Coupling between spontaneous pupillary fluctuations and brain activity relates to inattentiveness

Autonomic activity in neurological and psychiatric disorders is often dysregulated, particularly in the context of attentional behaviors. This suggests that interplay between the autonomic nervous system and aspects of the central nervous system subserving attention may be disrupted in these conditions. Better understanding these interactions and their relationship with individual variation in attentional behaviors could facilitate development of mechanistic biomarkers. We identified brain regions defined by trait‐sensitive central–autonomic coupling as a first step in this process. As spontaneous neural activity measured during the resting state is sensitive to phenotypic variability, unconfounded by task performance, we examined whether spontaneous fluctuations in brain activity and an autonomic measure, pupil diameter, were coupled during the resting state, and whether that coupling predicted individual differences in attentional behavior. By employing concurrent pupillometry and fMRI during the resting state, we observed positive coupling in regions comprising cingulo‐opercular, default mode, and fronto‐parietal networks, as well as negative coupling with visual and sensorimotor regions. Individuals less prone to distractibility in everyday behavior demonstrated stronger positive coupling in cingulo‐opercular regions often associated with sympathetic activity. Overall, our results suggest that individuals less prone to distractibility have tighter intrinsic coordination between specific brain areas and autonomic systems, which may enable adaptive autonomic shifts in response to salient environmental cues. These results suggest that incorporating autonomic indices in resting‐state studies should be useful in the search for biomarkers for neurological and psychiatric disorders.

[1]  E. Szabadi,et al.  Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part I: Principles of Functional Organisation , 2008, Current neuropharmacology.

[2]  R. O’Connell,et al.  Pupil diameter covaries with BOLD activity in human locus coeruleus , 2014, Human brain mapping.

[3]  T. Beauchaine,et al.  Vagal tone, development, and Gray's motivational theory: Toward an integrated model of autonomic nervous system functioning in psychopathology , 2001, Development and Psychopathology.

[4]  Greg J Siegle,et al.  Use of concurrent pupil dilation assessment to inform interpretation and analysis of fMRI data , 2003, NeuroImage.

[5]  Rafael Malach,et al.  Coupling between pupil fluctuations and resting-state fMRI uncovers a slow build-up of antagonistic responses in the human cortex , 2015, NeuroImage.

[6]  M. Viljoen,et al.  Autonomic Correlates at Rest and during Evoked Attention in Children with Attention-Deficit/Hyperactivity Disorder and Effects of Methylphenidate , 2010, Neuropsychobiology.

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

[8]  S. Steinhauer,et al.  Blink before and after you think: blinks occur prior to and following cognitive load indexed by pupillary responses. , 2008, Psychophysiology.

[9]  J. Haxby,et al.  Localization of Cardiac-Induced Signal Change in fMRI , 1999, NeuroImage.

[10]  D. Schacter,et al.  Correlated low-frequency BOLD fluctuations in the resting human brain are modulated by recent experience in category-preferential visual regions. , 2010, Cerebral cortex.

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

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

[13]  C. Tallon-Baudry,et al.  The neural subjective frame: from bodily signals to perceptual consciousness , 2014, Philosophical Transactions of the Royal Society B: Biological Sciences.

[14]  O. Lowenstein,et al.  Pupillary Reflex Shapes and Topical Clinical Diagnosis , 1955, Neurology.

[15]  Evan M. Gordon,et al.  Working memory‐related changes in functional connectivity persist beyond task disengagement , 2014, Human brain mapping.

[16]  M. D’Esposito,et al.  Functional Characterization of the Cingulo-Opercular Network in the Maintenance of Tonic Alertness. , 2015, Cerebral cortex.

[17]  Martin Vinck,et al.  Arousal and Locomotion Make Distinct Contributions to Cortical Activity Patterns and Visual Encoding , 2014, Neuron.

[18]  Archana Venkataraman,et al.  Intrinsic functional connectivity as a tool for human connectomics: theory, properties, and optimization. , 2010, Journal of neurophysiology.

[19]  V. Napadow,et al.  The Autonomic Brain: An Activation Likelihood Estimation Meta-Analysis for Central Processing of Autonomic Function , 2013, The Journal of Neuroscience.

