Optimising non-invasive brain stimulation to enhance working memory.

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.

Themes

This 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.