Aberrant Brain Activation and Behavior During Self-Evaluation in Depression

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Aberrant Brain Activation and Behavior During Self-Evaluation in Depression (a) Purpose of the study Negative judgment about the self (self-evaluation) is a hallmark of depression, and continued negative self-evaluation after treatment is a risk factor for depression relapse. Despite this, we know little about what is happening in the brain that leads to this persistent negative self-evaluation in depressed adults. Non-depressed individuals experience a self-reference effect, meaning statements about the self are evaluated faster than statements about others. Previous work has shown that this self-reference effect is supported by the medial prefrontal cortex (mPFC) in the brain, whereas a broader network of regions supports other-directed evaluations. In this study, we hypothesized that self-related processing would be altered in depressed adults, such that they would 1) activate a wider network of brain areas and 2) show a decreased behavioral self-reference effect (i.e., reaction times about the self and others would be more similar) during self-evaluation compared to non-depressed adults. (b) Research method Our sample consisted of 58 participants (age 18-25, 72% Female), 35 depressed (Quick Inventory of Depressive Symptoms, QIDS score > 6), and 23 non-depressed (no history of psychiatric illness + QIDS score < 6). During fMRI scanning, participants completed a self/other-evaluation task, during which they rated how much they believed a positive or negative statement about themselves or a famous person. Twenty trials of each type were presented. fMRI data was preprocessed, and first-level models were constructed to evaluate the change in regional brain activation during positive and negative self/other evaluation. We assessed activation in regions of interest previously implicated in self/other evaluation, namely: bilateral dorsal anterior insula, mPFC, precuneus/posterior cingulate cortex (PCC), dorso- and ventrolateral prefrontal cortex (dlPFC, vlPFC), dorsal anterior cingulate cortex (dACC), and the temporo-parietal junction (TPJ). A mixed-effect repeated measures model with False Discovery Rate (multiple comparison) correction was used to analyze the effect of each condition on the fMRI signal. Separately, we also analyzed the trial-by-trial reaction time data for each subject, using a similar mixed-effects repeated measures model. (c) Findings Overall, the depressed group showed increased activation in multiple brain regions during self-evaluation compared to the non-depressed group. Depressed and non-depressed individuals showed differences in neural activation within the mPFC (F(1,85.9)=5.93, FDR q=0.02) Precuneus/PCC(F(1,85.9)=5.93, FDR q=0.01), left dorsal anterior insula (F(1,94.2)=7.11 FDR q=0.009), dACC (F(1,94.9)=11.13, FDR q=0.004), and left vlPFC (F(1,90.8)=5.31, FDR q=0.02). In the mPFC (t(56)=3.10, d=0.83, p=0.003), left dorsal anterior insula (insula: t(56) =2.29 , d=0.62, p=0.03), dACC (t(56) =3.86, d=1.04, p=<0.001), and left vlPFC (t(56)=2.22, d=0.60, p=0.03), group differences were due to increased activation in depressed individuals in response to negative statements about the self. In the precuneus/PCC, depressed individuals showed increased neural activation to self- vs other-related statements (F(1,56)=5.30, d=0.63, p=0.03). Behaviorally, we observed a group-by-target (self/other) interaction for reaction times (F(1,56)=9.63, p=0.003). While non-depressed individuals showed the expected self-reference effect and were faster at evaluating self- vs other-related statements (t(56)=3.27, p=0.002), the depressed group was not (t(56)=-0.89 p=0.38). The two groups did not differ in other-related response times, further emphasizing that the differences observed are due to changes in self-related processing. (d) Implications Our findings support the idea that self-related processing is disrupted in depression. Depressed individuals showed a wider network of activation than non-depressed individuals during self-evaluation, particularly in response to negative statements about the self. These findings were backed by behavioral evidence that the efficient self-reference effect seen in non-depressed individuals is lost in depression, such that depressed individuals respond to statements about themselves and others with similar speed. Addressing this aberrant self-evaluation in depression through treatments targeting these neural areas—and what's activating them—may lead to more efficacious and long-lasting treatment in depressed individuals.


Biological Sciences: 1st Place (The Ohio State University Edward F. Hayes Graduate Research Forum)


Depression, fMRI, Self-Evaluation, Psychiatry