[20]  S. Sara,et al.  Network reset: a simplified overarching theory of locus coeruleus noradrenaline function , 2005, Trends in Neurosciences.

[21]  Claire Braboszcz,et al.  Oculometric variations during mind wandering , 2014, Front. Psychol..

[22]  Daniel Smilek,et al.  On the relation of mind wandering and ADHD symptomatology , 2015, Psychonomic bulletin & review.

[23]  LAWRENCE STARK,et al.  Pupil Unrest: An Example of Noise in a Biological Servomechanism , 1958, Nature.

[24]  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.

[25]  J. H. Steiger Tests for comparing elements of a correlation matrix. , 1980 .

[26]  B Wilhelm,et al.  Pupillographic assessment of sleepiness in sleep-deprived healthy subjects. , 1998, Sleep.

[27]  E. Gordon,et al.  Fronto-limbic and autonomic disjunctions to negative emotion distinguish schizophrenia subtypes , 2007, Psychiatry Research: Neuroimaging.

[28]  V. Menon,et al.  A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks , 2008, Proceedings of the National Academy of Sciences.

[29]  H. Lüdtke,et al.  Mathematical procedures in data recording and processing of pupillary fatigue waves , 1998, Vision Research.

[30]  Stephen M. Smith,et al.  fMRI resting state networks define distinct modes of long-distance interactions in the human brain , 2006, NeuroImage.

[31]  Nash Unsworth,et al.  Individual differences in the allocation of attention to items in working memory: Evidence from pupillometry , 2015, Psychonomic bulletin & review.

[32]  Olga V. Demler,et al.  The World Health Organization adult ADHD self-report scale (ASRS): a short screening scale for use in the general population , 2005, Psychological Medicine.

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

[34]  Tanuj Gulati,et al.  Neuromodulators Produce Distinct Activated States in Neocortex , 2014, The Journal of Neuroscience.

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

[36]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.

[37]  Evan M. Gordon,et al.  Phenotypic Variability in Resting-State Functional Connectivity: Current Status , 2013, Brain Connect..

[38]  Peter T. Fox,et al.  Changes occur in resting state network of motor system during 4weeks of motor skill learning , 2011, NeuroImage.

[39]  R. Geva,et al.  Alerting, orienting or executive attention networks: differential patters of pupil dilations , 2013, Front. Behav. Neurosci..

[40]  R. Malach,et al.  The Day-After Effect: Long Term, Hebbian-Like Restructuring of Resting-State fMRI Patterns Induced by a Single Epoch of Cortical Activation , 2013, The Journal of Neuroscience.

[41]  Justin L. Vincent,et al.  Distinct brain networks for adaptive and stable task control in humans , 2007, Proceedings of the National Academy of Sciences.

[42]  Sean D. Kristjansson,et al.  Detecting phasic lapses in alertness using pupillometric measures. , 2009, Applied ergonomics.

[43]  Jin Fan,et al.  Abnormal autonomic and associated brain activities during rest in autism spectrum disorder. , 2014, Brain : a journal of neurology.

[44]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

[45]  S. Bouret,et al.  Noradrenaline and Dopamine Neurons in the Reward/Effort Trade-Off: A Direct Electrophysiological Comparison in Behaving Monkeys , 2015, The Journal of Neuroscience.

[46]  Jin Fan,et al.  Spontaneous Brain Activity Relates to Autonomic Arousal , 2012, The Journal of Neuroscience.

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

[48]  A. Ward,et al.  Mechanism of pupillary dilatation elicited by cortical stimulation. , 1946, Journal of neurophysiology.

[49]  Hugo D. Critchley,et al.  Dissecting axes of autonomic control in humans: Insights from neuroimaging , 2011, Autonomic Neuroscience.

[50]  Benjamin W. Mooneyham,et al.  The Amsterdam Resting-State Questionnaire reveals multiple phenotypes of resting-state cognition , 2013, Front. Hum. Neurosci..

[51]  Leanne M Williams,et al.  Dysregulation of arousal and amygdala-prefrontal systems in paranoid schizophrenia. , 2004, The American journal of psychiatry.

[52]  J. Diamond,et al.  Sclerotomy complications following pars plana vitrectomy , 2000, The British journal of ophthalmology.

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