5 Chapter 5: Levels of Consciousness

The Essential Neuroscience of Human Consciousness

The Essential Neuroscience of Human Consciousness

Amedeo D’Angiulli

Chapter 5: Levels of Consciousness

5.1. Coma

5.2. Locked-in Syndrome

5.3. Brain Death

5.4. Vegetative State

5.5. Minimally Conscious State

5.6. A model of functional states across the spectrum of consciousness levels

Chapter 5: Levels of Consciousness

5.1. Coma

Coma is generally defined as a condition of unarousable unconsciousness. Physiologically, it is associated with failure of the ascending reticular activating system (ARAS); behaviourally, it is classified as failure to respond with eye opening to stimulation, a motor response no better than withdrawal movements, and verbal response no better than simple vocalizations with nonword sounds. Coma is generally assumed to have a gradient and can develop into other, improved conditions such as vegetative states.

Since ARAS has a dorsal pathway (via the thalamus) and ventral pathway (via the hypothalamus and basal forebrain) projecting to the cortex, and given the redundancies of pathways and neurotransmitters, recovery of arousal occurs in most cases within 3 weeks of coma onset. Inhibition of those two pathways causes the reversible unconsciousness of sleep. Disorders that produce transient or permanent coma include:

1. Lesions to brain structure
2. Metabolic and nutritional disorders
3. Exposure to exogenous toxins
4. CNS infections and septic illness
5. Seizures
6. Hypothermia and Hyperthermia
7. Trauma.

Structural brain lesions that produce coma involve destruction or compression of brain tissue. Single destructive lesions include ischemic stroke, hemorrhage, inflammatory lesions and tumors. In most cases, in order to cause coma, destruction must involve the rostral ARAS, diencephalons, and cortex bilaterally (though sometimes only the left hemisphere), in addition to parts connecting these structures. The more rostral (anterior, ventral) the insult, the more reversible the state of coma; this means the sleep-wake cycles could be restated relatively rapidly, and optimally within 2-3 weeks. However, the most important thing to understand here is that supratentorial mass lesions (above the tentorium cerebelli) can produce coma by herniation and compression. Herniation is a shift of brain structures from one intracranial compartment to another. Lateral herniation (shift of the midline supratentorial structures) of 9 mm or more usually determine coma with compression of the 3rd cranial nerve, leading to oculomotor nerve palsy. Uncal/Central Transtentorial herniation, which compresses downward, occurs less often. However, uncal and supratentorial herniations can worsen to become tonsillar herniation, which is terminal. It can occur not just as a condition worsens but by direct damage to the associated structures. This involves compression of the brainstem and medulla, behaviourally manifested by a lack of reflex in the contra- or ipsi- lateral pupil.

Coma can be caused by metabolic and toxic encephalopathies that produce diffuse disturbances with no localizing signs. These include

1) Metabolic failures (organs or hyper or hypo production of metabolites)

2) Syndromes linked to substances

• • Sympathomimetic (Cocaine)
  • Sympatholytic (Opiates, sedatives)
  • Cholinergic syndrome (insecticides)
  • Anticholinergic syndrome (antidepressants)

3) Interaction between respiration and metabolic pattern, such as hyper or hypoventilation causing excess base (alkali) or acid (acidosis) in the blood & body fluids

4) Reversible dysfunction of ARAS.

Systemic and CNS inflammation, such as meningitis, cause coma by indirectly affecting the cerebrospinal fluid circulation (CSF). Cytokines and chemokines are inflammatory agents responsible for the cascade effects that lead to coma, the most understood ones being Tumor necrosis factor (TNF) and interleukin-1 (IL-1). In short, these agents lead to the obstruction of CSF and then alterations of cerebral blood flow (CBF), which cause alterations in intracranial pressure and then coma. Encephalitis from virus or immune-mediated causes produces all sorts of inflammations just as mentioned, in addition to destroying tissue diffusely.

Hypothalamic or brainstem disorders from strokes, trauma or encephalitis that affect the temperature-regulating centres can also lead to coma. Hypothermia, a core body temperature    < 28oC, can produce coma. It is often secondary to hypothalamic or autonomic disorders. EEG shows a burst-suppression pattern between 30 and 22oC and becomes isoelectric (“flat”) at 20oC. CBF loses autoregulation at < 25oC. On the other hand, hyperthermia (fever), a core body temperature of > 42oC, can also cause coma. It produces encephalopathy, slowing of EEG and seizures.

