Altered functional connectivity between medial prefrontal cortex and the inferior brainstem in major depression during appraisal of subjective emotional responses: A preliminary study

OBJECTIVE We tested the hypothesis that reduced rostral anterior cingulate cortex (rACC)-subcortical functional connectivity in depressed subjects might account for depression-related autonomic dysregulation. METHODS Ten healthy and ten depressed subjects categorized their immediate subjective emotional responses to picture sets while undergoing functional magnetic resonance imaging and electrocardiography. Using an rACC cluster commonly activated in both groups by emotion categorization as a seed region, we then performed voxel-wise functional connectivity analyses to examine rACC connectivity across the brain in depressed and control subjects. RESULTS rACC had significantly stronger connectivity with a region of the inferior pons in controls than in depressed subjects. Within-subjects differences in rACC-pons connectivity also significantly correlated with measures of both heart rate variability and depression severity. CONCLUSIONS These findings support the hypothesis that autonomic dysregulation in depression may be associated with a functional disconnection between rACC and autonomic brainstem nuclei.

[1]  G. Glover,et al.  Reflecting upon Feelings: An fMRI Study of Neural Systems Supporting the Attribution of Emotion to Self and Other , 2004, Journal of Cognitive Neuroscience.

[2]  Robert Rosenthal,et al.  Effect Sizes Why, When, and How to Use Them , 2009 .

[3]  A. Seth Interoceptive inference, emotion, and the embodied self , 2013, Trends in Cognitive Sciences.

[4]  Jeffrey L. Birk,et al.  Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder. , 2009, The American journal of psychiatry.

[5]  D. Mitchell,et al.  Conscious Perception of Emotional Stimuli , 2012, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[6]  Sidney H. Kennedy,et al.  Differences in brain glucose metabolism between responders to CBT and venlafaxine in a 16-week randomized controlled trial. , 2007, The American journal of psychiatry.

[7]  J. Gollan,et al.  Identifying differences in biased affective information processing in major depression , 2008, Psychiatry Research.

[8]  John J. B. Allen,et al.  Increased association over time between regional frontal lobe BOLD change magnitude and cardiac vagal control with sertraline treatment for major depression , 2014, Psychiatry Research: Neuroimaging.

[9]  P. Salovey,et al.  Perceived Emotional Intelligence, Stress Reactivity, and Symptom Reports: Further Explorations Using the Trait Meta-Mood Scale , 2002 .

[10]  Brunna Tuschen-Caffier,et al.  Characteristics of emotion regulation in recovered depressed versus never depressed individuals , 2008 .

[11]  R. DeRubeis,et al.  Antidepressant drug effects and depression severity: a patient-level meta-analysis. , 2010, JAMA.

[12]  Eva Meisenzahl,et al.  Enlargement of the amygdala in patients with a first episode of major depression , 2002, Biological Psychiatry.

[13]  D. Wolpert,et al.  Abnormalities in the awareness of action , 2002, Trends in Cognitive Sciences.

[14]  D. Hu,et al.  Identifying major depression using whole-brain functional connectivity: a multivariate pattern analysis. , 2012, Brain : a journal of neurology.

[15]  Ian H. Gotlib,et al.  Reduced caudate gray matter volume in women with major depressive disorder , 2008, Psychiatry Research: Neuroimaging.

[16]  Damiaan Denys,et al.  Relation Between Structural and Functional Connectivity in Major Depressive Disorder , 2013, Biological Psychiatry.

[17]  Lisa Feldman Barrett,et al.  Functional grouping and cortical–subcortical interactions in emotion: A meta-analysis of neuroimaging studies , 2008, NeuroImage.

[18]  Jordan Grafman,et al.  The functional neuroanatomy of depression: Distinct roles for ventromedial and dorsolateral prefrontal cortex , 2009, Behavioural Brain Research.

[19]  Michael Angstadt,et al.  Beyond threat: Amygdala reactivity across multiple expressions of facial affect , 2006, NeuroImage.

[20]  Blair T. Johnson,et al.  Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration , 2008, PLoS medicine.

[21]  David N. Towers,et al.  The many metrics of cardiac chronotropy: A pragmatic primer and a brief comparison of metrics , 2007, Biological Psychology.

[22]  Stephan Eliez,et al.  Amygdalar activation associated with positive and negative facial expressions , 2002, Neuroreport.

