Poster No:
182
Submission Type:
Abstract Submission
Authors:
Filippo Zappasodi1,2, Pierpaolo Croce1,2, Biagio Sancetta3,4, Lorenzo Ricci3,4, Marilisa Boscarino4, Marcella Brunetti1,2, MArio Tombini3,4, Giovanni Assenza3,4
Institutions:
1Dept. of Neuroscience, Imaging and Clinical Sciences, 'Gabriele D'Annunzio' University, Chieti, Italy, 2Institute for Advanced Biomedical Technologies, Chieti, Italy, 3Operative Research Unit of Neurology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy, 4Research Unit of Neurology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
First Author:
Filippo Zappasodi
Dept. of Neuroscience, Imaging and Clinical Sciences, 'Gabriele D'Annunzio' University|Institute for Advanced Biomedical Technologies
Chieti, Italy|Chieti, Italy
Co-Author(s):
Pierpaolo Croce
Dept. of Neuroscience, Imaging and Clinical Sciences, 'Gabriele D'Annunzio' University|Institute for Advanced Biomedical Technologies
Chieti, Italy|Chieti, Italy
Biagio Sancetta
Operative Research Unit of Neurology, Fondazione Policlinico Universitario Campus Bio-Medico|Research Unit of Neurology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma
Rome, Italy|Rome, Italy
Lorenzo Ricci
Operative Research Unit of Neurology, Fondazione Policlinico Universitario Campus Bio-Medico|Research Unit of Neurology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma
Rome, Italy|Rome, Italy
Marilisa Boscarino
Research Unit of Neurology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma
Rome, Italy
Marcella Brunetti
Dept. of Neuroscience, Imaging and Clinical Sciences, 'Gabriele D'Annunzio' University|Institute for Advanced Biomedical Technologies
Chieti, Italy|Chieti, Italy
MArio Tombini
Operative Research Unit of Neurology, Fondazione Policlinico Universitario Campus Bio-Medico|Research Unit of Neurology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma
Rome, Italy|Rome, Italy
Giovanni Assenza
Operative Research Unit of Neurology, Fondazione Policlinico Universitario Campus Bio-Medico|Research Unit of Neurology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma
Rome, Italy|Rome, Italy
Introduction:
One-third of people with epilepsy (PwE) have a condition of drug-resistant epilepsy (DRE), defined as the persistence of seizures despite medications. Recent advances demonstrated that epilepsy is a neural network disorder, where the epileptic focus impairs the connectivity and functions of the connected cortical neurons (Englot et al., 2016), possibly impacting the dynamics of brain states. This study aims to assess the value of metrics quantifying the sequence of brain states, evaluated from Electroencephalography (EEG), as a potential biomarker of DRE, by testing the following hypotheses: 1) Brain dynamics is different between people with DRE and people with drug-responsive epilepsy (nDRE), thus qualifying as a potential diagnostic biomarker; 2) Brain dynamics can be modulated in people with DRE, thus qualifying as a potential response biomarker.
Methods:
Dataset-1: EEG activity at rest (closed eyes) was acquired in 60 DRE (mean age 46.4 ± 22.4, 36 female) and 60 nDRE patients (mean age 51.8 ± 19.1, 33 female). Three minutes of EEG free from interictal activity (spikes, spike, and wave complexes, sharp waves) were manually selected by experienced neurophysiologists blind to the clinical data.
Dataset-2: EEG rest-activity was also collected in 10 DRE patients before (time T0) and 6 months after Vagus Nerve Stimulation (VNS) therapy (time T1), a well-standardized neuromodulation technique approved by the European Medical Agency for its clinical use in DRE. The VSN device was surgically implanted following standard guidelines. The initially settled parameters, according to the standardized protocol, were 30 Hz for stimulation frequency, a pulse width of 500 µs, a duty cycle of 10% (30 seconds ON and 5 minutes OFF), and an output current of 0.25 mA, which was increased by 0.25 mA every two weeks with an auto-titration schedule to reach an output current equal or higher than 1.5 mA, which has been defined as therapeutic [2]. The clinical response of the neuromodulation intervention was assessed by evaluating changes in seizure frequency and the severity of clinical manifestations.
Microstate analysis [3] was performed on dataset-1 and dataset-2 at T0 and T1. Seven microstates were extracted, and brain state sequences were obtained from the original EEG data. From these sequences, metrics (duration, coverage) and transition probabilities were calculated, as well as complexity metrics (Hurst exponent and Lempel–Ziv complexity).
For study 1, DRE and nDRE microstate sequence measures were compared with an independent t-test (Bonferroni corrected) to evidence possible differences between the 2 groups.
For study 2, a comparison of T0 and T1 microstate sequence measures was performed with the non-parametric Kruskal-Wallis test due to the small sample size, to evidence modifications induced by VNS.
Results:
No difference in microstate metrics and transition probabilities was found between the DRE and nDRE groups. Microstate complexity was significantly higher in DRE than in nDRE patients (0.87 ± 0.03 vs. 0.84 ± 0.03), indicating a more significant amount of 'randomness' in the brain dynamics of DRE. Similar changes in microstate dynamics were also found in T1 with respect to T0, parallel to clinical improvement.
Conclusions:
Results show that brain state sequence complexity may have the potential to be a noninvasive functional biomarker for DRE. The discovery of a biomarker for DRE would help its early recognition, save years of illness, reduce the burden of disease, and improve the quality of life of PwE. It will also allow a better understanding of the DRE pathophysiology to develop precision and individualized treatments.
Brain Stimulation:
Invasive Stimulation Methods Other 2
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Keywords:
Electroencephaolography (EEG)
Epilepsy
Other - Drug resistant epilepsy, brain state dynamics
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Resting state
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Patients
Was this research conducted in the United States?
No
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Yes
Were any animal research approved by the relevant IACUC or other animal research panel?
NOTE: Any animal studies without IACUC approval will be automatically rejected.
Not applicable
Please indicate which methods were used in your research:
EEG/ERP
Which processing packages did you use for your study?
Other, Please list
-
Brainstorm, eeglab
Provide references using APA citation style.
1) Englot, P.E., Konrad, P.E., Morgan, V.L. (2016).. Regional and global connectivity disturbances in focal epilepsy, related neurocognitive sequelae, and potential mechanistic underpinnings. Epilepsia 57(10):1546-1557.
2) McHugh, J., Singh, H.,W., Phillips, J., Murphy, K., Doherty, C.,P., Delanty, N. (2007). Outcome measurement after VNS therapy: proposal of a new classification. Epilepsia, 48(2):375-378.
3) Michel, C.M., Koenig, T. (2017). EEG microstates as a tool for studying the temporal dynamics of whole-brain neuronal networks: A review. Neuroimage, 180(Pt B):577-593.
No