Consistent linear and non-linear responses to invasive electrical brain stimulation across individuals and primate species with implanted electrodes
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BACKGROUND: Electrical neuromodulation via implanted electrodes is used in treating numerous neurological disorders, yet our knowledge of how different brain regions respond to varying stimulation parameters is sparse. OBJECTIVE/HYPOTHESIS: We hypothesized that the neural response to electrical stimulation is both region-specific and non-linearly related to amplitude and frequency. METHODS: We examined evoked neural responses following 400 ms trains of 10-400 Hz electrical stimulation ranging from 0.1 to 10 mA. We stimulated electrodes implanted in cingulate cortex (dorsal anterior cingulate and rostral anterior cingulate) and subcortical regions (nucleus accumbens, amygdala) of non-human primates (NHP, N = 4) and patients with intractable epilepsy (N = 15) being monitored via intracranial electrodes. Recordings were performed in prefrontal, subcortical, and temporal lobe locations. RESULTS: In subcortical regions as well as dorsal and rostral anterior cingulate cortex, response waveforms depended non-linearly on frequency (Pearson's linear correlation r < 0.39), but linearly on current (r > 0.58). These relationships between location, and input-output characteristics were similar in homologous brain regions with average Pearson's linear correlation values r > 0.75 between species and linear correlation values between participants r > 0.75 across frequency and current values per brain region. Evoked waveforms could be described by three main principal components (PCs) which allowed us to successfully predict response waveforms across individuals and across frequencies using PC strengths as functions of current and frequency using brain region specific regression models. CONCLUSIONS: These results provide a framework for creation of an atlas of input-output relationships which could be used in the principled selection of stimulation parameters per brain region.
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Recent work from the authors' lab suggests that circuit responses to DBS-like neurostimulation are sufficiently consistent across individuals to make modeling a specific construct in a non-human animal and focusing patients' DBS programming around those parameters feasible.
“Recent work from our lab suggests that circuit responses to DBS-like neurostimulation are sufficiently consistent across individuals to make this paradigm feasible (Basu et al. 2019).”
From Deep brain stimulation for psychiatric disorders: From focal brain targets to cognitive networks (2021) · cites this paper as Basu et al. 2019
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Basu, I., Crocker, B., Farnes, K., Robertson, M. M., Paulk, A. C., Vallejo-Lopez, D. I., Dougherty, D. D., Cash, S. S., Eskandar, E. N., Kramer, M., et al. (2018) · Journal of Neural Engineering · doi:10.1088/1741-2552/aae136 · Cited by 25 · see citing works
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Research works printed but not linked: 2
- [17]Krames ES, Peckham PH, Rezai AR, editors. Neuromodulation 2nd Edition Academic Press; 2018.
- [34]Camprodon JA, Rauch SL, Greenberg BD, Dougherty DD, editors. Psychiatric neurotherapeutics: contemporary surgical and device-based treatments 1st ed. New York, NY: Humana Press; 2015.
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Deep brain stimulation for psychiatric disorders: From focal brain targets to cognitive networks
Sullivan, C. R. P., Olsen, S., & Widge, A. S. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2020.117515 · Cited by 112 · see citing works
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- Authors
- Basu, I., Robertson, M. M., Crocker, B., Peled, N., Farnes, K., Vallejo-Lopez, D. I., Deng, H., Thombs, M., Martinez-Rubio, C., Cheng, J. J., McDonald, E., Dougherty, D. D., Eskandar, E. N., Widge, A. S., Paulk, A. C., & Cash, S. S.
- Affiliations
- Harvard University (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Paulk, Angelique C.
- ORCID
- Venue
- Brain Stimulation
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 12
- Issue
- 4
- Pages
- 877-892
- ISSN
- 1876-4754 (ISSN-L)
- 1935-861X
- PMC
- PMC6752738
- OpenAlex
- W2921548349
- Cited by
- 50
- References
- 60
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 7 · 2023: 6 · 2022: 10 · 2021: 10 · 2020: 6 · 2019: 3 · 2018: 1
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain stimulation (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- Defense Advanced Research Projects Agency
- Topics
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Keywords
- electrical neuromodulation, implanted electrodes, input-output relationship, stimulation frequency, stimulation amplitude, nonlinear response, anterior cingulate cortex, nucleus accumbens, amygdala, drug-resistant epilepsy, non-human primates, principal component analysis, stimulation parameter selection
- MeSH terms
- Adult, Amygdala, Animals, Brain, Brain Mapping, Electrodes, Implanted, Female, Gyrus Cinguli, Humans, Macaca mulatta, Male, Middle Aged, Nucleus Accumbens, Primates, Species Specificity, Stereotaxic Techniques, Deep Brain Stimulation
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