Implanted electrodes allowed one man to climb stairs unaided
The spinal cord is the control cable that connects the brain to the rest of the body. If it is severed, people lose the ability to move their body below the site of the injury. But if it is only partly cut, the brain can sometimes adapt to the damage. Some people who are paralysed by a spinal-cord injury can gradually regain at least a limited ability to walk.
Exactly which bits of the brain are involved in this adaptation is not clear. But, in a paper just published in Nature Medicine, a group of researchers led by Jocelyne Bloch of Lausanne University Hospital and Grégoire Courtine at the Swiss Federal Institute of Technology in Lausanne shed some light. In doing so, they demonstrate that stimulation of the right bits of the brain can produce dramatic—and seemingly permanent—improvements in the ability of patients to walk again.
“We already knew that [changes in] the brain were key to regaining walking after a spinal-cord injury,” says Dr Courtine. “But we didn’t know which regions were the most important.” To find out, the researchers built detailed maps of the brains of a dozen mice whose spinal cords had been partially severed.
By examining some brains shortly after the injury, and others later, as their animal owners were regaining the ability to walk, the researchers were led to a set of neurons in the lateral hypothalamus (LH; a part of the brain buried deep towards the bottom of the organ) as the likely culprit. That was unexpected, says Dr Bloch, for the LH is best known for being involved with hunger, thirst and other involuntary functions of the nervous system.
To check they were on the right track, the researchers turned to a technique called optogenetics. This involves modifying living cells so that they express light-sensitive proteins called channelrhodopsins. These act as switches, allowing cellular activity to be controlled with bursts of illumination. Sure enough, artificially stimulating the activity of neurons in the LH improved the ability of injured animals to walk. In some cases, it was even able to make the mice jump.
Optogenetics is not generally approved for use in humans. But an alternative method of stimulating neurons, deep-brain stimulation (DBS), is. Rather than modifying cells to respond to light, this involves inserting fine electrodes into the brain and stimulating neurons with electric currents. Switching to DBS required a second round of testing, this time on rats. (Rats have slightly bigger brains than mice, says Dr Courtine, which makes the delicate job of placing the electrodes a bit easier.)
As hoped, zapping neurons in the brains of injured rats over the course of several weeks helped them, too, to regain the ability to walk. The improvements persisted even when the current was turned off, with analysis of their spinal cords showing an increased density of neuronal wiring below the site of their injuries.
The final step was to try it in people. The researchers recruited two volunteers who had suffered spinal injuries and then relearned how to walk with assistance. The electrodes were implanted in them while they were conscious. This helped the doctors ensure they were in the right place, with both patients reporting an urge to walk when the current was switched on.
After three months of rehabilitation, both reported big improvements in walking, as assessed by tests of how far they could travel in a set time, and by the subjective difficulty they experienced. Before the operation, one of them had hoped to walk without braces; the other to climb and descend a staircase unaided. Both achieved their goals.
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