Curvilinear locus coeruleus functional connectivity trajectories over the adult lifespan: a 7T MRI study

The locus coeruleus (LC) plays a crucial role in modulating several higher order cognitive functions via its widespread projections to the entire brain. We set out to investigate the hypothesis that LC functional connectivity (FC) may fluctuate nonlinearly with age and explored its relation to memory function. To that end, 49 cognitively healthy individuals (19-74 years) underwent ultra high-resolution 7T resting-state functional magnetic resonance imaging and cognitive testing. FC patterns from the LC to regions of the isodendritic core network and cortical regions were examined using region of interest-to-region of interest analyses. Curvilinear patterns with age were observed for FC between the left LC and cortical regions and the nucleus basalis of Meynert. A linear negative association was observed between age and LC-FC and ventral tegmental area. Higher levels of FC between the LC and nucleus basalis of Meynert or ventral tegmental area were associated with lower memory performance from age of 40 years onward. Thus, different LC-FC patterns early in life can signal subtle memory deficits. Furthermore, these results highlight the importance of intact interactions between neurotransmitter systems for optimal cognitive aging.

[1]  Tobias Kober,et al.  MP2RAGE, a self bias-field corrected sequence for improved segmentation and T1-mapping at high field , 2010, NeuroImage.

[2]  D. Bangasser,et al.  Sex differences in stress regulation of arousal and cognition , 2017, Physiology & Behavior.

[3]  Paul M. Matthews,et al.  Relevance of parahippocampal-locus coeruleus connectivity to memory in early dementia , 2015, Neurobiology of Aging.

[4]  David H. Salat,et al.  Distinct functional networks within the cerebellum and their relation to cortical systems assessed with independent component analysis , 2012, NeuroImage.

[5]  R. Morris,et al.  Locus coeruleus and dopaminergic consolidation of everyday memory , 2016, Nature.

[6]  Shenmin Zhang,et al.  Resting-State Functional Connectivity of the Locus Coeruleus in Humans: In Comparison with the Ventral Tegmental Area/Substantia Nigra Pars Compacta and the Effects of Age. , 2016, Cerebral cortex.

[7]  I. Robertson.  A right hemisphere role in cognitive reserve , 2014, Neurobiology of Aging.

[8]  Jessica S. Damoiseaux,et al.  Effects of aging on functional and structural brain connectivity , 2017, NeuroImage.

[9]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[10]  M. Hamilton.  A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.

[11]  G. Paxinos,et al.  THE HUMAN NERVOUS SYSTEM , 1975 .

[12]  J. Jolles,et al.  Normative data for the Animal, Profession and Letter M Naming verbal fluency tests for Dutch speaking participants and the effects of age, education, and sex , 2006, Journal of the International Neuropsychological Society.

[13]  D. Hu,et al.  Decoding Lifespan Changes of the Human Brain Using Resting-State Functional Connectivity MRI , 2012, PloS one.

[14]  P. Yates,et al.  The effects of ageing on the pigmented nerve cells of the human locus caeruleus and substantia nigra , 1979, Acta Neuropathologica.

[15]  Keith A. Johnson,et al.  Tau and amyloid β proteins distinctively associate to functional network changes in the aging brain , 2017, Alzheimer's & Dementia.

[16]  C. Jack,et al.  Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers , 2013, The Lancet Neurology.

[17]  A. Dale,et al.  Critical ages in the life course of the adult brain: nonlinear subcortical aging , 2013, Neurobiology of Aging.

[18]  Olivier Salvado,et al.  Basal forebrain atrophy correlates with amyloid β burden in Alzheimer's disease , 2014, NeuroImage: Clinical.

[19]  Dimo Ivanov,et al.  High-resolution in vivo imaging of human locus coeruleus by magnetization transfer MRI at 3T and 7T , 2017, NeuroImage.

[20]  Paul S. Morgan,et al.  In vivo mapping of the human locus coeruleus , 2009, NeuroImage.

[21]  P. Viviani,et al.  The relation between linear extent and velocity in drawing movements , 1983, Neuroscience.

