The first person to electrically stimulate the brain of a living human during surgery was the 19th-century British neurosurgeon Sir Victor Horsley. The operation was to treat a deformation called an encephalocele, where the bones of the skull do not close properly in the womb, causing the brain to protrude from the head. Horsely applied a weak electrical current to the surgically exposed brain tissue, making the patient’s eyes swivel to the side, which told the surgeon that the out-of-place area was the top of the midbrain — normally a deeply embedded neural structure essential for directing vision.
The technique was later picked up to treat epilepsy as it became clear that removing the part of the brain that triggered seizures could be an effective treatment, even if identifying it could be tricky. Small, clearly identified points of damage or localized tumors could often trigger seizures, but sometimes the errant waves of epileptic activity would start far away from the original point of visible injury. Horsley used the electrical stimulation technique while patients were awake to find the sensitive area and remove it. Not bad for 1886.
Although initially invented for medical reasons, this surgical technique began to throw up some curious scientific data. In the 1930s, the Canadian neurosurgeon Wilder Penfield asked patients undergoing epilepsy surgery if he could perform brief experiments while they were being operated on. He found that stimulating parts of the brain could cause a range of reactions from tingling to weeping to a “desire to move” — providing crucial evidence that activity in specific brain areas could trigger surprisingly complex behaviors.
People with epilepsy have remained an important part of our quest to understand ourselves as they have regularly volunteered to take part in neuroscience experiments while undergoing open-brain operations. Even though these experiments are a relatively brief pause in the procedure they still require people to offer some of their time while their skull has been opened and their brain exposed, and we know much more about the brain thanks to their generosity.
As surgical techniques have moved on, so has the science. The starting points of some seizures are not easily localized in the relatively short period available during surgery. To compensate for this, neurosurgeons have taken to implanting electrodes in the brains of people with epilepsy before the skull is replaced and the skin sewn up, which allows the medical team to record brain activity as the patients go about their daily life. One form of this “in brain” recording, known as electrocorticography, involves surgically inserting a grid of electrodes over the surface of the brain.
This has allowed neuroscientists to measure the brain at work in the real world via cables which go from the brain into a small digital recorder. A study published last year in the Journal of Neurosurgery mapped the main language areas of the cortex, the brain’s outer layer, using an implanted electrode grid and a simple word task which took an average of just 47 seconds. More than 100 other studies have used this technique with similarly impressive results.
One innovation is particularly mind-boggling. After years of using implanted electrode grids to read from the brain, neuroscientists have begun to use the electrodes to write to it — in other words, to alter the function of the brain through the same electrodes that record its activity.
“By having a grid of electrodes in place,” says Matthew Lambon Ralph, professor of cognitive neuroscience at Manchester University, “it is possible to probe many different regions rather than just one.”
The precision is such that the Lambon Ralph team and a team at Kyoto University Medical School, led by Riki Matsumoto, have used an implanted grid to temporarily simulate characteristics of a brain disease called semantic dementia. Like Alzheimer’s, semantic dementia is a degenerative disorder, but one in which brain cells that specifically support our understanding of meaning rapidly decline. Studies of patients with semantic dementia have taught us a great deal about how memory is organized in the brain, but the disorder is swift and unpredictable, and a method that can simultaneously mimic the effects while recording directly from the cortex is a powerful tool.
The technique is safe and reversible, as we know from a simple version that is often done pre-neurosurgery to ensure that no tissue that supports key mental functions is removed during the operation. Using it as a way of briefly simulating more complex cognitive difficulties is an exciting development.
“Stimulation is injected in one part of a grid and the evoked response across other grids is measured. It’s a direct measure of functional connectivity,” explains Lambon Ralph, highlighting how these sorts of studies can allow the brain’s function, in terms of thinking skills, to be closely linked to its physical connections.
The research was presented at the British Neuropsychological Society spring conference by UK-based team member Taiji Ueno. The main findings are still being prepared for peer review, but the use of implant grids in neuroscience research is sure to become more common as the surgical procedure becomes more widely used.
These procedures are only done for medical reasons, and researchers get no say about how and on whom they are performed. However, as ever, patients have been generous with their time. From 1886 until now, these exciting discoveries have been given to us by people on the operating table.
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