Elsevier

NeuroImage

Volume 27, Issue 4, 1 October 2005, Pages 737-752
NeuroImage

How do children prepare to react? Imaging maturation of motor preparation and stimulus anticipation by late contingent negative variation

https://doi.org/10.1016/j.neuroimage.2005.05.020Get rights and content

Abstract

Both the motor system and the frontal executive control system show a late maturation in humans which continues into school-age and even adolescence. We investigated the maturation of preparation processes towards a fast motor reaction in 74 healthy right-handed children aged 6 to 18 years and analyzed the topography of the late component of contingent negative variation (lCNV) in a 64-electrode high density sensor array. While adolescents from about 12 years on showed a bilaterally distributed centro-parietal maximum like adults do, younger children almost completely missed the negativity over the left central area contralaterally to the side of the anticipated movement. The reason, as revealed by current source density, was that only adolescents showed significant evoked activity of the left pre-/primary motor and supplementary/cingulate motor areas, while in contrast both age groups displayed significant current sinks over the right (ipsilateral) centro-temporal area and right posterior parietal cortex. Spatio-temporal source analysis confirmed that negativity over the right posterior parietal area could not be explained by a projection via volume conduction from frontal areas involved in motor preparation but represented an independent component with a different maturational course most likely related to sensory attention. Significant event-related desynchronization of alpha-power over the contralateral sensorimotor cortex was found in the younger age group, indicating that also 6- to 11-year-old children were engaged in motor preparation. Thus, the missing current sink over the contalateral sensorimotor cortex during late CNV in 6- to 11-year-old children might reflect the immaturity of a specific subcomponent of the motor preparation system which is related to evoked (late CNV) but not induced activity (alpha-ERD).

Introduction

Both the motor system as well as the (pre-)frontal executive control/attention system undergo prolonged maturation through school-age until adolescence in human subjects (Bender et al., 2002, Casey et al., 2000, Chiarenza et al., 1983, Diamond, 2000, Timsit-Berthier and Hausmann, 1972, Warren and Karrer, 1984a, Warren and Karrer, 1984b). Electrophysiological methods such as multichannel analysis of contingent negative variation (CNV, the negative potential occurring between a warning and an imperative stimulus) with their high temporal resolution are able to map maturational functional differences in the time course of cortical activation during motor preparation and sensory attention (Brunia, 1988, Brunia et al., 2000, Cui et al., 1999, Deecke, 1996, Hallett, 1994). Understanding the maturation of the brain during childhood and adolescence seems important, not only to prove that children are no “little adults” and to show specific differences in information processing, but also to understand the course and pathogenesis of a variety of illnesses such as attention-deficit/hyperactivity disorder (ADHD), schizophrenia or migraine, where different developmental models have been proposed (Gittelman et al., 1985, Klein and Mannuzza, 1991, Kropp et al., 1999a, Kropp et al., 1999b, Oelkers-Ax et al., 2004, Weinberger, 1987), and CNV shows abnormalities during childhood and/or adult age (Banaschewski et al., 2003, Bender et al., 2002, Besken et al., 1993, Cherniak et al., 2001, Klein et al., 1996a, Kropp et al., 1999a, Kropp et al., 1999b, Rockstroh et al., 1989, van Leeuwen et al., 1998, Verleger et al., 1999). However, so far, there are no data available about the cortical CNV generators during childhood and adolescence which could elucidate possible maturational and/or pathogenetic changes.

A network model of frontal lobe executive functioning based on primate research has been established for the CNV paradigm (Fuster, 2000, Fuster, 2002), according to which distinct neuronal populations in dorsolateral prefrontal cortex (DLPFC) form recurrent circuits with posterior polymodal association cortices (related to short-term memory and sensory attention) and (pre-)motor areas (related to motor preparation and memory). Temporal gaps between the warning and the imperative stimulus are bridged by reentering excitation between these areas and DLPFC. This model is corroborated by subdural recordings in humans (Hamano et al., 1997) showing sustained activation during the interstimulus interval in prefrontal cortex (PFC), motor areas and posterior sites depending on stimulus modality. Though in scalp surface EEG recordings movement-related PFC activity is often not detected as a separate generator (Babiloni et al., 1999, Botzel et al., 1993, Cui et al., 1999, Picton et al., 1995), the potentials produced by the areas which DLPFC interacts with (cortical motor areas and posterior association areas) produce characteristic far fields during late CNV.

The late component lCNV prior to the target stimulus S2 reflects both expectancy and motor preparation (Rockstroh et al., 1989, Gaillard, 1977). Though negativity related to motor preparation provides a major contribution to late CNV, it is not identical with the Bereitschaftspotential (BP, reflecting mostly supplementary motor and pre-/primary motor cortex activation) (Cui et al., 2000, Gaillard, 1977) and can also be elicited under non-motor conditions (Ruchkin et al., 1986), suggesting also “non-motor” stimulus-dependent components which reflect anticipatory sensory attention (“stimulus preceding negativity”, SPN, Brunia and Damen, 1988, Gomez et al., 2001) in posterior association/sensory areas.

The early component iCNV after the warning stimulus S1 represents most likely an orienting response (Rockstroh et al., 1989) as well as early response selection and task anticipation processes (Bender et al., 2004a, Rockstroh et al., 1989).

