{
  "abstract": "There is an urgent need for better treatment options for many neurological conditions, including Alzheimer’s disease, Parkinson’s disease, depression, and epilepsy. Transcranial electrical stimulation (tES) is a non-invasive, safe, inexpensive, and promising method that could address some of this unmet need. The therapeutic value of tES has been well demonstrated, but the effect is highly variable. To enable tES to reach its full potential requires a better understanding of how tES modulates neural activity so that tES treatments can be tailored to specific neurological conditions and individual patients. The neural response to tES is, however, highly complex, and the parameter space involved in optimizing tES treatments is daunting. This has made it difficult to obtain general insights into how tES modulates neural activity, and a central challenge lies in the cell-type-specific and frequency-dependent nature of these responses. In this study, we investigated cell-type-specific neuronal responses to tES over a broad frequency range, using a large database of biophysically detailed neuron models. We found that pyramidal cells respond strongly to low-frequency tES, but their responses drop sharply with frequency. In contrast, inhibitory neurons show a smaller reduction and, on average, become more responsive than pyramidal cells above ~60 Hz. By leveraging a reciprocity theorem we demonstrated that the effect of tES on a given cell-type is proportional to the frequency-dependent current-dipole moment that determines the EEG-signal contribution of this cell-type. We further identified the dendritic asymmetry as key in determining tES responses across the frequency spectrum. Counterintuitively, we also found that while total cell length increases tES sensitivity at low frequencies, it can have the opposite effect at high frequencies. Furthermore, we derived an analytical formula for idealized neuron models which can approximately predict the tES sensitivity of different cell types at any given frequency. By characterizing the role of morphology and stimulation frequency in determining tES responses of single cells, this is an important step towards a better understanding of tES at the fundamental level. These results also provide an efficient and accurate method for characterizing and comparing the tES responses of different neural populations across the frequency spectrum, which facilitates optimizing tES for cell-type specific targeting. Author summary: Transcranial electric stimulation (tES) is a promising, non-invasive treatment for several neurological conditions. It is, however, difficult to optimize, and its therapeutic effect is highly variable. A central challenge is predicting how tES affects neural activity, which is complicated by the cell-type-specific and frequency-dependent nature of tES responses. Here we investigated cell-type specific tES responses across a broad frequency range. We found that pyramidal cells respond strongly to low frequency tES, but their sensitivity drops sharply as frequency increases. In contrast, inhibitory neurons maintain responsiveness, becoming more sensitive than pyramidal cells above ~60 Hz. Using a reciprocity theorem, we demonstrated that a cell’s tES response is proportional to its frequency-dependent current-dipole moment. We identified the key role of dendritic asymmetry in determining these responses. Counterintuitively, while greater cell length increases low-frequency sensitivity, it can reduce high-frequency sensitivity. Finally, we derived an analytical formula to predict the tES sensitivity of idealized neuron models at any frequency. These findings advance our fundamental understanding of tES, and provide an efficient method to characterize neural responses at the single-cell level. This paves the way for improved tES optimization and cell-type specific targeting by facilitating efficient and accurate investigations of tES at the network level.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Physics, Norwegian University of Life Sciences, Ås, Norway",
    "Department of Physics, University of Oslo, Oslo, Norway"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Susanne Dahle"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Gaute T. Einevoll"
    },
    {
      "affs": [
        0
      ],
      "name": "Torbjørn V. Ness",
      "orcid": "0000-0001-9080-8502"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1f0yrkqp294c5.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pcbi.1014895",
  "fulltext_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014895",
  "id": "1f0yrkqp294c5",
  "issns": [
    "1553-7358",
    "1553-734X"
  ],
  "landing_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014895",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Animal Cells"
    ],
    [
      "heading",
      "Biology and Life Sciences"
    ],
    [
      "heading",
      "Cell Biology"
    ],
    [
      "heading",
      "Cellular Neuroscience"
    ],
    [
      "heading",
      "Cellular Types"
    ],
    [
      "heading",
      "Electric Field"
    ],
    [
      "heading",
      "Electricity"
    ],
    [
      "heading",
      "Electrophysiology"
    ],
    [
      "heading",
      "Functional Electrical Stimulation"
    ],
    [
      "heading",
      "Ganglion Cells"
    ],
    [
      "heading",
      "Interneurons"
    ],
    [
      "heading",
      "Medicine and Health Sciences"
    ],
    [
      "heading",
      "Membrane Potential"
    ],
    [
      "heading",
      "Neuronal Dendrites"
    ],
    [
      "heading",
      "Neuronal Morphology"
    ],
    [
      "heading",
      "Neurons"
    ],
    [
      "heading",
      "Neuroscience"
    ],
    [
      "heading",
      "Physical Sciences"
    ],
    [
      "heading",
      "Physics"
    ],
    [
      "heading",
      "Physiology"
    ],
    [
      "heading",
      "Pyramidal Cells"
    ],
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      "Research Article"
    ],
    [
      "heading",
      "Surgical and Invasive Medical Procedures"
    ],
    [
      "openalex",
      "2808|Transcranial Magnetic Stimulation Studies"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Neurons"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Neurons/Ganglion cells/Pyramidal cells"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Neurons/Interneurons"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Neurons/Neuronal dendrites"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Cellular neuroscience/Neuronal morphology"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Cellular neuroscience/Neurons"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Cellular neuroscience/Neurons/Ganglion cells/Pyramidal cells"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Cellular neuroscience/Neurons/Interneurons"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Cellular neuroscience/Neurons/Neuronal dendrites"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Electrophysiology/Membrane potential"
    ],
    [
      "plos",
      "/Medicine and health sciences/Surgical and invasive medical procedures/Functional electrical stimulation"
    ],
    [
      "plos",
      "/Physical sciences/Physics/Electricity/Electric field"
    ]
  ],
  "openalex": "W7223212150",
  "pdf_url": "https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1014895&type=printable",
  "pmcid": "PMC13722302",
  "pmid": "42911957",
  "published": "2026-10-22",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/1f0yrkqp294c5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:23Z",
      "native_id": "10.1371/journal.pcbi.1014895",
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  "subjects": [
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "plos:neuroscience",
      "subfield": "neuroscience"
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    {
      "field": "medicine",
      "origin": "heading:Physiology",
      "subfield": "physiology"
    },
    {
      "field": "medicine",
      "origin": "heading:Surgical and Invasive Medical Procedures",
      "subfield": "surgery"
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      "field": "physics",
      "origin": "heading:Physics",
      "subfield": "general"
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  "title": "Cell-type dependence of effects from transcranial electric brain stimulation",
  "title_text": "Cell-type dependence of effects from transcranial electric brain stimulation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:50Z",
  "url": "https://research.draconitic.com/paper/1f0yrkqp294c5",
  "venue": "PLOS Computational Biology",
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}