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Aim Event-related potentials (ERPs) obtained when focused attention is kept away from the stimulus (unnoticed stimulation) are possibly linked to automatic mismatch-detection mechanisms, and could be a useful tool to investigate sensory discrimination ability. By considering the high impact of impaired somatosensory integration on many neurological disturbances in children, we aimed to verify whether mismatch-related responses to somatosensory stimulation could be obtained in healthy children.
Method Eleven healthy participants (age range 6–11y, mean 8y 2mo, SD 1y 7mo; seven males, four females) underwent ‘oddball’ electrical stimulation of the right hand (80% frequent stimuli delivered to the thumb, 20% deviant stimuli delivered to the fifth finger). Data were compared with those obtained when the frequent stimuli to the thumb were omitted (‘standard-omitted’ protocol). ERPs were recorded at frontal, central, and parietal scalp locations. Children’s overt attention was engaged by a demanding video game.
Results In the oddball protocol, deviant stimulation elicited a left central negativity at about 160ms latency, followed by a left frontal negative response at about 220ms latency. Standard-omitted traces showed only a left parietal negative response spreading to right parietal regions.
Interpretation Mismatch-related somatosensory responses can be reliably obtained in children, providing that appropriate technical contrivances are used. In clinical use, the frontal components, which are present only during the oddball protocol, could be a reliable and unequivocal neurophysiological marker of the automatic mismatch-detection mechanism.
In recent years, increasing attention has been paid to the study of event-related potentials (ERPs) elicited when focused attention is kept away from the stimulus (unnoticed stimulation). In particular, for acoustic stimulation, earlier studies have clarified that two main types of ERPs can be elicited by unnoticed, deviant stimuli interspersed between regular and frequent stimuli, depending on their physiological characteristics.1 Deviant stimuli whose physiological features are different from regular ones, but which are not intrusive enough to cause an overt attention shift, usually elicit a frontal negative response in the 120 to 180ms latency range, labelled mismatch negativity (MMN).1,2 By contrast, intrusive deviant stimuli (i.e. stimuli that are able to catch the attention) elicit a frontal positive response at about 300ms latency (labelled P3a3), preceded by a negative response in the 120 to 180ms latency range (labelled N2b4). MMN and P3a often coexist in the same recording; however, MMN can also be elicited in the absence of a P3a response and when the stimulus does not catch the attention of the participant. In particular, earlier reports strongly indicate that MMN can also be elicited in comatose patients5 or when the stimulus is fully unnoticed,6 although focused attention can partially modify the final response.7 Assuming that the preattentive comparison between the memory track of the regular stimulus and the physiological features of the incoming one plays a crucial role in MMN elicitation, its recording can, in theory, provide useful information about a person’s ability to automatically discriminate unnoticed, slightly different, sensory stimuli.
So far, MMN responses have been studied more in auditory than in somatosensory modalities. In fact, because of the physiological characteristics of any somatosensory stimulus, it is difficult to conceive that a deviant somatosensory stimulation could not catch the overt attention of the participant. Nevertheless, somatosensory MMN-like responses have been reliably obtained in adults.8–13 In particular, it has been demonstrated recently that somatosensory MMN-like responses are often abnormal in patients with unilateral cerebellar lesions,13 suggesting that the discrimination of slightly different somatosensory stimuli is impaired in these patients. This finding seems particularly relevant given that, when patients with cerebellar lesions focused their attention on the stimulus during a clinical sensory test, they did not show significant somatosensory deficits. Therefore, MMN recording should be particularly promising in the assessment of disturbances characterized by a reduced somatosensory discrimination. Looking at potential clinical uses of somatosensory MMN in the paediatric neurological field, somatosensory discrimination impairment has been claimed to play a role in some developmental disorders, such as developmental coordination disorder,14 autism,15 and dyslexia.16
Because no data are yet available about somatosensory mismatch-related responses in children, we aimed to verify whether reliable mismatch-related responses could be obtained in a population of healthy children, whether the characteristics of the MMN-related responses in children were similar to those reported in adults, and whether their recording in children required specific technical contrivances. We therefore recorded scalp responses in children following electrical stimulation of the fifth right finger interspersed among frequent electrical stimulation of the right thumb (‘oddball’ protocol). Predictably, the technical procedure that we previously used in adults13 could not be automatically applied to young participants, because of their high distractibility by the deviant stimulus, as well as by electrical stimulation in general; the ultimate procedure was therefore adjusted after a number of preliminary experiments, described below. We also recorded responses elicited by the deviant stimulus alone, omitting the frequent stimulus (‘standard-omitted’ protocol). A similar procedure, already described in earlier reports8,9,13 is specifically addressed to ensure that differences between ERPs obtained after frequent and deviant stimulation during the oddball protocol are due to mechanisms related to the mismatch detection, rather than to the lower deviant stimulation rate, because it is well known that the stimulation rate is critical in affecting ERPs.17