Trauma leading to coma can include concussion, diffuse axonal injury (DAI) and secondary brain injury. Concussions are defined as a transient loss of consciousness or dazed state after a blow to the head (minicoma). Symptoms associated with it are anterograde amnesia (inability to build new memories, minutes to days after trauma) and retrograde amnesia (inability to recall events that occurred shortly before injury). After the blow, an initial hypermetabolic state is observed with transient brainstem impairment (no pupillary reflex, immobile or convulsive seizures). Concussions are typically due to dynamic physical distortion of rostral ARAS structures, consequent to a blow during acceleration/deceleration with some rotation. There is no accepted theory regarding loss of consciousness: current major hypotheses have vascular (causing global CBF reduction) or convulsive (seizures) mechanisms.

Diffuse Axonal Injury manifests as a real 2-3 weeks coma. The prognosis associated with it is generally less positive than other types of coma. DAI is due to serious blows to white matter. Originally thought of as a severing of the axons but not conclusively demonstrated as such, it turns out axons are often intact but severely damaged. The impression of severing is a secondary effect of axons disintegrating. In contrast, coma resulting from secondary brain injury is a complication following intracranial hemorrhage after structural brain lesions. Raised intracranial pressure (ICP) over and a beyond a certain normally observed range is generally the major factor associated with coma in these cases. There tends to be a continuous drain of blood and fluids (Cerebro-Spinal Fluid, CSF) in the skull proportional to arterial pressure due to pumping of blood from heart Cerebral Perfusion Pressure or CPP), but ICP above this mean normal average range blood pressure can make coma irreversible and lead to further complications, such as massive ischemic damage or brain death; this is because CCP is inversely related to ICP, when the latter surpasses the former beyond a critical level all fluids circulation stops in the brain and during brain death blood actually flows backward away from the brain). In some cases, intracranial hemorrhages are associated with prolonged seizures (status epilepticus) that cannot be stopped, which can be preventively monitored and possibly controlled through therapy intervention via a bedside EEG; if this does not happen, during status epilepticus nervous tissue is destroyed very quickly by out of control persistent seizures and this in turn creates CSF and CBF blockages and ICP to raise, so a very similar scenario as above.

Differential diagnosis of coma needs to be practiced to disambiguate the latter from other syndromes. Specifically, individuals with locked-in syndrome (LIS) only have the ability to open/close their eyes and move them vertically, which are the only signs that can discriminate between the behavioural presentation of these conditions. Another behaviourally similar but distinct condition is psychogenic unresponsiveness, in which individuals are awake and conscious but unable to communicate. These patients have various indications of consciousness that distinguish this condition from coma, most notably normal EEGs.

In many ways, coma represents a sort of fork leading towards two roads: improvement leading to a vegetative state or deterioration leading towards brain death. For now, let’s consider when things turn to worst.

5.2. Brain Death

It is quite uncontroversial to say that the invention of ventilators (positive-pressure ventilators) has created the artificial problem of brain death. The dissociation of brain functions from vital functions created ambiguity in determining what death is, in the sense that death cannot be established without determining what ‘vital functions’ are most vital to human life.

The most complete bio-philosophical conceptualization of brain death has been provided by the Dartmouth analysis of death (for a review see Bernat, 2009). The Darmouth analysis of death provides four conceptual phases to the process determining brain death.

• Phase 1: Agreement that we need an analysis to define death (paradigm of death)
• Phase 2: Defining death by explicitly agreeing on a consensual concept that has been confounded by technology
• Phase 3: Medical task of finding sufficient & necessary criteria that fulfill the definition
• Phase 4: Medical-scientific task of determining tests of death with no false positives (declaring people dead when they are not) and minimal false negatives (declaring people alive when they are not).

