Evaluating Brain Responses to Facial Expressions in Major Depressive Disorder
Condition: Current Major Depressive Disorder; Healthy; Remitted Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Study type: Observational

Summary: 
      This study will evaluate emotional processing biases in the brain while viewing facial
      expressions in adults with current or remitted major depressive disorder and healthy
      volunteers.
    

Detailed description: 
      The goal of this research is to elucidate the neurophysiological abnormalities associated
      with processing emotionally valenced stimuli in MDD. Neuroimaging technology has led to the
      identification of specific abnormalities in the amygdala, ventral striatum and medial
      prefrontal cortex in response to affective pictures. Much of the knowledge involving these
      structures in emotion processing has been elucidated through animal models including
      classical fear conditioning and reversal-learning paradigms. Functional magnetic resonance
      imaging (fMRI) studies have applied similar techniques in humans to study emotional
      processing. The amygdala has been shown to play a role in the learning of fear (aversive)
      conditioning to emotional stimuli, the ventral striatum has been shown to play a role in
      appetitive conditioning, and areas of the prefrontal cortex are recruited for extinction of
      conditioned responses. These areas have also been implicated as key structures in the
      abnormal expression of emotion in MDD. Dysregulation of connections between the amygdala and
      prefrontal cortex has been hypothesized to influence depressed subjects' tendency to ruminate
      on emotional events and memories, which may be associated with an inability to properly
      regulate emotional processing through habituation and extinction mechanisms. Research
      suggests that depressed individuals have an impaired ability to disengage from or habituate
      to emotional stimuli perceived as sad.

      In addition to studying emotional processing at a conscious, cortical level, significant
      evidence suggests that many aspects of emotional processing occur below conscious awareness,
      at a preconscious level. The technique of backward masking assesses the automaticity of
      emotional processing and responses to affective stimuli. In MDD, backward masking serves to
      avoid confounding interpretation by the presence of other cognitive processing, which may
      result from depressed subjects perseverating on emotional stimuli. The proposed study builds
      on previous fMRI research to investigate neurophysiological differences in the processing of
      aversively conditioned emotional stimuli in depressed compared to healthy individuals. Using
      fMRI technology and a variation of the paradigm developed by Morris et al., subjects with MDD
      will be classically conditioned to the presence of an unmasked specific target face (angry or
      sad) and the subsequent neural responses to the stimuli will be assessed utilizing the
      backward masking technique. The BOLD hemodynamic response and rates of habituation and
      extinction to the faces will be compared between depressed subjects with MDD and healthy
      controls, currently depressed versus currently remitted subjects with MDD, and MDD subjects
      pre- and post-antidepressant therapy.

      The present amendment proposes to include an additional paradigm in the testing battery. This
      new paradigm has been extensively examined under different pharmacological manipulations, and
      in healthy individuals undergoing fMRI but has yet to be examined in patient populations. The
      task complements the paradigms presently included by extending the research to encompass
      appetitive as well as aversive emotional processing.

      This research will be used to evaluate neural processes involved in emotional dysregulation
      in MDD and may direct future research to potential therapeutic approaches for the treatment
      of mood and anxiety disorders with abnormalities in emotional processing.
    

Keywords: fMRI; Habituation; Extinction; Amygdala; Emotion; Major Depressive Disorder; Medial Prefrontal Cortex; Backward Masking; Depression; MDD; Healthy Volunteer; HV