Inter-individual Variability in Response to Non-invasive Brain Stimulation Paradigms
Open accessAbstract
Background Non-invasive Brain Stimulation (NIBS) paradigms are unique in their ability to safely modulate cortical plasticity for experimental or therapeutic applications. However, increasingly, there is concern regarding inter-individual variability in the efficacy and reliability of these paradigms.Hypothesis Inter-individual variability in response to NIBS paradigms would be better explained if a multimodal distribution was assumed.Methods In three different sessions for each subject (n = 56), we studied the Paired Associative Stimulation (PAS25), Anodal transcranial DC stimulation (AtDCS) and intermittent theta burst stimulation (iTBS) protocols. We applied cluster analysis to detect distinct patterns of response between individuals. Furthermore, we tested whether baseline TMS measures (such as short intracortical inhibition (SICI), resting motor threshold (RMT)) or factors such as time of day could predict each individual's response pattern.Results All three paradigms show similar efficacy over the first hour post stimulation--there is no significant effect on excitatory or inhibitory circuits for the whole sample, and AtDCS fares no better than iTBS or PAS25. Cluster analysis reveals a bimodal response pattern--but only 39%, 45% and 43% of subjects responded as expected to PAS25, AtDCS, and iTBS respectively. Pre-stimulation SICI accounted for 10% of the variability in response to PAS25, but no other baseline measures were predictive of response. Finally, we report implications for sample size calculation and the remarkable effect of sample enrichment.Conclusion The implications of the high rate of 'dose-failure' for experimental and therapeutic applications of NIBS lead us to conclude that addressing inter-individual variability is a key area of concern for the field.
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In non-invasive brain stimulation and other intervention studies, non-responders are routinely excluded or treated differently.
“in non-invasive brain stimulation studies84,85 or other intervention studies, such as those focusing on physical exercise or nutrition86–89, ‘non-responders’ are routinely excluded from data analyses or treated differently.”
From Near transfer to an unrelated N-back task mediates the effect of N-back working memory training on matrix reasoning (2022) · cites this paper as [84]
Study design and stimulation protocol parameters contribute to mixed results in response to NIBS protocols.
“Firstly, study design and stimulation protocol parameters contribute to mixed results in response to NIBS protocols (Huang et al., 2017;Lopez-Alonso et al., 2014).”
From Investigation of neurobiological responses to theta burst stimulation during recovery from mild traumatic brain injury (mTBI) (2023) · cites this paper as Lopez-Alonso et al., 2014
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- Authors
- López-Alonso, V., Cheeran, B., Río-Rodríguez, D., & Fernández-del-Olmo, M.
- Affiliations
- Universidade da Coruña (ES)
- John Radcliffe Hospital (GB)
- Venue
- Brain Stimulation
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 7
- Issue
- 3
- Pages
- 372-380
- ISSN
- 1876-4754 (ISSN-L)
- 1935-861X
- OpenAlex
- W1983834279
- Cited by
- 810
- References
- 41
- Citations by year
- 2026: 57 · 2025: 61 · 2024: 65 · 2023: 54 · 2022: 61 · 2021: 94 · 2020: 87 · 2019: 72 · 2018: 57 · 2017: 74 · 2016: 60 · 2015: 52 · 2014: 15
- FWCI
- 34.59
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Brain stimulation (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- non-invasive brain stimulation, interindividual variability, paired associative stimulation, anodal tDCS, intermittent theta burst stimulation, cortical plasticity, short-interval intracortical inhibition, resting motor threshold, sample size determination, sample enrichment, time of day effects
- MeSH terms
- Adult, Brain, Electromyography, Female, Humans, Male, Motor Cortex, Neuronal Plasticity, Rest, Stereotaxic Techniques, Theta Rhythm, Reproducibility of Results, Cluster Analysis, Evoked Potentials, Motor, Transcranial Magnetic Stimulation, Young Adult
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