According to the paradigm of death, death is a non-technical word which makes explicit its ordinary consensual meaning. Death is biological, not social, and must thus conform to empirical biological facts; it only applies to organisms. Higher organisms are dead or alive and cannot be both. The definition is valid for Homo sapiens and related higher vertebrates. Death is an event, not a process: this statement has the purpose to separate the dying process from body disintegration. Finally, death is irreversible. The task of determining sufficient and necessary criteria that fulfill the definition of death has generated various models which have different degrees of consensus around the world. The existing models are

1. Whole-brain death (most accepted worldwide)
2. Brain stem death (U.K., India and Trinidad & Tobago)
3. Higher-brain formulation (not accepted by any institutional group).

Whole brain death is defined as irreversible cessation of the critical functions of the organism as a whole. The crucial vital functions are assumed to be the critical emergent properties that create the unity of the organism as a whole system. Consequently, the best satisfying criterion for death is the irreversible cessation of the entire brain’s clinical functions. Death is brain death and vice versa. Still, what corresponds to brain death? Brain death is satisfied by irreversible cessation of

1. Brain stem functions: Respiration and circulation
2. Diencephalon functions: Neuroendocrine and homeostatic regulation
3. Conscious awareness: Thalami, cerebral hemisphere and interconnections
4. All conditions determining intracranial circulatory arrest. An important implication is that observed isolated neural activity does not reflect critical functions (even if recorded by EEG)

The model of brainstem death is similar to whole-brain death. However, the criteria vary slightly, as it describes the irreversible loss of consciousness and breathing. This model’s logic is that brainstem impairment produces loss of functions that are sufficient for death, so all that should be assessed is the brainstem’s operation. Practically, differences between models are not substantial since most assessments of whole-brain death measure the loss of brainstem functions. However, an issue with this model is that the possibility of super locked-in syndrome remains: some consciousness might be preserved due to the diencephalon or cerebral hemispheres even when the brainstem is fully destroyed. If the only tests are at the level of the brainstem, this cannot be detected and creates a false positive. Another issue with this model is that it does not require an intracranial circulatory arrest test, which effectively eliminates false positives (i.e., it shows certain and sufficient global neuronal destruction).

According to the Higher-brain formulation, death equals loss of higher functions served by the cortex. This model is unique to Homo sapiens. The emphasis is on loss of conscious awareness with some important implications. Death would be practically determined by loss of consciousness and cognition, especially communication and verbal ability. But, by this definition, a condition such as vegetative state would mean death. An insurmountable issue with this model, therefore, is that individuals in persistent vegetative states are considered living or alive in many cultures.

At the other end of the spectrum, another radical idea called circulatory formulation proposes that the organism is dead when its systemic circulation ceases irreversibly. Thus, death would be established only based on evidence that the brain does not regulate circulation any differently than the spinal cord. This was initially based on Alan Shewmon’s cases of “chronic brain death”  whose circulation was preserved for months (for example, the  case of a child ventilated for 16 years with no recognizable brain tissue at autopsy, but manifesting some body growth). Currently, the circulatory formulation model has very limited following given a crucial flaw: in all cases used as supporting evidence, circulation was maintained because of ventilation, hence through technology.

What does the test of death imply? The test of “natural death” without artificial ventilation is relatively simple. Since loss of breathing and heartbeat produce hypoxemia from apnea and ischemia from asystole, which quickly destroys the brain, loss of those two functions is sufficient to declare death. The scenario becomes a lot more complex for the test of death with artificial ventilation, which warrants a full protocol. First, preconditions must be found showing irreversible loss of functions that are documented in brain structure and correlated neurological examination signs. Key findings from the neurological examination must be present, including deep coma; unresponsiveness to painful stimuli; absence of brainstem reflexes (pupillary, corneal, vestibulo-ocular, gag, cough); apnea in presence of hypercapnia (critical excess of carbon dioxide/CO2 probed in the blood via injection IV and then compared from and initial baseline test; meaning, if same CO2 concentration persists there is no “cleaning” of the blood from that toxin through voluntarily inhaled and metabolized oxygen, no real breathing).

