The auditory oddball paradigm revised to improve bedside detection of consciousness in behaviorally unresponsive patients.

Active paradigms requiring subjects to engage in a mental task on request have been developed to detect consciousness in behaviorally unresponsive patients. Using auditory ERPs, the active condition consists in orienting patient's attention toward oddball stimuli. In comparison with passive listening, larger P300 in the active condition identifies voluntary processes. However, contrast between these two conditions is usually too weak to be detected at the individual level. To improve test sensitivity, we propose as a control condition to actively divert the subject's attention from the auditory stimuli with a mental imagery task that has been demonstrated to be within the grasp of the targeted patients: navigate in one's home. Twenty healthy subjects were presented with a two-tone oddball paradigm in the three following condition: (a) passive listening, (b) mental imagery, (c) silent counting of deviant stimuli. Mental imagery proved to be more efficient than passive listening to lessen P300 response to deviant tones as compared with the active counting condition. An effect of attention manipulation (oriented vs. diverted) was observed in 19/20 subjects, of whom 18 showed the expected P300 effect and 1 showed an effect restricted to the N2 component. The only subject showing no effect also proved insufficient engagement in the tasks. Our study demonstrated the efficiency of diverting attention using mental imagery to improve the sensitivity of the active oddball paradigm. Using recorded instructions and requiring a small number of electrodes, the test was designed to be conveniently and economically used at the patient's bedside.

Brain reactivity differentiates subjects with high and low dream recall frequencies during both sleep and wakefulness.

The neurophysiological correlates of dreaming remain unclear. According to the "arousal-retrieval" model, dream encoding depends on intrasleep wakefulness. Consistent with this model, subjects with high and low dream recall frequency (DRF) report differences in intrasleep awakenings. This suggests a possible neurophysiological trait difference between the 2 groups. To test this hypothesis, we compared the brain reactivity (evoked potentials) of subjects with high (HR, N = 18) and low (LR, N = 18) DRF during wakefulness and sleep. During data acquisition, the subjects were presented with sounds to be ignored (first names randomly presented among pure tones) while they were watching a silent movie or sleeping. Brain responses to first names dramatically differed between the 2 groups during both sleep and wakefulness. During wakefulness, the attention-orienting brain response (P3a) and a late parietal response were larger in HR than in LR. During sleep, we also observed between-group differences at the latency of the P3a during N2 and at later latencies during all sleep stages. Our results demonstrate differences in the brain reactivity of HR and LR during both sleep and wakefulness. These results suggest that the ability to recall dreaming is associated with a particular cerebral functional organization, regardless of the state of vigilance.

MMN and novelty P3 in coma and other altered states of consciousness: a review.

In recent decades, there has been a growing interest in the assessment of patients in altered states of consciousness. There is a need for accurate and early prediction of awakening and recovery from coma. Neurophysiological assessment of coma was once restricted to brainstem auditory and primary cortex somatosensory evoked potentials elicited in the 30 ms range, which have both shown good predictive value for poor coma outcome only. In this paper, we review how passive auditory oddball paradigms including deviant and novel sounds have proved their efficiency in assessing brain function at a higher level, without requiring the patient's active involvement, thus providing an enhanced tool for the prediction of coma outcome. The presence of an MMN in response to deviant stimuli highlights preserved automatic sensory memory processes. Recorded during coma, MMN has shown high specificity as a predictor of recovery of consciousness. The presence of a novelty P3 in response to the subject's own first name presented as a novel (rare) stimulus has shown a good correlation with coma awakening. There is now a growing interest in the search for markers of consciousness, if there are any, in unresponsive patients (chronic vegetative or minimally conscious states). We discuss the different ERP patterns observed in these patients. The presence of novelty P3, including parietal components and possibly followed by a late parietal positivity, raises the possibility that some awareness processes are at work in these unresponsive patients.

Attention orienting dysfunction with preserved automatic auditory change detection in migraine.

OBJECTIVE: To investigate automatic event-related potentials (ERPs) to an auditory change in migraine patients. METHODS: Auditory ERPs were recorded in 22 female patients suffering from menstrually-related migraine and in 20 age-matched control subjects, in three sessions: in the middle of the menstrual cycle, before and during menses. In each session, 200 trains of tone-bursts each including two duration deviants were presented in a passive listening condition. RESULTS: In all sessions, duration deviance elicited a mismatch negativity (MMN) showing no difference between the two groups. However, migraine patients showed an increased N1 orienting component to all incoming stimuli and a prolonged N2b to deviance. They also presented a different modulation of P3a amplitude along the menstrual cycle, which tended to normalise during migraine attacks. None of the studied ERP components showed a default of habituation. CONCLUSIONS: This passive paradigm highlighted increased automatic attention orienting to auditory changes but normal auditory sensory processing in migraineurs. SIGNIFICANCE: Our observations suggest normal auditory processing up to attention triggering but enhanced activation of attention-related frontal networks in migraineurs.