[23]  Deanna M Barch,et al.  Antidepressant treatment normalizes hypoactivity in dorsolateral prefrontal cortex during emotional interference processing in major depression. , 2009, Journal of affective disorders.

[24]  Peter Boesiger,et al.  Reduced negative BOLD responses in the default-mode network and increased self-focus in depression , 2011, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[25]  Julian F. Thayer,et al.  21. Activity in medial prefrontal cortex correlates with vagal component of heart rate variability during emotion , 2001 .

[26]  R. Lane Neural substrates of implicit and explicit emotional processes: a unifying framework for psychosomatic medicine. , 2008, Psychosomatic medicine.

[27]  K. Doya,et al.  A unifying computational framework for motor control and social interaction. , 2003, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[28]  J. Gross,et al.  The cognitive control of emotion , 2005, Trends in Cognitive Sciences.

[29]  R. Davidson,et al.  Anterior cingulate activity as a predictor of degree of treatment response in major depression: evidence from brain electrical tomography analysis. , 2001, The American journal of psychiatry.

[30]  Ken-ichi Amemori,et al.  Localized Microstimulation of Primate Pregenual Cingulate Cortex Induces Negative Decision-Making , 2012, Nature Neuroscience.

[31]  N. Frasure-smith,et al.  Reflections on Depression as a Cardiac Risk Factor , 2005, Psychosomatic medicine.

[32]  Leanne M Williams,et al.  Amygdala–prefrontal dissociation of subliminal and supraliminal fear , 2006, Human brain mapping.

[33]  H. Critchley Neural mechanisms of autonomic, affective, and cognitive integration , 2005, The Journal of comparative neurology.

[34]  Evette Ludman,et al.  The association of comorbid depression with mortality in patients with type 2 diabetes. , 2005, Diabetes care.

[35]  A. Lozano,et al.  Subcallosal Cingulate Gyrus Deep Brain Stimulation for Treatment-Resistant Depression , 2008, Biological Psychiatry.

[36]  M. Phillips,et al.  A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder , 2008, Molecular Psychiatry.

[37]  A. Clark Whatever next? Predictive brains, situated agents, and the future of cognitive science. , 2013, The Behavioral and brain sciences.

[38]  M. Paulus,et al.  Interoception in anxiety and depression , 2010, Brain Structure and Function.

[39]  J. Price Prefrontal Cortical Networks Related to Visceral Function and Mood , 1999, Annals of the New York Academy of Sciences.

[40]  Katiuscia Sacco,et al.  Functional connectivity of the insula in the resting brain , 2011, NeuroImage.

[41]  H. Critchley,et al.  Extending predictive processing to the body: emotion as interoceptive inference. , 2013, The Behavioral and brain sciences.

[42]  T. Palfai,et al.  Emotional attention, clarity, and repair : Exploring emotional intelligence using the Trait Meta-Mood Scale , 1995 .

[43]  John J. B. Allen,et al.  Subgenual anterior cingulate cortex activity covariation with cardiac vagal control is altered in depression. , 2013, Journal of affective disorders.

[44]  T. Egner,et al.  Emotional processing in anterior cingulate and medial prefrontal cortex , 2011, Trends in Cognitive Sciences.

[45]  A. Onitilo,et al.  Effect of depression on all-cause mortality in adults with cancer and differential effects by cancer site. , 2006, General hospital psychiatry.

[46]  G. Glover,et al.  Resting-State Functional Connectivity in Major Depression: Abnormally Increased Contributions from Subgenual Cingulate Cortex and Thalamus , 2007, Biological Psychiatry.

[47]  K. Felmingham,et al.  Impact of Depression and Antidepressant Treatment on Heart Rate Variability: A Review and Meta-Analysis , 2010, Biological Psychiatry.

[48]  R. Lane,et al.  Claude Bernard and the heart–brain connection: Further elaboration of a model of neurovisceral integration , 2009, Neuroscience & Biobehavioral Reviews.

[49]  E. Kandel,et al.  Resolving Emotional Conflict: A Role for the Rostral Anterior Cingulate Cortex in Modulating Activit , 2006 .

[50]  L. Abramson,et al.  Depressive Realism and Nondepressive Optimistic Illusions: The Role of the Self , 1990 .

[51]  L. Parsons,et al.  Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. , 1999, The American journal of psychiatry.

[52]  M. Milders,et al.  The insular cortex and the neuroanatomy of major depression. , 2011, Journal of affective disorders.

