Exploring neurotransmission and pupil response changes in learning: A combined neuroimaging and eye tracking study

Glutamate and GABA are two important neurotransmitters in the brain. Glutamate is the main excitatory neurotransmitter, while GABA is the main inhibitory neurotransmitter. Glutamate and GABA work together to maintain a

balance between excitation and inhibition in the brain, which is essential for normal cognitive function. Imbalance in glutamate and GABA levels has been linked to various neurological and psychiatric disorders and may underlie cognitive

impairments (e.g., learning and memory disturbance) associated with these conditions. At the same time, oculomotor behaviour (eye movements) has been linked to memory encoding and retrieval processes, while an important

physiological indicator of cognitive and memory processing is the pupillary response, which reflects the activity of the autonomic nervous system. Previous studies (see e.g., Kafkas, 2021) have shown that variations in pupillary responses in

memory tasks are linked to differential neurotransmission in the brain and especially within prefrontal and hippocampal pathways, which are involved in memory formation and consolidation. However, to date, the degree to which glutamate

and GABA neurotransmission modulates oculomotor and pupillary responses in learning and memory tasks has not been investigated. This kind of association may provide a novel biomarker for cognitive/memory function and will allow understanding of the mechanisms that result in cognitive deficits in neurodevelopmental disorders.

In this proposed PhD projects, we will use the Rasopathies as model disorders known to be associated with GABA/Glutamate imbalances to investigate the relationship with oculomotor and pupil response. Cognitive disturbance, including learning, working memory and long-term memory difficulties, are common in the Rasopathies. The molecular and cellular mechanisms underlying cognitive impairment in Rasopathies have been studied using mouse models and show imbalance between GABA and Glutamate.

In this project, we will use cutting edge neuroimaging methods including MR Spectroscopy to measure the levels of GABA and glutamate in patients with Rasopathies as compared to healthy controls and to associate them with concurrently

acquired oculomotor and pupillary responses. We will also examine how these variables change while participants perform a memory task using functional MRS and concurrent eye tracking. By doing so, we hope to gain a better

understanding of how neurotransmitters modulate oculomotor activity and in turn learning and memory processes both in clinical and control populations. This understanding can help develop new targets for treatments or validate oculomotor and pupillary function as biomarkers for treatment and non-invasive brain stimulation.