Abstract
Chronic brain recordings suggest that seizure risk is not uniform, but rather varies systematically relative to daily (circadian) and multiday (multidien) cycles. Here, one human and seven dogs with naturally occurring epilepsy had continuous intracranial EEG (median 298 days) using novel implantable sensing and stimulation devices. Two pet dogs and the human subject received concurrent thalamic deep brain stimulation (DBS) over multiple months. All subjects had circadian and multiday cycles in the rate of interictal epileptiform spikes (IES). There was seizure phase locking to circadian and multiday IES cycles in five and seven out of eight subjects, respectively. Thalamic DBS modified circadian (all 3 subjects) and multiday (analysis limited to the human participant) IES cycles. DBS modified seizure clustering and circadian phase locking in the human subject. Multiscale cycles in brain excitability and seizure risk are features of human and canine epilepsy and are modifiable by thalamic DBS.
Highlights
Anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) has CE mark and FDA approval for the treatment of drug resistant focal e pilepsy[27]
Subjects were monitored with the NV device (n = 3 dogs), NV transitioned to RC + STM (n = 2 dogs), or RC + STM device (n = 2 dogs; n = 1 human); both devices provide continuous intracranial EEG recordings
Using long-term brain recordings from novel implantable sensing and stimulation devices in one human and two pet dogs living in natural environments, and five kennel dwelling research dogs, we demonstrate that circadian and multiday cycles of seizure risk are features of human and canine epilepsy and can be modified by thalamic DBS
Summary
Anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) has CE mark and FDA approval for the treatment of drug resistant focal (partial) e pilepsy[27]. Prior human and animal studies have demonstrated increased thalamocortical excitability in focal e pilepsy[28], and a basic role of the thalamus in the initiation, propagation, and continuation of seizures[28,29,30]. Three subjects received concurrent thalamic deep brain stimulation (DBS), including high frequency and low frequency DBS settings. We demonstrate that circadian and multiday IES rate and seizure cycles are common in human and canine epilepsy, and provide the first evidence that thalamic DBS produces frequency dependent modulation of cycles in epilepsy
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