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

• Published in: Journal of computational neuroscience Vol. 52; no. 3; pp. 183 - 196
• Main Authors: Farahani, Mohammadreza Vasheghani, Shariatpanahi, Seyed Peyman, Goliaei, Bahram
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2024; Springer Nature B.V
• Subjects: Achievement tests; Biological effects; Biomedical and Life Sciences; Biomedicine; Brain; Computational neuroscience; Firing pattern; Functional plasticity; Human Genetics; Magnetic fields; Neurology; Neurons; Neurosciences; Plasticity; Synapses; Synaptic plasticity; Theory of Computation; Transcranial magnetic stimulation; Variability; Transcranial magnetic stimulation (TMS); Theta burst stimulation (TBS); Long-term depression (LTD); Computational modeling; TBS variability of responses; Long-term potentiation (LTP)
• ISSN: 0929-5313; 1573-6873; 1573-6873
• DOI: 10.1007/s10827-024-00875-1

Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation (rTMS) with unknown underlying mechanisms and highly variable responses across subjects. To investigate these issues, we developed a simple computational model. Our model consisted of two neurons linked by an excitatory synapse that incorporates two mechanisms: short-term plasticity (STP) and spike-timing-dependent plasticity (STDP). We applied a variable-amplitude current through I-clamp with a TBS time pattern to the pre- and post-synaptic neurons, simulating synaptic plasticity. We analyzed the results and provided an explanation for the effects of TBS, as well as the variability of responses to it. Our findings suggest that the interplay of STP and STDP mechanisms determines the direction of plasticity, which selectively affects synapses in extended neurons and underlies functional effects. Our model describes how the timing, number, and intensity of pulses delivered to neurons during rTMS contribute to induced plasticity. This not only successfully explains the different effects of intermittent TBS (iTBS) and continuous TBS (cTBS), but also predicts the results of other protocols such as 10 Hz rTMS. We propose that the variability in responses to TBS can be attributed to the variable span of neuronal thresholds across individuals and sessions. Our model suggests a biologically plausible mechanism for the diverse responses to TBS protocols and aligns with experimental data on iTBS and cTBS outcomes. This model could potentially aid in improving TBS and rTMS protocols and customizing treatments for patients, brain areas, and brain disorders.