Default Mode Network and Depression Treatment – Ketamine and TMS

Peter ForsterBipolar Treatment, Major Depression, Psychobiology, Treatments of Depression Leave a Comment

Previously we wrote about how changes in the Default Mode Network may help to explain how TMS works, in this article we’ll talk about the relationship between ketamine and the Default Mode Network.

The Default Mode Network

The Default Mode Network is the dynamic set of brain systems that are active when we are not engaged in a specific task. The picture to the right illustrates the reciprocal Default-Mode-Network-and-Task-Positive-Mode-Network-644x500relationship between areas of the brain activated by one specific task (focused visual attention). When you are engaged in that task the DMN is turned off, by contrast, once you stop focusing on the task the DMN immediately activates.

This excerpt from Wikipedia’s excellent article on the subject will give you a rough idea of the role’s played by the DMN.

“The default mode network is known to be involved in many seemingly different functions. 

It is the neurological basis for the self:

  • Autobiographical information: Memories of collection of events and facts about one’s self
  • Self-reference: Referring to traits and descriptions of one’s self
  • Emotion of one’s self: Reflecting about one’s own emotional state

 Thinking about others:

  • Theory of Mind: Thinking about the thoughts of others and what they might or might not know
  • Emotions of other: Understanding the emotions of other people and empathizing with their feelings
  • Moral reasoning: Determining just and unjust result of an action
  • Social evaluations: Good-bad attitude judgments about social concepts
  • Social categories: Reflecting on important social characteristics and status of a group

Remembering the past and thinking about the future:

  • Remembering the past: Recalling events that happened in the past
  • Imagining the future: Envisioning events that might happen in the future
  • Episodic memory: Detailed memory related to specific events in time
  • Story comprehension: Understanding and remembering a narrative”

The Default Mode Network in Depression

Since the DMN is involved in a number of tasks that can become preoccupations, or ruminations, in people with depression (thinking about the past and future, social evaluations, theories of the self, etcetera), researchers have been interested in the relationship between the DMN and depression.

However, although they have looked, researchers have not found any consistent differences in the overall activity of the DMN in depression.

What appears to be the case is that the change that happens with depression doesn’t have to do with overall activity, but rather with the relationship between the DMN and parts of the brain involved in emotional thinking (particularly the medial prefrontal Midline Cortical Regionscortex and the subgenual anterior cingulate cortex).

In depression, the DMN is hijacked by these parts of the brain, with the result that resting thought becomes entirely consumed with negative ruminations.

TMS and the DMN

TMS strengthens the connection between the dorsolateral prefrontal cortex (DLPFC) and the DMN. The DLPFC seems to be more involved in thoughtful consideration of a problem, rather than emotional thinking, and strengthening the DLPFC – DMN TMS - DMN Effectconnection allows the resumption of more thoughtful and reflective activity.

Instead of thinking only about negative outcomes that are possible, the brain begins to consider all possible outcomes.

Ketamine and the DMN

Ketamine disrupts the frontal control of the DMN and disconnects the medial prefrontal cortex and the subgenual cortex from the DMN for a period of time, allowing other parts of the brain to take over resting thought.

This disruption of the frontal control is why ketamine is associated with dissociation and hallucinations… these are the equivalent of “release phenomena” that occur in various Ketamine DMNbrain networks when one node is disconnected from the network.

No longer able to follow the well worn path of negative rumination, the brain comes up with alternative resting state activities.


Hamilton JP, Farmer M, Fogelman P, Gotlib IH. Depressive Rumination, the Default-Mode Network, and the Dark Matter of Clinical Neuroscience. Biol Psychiatry. 2015 Aug 15;78(4):224-30. doi: 10.1016/j.biopsych.2015.02.020. Epub 2015 Feb 24. Review. PubMed PMID: 25861700; PubMed Central PMCID: PMC4524294.

Bonhomme V, Vanhaudenhuyse A, Demertzi A, Bruno MA, Jaquet O, Bahri MA, Plenevaux A, Boly M, Boveroux P, Soddu A, Brichant JF, Maquet P, Laureys S. Resting-state Network-specific Breakdown of Functional Connectivity during Ketamine Alteration of Consciousness in Volunteers. Anesthesiology. 2016 Nov;125(5):873-888. PubMed PMID: 27496657.

Scheidegger M, Walter M, Lehmann M, Metzger C, Grimm S, Boeker H, Boesiger P, Henning A, Seifritz E. Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action. PLoS One. 2012;7(9):e44799. doi: 10.1371/journal.pone.0044799. Epub 2012 Sep 24. PubMed PMID: 23049758; PubMed Central PMCID: PMC3461985.

For More Information

Ketamine Infusion for Depression

Ketamine for Depression – 2017