Results and Publications

Publications:

For a list of our publications, see https://the-epic-study.quarto.pub/the-epic-project/Publications.html

Results:

A preprint of our first study is available here: https://doi.org/10.64898/2026.02.13.705729.

Before testing participants with psychosis we began by testing the scanning protocols and experimental task in healthy control participants. We recorded neurochemical levels from a region of medial frontal cortex non-invasively using an MRI technique called MR spectroscopy (MRS) while participants performed a working memory task and a simple visual (control) task.

In the memory task participants learned the colour, shape and location of four stimuli (the encoding phase) and then recalled the colour of one item from either a shape cue or a location cue (the recall phase). In the control task participants selected the colour of a single item from four colour options.

In our exciting results, we were able to see the change in glutamate (the brain’s main excitatory neurotransmitter) over time from the onset of the stimuli. We observed an increase in glutamate peaking at 1.1 seconds during the encoding phase and peaking at 1.4 seconds in the recall phase, compared to the during the control task in which there was no systematic change in glutamate over time. Ours study is the first MR spectroscopy study to show how the glutamate response changes over time after stimulus onset. This is really important as it means we can determine the best time to record glutamate from in future studies. Individuals with psychosis often report being slowed in their processing speed, so we can also assess if the glutamate time course is slower in individuals with psychosis.

We did not find any overall change in GABA (the main inhibitory neurotransmitter) across participants during the memory trials compared to the control trials, but individuals who had higher GABA levels during the memory trials compared to the control trials tended to be better at the working memory task than those who had lower GABA levels in the memory trials.

0.00.51.01.52.02.5Time since stimulus onset (seconds)-2-1012345678Glutamate (% change from control)EncodingRecall-3-2-10123456Glutamate (% change from baseline)0.00.51.01.52.02.5ControlEncodingRecallTime since stimulus onset (s)-3-3-2-2-1-100112233445566****Front ofheadFront of headBack ofheadBack of headCross section from side viewLeft ofheadRight ofheadRightLeftCross section from face-onCross section from underneathOrange/red and blue areas show areas of activation from fMRI, which measures changes indeoxygenated and oxygenated blood concentration as an indicator of brain activity.Orange/red areas are more active for trials involving a working memory task compared to a simplevisual task. Blue areas are more active during the simple visual task.We recorded brain chemicals from the square region in green.In the above plots, we can see the change in glutamate in response to the stimuli over time. Duringcontrol trials, there is little change in the glutamate levels. In the encoding phase and the recallphase of the working memory trials we see a significant increase in glutamate.The plots above show the % change in glutamate (top) and GABA (bottom) during the encoding phase (orange) and the recall phase (red) compared to control trials (indicated by the bluelines). This data is taken from the middle 1.25 s of the response window rather than the full 2.5 s, to focus on the peak of the glutamate response.The middle and right plots show the correlations between the change in glutamate and GABA during encoding and recall compared to working memory accuracy (middle) and reaction time(right).Spot that participants with higher GABA levels are more accurate and are faster.In control trials, participants had to respond to the coloured item.In the memory trials, participants learned the colour, shape and location of four items,and then had to recall the colour of the shape from either a location cue or a shape cue.(Arrows are just to demonstrate the correct answers for these examples)ORRecallphase2.5sEncodingphase2.5sTimeTimeMask topreventafterimagesMask topreventafterimagesMask topreventafterimagesMask topreventafterimagesControltrial 2.5sMemory TrialControl Trial505560657075808590Working memory accuracy (%)Working memory accuracy (%)505560657075808590Glu (% change from control)1.151.251.351.451.55Working memory reaction time (s)Working memory reaction time (s)1.151.251.351.451.55EncodingRecall*******EncodingRecallGlu (% change from control)0.00.51.01.52.02.53.54.04.53.0-2.0-1.0GABA (% change from control)GABA (% change from control)0.01.02.03.04.0-5.0-4.0-3.0-10-505101520Glu (% change from control)-10-505101520GABA (% change from control)-30-20-100102030-30-40-20-10010203040RecallEncodingr= 0.10p= .695r= 0.18p= .455RecallEncodingr= -0.10p= .669r= -0.15p= .537RecallEncodingr= -0.47p= .049r= -0.43p= .074RecallEncodingr= 0.60p= .008r= 0.42p= .0831.151.251.351.451.551.151.251.351.451.55GlutamateGABA