Optimising non-invasive brain stimulation to enhance working memory.

经颅直流电刺激（tDCS），电流直接应用于头皮，已被证明可以改善健康成年人的记忆力。最近，研究人员研究了使用交流电（tACS）设置在特定频率下振荡的好处，该频率被选择用于与大脑中的特定网络相互作用并夹带特定网络。人们认为，通过优化刺激的参数，有可能针对特定的神经网络并调节它们的神经化学（如在运动系统中），以增强大脑的可塑性（我们学习新事物的机制）。开发一个数学框架来测试非侵入性脑刺激对网络可塑性和连接性的影响，对于促进我们对正常发育、预防性衰老、并作为临床人群的潜在治疗干预。工作记忆或“短-术语记忆能力在发展过程中的复杂技能的获得中起着重要作用，并且与学术能力和语言理解密切相关。工作记忆障碍常见于神经发育障碍，如自闭症和多动症，以及神经精神障碍，如精神分裂症和抑郁症，我们作为我们更广泛的研究团队的一部分研究的患者。除了认知训练，目前还没有治疗工作记忆障碍的方法。虽然有几项研究使用了脑刺激，但由于缺乏对健康和病理状态下支持工作记忆的生物过程的机械理解，结果好坏参半。在最近的一项研究中，人们发现，theta-tACS（6 Hz）刺激与健康成年人的学习范式同时应用，导致增强的性能相比，假的任务。在另一项研究中，作者将4.5Hz的频率应用于双侧半球，发现与假手术相比，tACS条件下的工作记忆得到了改善。如果不严格测试所有可能的范例，就不清楚哪种设置是最佳的。在这个项目中，您将使用数学建模和模拟来预测最佳刺激范式，以实现大脑网络连接的特定变化。您将结合联合收割机多种成像方式（磁共振成像- MRI，磁共振波谱- MRS，脑电图- EEG）与心理物理学，以探索大脑刺激对工作记忆的影响以及支持人类这种功能的神经网络。实验工作的结果将用于优化未来的刺激模式。主题本项目与医疗保健技术主题中的开发新疗法和拓展物理干预前沿（物理干预技术的个性化）挑战保持一致。使用非侵入性感觉、电和磁脑刺激（NIBS）来改善认知功能，用于脑损伤（如中风）后的康复，或延迟神经退行性变越来越受欢迎。刺激设备开发成本低，使用方便安全，甚至可以由患者在家中管理。尽管NIBS技术很受欢迎，但人们对NIBS技术如何与持续的大脑动力学相互作用的理解有限，这导致了临床环境中的混合结果，这意味着它的好处只是部分实现。候选人将利用我们实验室正在进行的工作，我们已经使用数学建模来预测如何使用NIBS来实现背外侧前额叶皮层的特定神经可塑性结果，辅助工作记忆这些预测将在健康队列中进行测试，提供原理证明，并为使用可应用于临床队列的这种刺激的标准化治疗方案奠定基础。

Transcranial direct current stimulation(tDCS), the application of electrical current directly to the scalp, has been shown to improve memory in healthy adults. More recently, researchers have investigated the benefits of using an alternating current(tACS) set to oscillate at a specific frequency chosen to interact with and entrain specific networks in the brain. It is thought that by optimising the parameters of the stimulation it might be possible to target specific neural networks and modulate their neurochemistry (as in the motor system) to enhance brain plasticity (the mechanism by which we learn new things). Developing a mathematical framework within which to test the effect of non-invasive brain stimulation on network plasticity and connectivity is crucial to furthering our understanding of working memory for normal development, preventative ageing, and as a potential therapeutic intervention for clinical populations.Working memory or 'short-term' memory abilities play an important role in the acquisition of complex skills during development and are strongly associated with academic abilities and language comprehension. Working memory impairments are commonly seen in neurodevelopmental disorders such as Autism and ADHD and neuropsychiatric disorders such as schizophrenia and depression, in patients that we study as part of our broader research team. Apart from cognitive training, there are no current treatments available for working memory impairments. Whilst several studies have used brain stimulation, the results are mixed due to the lack of mechanistic understanding of the biological processes that underpin working memory in healthy and pathological states. In a recent study, it was found that theta-tACS (6Hz) stimulation applied concurrently with a learning paradigm in healthy adults led to enhanced performance on a task compared to sham. In another study, the authors applied 4.5Hz bilaterally to both hemispheres and found that working memory was improved in the tACS condition compared to sham. Without rigorously testing all possible paradigms, it is unclear which set-up is optimal. In this project, you will use mathematical modelling and simulations to predict the optimal stimulus paradigm to achieve specific changes in brain network connectivity. You will combine multiple imaging modalities (magnetic resonance imaging - MRI, magnetic resonance spectroscopy - MRS, electroencephalography - EEG) in combination with psychophysics to probe the effects of brain stimulation on working memory and the neural networks that support this function in humans. The results of the experimental work will be used to optimise future stimulation paradigms. ThemesThis project specifically aligns with Developing New Therapies and Expanding the Frontiers of Physical Intervention (Personalisation of physical intervention technologies) challenges within the Healthcare Technology theme.The use of non-invasive sensory, electrical, and magnetic brain stimulation (NIBS) to improve cognitive function, for rehabilitation after brain damage, such as stroke, or to delay neurodegeneration is becoming increasingly popular. Stimulation devices are cheap to develop, easy and safe to use, and can even be administered by the patient in their home. Despite their popularity, there is limited understanding of how NIBS techniques interact with ongoing brain dynamics, which has led to mixed outcomes in clinical settings meaning that its benefits are only being partially realised.In this project, the candidate will capitalise on ongoing work from our lab where we have used mathematical modelling to predict how to use NIBS to achieve specific neuroplasticity outcomes in the dorsolateral prefrontal cortex to aid working memory. These predictions will be tested in a healthy cohort providing a proof-of-principle and laying the foundation towards standardising treatment protocols using stimulation of this kind that can be applied to clinical cohorts.