Insulin sensitivity predicts brain network connectivity following a meal

&NA; There is converging evidence that insulin plays a role in food‐reward signaling in the brain and has effects on enhancing cognition. Little is known about how these effects are altered in individuals with insulin resistance. The present study was designed to identify the relationships between insulin resistance and functional brain connectivity following a meal. Eighteen healthy adults (7 male, 11 female, age: 41‐57 years‐old) completed a frequently‐sampled intravenous glucose tolerance test to quantify insulin resistance. On separate days at least one week apart, a resting state functional magnetic resonance imaging scan was performed: once after a mixed‐meal and once after a 12‐h fast. Seed‐based resting state connectivity of the caudate nucleus and eigenvector centrality were used to identify relationships between insulin resistance and functional brain connectivity. Individuals with greater insulin resistance displayed stronger connectivity within reward networks following a meal suggesting insulin was less able to suppress reward. Insulin resistance was negatively associated with eigenvector centrality in the dorsal anterior cingulate cortex following a meal. These data suggest that individuals with less sensitivity to insulin may fail to shift brain networks away from reward and toward cognitive control following a meal. This altered feedback loop could promote overeating and obesity. HighlightsInsulin plays a role in food‐reward signaling in the brain.It is not understood how insulin resistance affects insulin's ability to modulate brain networks.We examined associations between insulin resistance and brain connectivity.Individuals with lower insulin sensitivity maintain reward connectivity after a meal.Higher insulin sensivity is associated with stronger connectivity in cognitive control regions.

[1]  S. Spoor,et al.  1 AlleleTaqResponse to Food Is Moderated by Relation Between Obesity and Blunted Striatal , 2008 .

[2]  C. Benedict,et al.  Intranasal administration of insulin to the brain impacts cognitive function and peripheral metabolism , 2012, Diabetes, obesity & metabolism.

[3]  O. Sporns,et al.  Network hubs in the human brain , 2013, Trends in Cognitive Sciences.

[4]  H. Lu,et al.  Resting-State Functional Connectivity in Rat Brain , 2005 .

[5]  Danielle S Bassett,et al.  Brain graphs: graphical models of the human brain connectome. , 2011, Annual review of clinical psychology.

[6]  Paul Witkovsky,et al.  Insulin enhances striatal dopamine release by activating cholinergic interneurons and thereby signals reward , 2015, Nature Communications.

[7]  Hubert Preissl,et al.  Intranasal Insulin Modulates Intrinsic Reward and Prefrontal Circuitry of the Human Brain in Lean Women , 2012, Neuroendocrinology.

[8]  Y. Z. Ider,et al.  Quantitative estimation of insulin sensitivity. , 1979, The American journal of physiology.

[9]  Hubert Preissl,et al.  Insulin modulates food-related activity in the central nervous system. , 2010, The Journal of clinical endocrinology and metabolism.

[10]  J. Michael Schurr,et al.  Relation Between Obesity and Blunted Striatal Response to Food Is Moderated by TaqIA A1 Allele , 2008, Science.

[11]  Frederico G. S. Toledo,et al.  Antidiabetogenic effects of hydroxychloroquine on insulin sensitivity and beta cell function: a randomised trial , 2015, Diabetologia.

[12]  E T Rolls,et al.  Taste, olfactory and food texture reward processing in the brain and obesity , 2011, International Journal of Obesity.

[13]  Paul J. Laurienti,et al.  Meal replacement: calming the hot-state brain network of appetite , 2014, Front. Psychol..

[14]  Johan N Lundström,et al.  Identification of human gustatory cortex by activation likelihood estimation , 2011, Human brain mapping.

[15]  L. Nummenmaa,et al.  Dorsal Striatum and Its Limbic Connectivity Mediate Abnormal Anticipatory Reward Processing in Obesity , 2012, PloS one.

[16]  G. E. Alexander,et al.  Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions. , 1990, Progress in brain research.

[17]  D. Small,et al.  Relation of reward from food intake and anticipated food intake to obesity: a functional magnetic resonance imaging study. , 2008, Journal of abnormal psychology.

[18]  T C Adam,et al.  Insulin sensitivity and brain reward activation in overweight Hispanic girls: a pilot study , 2015, Pediatric obesity.

[19]  H. Critchley,et al.  A Neural Circuitry Linking Insulin Resistance to Depressed Mood , 2012, Psychosomatic medicine.

[20]  E. Ravussin,et al.  Neuroimaging and Obesity , 2002, Annals of the New York Academy of Sciences.

[21]  D. V. Van Vugt,et al.  Insulin sensitivity affects corticolimbic brain responses to visual food cues in polycystic ovary syndrome patients , 2015, Hormone molecular biology and clinical investigation.

[22]  Eugene J. Barrett,et al.  Insulin Regulates Brain Function, but How Does It Get There? , 2014, Diabetes.

[23]  Edmund T. Rolls,et al.  Taste, olfactory and food texture reward processing in the brain and the control of appetite , 2012, Proceedings of the Nutrition Society.

[24]  A. Craig,et al.  How do you feel — now? The anterior insula and human awareness , 2009, Nature Reviews Neuroscience.

[25]  Angela R Laird,et al.  Neural Bases Of Food Perception: Coordinate-Based Meta-Analyses Of Neuroimaging Studies In Multiple Modalities , 2013, Obesity.

