An exploration of the application of non-invasive cerebellar stimulation in the neurorehabilitation of dysphagia after stroke

中风后的吞咽问题（吞咽困难）是NHS的一个主要临床问题，每年有超过40,000名患者患有吞咽困难并随之而来的误吸/肺炎。这导致住院时间更长，对喂养资源的需求增加，疗养院的入院人数增加，生存率下降，每年花费NHS约4亿英镑。传统上，言语和语言治疗师使用饮食调整和床边策略来恢复吞咽，尽管很少有证据表明有益。虽然管饲可以改善营养，但没有证据表明（食物）误吸的风险降低了。随着中风的发病率预计将在未来20年增加，吞咽困难的问题可能会增加，因此更好地了解如何控制吞咽恢复将对人类健康和疾病有明显的好处。我们小组之前的工作已经研究了中风患者吞咽困难成功恢复的因素，其中一些工作导致了通过吞咽导管进行咽刺激疗法的发展，目前正在进行III期临床试验。不幸的是，许多患者不能参加这样的试验，因为他们的中风导致口腔/喉咙感觉受损，或者因为他们不能遵守导管放置。此外，大约三分之一的吞咽困难中风患者似乎对这种感官干预没有反应。因此，有必要探索其他策略来改善这组患者的吞咽控制。在这个建议中，我们将探索一种新的和令人兴奋的方法的有效性，非侵入性小脑刺激，以增强中风后吞咽皮层的运动可塑性。这种方法主要在动物实验中进行了检验，直接小脑刺激显示了大鼠人工中风后肢体运动反应的增强和运动恢复的增强。相比之下，我们已经证明，人类的小脑在吞咽过程中被强烈激活，当用磁脉冲刺激后脑时，可以强烈改善人类大脑皮层到吞咽肌肉的通路。最近，我们已经确定了最相关的小脑磁刺激频率（10Hz），可以对人类吞咽运动系统产生长期的改善。因此，我们相信小脑刺激在改善吞咽方面的潜力比其他方法要大得多。我们的计划是通过三项研究来研究这种新方法，每项研究都建立在另一项研究的基础上。首先，我们将使用“虚拟损伤”技术来抑制大脑的吞咽区域，然后对健康参与者进行小脑刺激，看看刺激小脑的任何一侧是否能使吞咽区域恢复正常。然后，我们将测试对吞咽困难中风患者的最佳小脑侧/部位的刺激，看看我们是否可以在刺激后立即（1小时）改善吞咽。假设这种方法有效，我们将对吞咽困难中风患者进行小剂量范围的小脑刺激研究，看看哪种刺激方法（每天多少天，每天多少次）在吞咽方面产生最大的长期变化（超过1小时，到2周）。如果有一个最佳的/最好的处方，我们期望这将导致未来更大规模的研究小脑刺激在吞咽困难的中风，预期这将最终成为这些痛苦和衰弱的中风受害者的治疗选择。

Swallowing problems (dysphagia) after stroke represent a major clinical problem for the NHS, with over 40,000 patients annually suffering from dysphagia with consequent aspiration/pneumonia. This leads to longer hospital stays, increased demands on feeding resources, higher admissions to care homes and poorer survival, costing the NHS an estimated £400 million a year. Traditionally, speech and language therapists have used dietary modifications and bedside strategies to rehabilitate swallowing albeit with little evidence base for benefit. And while tube feeding can improve nutrition, there is no evidence that the risk of (food) aspiration is reduced. With the incidence of stroke projected to increase over the next 20 years, the problem of dysphagia is likely to grow, so a better understanding of how swallowing recovery can be manipulated would of clear benefit to human health and disease. Previous work from our group has looked at the factors that might make for successful recovery from dysphagia in stroke patients, and some of this work led to development of a pharyngeal stimulation therapy via a swallowing catheter that is now undergoing phase III clinical trials. Unfortunately, many patients cannot participate in such trials because their stroke has resulted in either impaired sensation in the mouth/throat or because they cannot comply with catheter placement. Moreover, about a third of dysphagic stroke patients don't seem to respond to this sensory intervention. There is therefore a need to explore alternative strategies to improve control of swallowing in this group of patients.In this proposal we will explore the effectiveness of a new and exciting approach, non-invasive cerebellar stimulation, to enhance motor plasticity in the swallowing cortex after stroke. This approach has mainly been examined in animals where direct cerebellar stimulation has showed enhancement of limb motor responses and enhanced motor recovery after artificial stroke in rats. By comparison, we have shown that the human cerebellum is strongly activated during the act of swallowing and when stimulated with magnetic pulses over the back of the head can strongly improve the cortex to swallowing muscles pathway in humans. More recently we have identified the most relevant frequency of magnetic stimulation of the cerebellum (10Hz) that can produce longer term improvements in the human swallowing motor system. We therefore believe that the potential for cerebellar stimulation in improving swallowing is much greater than other methods.Our plans are to look at this new approach through three studies that each build on the other. First we will use a "virtual lesion" technique to suppress the swallowing areas of the brain before applying the cerebellar stimulation in health participants to see if stimulation either side of the cerebellum can restore the swallowing regions to normal. We will then test out stimulation of best cerebellar side/site in dysphagic stroke patients to see if we can improve swallowing in the period immediately after stimulation (1 hour). Assuming this works, we will then run a small dose ranging study of cerebellar stimulation in dysphagic stroke patients to see which recipe of stimulation (how many days and how many times per day) produces the greatest long term changes in swallowing (beyond 1 hour, to 2 weeks). If there is an optimal/best recipe for this, we expect this will then lead on to future larger scale studies of the cerebellar stimulation in dysphagic stroke with the anticipation that this will eventually become a treatment option for these distressed and debilitated victims of stroke.