Multimodal TMS: Finding biomarkers for epilepsy

Research output: ThesisPhD Thesis - Research UT, graduation UTAcademic

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Abstract

Epilepsy is characterized by the occurrence of epileptic seizures, resulting from an imbalance between excitatory and inhibitory brain activity. The tendency to generate seizures is reflected in the electroencephalogram (EEG) by the presence of epileptiform discharges. However, the limited sensitivity of the EEG motivated our search for biomarkers to improve the diagnostic process. We explored the potential of transcranial magnetic stimulation (TMS) as a novel biomarker for the diagnosis of epilepsy. We applied single and paired pulse TMS, while the stimulation effect was assessed using the muscle response (motor evoked potential: MEP), the brain response (TMS evoked potential: TEP), and MEP and TEP inhibition for intervals > 50 ms between paired pulses (long intracortical inhibition: LICI). Chapters 2-4 focusses on the clinical feasibility of multimodal TMS. Repeatability of the TEP and LICI after one week was good on a group level, whereas individual subjects showed a large variation in LICI repeatability. Additionally, we found no significant effect of a change in coil positioning on the MEP, TEP or LICI on a group level, while on the subject level significant effects were found for a 5 mm change in coil location and a 10° change in coil orientation. Chapter 5 focusses on finding biological modulators of cortical excitability. Very slow fluctuations may cause TMS responses to vary over time. Our findings indicate that infraslow EEG activity contributes to the variability, although other mechanisms are likely involved as well. By targeting TMS to a specific oscillatory phase, it might be possible to reduce the large response variation. Chapters 6-8 focusses on the diagnostic value of multimodal TMS in epilepsy. Previous findings in drug naïve epilepsy patients were most consistent for paired pulse TMS, showing a significant increase in cortical excitability. We were unable to confirm this finding in refractory epilepsy patients and first seizure patients. However, we could differentiate first seizure patients diagnosed with epilepsy from those without epilepsy and from healthy subjects, using LICI of the MEP and TEP. In conclusion, we showed the clinical feasibility and potential of multimodal TMS to improve the diagnostic process in epilepsy.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Twente
Supervisors/Advisors
  • van Putten, Michel J.A.M., Supervisor
Award date27 Mar 2019
Place of PublicationEnschede
Publisher
Electronic ISBNs978-90-365-4734-5
DOIs
Publication statusPublished - 27 Mar 2019

Fingerprint

Transcranial Magnetic Stimulation
Epilepsy
Biomarkers
Electroencephalography
Seizures
Motor Evoked Potentials
Brain
Evoked Potentials
Healthy Volunteers
tetraethylpyrazine
Muscles

Keywords

  • Transcranial magnetic stimulation
  • Epilepsy
  • Electroencephalography
  • Electromyography
  • Evoked Potential
  • Biomarker
  • Diagnostics
  • Motor evoked potential
  • TMS evoked potential
  • Multimodal

Cite this

de Goede, Annika A.. / Multimodal TMS : Finding biomarkers for epilepsy. Enschede : University of Twente, 2019. 218 p.
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title = "Multimodal TMS: Finding biomarkers for epilepsy",
abstract = "Epilepsy is characterized by the occurrence of epileptic seizures, resulting from an imbalance between excitatory and inhibitory brain activity. The tendency to generate seizures is reflected in the electroencephalogram (EEG) by the presence of epileptiform discharges. However, the limited sensitivity of the EEG motivated our search for biomarkers to improve the diagnostic process. We explored the potential of transcranial magnetic stimulation (TMS) as a novel biomarker for the diagnosis of epilepsy. We applied single and paired pulse TMS, while the stimulation effect was assessed using the muscle response (motor evoked potential: MEP), the brain response (TMS evoked potential: TEP), and MEP and TEP inhibition for intervals > 50 ms between paired pulses (long intracortical inhibition: LICI). Chapters 2-4 focusses on the clinical feasibility of multimodal TMS. Repeatability of the TEP and LICI after one week was good on a group level, whereas individual subjects showed a large variation in LICI repeatability. Additionally, we found no significant effect of a change in coil positioning on the MEP, TEP or LICI on a group level, while on the subject level significant effects were found for a 5 mm change in coil location and a 10° change in coil orientation. Chapter 5 focusses on finding biological modulators of cortical excitability. Very slow fluctuations may cause TMS responses to vary over time. Our findings indicate that infraslow EEG activity contributes to the variability, although other mechanisms are likely involved as well. By targeting TMS to a specific oscillatory phase, it might be possible to reduce the large response variation. Chapters 6-8 focusses on the diagnostic value of multimodal TMS in epilepsy. Previous findings in drug na{\"i}ve epilepsy patients were most consistent for paired pulse TMS, showing a significant increase in cortical excitability. We were unable to confirm this finding in refractory epilepsy patients and first seizure patients. However, we could differentiate first seizure patients diagnosed with epilepsy from those without epilepsy and from healthy subjects, using LICI of the MEP and TEP. In conclusion, we showed the clinical feasibility and potential of multimodal TMS to improve the diagnostic process in epilepsy.",
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Multimodal TMS : Finding biomarkers for epilepsy. / de Goede, Annika A.