What is the specificity of the response to the own first-name when presented as a novel in a passive oddball paradigm? An ERP study.

One's own first-name is a special stimulus: one's attention is more likely captured by hearing one's own first-name than by hearing another first-name. Previous event-related potential (ERP) studies demonstrated that this special stimulus produces differential responses both in active and in passive condition. Such results suggest that passively hearing one's own first-name triggers processing levels generally activated by the explicit detection of stimuli. This questions about the particular power of the own first-name to automatically orient attention, but no study investigated the specific response to this special stimulus in a paradigm designed to study automatic attention orienting. In this ERP study, we compared the responses elicited by the own first-name (OWN) and one unfamiliar first-name (OTHER) presented, rarely, randomly and at the same frequency among repetitive tones (i.e., as novel stimuli in an oddball paradigm) while subjects (N=36) were watching a silent movie with subtitles. We tested at what latency the responses to OWN and OTHER diverge, and whether OWN modulates the brain orienting response (novelty P3). Data analysis showed specific responses to OWN after 300 ms. OWN only evoked a central negativity (320 ms) and a parietal positivity (550 ms). However, OWN had no significant effect on the brain orienting response (260 ms). Our results confirm that the own first-name does elicit a late specific brain response. However, they challenge the idea that in passive condition, the own first-name is systematically more powerful than another first-name to orient attention when it is heard unexpectedly.

Exacerbated attention orienting to auditory stimulation in migraine patients.

OBJECTIVE: To investigate long-term (LTH) and short-term (STH) habituation of auditory event-related potentials (ERPs) during a migraine cycle, using a classic habituation paradigm. METHODS: In 22 patients suffering from menstrually-related migraine and in 20 age-matched control subjects, auditory ERPs were recorded in 3 sessions: in the middle of the menstrual cycle, before menses, and during menses. In 12 patients, a migraine attack occurred during one of the peri-menses sessions. In each session, 200 trains of stimuli were presented, with an average of 10 stimuli per train. RESULTS: In response to the first stimuli of the trains, migraineurs exhibited in all sessions a larger orienting component of N1 than matched controls and a larger P3a in the interictal session, which normalized during attacks. They also showed a residual orienting component in response to the subsequent stimuli inside the trains. In contrast, the sensory component of N1 showed no difference between the two groups, with similar STH and LTH. CONCLUSIONS: Migraineurs show an exacerbated attention orienting to auditory stimulation, without any habituation deficit. SIGNIFICANCE: Previous migraine studies reported interictal habituation deficits of ERPs, but demonstrated in the auditory modality only in paradigms testing intensity dependence. Previous and current results can be interpreted as an increased attention orienting, possibly relying on an abnormal involvement of frontal cortex in auditory processing.

Novelty P3 elicited by the subject's own name in comatose patients.

OBJECTIVE: To assess patterns of novelty P3 elicited by the subject's own name (SON) in comatose patients and to compare SON novelty P3 prognostic value with that of mismatch negativity (MMN). METHODS: A passive oddball paradigm, previously validated in healthy subjects, including duration deviants and SON presented as a novel was applied in 50 severe comatose patients on average 20 days after coma onset. The outcome was assessed 3 months after coma onset. RESULTS: MMN to deviants was found in 14/50 patients and a central-parietal P3 to SON was found in 21/50 patients. In 12 patients, a parietal component (P3b) was also clearly present in the late part of P3. Four patients showed an MMN but no P3. Eleven patients had a novelty P3, with a late parietal component for 5 of them, but no MMN. The presence of a P3 was highly correlated with awakening. Compared to MMN, P3 showed as large a specificity for awakening (0.85). It showed a much higher sensitivity (0.71 versus 0.42). All but one patient with P3b woke up. CONCLUSIONS: The use of novelty P3 elicited by SON increases the prognostic value of MMN alone and improves the assessment of comatose patients by demonstrating the activation of higher-level cognitive functions in some of them. It shows that unconsciously perceived stimuli are processed and activate brain areas similarly to consciously perceived stimuli. SIGNIFICANCE: SON as a novel in an MMN design can be used to increase the prognostic value of ERPs in comatose patients and to assess unconscious cognitive processes in uncommunicative patients.

Odd sound processing in the sleeping brain.

