Development of cortical motor circuits between childhood and adulthood: A navigated TMS‐HdEEG study

Abstract

Motor functions improve during childhood and adolescence, but little is still known about the development of cortical motor circuits during early life. To elucidate the neurophysiological hallmarks of motor cortex development, we investigated the differences in motor cortical excitability and connectivity between healthy children, adolescents, and adults by means of navigated suprathreshold motor cortex transcranial magnetic stimulation (TMS) combined with high-density electroencephalography (EEG). We demonstrated that with development, the excitability of the motor system increases, the TMS-evoked EEG waveform increases in complexity, the magnitude of induced activation decreases, and signal spreading increases. Furthermore, the phase of the oscillatory response to TMS becomes less consistent with age. These changes parallel an improvement in manual dexterity and may reflect developmental changes in functional connectivity. Hum Brain Mapp 38:2599-2615, 2017. © 2017 Wiley Periodicals, Inc.

Maturation changes the excitability and effective connectivity of the frontal lobe: A developmental TMS–EEG study

“…In this study, TMS elicited a larger GMFP response in children compared to adults, with the responses in adolescents lying between those of children and adults. This finding is consistent with the results of our previous study using suprathreshold TMS of the motor cortex (Määttä et al, ), as well as with the results of other developmental TMS–EEG (Bender et al, ; Jarczok et al, ) and EEG studies (Matousek & Petersen, ; Tarokh & Carskadon, ; Whitford et al, ) demonstrating higher TEP amplitudes and EEG power in children and adolescents than in adults. With development, EEG shows a similar curvilinear decline to gray matter volume, and it has therefore been suggested that the smaller EEG responses in adults may be associated with gray matter loss in the prepubescent and peripubescent period (Whitford et al, ).…”

“…Following these lines of interpretation, the increased P180 in children in response to frontal cortex stimulation may reflect developmental differences in GABA B ergic neurotransmission and/or in frontal cortico–subcortical–cortical loops (e.g., through the thalamus [McFarland & Haber, ]). It is well‐known that the functional maturation of the GABAergic system continues until the end of adolescence (Kilb, ), and the GABA B hypothesis for the increased P180 in children is in line with the results from previous motor cortex TMS studies suggesting stronger inhibition in children compared to adults (Bender et al, ; Määttä et al, ; Säisänen et al, ). The functional significance of the suggested increase in inhibition in children remains uncertain.…”

“…The results from these studies indicate that the TMS‐evoked N100 component, the most prominent TEP after motor cortex stimulation, declines with maturation and could serve as a test of cortical inhibitory function in children (Bender et al, ; D'Agati et al, ; Helfrich et al, ). Moreover, these results demonstrate that interhemispheric signal propagation between motor cortices increases as a function of age (Jarczok et al, ; Määttä et al, ) and that the complexity of TEP morphology increases and signal spreading facilitates within ipsilateral and contralateral cortices, reflecting developmental changes in motor cortex functional connectivity (Määttä et al, ). Furthermore, according to the results, motor cortex reactivity to TMS decreases with development (Määttä et al, ).…”

“…Moreover, these results demonstrate that interhemispheric signal propagation between motor cortices increases as a function of age (Jarczok et al, ; Määttä et al, ) and that the complexity of TEP morphology increases and signal spreading facilitates within ipsilateral and contralateral cortices, reflecting developmental changes in motor cortex functional connectivity (Määttä et al, ). Furthermore, according to the results, motor cortex reactivity to TMS decreases with development (Määttä et al, ).…”

“…Thereafter, a linear mixed model was run with GROUP_AP_LAT as fixed factor and the peak of interest as the dependent variable. For TEP analyses, only results indicating statistically significant differences between the groups are reported. As SCD was expected to differ between the age groups (Määttä et al, ), we wanted also to evaluate whether SCD had a significant influence on the possible between‐group differences in GMFP area or in TEP amplitudes or topographical distribution. To this end, we performed GMFP area comparison with univariate analysis of variance using SCD as a covariate, and the LMM analysis of TEPs were repeated with SCD as a covariate. The TEP latencies were analyzed as the mean latency in the region where the mean response was largest in amplitude in each group.…”