First human study targets cortical neurons in the brain to improve motor function.


The spinal cord is very sensitive to injury, however, unlike other parts of the body, the spinal cord does not have the ability to repair itself when damaged. A spinal cord injury occurs when there is damage either from trauma, loss of its normal blood supply, or pressure due to a tumour or infection. A main goal of rehabilitation strategies in humans with spinal cord injury is to strengthen transmission in spared neural networks. Although neuromodulation has the ability to target many different sites within the central nervous system to restore motor function following spinal cord injury, the role of cortical targets remains poorly understood.  Now, a study from researchers at the University of Miami uses a non-invasive cortical target in the brain to enhance hand motor function in patients with spinal cord injury.  The team state their study provides the first evidence that cortical targets in the frontal lobe could represent a novel therapeutic site for improving motor function in humans paralyzed by spinal cord injury.  The study is published in the journal Brain.

Previous studies show that in movement disorders, neuromodulation targets brain structures, cranial nerves, spinal cord, and peripheral nerves via the interaction of an electrical or neurochemical input with specific neural circuits.  Usually electrical epidural spinal cord stimulation is used to alleviate various disorders of the motor system in patients with spinal cord injury.  It has been hypothesised that neurostimulation may lead to the development of new nerve pathways or reawaken existing pathways between the brain and limbs.  The current study provides the first evidence that cortical targets could represent a novel therapeutic site for improving motor function following spinal cord injury.

The current study utilises noninvasive transcranial magnetic stimulation over the primary motor cortex, one of the principal brain areas involved in motor function housing corticospinal neurons.  The transcranial magnetic stimulation was set at an interval of 4.3 ms; late indirect (I)-wave protocol, mimicking the rhythmicity of descending late I-waves in corticospinal neurons.  An interval of 3.5 ms; control protocol, was also used between I-waves on separate days in a randomized order.  The group explain that late I-waves are thought to arise from trans-synaptic cortical inputs and have a crucial role in the recruitment of spinal motor neurons following spinal cord injury.

Results show that the excitability of corticospinal projections to intrinsic finger muscles increased in spinal cord injury and uninjured participants after the late I-wave, and not the control protocol, for 30 to 60 minutes after the stimulation. Data findings show that individuals with spinal cord injury were able to exert more force and electromyographic activity with finger muscles after the stimulation showing an enhanced ability to grasp small objects with their hands.

The lab state that this carefully conducted study provides several pieces of important information in developing strategies to improve function following spinal cord injury. They go on to add that they provide further evidence demonstrating rather clearly, contrary to years of dogma, that positive functional plasticity potential persists within the sensorimotor system for years after a spinal injury.  Another hypothesis is that a drug regimen, also long-term, targeting cortical neurons can be developed to form and maintain new neural circuitry to improve motor function.

The team surmise that their study provides a novel long-term cortical target to enhance hand motor output in humans with spinal cord injury.  They go on to add that their findings are a major contribution to the realization of a powerful new class of rehabilitation therapies which can target beneficial plasticity to crucial sites in the nervous system.  For the future, the researchers state that their results emphasize the need to develop new rehabilitation therapies based on mechanistic approaches to improve motor function in humans with paralysis due to spinal cord injury. They conclude that they are testing the effect of this intervention when given on consecutive days and in individuals with more severe muscle paralysis.

Source: University of Miami

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