A computational model elucidating mechanisms and variability in theta burst stimulation responses

Area of Science:

• Computational neuroscience
• Neuroplasticity
• Brain stimulation

Background:

• Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation (rTMS) with poorly understood mechanisms and highly variable individual responses.
• Understanding these mechanisms is crucial for optimizing rTMS protocols and therapeutic applications.

Purpose of the Study:

• To develop a computational model investigating the mechanisms underlying TBS effects and response variability.
• To elucidate the roles of short-term plasticity (STP) and spike-timing-dependent plasticity (STDP) in TBS-induced synaptic changes.

Main Methods:

• A simple computational model of two linked neurons with an excitatory synapse incorporating STP and STDP was developed.
• Variable-amplitude current with a TBS pattern was applied to simulate synaptic plasticity.
• Model outputs were analyzed to explain TBS effects and response variability.

Main Results:

• The interplay between STP and STDP mechanisms determines the direction and functional effects of synaptic plasticity.
• The model successfully explains differential effects of intermittent TBS (iTBS) and continuous TBS (cTBS), and predicts outcomes for other protocols like 10 Hz rTMS.
• Variability in neuronal thresholds across individuals and sessions is proposed as a key factor for diverse TBS responses.

Conclusions:

• The developed model offers a biologically plausible mechanism for diverse responses to TBS protocols, aligning with experimental data.
• This model can potentially improve TBS and rTMS protocols, enabling customized treatments for patients.
• Further research using this model could refine personalized neuromodulation strategies.