Impaired prefrontal–amygdala effective connectivity is responsible for the dysfunction of emotion process in major depressive disorder: A dynamic causal modeling study on MEG

Depression is proved to be associated with the dysfunction of prefrontal-limbic neural circuit, especially during emotion processing procedure. Related explorations have been undertaken from the aspects of abnormal activation and functional connectivity. However, the mechanism of the dysfunction of coordinated interactions remains unknown and is still a matter of debate. The present study gave direct evidence of this issue from the aspect of effective connectivity via dynamic causal modeling (DCM). 20 major depressive disorder (MDD) patients and 20 healthy controls were recruited to attend facial emotional stimulus during MEG recording. Bayesian model selection (BMS) was applied to choose the best model. Results under the optimal model showed that top-down endogenous effective connectivity from the dorsolateral prefrontal cortex (DLPFC) to the amygdala was greatly impaired in patients relative to health controls; while bottom-up endogenous effective connectivity from the amygdala to the anterior cingulate cortex (ACC) as well as modulatory effective connectivity from ACC to DLPFC was significantly increased. We inferred the incapable DLPFC failed to exert influence on amygdala, and finally lead to enhanced amygdala-ACC and ACC-DLPFC bottom-up effects. Such impaired prefrontal-amygdala connectivity was supposed to be responsible for the dysfunction in MDD when dealing with emotional stimuli.

[1]  Karl J. Friston,et al.  Dynamic causal modeling of evoked responses in EEG and MEG , 2006, NeuroImage.

[2]  Karl J. Friston,et al.  Ten simple rules for dynamic causal modeling , 2010, NeuroImage.

[3]  Pienie Zwitserlood,et al.  Automatic Mood-Congruent Amygdala Responses to Masked Facial Expressions in Major Depression , 2010, Biological Psychiatry.

[4]  Karl J. Friston,et al.  Dynamic causal modelling , 2003, NeuroImage.

[5]  Á. Pascual-Leone,et al.  Down-Regulation of Negative Emotional Processing by Transcranial Direct Current Stimulation: Effects of Personality Characteristics , 2011, PloS one.

[6]  W. Drevets Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders , 2001, Current Opinion in Neurobiology.

[7]  R. Adolphs Neural systems for recognizing emotion , 2002, Current Opinion in Neurobiology.

[8]  Marcus E Raichle,et al.  Glucose metabolism in the amygdala in depression: Relationship to diagnostic subtype and plasma cortisol levels , 2002, Pharmacology Biochemistry and Behavior.

[9]  P. Boesiger,et al.  Imbalance between Left and Right Dorsolateral Prefrontal Cortex in Major Depression Is Linked to Negative Emotional Judgment: An fMRI Study in Severe Major Depressive Disorder , 2008, Biological Psychiatry.

[10]  J. Gabrieli,et al.  Rethinking Feelings: An fMRI Study of the Cognitive Regulation of Emotion , 2002, Journal of Cognitive Neuroscience.

[11]  Richard Levy,et al.  Cognitive control and brain resources in major depression: An fMRI study using the n-back task , 2005, NeuroImage.

[12]  W. Drevets Prefrontal Cortical‐Amygdalar Metabolism in Major Depression , 1999, Annals of the New York Academy of Sciences.

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

[14]  Karl J. Friston,et al.  Dynamic causal modelling of evoked responses in EEG/MEG with lead field parameterization , 2006, NeuroImage.

[15]  M. Thase,et al.  Increased Amygdala and Decreased Dorsolateral Prefrontal BOLD Responses in Unipolar Depression: Related and Independent Features , 2007, Biological Psychiatry.

[16]  John Suckling,et al.  Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study. , 2004, Archives of general psychiatry.

[17]  Gerd Wagner,et al.  Fronto-cingulate effective connectivity in major depression: A study with fMRI and dynamic causal modeling , 2008, NeuroImage.

[18]  K. Douglas,et al.  Processing of Facial Emotion Expression in Major Depression: A Review , 2010, The Australian and New Zealand journal of psychiatry.

[19]  R. Davidson,et al.  Depression: perspectives from affective neuroscience. , 2002, Annual review of psychology.

[20]  Yasumasa Okamoto,et al.  Rostral anterior cingulate cortex activity mediates the relationship between the depressive symptoms and the medial prefrontal cortex activity. , 2010, Journal of affective disorders.

[21]  Heather L. Urry,et al.  Failure to Regulate: Counterproductive Recruitment of Top-Down Prefrontal-Subcortical Circuitry in Major Depression , 2007, The Journal of Neuroscience.

[22]  Pienie Zwitserlood,et al.  Reduced amygdala-prefrontal coupling in major depression: association with MAOA genotype and illness severity. , 2009, The international journal of neuropsychopharmacology.

[23]  Richard J. Davidson,et al.  The neural circuitry of emotion and affective style: prefrontal cortex and amygdala contributions , 2001 .

[24]  Johannes Pohl,et al.  Attention and executive functions in remitted major depression patients. , 2005, Journal of affective disorders.

[25]  S. Langenecker,et al.  Abnormal Left-Sided Orbitomedial Prefrontal Cortical–Amygdala Connectivity during Happy and Fear Face Processing: A Potential Neural Mechanism of Female MDD , 2011, Front. Psychiatry.

[26]  S. Rauch,et al.  Neurobiology of emotion perception II: implications for major psychiatric disorders , 2003, Biological Psychiatry.

[27]  A. Cavanna,et al.  The precuneus: a review of its functional anatomy and behavioural correlates. , 2006, Brain : a journal of neurology.

[28]  R. Davidson Affective Style and Affective Disorders: Perspectives from Affective Neuroscience , 1998 .

[29]  H. Walter,et al.  Acute and Sustained Effects of Cognitive Emotion Regulation in Major Depression , 2010, The Journal of Neuroscience.

[30]  D. Kupfer,et al.  Abnormal Amygdala-Prefrontal Effective Connectivity to Happy Faces Differentiates Bipolar from Major Depression , 2009, Biological Psychiatry.

[31]  Karl J. Friston,et al.  Dynamic causal modelling of evoked potentials: A reproducibility study , 2007, NeuroImage.

[32]  H. Mayberg Limbic-cortical dysregulation: a proposed model of depression. , 1997, The Journal of neuropsychiatry and clinical neurosciences.

[33]  Mario Beauregard,et al.  Dysfunction in the neural circuitry of emotional self-regulation in major depressive disorder , 2006, Neuroreport.

[34]  M. Posner,et al.  Cognitive and emotional influences in anterior cingulate cortex , 2000, Trends in Cognitive Sciences.

[35]  Karl J. Friston,et al.  Comparing Families of Dynamic Causal Models , 2010, PLoS Comput. Biol..

[36]  A. Friederici,et al.  Dynamic Causal Modeling of Subcortical Connectivity of Language , 2011, The Journal of Neuroscience.