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High-frequency oscillations arise through distinct mechanisms in models of α- synucleinopathy and channelopathy-induced epilepsy
Vaknalli RN, Addo-Osafo K, C VSM, Hwang K, Vicente M, Bragin A, Vossel K.. Research Square, 2026-08-13
Topic: Brain imaging, connectivity and assessment
Background Pathological high-frequency oscillations (HFOs), widely researched in epilepsy, are increasingly being investigated as potential biomarkers of network hyperexcitability in neurodegenerative disorders. This interest is driven by growing evidence of comorbidity between epilepsy and neurodegenerative diseases, particularly Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB), suggesting that these HFOs could be useful biomarkers in these disorders. Patients with AD and mouse models of AD exhibit elevated HFOs during neurophysiology recordings, but whether HFOs occur in DLB remains unknown. Methods To address this question, we quantified cortical HFOs within the spectral range of 250–500 Hz and interictal spikes using surface electroencephalography recordings in a transgenic model of α-synucleinopathy that exhibits features of DLB (A53T mice) and a model of channelopathy-induced epilepsy ( Kcna1 -/- mice) . Results Both A53T and Kcna1 -/- mice exhibited significantly more HFOs than their respective control mice across all vigilance states. A53T mice exhibited more HFOs and interictal spikes than Kcna1 -/- mice, and the HFOs in A53T mice had higher frequencies and longer durations than those in Kcna1 -/- mice. Additionally, HFOs were most prevalent during non-REM sleep in A53T mice, coinciding with the vigilance state in which interictal spikes were most frequent in this model. However, they did not consistently co-occur with interictal spikes or seizures, and HFO counts did not correlate with interictal spike counts during 10-minute recording epochs. Conclusions Our findings indicate that HFOs likely arise from different neuronal populations and are generated through distinct mechanisms in these two models. Importantly, this work shows that HFOs are an electroencephalographic abnormality in a model of DLB and supports their potential as a new biomarker for neurodegenerative disorders.
Key findings
- This interest is driven by growing evidence of comorbidity between epilepsy and neurodegenerative diseases, particularly Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB), suggesting that these HFOs could be useful biomarkers in these disorders.
- Results Both A53T and Kcna1 -/- mice exhibited significantly more HFOs than their respective control mice across all vigilance states.
- Conclusions Our findings indicate that HFOs likely arise from different neuronal populations and are generated through distinct mechanisms in these two models.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Vaknalli, R. N., Addo-Osafo, K., C, V. S. M., Hwang, K., Vicente, M., Bragin, A., et al. (2026). High-frequency oscillations arise through distinct mechanisms in models of α- synucleinopathy and channelopathy-induced epilepsy. Research Square. https://doi.org/10.21203/rs.3.rs-10385398/v1
Vancouver
Vaknalli RN, Addo-Osafo K, C VSM, Hwang K, Vicente M, Bragin A, et al. High-frequency oscillations arise through distinct mechanisms in models of α- synucleinopathy and channelopathy-induced epilepsy. Research Square. 2026. doi:10.21203/rs.3.rs-10385398/v1.
BibTeX
@article{vaknalli2026-370e6321,
author = {Vaknalli, R. N. and Addo-Osafo, K. and C, V. S. M. and Hwang, K. and Vicente, M. and Bragin, A. and Vossel, K.},
title = {{High-frequency oscillations arise through distinct mechanisms in models of α- synucleinopathy and channelopathy-induced epilepsy}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10385398/v1},
url = {https://doi.org/10.21203/rs.3.rs-10385398/v1}
}
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