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The Work in Progress (WIP) meetings provide an informal and constructive forum for researchers to get feedback on planned imaging projects from a diverse WIN audience.

 

WIN Wednesday Works In Progress

RoADPain - Understanding the Role of Adolescent Dysmenorrhoea as a risk factor for the transition to chronic Pain: Clinical Cohort Study

Lydia Coxon, Katy Vincent, Krina Zondervan, Mina Fazel, Gemma Sharp, Sharon Dixon, Kate Stein, MaryAnn Noonan, Emma Cox.

Chronic pain is defined as pain that lasts for more than 3 months. It is really common, affecting up to 30% of people worldwide with impacts on all areas of life. Chronic pain is difficult to treat once it has developed. Therefore, understanding which people might be at risk of developing chronic pain and protecting them from it starting, would be a really positive step forward.
We know that women are more likely to develop almost all types of chronic pain than men. We start to see this sex difference in chronic pain after puberty, suggesting that changes happening at this time may be contributing to this increased risk. One important change that happens at this time is periods starting. Despite periods often being very painful, period pain has traditionally been dismissed as “normal” and something girls must learn to live with.
However, in adult women with period pain we see many differences across a range of body systems when compared to women without period pain. These include increased sensitivity to pain; increased sensitivity of the bladder, bowel and womb; altered brain structure and function; and altered responses to stress. Similar changes to those seen with period pain can be seen in other chronic pain conditions. We don’t know whether these changes are caused by repeated or continuous pain or if they are part of the reason why chronic pain develops, or a combination of both.
For this we are undertaking a clinical study (as well as epidemiological work) with the aim to see whether the differences in other body systems described above in adult women with period pain are also seen in girls in the first few years of having periods.
For this clinical study we will recruit a group of adolescent girls, including those with and without period pain, 1, 3 and 5 years after starting their periods; with 20 individuals in each of the six groups. With their agreement, we will undertake tests to understand more about their body systems and pain. These will include phyiosological assessment and fMRI data at two time points (during menstruation and during follicular phase).

 

WIN Wednesday Works In ProgressQuantifying brain glutamate alterations after flickering checkerboard stimulation

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Effects of esketamine challenge on brain glutamate release measured via 7-Tesla functional magnetic resonance spectroscopy (7T-fMRS) in healthy participants.

Sylvana Vilca-Melendez, Riccardo De Giorgi, Dr Beata Godlewska, Dr Betina Ip, Dr William Clarke and Professor Phil Cowen

With the advancement of MRS techniques, exploring the dynamics of brain neurochemistry has become novel method of understanding and treating psychiatric disorders. Glutamate, the primary excitatory neurotransmitter in the brain, has been implicated in various psychiatric diseases like depression. However, assessing this glutamate activity for psychiatric use has been larely inconclusive. Addressing this gap, our team has piloted a novel 7T functional Magnetic Resonance Spectroscopy (fMRS) protocol. This non-invasive technique utilises a "flickering checkerboard" visual stimulus to measure brain (V1) glutamate levels, in a simplified protocol.

The first of our two studies aims to validate this method in a larger group of healthy participants, that replicates our previous tech dev research. By examining changes in glutamate levels during visual stimulation, we seek to establish a robust and clinically applicable measure for glutamate release.

The second study builds upon this foundation to explore the effects of esketamine, a licensed NMDA-R antagonist for treatment-resistant depression, on brain glutamate release in healthy individuals. Utilizing a controlled, cross-over design, participants will be administered esketamine or a placebo, hypothesizing that esketamine will prompt a significant increase in glutamate release. This study has the potential to greatly impact our understanding of the mechanistic role of glutamate in depression and the therapeutic response to antidepressants.

 

WIN Wednesday Works In Progress

How does the human brain construct narratives?

Xenia Grande, Jill O'Reilly, Helen Barron

To guide our everyday decisions and social interactions, we construct narratives that organise events by 'when' and 'where' they happened. As everyday experiences rarely unfold in a linear manner along 'when/where' dimensions, we usually construct narratives from entangled and indirectly experienced events. Here we ask: What enables the brain to first segregate events into their basic 'when/where' structure, and then relate these events into a coherent narrative based on that structure? Different entorhinal subregions can code for distinct structural 'when/where' information and hippocampal replay can reorganize and link distant events. Therefore, we propose that replay may link events according to structural information from distinct entorhinal-hippocampal functional anatomical loops. We plan to obtain high-field fMRI data during a narrative learning task, alongside intracranial EEG data collection in patients with epilepsy. Using resting-state connectivity and representational similarity analysis, we aim to identify entorhinal-hippocampal functional anatomical loops for 'when/where' structural information and to probe changes in event structure after narrative learning. Additionally, we aim to apply probabilistic classifier decoding to identify sequential reactivation (‘replay’) of events along the dimensions of 'when' and 'where' as narratives are reconstructed during rest.