Catecholaminergic neuromodulation shapes intrinsic MRI functional connectivity in the human brain

TY - JOUR

T1 - Catecholaminergic neuromodulation shapes intrinsic MRI functional connectivity in the human brain

AU - van den Brink, Ruud Lucas

AU - Pfeffer, Thomas

AU - Warren, Christopher

AU - Murphy, Peter

AU - Tona, Klodiana-Daphne

AU - van der Wee, Nic

AU - Giltay, Eric

AU - van Noorden, Martijn

AU - Rombouts, Serge

AU - Donner, Tobias

AU - Nieuwenhuis, Sander

PY - 2016/7/27

Y1 - 2016/7/27

N2 - The brain commonly exhibits spontaneous (i.e., in the absence of a task) fluctuations in neural activity that are correlated across brainregions. It has been established that the spatial structure, or topography, of these intrinsic correlations is in part determined by the fixedanatomical connectivity between regions. However, it remains unclear which factors dynamically sculpt this topography as a function ofbrain state. Potential candidate factors are subcortical catecholaminergic neuromodulatory systems, such as the locus ceruleusnorepinephrinesystem, which send diffuse projectionsto most parts ofthe forebrain. Here, we systematically characterizedthe effects ofendogenous central neuromodulation on correlated fluctuations during rest in the human brain. Using a double-blind placebocontrolledcrossover design, we pharmacologically increased synaptic catecholamine levels by administering atomoxetine, an NE transporterblocker, and examined the effects on the strength and spatial structure of resting-state MRI functional connectivity. First,atomoxetine reducedthe strength ofinter-regional correlations acrossthree levels of spatial organization,indicatingthat catecholaminesreducethe strength of functional interactions during rest. Second,this modulatory effect on intrinsic correlations exhibited a substantialdegree of spatial specificity:the decrease infunctional connectivity showed an anterior–posterior gradient inthe cortex, depended onthestrength of baseline functional connectivity, and was strongest for connections between regions belonging to distinct resting-statenetworks. Thus, catecholamines reduce intrinsic correlations in a spatially heterogeneous fashion. We concludethat neuromodulation isan important factor shaping the topography of intrinsic functional connectivity.

AB - The brain commonly exhibits spontaneous (i.e., in the absence of a task) fluctuations in neural activity that are correlated across brainregions. It has been established that the spatial structure, or topography, of these intrinsic correlations is in part determined by the fixedanatomical connectivity between regions. However, it remains unclear which factors dynamically sculpt this topography as a function ofbrain state. Potential candidate factors are subcortical catecholaminergic neuromodulatory systems, such as the locus ceruleusnorepinephrinesystem, which send diffuse projectionsto most parts ofthe forebrain. Here, we systematically characterizedthe effects ofendogenous central neuromodulation on correlated fluctuations during rest in the human brain. Using a double-blind placebocontrolledcrossover design, we pharmacologically increased synaptic catecholamine levels by administering atomoxetine, an NE transporterblocker, and examined the effects on the strength and spatial structure of resting-state MRI functional connectivity. First,atomoxetine reducedthe strength ofinter-regional correlations acrossthree levels of spatial organization,indicatingthat catecholaminesreducethe strength of functional interactions during rest. Second,this modulatory effect on intrinsic correlations exhibited a substantialdegree of spatial specificity:the decrease infunctional connectivity showed an anterior–posterior gradient inthe cortex, depended onthestrength of baseline functional connectivity, and was strongest for connections between regions belonging to distinct resting-statenetworks. Thus, catecholamines reduce intrinsic correlations in a spatially heterogeneous fashion. We concludethat neuromodulation isan important factor shaping the topography of intrinsic functional connectivity.

M3 - SCORING: Journal article

C2 - 27466332

VL - 36

SP - 7865

EP - 7876

JO - J NEUROSCI

JF - J NEUROSCI

SN - 0270-6474

IS - 30

ER -