Two Types of Grasp: Dissecting Cortical and Sub-cortical Contributions to Primate Hand Function

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The primate hand is a highly versatile actuator, capable of flexible reconfiguration to achieve task goals. This is very different from the paw of lower mammals, which has a capability restricted to whole-hand grasp. There is some evidence that primates may have retained capacities for more primitive grasp, alongside the evolutionary development of dexterous hand function. This suggests that the hand can operate in two modes. In one, the fingers flex or extend together to grasp an object (the power grip). In the other mode, single fingers can be independently controlled, to produce arbitrary gestures or complex grasps exemplified by the precision (pinch) grip. We propose that these modes are underpinned by different control circuits within the brain and spinal cord. Whilst interesting to the basic science of the neural control of movement, this idea becomes especially important in patients who are recovering from damage such as after stroke or spinal cord injury. Then, key components of the precision grip network seem to be lost; recovery is limited to gross grasp. The hand becomes a paw.In this proposal, we will determine which neural circuits contribute to the different types of hand use, using macaque monkeys which have very similar hand function to humans. We will first train monkeys to perform power grip, precision grip and an isolated index finger movement. Using fine microelectrodes, we will then record neural activity from the motor and pre-motor cortex, brainstem and spinal cord during performance of the different hand movements. By measuring the changes in cell activity as the tasks are carried out, we will be able to tell which areas contribute to each mode of hand operation. In some sessions, we will inject tiny quantities of a drug into an area to silence it; observing the types of hand deficits produced will confirm the role each area plays.Commands to make any movement originate in the cerebral cortex, and must be transmitted to lower centres to allow them to be executed. In a second series of experiments using anaesthetised monkeys, we will place stimulating electrodes in the motor and pre-motor areas of the cortex, and measure cell responses in the brainstem and spinal cord following cortical stimulation. This will tell us how the cortex communicates its instructions to sub-cortical structures. In humans, it is possible to activate cortical outputs non-invasively using transcranial magnetic brain stimulation (TMS). If we change how the coil is held on the head, TMS seems to stimulate the brain differently, but we don't know what is activated in the various conditions. We will address this by also using TMS in the anaesthetised monkeys, to tell us if TMS can selectively access the circuits for power and precision grips depending on how the coil is oriented. Finally, we will test how cells in the various areas respond to stimulation of the sensory receptors in skin and muscle.In studies in humans, we will apply the knowledge gained, using TMS in different orientations combined with sensory stimuli to probe specific components of the power and precision grip networks. After validating the methods in healthy human subjects, we will apply them to individuals who have recovered from spinal cord injury, thereby showing how the various circuits reconfigure to mediate recovery.This work will reveal core information about the control of human hand function and its recovery after damage. This foundation is required to develop novel, principled approaches to grasp rehabilitation. As the hand is so central to activities of daily living, even small future improvements in function could have major impacts in alleviating disability and raising quality of life.