Catecholaminergic manipulation alters dynamic network topology across cognitive states

The human brain is able to flexibly adapt its information processing capacity to meet a variety of cognitive challenges. Recent evidence suggests that this flexibility is reflected in the dynamic reorganization of the functional connectome. The ascending catecholaminergic arousal systems of the brain are a plausible candidate mechanism for driving alterations in network architecture, enabling efficient deployment of cognitive resources when the environment demands them. We tested this hypothesis by analyzing both resting state and task-based fMRI data following the administration of atomoxetine, a noradrenaline reuptake inhibitor, compared to placebo, in two separate human fMRI studies. Our results demonstrate that the manipulation of central catecholamine levels leads to a reorganization of the functional connectome in a manner that is sensitive to ongoing cognitive demands.

[1]  Thomas E. Nichols,et al.  Nonparametric permutation tests for functional neuroimaging: A primer with examples , 2002, Human brain mapping.

[2]  D. McCormick,et al.  Pupil fluctuations track rapid changes in adrenergic and cholinergic activity in cortex , 2016, Nature Communications.

[3]  Ricardo M. Neves,et al.  Modeling the effect of locus coeruleus firing on cortical state dynamics and single-trial sensory processing , 2015, Proceedings of the National Academy of Sciences.

[4]  S. Nieuwenhuis,et al.  The anatomical and functional relationship between the P3 and autonomic components of the orienting response. , 2011, Psychophysiology.

[5]  Kent A. Kiehl,et al.  A method for evaluating dynamic functional network connectivity and task-modulation: application to schizophrenia , 2010, Magnetic Resonance Materials in Physics, Biology and Medicine.

[6]  G. Aston-Jones,et al.  Atomoxetine modulates spontaneous and sensory-evoked discharge of locus coeruleus noradrenergic neurons , 2013, Neuropharmacology.

[7]  Jonathan D. Power,et al.  Multi-task connectivity reveals flexible hubs for adaptive task control , 2013, Nature Neuroscience.

[8]  Jonathan D. Cohen,et al.  An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. , 2005, Annual review of neuroscience.

[9]  Russell A. Poldrack,et al.  Principles of dynamic network reconfiguration across diverse brain states , 2017, NeuroImage.

[10]  R. Guimerà,et al.  Functional cartography of complex metabolic networks , 2005, Nature.

[11]  Silvio Garattini,et al.  Role of presynaptic α2-adrenoceptors in antidepressant action: recent findings from microdialysis studies , 2004, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[12]  R. Wise,et al.  Dopamine Uptake through the Norepinephrine Transporter in Brain Regions with Low Levels of the Dopamine Transporter: Evidence from Knock-Out Mouse Lines , 2002, The Journal of Neuroscience.

[13]  Olaf Sporns,et al.  Complex network measures of brain connectivity: Uses and interpretations , 2010, NeuroImage.

[14]  D. McCormick,et al.  Waking State: Rapid Variations Modulate Neural and Behavioral Responses , 2015, Neuron.

[15]  R. Oostenveld,et al.  Stress-Related Noradrenergic Activity Prompts Large-Scale Neural Network Reconfiguration , 2011, Science.

[16]  O. Sporns,et al.  The economy of brain network organization , 2012, Nature Reviews Neuroscience.

[17]  J D Cohen,et al.  A network model of catecholamine effects: gain, signal-to-noise ratio, and behavior. , 1990, Science.

[18]  B. T. Thomas Yeo,et al.  Interpreting temporal fluctuations in resting-state functional connectivity MRI , 2017, NeuroImage.

[19]  George H. Denfield,et al.  Pupil Fluctuations Track Fast Switching of Cortical States during Quiet Wakefulness , 2014, Neuron.

[20]  Peter R Murphy,et al.  Catecholaminergic Neuromodulation Shapes Intrinsic MRI Functional Connectivity in the Human Brain , 2016, The Journal of Neuroscience.

[21]  David A. Leopold,et al.  Dynamic functional connectivity: Promise, issues, and interpretations , 2013, NeuroImage.

[22]  Jörn Diedrichsen,et al.  A probabilistic MR atlas of the human cerebellum , 2009, NeuroImage.

[23]  Jukka-Pekka Onnela,et al.  Community Structure in Time-Dependent, Multiscale, and Multiplex Networks , 2009, Science.

[24]  Dennis Hernaus,et al.  Noradrenaline transporter blockade increases fronto-parietal functional connectivity relevant for working memory , 2017, European Neuropsychopharmacology.

[25]  Harold W. Kuhn,et al.  The Hungarian method for the assignment problem , 1955, 50 Years of Integer Programming.

[26]  Sharon L. Thompson-Schill,et al.  A Functional Cartography of Cognitive Systems , 2015, PLoS Comput. Biol..

[27]  S. Sara,et al.  Orienting and Reorienting: The Locus Coeruleus Mediates Cognition through Arousal , 2012, Neuron.

[28]  C. Berridge,et al.  The locus coeruleus–noradrenergic system: modulation of behavioral state and state-dependent cognitive processes , 2003, Brain Research Reviews.

