Macaque study examines role of interhemispheric pathways in recovery from spinal cord injury

Strokes and spinal cord injuries can severely impair motor functions. Understanding how to promote recovery is a major challenge. While damaged neurons in the brain and spinal cord have limited ability to regenerate, the brain can form or strengthen alternative neural pathways that involve uninjured parts of the brain, allowing for functional recovery. Such reorganization of neural pathways in the brain is called neural plasticity. Identifying the neural pathways involved and understanding their functions can help researchers develop more effective rehabilitation strategies.

Previous research has shown that when one side of the corticospinal tract – a key pathway that carries movement signals from the brain to the spinal cord – is damaged, activity increases in the motor cortex on the opposite side of the brain. This has raised questions about whether this increased activity helps or hinders recovery, and the exact role of these pathways has been unclear.

In a study published in Nature communicationResearchers from WPI-ASHBi, Kyoto University, and the National Institute of Physiological Sciences conducted experiments on macaque monkeys to investigate how this change in neuronal activity affects recovery from spinal cord injury.

To manipulate neural activities in both motor cortices, viral vectors were injected into targeted brain areas to block communication between the left and right motor cortices through the administration of drugs, with the effect being reversible. This allowed the researchers to observe how disrupting these pathways affected the monkeys' ability to perform precise reaching and grasping tasks before and after the injury. In addition, they measured neural activity in the motor cortex on both sides during the task. The results showed that blocking the pathways without injury had no effect on the monkeys' ability.

However, due to the blockade, there was a significant decline in the monkeys' abilities in the early phase of recovery. This suggests that the interhemispheric pathway, which is not normally involved in motor functions, becomes relevant for motor recovery in the early phase. The study also revealed changes in the activity patterns of the motor cortex when the pathways were blocked. When the signal from the opposite side was blocked, activity on the affected side decreased in the early phase of recovery from the injury. On the other hand, the same blockade increased activity in the intact state.

These results suggest that the interhemispheric pathway between the left and right motor cortex, which plays an inhibitory role in the intact state, plays a facilitatory role in the early phase of recovery after injury. This pathway activates the motor cortex on the side that is generally not involved in motor functions, thereby contributing to the recovery of motor function.

“These results highlight that although the interhemispheric pathway is inhibitory when intact, it becomes facilitative during the early recovery period, supporting the recovery of motor function by activating the motor cortex on the unaffected side,” explained Dr. Masahiro Mitsuhashi, the study's lead researcher. This discovery highlights the adaptive capacity of spared neural pathways in promoting recovery from central nervous system injury.

The findings from this study provide valuable insights into the role of brain pathways in motor control and how the brain responds to perturbations. These findings are critical for developing better strategies for rehabilitation and treatment of motor impairments resulting from brain injury.

The researchers plan to study how similar pathways work in other types of central nervous system injuries, such as those caused by stroke. By integrating these findings into traditional rehabilitation methods, they hope to improve therapies for severe central nervous system injuries and reduce long-term impairment.

“More research is needed, but we hope that uncovering the neural pathways critical for recovery and developing methods to activate them will lead to advances in future neurorehabilitation therapies,” Mitsuhashi said.