Enschede : University of Twente, 2019. 218 p.

Research output: ThesisPhD Thesis - Research UT, graduation UTAcademic

TY - THES

T1 - Multimodal TMS

T2 - Finding biomarkers for epilepsy

AU - de Goede, Annika A.

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N2 - Epilepsy is characterized by the occurrence of epileptic seizures, resulting from an imbalance between excitatory and inhibitory brain activity. The tendency to generate seizures is reflected in the electroencephalogram (EEG) by the presence of epileptiform discharges. However, the limited sensitivity of the EEG motivated our search for biomarkers to improve the diagnostic process. We explored the potential of transcranial magnetic stimulation (TMS) as a novel biomarker for the diagnosis of epilepsy. We applied single and paired pulse TMS, while the stimulation effect was assessed using the muscle response (motor evoked potential: MEP), the brain response (TMS evoked potential: TEP), and MEP and TEP inhibition for intervals > 50 ms between paired pulses (long intracortical inhibition: LICI). Chapters 2-4 focusses on the clinical feasibility of multimodal TMS. Repeatability of the TEP and LICI after one week was good on a group level, whereas individual subjects showed a large variation in LICI repeatability. Additionally, we found no significant effect of a change in coil positioning on the MEP, TEP or LICI on a group level, while on the subject level significant effects were found for a 5 mm change in coil location and a 10° change in coil orientation. Chapter 5 focusses on finding biological modulators of cortical excitability. Very slow fluctuations may cause TMS responses to vary over time. Our findings indicate that infraslow EEG activity contributes to the variability, although other mechanisms are likely involved as well. By targeting TMS to a specific oscillatory phase, it might be possible to reduce the large response variation. Chapters 6-8 focusses on the diagnostic value of multimodal TMS in epilepsy. Previous findings in drug naïve epilepsy patients were most consistent for paired pulse TMS, showing a significant increase in cortical excitability. We were unable to confirm this finding in refractory epilepsy patients and first seizure patients. However, we could differentiate first seizure patients diagnosed with epilepsy from those without epilepsy and from healthy subjects, using LICI of the MEP and TEP. In conclusion, we showed the clinical feasibility and potential of multimodal TMS to improve the diagnostic process in epilepsy.

AB - Epilepsy is characterized by the occurrence of epileptic seizures, resulting from an imbalance between excitatory and inhibitory brain activity. The tendency to generate seizures is reflected in the electroencephalogram (EEG) by the presence of epileptiform discharges. However, the limited sensitivity of the EEG motivated our search for biomarkers to improve the diagnostic process. We explored the potential of transcranial magnetic stimulation (TMS) as a novel biomarker for the diagnosis of epilepsy. We applied single and paired pulse TMS, while the stimulation effect was assessed using the muscle response (motor evoked potential: MEP), the brain response (TMS evoked potential: TEP), and MEP and TEP inhibition for intervals > 50 ms between paired pulses (long intracortical inhibition: LICI). Chapters 2-4 focusses on the clinical feasibility of multimodal TMS. Repeatability of the TEP and LICI after one week was good on a group level, whereas individual subjects showed a large variation in LICI repeatability. Additionally, we found no significant effect of a change in coil positioning on the MEP, TEP or LICI on a group level, while on the subject level significant effects were found for a 5 mm change in coil location and a 10° change in coil orientation. Chapter 5 focusses on finding biological modulators of cortical excitability. Very slow fluctuations may cause TMS responses to vary over time. Our findings indicate that infraslow EEG activity contributes to the variability, although other mechanisms are likely involved as well. By targeting TMS to a specific oscillatory phase, it might be possible to reduce the large response variation. Chapters 6-8 focusses on the diagnostic value of multimodal TMS in epilepsy. Previous findings in drug naïve epilepsy patients were most consistent for paired pulse TMS, showing a significant increase in cortical excitability. We were unable to confirm this finding in refractory epilepsy patients and first seizure patients. However, we could differentiate first seizure patients diagnosed with epilepsy from those without epilepsy and from healthy subjects, using LICI of the MEP and TEP. In conclusion, we showed the clinical feasibility and potential of multimodal TMS to improve the diagnostic process in epilepsy.

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PB - University of Twente

CY - Enschede

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