Primate neuroscience from lab to clinic part 3 - restoring movement

We use animals to advance scientific understanding or as models to study human diseases when the research cannot be done any other way. To work with research animals in the UK or Europe, scienitists must provide clear justifications explaining why their line of research is needed, the expected benefits that will come from a particular study and why this work is so important that it justifies the use of animals. This is even-more the case when our close relatives, non-human-primates are the species being studied. When monkeys are used in research they are considered ‘specially protected’ and extra ethical requirements, checks and justifications must be met to ensure that they are not used unnecessarily and that the research will deliver clear benefits to humankind.

Last year I partnered with leading neuroscientists to review three very different fields of research where findings from primate-studies are transforming human-treatments and making a real difference to people's lives. This third article looks at how our understanding of the circuitry that allows hand movement is changing, allowing patients who have lost control of their hands hope of recovery.

The full paper is available at https://doi.org/10.1016/j.crneur.2022.100049

In a snap of their fingers: understanding movement recovery after stroke

Primates have advanced circuitry for controlling movement, and understanding how these work, can help people whose control over their bodies has been damaged by stroke or other injury. While rodents have only two distinct regions of the brain’s motor-cortex controlling their movement, primates have at least eight, enabling them to walk with different postures (including upright on two legs, hold things in their hands (and feet), use tools and communicate through complex gestures. These new regions all form complex circuits, connected to parts of the nervous system, including the brainstem and spinal cord, in ways that give rise to some unique abilities of primates: a wide range of hand-grasps and a fine range of finger movements that allow us to pick up objects, write and use the touch screen of a mobile phone.

As well as these new, unique, regions of the cortex, primates also have the old regions for controlling movement, like those found in other mammals. Around 15 years ago a group of neuroscientists in the UK showed that while the new circuits found in primates were important to controlling movement, that control of movement in the hands of primates is shared between the old nerve pathways travelling between the spinal cord and the brainstem, and the newer pathways between the spinal cord and higher, exclusively-primate, brain. These parallel pathways both contribute to aspects of motor function in macaque monkeys, and similar pathways are found in humans.

After a stroke, parts of the brain are damaged, either by bleeding into the tissue, or because regions were starved of essential oxygen for a period. These damaged areas, which often include the ‘higher brain’ cortical areas responsible for primate movement, cannot be repaired. But understanding that primate control of hand movement involves multiple pathways that working together, mean that when the cortical ‘higher brain’ circuit is damaged the other pathway may be more needed.

When this idea was tested in monkeys by specifically damaging the cells of the brain areas responsible for hand movements, they found that the other, more primitive pathway did indeed strengthened in response. There was a problem though. The strengthening to take over the lost function occurred in some muscles but not in all. The hand muscles recovered their ability to grip objects, using the alternative pathway, but those for releasing objects did not follow the same diversion. This phenomenon is also common in stroke patients who recover the ability to grip but not to let go of things they pick up.

With this new knowledge researchers looked for a way to adapt the motor pathways so that they would recover better muscle function. More recent research in monkeys built on this knowledge, finding that click sounds from a machine paired with electrically stimulating a muscle through a simple wearable device, could affect these deep cells of reticulospinal pathway. In monkeys, this device seems to create long-term improvements to the control of hand movements as movement recovers after damage to the brain’s motor circuits. The device has undergone trials in human patients, and in 2020 findings showed that stroke patients experienced a long-lasting improvement in their ability to use their hands.

The accompanying paper to this article https://doi.org/10.1016/j.crneur.2022.100049 provides further examples of this enormously important area of research, and the wealth of research that underpins it provides more detail still. The outcomes and changes to treatment protocols that result from studies like these have profound effects on people’s lives, and understanding the primate brain crucial, not only to knowing ourselves better, but to be able to provide help where it is greatly needed.

Monkeys are intelligent, social and experience a huge range of emotions, just as people do. Their use in research is rightly limited, with checks and safeguards on their use. But this must be balanced with the enormous social benefit of this research, as we develop better understanding of the primate brain.?