[22]  Dietmar R. Thal,et al.  Stages of the Pathologic Process in Alzheimer Disease: Age Categories From 1 to 100 Years , 2011, Journal of neuropathology and experimental neurology.

[23]  Hang Joon Jo,et al.  Correcting Brain-Wide Correlation Differences in Resting-State FMRI , 2013, Brain Connect..

[24]  Hui Zheng,et al.  Differential age-dependent associations of gray matter volume and white matter integrity with processing speed in healthy older adults , 2015, NeuroImage.

[25]  Steven Mennerick,et al.  Synaptic Activity Regulates Interstitial Fluid Amyloid-β Levels In Vivo , 2005, Neuron.

[26]  W. Kamphorst,et al.  Increased activity of surviving locus ceruleus neurons in Alzheimer's disease , 1999, Annals of neurology.

[27]  Cheryl L Grady,et al.  Changes in memory processing with age , 2000, Current Opinion in Neurobiology.

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

[29]  G. Fink,et al.  Noradrenergic modulation of cortical networks engaged in visuomotor processing. , 2010, Cerebral cortex.

[30]  P. Goldman-Rakic,et al.  Catecholamines and Cognitive Decline in Aged Nonhuman Primates , 1985, Annals of the New York Academy of Sciences.

[31]  Stefan Teipel,et al.  Cholinergic basal forebrain atrophy predicts amyloid burden in Alzheimer's disease , 2014, Neurobiology of Aging.

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

[33]  R. Dixon,et al.  Age-related cognitive deficits mediated by changes in the striatal dopamine system. , 2000, The American journal of psychiatry.

[34]  Jonathan D. Power,et al.  Prediction of Individual Brain Maturity Using fMRI , 2010, Science.

[35]  Yong He,et al.  Topological organization of the human brain functional connectome across the lifespan , 2013, Developmental Cognitive Neuroscience.

[36]  Michael W. L. Chee,et al.  Reduced functional segregation between the default mode network and the executive control network in healthy older adults: A longitudinal study , 2016, NeuroImage.

[37]  L. K. Hansen,et al.  Independent component analysis of functional MRI: what is signal and what is noise? , 2003, Current Opinion in Neurobiology.

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

[39]  Katrin Amunts,et al.  Stereotaxic probabilistic maps of the magnocellular cell groups in human basal forebrain , 2008, NeuroImage.

[40]  M. Mather,et al.  Neuromelanin marks the spot: identifying a locus coeruleus biomarker of cognitive reserve in healthy aging , 2016, Neurobiology of Aging.

[41]  Joaquín Goñi,et al.  Changes in structural and functional connectivity among resting-state networks across the human lifespan , 2014, NeuroImage.

[42]  Steen Moeller,et al.  Multiband multislice GE‐EPI at 7 tesla, with 16‐fold acceleration using partial parallel imaging with application to high spatial and temporal whole‐brain fMRI , 2010, Magnetic resonance in medicine.

[43]  G. Aston-Jones,et al.  Locus coeruleus activity in monkey: Phasic and tonic changes are associated with altered vigilance , 1994, Brain Research Bulletin.

[44]  Daniel J Bauer,et al.  Probing Interactions in Fixed and Multilevel Regression: Inferential and Graphical Techniques , 2005, Multivariate behavioral research.

[45]  Markus H. Sneve,et al.  Functional connectivity change across multiple cortical networks relates to episodic memory changes in aging , 2015, Neurobiology of Aging.

[46]  N B Smith,et al.  New high dielectric constant materials for tailoring the B1+ distribution at high magnetic fields. , 2010, Journal of magnetic resonance.

[47]  S. Gentleman,et al.  Nucleus basalis of Meynert revisited: anatomy, history and differential involvement in Alzheimer’s and Parkinson’s disease , 2015, Acta Neuropathologica.

[48]  Arno Klein,et al.  Evaluation of 14 nonlinear deformation algorithms applied to human brain MRI registration , 2009, NeuroImage.

[49]  Jelle Jolles,et al.  The Stroop Color-Word Test , 2006, Assessment.

[50]  Susan L. Whitfield-Gabrieli,et al.  Conn: A Functional Connectivity Toolbox for Correlated and Anticorrelated Brain Networks , 2012, Brain Connect..

