TY - JOUR

T1 - Functional neurochemical imaging of the human striatal cholinergic system during reversal learning

AU - Bell, Tiffany

AU - Lindner, Michael

AU - Mullins, Paul Gerald

AU - Christakou, Anastasia

N1 - Funding Information Human Frontier Science Program. Grant Number: RGP0048/2012 Engineering and Physical Sciences Research Council. Grant Number: EP/L505043/1

PY - 2018/5/23

Y1 - 2018/5/23

N2 - Animal studies have shown that acetylcholine (ACh) levels in the dorsal striatum play a role in reversal learning. However, this has not been studied in humans due to a lack of appropriate non-invasive techniques. Proton magnetic resonance spectroscopy (1 H-MRS) can be used to measure metabolite levels in humans in vivo. Although it cannot be used to study ACh directly, 1 H-MRS can be used to study choline, an ACh precursor which is linked to activity-dependent ACh release. The aim of this study was to use functional-1 H-MRS (fMRS) to measure changes in choline levels in the human dorsal striatum during performance of a probabilistic reversal learning task. We demonstrate a task-dependent decrease in choline, specifically during reversal, but not initial, learning. We interpret this to reflect a sustained increase in ACh levels, which is in line with findings from the animal literature. This task-dependent change was specific to choline and was not observed in control metabolites. These findings provide support for the use of fMRS in the in vivo study of the human cholinergic system. This article is protected by copyright. All rights reserved.

AB - Animal studies have shown that acetylcholine (ACh) levels in the dorsal striatum play a role in reversal learning. However, this has not been studied in humans due to a lack of appropriate non-invasive techniques. Proton magnetic resonance spectroscopy (1 H-MRS) can be used to measure metabolite levels in humans in vivo. Although it cannot be used to study ACh directly, 1 H-MRS can be used to study choline, an ACh precursor which is linked to activity-dependent ACh release. The aim of this study was to use functional-1 H-MRS (fMRS) to measure changes in choline levels in the human dorsal striatum during performance of a probabilistic reversal learning task. We demonstrate a task-dependent decrease in choline, specifically during reversal, but not initial, learning. We interpret this to reflect a sustained increase in ACh levels, which is in line with findings from the animal literature. This task-dependent change was specific to choline and was not observed in control metabolites. These findings provide support for the use of fMRS in the in vivo study of the human cholinergic system. This article is protected by copyright. All rights reserved.

KW - Journal Article

KW - choline

KW - Magnetic Resonance Spectroscopy

KW - Reversal Learning

KW - Striatum

UR - https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1111%2Fejn.13803&file=ejn13803-sup-0001-reviewer_comments.pdf

U2 - 10.1111/ejn.13803

DO - 10.1111/ejn.13803

M3 - Article

C2 - 29265530

VL - 47

SP - 1184

EP - 1193

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 10

ER -