Assessment of wakefulness in comatose patients using transcranial magnetic stimulation

  The clinical assessment of patients with disorders of consciousness is a repeated behavioral scale performed by experienced clinicians to study and evaluate the patient’s spontaneous movements and his/her responses to multisensory stimuli. In particular: 1) signs of perception of self or external environment; 2) sustained, reproducible, or voluntary responses to tactile, auditory, or noxious stimuli; 3) signs of language comprehension or expression, etc. Patients who fail to detect any of these behavioral features during a careful and repetitive examination are recognized as being unconscious; whereas patients who exhibit nonreflexive behavior but have mild communication are considered to be in a minimally conscious state. Thus, according to the clinical definition of consciousness, it is possible to demonstrate that the patient is conscious, “conscious”. Motor function is also impaired in patients with severe brain injury, where neither movement nor speech may occur. The presence of consciousness can be inferred from a patient’s clinical signs of voluntary behavior, but the absence of these signs does not imply unconsciousness.  Recently, new functional neuroimaging techniques have been developed that make it possible to detect signs of complete unconsciousness. For example, a patient with a clinical diagnosis of vegetative state who appeared to be unconscious was scanned and instructed by the investigator to imagine playing tennis or walking around the house. This patient showed an activation image similar to that of a normal person performing this task, indicating that the patient could comply with the command by thinking despite the lack of motor response. In contrast, many patients cannot respond positively to this paradigm, but are conscious. Patients with aphasia, motor mutism, catatonic depression, or diffuse dopaminergic impairment, for example, are likely to respond extremely weakly to commands despite the presence of cognitive function. In addition, given the frequent motor artifacts and possible altered neurovascular coupling in patients with disorders of consciousness, functional MRI data are extremely challenging to obtain and interpret.  Behavioral assessment and functional imaging reflect two different levels of consciousness levels in patients with disorders of consciousness. Neither can be certain whether a nonresponding patient represents unconsciousness.  Recently we have proposed that the application of transcranial magnetic stimulation and EEG to assess the brain’s ability to produce consciousness, even if the patient is unable to communicate through behavioral or neurological activity, allows another level of consciousness to be studied. The ability of the subject’s brain to generate conscious perception is directly assessed. Requirements are: (1) to know theoretically which features are important and essential in the organizational system that produces conscious experience; and (2) to find and implement measures to detect these features. Here we take the theory of integrated information. It stipulates that consciousness is equivalent to integrated information, and that the human body should have the capacity to produce conscious perception and to reach the point of presenting a large number of different states of input (information) in an integrated and comprehensive manner, rather than isolated and fragmented subsystems separately (integration). A specific method for assessing the brain’s ability to integrate information is then established. Combined application of transcranial magnetic stimulation and EEG with TMS-EEG testing method. This technique allows the direct stimulation of different clusters of cortical neurons and the recording of immediate responses in the remaining unstimulated brain regions. This method is currently considered to be an effective method for specific responses (information) and interactions (integration) in different regions of the thalamocortical system.  Some tests of the theoretical predictive value behind this technique in sleep and anesthesia states It was shown that in the reduced consciousness state, brain responses were clearly found to lose the characteristics of the waking state. The first study was conducted during slow-wave sleep, which is known to be a significantly reduced content of consciousness in the slow-wave sleep state. As observed in the waking state, the brain in slow-wave sleep has a very restricted response area to TMS, and its integration is also observed to be missing. Even when more extensive responses were observed, these responses were spatially diffuse and evenly transmitted in the brain, unlike the complexity observed in the waking state.  The second study was conducted under deep sedation using midazolam. The responses monitored by TMS when subjects lost consciousness were very different from those in the waking state. TMS under deep sedation produced a typically restricted and fixed response, similar to a restricted slow wave, and did not spread to the rest of the cortex. Brain connectivity is substantially reduced, especially in long-range connectivity, and the response is brief, lasting no more than a few tens of milliseconds, in contrast to the complex and sustained response in the awake state. The results suggest that the state of loss of consciousness under anesthesia is associated with a loss of brain integration capacity. Moreover, this typically fixed response also indicates a loss of brain region-specificity, i.e., loss of information. In sleep as well as in the anesthetized state, TMS elicits the generation of consistent fixation responses not only due to the loss of brain integration capacity, but also the loss of specificity of different brain regions (information loss)