Robotic-Assisted Transcranial Magnetic Stimulation: Development and Validation of Advanced Protocols for Precision Brain Stimulation

Transcranial Magnetic Stimulation (TMS) is a non-invasive brain stimulation technique used to modulate cortical excitability by generating brief-lasting and high-intensity magnetic fields which bypass the skull and induce an electric field in the cerebral cortex. TMS has been widely employed in clinical settings to treat neurological conditions (e.g., migraine, tinnitus, neuropathic pain) and psychiatric disorders (e.g., major depressive disorder, obsessive–compulsive disorder, addiction), as well as in research to investigate brain functional organization, connectivity and neuronal plasticity. However, the conventional TMS administration is affected by coil placement inaccuracies, operator-dependent variability, and the lack of subject-specific protocol adaptation. This issue is addressed in the present work by designing and validating a modular, high-performance, and economically sustainable robot-aided TMS platform able to deliver TMS simulation with minimal positional and orientation errors and with great versatility. The proposed system was assessed in both static conditions, replicating conventional experimental setups where the subject remains stationary, and dynamic conditions, allowing head rotations, translations, and more complex motion patterns similar to those occurring during walking. Implementing and assessing different control strategies, the results showed that hybrid force-position control performs better under dynamic conditions, while selective impedance is more suitable for static ones, suggesting the opportunity to develop a platform capable of dynamically switching between the two strategies according to operational requirements. Successively, robot-aided TMS was then employed to develop and implement more advanced stimulation paradigms which would be exceedingly challenging for a human operator. A robot-aided rTMS protocol combined with a priming paradigm was proposed to explore whether direction-specific neuronal populations in the primary motor cortex (M1) can be selectively modulated during movement preparation, hilighting how the accuracy and rapidity offered by the robotic platform enable experimental designs that were previously difficult to achieve. Lastly, robot-aided TMS was combined with EEG to achieve precise spatial targeting and temporal alignment of stimulation. Through an EEG-informed TMS approach, stimulation was synchronized with specific phases of each participant’s mu rhythm, revealing a phase-dependent modulation of corticospinal excitability and supporting the important role of cortical state in shaping stimulation effects. In conclusion, this work, by introducing advanced engineering strategies into the field of TMS, demonstrates how methodological innovation can drive the development of more reliable, individualized, and effective stimulation protocols.