Long-term effects of repetitive transcranial magnetic stimulation on markers for neuroplasticity: Differential outcomes in anesthetized and awake animals
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Long-term effects of repetitive transcranial magnetic stimulation (rTMS) have been associated with neuroplasticity, but most physiological studies have evaluated only the immediate effects of the stimulation on neurochemical markers. Furthermore, although it is known that baseline excitability state plays a major role in rTMS outcomes, the role of spontaneous neural activity in metaplasticity has not been investigated. The first aim of this study was to evaluate and compare the long-term effects of high- and low-frequency rTMS on the markers of neuroplasticity such as BDNF and GluR1 subunit of AMPA receptor. The second aim was to assess whether these effects depend on spontaneous neural activity, by comparing the neurochemical alterations induced by rTMS in anesthetized and awake rats. Ten daily sessions of high- or low-frequency rTMS were applied over the rat brain, and 3 d later, levels of BDNF, GluR1, and phosphorylated GluR1 were assessed in the hippocampus, prelimbic cortex, and striatum. We found that high-frequency stimulation induced a profound effect on neuroplasticity markers; increasing them in awake animals while decreasing them in anesthetized animals. In contrast, low-frequency stimulation did not induce significant long-term effects on these markers in either state. This study highlights the importance of spontaneous neural activity during rTMS and demonstrates that high-frequency rTMS can induce long-lasting effects on BDNF and GluR1 which may underlie the clinical benefits of this treatment in neuroplasticity-related disorders.
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Post-treatment cognitive testing took place right after brain stimulation, so the potential long-term effect of NIBS on cognition remains understudied.
“Also, post-treatment cognitive testing took place right after brain stimulation and therefore the potential long-term effect of NIBS on cognition remains understudied (Cirillo et al., 2017; Gersner, Kravetz, Feil, Pell, & Zangen, 2011).”
From Efficacy of non-invasive brain stimulation on cognitive functioning in brain disorders: a meta-analysis (2020) · cites this paper as Gersner, Kravetz, Feil, Pell, & Zangen, 2011
The Introduction says most neurobiological studies assessed immediate effects of rTMS and that its long-lasting neurochemical and physiological effects were poorly understood. It does not say cognitive testing occurred immediately after stimulation or establish that long-term effects on cognition were understudied. The Methods describe measuring neuroplasticity markers in rats three days after stimulation, not cognitive testing. (LLM, conf=0.84)
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References 48 · Cited by 313
Research works printed but not linked: 2
- Fitzgerald PB, Fountain S, Daskalakis ZJ (2006) A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition. Clin Neurophysiol 117:2584 -2596.
- Galloway GM, Nuwer MR, Lopez JR, Zamel KM (2010) Intraoperative neu- rophysiologic monitoring. Cambridge, UK: Cambridge UP.
- Authors
- Gersner, R., Kravetz, E., Feil, J., Pell, G., & Zangen, A.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Zangen, Abraham
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-05-18
- Volume
- 31
- Issue
- 20
- Pages
- 7521-7526
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6622610
- OpenAlex
- W2166890181
- Cited by
- 313
- References
- 48
- Citations by year
- 2026: 22 · 2025: 27 · 2024: 24 · 2023: 20 · 2022: 24 · 2021: 19 · 2020: 21 · 2019: 17 · 2018: 20 · 2017: 20 · 2016: 17 · 2015: 15 · 2014: 28 · 2013: 20 · 2012: 15
- FWCI
- 11.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- repetitive transcranial magnetic stimulation, neuroplasticity, metaplasticity, spontaneous neuronal activity, brain-derived neurotrophic factor, GluR1, AMPA receptors, high-frequency stimulation, low-frequency stimulation, hippocampus, prelimbic cortex, striatum, long-term effects
- MeSH terms
- Anesthesia, General, Animals, Brain, Male, Neuronal Plasticity, Time Factors, Wakefulness, Biomarkers, Treatment Outcome, Rats, Sprague-Dawley, Receptors, AMPA, Brain-Derived Neurotrophic Factor, Transcranial Magnetic Stimulation, Rats
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