Neuroplasticity

Neuroplasticity is the brain’s ability to reorganize synapses, neural circuits, and functional connections in response to stimuli. rTMS makes use of exactly this mechanism. It induces long-term changes in synaptic strength that persist beyond the duration of the stimulation itself. Therefore, rTMS does not simply stimulate neurons temporarily — it produces lasting changes in brain function.

Why it matters

The use of rTMS for depression targets this mechanism directly: depression is associated with reduced neuroplasticity, especially in the prefrontal cortex and hippocampus. Therefore, rTMS does not simply “tap” neurons — it restores the brain’s capacity to change. This process is based on the initial measurement of motor threshold.

As a result, clinical improvement often appears gradually, after the second or third week, and may persist after the treatment course has ended.

This also explains why a full course of sessions is necessary for a stronger and more durable clinical effect.

Mechanism

• LTP (Long-Term Potentiation): high-frequency protocols (≥5 Hz, iTBS) enhance synaptic transmission. Repeated stimulation increases AMPA receptor density and BDNF expression.
• LTD (Long-Term Depression): low-frequency protocols (≤1 Hz) reduce excitability. This is useful in structures with pathological hyperexcitability, such as in increased anxiety.
• BDNF upregulation: rTMS increases levels of Brain-Derived Neurotrophic Factor, which supports neuronal survival and the formation of new synapses.
• Synaptogenesis: new dendritic spines appear after repeated stimulation in animal models.
• Network-level remodeling: effects spread to connected structures through cortico-subcortical loops, such as DLPFC → ACC → amygdala → hippocampus.

Clinical significance

Patients with major depressive disorder show reduced activity in networks involving the DLPFC. rTMS reverses these findings through neuroplasticity mechanisms. fMRI studies also document increased functional connectivity between the DLPFC and sgACC after rTMS.

Therefore, neuroplasticity is the central mechanism through which rTMS produces durable clinical improvement.

Explicit relations (Entity Graph)

• Neuroplasticity → mechanism of → rTMS effect
• Neuroplasticity → involves → LTP / LTD
• Neuroplasticity → requires → repeated stimulation
• Neuroplasticity → mediated by → BDNF
• Neuroplasticity → impaired in → MDD
• Neuroplasticity → restored by → rTMS
• Neuroplasticity → measured via → fMRI connectivity / MEP amplitude changes

References

• Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC (2005). Theta burst stimulation of the human motor cortex. Neuron.
• Hoogendam JM, Ramakers GMJ, Di Lazzaro V (2010). Physiology of repetitive transcranial magnetic stimulation of the human brain. Brain Stimulation.
• Ziemann U, Paulus W, Nitsche MA, et al. (2008). Consensus: motor cortex plasticity protocols. Brain Stimulation.
• Lefaucheur JP, Aleman A, Baeken C, et al. (2020). Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update. Clinical Neurophysiology.