Music in the brain

Well not really, but indulge the metaphor because it’s a nice description of a phenomenon observed in epileptic brains. A recent paper in the journal Epilepsia (unfortunately behind a paywall, sorry) describes a pattern of electrical activity recorded from the brains of epilepsy patients that may be helpful in predicting when seizures occur. The paper is a good example of useful cross-disciplinary work: it combines clinical, basic and computational research to arrive at a convincing mechanistic explanation for the observed electrical patterns, and proposes some hypotheses about epileptic seizures that, if correct, could lead to better treatments for patients [conflict of interest warning: one of the authors is my second supervisor].

The pattern described is an electrical rhythm that rapidly increases in frequency over a time span of about one second, which seems to happen shortly before a seizure occurs. The electrical signal recorded from the patient’s brain rapidly increases in frequency; in our musical analogy, this electrical pattern is similar to the sound pattern produced when you rapidly slide your hand up the notes of a piano, from low to high. In music, this slide is called a glissando, and the authors adopted this name to describe the pattern of brain activity. This pattern was noticed in electrocorticogram (ECoG) signals – recordings made by placing electrodes directly on the surface of the brain, usually used before epilepsy surgery to give the surgical team information on the location of the small region of brain tissue that initiates seizures (the seizure focus). After surgery, the tissue removed from the seizure focus was kept alive and studied in the lab. Recordings from this removed brain tissue also displayed the glissando pattern of activity.

The mechanism proposed by the authors is complex and derives from a lot of the previous literature on the subject of brain rhythms in epilepsy (for a technical review, see this book). Much previous work on fast rhythms, as seen in glissandi, has pointed towards the importance of electrical connections, called gap junctions, between neurons as being crucial, rather than more conventional chemical synapses. Specifically, the proposed mechanism requires gap junctions to exist between the axons of excitatory neurons (the axon being the part of the neuron that transmits electrical signals to other neurons, which then receive these signals via chemical synapses). When a neuron sends a signal down its axon in the form of an electrical spike and the axon is connected to other axons by gap junctions, under some conditions the spike can be transmitted into these other axons, causing a wide spread of excitatory signals in the neuron network. This spread is fast, as the direct electrical connection of a gap junction transmits signals more rapidly than conventional chemical synapses. A proposed property of the gap junctions between axons is that their electrical resistance decreases the more alkaline their surroundings are*. As shown in the paper, this decrease in resistance allows even faster propagation of electrical spikes between axons, so when the alkalinity of the tissue increases, the frequency of the activity increases, creating the glissando effect.

Previous clinical reports have suggested that increased alkalinity can contribute to starting seizures in some cases, and this paper proposes a mechanism for how this alkalinisation could contribute. Further experiments are required to establish this proposed mechanism as correct, but if it is proved right, it opens up some interesting possibilities for treatment in some patients. If suitable monitoring equipment could be worn, glissandi could be used to predict seizures, and local brain alkalinity controlled in response. Alternatively, drugs acting on gap junctions between excitatory cell axons could be used – though the significance of axonal gap junctions in healthy brain function is unknown.

You can read the Newcastle University press release about this research here.

*other types of gap junction apparently increase in resistance under alkaline conditions