A third negative component following after the imperative stimulus and the response, postimperative negative variation (PINV), seems to consist of at least two different subcomponents (Bender et al., 2004b, Verleger et al., 1999). PINV from about 1000 ms after the response shows a lateral fronto-temporal maximum with a small right-sided preponderance and has been related to contingency evaluation or uncertainty about the correct response (Klein et al., 1996a, Klein et al., 1996b, Rockstroh et al., 1997, Bender et al., 2004b). An earlier motor PINV component occurs over central areas and is strongly lateralized contralaterally to the side of a response movement with the dominant right hand (Bender et al., 2004b, Verleger et al., 1999). It differs topographically from late CNV which includes rather bilateral centro-parietal negativity (Bender et al., 2004b).

Recently, low-resolution electromagnetic tomography analysis (LORETA) has suggested that supplementary motor area and anterior cingulate become activated early during CNV and together with prefrontal cortex recruit during late CNV those motor and sensory areas needed for a fast response after the imperative stimulus (Gomez et al., 2003). The importance of thalamus, anterior cingulate and the supplementary motor area for CNV generation is corroborated by fMRI data (Nagai et al., 2004).

Previous developmental studies have shown that the BP–the slow negative potential preceding voluntary self-paced movements which is thought to be related to the motor preparation component of lCNV–develops with increasing age, inverting its polarity from positive to negative at around 6–8 years (Chiarenza et al., 1983, Otto and Reiter, 1984, Warren and Karrer, 1984a, Warren and Karrer, 1984b).

With respect to CNV maturation, most authors report increasing CNV amplitudes with increasing age over the vertex (Cohen, 1970, Cohen et al., 1967, Klorman, 1975, Tecce, 1971, Timsit-Berthier and Hausmann, 1972, Low et al., 1966, Segalowitz and Davies, 2004), however, the pioneering studies used only a few electrodes and do not allow conclusions with respect to underlying cortical generators.

Event-related desynchronization (ERD) of alpha power over the sensorimotor area (μ-rhythm) (Crone et al., 1998, Pfurtscheller and Lopes da Silva, 1999, Szurhaj et al., 2003) is a complementary method to image motor preparation. Alpha-ERD starts about 2 s prior to self-paced movements contralaterally to the movement side over the primary motor area and spreads out bilaterally during movement execution (Babiloni et al., 1999). Alpha-ERD and evoked activity (BP/CNV) have been shown to reflect different aspects of motor processing as reflected by different time courses (Babiloni et al., 1999).

In the current paper, we used a simple motor CNV paradigm where every warning stimulus predicted an imperative stimulus which occurred after a rather short delay and always required the same right hand motor response in order to analyze whether during CNV maturation during childhood and adolescence a central motor component (lateralization contralaterally to the movement, i.e. to the left) would be dissociable from a posterior sensory attention component related with stimulus anticipation with a lateralization to the right (Brunia, 1988). Additionally, we have applied central alpha-ERD in order to map the localization of primary motor cortex and to obtain a second independent measurement of the extent of motor preparation apart from late CNV over motor areas. By ERD analysis, we intended to differentiate whether age-related CNV differences could be caused by reduced or absent motor preparation resulting in reduced or absent central alpha-ERD (e.g. due to PFC immaturity and difficulties to establish temporal contingency) or whether age-related qualitative changes within the motor system would rather account for these differences (resulting in late CNV changes without affecting central alpha-ERD). By comparing late CNV and motor PINV, we could assess whether maturational changes would be temporally specific to the late CNV interval.

Section snippets

Subjects

We recruited 81 healthy children from 6 to 18 years who did not show clinical hearing impairments, neurological or psychiatric diseases and did not take any drugs affecting the central nervous system. Subjects were neither permitted to have first degree relatives suffering from migraine nor chronic pain as these factors have been shown to influence CNV (Bocker et al., 1990). The sample formed the control group of a larger study concerning headache during childhood and adolescence, first results

Grand averages referred to average reference

Topography of late CNV changed markedly with age (see Fig. 1 and Table 2): while 6- to 7-year-old subjects presented a rather widespread and diffuse posterior negativity with a right-sided preponderance (left-sided negativity showed more variability, see Table 2), 8- to 9-year-old showed a clear right centro-parietal maximum. In both age groups, negativity over the left central region (contralateral to the response movement side) was absent. In 10- to 11-year-old subjects, there was already a

Discussion

The main finding of our study was the dissociation of the maturational courses of right-sided (ipsilateral to the anticipated response) posterior negativity and negativity over left central (contralateral to the anticipated response) and midfronto-central areas during late CNV in childhood and adolescence. Left and midfronto-central negativity showed a continuous curvilinear decelerated increase during age-dependent development (from around zero at the age of 6 years to consistent significant

Conclusions

We conclude that either because of an immaturity of motor cortex itself, motor system circuitry or because of less attentional capacity (e.g. due to immaturity of prefrontal cortex), the children in our sample (6–11 years) seem to have remained in an early stage of motor preparation during late CNV as reflected by significant induced (alpha-ERD) yet missing evoked (late CNV) activity over the contralateral pre-/primary motor area. The combined spatio-temporal analysis of evoked and induced

Acknowledgments

This work was supported by the Pain Research Programme of the Medical Faculty, University of Heidelberg (F207040, E1) and the Medical Young Investigator Award of the University of Heidelberg, the latter to the first author. The authors would like to thank Kerstin Herwig for her competent support with the EEG recordings and Prof. Michael Scherg as well as two anonymous reviewers for their comments on the manuscript.

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