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ItemTracking the changes of brain states during epileptogenesis by probingCheung, Chi Lik Warwick ( 2017)Epilepsy affects around 50 million people worldwide. Brain injuries and lesions, such as traumatic brain injury, central nervous system infection and stroke, are associated with higher risk of developing epilepsy. It is hypothesised that electrically-induced brain responses (probing responses) can reflect physiological changes during epileptogenesis, which may provide insights into epileptogenesis and possible new therapies. A systematic continuous longitudinal study of probing responses in a well-controlled environment with both normal and epileptic brains is presented. The objective of this study is to demonstrate how electrically-induced neural responses (probing) track the physiological changes in the brain during epileptogenesis. Intrahippocampal tetanus toxin rat models were used as the model of epilepsy. Control rats received injections without tetanus toxin. Epidural electrodes were implanted to deliver electrical stimulation and record EEG over periods of 9 to 10 weeks in a room with controlled temperature and automatic dark/light switching. It is demonstrated that probing responses can expose sleep/wake cycles, recovery from surgery and epileptogenesis over the study period. The differences between probing responses in sleep and wake states are quantified by a two-level mixed-effects linear regression model. The changes of probing responses related to the recovery from surgery are modelled by a modified logistic function. The probing responses related to epileptogenesis in tetanus toxin models are uncovered after the effects of surgical recovery and sleep/wake cycle are removed. The changes can be observed in the infradian time scale and several markers are found that are associated with the time of the peak of seizure occurrence and the time of seizure remission. This study is the first step to identify stages of epileptogenesis using probing responses. The potential clinical application of probing can be a biomarker for epileptogenesis, a prognostic tool to assess whether epilepsy will develop after a trauma, a way to predict whether remission will occur after posttraumatic epilepsy has developed or a biomarker to assess the effectiveness of traumatic brain injury therapies.