Brain Stimulation for Seizure Control: Considerations and Potential Mechanisms

Attempts at nervous system electrical stimulation (a.k.a., brain stimulation, neurostimulation, electrical stimulation, neuromodulation, or deep brain stimulation (DBS)) have been made to treat drug-resistant forms of movement disorders and other conditions such as chronic pain, major depression, and more recently, seizure disorders (Theodore and Fisher 2004; Theodore 2005). Experimental results in some cases have been promising and DBS, a form of electrical stimulation, has been approved (2002) by the Food and Drug Administration (FDA) as a treatment for Parkinson’s Disease. Recent lab and clinical data also suggest that electrical brain stimulation in central and peripheral nervous system targets reduces seizure frequency in epileptic patients and in animal models of recurrent seizures (Cooper, Upton et al. 1982; Engbaek, Ostergaard et al. 1989; Benabid, Pollak et al. 1991; Brusa, Pierantozzi et al. 2001; Benabid, Minotti et al. 2002; Vitek 2002; Lang, Kleiner-Fisman et al. 2003; Vonck, Boon et al. 2003; Benabid, Wallace et al. 2005; Boon, Vonck et al. 2007; Velasco, Velasco et al. 2007; Arai, Yokochi et al. 2008; Montgomery and Gale 2008; Aybek, Lazeyras et al. 2009; Baumer, Hidding et al. 2009; Berweck 2009; Boon, Raedt et al. 2009; Rezai 2009). These findings may seem counter intuitive given the fact that electrical stimulation in the nervous system has been used in many cases to excite neurons, or to replace a lost function following injury. Nevertheless, electrical stimulation under certain conditions has been shown to reduce seizure activity. For example, in the peripheral nervous system, vagus nerve stimulation (VNS) has been performed in humans for many years (FDA approved 1997) where clinical studies show reductions in seizure frequency (Woodbury and Woodbury 1990; Vonck, De Herdt et al. 2009). More recently electrical stimulation of the central nervous system has been attempted to treat epilepsy in both animals and humans where animal studies have varied in efficacy and human studies, although very promising, have not always been well designed or controlled. Neurostimulation for seizure control typically involves the stimulation of brain structures that can be conceptually divided into three groups. These include structures that are: 1)