PT  - JOURNAL ARTICLE
AU  - Christopher M. Warren
AU  - Eran Eldar
AU  - Ruud L. van den Brink
AU  - Klodiana-Daphne Tona
AU  - Nic J. van der Wee
AU  - Eric J. Giltay
AU  - Martijn S. van Noorden
AU  - Jos A. Bosch
AU  - Robert C. Wilson
AU  - Jonathan D. Cohen
AU  - Sander Nieuwenhuis
TI  - Catecholamine-Mediated Increases in Gain Enhance the Precision of Cortical Representations
AID  - 10.1523/JNEUROSCI.3475-15.2016
DP  - 2016 May 25
TA  - The Journal of Neuroscience
PG  - 5699--5708
VI  - 36
IP  - 21
4099  - http://www.jneurosci.org/content/36/21/5699.short
4100  - http://www.jneurosci.org/content/36/21/5699.full
SO  - J. Neurosci.2016 May 25; 36
AB  - Neurophysiological evidence suggests that neuromodulators, such as norepinephrine and dopamine, increase neural gain in target brain areas. Computational models and prominent theoretical frameworks indicate that this should enhance the precision of neural representations, but direct empirical evidence for this hypothesis is lacking. In two functional MRI studies, we examine the effect of baseline catecholamine levels (as indexed by pupil diameter and manipulated pharmacologically) on the precision of object representations in the human ventral temporal cortex using angular dispersion, a powerful, multivariate metric of representational similarity (precision). We first report the results of computational model simulations indicating that increasing catecholaminergic gain should reduce the angular dispersion, and thus increase the precision, of object representations from the same category, as well as reduce the angular dispersion of object representations from distinct categories when distinct-category representations overlap. In Study 1 (N = 24), we show that angular dispersion covaries with pupil diameter, an index of baseline catecholamine levels. In Study 2 (N = 24), we manipulate catecholamine levels and neural gain using the norepinephrine transporter blocker atomoxetine and demonstrate consistent, causal effects on angular dispersion and brain-wide functional connectivity. Despite the use of very different methods of examining the effect of baseline catecholamine levels, our results show a striking convergence and demonstrate that catecholamines increase the precision of neural representations.SIGNIFICANCE STATEMENT Norepinephrine and dopamine are among the most widely distributed and ubiquitous neuromodulators in the mammalian brain and have a profound and pervasive impact on cognition. Baseline catecholamine levels tend to increase with increasing task engagement in tasks involving perceptual decisions, yet there is currently no direct evidence of the specific impact of these increases in catecholamine levels on perceptual encoding. Our results fill this void by showing that catecholamines enhance the precision of encoding cortical object representations, and by suggesting that this effect is mediated by increases in neural gain, thus offering a mechanistic account of our key finding.