Research Article: In vivo functional neurochemistry of human cortical cholinergic function during visuospatial attention

Date Published: February 13, 2017

Publisher: Public Library of Science

Author(s): Michael Lindner, Tiffany Bell, Somya Iqbal, Paul Gerald Mullins, Anastasia Christakou, Andrea Motta.


Cortical acetylcholine is involved in key cognitive processes such as visuospatial attention. Dysfunction in the cholinergic system has been described in a number of neuropsychiatric disorders. Levels of brain acetylcholine can be pharmacologically manipulated, but it is not possible to directly measure it in vivo in humans. However, key parts of its biochemical cascade in neural tissue, such as choline, can be measured using magnetic resonance spectroscopy (MRS). There is evidence that levels of choline may be an indirect but proportional measure of acetylcholine availability in brain tissue. In this study, we measured relative choline levels in the parietal cortex using functional (event-related) MRS (fMRS) during performance of a visuospatial attention task, with a modelling approach verified using simulated data. We describe a task-driven interaction effect on choline concentration, specifically driven by contralateral attention shifts. Our results suggest that choline MRS has the potential to serve as a proxy of brain acetylcholine function in humans.

Partial Text

Cholinergic neurotransmission in the brain is important for cognitive functions such as selective attention [1] and various forms of learning [2], and has been implicated in a number of pathologies, including Alzheimer’s disease [3] and schizophrenia [4]. Cortical acetylcholine (ACH) involvement in visuospatial and sustained attention is well-documented in both animal [5,6] and, indirectly, in human research [7]. Despite its importance, although levels of ACH can be pharmacologically manipulated in both animals and humans, it is not possible to directly measure brain ACH in humans. Therefore, until now, it has not been possible to monitor the unperturbed central cholinergic system in humans. This study was designed to address this gap, using functional magnetic resonance spectroscopy (fMRS).

Using fMRS, we detected a task-related increase in CHO following visuospatial attention shifts. Importantly, this effect was specific to CHO, and specific to the MRS acquisition voxel contralateral to the attentional shift, in line with predictions.

This study provides direct evidence for the involvement of the human cortical cholinergic system in visuospatial attention. We used event-related MRS to track changes in the concentration of CHO in the POC during visuospatial attention shifts. We show task-related changes in CHO driven by concentration increases after attention shifts in the contralateral, but not in the ipsilateral hemi-field. This finding is in line with prior evidence for cholinergic involvement in visuospatial attention in this region [7], and for the laterality of processing attentional shifts [15,17,18]. This laterality effect is thought to be related to an indirect unilateral coupling of ACH release from the prefrontal to the parietal cortex in attention processes [33].




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