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The results of this study confirm that mismatch-related responses can be reliably obtained in children. In a mismatch-detection condition (oddball protocol), traces issued from deviant stimulation clearly show a significant difference from those issued from frequent stimulation. Such a difference was mainly due to the constant presence of two successive components in deviant traces, the former peaking at about 160ms and the latter at about 220ms. The first component is recorded as a negativity in parieto-central regions contralateral to the stimulus, whereas the second one is recorded as a negativity in frontal regions contralateral to the stimulus. Moreover, traces issued from the standard-omitted protocol did not show any reliable left frontal component, thus confirming that this wave is unequivocally linked to a mismatch-detection mechanism. By contrast, despite some slight differences in scalp distribution, statistical analysis was not able to demonstrate any significant difference between the central negativity in the oddball protocol and the parietal negativity in the standard-omitted protocol. This could, however, be due to the small sample and to the low number of recording electrodes, which make it unlikely that statistical significance could be reached by means of the classical interaction approach. A definitive answer to the question whether the centro-parietal components in the oddball and standard-omitted protocols are generated by different mechanisms might be provided by a clear-cut dissociation in pathological conditions (see, for instance, cerebellar patients in Restuccia et al.13), but this is obviously impossible in our sample of healthy children.
Comparison with earlier data
As far as auditory MMN is concerned, Näätänen and Michie2 hypothesized that MMN-generating mechanisms require two successive steps: mismatch detection in the temporal lobes (sensory-specific for the auditory modality) and covert attention switching toward the unnoticed stimulus, involving frontal areas. Further studies largely confirmed that auditory MMN is built from temporal as well as frontal components.23,24 Thus, our present data seem to fit well with this general mechanism, as they demonstrate two main components of the somatosensory MMN, the former located in centro-parietal regions (sensory-specific for the somatosensory modality), and the latter in frontal areas contralateral to the stimulus.
Surprisingly, earlier studies in adults did not always show the coexistence of these two components. Frontal responses have been described by Kekoni et al.8 and by Kida et al.10 Shinozaki et al.9 also found a frontal extranegativity when the interstimulus interval was 1000ms as in our present study. Akatsuka et al.12 during an automatic 2-point discrimination protocol, found that parietal (SII) areas were mainly involved in building a mismatch-related somatosensory response, but, in a successive functional magnetic resonance imaging study, they found that not only parietal but also frontal regions are activated during a 2-point discrimination task.25 In our earlier study in adults13 we were not able to find frontal components, whereas mismatch responses to somatosensory stimulation were mainly localized on parieto-occipital scalp regions.
The simplest explanation for this discrepancy is related to the recording technique. In the earlier study, we used a reference electrode located over the nose; this recording technique can allow a reduction in amplitude of frontal responses, which are picked up not only from active leads, but also from the nose reference electrode, leading to an obvious decrease of the voltage difference between active and reference leads. However, another possible explanation could be related to the different characteristics of the primary task. Although the precise mechanism of this phenomenon has not been fully elucidated, many earlier findings suggest that frontal generators are mainly active when attentional resources are allocated toward a very demanding primary task,22 or when the deviance detection is difficult: for example, recent neuroimaging studies found that the magnetic resonance signal change in the right frontal cortex was larger for smaller deviants.26,27 It is, therefore, conceivable that frontal components are enhanced when stimuli are difficult to discriminate (e.g. vibratory stimuli8) or when attentional resources are allocated toward a very demanding primary task, as in the present study. However, whatever the reason the frontal response has been so variably recorded in previous adult studies, our present data demonstrate that a frontal response can be reliably recorded in children, and that this ERP is unequivocally related to mismatch-detection mechanisms, because it is fully lacking in control (standard-omitted) protocols.
From a practical point of view, our data demonstrate that somatosensory MMN responses can be reliably recorded in children, providing that appropriate contrivances are used. The use of a very demanding primary task seems to be mandatory, for two reasons. First, traces recorded during a less demanding primary task were characterized by a clear P3a component. In theory, this might suggest an overt attention shift toward the deviant stimulation and, in general, toward the stimulated hand; looking at some possible clinical uses of the somatosensory MMN, in particular the assessment of disturbances of the automatic somatosensory discrimination, this phenomenon should be avoided. Second, the use of a demanding primary task seems to allow an enhancement of the frontal MMN component, which is unequivocally related to a mismatch-detection mechanism.