Subsequently, a process of confirmation and declaration is triggered. The patient must show diffuse brain damage, coma and apnea during the neurological exam and evidence of structural lesions that explains the clinical signs. All potentially reversible metabolic or toxic conditions must be excluded. Findings must be confirmed by at least two examinations separated by some time, but the second exam can be omitted if a confirmatory test is performed. Objective confirmatory tests include EEG and brainstem auditory evoked potentials as well as tests showing cessation of intracranial blood flow (intracranial pressure being higher than arterial blood pressure), such as angiographies. It is important to note that intracranial blood flow tests are inconclusive in case of direct brainstem or cerebellum destructive lesions or after several days of brain death. The declaration of death then occurs during the second test and family is offered the opportunity to donate organs. Official records of tests and declaration must be filled out.

Declaring brain death allows the withdrawal of artificial life-sustaining therapy in irreversible circumstances. This then allows ethical organ donation (Dead-Donor rule), which would otherwise be just short of “killing”. The Dead-Donor rule prescribes that the organ donor must first be dead; it is unethical to terminate hopelessly ill donors, even with their consent. Declaration of death is a crucial ritual for many reasons and especially for medical practice, especially considering such controversial ones as Donation After Cardiac Death (DCD) protocols. The patient’s surrogate decision maker consents to end life-sustaining therapy in agreement with the patient’s prior wishes; organ procurement is planned; the patient is extubated and after 5 min asystole, declared dead; organs are then immediately obtained after declaration of death (kidneys, liver, etc). The quick turnaround without objective confirmatory tests is seen as problematic by many. Unfortunately, practically speaking, objective confirmatory tests are not conducted as frequently as theoretical models call for.

5.3. Locked-in Syndrome (LIS)

Locked-in syndrome (LIS) is defined by sustained eye-opening, preserved cognitive abilities, inability of producing sounds or low sound production (aphonia or hypophonia), paralysis of the upper, lower, right and left body (quadriplegia) and communication via blinking or eye movements.

LIS has been subdivided in three observed types: Classical, total immobility except eye movements or blinking; Incomplete, with some voluntary movement; and Total, complete immobility (including eye movements!) with preserved consciousness. LIS is most frequently associated with bilateral lesions of the ventral pons. The lesion’s cause is often vascular, through either basilar artery occlusion or a pontine hemorrhage. Other diseases leading to LIS are peripheral polyneuropathies (damage to motor, sensory, or autonomic nerves of the peripheral nervous system) and the end-stage of Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease (disease of the nerve cells in the brain and spinal cord that control voluntary muscle movement). Some conditions can mimic LIS, such as surgical interventions when patients receive muscle relaxants but not enough anesthetics to knock out consciousness.

Misdiagnosis is rather frequent in that LIS is often mistaken as coma. The first to see signs of LIS and to realize patients are fully conscious are family members, not treating physicians. There is an average lag of 2.5 months average between brain insult and LIS diagnosis. After being medically stable for 1 year, 83% of cases survive up to 10 years with 40% reaching around 20 years. The mean time spent in LIS is estimated to be 6 ± 4 years. Causes of death are mostly infections, recurrent brainstem strokes and the patient’s refusal to life support. Recuperation from vascular LIS is rare but has been reported. For example, recovery of some motor functions from non-vascular LIS occurs in a small number of patients. No real knowledge of rehabilitation exists for LIS, but some studies in Italy have shown that rehabilitation can produce recovery of some limited functions. It is estimated that 44% of LIS patients live home, where recovery of motor functions is most often reported.

LIS is apart from conditions such as coma because those affected can communicate through simple Yes/No signals. Selection of letters with eye movement, blink recorded by interlocutor and other such techniques can be effectively managed so that patients can reach complex levels of communication, including writing books or managing computerized databases. Electrical devices and computers controlled through eye movements are means by which those with LIS can conduct relatively “normal” lives. A promising avenue of research in further augmenting accessibility for these patients is the field of brain-computer interfaces (BCI) or neuroprosthetics. Most use neuroimaging to mediate control and execution of tasks, though the body’s bio-signals are another alternative. An extremely interesting example of this involves salivary pH changes that correlate with imagination or formation of mental images. As compared to a neutral baseline, imagining milk decreases pH while imagining a lemon increases it, which were respectively mapped to yes and no.