[26]  A. Dagher,et al.  Basal ganglia functional connectivity based on a meta-analysis of 126 positron emission tomography and functional magnetic resonance imaging publications. , 2006, Cerebral cortex.

[27]  N. Volkow,et al.  Food and drug reward: overlapping circuits in human obesity and addiction. , 2012, Current topics in behavioral neurosciences.

[28]  Kewei Chen,et al.  Neuroimaging and obesity: mapping the brain responses to hunger and satiation in humans using positron emission tomography. , 2002, Annals of the New York Academy of Sciences.

[29]  Hubert Preissl,et al.  Differential effect of glucose ingestion on the neural processing of food stimuli in lean and overweight adults , 2014, Human brain mapping.

[30]  Jan Born,et al.  Comparable sensitivity of postmenopausal and young women to the effects of intranasal insulin on food intake and working memory. , 2010, The Journal of clinical endocrinology and metabolism.

[31]  Hubert Preissl,et al.  Processing of food pictures: Influence of hunger, gender and calorie content , 2010, Brain Research.

[32]  Uta Wolfensteller,et al.  (Still) longing for food: Insulin reactivity modulates response to food pictures , 2013, Human brain mapping.

[33]  Hubert Preissl,et al.  Dissociation of GLP-1 and insulin association with food processing in the brain: GLP-1 sensitivity despite insulin resistance in obese humans , 2015, Molecular metabolism.

[34]  Marisa O. Hollinshead,et al.  The organization of the human cerebral cortex estimated by intrinsic functional connectivity. , 2011, Journal of neurophysiology.

[35]  Frederik Barkhof,et al.  Fast Eigenvector Centrality Mapping of Voxel-Wise Connectivity in Functional Magnetic Resonance Imaging: Implementation, Validation, and Interpretation , 2012, Brain Connect..

[36]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[37]  D. Porte,et al.  Insulin signaling in the central nervous system: a critical role in metabolic homeostasis and disease from C. elegans to humans. , 2005, Diabetes.

[38]  Ali Haeri,et al.  Insulin in the Brain: Sources, Localization and Functions , 2013, Molecular Neurobiology.

[39]  R. Buckner,et al.  The organization of the human striatum estimated by intrinsic functional connectivity. , 2012, Journal of neurophysiology.

[40]  Benjamin Y Hayden,et al.  Dorsal Anterior Cingulate Cortex: A Bottom-Up View. , 2016, Annual review of neuroscience.

[41]  Karl J. Friston,et al.  Structural and Functional Brain Networks: From Connections to Cognition , 2013, Science.

[42]  V. Menon,et al.  Saliency, switching, attention and control: a network model of insula function , 2010, Brain Structure and Function.

[43]  Hubert Preissl,et al.  Brain Insulin Resistance at the Crossroads of Metabolic and Cognitive Disorders in Humans. , 2016, Physiological reviews.

[44]  B. Balleine,et al.  A specific role for posterior dorsolateral striatum in human habit learning , 2009, The European journal of neuroscience.

[45]  E. Stice,et al.  Relative ability of fat and sugar tastes to activate reward, gustatory, and somatosensory regions. , 2013, The American journal of clinical nutrition.

[46]  Paul J. Laurienti,et al.  A New Measure of Centrality for Brain Networks , 2010, PloS one.

[47]  G. Glover,et al.  Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control , 2007, The Journal of Neuroscience.

[48]  O. Sporns,et al.  Network centrality in the human functional connectome. , 2012, Cerebral cortex.

[49]  S. Woods,et al.  Intraventricular insulin increases dopamine transporter mRNA in rat VTA/substantia nigra , 1994, Brain Research.

[50]  Jan Born,et al.  Intranasal insulin improves memory in humans , 2004, Psychoneuroendocrinology.

[51]  Jean Logan,et al.  Brain dopamine and obesity , 2001, The Lancet.

[52]  K. Polonsky,et al.  Roles of insulin resistance and obesity in regulation of plasma insulin concentrations. , 2000, American journal of physiology. Endocrinology and metabolism.

[53]  Paul K. Marsden,et al.  Attenuation of Insulin-Evoked Responses in Brain Networks Controlling Appetite and Reward in Insulin Resistance , 2006, Diabetes.

[54]  M. Fantuzzi,et al.  Hyperinsulinaemia, obesity, and syndrome X , 1994, Journal of internal medicine.

[55]  R. Turner,et al.  Eigenvector Centrality Mapping for Analyzing Connectivity Patterns in fMRI Data of the Human Brain , 2010, PloS one.

[56]  Jeroen van der Grond,et al.  Resting-state functional connectivity of brain regions involved in cognitive control, motivation, and reward is enhanced in obese females. , 2014, The American journal of clinical nutrition.

[57]  Jonathan D. Cohen,et al.  Dorsal anterior cingulate cortex and the value of control , 2016, Nature Neuroscience.

[58]  Keith A. Young,et al.  The functional connectivity of the human caudate: An application of meta-analytic connectivity modeling with behavioral filtering , 2012, NeuroImage.

[59]  S. Benoit,et al.  Insulin, leptin, and food reward: update 2008. , 2009, American journal of physiology. Regulatory, integrative and comparative physiology.