Coma and Vegetative State

What is Coma and Vegetative State?

In terms of behavior, coma is defined as a state of not opening your eyes, not speaking, and not obeying orders. Coma is typically characterized by the absence of arousal (and thereby consciousness) and is often referred to as unarousable unresponsiveness. In the absence of autonomic motor activity, the recovery of spontaneous or induced eye-opening marks the transition from coma to vegetative state (VS). VS is characterized by unconscious awakening and no interaction with the environment. Usually, after one month of coma, the word “persistent VS” is used; after three months of nontraumatic insult or one year of a traumatic insult, some authors use “permanent VS”, which means there is no chance of recovery.

Fig.1 Awareness and wakefulness can be considered the two principal components of consciousness. (Bonsignore, 2014)

What Causes the VS?

In neuropathology, the VS is mainly marked by cortical or white matter and thalamic, rather than brain stem injury. Coma can be caused by diffuse bihemispheric cortical or white matter injury secondary to neuronal or axonal injury, or by focal brainstem injury affecting the bilateral pontine tegmentum and/or paramedian thalami bilaterally. Lower metabolism was reported in the thalamus, brainstem, and cerebellar cortex of comatose compared to non-comatose brain trauma survivors. The mechanisms underlying these changes in cerebral metabolism are not yet fully understood. In the VS, the brainstem is relatively spared whereas the grey and/or white matter of both cerebral hemispheres are widely and severely damaged. Overall cortical metabolism of vegetative patients is 40-50% of normal values. This progressive loss of metabolic functioning over time is the result of progressive Wallerian and transsynaptic neuronal degeneration. The other hallmark of the VS is a systematic impairment of metabolism in the polymodal associative cortices. These regions are known to be important in various functions that are necessary for consciousness, such as attention, memory, and language.

Fig.2 Simplified representation of the altered thalamocortical and cortico-cortical networks in the VS. (Laureys, 2002)

Role of Functional Neuroimaging in the VS

In recent years, techniques such as positron emission tomography, functional magnetic resonance imaging, and electroencephalography have been used to try to assess residual brain function and consciousness in vegetative patients without relying on motor behavior. Neuroimaging studies in patients in a VS have shown a consistent reduction in brain metabolism of as much as 50% and reduced basal resting-state activity. Although we agree that functional neuroimaging cannot confirm a diagnosis of VS, it is increasingly clear that functional neuroimaging can be used to rule out a diagnosis of VS and may even yield information about prognosis.

So-called “activation studies” using H₂¹⁵O positron emission tomography (PET) can be used to link changes in regional cerebral blood flow to specific cognitive processes, without the need for any overt response on the part of the patient. A significant development in this rapidly evolving field has been the relative shift of emphasis from PET activation studies using H₂¹⁵O methodology to functional MRI (fMRI) studies. Not only is MRI more widely available than PET, but it also offers increased statistical power and improved spatial and temporal resolution and does not involve radiation.

We have recently argued that fMRI studies in vegetative patients should be conducted hierarchically, beginning with the simplest form of processing in a particular domain and then progressing sequentially through more complex cognitive functions. In the auditory domain, such tasks would increase in complexity systematically from basic acoustic processing of non-speech sounds to more complex aspects of language comprehension and semantics.

Fig.3 A proposed hierarchical approach to the use of fMRI to assess residual cognitive function in patients in the vegetative state. (Owen, 2008)

The need to objectively measure phenomena associated with consciousness has promoted increased use of these neuroimaging and neurophysiological tools in this patient population. Functional neuroimaging has become the technique of choice for neuropsychologists, cognitive neuroscientists, and many others in the wider neuroscientific community with an interest in the relationship between the brain and behavior. At Creative Biolabs, we have the expertise to optimize each stage in neurosciences research to ensure you get your desired outcome, achieving the highest levels of efficiency throughout. Please feel free to contact us.

References

1. Bonsignore, L.T.; et al. Coma and vegetative states: state of the art and proposal of a novel approach combining existing coma scales. Ann Ist Super Sanita. 2014; 50(3): 241-8.
2. Laureys, S.; et al. Brain function in the vegetative state. Acta Neurol Belg. 2002 Dec; 102(4): 177-85.
3. Owen, A.M.; Coleman, M.R. Functional neuroimaging of the vegetative state. Nat Rev Neurosci. 2008 Mar; 9(3): 235-43.