Neuropsychological testing of LIS cases a year or more after injury shows no cognitive impairments. EEG of these patients is generally normal, though a slightly larger proportion of slow waves is observed. Typical alpha waves are a common sign that suggests LIS diagnosis. Some experiments have shown that ERP signatures, such as the P300, that occur in response to someone’s own name have normal morphology and timing in LIS cases. Consistent with these observations, structural and functional imaging show no metabolic or activation differences with healthy controls. In contrast, an increase in metabolic and task-related activation has been reported in the amygdala, suggesting negative emotional experiences (anxiety, stress, etc).

What is it like to live with LIS? Small-scale survey data shows that LIS individuals can conduct many daily activities and have a meaningful life, especially with assistive technology like the afore-mentioned BCIs. Self-reported quality of life from these surveys is no different than normal controls, contrary to the common belief that LIS individuals want to die. Instead, frequency and intensity of suicidal thoughts is actually lower in these patients than the general population. This is important to keep in mind to avoid giving ill-informed advice as physicians and contributing to a wrong perception of this condition by the general public.

5.4. Vegetative State

The best prognosis for individuals in a coma is improving to a vegetative state (VS). The trademarks of VS are a lack of, inconsistent, unclear, or subjectively vague responses to commands. Hence, we are once more faced with the tragic problem of misdiagnosis. New neuroscience advances in this domain are again represented by the application of neuroimaging in bedside assessment. It can detect residual cognitive functions or even conscious awareness in patients considered to be in VS. Neuroimaging detects functions that standard clinical methods, such as the neurological examination, cannot. Thus, the background of this discussion of VS is how neuroimaging can give us insights into levels of consciousness beyond coma, starting from VS.

Patients in VS are awake but assumed to be totally unaware of their self and the environment. The term “vegetative” stands (not totally correctly) for mere physical life without intellectual or social activity, a body capable of growth and development but without sensation or thought. VS is classified as persistent VS (if persisting 1 month after brain injury) or permanent VS (if irreversible; 3 months after a non-traumatic brain injury, 12 months after a traumatic brain injury). If, at neurological examination, visual pursuit, reproducible visual fixation or responses to threats can be demonstrated reliably, then the VS diagnosis must be questioned.

Structural resting brain studies (without task stimulation) in VS have shown that cortical grey and white matter is compromised, with a relatively normal brainstem. Overall cortical metabolism is reduced to 40-50%, falling around 30-40% in permanent VS. ARAS metabolism is largely spared but polymodal associative cortices, i.e. Luria’s tertiary areas (prefrontal, lateral premotor, parieto-temporal, posterior parietal, precuneus; see Chapter 2, pp. 10-13), show metabolic impairment. Thus, the neural substrate for wakefulness is intact, but cognitive and behavioural functions are impaired. Note that rare cases of speech exist, with neuroimaging evidence of spared isolated networks. It is still not known if the impaired and depressed metabolism corresponds to irreversible structural neural loss or reversible functional damage. In individuals recovering from VS, recovery of metabolism in associative cortices detected by PET correlates with regaining awareness. In several cases, resumption of long-range thalamic connection with associative cortices correlates with recovery of cognitive functions.

Functional neuroimaging studies involving task-stimulation offer a growing understanding of VS as a very interesting level of consciousness. To begin with, PET studies have shown

1. Activation of anterior cingulate and temporal cortices to affective speech by the VS patient’s mother
2. Activation of the fusiform gyrus (FFA, the “face area”) to photos of family and close friends as compared to photos of scrambled controls, using the same amount and content of information in the visual displays shown to the patients
3. “Patchy” or “Isolated” activity in primary sensory cortices, not functional connectivity. In other words, integrative processing normally associated with awareness.

Hierarchical cognitive testing is a cognitive-behavioural technique used to discriminate the depth of VS among patients in terms of how integrated or functionally connected their brain areas are. This technique consists in testing a sequential progression of more complex cognitive functions, from acoustic stimuli (sounds) to complex language comprehension. One reason to use hierarchical cognitive testing is that activation responses to visual, auditory or noxious stimuli could be automatic, having nothing to do with awareness. We have seen that very complex aspects of language are subliminally processed, so even activation of entire pathways might not be meaningful enough to define the level of consciousness in VS. Very frequent stimuli such as names, faces or brief sentences are automatically processed without awareness, thus the “ultimate test” of conscious awareness still relies upon asking the person to communicate that they are conscious. Consequently, the tests stand on the ability to somehow communicate conscious awareness when the question is asked… which is exactly where the problem is, since VS is defined based on a lack of behavioural response!

