Interictal spikes with and without high-frequency oscillation have different single-neuron correlates

Brain, vol. 144, pp. 3078–3088

Abstract

Interictal epileptiform discharges (IEDs) are a widely used biomarker in patients with epilepsy but lack specificity. It has been proposed that there are truly epileptogenic and less pathological or even protective IEDs. Recent studies suggest that highly pathological IEDs are characterized by high-frequency oscillations (HFOs). Here, we aimed to dissect these 'HFO-IEDs' at the single-neuron level, hypothesizing that the underlying mechanisms are distinct from 'non-HFO-IEDs'. Analysing hybrid depth electrode recordings from patients with temporal lobe epilepsy, we found that single-unit firing rates were higher in HFO- than in non-HFO-IEDs. HFO-IEDs were characterized by a pronounced pre-peak increase in firing, which coincided with the preferential occurrence of HFOs, whereas in non-HFO-IEDs, there was only a mild pre-peak increase followed by a post-peak suppression. Comparing each unit's firing during HFO-IEDs to its baseline activity, we found many neurons with a significant increase during the HFO component or ascending part, but almost none with a decrease. No such imbalance was observed during non-HFO-IEDs. Finally, comparing each unit's firing directly between HFO- and non-HFO-IEDs, we found that most cells had higher rates during HFO-IEDs and, moreover, identified a distinct subset of neurons with a significant preference for this IED subtype. In summary, our study reveals that HFO- and non-HFO-IEDs have different single-unit correlates. In HFO-IEDs, many neurons are moderately activated, and some participate selectively, suggesting that both types of increased firing contribute to highly pathological IEDs.

Authors 9

1. Tim A Guth

   University of Freiburg · University Medical Center Freiburg

   Affiliation as printed

   Department of Neuropediatrics and Muscle Disorders, Medical Center, University of Freiburg , Freiburg, Germany

   Epilepsy Center, Medical Center, University of Freiburg , Freiburg, Germany

   Faculty of Medicine, University of Freiburg , Freiburg, Germany

2. Lukas Kunz

   University of Freiburg · University Medical Center Freiburg · Columbia University

   Affiliation as printed

   Department of Biomedical Engineering, Columbia University , New York, NY, USA

   Epilepsy Center, Medical Center, University of Freiburg , Freiburg, Germany

   Faculty of Biology, University of Freiburg , Freiburg, Germany

   Faculty of Medicine, University of Freiburg , Freiburg, Germany

   Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg , Freiburg, Germany

3. Armin Brandt

   University of Freiburg · University Medical Center Freiburg

   Affiliation as printed

   Epilepsy Center, Medical Center, University of Freiburg , Freiburg, Germany

   Faculty of Medicine, University of Freiburg , Freiburg, Germany

4. Matthias Dümpelmann

   University of Freiburg · University Medical Center Freiburg

   Affiliation as printed

   Epilepsy Center, Medical Center, University of Freiburg , Freiburg, Germany

   Faculty of Medicine, University of Freiburg , Freiburg, Germany

5. Kerstin Alexandra Klotz

   University of Freiburg · University Medical Center Freiburg

   Affiliation as printed

   Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg , Freiburg, Germany

   Department of Neuropediatrics and Muscle Disorders, Medical Center, University of Freiburg , Freiburg, Germany

   Epilepsy Center, Medical Center, University of Freiburg , Freiburg, Germany

   Faculty of Medicine, University of Freiburg , Freiburg, Germany

6. Peter Christoph Reinacher Aachen Fraunhofer Institute for Laser Technology (ILT)

   University of Freiburg · University Medical Center Freiburg · Fraunhofer Institute for Laser Technology

   Affiliation as printed

   Faculty of Medicine, University of Freiburg , Freiburg, Germany

   Fraunhofer Institute for Laser Technology , Aachen, Germany

   Stereotactic and Functional Neurosurgery, Medical Center—University of Freiburg , Freiburg, Germany

7. Andreas Schulze‐Bonhage

   University of Freiburg · University Medical Center Freiburg

   Affiliation as printed

   Epilepsy Center, Medical Center, University of Freiburg , Freiburg, Germany

   Faculty of Medicine, University of Freiburg , Freiburg, Germany

8. Julia Jacobs

   University of Freiburg · University of Calgary · University Medical Center Freiburg · Alberta Children's Hospital Research Institute · Hotchkiss Brain Institute

   Affiliation as printed

   Department of Neuropediatrics and Muscle Disorders, Medical Center, University of Freiburg , Freiburg, Germany

   Department of Paediatrics and Department of Neuroscience, Cumming School of Medicine, University of Calgary , Calgary, Alberta, Canada

   Faculty of Medicine, University of Freiburg , Freiburg, Germany

   Hotchkiss Brain Institute and Alberta Children’s Hospital Research Institute, University of Calgary , Calgary, Alberta, Canada

9. Jan Schönberger corresponding

   University of Freiburg · University Medical Center Freiburg

   Affiliation as printed

   Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg , Freiburg, Germany

   Department of Neuropediatrics and Muscle Disorders, Medical Center, University of Freiburg , Freiburg, Germany

   Epilepsy Center, Medical Center, University of Freiburg , Freiburg, Germany

   Faculty of Medicine, University of Freiburg , Freiburg, Germany