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Long-Term Neuromodulatory Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Plasmatic Matrix
Giovanni Cirillo1, Roberta Pepe2, Mattia Siciliano2
1Neuronal Networks Morphology & Systems Biology Lab, Division of Human Anatomy, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Abstract:
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that is used against cognitive impairment in mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, the neurobiological mechanisms underlying the rTMS therapeutic effects are still only partially investigated. Maladaptive plasticity, glial activation, and neuroinflammation, including metalloproteases (MMPs) activation, might represent new potential targets of the neurodegenerative process and progression from MCI to AD. In this study, we aimed to evaluate the effects of bilateral rTMS over the dorsolateral prefrontal cortex (DLPFC) on plasmatic levels of MMP1, -2, -9, and -10; MMPs-related tissue inhibitors TIMP1 and TIMP2; and cognitive performances in MCI patients. Patients received high-frequency (10 Hz) rTMS (MCI-TMS, n = 9) or sham stimulation (MCI-C, n = 9) daily for four weeks, and they were monitored for six months after TMS. The plasmatic levels of MMPs and TIMPs and the cognitive and behavioral scores, based on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Beck Depression Inventory II, Beck Anxiety Inventory, and Apathy Evaluation Scale, were assessed at baseline (T0) and after 1 month (T1) and 6 months (T2) since rTMS. In the MCI-TMS group, at T2, plasmatic levels of MMP1, -9, and -10 were reduced and paralleled by increased plasmatic levels of TIMP1 and TIMP2 and improvement of visuospatial performances. In conclusion, our findings suggest that targeting DLPFC by rTMS might result in the long-term modulation of the MMPs/TIMPs system in MCI patients and the neurobiological mechanisms associated with MCI progression to dementia.
Insights
Repetitive transcranial magnetic stimulation (rTMS) may modulate metalloprotease and tissue inhibitor levels in mild cognitive impairment (MCI) patients. This neuromodulation technique showed potential in improving cognitive function and targeting neuroinflammation markers.
Area of Science:
- Neuroscience
- Neuromodulation
- Neurodegenerative Diseases
Background:
- Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique used for cognitive impairment in mild cognitive impairment (MCI) and Alzheimer's disease (AD).
- The underlying neurobiological mechanisms of rTMS therapeutic effects, including maladaptive plasticity, glial activation, and neuroinflammation (e.g., metalloproteases activation), are not fully understood.
- These factors are potential targets in the neurodegenerative process and progression from MCI to AD.
Purpose of the Study:
- To evaluate the effects of bilateral rTMS over the dorsolateral prefrontal cortex (DLPFC) on plasmatic levels of MMP1, -2, -9, and -10, and their inhibitors TIMP1 and TIMP2.
- To assess the impact of rTMS on cognitive performance in MCI patients.
- To investigate the long-term modulation of the MMPs/TIMPs system and its association with MCI progression.
Main Methods:
- Patients with MCI received daily high-frequency (10 Hz) rTMS or sham stimulation for four weeks.
- Plasmatic levels of MMPs and TIMPs were assessed at baseline, 1 month, and 6 months post-stimulation.
- Cognitive and behavioral scores were evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Beck Depression Inventory II, Beck Anxiety Inventory, and Apathy Evaluation Scale.
Main Results:
- In the rTMS group, at 6 months post-stimulation, plasmatic levels of MMP1, -9, and -10 were reduced.
- Concurrently, plasmatic levels of TIMP1 and TIMP2 increased in the rTMS group.
- Improvement in visuospatial performances was observed in the rTMS group.
Conclusions:
- Targeting the DLPFC with rTMS may lead to long-term modulation of the MMPs/TIMPs system in MCI patients.
- rTMS could influence neurobiological mechanisms associated with the progression of MCI to dementia.
- These findings suggest rTMS as a potential therapeutic strategy for MCI by targeting neuroinflammation and plasticity pathways.
