Feasibility of a direct brain-to-muscle upper-limb neuroprosthesis

描述(由申请人提供)： 植入的神经肌肉刺激系统能够恢复手臂和手的全部运动，现在已经在因脊髓损伤而瘫痪在颈部以下的人身上实施。皮质内微电极阵列现在也在其他瘫痪患者身上进行测试，用于长期记录运动皮质的神经活动。通过将这两项技术结合起来，我们可能会开发出完整的系统，绕过脊髓损伤，恢复脊髓损伤患者的自然运动。然而，如果大脑信号被解码为运动的运动学方面(例如肢体位置、速度、关节角度等)，那么我们仍然需要开发额外的技术来将这些运动学命令转换为产生所需动作所需的肌肉刺激模式。这不是一项微不足道的任务。在这项研究中，我们将评估重新训练贝恩公司直接控制肌肉刺激器的替代方法，从而绕过如何最好地将一个人的预期动作转化为产生这些动作的肌肉激活水平这一具有挑战性且仍然悬而未决的问题。一些研究表明，在身体健全的动物中，运动皮质神经元的局部场电位和放电率与记录到的肌肉活动相关。然而，在这项研究中，我们专门测试是否可以重新训练运动皮质，以控制瘫痪肢体产生所需动作所需的肌肉激活水平，在瘫痪肢体中，只有一部分正常肌肉可以被刺激，瘫痪后肌肉已经萎缩。由于随着时间的推移，皮质内记录电极并不总是能够检测到单个神经元的FIRIN，因为随着时间的推移，身体包裹着电极，我们也将比较使用记录的神经元的放电频率来控制肌肉刺激器的有效性，以及使用更强有力的记录的局部场电位来控制肌肉刺激器的有效性。我们将在这项研究中使用的新的解码方法可以在临床上应用于瘫痪的个体，而不仅仅是健全的动物。在AIMS 1-2中，猴子将被训练使用运动和运动前皮质神经元集合的放电率来控制肌肉亚群的激活水平，这是对瘫痪手臂的实时肌肉骨骼模拟。当猴子成功地将模拟手臂移动到不同的目标时，他们将获得果汁奖励。在目标1中，猴子将通过控制六块肌肉的激活水平来控制模型手臂在水平面上的运动。在Aim 2中，外力将应用于模型手臂。动物将不得不改变肌肉的激活水平(通过改变他们的神经 射击)，以便仍然将手臂对准目标。目标3将确定相同水平的ARM 仅使用从皮质内微电极阵列记录的局部场电位也可以实现目标1和2中的控制。

DESCRIPTION (provided by applicant): Implanted neuromuscular stimulation systems capable of restoring full arm and hand motion have now been implemented in people paralyzed below the neck due to spinal cord injury. Intracortical microelectrode arrays are also now being tested in other paralyzed individuals for chronically recording neural activity in the motor cortex. By combining these two technologies, we can potentially develop complete systems that will bypass damage in the spinal cord and restore natural movement by thought to people with spinal cord injuries. However, if the brain signals are decoded into kinematic aspects of movements (e.g. limb position, velocity, joint angles etc.), then we still have to develop additional technology to convert those kinematic commands into the muscle stimulation patterns needed to generate the desired movement. This is not a trivial task. In this study, we will evaluate the alternative approach of retraining the bain to control the muscle stimulators directly, therefore bypassing the challenging and still open problem of how best to translate one's intended movement into the muscle activation levels that will generate those movements. Several studies have shown that local field potentials and the firing rates of motor cortical neurons correlate with recorded muscle activity in able- bodied animals. However, in this study we are specifically testing if motor cortex can be retrained to command the muscle activation levels needed to generate the desired motion of a paralyzed limb where only a subset of the normal muscles can be stimulated and muscles have atrophied after paralysis. Since intracortical recording electrodes are not always capable of detecting firin of individual neurons as the body encapsulates the electrodes over time, we will also compare the effectiveness of using firing rates of the recorded neurons to control the muscle stimulators versus using the more robustly recorded local field potentials to control muscle stimulators. The novel decoding methods we will use in this study can be applied clinically to paralyzed individuals and not just able-bodied animals. In aims 1-2, monkeys will be trained to use the firing rates of ensembles of motor and premotor cortical neurons to control the activation levels of subsets of muscles in a real-time musculoskeletal simulation of a paralyzed arm. The monkeys will be given juice rewards when they successfully move the simulated arm to different targets. In aim1 the monkeys will control movements of the model arm in the horizontal plane by controlling the activation levels of six muscles. In aim 2 external forces will be applied to the model arm. The animals will have to alter the muscle activation levels (by alternating their neural firing) in order to still get the arm to the targets. Aim 3 will determine if the same level of arm control seen in aims 1 & 2 can also be achieved using only local field potentials recorded from intracortical microelectrode arrays.