The default mode network and psychedelics

[Cotcha Yankinov]

Lack of suppression of the default mode network (DMN) has been associated with neuropsychiatric disorders like schizophrenia, ruminating depression, ADHD, and insomnia (see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501603/ for more on the DMN and disease).

A 2016 Nichols article http://www.ncbi.nlm.nih.gov/pubmed/26841800 -" Recent and exciting developments in the field have occurred in clinical research, where several double-blind placebo-controlled phase 2 studies of psilocybin-assisted psychotherapy in patients with cancer-related psychosocial distress have demonstrated unprecedented positive relief of anxiety and depression. Two small pilot studies of psilocybin-assisted psychotherapy also have shown positive benefit in treating both alcohol and nicotine addiction. Recently, blood oxygen level-dependent functional magnetic resonance imaging and magnetoencephalography have been employed for in vivo brain imaging in humans after administration of a psychedelic, and results indicate that intravenously administered psilocybin and LSD produce decreases in oscillatory power in areas of the brain's default mode network."

It appears that psilocybin increases suppression of the DMN http://www.ncbi.nlm.nih.gov/pubmed/22308440/ while ketamine either increases activity of the DMN and/or decreases task positive mediated suppression of the DMN http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478611/ (Any comments on the role of NMDA antagonism vs. AMPA modulation with metabolites on increasing DMN activity with ketamine is welcome)

Modafinil also interacts with the DMN, with the ventromedial prefrontal cortex apparently playing an important role in the increase in task induced deactivation of DMN and the increase in reaction time http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072511/

It appears LSD may decrease rumination of the past? http://www.ncbi.nlm.nih.gov/pubmed/26979587

Any discussion on the role of the DMN in mental illness and psychedelic's effects is welcome.

Edit: I'll add in this study regarding acute tryptophan depletion, ADHD and DMN http://www.ncbi.nlm.nih.gov/pubmed/27145324
Although I don't know what exactly to make of it; Maybe it has implications for MDMA related adverse effects?

 

[Jonneh]

I made some notes on Robin Carhart-Harris' research a while back. Some of them address a couple of your questions.

Default mode network

Ego/self
Higher global connectivity in depression
Higher inter regional connectivity predicts rumination scores

Results

Decreased blood flow in brain after psilocybin, esp. in DMN
Magnitude of decrease predicts intensity of effects
Consistent with effects of meditation
Ketamine (treatment for depression) decreases mPFC activity


Functional connectivity

Fluctuating activity of different regions in brain (even distal) can be synchronous
Can also be competitive (asynchronous)
Coupling strength between hippocampus and DMN regions predicts introspection and falling out of the moment (more predicts more)

Results

Psilocybin decreased functional connectivity between hippocampus and subcortical nodes belongin to DMN


Oscillatory power

Amplitude of oscillations in a given frequency band are a measure of firing synchrony

Results

Psilocybin decreased oscillatory power in bands from delta to high gamma, particularly pronounced in the alpha band
Alpha band decrease correlated with subjective rating of ego disintegration and with magical thinking (note: Freud linked the ego to animistic magical thinking style)


Cell activation

Psilocybin acts on serotonin 2A receptors

Results

Psilocybin activated deep (layer V) cortical pyramidal cells (according to MEG-based modelling approach), which have a concentration of serotonin 2A receptors
These cells are responsible for top-down predictions (providing context) under the free energy principle - overactivity might contaminate consciousness ('impetuous inference'). May explain visual distortions and hallucinations (seeing faces, for example)


Sense of oneness

DMN (self, internal) and attention (objects, external) networks compete.

Results

Psilocybin breaks down competition between DMN and attention networks
Competition decreases in schizophrenia and deep meditation
Network metastability decreases with psilocybin


MODEL

General theory of conscious states: sweet spot for brain entropy (low, but not too low)
In sweet spot: constrained, precise, confident cogition. Not easily surprised.

High entropy states (formlessness, disorder)

Sensory depreived
Early psychosis
REM sleep
Near death experience
Deep meditatory states
Psychedelic state

Low entropy states (petrification, inflexibility)

Depression (dominance of DMN)
Deep sleep
Seizure (hyper-synchronous neural activity)
Sedation

 

[Cotcha Yankinov]

Thank you very much

 

[Jonneh]

You're welcome!

I was absolutely obsessed with this stuff a couple of years ago (I found it through Karl Friston's work, which was my main focus - he's something of an intellectual hero of mine) and I still find it fascinating. A very entertaining aside. If you're comfortable with the more speculative aspects to these ideas, Robin has a paper called 'The Entropic Brain'. It's a fun read, and it brings together some of the most elegant ideas in neuroscience and philosophy (Tononi's Integrated Information Theory, Friston's Free Energy Principle, metastability etc) - and I think it'll have some more on the Default Mode Network (edit: lots more).

The biggest perspective shift I've ever known came from this obsession - truly psychedelic in its own right, and no drugs in sight - all expressed in the simplest of metaphors: that of the map and the territory. Don't go too deep with all this - actually do, it only gets better!