Neurobiological correlates of impulsivity in healthy adults: Lower prefrontal gray matter volume and spontaneous eye-blink rate but greater resting-state functional connectivity in basal ganglia-thalamo-cortical circuitry

&NA; Studies consistently implicate aberrance of the brain's reward‐processing and decision‐making networks in disorders featuring high levels of impulsivity, such as attention‐deficit hyperactivity disorder, substance use disorder, and psychopathy. However, less is known about the neurobiological determinants of individual differences in impulsivity in the general population. In this study of 105 healthy adults, we examined relationships between impulsivity and three neurobiological metrics – gray matter volume, resting‐state functional connectivity, and spontaneous eye‐blink rate, a physiological indicator of central dopaminergic activity. Impulsivity was measured both by performance on a task of behavioral inhibition (go/no‐go task) and by self‐ratings of attentional, motor, and non‐planning impulsivity using the Barratt Impulsiveness Scale (BIS‐11). Overall, we found that less gray matter in medial orbitofrontal cortex and paracingulate gyrus, greater resting‐state functional connectivity between nodes of the basal ganglia‐thalamo‐cortical network, and lower spontaneous eye‐blink rate were associated with greater impulsivity. Specifically, less prefrontal gray matter was associated with higher BIS‐11 motor and non‐planning impulsivity scores, but was not related to task performance; greater correlated resting‐state functional connectivity between the basal ganglia and thalamus, motor cortices, and prefrontal cortex was associated with worse no‐go trial accuracy on the task and with higher BIS‐11 motor impulsivity scores; lower spontaneous eye‐blink rate was associated with worse no‐go trial accuracy and with higher BIS‐11 motor impulsivity scores. These data provide evidence that individual differences in impulsivity in the general population are related to variability in multiple neurobiological metrics in the brain's reward‐processing and decision‐making networks. HighlightsDifferences in impulsivity are linked to variability in multiple metrics.Greater impulsivity is associated with less prefrontal gray matter volume.Greater impulsivity is associated with increased functional connectivity.Greater impulsivity is associated with lower spontaneous eye‐blink rate.

[1]  Kerstin Konrad,et al.  Is the ADHD brain wired differently? A review on structural and functional connectivity in attention deficit hyperactivity disorder , 2010, Human brain mapping.

[2]  E. Butelman,et al.  Genetic influences on impulsivity, risk taking, stress responsivity and vulnerability to drug abuse and addiction , 2005, Nature Neuroscience.

[3]  J. Patton,et al.  Factor structure of the Barratt impulsiveness scale. , 1995, Journal of clinical psychology.

[4]  Matthew S. Stanford,et al.  Barratt Impulsiveness Scale-11 , 2011 .

[5]  Stephen M. Smith,et al.  A global optimisation method for robust affine registration of brain images , 2001, Medical Image Anal..

[6]  Marisa O. Hollinshead,et al.  Individual Differences in Cognitive Control Circuit Anatomy Link Sensation Seeking, Impulsivity, and Substance Use , 2016, The Journal of Neuroscience.

[7]  Robert M. Kessler,et al.  Mesolimbic Dopamine Reward System Hypersensitivity in Individuals with Psychopathic Traits , 2010, Nature Neuroscience.

[8]  V. Calhoun,et al.  Paralimbic Gray Matter Reductions in Incarcerated Adolescent Females with Psychopathic Traits , 2014, Journal of abnormal child psychology.

[9]  Y. Liu,et al.  Resting-State Functional Connectivity Predicts Impulsivity in Economic Decision-Making , 2013, The Journal of Neuroscience.

[10]  G. Barbato,et al.  Diurnal variation in spontaneous eye-blink rate , 2000, Psychiatry Research.

[11]  J. Patton,et al.  Fifty years of the Barratt Impulsiveness Scale: An update and review , 2009 .

[12]  K. Kiehl,et al.  Impulsive-antisocial psychopathic traits linked to increased volume and functional connectivity within prefrontal cortex , 2017, Social cognitive and affective neuroscience.

[13]  C. Karson,et al.  Blink rates in parkinsonism , 1982, Annals of neurology.

[14]  D. Hommer,et al.  Delay Discounting Correlates with Proportional Lateral Frontal Cortex Volumes , 2009, Biological Psychiatry.

[15]  R. Roth,et al.  In the Blink of an Eye: Relating Positive-Feedback Sensitivity to Striatal Dopamine D2-Like Receptors through Blink Rate , 2014, The Journal of Neuroscience.

[16]  Norbert Kathmann,et al.  Cortical thickness correlates with impulsiveness in healthy adults , 2012, NeuroImage.

[17]  R. Kahn,et al.  Function of striatum beyond inhibition and execution of motor responses , 2005, Human brain mapping.

