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WIN Wednesday Works In Progress

Glutamate Response to Photostimulation in People Recovered from Depression (GLADE)

Presented by Sylvana Vilca-Melendez

Abstract: Glutamate is thought to play an important role in the causation and treatment of depression. It is possible to measure glutamate in the human brain using safe magnetic resonance imaging but results of studies of glutamate levels in people with depression and those at risk of depression have been inconclusive.

We have devised a functional magnetic resonance protocol whereby viewing a flickering checkerboard for a few minutes provides a measure of stimulated glutamate release. The aim of this study is to look at the effect of a flickering checkerboard on glutamate release in people who have recovered from depression and compare it to people who have not experienced depression. We hope from this to discover whether changes in glutamate activity might be a risk factor for the development of depression. This could be helpful both for diagnostic purposes and for the development of medications that can relieve depression by modifying glutamate release.

 

 

  

WIN Wednesday Works In Progress

Multimodal MRI characterisation of impact of metformin treatment on adult brain structure and function in Four Core Genotype (FCG) mice

Presented by Kamila Szulc-Lerch 

Abstract: Metformin, a commonly prescribed medication for managing type 2 diabetes, has recently gained attention for its potential as an anti-aging drug. While its primary role is to regulate blood sugar levels, studies have revealed that individuals taking metformin may experience a range of health benefits beyond glycaemic control. These potential benefits include an extension of both healthspan and lifespan, making metformin an exciting subject in the field of longevity science. Nonetheless, it's essential to highlight that further research and clinical trials are necessary to fully understand its long-term impact and safety when used for anti-aging purposes in the general population. In particular, our recent analysis of UK Biobank data, inspired by preclinical findings showing brain volume loss in mice following metformin treatment, investigated the impact of metformin on the human brain. This analysis revealed exacerbated brain volume loss in patients with diabetes who were taking metformin in an age and sex dependent manner. Recent studies in humans have shown that metformin also has the potential to lower testosterone levels. Given the overall association of testosterone levels with brain volume, it is plausible that metformin exerts its effects on the brain via its impact on testosterone. In this study, we will use Four Core Genotype mice to test this hypothesis. The use of this model will allow us to separate the impact of sex hormones (testosterone and oestrogen) from sex chromosomes by studying the response to metformin in XY and XX mice both having either male or female gonads. Our hypothesis is that the brain volume lowering effects of metformin are mediated by testosterone. We expect that this response will be diminished in XY mice with female gonads. We also expect that XX mice with male gonads will display a similar brain response to metformin as the standard male mice (XY mice with male gonads).

 

 

 

 

WIN Wednesday Works In Progress

Controlling social interactions using real-time fMRI neurofeedback 

Presented by Lanting Zhang 

Abstract: Observational learning encompasses the acquisition of cognitive and behavioural patterns from others through the process of observation, playing an important role in acquiring various social, occupational, and recreational skills. Previous computational models have successfully delineated the neural mechanisms linked to the capacity to observe others receiving rewards and subsequently adjusting one's own actions. For instance, individuals exhibit heightened activation in the inferior frontal gyrus (IFG) in the context of externally guided decision-making within social scenarios. However, this innate learning ability varies widely between individuals and is sometimes challenging to acquire and apply. We are now investigating whether reinforcing specific neural representations using real-time fMRI neurofeedback may improve an individuals' ability to make decisions based on the perceived value of others.

To do so, we will test whether people can use real-time fMRI neurofeedback to increase brain activation in the IFG regions, and to assess whether this enhancement results in improved performance in social decision-making tasks. The neurofeedback modulation involves two conditions: either up-regulating or down-regulating activity in the IFG, whilst performing the task, which reflects increasing or decreasing how much weight you place on others’ actions. We hypothesize that participants will be more likely to follow the agents’ choice in the up-regulated group, while the down-regulated group is expected to make decisions based on their own learning results. This behaviour change will be more prominent in the up-regulated group and will be positively correlated with ROI activation. We will also explore changes in other associated brain activations without making specific predictions.