Each year, it’s estimated that 1.5 million Americans sustain traumatic brain injury. As a result, many patients experience disorders of consciousness after the impairment.
Some patients experience vegetative state (VS), where a person is awake but shows no sign of awareness. Coma states in contrast are where patients both lack awareness and wakefulness.Other people go into a minimally conscious state (MCS) where patients experience partial preservation of conscious awareness. This state usually lasts four weeks.
Most patients endure a similar set of therapies for consciousness disorders. Patients go through various pharmacological treatments including zolpidem and amantadine.
Invasive treatments include deep brain stimulation (DMS). DMS includes an electrode being surgically implanted into the brain which send electrical signals to brain areas responsible for movement.
Other methods of therapy include vagal nerve stimulation (VNS), transcranial direct current stimulation (TDCS) and transcranial magnetic stimulation (TMS). You can learn more about these therapies by reading through my previous article.
However, no treatment has consistently shown beneficial effects on conscious awareness or functional recovery.
Brain Complexity and Consciousness
Many theoretical accounts of consciousness have related to the complexity in the neural system. One fo the most influential theories has been neural complexity. The neural complexity theory is divided into two fundamental features: differentiation and integration.
Differentiation is the property that any particular experience is composed of many different components and is distinguishable from any other experience. Integration is the property that any given conscious experience involves the integration of components into the unified whole.
Several theories of consciousness have emphasized a link between different formulations of complexity within brain activity at the conscious level. A prediction shared by many theories is that complexity should be high in the normal awake state and low whenever consciousness is lost (anaesthesia, REM sleep, brain injury).
The past few decades have shown increased advancement in consciousness. Including the perturbational complexity index (PCI). PCI quantifies the complexity of EEG responses to pulses of transcranial magnetic stimulation (TMS). The PCI approach is linked to hitting a bell and measuring the complexity of the reverberations that follow. PCI is highest during wakefulness, following MCS, and VS.
Psychedelics for Increased Brain Complexity
Since now, it was assumed that brain complexity is maximal during normal wakefulness, due to other tests showing reduced consciousness. It has since been found that brain complexity values recorded during psychedelic state exceed those found in normal waking consciousness.
Specifically, in humans, increased complexity is seen through psilocybin, lysergic acid diethylamide (LSD), and ketamine. These measurements can be replicated through the use of EEGs, MEGs, and fMRI.
Does Increasing Brain Complexity, Increase Conscious Awareness?
Knowing that impairments in conscious awareness are closely related to measures of brain complexity, should psychedelics elevate conscious awareness in patients with disorders of consciousness?
Psilocybin is currently going through substantial clinical investment. Psilocybin is a prodrug of psilocin whose principal psychoactive effects are mediated by serotonin 2A receptor. These drugs block the action of serotonin on nerves that transit impulses from the intestines to the brain.
The serotonin 2A receptor are densest in high-level cortical areas belonging to the default mode network which is implicated in conscious processing and psychedelic state. It’s also been found that cognitive flexibility is enhanced in humans under psychedelics.
Stimulants and Arousal for Conscious Awareness
There is currently no evidence that stimulant drugs such as D-amphetamine or methylphenidate (Ritalin and Adderall) increase brain complexity through increasing arousal.
Observations suggest that targeting increases in conscious content rather than arousal may be key to increasing conscious awareness in disorder of consciousness patients. The working hypothesis is that psilocybin is able to enhance conscious awareness to a greater extent than these stimulant- based alternatives.
The Ethics Behind Psychedelics
There’s also several ethical considerations that need to be taken with interventional research in patients with disorders of consciousness. On one hand, there’s concerns to harming a patient lacking the capacity to consent and on the other hand, research must be done if we want to progress our ability to improve the health of patients experiencing consciousness impairment.
Psilocybin has a particularly favourable psychedelic profile with low toxicity and addiction potential. Psychedelics with relevant safeguards produce positive rather than negative effects.
The psychedelic effects of psilocybin are detectable 30–60 min after oral dosing (10–25 mg), peaking at 2–3 h, and subsiding to negligible levels at least 6 h post-dose. Intravenous administration shortens the duration of the experience and accelerate the onset of the psychedelic.
In comparison to other therapies, deep brain stimulation has been carried out for 50 years with surgical implantation of electrodes. However, there’s a lack of consistent evidence of the benefits for improving conscious awareness.
People can also experience bad trips during psilocybin treatments. It’s difficult to understand the likelihood of a bad trip for patients given a psychedelic. A low baseline level of awareness might intuitively imply that unpleasant psychological phenomena will be less likely and less severe than in fully aware subjects.
The Future of Clinical Testing
While animal studies have informed our understanding the neural circuitry involved in information processing it’s less evident that any existing animal model acquired brain injury has relevance for the goal of understanding the recovery of conscious awareness in humans.
An alternative to injury models would be to test in sedated animals to see whether psilocybin increases measures of brain complexity from a baseline of sedative induced reduced complexity.
An advance on this would be to carry out the experiment in sedated healthy human volunteers. This could be done through measuring complexity with EEG on spontaneous EEG signals or using PCI, accompanied by behavioural measurements of consciousness, before and after psilocybin.
An incremental approach should be taken for the experiment, where the first steps are to establish safety and tolerability and examine the signal changes of interest. This would be followed by a focus on optimizing the dosage parameters, and measuring and searching for the desired behavioural effects.
Exclusion criteria should include a history of psychotic disorder. Serotonergic antidepressants have been found to down regulate the 5-HT2A receptor, and unfavoruable responses to psychedelics have previously been reported in individuals chronically medicated with serotonergic antidepressants. Therefore exclude any patients receiving these drugs or request controlled washout from these medications.
- Current therapy methods for disorders of consciousness include DMS, VNS, TDCS, and TMS which have not consistently shown beneficial effects on conscious awareness or functional recovery
- A prediction shared by many theories is that complexity should be high in the normal awake state and low whenever consciousness is lost (anaesthesia, REM sleep, brain injury)
- Brain complexity values recorded during psychedelic state exceed those found in normal waking consciousness.
- The hypothesis is that psychedelics may elevate conscious awareness in patients with disorders of consciousness
- There’s concerns to harming a patient lacking the capacity to consent and on the other hand but research must be done if we want to progress our ability to improve the health of patients experiencing consciousness impairment