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An fMRI-EEG Profile Underlying Comorbidity Load and Prospective Increases in Dysphoria in a Focal Fear Sample

      Abstract

      Background

      Knowledge of the neural mechanisms underlying increased disease burden in the anxiety disorders that is unaccounted for by individual categorical diagnoses could lead to improved clinical care. Here, we tested the utility of a joint fMRI-EEG neurobiological profile characterized by overvaluation of negative stimuli (amygdala) in combination with blunted elaborated processing of these same stimuli (the late positive potential/LPP, an event-related potential), in predicting increased psychopathology across a two-year period in the anxiety disorders.

      Methods

      One-hundred and ten participants (64 female), comprised of 78 phobic participants who varied in extent of internalizing comorbidity and 32 participants who were free from psychopathology, viewed negative and neutral pictures during separate fMRI BOLD and EEG recordings. Dysphoria was assessed at baseline and two years later.

      Results

      Participants with heightened amygdala activation and blunted LPPs to negative pictures showed the greatest increases in dysphoria two years later. Cross-sectionally, participants with higher comorbidity load (n = 34; ≥ two additional diagnoses) showed increased amygdala activation to negative pictures, compared to participants with lower comorbidity load (n = 44; ≤ one additional diagnosis) and compared to participants free from psychopathology. In addition, high versus low comorbid participants showed reduced LPPs to negative pictures.

      Conclusions

      Heightened amygdala “alarm” in response to negative stimuli in combination with blunted LPPs could indicate overvaluation of threatening stimuli in the absence of elaborated processing that might otherwise help regulate threat responding. This brain profile could underlie the worsening and maintenance of internalizing psychopathology over time.

      Keywords

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