[51]  Jonathan D. Cohen,et al.  Reduced Sensitivity to Immediate Reward during Decision-Making in Older than Younger Adults , 2012, PloS one.

[52]  Jelle Jolles,et al.  Rey's verbal learning test: Normative data for 1855 healthy participants aged 24–81 years and the influence of age, sex, education, and mode of presentation , 2005, Journal of the International Neuropsychological Society.

[53]  Alberto Gatti,et al.  The role of iron and copper molecules in the neuronal vulnerability of locus coeruleus and substantia nigra during aging. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[54]  L. Grinberg,et al.  Turning on the Light Within: Subcortical Nuclei of the Isodentritic Core and their Role in Alzheimer's Disease Pathogenesis. , 2015, Journal of Alzheimer's disease : JAD.

[55]  Darrell A. Worthy,et al.  Adult age differences in frontostriatal representation of prediction error but not reward outcome , 2014, Cognitive, affective & behavioral neuroscience.

[56]  Nick C. Fox,et al.  Longitudinal and cross-sectional analysis of atrophy in Alzheimer's disease: Cross-validation of BSI, SIENA and SIENAX , 2007, NeuroImage.

[57]  N. Lemon,et al.  Dopamine D1/D5 Receptors Contribute to De Novo Hippocampal LTD Mediated by Novel Spatial Exploration or Locus Coeruleus Activity , 2011, Cerebral cortex.

[58]  Zul Merali,et al.  Functional interactions between dopamine, serotonin and norepinephrine neurons: an in-vivo electrophysiological study in rats with monoaminergic lesions. , 2008, The international journal of neuropsychopharmacology.

[59]  Christian Sorg,et al.  A new integrative model of cerebral activation, deactivation and default mode function in Alzheimer’s disease , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[60]  P. Goldman-Rakic,et al.  Regional changes of monoamines in cerebral cortex and subcortical structures of aging rhesus monkeys , 1981, Neuroscience.

[61]  L. Grinberg,et al.  Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer's disease , 2017, Neuropathology and applied neurobiology.

[62]  S. Mizumori,et al.  Ventral tegmental area and substantia nigra neural correlates of spatial learning. , 2011, Learning & memory.

[63]  D. German,et al.  Locus coeruleus cell loss in the aging human brain: A non‐random process , 1995, The Journal of comparative neurology.

[64]  Denise C. Park,et al.  Decreased segregation of brain systems across the healthy adult lifespan , 2014, Proceedings of the National Academy of Sciences.

[65]  G. Dai,et al.  Neuroanatomic Connectivity of the Human Ascending Arousal System Critical to Consciousness and Its Disorders , 2012, Journal of neuropathology and experimental neurology.

[66]  Palmer O. Johnson,et al.  The Johnson-Neyman technique, its theory and application , 1950, Psychometrika.

[67]  H. Braak,et al.  The pathological process underlying Alzheimer’s disease in individuals under thirty , 2011, Acta Neuropathologica.

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

[69]  Ching-Po Lin,et al.  Age‐Related Changes in Resting‐State Networks of A Large Sample Size of Healthy Elderly , 2015, CNS neuroscience & therapeutics.

[70]  Mark A. Eckert,et al.  Histologic validation of locus coeruleus MRI contrast in post-mortem tissue , 2015, NeuroImage.

[71]  Wade K. Smith,et al.  The human locus coeruleus: computer reconstruction of cellular distribution , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[72]  Emery N. Brown,et al.  In vivo functional connectome of human brainstem nuclei of the ascending arousal, autonomic, and motor systems by high spatial resolution 7-Tesla fMRI , 2016, Magnetic Resonance Materials in Physics, Biology and Medicine.

[73]  Chris Zarow,et al.  Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. , 2003, Archives of neurology.

[74]  H. Olpe,et al.  Age-related decline in the activity of noradrenergic neurons of the rat locus coeruleus , 1982, Brain Research.

[75]  J. Gabrieli,et al.  Insights into the ageing mind: a view from cognitive neuroscience , 2004, Nature Reviews Neuroscience.