[18]  Magnus Dahlbom,et al.  Striatal Dopamine D2/D3 Receptor Availability Is Reduced in Methamphetamine Dependence and Is Linked to Impulsivity , 2009, The Journal of Neuroscience.

[19]  J. Pekar,et al.  Meta-analysis of Go/No-go tasks demonstrating that fMRI activation associated with response inhibition is task-dependent , 2008, Neuropsychologia.

[20]  J. Richards,et al.  Dimensions of impulsive behavior: Personality and behavioral measures , 2006 .

[21]  V. Calhoun,et al.  Examining the effect of psychopathic traits on gray matter volume in a community substance abuse sample , 2012, Psychiatry Research: Neuroimaging.

[22]  K. Kiehl,et al.  Event‐related fMRI study of response inhibition , 2001, Human brain mapping.

[23]  Jean Decety,et al.  Impulsive-antisocial dimension of psychopathy linked to enlargement and abnormal functional connectivity of the striatum. , 2017, Biological psychiatry. Cognitive neuroscience and neuroimaging.

[24]  H. de Wit Impulsivity as a determinant and consequence of drug use: a review of underlying processes , 2009, Addiction biology.

[25]  Stephen M. Smith,et al.  Permutation inference for the general linear model , 2014, NeuroImage.

[26]  M. Frank,et al.  Conflict acts as an implicit cost in reinforcement learning , 2014, Nature Communications.

[27]  Chiarella Sforza,et al.  Spontaneous blinking in healthy persons: an optoelectronic study of eyelid motion , 2008, Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians.

[28]  M. Jenkinson,et al.  Non-linear optimisation FMRIB Technial Report TR 07 JA 1 , 2007 .

[29]  D. Zald,et al.  Dopaminergic Network Differences in Human Impulsivity , 2010, Science.

[30]  Shani Shalgi,et al.  On the positive side of error processing: error‐awareness positivity revisited , 2009, The European journal of neuroscience.

[31]  Dardo Tomasi,et al.  Functional connectivity of substantia nigra and ventral tegmental area: maturation during adolescence and effects of ADHD. , 2014, Cerebral cortex.

[32]  B. J. Casey,et al.  Implication of right frontostriatal circuitry in response inhibition and attention-deficit/hyperactivity disorder. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[33]  Angela L. Duckworth,et al.  Self-Discipline Outdoes IQ in Predicting Academic Performance of Adolescents , 2005, Psychological science.

[34]  H. Heinze,et al.  Mesolimbic Functional Magnetic Resonance Imaging Activations during Reward Anticipation Correlate with Reward-Related Ventral Striatal Dopamine Release , 2008, The Journal of Neuroscience.

[35]  R W Cox,et al.  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. , 1996, Computers and biomedical research, an international journal.

[36]  B. Biswal,et al.  Functional connectivity of human striatum: a resting state FMRI study. , 2008, Cerebral cortex.

[37]  David P. Daberkow,et al.  Amphetamine Paradoxically Augments Exocytotic Dopamine Release and Phasic Dopamine Signals , 2013, The Journal of Neuroscience.

[38]  Andrew T. Morgan,et al.  Behavioral/systems/cognitive Striatal Dopamine D 2 /d 3 Receptors Mediate Response Inhibition and Related Activity in Frontostriatal Neural Circuitry in Humans Impulsive Behavior Is Thought to Reflect a Traitlike Characteristic That Can Have Broad Consequences for an Individual's Success and Well-be , 2022 .

[39]  Kaileigh A. Byrne,et al.  Striatal Dopamine, Externalizing Proneness, and Substance Abuse , 2016, Clinical psychological science : a journal of the Association for Psychological Science.

[40]  B. Harrison,et al.  Functional Connectivity Bias in the Prefrontal Cortex of Psychopaths , 2015, Biological Psychiatry.

[41]  Samuel M. McClure,et al.  Time Discounting for Primary Rewards , 2007, The Journal of Neuroscience.

[42]  N. Volkow,et al.  Abnormal Functional Connectivity in Children with Attention-Deficit/Hyperactivity Disorder , 2012, Biological Psychiatry.

[43]  M. Lawrence,et al.  MPTP lesions and dopaminergic drugs alter eye blink rate in African green monkeys , 1991, Pharmacology Biochemistry and Behavior.

[44]  M. Jenkinson Non-linear registration aka Spatial normalisation , 2007 .

[45]  D. E. Redmond,et al.  Spontaneous Blink Rates Correlate with Dopamine Levels in the Caudate Nucleus of MPTP-Treated Monkeys , 1999, Experimental Neurology.

[46]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[47]  A. Bentivoglio,et al.  Analysis of blink rate patterns in normal subjects , 1997, Movement disorders : official journal of the Movement Disorder Society.

[48]  N L Foster,et al.  Blink rates and disorders of movement , 1984, Neurology.

