Brain mechanisms underlying the emotion processing bias in treatment-resistant depression

Neurology Medicine Psychiatry Clinical Psychology Medical Imaging
Brain mechanisms Emotion processing Treatment-resistant depression Emotion bias

Brain Mechanism Study on Emotion Processing Bias in Patients with Highly Treatment-Resistant Depression

Background Introduction

Depression is one of the mental diseases prevalent in modern society that severely affect individuals’ physical and mental health. According to Beck’s cognitive model, the development and maintenance of depression are largely related to the biased acquisition and processing of information. Numerous studies have shown that patients with depression commonly exhibit a negative bias in cognitive domains (such as perception, attention, and memory). For instance, they tend to interpret neutral faces as sad and happy faces as unhappy. Understanding the neural mechanisms of these biased processes in handling emotional stimuli is of vital clinical significance for predicting, detecting, and treating depression.

However, despite functional magnetic resonance imaging (fMRI) studies showing that the amygdala response in patients with depression is amplified when processing sad faces and reduced when processing happy faces, these studies mostly adopted methods with high spatial resolution but low temporal resolution or the opposite. Consequently, they fall short in understanding the neural mechanisms of emotional stimulus processing bias in depression.

Source of the Study

This paper was written by scholars Xiaoxu Fan, Madaline Mocchi, Bailey Pascuzzi, Jiayang Xiao, etc., who are affiliated to Baylor College of Medicine, Swarthmore College, Washington University School of Medicine, University of California San Francisco, University of Texas Southwestern Medical Center, etc. The paper was published on the Journal of Nature Mental Health in May 2024.

Experimental Procedure and Methodology

This experiment aims to study the neural mechanisms behind the emotional processing bias in patients with Treatment Resistant Depression (TRD) using Stereotactic Electroencephalography (SEEG) recordings with high spatial and temporal resolutions. The subjects included 5 TRD patients and 12 epileptic patients (as a control group). During the experiment, participants were engaged in an emotional bias task, evaluating happy and sad faces displayed on the screen.

Specific Procedures

  1. Experimental design and task stimulation

    • The experiment used an emotional bias task involving morphing faces from maximum emotional intensity to neutral (100% sad, 50% sad, 30% sad, 10% sad, neutral, 10% happy, 30% happy, 50% happy, and 100% happy).
    • Participants evaluated emotional intensity by clicking positions on a slider.

  2. Data recording

    • SEEG was used to record the local field potentials (LFP) of the patient’s amygdala and prefrontal cortex (PFC).
    • In the TRD group, a total of 180 contact points were recorded in the PFC and 36 in the amygdala. In the control group, 119 contact points were recorded in the PFC and 52 in the amygdala.

  3. Data processing and analysis

    • IEPR analysis was conducted in the PFC and amygdala, revealing significant differences between the two groups’ amygdala IEPR responses during emotional face processing.

Main Experimental Results

  1. Time dynamics of amygdala response

    • When TRD patients first see a sad face (around 300ms), a significantly amplified negative potential peak is observed, but this response is significantly reduced when processing happy faces (around 600ms).
    • It has been proposed that during the early stages of processing sad faces, activation in the amygdala increases, suggesting that TRD patients have an overly active bottom-up processing system. During the late stage of processing happy faces, the inhibitory effect of the PFC on the amygdala through its alpha oscillations may lead to a reduced amygdala response.

  2. Alpha band activity in the PFC

    • Compared to the control group, TRD patients show a significantly increased alpha band power during the late stage of happy face processing.
    • Further analysis showed that the phase-locking value (PLV) in the alpha band between the PFC and the amygdala during the late stage of happy face processing in the TRD group was significantly higher than that in the control group, indicating an increased inhibitory effect of the PFC on the amygdala during this stage of emotion processing in TRD patients.

  3. The effect of Deep Brain Stimulation (DBS) on the neural response of TRD patients

    • All 5 TRD patients repeated the emotional bias task after receiving DBS.
    • The experiment found that after DBS, the IEPR response of the amygdala in TRD patients when processing happy faces significantly increased, while the power of the alpha band in the PFC significantly decreased.
    • These changes suggest that DBS might correct emotional processing bias in TRD patients by improving the regulation of the PFC on the amygdala.

Conclusion

Using SEEG recordings with high spatial and temporal resolutions, this study is the first to directly observe the specific neural mechanisms behind emotional processing bias in TRD patients. The results indicate that TRD patients exhibit different neural mechanisms when processing emotional stimuli: an overly active bottom-up processing system when processing sad faces and increased inhibitory function of the PFC on the amygdala through its alpha oscillations when processing happy faces. Further research found that DBS can alleviate emotional processing bias in TRD patients by improving these neural mechanisms.

Significance and Application Value of the Study

  1. Scientific value

    • Provides direct electrophysiological evidence on the neural mechanisms of emotional processing bias in TRD patients.
    • Clarifies specific neural mechanisms between the amygdala and prefrontal cortex during different emotional stimulus processing stages.

  2. Application value

    • The potential effect of Deep Brain Stimulation (DBS) in ameliorating emotional processing bias in TRD patients, presenting a new perspective for clinical treatments.
    • Insights into the regulatory function of the PFC on the amygdala may help develop more effective treatments for depression.

This study offers a new perspective and solid electrophysiological evidence for understanding and treating treatment-resistant depression, emphasizing specific neural mechanisms during different emotional stimulus processing stages and their potential applications in depression treatment.