[53]  R. Dolan,et al.  Effects of Attention and Emotion on Face Processing in the Human Brain An Event-Related fMRI Study , 2001, Neuron.

[54]  S. Porges The polyvagal perspective , 2007, Biological Psychology.

[55]  R. Ingram Contemporary Psychological Approaches to Depression , 1990 .

[56]  D. Shohamy,et al.  Ventromedial prefrontal-subcortical systems and the generation of affective meaning , 2012, Trends in Cognitive Sciences.

[57]  William B. Gudykunst,et al.  Dimensions of intercultural effectiveness: An exploratory study , 1978 .

[58]  Raymond J. Dolan,et al.  Levels of appraisal: A medial prefrontal role in high-level appraisal of emotional material , 2006, NeuroImage.

[59]  R. Lane,et al.  A model of neurovisceral integration in emotion regulation and dysregulation. , 2000, Journal of affective disorders.

[60]  K. Bredemeier,et al.  Worry, Anhedonic Depression, and Emotional Styles , 2012, Cognitive Therapy and Research.

[61]  J. Hohwy The Predictive Mind , 2013 .

[62]  A. Craig How do you feel? Interoception: the sense of the physiological condition of the body , 2002, Nature Reviews Neuroscience.

[63]  D. Yurgelun-Todd,et al.  Impaired attention in depressive states: a non-specific deficit? , 1996, Psychological Medicine.

[64]  E. Rolls,et al.  From affective value to decision‐making in the prefrontal cortex , 2008, The European journal of neuroscience.

[65]  D. Pizzagalli Frontocingulate Dysfunction in Depression: Toward Biomarkers of Treatment Response , 2011, Neuropsychopharmacology.

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

[67]  Peter Boesiger,et al.  The relationship between aberrant neuronal activation in the pregenual anterior cingulate, altered glutamatergic metabolism, and anhedonia in major depression. , 2009, Archives of general psychiatry.

[68]  Anthony R. McIntosh,et al.  Limbic–frontal circuitry in major depression: a path modeling metanalysis , 2004, NeuroImage.

[69]  J. Thayer,et al.  eview meta-analysis of heart rate variability and neuroimaging studies : Implications or heart rate variability as a marker of stress and health , 2012 .

[70]  P. Lang International affective picture system (IAPS) : affective ratings of pictures and instruction manual , 2005 .

[71]  G. Shulman,et al.  Medial prefrontal cortex and self-referential mental activity: Relation to a default mode of brain function , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[72]  M. Mintun,et al.  Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study , 2001, Biological Psychiatry.

[73]  G. Fink,et al.  Neural activation during selective attention to subjective emotional responses , 1997, Neuroreport.

[74]  Huiguang He,et al.  Glutamatergic and Resting-State Functional Connectivity Correlates of Severity in Major Depression – The Role of Pregenual Anterior Cingulate Cortex and Anterior Insula , 2010, Front. Syst. Neurosci..

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

[76]  V. Orgeta Specificity of age differences in emotion regulation , 2009, Aging & mental health.

[77]  R. Lane,et al.  Role of medial prefrontal cortex in representing one’s own subjective emotional responses: A preliminary study , 2014, Consciousness and Cognition.

[78]  Florian Beissner,et al.  Advances in functional magnetic resonance imaging of the human brainstem , 2014, NeuroImage.

[79]  H. Koot,et al.  Multidimensional Assessment of Emotion Regulation Difficulties in Adolescents Using the Difficulties in Emotion Regulation Scale , 2010, Assessment.

[80]  Geoffrey Bird,et al.  Levels of emotional awareness and autism: An fMRI study , 2008, Social neuroscience.

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

[82]  Benjamin Thyreau,et al.  Detecting outliers in high-dimensional neuroimaging datasets with robust covariance estimators , 2012, Medical Image Anal..

[83]  D. Mitchell The nexus between decision making and emotion regulation: A review of convergent neurocognitive substrates , 2011, Behavioural Brain Research.

[84]  T. Brown,et al.  Emotion regulation in unipolar depression: the effects of acceptance and suppression of subjective emotional experience on the intensity and duration of sadness and negative affect. , 2008, Behaviour research and therapy.

[85]  J. Gross,et al.  Explicit and implicit emotion regulation: A dual-process framework , 2011, Cognition & emotion.

[86]  P. Fox,et al.  Cingulate function in depression: a potential predictor of treatment response , 1997, Neuroreport.