Imagine sitting in the front row of the Walt Disney Concert Hall on opening night. The LA Philharmonic’s conductor, Gustavo Dudamel, has tirelessly prepared an amazing performance: Mozart’s Symphony No. 40 in G minor. The lights dim as Gustavo enters, and the orchestra stands as he steps on the podium. After a short pause, the musicians sit quietly and ready their instruments. Gustavo reaches for his baton, raises his arms slowly and stands silently for a brief moment. Then, with a slight nod, he leads the orchestra through the subtle first measures of the allegro. The symphony is absolutely wonderful! Every musician plays each individual note beautifully, and every measure of the symphony breathes with a steady rhythm and wonderful harmony.
A few minutes into the first movement, one of the bassoons begins making most horrific squeals! At first, the orchestra tries to ignore the off-putting noise, but soon they, too, lose their organization, and each musician struggles to continue playing in spite of the terrible din. Soon, the symphony becomes a mess of squeaks and squeals, and you cover your ears in pain. In a desperate attempt to regain control, Gustavo yells over the noise, and the orchestra finally quiets down. After a few moments of silence, he nudges the orchestra to continue the allegro. The rest of the symphony is a wonderful success and receives a standing ovation despite that horrific cacophony during the first moment.
A symphony and the beautiful music it can produce is a great analogy for the billions of neurons in the human brain and the wonderful computations that they perform. Their coordinated computation is what gives the human brain the ability to perform multiple levels of computation that produce everything that makes us who we are. Unfortunately, millions of people around the world suffer from a disorder, which disrupts the brain’s symphony and, consequently, the very essence of their existence.
Epilepsy is defined as a disease in which the brain produces unprovoked and unpredictable seizures. A seizure is similar to what was described above, in that the horrific squealing of a group of neurons disrupts the normal symphony of neuronal activity. Unfortunately, this activity often spreads to multiple brain regions and disrupts computations throughout the brain. Those who suffer from epilepsy often have extremely low qualities of life and live in fear of the next unpredictable seizure. When a seizure occurs, the consequences can be devastating. Patients almost always lose consciousness without warning and are slow to regain full awareness after the seizure is over. For some, seizures may only occur once every few months, while others may suffer from ten to twenty seizures each day!
The types of seizures that patients experience are incredibly diverse. Some patients experience very subtle seizures, where they may freeze for a moment or two and then continue on, completely unaware that they had just experienced a seizure. Other patients experience partial seizures, which are often characterized by facial or limb twitching for up to a few minutes. The most severe forms of seizures are tonic clonic or grand mal seizures. Patients who experience these seizures will lose consciousness, stiffen every muscle in their body, and fall to the ground. As the seizure evolves, the patient’s body may begin convulsing violently for many seconds until the seizure subsides. Depending on the severity of the seizure and the regions of the brain involved, a patient will experience severe disorientation, memory loss, and mood disorders, which can persist for several hours after a single seizure. Consequently, epilepsy patients are often unable to do any activity in which sudden loss of consciousness could be dangerous.
Although many antiepileptic drugs have been developed in the past 50 years, up to a third of all people with epilepsy do not achieve a seizure-free life, and some never respond to any form of drug therapy. The research article discussed in Monday’s post describes a unique strategy for seizure treatment. Using new genetic tools and new understandings of how seizures are generated and evolve, it may be possible to dampen a seizure before it is even able to disrupt the brains symphony.