligning stimulation with IAF subharmonics, the proposed approach enhances neural plasticity and reduces outcome variability. These findings underscore the importance of individualized interventions in advancing rTMS efficacy for MDD treatment.
Brain Stimulation:
TMS 1
Modeling and Analysis Methods:
EEG/MEG Modeling and Analysis 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Microcircuitry and Modules
Neuroinformatics and Data Sharing:
Informatics Other
Keywords:
Electroencephaolography (EEG)
Modeling
Plasticity
Transcranial Magnetic Stimulation (TMS)
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Resting state
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Healthy subjects
Was this research conducted in the United States?
No
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
NOTE: Any human subjects studies without IRB approval will be automatically rejected.
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Were any animal research approved by the relevant IACUC or other animal research panel?
NOTE: Any animal studies without IACUC approval will be automatically rejected.
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Please indicate which methods were used in your research:
EEG/ERP
TMS
Computational modeling
Provide references using APA citation style.
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No