Abnormal high-frequency brain oscillations and infantile spasms
Rajalaxmi Natarajan, PhD
It is known that the human brain has its own rhythmic activity. Some of these brain rhythms are relatively slow - occurring only a few times per second while others are faster and occur 30 to 80 times every second. However, with recent advances in electronic instrumentation it is now very clear that the brain produces even faster rhythms. Some of these rhythms are perfectly normal like “ripples” that occur 80-200 times per second. Others are even faster but most of these high frequency oscillations (HFOs), which sometimes occur 600 times per second, are thought to be abnormal.
In epilepsy research, the study of abnormal HFOs has become an area of intense investigation since they have been found in regions of seizure generation. Thus, these abnormal HFOs are suspected to be biomarkers of sites of seizure generation and are beginning to be used to guide epilepsy surgery. Despite this growing interest in the role of HFO’s in epilepsy, their direct role in the generation of seizures has not been conclusively demonstrated.
Recently, an interesting study1 from Dr. John Swann’s team at the Baylor College of Medicine and the Cain Foundation laboratories of Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital demonstrated that abnormal HFOs are very likely critical contributors to a childhood seizure disorder called infantile spasms.
Infantile spasms (aka West Syndrome) is the most common form of severe childhood epilepsy and is associated with many congenital or acquired etiologies. Most of the common anticonvulsants are not effective in curbing infantile spasms. Sometimes, children with infantile spasms respond to vigabatrin, an anticonvulsant drug that increases the levels of inhibitory neurotransmitter, GABA.
In this study, researchers examined the effects of vigabatrin in a rodent model of infantile spasms that shares many features of the human seizure disorder. Once spasms were established in the animals, behavioral and physiological activity were continuously monitored with long-term video and electroencephalogram (EEG) recordings and vigabatrin was administered for 2 weeks.
The authors found that vigabatrin administration suppressed epileptic spasms and most animals became seizure-free. Interestingly, they also found that the drug gradually suppressed the HFO’s during and between the seizures. The authors argued that in blocking seizure activity, vigabatrin acts in a selective way to suppress the generation of HFOs and not on other brain rhythms. This is because in control rats vigabatrin had no effects on other rhythms that occur normally in the brain including ripples. Since vigabatrin resolves seizures by preferentially reducing the formation of HFO’s, this study provides experimental evidence that abnormal HFO’s are at least critical contributors to infantile spasms and could be the target for future anticonvulsant drug development.
- Frost et al., Vigabatrin Therapy Implicates Neocortical High Frequency Oscillations in an Animal Model of Infantile Spasms. Neurobiol Dis. 2015 May 27; 82:1-11. doi: 10.1016/j.nbd.2015.04.019
Infantile Spasms/West syndrome Foundations: