Neuromodulation-induced prehabilitation to leverage neuroplasticity before brain tumor surgery: a single-cohort feasibility trial protocol

IntroductionNeurosurgery for brain tumors needs to find a complex balance between the effective removal of targeted tissue and the preservation of surrounding brain areas. Neuromodulation-induced cortical prehabilitation (NICP) is a promising strategy that combines temporary inhibition of critical areas (virtual lesion) with intensive behavioral training to foster the activation of alternative brain resources. By progressively reducing the functional relevance of targeted areas, the goal is to facilitate resection with reduced risks of neurological sequelae. However, it is still unclear which modality (invasive vs. non-invasive neuromodulation) and volume of therapy (behavioral training) may be optimal in terms of feasibility and efficacy.Methods and analysisPatients undertake between 10 and 20 daily sessions consisting of neuromodulation coupled with intensive task training, individualized based on the target site and neurological functions at risk of being compromised. The primary outcome of the proposed pilot, single-cohort trial is to investigate the feasibility and potential effectiveness of a non-invasive NICP protocol on neuroplasticity and post-surgical outcomes. Secondary outcomes investigating longitudinal changes (neuroimaging, neurophysiology, and clinical) are measured pre-NICP, post-NICP, and post-surgery.Ethics and disseminationEthics approval was obtained from the Research Ethical Committee of Fundació Unió Catalana d'Hospitals (approval number: CEI 21/65, version 1, 13/07/2021). The results of the study will be submitted to a peer-reviewed journal and presented at scientific congresses.Clinical trial registrationClinicalTrials.gov, identifier NCT05844605

Non-invasive prehabilitation to foster widespread fMRI cortical reorganization before brain tumor surgery: lessons from a case series

PurposeThe objective of this prospective, single-centre case series was to investigate feasibility, clinical outcomes, and neural correlates of non-invasive Neuromodulation-Induced Cortical Prehabilitation (NICP) before brain tumor surgery. Previous studies have shown that gross total resection is paramount to increase life expectancy but is counterbalanced by the need of preserving critical functional areas. NICP aims at expanding functional margins for extensive tumor resection without functional sequelae. Invasive NICP (intracranial neuromodulation) was effective but characterized by elevated costs and high rate of adverse events. Non-invasive NICP (transcranial neuromodulation) may represent a more feasible alternative. Nonetheless, up to this point, non-invasive NICP has been examined in only two case reports, yielding inconclusive findings.MethodsTreatment sessions consisted of non-invasive neuromodulation, to transiently deactivate critical areas adjacent to the lesion, coupled with intensive functional training, to activate alternative nodes within the same functional network. Patients were evaluated pre-NICP, post-NICP, and at follow-up post-surgery.ResultsTen patients performed the intervention. Feasibility criteria were met (retention, adherence, safety, and patient's satisfaction). Clinical outcomes showed overall stability and improvements in motor and executive function from pre- to post-NICP, and at follow-up. Relevant plasticity changes (increase in the distance between tumor and critical area) were observed when the neuromodulation target was guided by functional neuroimaging data.ConclusionThis is the first case series demonstrating feasibility of non-invasive NICP. Neural correlates indicate that neuroimaging-guided target selection may represent a valid strategy to leverage neuroplastic changes before neurosurgery. Further investigations are needed to confirm such preliminary findings

Exploring the neural basis of non-invasive prehabilitation in brain tumour patients: An fMRI-based case report of language network plasticity

Primary brain neoplasms are associated with elevated mortality and morbidity rates. Brain tumour surgery aims to achieve maximal tumour resection while minimizing damage to healthy brain tissue. Research on Neuromodulation Induced Cortical Prehabilitation (NICP) has highlighted the potential, before neurosurgery, of establishing new brain connections and transfer functional activity from one area of the brain to another. Nonetheless, the neural mechanisms underlying these processes, particularly in the context of space-occupying lesions, remain unclear. A patient with a left frontotemporoinsular tumour underwent a prehabilitation protocol providing 20 sessions of inhibitory non-invasive neuromodulation (rTMS and multichannel tDCS) over a language network coupled with intensive task training. Prehabilitation resulted in an increment of the distance between the tumour and the language network. Furthermore, enhanced functional connectivity within the language circuit was observed. The present innovative case-study exposed that inhibition of the functional network area surrounding the space-occupying lesion promotes a plastic change in the network’s spatial organization, presumably through the establishment of novel functional pathways away from the lesion’s site. While these outcomes are promising, prudence dictates the need for larger studies to confirm and generalize these findings

Neuromodulation-induced prehabilitation to leverage neuroplasticity before brain tumor surgery: a single-cohort feasibility trial protocol

Introduction: Neurosurgery for brain tumors needs to find a complex balance between the effective removal of targeted tissue and the preservation of surrounding brain areas. Neuromodulation-induced cortical prehabilitation (NICP) is a promising strategy that combines temporary inhibition of critical areas (virtual lesion) with intensive behavioral training to foster the activation of alternative brain resources. By progressively reducing the functional relevance of targeted areas, the goal is to facilitate resection with reduced risks of neurological sequelae. However, it is still unclear which modality (invasive vs. non-invasive neuromodulation) and volume of therapy (behavioral training) may be optimal in terms of feasibility and efficacy.Methods and analysis: Patients undertake between 10 and 20 daily sessions consisting of neuromodulation coupled with intensive task training, individualized based on the target site and neurological functions at risk of being compromised. The primary outcome of the proposed pilot, single-cohort trial is to investigate the feasibility and potential effectiveness of a non-invasive NICP protocol on neuroplasticity and post-surgical outcomes. Secondary outcomes investigating longitudinal changes (neuroimaging, neurophysiology, and clinical) are measured pre-NICP, post-NICP, and post-surgery.Ethics and dissemination: Ethics approval was obtained from the Research Ethical Committee of Fundacio Unio Catalana d'Hospitals (approval number: CEI 21/65, version 1, 13/07/2021). The results of the study will be submitted to a peer-reviewed journal and presented at scientific congresses