Currently, fMRI studies pioneered by Adrian Owen show remarkable advances towards understanding VS. Single case studies or series by Owen have involved typical VS patients, such as after trauma or a traffic accident. Patients were given fMRI scan practice in creating two types of mental imagery (“playing tennis” and “visiting the rooms of your house”) and a control task (“just relax”). Prior studies in normal participants show activation of somatosensory areas in tennis imagery (and real-life play), while room imagery activates dorsal and ventral visual pathways in imagined or real “spatial navigation”. In VS individuals, Owen observed brain activation in the same areas, completely indistinguishable from normal controls. These occurred without being automatically elicited by language, lasted far longer than sentence processing and did so until the patient was told to relax. Although still hotly debated, these findings have suggested that for around 20% of the patients in which fMRI “interrogation” works, the residual conscious functions preserved in VS are far more present and subtler than predicted.

In light of such recent discoveries using fMRI (and EEG), there are a number of ethical implications involved in assessing VS and other states of impaired consciousness that lend themselves to the ethical problem of life-sustaining therapy. Misdiagnosis or misunderstanding of VS is still bound to happen; fMRI is an uncommon method of assessment and the neurological exam remains standard bedside practice. Other issues remain, such as invasiveness in performing some neuroimaging activation studies (i.e., PET) and the problem of consent, since these patients cannot properly consent to such procedures. Finally, and most importantly, the potential denial of life-saving therapy is ever-present if VS is not known and understood more appropriately via research. In this objective, neuroimaging research is not only desirable but imperative.

5.5. Minimally Conscious State

The minimally conscious state represents some improvement towards recovery from the vegetative state. Slow, subtle signs of recovery of environmental awareness manifest through inconsistent and ambiguous command-following. However, the signs of conscious behavior are initially difficult to replicate within or across examinations. Again, a major problem is misdiagnosis, since 15-43% of MCS cases are erroneously diagnosed as VS. Differential diagnostic of MCS is defined as minimal or intermittently clear behavioural signs of conscious awareness. Real consensus on these diagnostic criteria was only reached very recently.

At least one or more of the following signs should be replicable within the same examination and across different series of examinations (one or more of signs below): Yes/no responses (even if inaccurate); understandable verbalizations; movements or affective behaviours appropriate to context (not reflexive and meaningless). Recovery from MCS is shown by reliable and consistent interactive communication in any form (be it speech, writing, augmentative devices, gestures or behavior), as well as functional object use. That is, appropriate use (function of the object rather than simple manipulation) of 2 or more objects. Apraxia, aphasia and post traumatic amnesias must be ruled out both in transitioning to and exiting from MCS.

Table 2. Comparison between MCS, VS and Coma

In clearer, more consistent and easier cases, it is possible to use standardized neurobehavioural assessment measures. Items vary across measures, but all evaluate behavioural responses to auditory, visual, motor and communication prompts. Most have adequate reliability and validity but there is a lot of variability. One of the most widely used checklists is the Coma Recovery Scale-R (CRS-R), in particular because it is the only instrument that offers direct differential diagnostics of Coma, VS and MCS. To assess changes over time and improvement, conventional neurological exams and rating scales are generally inappropriate because of constant fluctuation and a lack of specificity/sensitivity. This is especially notable in differentiating random/reflexive from purposeful behaviors. In addition to standardized neurobehavioural assessment measures, clinicians also adopt individualized behavioural assessment protocols and Individualized Quantitative Behavioural Assessments (IQBA). For the most difficult, ambiguous, inconsistent cases, however, it is necessary to use the scientific experimental method and follow a step by step strategy. First, a target behaviour (ex: command-following) must be selected for assessment. Second, a systematic protocol must be established to record the frequency of behaviour to A) Appropriate match to command; B) Inappropriate match to command; C) Resting interval(s). Finally, statistical analysis needs to establish whether the target behaviour occurs significantly more in (a) than in (b) or (c).

