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Your Brain on Depression (and After Treatment)

Depression might alter functional brain connectivity; treatment may change it.

Key points

  • The default mode network (DMN) describes the pattern of brain activity associated with the brain at rest.
  • Meta-analysis has shown an association between the DMN and rumination in people with depression.
  • Studies suggest therapies like psychotherapy, mindfulness, and ketamine may alter the DMN.

When I first heard the term "default mode network," I wondered if it had something to do with telephones or the internet. It doesn't. What it does have to do with is much more intriguing.

The default mode network describes the pattern of brain activity present when a person is at rest. It depicts what happens to our minds when we are not focused on anything. It's where our minds go when they wander.

For many living with depression, minds disappear into negativity, rumination over bad memories, and self-criticism.

Research into default mode networks using fMRI studies has reflected differences in the patterns of activity in depressed individuals and those without depression. A meta-analysis showed a correlation between the default mode network and rumination in individuals living with depression (Zhou et al., 2020). Specifically, areas of the brain associated with negative rumination show hyperconnectivity while at rest.

Such patterns may reinforce a vicious cycle of rumination in which a person can find themselves trapped.

If It's Neurology, Is It Destiny?

As both a clinician and a person who has experienced depression, I found this research at once validating and fearsome. If depression is related to such neurological processes, is there anything we can do about it? The answer is yes.

Research has shown that functional connectivity in the default mode network changed after a course of psychodynamic therapy in individuals living with borderline personality disorder, a condition often associated with depression (Amiri et al., 2023). Research has also shown that mindfulness training may alter default mode network connectivity (Rahig et al., 2022). A double-blind placebo-controlled trial found changes in the default mode network among individuals living with depression as measured by a resting fMRI scan after administration of ketamine, an investigational treatment for depression (Wang et al., 2022).

The presence of specific biomarkers of depression, as shown through the default mode network on fMRI—specifically hyperconnectivity between the right insula with the right middle temporal gyrus and the left intraparietal sulcus with the orbital frontal cortex, was even found to predict a positive response to psychotherapy focused on behavior activation (Crowder et al., 2015).

While the exact mechanism of change cannot fully be inferred, it could be hypothesized that treatments such as psychotherapy, mindfulness training, and ketamine may improve the flexibility of thinking, thereby releasing one from these ruminative traps.

Mindfulness training teaches us to be in the moment, something that is contrary to rumination. Psychotherapy can change how we see ourselves, the world, and others. This may change our habits of negativity. While the mechanism of change in ketamine treatment is still being explored, ketamine is what is known as an NMDA receptor antagonist. NMDA is one of the primary excitatory receptor sites in the brain, meaning that its activation may be associated with our usual patterns (Andrade, 2017). Some have hypothesized that ketamine may interrupt the default mode network directly by modulating this.

In Closing

Although fMRI is not currently used in the diagnosis of depression, there do appear to be some biomarkers shown through fMRI scans of individuals living with depression at a resting state. Normalization of these patterns might correlate with recovery and response to various treatments currently utilized for depression. This is exciting research that is likely to guide advances in the diagnosis and intervention of depression.

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Amiri, S., Mirfazeli, F. S., Grafman, J., Mohammadsadeghi, H., Eftekhar, M., Karimzad, N., ... & Nohesara, S. (2023). Alternation in functional connectivity within default mode network after psychodynamic psychotherapy in borderline personality disorder. Annals of General Psychiatry, 22(1), 1-12.

Andrade, C. (2017). Ketamine for depression, 1: clinical summary of issues related to efficacy, adverse effects, and mechanism of action. The Journal of clinical psychiatry, 78(4), 10108.

Crowther, A., Smoski, M. J., Minkel, J., Moore, T., Gibbs, D., Petty, C., ... & Dichter, G. S. (2015). Resting-state connectivity predictors of response to psychotherapy in major depressive disorder. Neuropsychopharmacology, 40(7), 1659-1673.

Rahrig, H., Vago, D. R., Passarelli, M. A., Auten, A., Lynn, N. A., & Brown, K. W. (2022). Meta-analytic evidence that mindfulness training alters resting state default mode network connectivity. Scientific Reports, 12(1), 12260.

Wang, M., Chen, X., Hu, Y., Zhou, Y., Wang, C., Zheng, W., & Zhang, B. (2022). Functional connectivity between the habenula and default mode network and its association with the antidepressant effect of ketamine. Depression and Anxiety, 39(5), 352-362.

Zhou, H. X., Chen, X., Shen, Y. Q., Li, L., Chen, N. X., Zhu, Z. C., & Yan, C. G. (2020). Rumination and the default mode network: Meta-analysis of brain imaging studies and implications for depression. Neuroimage, 206, 116287.

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