Auditory processing in the vegetative state

2004

The interest of functional imaging in patients in a vegetative state is twofold. First, the vegetative state continues to represent a major clinical and ethical problem, in terms of diagnosis, prognosis, treatment, everyday management and end-of-life decisions. Second, it offers a lesional approach to the study of human consciousness and adds to the international research effort on identifying the neural correlate of consciousness. Cerebral metabolism has been shown to be massively reduced in the vegetative state. However, recovery of consciousness from vegetative state seems not always associated with substantial changes in global metabolism. Recent PET data indicate that some vegetative patients are unconscious not just because of a global loss of neuronal function, but due to an altered activity in a critical fronto-parietal cortical network and to abolished functional connections within this network and with non-specific thalamic nuclei. Recovery of consciousness was shown to be paralleled by a restoration of this cortico-thalamo-cortical interaction. Despite the metabolic impairment, external stimulation still induces neuronal activation as shown by both auditory and noxious stimuli. However, this activation is limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception.

… on Disability and …, 2010

Previous studies, using neuroimaging and electrophysiology, have identifi ed the presence of cerebral responses to auditory stimulation in clinically unresponsive persistent vegetative state (PVS) patients. In normal individuals, it has been shown that stimulation with emotional content has a strong infl uence on autonomic cardiovascular regulation tested by heart rate variability (HRV). In this paper, we assessed responses to auditory stimulation with emotional content in PVS and minimally conscious (MCS) cases by HRV. We found patterns of changes induced by auditory stimulation in three of our patients (decreased heart rate, increased HRV, decrease power in the low and increased power in high frequencies) is consistent with increased cardiovagal stimulation. Both time and frequency domain changes were more pronounced during affective than during non-affective auditory stimulation, suggesting that PVS patients are able to discriminate between stimuli of different content and are more reactive to emotional than non-emotional stimulation. Our results demonstrated that auditory stimulation can induce recordable changes in HRV in some PVS cases, providing evidence that these patients retain some preserved cognitive function examined by cardiovascular correlates. The use of HRV to study residual cognitive functions could have practical implications for the management of PVS and MCS.

2004

Cerebral metabolism is massively reduced in the vegetative state. However, recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. We could show that the most dysfunctional brain regions in vegetative patients are bilateral frontal and parieto-temporal associative cortices. Yet, despite the metabolic impairment, external stimulation still induces a significant neuronal activation in vegetative patients as shown by both auditory and noxious stimuli. However, this activation is limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we could show that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction.

2002

Abstract Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates for glucose are massively reduced in this condition. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism.

Clinical Medicine, 2008

The vegetative state (VS) is a devastating clinical condition characterised by wakefulness without awareness. Functional neuroimaging permits to objectively measure brain responsiveness to external stimuli in VS. The literature on functional magnetic resonance imaging and positron emission tomography studies in these patients has been reviewed. Results from 15 studies were classified in: absent cortical activation or 'typical' activation of 'low level' primary sensory cortices and 'atypical' activation spreading to 'higher level' associative cortices. This descriptive review on 48 published cases suggests that 'atypical' activation patterns seem to herald recovery from VS with a 93% specificity and 69% sensitivity. Passive stimulation paradigms, however, do not permit to make strong claims about the absence or presence of consciousness. Recently proposed mental imagery paradigms permit to identify signs of consciousness in non-communicative brain damaged patients. The clinical application of these functional neuroimaging techniques awaits validation from ongoing multi-centric cohort studies in these challenging patients with chronic disorders of consciousness.

Archives of Neurology, 2004

The minimally conscious state (MCS) is a recently defined clinical condition; it differs from the persistent vegetative state (PVS) by the presence of inconsistent, but clearly discernible, behavioral evidence of consciousness.

