Reprogramming the Nervous System through a Wearable Neurostimulation Device

脑细胞之间通过称为突触的连接进行交流。这些连接的强度随着大脑的学习而变化，或者随着电路的重新连接而变化，以便在受伤后恢复。我们现在知道，重塑突触的一个重要因素是活动的时机。当突触与其连接的细胞同时处于活动状态时，这种联系就会加强。在过去的十年里，神经科学家已经证明，通过在正确的时间传递一对刺激，可以重塑某些大脑回路？一个例子是对运动皮质的磁刺激，以及对手臂神经的电刺激。然而，这些工作都是在实验室环境中完成的。突触的变化通常只是短暂的，因为刺激作用的时间很短。在这个项目中，我们将开发一种能够传递精确定时刺激的新型电子设备。它还将能够测量肌肉的活动和肢体的运动，以便刺激可以相对于神经系统自然发生的活动进行计时。这种设备将是微型化和可穿戴的，使其能够在受试者进行正常日常活动时持续工作。我们预计这将导致神经连接的长期变化。我们将首先在健康受试者身上测试该设备。我们将尝试重新连接脊髓中被认为对减少震颤很重要的连接，以及运动皮质中可能限制我们独立激活肌肉的能力的连接。一旦我们开发出有效的范例，我们将在患者身上进行测试。最初，我们将针对病理性震颤、局限性任务特定的肌张力障碍和中风患者。在震颤中，我们预测有可能降低震颤的幅度，从而部分缓解病理性震颤可能造成的严重残疾。对于中风和肌张力障碍，我们希望减少控制上肢的不同肌肉的异常协同激活；这将使患者能够更独立地开展日常生活活动。如果成功，这种方法可能会为广泛的神经疾病开辟一系列新的治疗选择。

Brain cells communicate with each other via connections called synapses. The strength of these connections changes as the brain learns, or as circuits are rewired to allow recovery after injury. We now know that an important factor in remodelling synapses is the timing of activity. When a synapse is active at the same time as the cell it connects to, this connection is strengthened.Over the last ten years, neuroscientists have shown that certain brain circuits can be remodelled by delivering pairs of stimuli at the correct time ? an example would be a magnetic stimulus to the motor cortex, paired with electrical stimulation of a nerve in the arm. However, this work has all been done in a laboratory setting. Changes in synapses are often only short-lived, because the stimuli are only applied for a short time. In this project, we will develop a novel electronic device capable of delivering precisely timed stimuli. It will also be capable of measuring activity in muscle, and limb movement, so that stimuli can be timed relative to the naturally-occurring activity of the nervous system. This device will be miniaturised and wearable, allowing it to work continually as the subject carries out their normal daily activities. We expect that this will lead to long term changes in neural connections.We will initially test the device in healthy subjects. We will attempt to rewire connections in the spinal cord believed to be important in reducing tremor, and connections in the motor cortex which may constrain our ability to activate muscles independently. Once we have developed effective paradigms, we will then test them in patients. Initially, we will target people with pathological tremor, focal task-specific dystonias and stroke. In tremor, we predict that it will be possible to reduce tremor amplitude, thereby partially alleviating the severe disability which pathological tremor can produce. In stroke and dystonias, we hope to reduce abnormal co-activation of different muscles controlling the upper limb; this would allow patients to carry out activities of daily living more independently. If successful, this approach could open up a new range of therapeutic options for a wide range of neurological disease.