The Brain in Health and Disease

Macroscopic Brain Function and Malfunction

Normal brain functioning is remarkably complex and involves the firing of the billions of neurons via electrochemical processes. Although more is known about the brain all the time, many of the mechanisms by which these few pounds of matter are able to produce the intricate processes of the human mind are still mysterious. The brain's evolution, evidenced by its anatomical structure and functioning, has culminated in the large cortical region in humans, which is responsible for higher level reasoning. Many models of neural and cognitive modeling have been proposed, such as the Hodgkin-Huxley model, but these mathematical non-linear models cannot replicate completely the firing of a single neuron, much less achieve the functional magnitude of the human brain. This is partly the consequence of the brain being a chaotic system, which is the mathematical state of apparent randomness that is highly structured and oscillates around strange attractors or values. The importance of this is that normal brain functioning does not produce a regular electrical brain pattern. In fact, regular brain patterns manifest in the malfunction of the brain known as seizures. Repeated seizures are known as epilepsy. Although the mathematical models are too difficult to understand, my students will be able to appreciate the fact that ordered brain signaling or synchronization, called entrainment, can help explain the normal, desynchronized electrical brain activity that enables normal macroscopic brain functioning and processing. This will add to the relevancy of this electrical brain unit.

In May, 2009, I received a patent for a Radio Frequency (RF) powered vagus nerve stimulator. ^{1 0} The RF vagus nerve stimulator utilizes radio waves to power the VNS device without the need for an implanted battery. The patent is titled "Vagus Nerve Stimulation Apparatus, and Associated Methods." The VNS has been approved for treatment of epileptic patients who do not respond to drug treatment and for the treatment of severe pharmacologically resistant depression. My interest in this unit is to explain the normal state of brain patterns, the entrainment of neuronal signaling, that manifests in epileptic seizures and the means by which the VNS can help the brain to retain its unsynchronized signal pattern. It is another goal to indicate that scientific pursuit and application of knowledge can add to the understanding of previously unexplained diseases, to the development of technologies that may be applied to the improvement of treating disease, and hopefully to the scientific understanding of biological or physical systems like the amazing brain.

An Explanation of Epileptic Seizures

Epilepsy results from the synchronization of neuronal signaling that results in an entrainment. When the brain is in its normal state, the global signal is desynchronized and chaotic. This means that, for the most part, neurons are not firing action potentials in rhythm. In epilepsy, neuronal signaling becomes rhythmic in parts of the brain, which is an unnatural state, and results in a seizure. According to Iasemidis et al. the seizure is actually not the result of entrainment but instead is the brain's attempt to reset the neuronal firing pattern and desynchronize the EEG pattern. Seizures occur after a period of sustained dynamical entrainment of the epileptic brain. It is suggested that seizures actually occur in order to reset the entrainment. ¹¹ This theory—in conjunction with the observation that there is a period after the seizure that inhibits further seizures—helps to explain why the vagus nerve electrical stimulation prevents epileptic seizures by actually causing miniature, localized seizures! It is possible that electromagnetic stimulation by the vagus nerve stimulator intervenes in entrainment of brain signals by periodically disentraining entrained critical sites and thereby may alleviate the need for a seizure to occur because the brain is reset. ¹² This sentiment is supported by Bewernitz et al. and the efficacy of the VNS is explained, indicating that there is evidence that electrical stimulation mimics the electroencephalographic resetting effect of a seizure. Therefore it is reasonable to consider that VNS therapy mimics the effect of a seizure. ¹³ This explanation leads to the only explanation that I am aware of as to how and why the VNS works. The molecular mechanism was further clarified in a 2007 study which indicated that VNS triggers neurochemical and molecular changes in the rat brain involving the neurotransmitters and growth factors that play a crucial role in neuronal health. ¹⁴ This explanation of the neurochemical affect adds to the electrical understanding of the VNS's mediation of seizure activity.

There have been recent efforts to use the Hodgkin-Huxley mathematical model of the neuron to explain how VNS can be tuned to maximize the reduction in epileptic seizures. ¹⁵ Although these efforts are in their early stages, I believe that an understanding of the onset of seizures and the ability to improve the tuning of the VNS for individuals would greatly improve our comprehension of brain function. Before fMRI and PET scans, neuroscientists utilized the existence of imperfections in brain functioning, caused by lesions and or brain damage to understand the brain's underlying anatomical structure and how it worked. I believe that seizures may well enable an equivalent insight into the electrical-chemical functioning of the brain using EEG and mathematical modeling. I hope that this research will lead to a greater comprehension of the working of the human brain.