AsianScientist (May 5, 2015) – In 46 AD, a patient anxiously awaited treatment. The physician rolled back his sleeves, plunged his hand into a bucket of water, and slapped a flapping fish onto his patient’s forehead. It was an attempt to treat a chronic headache with cutting-edge Roman technology: a shock from an electric fish. The Romans had discovered, without realizing it, that electric impulses could be used to switch nerve activity on or off. Thus began a 2,000-year preoccupation with the medical use of electricity.
In recent decades, a panoply of medical devices that take advantage of this phenomenon have trickled into the marketplace. Hearing aids, cardiac pacemakers, gastric implants and muscle and spinal cord stimulators have catapulted medicine into the bionic age. The latest addition is a procedure called deep brain stimulation. After falling out of favor in the 1960s, brain stimulation is back, and it looks set to revolutionize the treatment of intractable brain diseases.
Going deep
Deep brain stimulation (DBS) is a surgical procedure that involves the implantation of a ‘pulse generator,’ an egg-sized device, under the skin below the collar bone. It generates electric impulses that travel up an insulated lead along the neck and into the skull. In the brain, one or more tiny electrodes that look like needles are positioned to deliver a constant electrical current.
DBS can be used to treat brain disorders because nerve cells communicate via electrochemical signals. Neurons have three major structures: a branched cell body that receives signals from other cells; a thin stem called the axon; and root-like structures called axon terminals that link the roots of one cell and the branches of another via a structure called the synapse. In this way, the neurons in our brains are embedded in an exceptionally well-connected network. A single cell can have as many as 1,000 synapses, and a human brain as many as 100 trillion.
However, rogue neurons may occasionally make inappropriate signals, which can in turn cause other neurons to fire defectively. This is where DBS can help. The treatment works similarly to halting an argument by shouting into a megaphone. The electrodes emit a continuous electrical signal that disrupts communication, effectively shutting down local nerve activity.
Until recently, there were only two ways to silence misbehaving neurons: lobotomy, in which brain tissue was removed or destroyed, or electro-convulsive therapy, where massive electrical shocks were delivered to the skull to induce convulsions. Both have the potential to go catastrophically wrong. Lobotomy famously left former US President John F. Kennedy’s sister, and thousands of others, permanently brain damaged.
DBS represents a radical shift. Its predecessors had been let down by the lack of a detailed map of brain function, but medical imaging techniques such as functional magnetic resonance imaging allow scientists to pinpoint subtle differences in activity between diseased and healthy individuals. Once a target has been identified, DBS can achieve controlled, highly localized alterations in activity which are, crucially, reversible.
Just a flick of the switch away
“Brain stimulation is capable of adjusting the activity in brain circuits, either turning them up or down, and in so doing shows great promise for the alleviation of a number of neurologic and psychiatric disorders that have so far been resistant to conventional therapy,” Dr. Andres Lozano, a pioneering neurosurgeon at the Toronto Western Research Institute in Canada, told Asian Scientist Magazine.
Electrodes can be placed anywhere in the brain, allowing surgeons to hack directly into our neural networks and influence a wide range of functions such as memory, cognition, appetite, pain, vision, muscle control and mood. Consequently, the therapy has a wide-ranging repertoire of applications, and with dramatic results.
DBS has been used to treat Parkinson’s disease, a degenerative disorder caused by the loss of neurons in the brain region involved in movement. Stimulation can abruptly ‘switch off’ some of the symptoms and calm violent tremors in seconds. According to Lozano, over 90,000 people have already received DBS for Parkinson’s disease.
The effect of brain stimulation on Alzheimer’s disease is unprecedented. There are 9.2 million people living with dementia in China, where the rapidly aging population has been described as a ‘time bomb.’ The condition is caused by a loss of nerve cells in the brain and the erosion of the communication network between them. The hippocampus, which ‘files’ short-term memories for long-term storage, is one of the first victims. Shrinkage in this area is responsible for memory loss and confusion in the early stages of the disease.
In a trial of six patients in 2010, Lozano and colleagues used DBS to stimulate the fornix, a region of the brain that regularly communicates with the hippocampus. Early results were startling. Instead of a gradual decline, the hippocampus became more active and actually grew. Larger trials are currently underway to confirm the findings, but the study hints at a tantalizing prospect: could brain stimulation be used to make people smarter?
Dr. Nanthia Suthana and colleagues at the University of California, Los Angeles in the US decided to find out. They stimulated the entorhinal cortex, which is embedded in the memory and navigation circuits. Patients were assessed by playing a video game in which they drove through a virtual town to complete tasks dependent on spatial memory. A week of stimulation resulted in significant improvements in their scores.
While these results sound exciting, DBS is an invasive procedure associated with inherent risks, and so it seems unlikely to take off as a form of cognitive enhancement. What if there was another way?
Transcranial stimulation involves applying either a magnetic field or electric current to the surface of the brain to stimulate neurons. Researchers at the University of Oxford in the UK, led by Dr. Roi Cohen Kadosh, used the technology, aptly termed a ‘thinking cap,’ to improve volunteers’ mathematical skills. Instead of being inserted into the brain, an electrical current is applied to the skull region above the ears, below which are found the parietal lobes, the brain regions involved in numeracy. Just 30 minutes of stimulation every day for a week produced a significant improvement in mathematical skills.
Brain stimulation offers something unique: the scope to reform neural activity anywhere. In a world where psychiatric disorders are increasingly common, and with an aging population at risk of degenerative disease, new treatments are essential. Long-term studies are required, but will brain implants soon become as conventional as cardiac pacemakers? The technology is 2,000 years old, after all.
This article was first published in the print version of Asian Scientist Magazine, Apr 2014.
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