[29]  Edith Hamel,et al.  Locus Coeruleus Stimulation Recruits a Broad Cortical Neuronal Network and Increases Cortical Perfusion , 2013, The Journal of Neuroscience.

[30]  T. Robbins,et al.  The neuropsychopharmacology of fronto-executive function: monoaminergic modulation. , 2009, Annual review of neuroscience.

[31]  B. Sahakian,et al.  Default Mode Dynamics for Global Functional Integration , 2015, The Journal of Neuroscience.

[32]  Timothy O. Laumann,et al.  Methods to detect, characterize, and remove motion artifact in resting state fMRI , 2014, NeuroImage.

[33]  Vince D. Calhoun,et al.  Resting-State fMRI Dynamics and Null Models: Perspectives, Sampling Variability, and Simulations , 2017, bioRxiv.

[34]  M Corbetta,et al.  A Dynamic Core Network and Global Efficiency in the Resting Human Brain. , 2016, Cerebral cortex.

[35]  Ludovica Griffanti,et al.  Automatic denoising of functional MRI data: Combining independent component analysis and hierarchical fusion of classifiers , 2014, NeuroImage.

[36]  Ruud L. van den Brink,et al.  Norepinephrine transporter blocker atomoxetine increases salivary alpha amylase , 2017, Psychoneuroendocrinology.

[37]  M. D’Esposito,et al.  Inverted-U–Shaped Dopamine Actions on Human Working Memory and Cognitive Control , 2011, Biological Psychiatry.

[38]  Evan M. Gordon,et al.  On the Stability of BOLD fMRI Correlations , 2016, Cerebral cortex.

[39]  Jonathan D. Cohen,et al.  The effects of neural gain on attention and learning , 2013, Nature Neuroscience.

[40]  J. Gold,et al.  Relationships between Pupil Diameter and Neuronal Activity in the Locus Coeruleus, Colliculi, and Cingulate Cortex , 2016, Neuron.

[41]  Krzysztof J. Gorgolewski,et al.  The Dynamics of Functional Brain Networks: Integrated Network States during Cognitive Task Performance , 2015, Neuron.

[42]  G. Gessa,et al.  Alpha2‐adrenoceptor mediated co‐release of dopamine and noradrenaline from noradrenergic neurons in the cerebral cortex , 2004, Journal of neurochemistry.

[43]  S. Sara.  The locus coeruleus and noradrenergic modulation of cognition , 2009, Nature Reviews Neuroscience.

[44]  Danielle S. Bassett,et al.  Cognitive Network Neuroscience , 2015, Journal of Cognitive Neuroscience.

[45]  Raid Amin,et al.  Applied Statistics: Analysis of Variance and Regression , 2004, Technometrics.

[46]  E. Szabadi,et al.  Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part II: Physiological and Pharmacological Manipulations and Pathological Alterations of Locus Coeruleus Activity in Humans , 2008, Current neuropharmacology.

[47]  Russell A. Poldrack,et al.  Estimation of dynamic functional connectivity using Multiplication of Temporal Derivatives , 2015, NeuroImage.

[48]  Richard E. Carson,et al.  Clinical doses of atomoxetine significantly occupy both norepinephrine and serotonin transports: Implications on treatment of depression and ADHD , 2014, NeuroImage.

[49]  Jie Yang,et al.  Atomoxetine increases histamine release and improves learning deficits in an animal model of attention-deficit hyperactivity disorder: the spontaneously hypertensive rat. , 2008, Basic & clinical pharmacology & toxicology.

[50]  Danielle S Bassett,et al.  Learning-induced autonomy of sensorimotor systems , 2014, Nature Neuroscience.

[51]  K. Deisseroth,et al.  Tuning arousal with optogenetic modulation of locus coeruleus neurons , 2010, Nature Neuroscience.

[52]  Stephen V. David,et al.  Cortical Membrane Potential Signature of Optimal States for Sensory Signal Detection , 2015, Neuron.

[53]  Timothy O. Laumann,et al.  Generation and Evaluation of a Cortical Area Parcellation from Resting-State Correlations. , 2016, Cerebral cortex.

[54]  David M Devilbiss,et al.  Phasic and tonic patterns of locus coeruleus output differentially modulate sensory network function in the awake rat. , 2011, Journal of neurophysiology.

[55]  M. Reith,et al.  Structure and function of the dopamine transporter. , 2000, European journal of pharmacology.

[56]  Manfred G Kitzbichler,et al.  Cognitive Effort Drives Workspace Configuration of Human Brain Functional Networks , 2011, The Journal of Neuroscience.

[57]  Michael Breakspear,et al.  The modulation of neural gain facilitates a transition between functional segregation and integration in the brain , 2017, bioRxiv.

[58]  Berrin Maraşligil,et al.  İnsanlarda Yenilik N2 Yanıtı Hedef Uyaranların Zamansal Sınıflamasını Yansıtır , 2011 .

[59]  Thomas T. Liu,et al.  A component based noise correction method (CompCor) for BOLD and perfusion based fMRI , 2007, NeuroImage.

[60]  D. Woodward,et al.  Noradrenergic modulation of somatosensory cortical neuronal responses to lontophoretically applied putative neurotransmitters , 1980, Experimental Neurology.