[49]  Gordon D. Logan,et al.  Effects of methylphenidate on inhibitory control in hyperactive children , 1989, Journal of abnormal child psychology.

[50]  Samuel M. McClure,et al.  Separate Neural Systems Value Immediate and Delayed Monetary Rewards , 2004, Science.

[51]  Edythe D. London,et al.  Striatal D1- and D2-type Dopamine Receptors Are Linked to Motor Response Inhibition in Human Subjects , 2015, The Journal of Neuroscience.

[52]  E. Stein,et al.  Right hemispheric dominance of inhibitory control: an event-related functional MRI study. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[53]  S. Rombouts,et al.  Dopamine-dependent architecture of cortico-subcortical network connectivity. , 2013, Cerebral cortex.

[54]  R. Mailman,et al.  D1 and D2 dopamine receptors independently regulate spontaneous blink rate in the vervet monkey. , 1991, The Journal of pharmacology and experimental therapeutics.

[55]  R. Elliott,et al.  Response inhibition and impulsivity: an fMRI study , 2003, Neuropsychologia.

[56]  A. Hariri,et al.  Neural basis of individual differences in impulsivity: contributions of corticolimbic circuits for behavioral arousal and control. , 2006, Emotion.

[57]  B. Hommel,et al.  Dopamine and inhibitory action control: evidence from spontaneous eye blink rates , 2009, Experimental Brain Research.

[58]  J. Suckling,et al.  Age-related grey matter volume correlates of response inhibition and shifting in attention-deficit hyperactivity disorder. , 2009, The British journal of psychiatry : the journal of mental science.

[59]  M. Vink,et al.  On the Role of the Striatum in Response Inhibition , 2010, PloS one.

[60]  Jennifer M. Mitchell,et al.  Dopamine, Corticostriatal Connectivity, and Intertemporal Choice , 2012, The Journal of Neuroscience.

[61]  Saeid Sanei,et al.  Removal of the Eye-Blink Artifacts From EEGs via STF-TS Modeling and Robust Minimum Variance Beamforming , 2008, IEEE Transactions on Biomedical Engineering.

[62]  E. Jutkiewicz,et al.  Effects of Dopamine D1 Ligands on Eye Blinking in Monkeys: Efficacy, Antagonism, and D1/D2 Interactions , 2004, Journal of Pharmacology and Experimental Therapeutics.

[63]  Karson Cn Physiology of normal and abnormal blinking. , 1988 .

[64]  G. Bush,et al.  Dorsolateral Prefrontal and Anterior Cingulate Cortex Volumetric Abnormalities in Adults with Attention-Deficit/Hyperactivity Disorder Identified by Magnetic Resonance Imaging , 2006, Biological Psychiatry.

[65]  Michael Brady,et al.  Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images , 2002, NeuroImage.

[66]  Nicola J. Ray,et al.  Morphometric Correlation of Impulsivity in Medial Prefrontal Cortex , 2012, Brain Topography.

[67]  M. Kleven,et al.  Differential effects of direct and indirect dopamine agonists on eye blink rate in cynomolgus monkeys. , 1996, The Journal of pharmacology and experimental therapeutics.

[68]  John P Hatch,et al.  A voxel‐based morphometry study of frontal gray matter correlates of impulsivity , 2009, Human brain mapping.

[69]  Rajita Sinha,et al.  Subcortical processes of motor response inhibition during a stop signal task , 2008, NeuroImage.

[70]  J. S. Liu,et al.  The validity of eye blink rate in Chinese adults for the diagnosis of Parkinson's disease , 2003, Clinical Neurology and Neurosurgery.

[71]  John J. Foxe,et al.  Prefrontal‐subcortical dissociations underlying inhibitory control revealed by event‐related fMRI , 2004, The European journal of neuroscience.

[72]  Adam R Aron,et al.  Methylphenidate improves response inhibition in adults with attention-deficit/hyperactivity disorder , 2003, Biological Psychiatry.

[73]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[74]  T. Vickery,et al.  Associating resting-state connectivity with trait impulsivity , 2017, Social cognitive and affective neuroscience.

[75]  E. Jutkiewicz,et al.  Effects of Dopamine D 1 Ligands on Eye Blinking in Monkeys: Efficacy, Antagonism, and D 1 /D 2 Interactions , 2004 .

[76]  T. Thiel,et al.  Frontoorbital volume reductions in adult patients with attention deficit hyperactivity disorder , 2002, Neuroscience Letters.

[77]  Kyle G. Horn,et al.  Characterizing the Spontaneous Blink Generator: An Animal Model , 2011, The Journal of Neuroscience.

[78]  J. Richards,et al.  Acute Administration of d-Amphetamine Decreases Impulsivity in Healthy Volunteers , 2002, Neuropsychopharmacology.