Modulation of Corticospinal Excitability during Transcranial Magnetic Stimulation (TMS) and Intraoperative Electrophysiological Monitoring

Summary description of the study

The aim of this project is to evaluate factors that can be used in clinical practice to modulate the excitability of the corticospinal tract, making its originating cortex more easily detectable and thus mappable through the use of TMS. The factors studied in this research will be sensory stimuli (visual, auditory, tactile, olfactory) that may engage cognition or emotions to varying degrees. If feasible in practice, some potentially sensitizing factors will also be evaluated intraoperatively by presenting them during direct electrical stimulation of the cortex, in order to sensitize the mapping and monitoring of the corticospinal tract and thus better preserve it during a resection of tumor/cerebral tissue. This intraoperative evaluation will particularly be possible during so-called awake surgeries, where all types of stimuli can then be applied, but it will also be feasible during general anesthesia where some reactivity of the nervous system may still be present. The primary objective is to detect an influence in terms of timing (latency) and magnitude (amplitude) of a parameterized stimulus on the recorded motor activity (motor evoked potential) triggered by transcranial magnetic stimulation (TMS) of the corticospinal tract. The comparison will be made with the same condition but without stimulus in order to obtain control data (baseline) per patient. The intraoperative conditions will be the same, except that the stimulation of the corticospinal tract will be performed through cortical electrical stimulation. The presence of a brain pathology or medication potentially modulating brain activity could influence the brain mapping. The secondary objective is to detect a spatial and anatomical modification of the motor mapping potentially induced by the simultaneous introduction of a parameterized stimulus.

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Intervention under investigation

After written consent is obtained, the patient will undergo a TMS motor mapping protocol routinely employed in our department. Multisensory stimuli, interspersed with control stimuli, will be presented with precise timing in conjunction with the standard recording of motor evoked potentials (MEPs). The clinical mapping procedure will remain unchanged, except for the addition of these stimuli and associated transcranial magnetic stimulation (TMS) pulses at the end of the clinical component (a few dozen in total). The ‘surgical’ portion of the study will be conducted with patients undergoing neurosurgical procedures, where intraoperative mapping and monitoring are planned. The intraoperative mapping will follow standard procedures, with the addition of routine clinical electrical impulses synchronized with the stimuli being evaluated. MEPs will be recorded using the technique integrated into the neuromonitoring device.

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Disease under investigation

The corticospinal tract is the most important projection pathway to preserve during an operation to remove a tumor that is located nearby or in contact with it, as damage to this pathway leads to motor deficits that can result in hemiplegia. This is why the motor cortex and this tract are mapped preoperatively using functional MRI or transcranial magnetic stimulation (TMS) as well as by MRI tractography, and are also mapped and monitored intraoperatively through electrophysiology. TMS is attractive because it is potentially more specific and precise than functional MRI (targeting the localization of the neuronal response rather than the localization of the vascular response), but appears less sensitive in certain locations due to geometric factors of orientation and depth relative to the skull. This is particularly the case for the motor area of the lower limb, which is paramedian and extends deeply into the interhemispheric fissure. It has also been shown that corticospinal excitability can be modulated by the perception of various stimuli, particularly by observing the actions of others, with a specific and dynamic increase in the excitability of the motor areas controlling the muscles perceived as involved in the observed action. This has been studied more specifically for the motor cortex of the hand. This modulation is less characterized for the motor cortex of the lower limb. If motor imagery seems particularly influential on corticospinal excitability, it is also generally modulated upwards by stimuli that have no direct relation to motor activity. These stimuli can be simply sensory, such as a sound or a smell, or stimuli that engage cognition more, such as speech. Similarly, emotionally charged stimuli can modulate it. Likewise, a tactile stimulus is also potentiating on the response. Thus, the application of factors that modulate corticospinal excitability upwards could serve to sensitize the mapping by TMS in a region where it is less sensitive, thereby allowing for better detection of certain subdivisions of the primary motor cortex, particularly the paracentral region. It could also be useful in cases of corticospinal impairment, where the number of motoneurons may be reduced and thus the whole may appear less reactive. The addition of factors sensitizing the anatomical identification of functional areas intraoperatively through the use of neuromonitoring is poorly reported and poorly defined in the literature. For this reason, the addition of stimuli to our intraoperative neuromonitoring protocol could show a facilitating effect on cortical mapping, particularly in awake surgery conditions.

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Sponsor

Hôpitaux Universitaires de Genève

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Name of the authorising ethics committee (for multicentre studies, only the lead committee)

Ethics Committee Geneva

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Date of authorisation

02.04.2025

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Results of the trial