How does the sleeping brain process external stimuli, and in particular, up to which extent does the sleeping brain detect and process modifications in its sensory environment? In order to address this issue, we investigated brain reactivity to simple auditory stimulations during sleep in young healthy subjects. Electroencephalogram signal was acquired continuously during a whole night of sleep while a classical oddball paradigm with duration deviance was applied. In all sleep stages, except Sleep Stage 4, a mismatch negativity (MMN) was unquestionably found in response to deviant tones, revealing for the first time preserved sensory memory processing during almost the whole night. Surprisingly, during Sleep Stage 2 and paradoxical sleep, both P3a-like and P3b-like components were identified after the MMN, whereas a P3a alone followed the MMN in wakefulness and in Sleep Stage 1. This totally new result suggests elaborated processing of external stimulation during sleep. We propose that the P3b-like response could be associated to an active processing of the deviant tone in the dream's consciousness.

Subject's own name as a novel in a MMN design: a combined ERP and PET study.

With a view to elaborating a clinical tool to assess cognitive functions in brain-damaged patients, we had previously displayed characteristic patterns of ERPs (32 electrodes) in awake healthy persons in response to their own name (SON) presented as a novel in a passive oddball paradigm. In the present combined ERP and PET study, in an attempt to identify brain correlates of duration MMN and response to SON uttered by a familiar (FV) or an unknown voice (NFV), we used a block design protocol as close as possible to the aforementioned SON protocol. ERP data showed robust duration MMN and novelty P3 in response to SON similar to our previous results. The PET technique did not allow true MMN generators to be disclosed, but blocks with duration deviants elicited an increase of activation in the right temporal pole as compared with the control condition with no deviants, supporting the hypothesis of right hemispheric dominance in early sound discrimination. For SON contrasts, robust cerebral blood flow activation present over temporal, frontal and parietal cortices, in the hippocampus and in the precuneus could be associated with speech, novelty and self-recognition processing. Familiar and unfamiliar voices activated the prefrontal cortex differently, suggesting different retrieval processes, although corresponding ERP responses could not be differentiated.

Brain responses to a subject's own name uttered by a familiar voice.

Hearing one's own first name automatically elicits a robust electrophysiological response, even in conditions of reduced consciousness like sleep. In a search for objective clues to superior cognitive functions in comatose patients, we looked for an optimal auditory stimulation paradigm mobilizing a large population of neurons. Our hypothesis was that wider ERPs would be obtained in response to the subject's own name (SON) when a familiar person uttered it. In 15 healthy awake volunteers, we tested a passive oddball paradigm with three different novels presented with the same probability (P = 0.02): SON uttered by a familiar voice (FV) or by an unknown voice (NFV) and a non-vocal stimulus (NV) which preserved most of the physical characteristics of SON FV. ERP (32 electrodes) and scalp current density (SCD) maps were analyzed. SON appeared to generate more robust responses related to involuntary attention switching (MMN/N2b, novelty P3) than NV. When uttered by a familiar person, the SON elicited larger response amplitudes in the late phase of novelty P3 (after 300 ms). Most important differences were found in the late slow waves where two components could be temporally and spatially dissociated. A larger parietal component for FV than for NFV suggested deeper high-level processing, even if the subjects were not required to explicitly differentiate or recognize the voices. This passive protocol could therefore provide a valuable tool for clinicians to test residual superior cognitive functions in uncooperative patients.

Mismatch negativity (MMN) in multiple sclerosis: an event-related potentials study in 46 patients.

OBJECTIVE: To assess pre-attentive detection mechanisms indexed by MMN component of auditory Event-Related Potentials (ERPs) in Multiple Sclerosis (MS) patients. METHODS: 46 MS patients (mean age 43.7 years, mean disease duration 10.1 years, mean EDSS 4.6) and 46 matched controls were assessed with ERPs elicited by a passive oddball paradigm using duration deviants. Auditory P50, N1, P2 components were recorded. MMN and P3a components were calculated as the difference potential between deviants and standard stimuli. Eighteen of these 46 patients underwent also global psychometrical assessment and were sorted in cognitively normal and impaired patients. ERPs of these two groups of patients were compared. RESULTS: MS patients showed reduced MMN and P3a areas as compared to controls, besides exogenous N1-P2 complex amplitude reduction. Among the 18 patients investigated with neuropsychological testings, six were cognitively impaired and 12 cognitively unimpaired. Patients with a global cognitive impairment had reduced MMN as compared to cognitively unimpaired patients. CONCLUSIONS: Auditory MMN and P3a components of auditory ERPs are altered in MS patients. MMN alterations are more pronounced in cognitively impaired patients. SIGNIFICANCE: MMN and P3a areas reduction suggests that MS patients are prone to pre-attentive auditory information processing deficits, besides previously described controlled information processing difficulties. Moreover, MMN alterations may represent an objective index of cognitive disturbances in MS patients.