Source of the Brain’s Odd Electrical Pulses Found — a Step Towards Treating Schizophrenia and Dementia
Researchers have solved a century-long mystery about the source and the function of the earliest type of electrical waves discovered in the human brain. Called the alpha rhythm, these brainwaves are changes in the electrical activity of neurons, the nerve cells of the brain that transmit information. The research may help scientists develop better treatments for schizophrenia and dementia.
Electrical currents flow through the tissues around the brain continuously and are a byproduct of neurons’ activities that allow us to think and talk. Until now, scientists had believed that alpha rhythm originated in the thalamus, a large structure lying centrally in the brain. The thalamus relays sensory signals to the cerebral cortex and regulates sleep, alertness and consciousness. But in a paper published in this month’s issue of Communications Biology, a team of neuroscientists from IBM Research in the US and Hull York Medical School in the UK has shown that it’s not the case. The brainwaves, they say, are generated by the so-called pyramidal cells in the middle layers of visual areas of the cerebral cortex itself.
Recorded by placing electrodes on the scalp, in a process called the electroencephalogram (EEG), the rhythm tends to slow down with advancing age, especially in the presence of dementia. Knowing the cellular mechanism that triggers the alpha rhythm may help shed light on why this slowing happens and whether it has any clinical consequences, says IBM neurologist and one of the lead authors of the study, Roger Traub.
Understanding the origin and the role of the brain waves could also help scientists find more effective treatments of schizophrenia. The leading hypothesis is that some people develop schizophrenia because their NMDA receptors — crucial for the development of the nervous system, in learning and memory — act abnormally. Traub’s team together with researchers from Hull York Medical School led by Miles Whittington found that these receptors are at the core of the alpha rhythm. “Whether brainwaves themselves are altered in schizophrenia — this is quite controversial,” says Traub. “But as we have found that the alpha rhythm originates in the cerebral cortex, it indicates that the rhythm depends on a very particular subtype of NMDA receptors. One question now is to determine which of the many NMDA subtypes are important in neuropsychiatric disorders, and whether drug therapies can target the distinctive sorts of receptor.”
The mystery of consciousness
All neurons generate voltages that change as ions flow in or out of the cell. And when groups of neurons discharge together, they produce a brainwave. After the discharge, the neurons go silent for some specific period of time, and then discharge again, following a rhythm. The duration of the silent period is usually determined by a process called synaptic inhibition, where the activity of some neurons reduces the activity of other neurons. However, there are also weird oscillations that don’t depend on synaptic inhibition, says Traub.
The first person to make effective measurements of the EEG in humans was German psychiatrist Hans Berger, who recorded brainwaves on July 6, 1924, by placing an electrode on a 17-year-old boy during a neurosurgery. Uncertain, he took five years to publish his findings, and even then, they were met with skepticism. However, Berger’s observations were confirmed by others in 1934.
Since then, researchers have been trying to study these rhythms to unlock the mysteries of thoughts, memory, intelligence and even consciousness, but without luck. They have, however, found that not all brainwaves are the same. Berger himself noticed that the strongest waves were at the back of the head, corresponding to brain regions responsible for vision. He called them the alpha rhythm and noticed that they were produced when his subjects were awake but had their eyes closed.
Later, researchers discovered other brainwaves that also communicate information, but differently. Delta and theta rhythms appear when we sleep, and faster gamma waves are generated when the brain is alert. Brainwave generation also depends on movement, attention, sensory input and other factors. Specific waves are observed when people have an epileptic seizure.
Thalamus out of the picture
To understand what cellular mechanism generates these electrical patterns, Traub and Wittington needed to record data from several cell types. Their idea was to apply drugs to block specific types of synaptic receptors — structures in the nervous system that allow a neuron to pass an electrical or chemical signal to another neuron.
But this time, Whittington’s team observed something different. The researchers placed tiny electrodes in a piece of the brain of a rat and focused on the visual cortex. They were in for a surprise — the visual cortex generated an alpha rhythm similar to the human alpha rhythm. Then the scientists applied a drug to the brain tissue, exciting it, and produced gamma brainwaves — which are normally generated after visual stimulation. Next, they blocked one of the two main processes where neurons excite each other with a drug, also blocking a specific type of ion channel. These manipulations corresponded to shutting off visual input.
The team obtained a stable alpha rhythm that lasted many minutes. It wasn’t generated by the thalamus at all, as previously believed, but by the visual cortex of the brain itself. And the silent periods of the rhythm corresponded to processes where neurons excite each other, rather than inhibit each other.
To understand the collective behavior of neurons, the researchers needed to compare the experimental data to computer simulations. Enter Traub and his colleagues at IBM Research. For their models, they used known properties of the cells and the connections as their input, in a bid to check whether it was possible to account in this way for the collective behavior. The models all had the fundamental properties of different types of neurons, as well as the properties of different synaptic interconnections.
The simulations predicted the shape of potentials in what’s known as the dendrites of pyramidal cells. Dendrites are branched extensions of a neuron that propagate inputs from other neurons to the cell body (a central part of the neuron, where the cell nucleus lies). In pyramidal cells, the dendrites are the parts of the cells that receive most of the synaptic inputs while also possessing their own membrane properties.
To the teams’ delight, the experimental and computational models agreed. The data shows that the alpha rhythm is produced by a combination of features: dendrites that are more than just passive recipients of synaptic inputs and a specific type of synaptic excitation between the pyramidal neurons that involves the NMDA receptors that produce a slow type of excitation.
It turned out, says Traub, that when the alpha rhythm is produced in middle layers of visual cortex, it propagates to other layers of the cortex. “The effect is to prevent the cortex from responding to sensory inputs arriving from outside visual cortex,” he says. “It was totally unexpected for us to find them at the center of an experimental alpha rhythm.”
While the researchers have only studied the alpha rhythm in visual areas of the brain, rhythms at similar frequency occur in other brain regions. The next step would be to explore whether they are also produced by the same mechanism, says Traub.