Scientific Reports

this study attempts to answer the question: "is hearing the last to go?" We present evidence of hearing among unresponsive actively dying hospice patients. Individual ERP (MMN, P3a, and P3b) responses to deviations in auditory patterns are reported for conscious young, healthy control participants, as well as for hospice patients, both when the latter were conscious, and again when they became unresponsive to their environment. Whereas the MMN (and perhaps too the P3a) is considered an automatic response to auditory irregularities, the P3b is associated with conscious detection of oddball targets. All control participants, and most responsive hospice patients, evidenced a "local" effect (either a MMN, a P3a, or both) and some a "global" effect (P3b) to deviations in tone, or deviations in auditory pattern. importantly, most unresponsive patients showed evidence of MMn responses to tone changes, and some showed a P3a or P3b response to either tone or pattern changes. Thus, their auditory systems were responding similarly to those of young, healthy controls just hours from end of life. Hearing may indeed be one of the last senses to lose function as humans die. In the last hours before an expected natural death many people enter a period of unresponsiveness, during which they no longer respond to their external environment. This can be a profound and spiritual time for families, but it is currently unknown whether unresponsive patients are aware of the touch or words of their loved ones. There is a persistent belief, however, that some unresponsive patients may still be aware of touch and sound 1 , despite being unable to reliably signal their awareness. Much of this belief comes from reports of near-death experiences (NDEs), where a common recurring element of this experience is hearing unusual noises or hearing oneself pronounced dead 2-4. Reports from NDEs, however, are difficult to interpret, because incidence of NDEs is low, between 6% 5 and 12% 6 of cardiac arrest survivors, and the cognitive neuroscience underlying NDEs remains hotly debated 7-9 and poorly understood 10-12. Further perpetuating the belief that "hearing is the last to go" are some family members and health care providers who have reported that unresponsive patients will occasionally groan or make a small facial movement in response to hearing a familiar voice, but to our knowledge there is no empirical evidence to corroborate these anecdotes 13. is it possible for a dying brain to sustain awareness? Neuroprotective mechanisms, mainly the blood-brain barrier, reduce neuronal firing in response to ischemia (a common physiological cause of unresponsiveness at the end of life), which could protect the brain from irreversible brain damage under these conditions 14. The brain's tolerance to ischemia has been demonstrated in autopsy, as only about 60% of patients who had been declared brain dead before death showed signs of moderate to severe cortical ischemia, and only about 30% in deep brain structures such as the thalamus and basal ganglia, and a similar percentage in the cerebellum 15 (see also the following responses 16,17). The brain, therefore, may be somewhat resistant to the effects of ischemic damage while the rest of the body shuts down just before death. In addition, opioids can reduce behavioural responses to external stimulation, without necessarily reducing awareness 18. Pain and shortness of breath are common symptoms among the physiological changes that occur at the end of life 19-21 , and are frequently controlled with opioids 22-24. Patients who are being treated for pain with opioid medications could, therefore, become less responsive to their external environment as they enter the final stage of dying, but may retain some covert awareness. Finally, a surge of cortical gamma power and connectivity is present in the rat brain for 30 seconds immediately following cardiac arrest 25 (see also the following response 26). Because synchronous gamma oscillations have been linked to conscious cognitive processing in humans 27-31 , increased gamma synchrony could generate an NDE immediately after cardiac arrest (this interpretation is, however, debated) 26. Although these studies point to the potential for awareness in the dying brain, they speak to neurophysiological

Electroencephalography and Clinical Neurophysiology/Evoked Potentials Section, 1991

BAEP records were obtained from 30 brain-dead patients. Three BAEP patterns were observed: (1) no identifiable waves (73.34%), (2) an isolated bilateral wave I (16.66%), and (3) an isolated unilateral wave I (10%). When wave I was present, it was always significantly delayed. Significant augmentation of wave I amplitude was present bilaterally in one case and unilaterally in another. On the other hand, in serial records from 3 cases wave I latency tended to increase progressively until this component disappeared. During the same period, wave I amplitude fluctuations were observed. A significant negative correlation was found for wave I latency with heart rate and body temperature in 1 case. Two facts might explain the progressive delay and disappearance of wave I in brain-dead patients: a progressive hypoxic-ischaemic dysfunction of the cochlea and the eighth nerve plus hypothermia, often present in brain-dead patients. Then the incidence of wave I preservation reported by different authors in single BAEP records from brain-dead patients might depend on the moment at which the evoked potential study was done in relation to the onset of the clinical state. It is suggested that, although BAEPs provide an objective electrophysiological assessment of brain-stem function, essential for BD diagnosis, this technique could be of no value for this purpose when used in isolation.

Neurosurgical Review, 1989

The Lancet Neurology, 2004

Running title: Brain function in severe brain damage Word count abstract : 155 words Word count text (excluding references): 4865 words N° of references: 115 2