Multi-site and state-dependent effects of Transcranial Ultrasound Stimulation on brain function and cognition

经颅超声刺激对脑功能和认知的多部位和状态依赖性影响

• 批准号: BB/Y001494/1
• 负责人: Elsa Fouragnan
• 金额: $ 131.21万
• 依托单位: Plymouth University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FY001494%2F1
• 关键词: Multi; site; state; dependent; effects

Ultrasound is best known for imaging unborn babies. In this instance, sound waves travel through the body and their echoes are used to form images, with a very limited amount of energy remaining in the body. By focusing the sound waves to a small region in space, a bit like a magnifying glass focusing sunlight increases the heat energy to one place, the focused ultrasound energy increases, and this can be used to change the way cells behave in the body. Through the skull, this can be used to change how our brain functions in a safe, transient, and reversible way. This has therapeutic potential for treating disorders of the brain, like neurological disorders (Parkinson's disease) but also psychiatric disorders (addiction, depression). The technique is called Transcranial Ultrasound Stimulation (TUS).In a series of studies, our team have shown that TUS can safely and reversibly change brain activity up to two hours after intervention (Yaakub et al. 2023). Because these changes exceed the intervention period, the effects promote neuroplasticity - the ability of the brain to re-wire itself, a key function when considering new treatment for disorders of the brain.Although TUS has the potential to revolutionize how we treat the brain throughout life, both in general health and disease, TUS outcomes are variable. In our prior work, we have observed that the TUS effects depend on the "state" that the person is in, for example awake or sleeping (physiological state), or resting or focusing on a task (cognitive state). Changes in physiological or cognitive states cause changes in brain regional activity which consequently change how TUS impacts these brain regions.In this novel project, we will investigate for the first time the relationships between brain states and TUS (Aim 1) and whether recruitment of targeted brain regions improves TUS-induced plasticity. This is crucial for optimizing future treatment designs, particularly those leveraging cognitive-behavioral tasks during TUS therapies. For Aim 1, we will use three work packages (WP1-3), all focusing on the effects of the same TUS intervention on different states: 1) different states of consciousness (manipulated with different depth of anaesthesia), 2) different states of pain sensitivity (manipulated through experimental manipulation of pain development) and 3) different cognitive load (manipulated through complex versus simple learning tasks). Better refining the relationship between TUS and states will be vital to pave the way for effective clinical interventions, particularly those combining cognitive-behavioral therapy and brain stimulation. Another important aspect of TUS is that it can reach any region in the brain - in the order of millimetres - even deep in the brain, unlike more traditional methods that remain superficial and not spatially accurate. This is important when trying to assess the role of specific nuclei in the brain or specific regions. Some regions of the brain have specific functions, for example, a region A can be linked to a function A, while another brain region B can be linked to a function B. By modulating regions A and B on different days, one can assess the role of these regions. However, sometimes a function is linked to the way regions communicate with one other and not solely on the region themselves. In theory, this could be assessed through concurrent brain stimulation of the two regions. In this new line of research, we will also pursue the idea that TUS can be used at different locations of the brain at the same time, in order to change communication between brain regions (Aim 2 - Work Package 4 [WP4]). We want to show that concurrent multisite TUS is safe and can increase outcome measures by providing additional ways of intervening in the brain. This will increase the potential of TUS applications and open a new avenue for thinking about non-invasive brain stimulation which considers the dynamism of brain networks.

超声波以成像未出生的婴儿而闻名。在这种情况下，声波穿过身体，它们的回声用于形成图像，体内剩下的能量非常有限。通过将声波聚焦到太空中的一个小区域，有点像放大玻璃聚焦的阳光会增加热能到一个地方，集中的超声能量增加，这可以用来改变细胞在体内的表现方式。通过头骨，可以用来以安全，短暂和可逆的方式改变我们的大脑的功能。这具有治疗大脑疾病的治疗潜力，例如神经系统疾病（帕金森氏病）和精神疾病（成瘾，抑郁症）。该技术称为经颅超声刺激（TUS）。在一系列研究中，我们的团队表明TUS可以安全，可逆地改变干预后两个小时的大脑活动（Yaakub etal。2023）。由于这些变化超过了干预期，因此影响促进了神经塑性 - 大脑重新连接本身的能力，这是考虑大脑疾病的新治疗方法时的关键功能。尽管TUS有可能在整个生活和疾病中如何彻底改变我们在一般健康和疾病中如何治疗大脑，但TUS肿瘤是可变的。在我们的先前工作中，我们观察到TUS效应取决于该人所处的“状态”，例如醒着或睡眠（生理状态），或者休息或专注于任务（认知状态）。生理或认知状态的变化会导致大脑区域活动的变化，从而改变TUS对这些大脑区域的影响。在这个新型项目中，我们将首次研究大脑状态与TUS之间的关系（AIM 1）（AIM 1）以及靶向大脑区域的募集是否改善TUS诱导的可变性。这对于优化未来的治疗设计至关重要，尤其是那些在TUS疗法期间利用认知行为任务的人。对于AIM 1，我们将使用三个工作包（WP1-3），所有工作套件都集中在相同的TUS干预对不同状态的影响上：1）不同的意识状态（用不同的麻醉深度操纵），2）疼痛敏感性的不同状态（通过疼痛开发实验性操纵而操纵）和通过不同的认知负载（通过不同的认知载荷来操纵）（操纵）。更好地完善TUS与国家之间的关系对于为有效的临床干预铺平道路至关重要，尤其是那些结合认知行为疗法和大脑刺激的方式至关重要。 TU的另一个重要方面是，它可以按照毫米的顺序到达大脑中的任何区域，甚至可以在大脑中深处，这与保持肤浅而不是空间准确的更传统的方法不同。当试图评估特定核在大脑或特定区域的作用时，这一点很重要。大脑的某些区域具有特定的功能，例如，一个区域A可以链接到一个功能A，而另一个大脑区域B可以链接到功能B。通过在不同的日子调节区域A和B，可以评估这些区域的作用。但是，有时函数与地区互动的方式相关联，而不仅仅是该地区本身。从理论上讲，这可以通过对两个区域的大脑刺激进行评估。在这一新的研究中，我们还将追求一个想法，即可以同时在大脑的不同位置使用TU，以改变大脑区域之间的沟通（AIM 2-工作包4 [WP4]）。我们想表明，并发的多站点TU是安全的，可以通过提供大脑中的其他方式来增加结果指标。这将增加TUS应用的潜力，并为考虑脑网络动态的非侵入性大脑刺激开辟新的途径。