**1. Introduction**

Over a long period of time of being constrained to experiment, bioelectricity has matured into the fundaments of bio-electronic interfaces, paving the way to new therapeutic systems in recording or stimulation modes of operation. Implantable electronic medical devices (IEMDs) have emerged in recent years, based on the success of early medical applications of bioelectricity, including for instance external electro-cardiograms (ECG), recording or external heart defibrillators (stimulation), as well as based on the advancements of low-power integrated microelectronics.

Commercial IEMD products are multiple and include, for instance, heart monitoring systems such as the CardioMEMS HF System provided by Abbott Laboratories for heart failure detection [1], heart pacemakers such as the Momentum X4 provided by Boston Scientific that applies electric pulses to the heart muscles to regulate its contractions [2]. Additional successful IEMDs include cochlear implants aimed at restoring hearing capability, pain control devices, deep-brain implantable systems aimed at controlling and eluding tremors due to Parkinson's disease, and recently, retina implants aimed at restoring lost vision by electrical stimulation of remaining healthy retina tissues.

This paper reviews microelectronic techniques aimed at epilepsy control in a closed loop. Epilepsy is briefly discussed from an engineering perspective in Section 1.1, i.e., with a focus on the conditions and parameters that are specific and relevant to electrical neuromodulation. The architecture of epilepsy-control implantable systems is presented in Section 2. Classical electrodes are presented along with a discussion of electrical recording and stimulation of the brain. Commercial systems aimed at epilepsy control are reviewed, as implantable and external systems, as open and closed-loop systems and discussed in terms of their operational principles, advantages and drawbacks in Section 3. Finally, analog front-end amplifiers are reviewed in terms of classical topologies aimed at single, and multi-channel recording from the brain in Section 4. The major blocks in the recording chain that are specific to epilepsy control are reviewed and discussed. A detailed review of the stimulation chain is deliberately not considered in this review.

#### *1.1. Engineering Overview of Epilepsy, Seizures and Treatment*

Neurological disorders are defined as diseases that affect the nervous system, including the central and peripheral nervous systems. Among multiple different neurological disorders, several diseases are prevalent such as amyotrophic lateral sclerosis, brain tumors, epilepsy, Parkinson, etc. Epilepsy consists of the recurrence of a phenomenon called a seizure. A seizure occurs when the brain produces a brief abnormal and uncontrollable electrical discharge. Clinically, according to the International League Against Epilepsy (ILAE) official report [3], epilepsy is considered to be a disease of the brain defined by any following conditions:


#### 1.1.1. Phases of a Seizure

Seizures often proceed over four consecutive phases; prodromal, auras, ictal and postictal. Some patients experience a prodromal stage which mostly involves emotional signals. This stage may develop over hours or even days before the start of the seizure. The second phase which is called aura occurs immediately before a seizure onset and may last for a few seconds. During aura, patients may experience déjà vu, jamais vu, headaches and other symptoms. The third phase, which is called ictal, covers the period over which a seizure extends. This period is correlated with the electrical seizure activity in the brain. The fourth phase, which is called postictal is a period of recovery from a seizure. The postictal stage is different among the patients and may last from a few minutes to a few hours. The recovery period is determined by the type of seizure (Section 1.1.2) as well as the part(s) of the brain involved in the seizure.

#### 1.1.2. Seizure Classification

Understanding and diagnosis of the seizure type bears a significant implication on the daily life of an epileptic patient. The type of seizure determines whether a patient can safely perform some common daily-life tasks, including driving, and sports. Natural tasks with potential high social impediment are affected by seizures, including walking and communicating. In addition, the type of seizure has a tremendous impact on understanding which medication is suitable for the treatment or which medication may potentially be harmful [4].

Describing the different types of seizures was initiated in the times of Hippocrates. In 1964, Gastaut proposed a new and modern classification of seizures [5]. The traditional classification of seizures is based on anatomy comprising temporal, frontal, parietal, occipital, diencephalic, or brainstem seizures. However, the understanding of the mechanism of seizures has evolved thanks to modern research. In 1981, an ILAE commission classified seizures into partial and generalized-onset, simple and complex partial seizures, as well as various specific generalized types [6,7]. This classification was established from the study of hundreds of video–electroencephalography (EEG) recordings of seizures. This latter classification is the main reference to date, with some terminology revisions [8,9]. One of the newest classifications is the 2017 classification proposed by ILAE [7]. The overview of the new classification is shown in Figure 1. With respect to the 1981 classification, the 2017 classification significantly reduces the number of unclassifiable cases. The combination of motor/non-motor and awareness level features

provides better flexibility and detailed seizure description [10]. The new classification is based on several important facts expressed as follows [4]:


**Figure 1.** The new classification of seizure types based on the International League Against Epilepsy (ILAE) report (Reprinted with permission of Wiley Periodicals, Inc. © 2017 International League Against Epilepsy) [7].

Based on the 2017 classification, three major groups of seizures are observed, including generalized onset seizures, focal onset seizures and unknown onset seizures. Generalized seizures affect both sides of the brain or group of cells located over both sides of the brain, simultaneously. Focal seizures (Partial seizures in the 1981 classification) start in one area or group of cells in the brain. Unknown onset seizures is the term used when the location of the seizure onset is unknown.