There are many issues around estimating reliable incidence of MCS. Several problems affect diagnostics like a lack of training, of surveillance outside primary or intensive care and the absence of reliable international diagnostic codes. The best estimates of prevalence come from California studies and population census extrapolations, that show prevalence of VS to MCS could vary between 1 to 10 and 1 to 7. Visual pursuit recovery predicts improvement and recovery from MCS. Improvement on the Disability Rating Scale over the first two weeks of rehabilitation also predicts recovery/positive outcome for MCS. Duration of MCS is not related to the level of recovery or outcome. Life expectancy is similar in persistent/permanent MCS and VS (~ 8 years).

Current clinical and pathological studies suggest two possible scenarios for MCS:

1. Extensive uniform brain injury (derived by the usual causes: hypoxia, ischemia, DAI)
2. Focal brain injury combined with minimal DAI or ischemia

The most interesting aspect of MCS, however, is the conceptual model it offers in terms of consciousness. In small sample studies, functional brain imaging via fMRI has shown activation of the language global network, whereas resting studies have shown low resting metabolism (as reflected by PET) globally and in damaged hemispheres. EEG “coherence” also seems reduced, but the distribution of EEG frequencies looks quite normal. These brain studies are consistent with observed behavioural fluctuations in MCS. Thus, evidence from different sources converges in suggesting that MCS involves a limited behavioural repertoire with intact large-scale networks. The current most plausible neuropathological account of MCS is that this syndrome reflects instability in initiating, maintaining and completing behavioural sets. In other words, it appears to be a pathology of the “gating systems” in the ascending ARAS (RAS, Thalami, Cortex).

Available evidence suggests MCS could reflect the preservation of some functional large-scale network with fluctuating baseline brain activation. The apparently normal EEG spectrum means that networks of thalamo-reticular and cortical pyramidal neurons are preserved to generate EEG in small local processing networks. If inter-regional coherence of EEG activity for thalamic firing during wakefulness is disrupted, hypothetically, this would disrupt organization of behavior. It is possible that the disruption of larger-scale neuronal networks may produce dysfacilitation or loss of long-range connectivity between brain areas. Further support for this hypothesis comes from findings of low metabolism in default mode networks of MCS patients.

5.6. A model of functional states across the spectrum of consciousness levels

Nicholas Schiff (2009) has proposed a synthesis of what is behaviourally observed in the impairment of levels of consciousness by mapping functional states and their corresponding inferred level of consciousness. In his model, normal consciousness corresponds to showing normal cognitive and motor functions. We have seen in previous sections that cognitive function has been reduced to the ability to communicate in different degrees and being able to move/act to a certain extent. In a normal, fully conscious state, we would predict an individual to report his cognitive functions and recognize his own state, as well as perform meaningful context-appropriate actions mostly through movement. The latter also is the “target” of full recovery for cases of impaired consciousness.

Following the above logic, both coma and VS can be conceptualized at the extreme end of the spectrum of total to substantial loss of cognitive and motor functions. VS is a bit better in terms of motor functions but equally deficient in terms of cognition. MCS represents a step forward in that the functions it includes are dramatically better for cognition, with the functions’ upper limit bordering on minimal functionally effective communication. However, MCS still lags behind in terms of motor function, since it represents a mild improvement when compared to coma and VS. The next state of improvement can be labeled as severe to moderate (mild) cognitive disability, which include a range of improved motor functions bordering on normal but impaired cognition. Recovering further cognitive functions with normal motor abilities is a full recovery. However, LIS and similar states are the exception, in that these states have normal cognitive functions but nearly non-existent motor functions.

Schiff also provides a discussion of the underlying neural mechanisms associated with these different states. In particular, the borderline MCS seems to have preserved functional cerebral integration of large-scale networks, which further elaborate and integrate the input from isolated modular networks. However, residual MCS functions in these isolated modular networks do not always receive the metabolic “fuel” they need to sustain ongoing baseline brain activation. We can refer to Luria’s primary, secondary and tertiary functions (see Chapter 2; pp. 10-13), though this recent systematization is more precise and subtle than Luria in terms of how distributed and specific processing is coordinated in the brain. While I have discussed the integrated, or global vs local, nature of mechanisms underlying conscious and unconscious processes, we will discuss ongoing baseline brain activity next.