Activation of a residual cortical network during painful stimulation in long-term postanoxic vegetative state: a 15O–H2O PET study
Introduction
Patients in the vegetative state (VS) are thought to be incapable of conscious experience of themselves and of external world while arousal is preserved [1]. VS is mostly caused by traumatic or nontraumatic (e.g. anoxic) brain injury and can be diagnosed using established clinical criteria (see below). If VS is still present 1 month after the underlying insult, it is called persistent vegetative state (PVS).
Functional neuroimaging, especially positron emission tomography (PET), has proven to contribute new aspects to the understanding of VS/PVS. Most PET studies measured resting brain metabolism and demonstrated a global reduction in cerebral metabolic rate for glucose [2]. Laureys et al. [3], [4] could show that in VS patients, the metabolically most impaired areas were the frontal and parietal associative cortices, whereas the most spared regions were basal forebrain, brainstem, and posterior hypothalamus and that cortico-cortical connectivity was altered [5]. In contrast to resting metabolism investigations, the imaging analysis of cerebral responses to external stimuli potentially provides deeper insights into preserved central processing of the patients' interaction with the external world. After single case reports [6], [7], functional disconnection was demonstrated in a systematic investigation in VS patients: primary auditory cortices, but not higher order multimodal association areas were activated during auditory stimulation [8].
One of the most important issues in the interaction with patients in the PVS is their sensation of pain. From the practical point of view, relatives and caregivers have to know if the patients feel pain during daily care, and this is often difficult to conclude from their reactions or mimicry and physical expressions. From the theoretical point of view, pain is an unpleasant experience that involves the conscious awareness of noxious sensations and aversive feelings associated with actual or potential tissue damage [9], and so cannot be separated from higher brain functions regulating consciousness and attention. The central nociceptive system as studied by various imaging techniques in normal subjects comprises the primary (SI) and secondary (SII) somatosensory cortices, the insular cortex, the anterior cingulate cortex (ACC), the dorsolateral prefrontal cortex (DLPFC), and the parietal cortex [10], [11], [12]. A recent PET study of noxious somatosensory stimulation in a group of patients in early stages of PVS (duration of about 1 month) described a partly functionally disconnected and dissociated central pain-related network [13]. In the present study, patients in considerably later stages of PVS were studied to investigate if correlates of cerebral nociceptive processing remain detectable in long-term PVS which is associated with severe brain atrophy.
Section snippets
Patients
The experiments were performed in accordance with the World Medical Association Declaration of Helsinki 2000. The protocol was approved by the Ethical Committee of the Faculty of Medicine of the University of Freiburg. The aims of the study were repeatedly explained to the relatives who were in close contact with the primary investigators; no financial support was offered to any of them. Written informed consent was obtained from the families of all patients (only spouses or parents were
15O–H2O PET
In response to painful stimulation, heart rate, respiration rate, and blood pressure increased markedly. However, there were no coarse movement artifacts in any patient. In the group analysis of 15O–H2O PET data, the comparison of the stimulation condition to the resting state showed significant perfusion changes at P<0.001 (uncorrected) in brain areas ipsi- and contralateral to the stimulation side. Effects consisted of regional perfusion increases only; there were no regional perfusion
Discussion
For persons who are involved in the care of patients in the PVS on a personal or professional level, it is often hard to interpret the patients' behaviours. With respect to pain, PVS patients for instance grimace or show fragmentary movement patterns after unpleasant external stimuli, and even in careful examinations, it is hardly possible to categorize these fractional patterns as related to limbic/brainstem networks or as expressions of activity at the cortical level. In general, partially
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- 1
Present address: Department of Neurology, University of Ulm, Ulm, Germany.
- 2
Present address: Department of Nuclear Medicine, University of Berne, Berne, Switzerland.