New 'Brain Atlas' Spurs Life-Changing Stimulation Therapy

Researchers in Switzerland have developed an extensive map of the human brain that highlights which neurons are most involved in locomotion recovery, or re-learning to walk after debilitating injury. Their work, which multiple peers have called a “tour de force,” has already allowed them to deliver deep brain stimulation (DBS) that has restored the ability to walk in two people with spinal cord injuries.

DBS is a relatively young form of therapy that involves surgically implanting electrodes into specific parts of the brain. These electrodes are paired with a pulse generator, typically placed under the skin in the patient’s chest. As the generator sends electrical pulses upwards, the electrodes in the brain stimulate nearby neurons, which—depending on the part of the brain in which they were installed—might be related to movement, seizures, depression, chronic pain, and other conditions. 

Although DBS has been FDA-approved for the treatment of certain tremor-related and mood disorders for a couple of decades, many scientists have had their eye on an even bigger prize: helping people with spinal cord injuries regain the ability to walk. Because most movement-related DBS work focuses on the parts of the brain responsible for motor control, not locomotion, restoring a patient’s ability to walk on their own is a tall order. 

Neuroscientists at the École Polytechnique Fédérale de Lausanne (EPFL) started by developing a vast “brain atlas” to map out different neurons’ responsibilities. They did so using 3D images of “cleared” brain tissue, or tissue whose lipids had been removed with organic solvents. Cleared tissue allows scientists to more easily locate and label target structures, such as proteins, peptides, and neuronal circuits, while maintaining an understanding of the tissue’s 3D structure. 

Examining these images revealed which parts of the brain underwent physical and functional changes after a spinal cord injury. Unexpectedly, the atlas revealed the lateral hypothalamus, a part of the brain typically associated with motivation and reward-related behavior, to be related to locomotion. Sure enough, stimulating the lateral hypothalamus in rodents helped them recover their ability to walk after spinal cord injury.

The team moved forward with investigating lateral hypothalamus DBS in humans. They recruited two people with spinal cord injuries, one of whom was a 54-year-old man who required a wheelchair full-time after a ski accident. Both people had been injured years prior and were thus ineligible for more conventional treatment options. 

“Once the electrode was in place and we performed the stimulation, the first patient immediately said, ‘I feel my legs.’ When we increased the stimulation, she said, ‘I feel the urge to walk!'” neurosurgeon Jocelyne Bloch said in an EPFL statement. “This real-time feedback confirmed we had targeted the correct region, even if this region had never been associated with the control of the legs in humans. At this moment, I knew that we were witnessing an important discovery for the anatomical organization of brain functions.”

Both patients received electrode implants and underwent DBS for three months. Throughout that period, the patients performed about nine hours of training each week. When the DBS was active and shortly thereafter, the patients were more easily able to move their legs. Eventually, they both learned to walk without braces and navigate stairs independently. Wolfgang Jäger, the man who had experienced the ski accident, said even small tasks, such as reaching tall kitchen cupboards, have become easier for him.

EPFL’s locomotion-related achievements are impressive and life-changing, but the effects of their work don’t stop with spinal cord injuries. Neuroscientists at other organizations are prepared for EPFL’s brain atlas to become a major tool within a wide range of disciplines, where it could be used to improve surgical techniques, lab research, medical treatment plans, and yes, rehabilitation efforts.