A shift in sensory processing that enables the developing human brain to discriminate touch from pain

Abstract

When and how infants begin to discriminate noxious from innocuous stimuli is a fundamental question in neuroscience [1]. However, little is known about the development of the necessary cortical somatosensory functional prerequisites in the intact human brain. Recent studies of developing brain networks have emphasized the importance of transient spontaneous and evoked neuronal bursting activity in the formation of functional circuits [2, 3]. These neuronal bursts are present during development and precede the onset of sensory functions [4, 5]. Their disappearance and the emergence of more adult-like activity are therefore thought to signal the maturation of functional brain circuitry [2, 4]. Here we show the changing patterns of neuronal activity that underlie the onset of nociception and touch discrimination in the preterm infant. We have conducted noninvasive electroencephalogram (EEG) recording of the brain neuronal activity in response to time-locked touches and clinically essential noxious lances of the heel in infants aged 28-45 weeks gestation. We show a transition in brain response following tactile and noxious stimulation from nonspecific, evenly dispersed neuronal bursts to modality-specific, localized, evoked potentials. The results suggest that specific neural circuits necessary for discrimination between touch and nociception emerge from 35-37 weeks gestation in the human brain.

Figure 1

Time-Locked Touch and Noxious Lance of the Heel Evoke Tactile and Nociceptive-Specific Potentials in Full-Term Infants (A) Electrode placements for EEG recordings (modified international 10/20 electrode placement system). (B) Dependence of the principal component (PC) weights on stimulus modality at CPz (mean ± standard error of the mean). The PC obtained between 50 and 300 ms after the stimulus onset represents a tactile potential, and the PC obtained between 300 and 700 ms after the stimulus onset represents a nociceptive-specific potential. The PCs (bold lines) are overlaid on the averages obtained across the three stimulation types (background EEG, touch, noxious lance). (C) Examples are shown here of the tactile potential at CPz evoked by touch in four full-term infants. (D) Examples are shown here of the nociceptive-specific potential at CPz evoked by noxious lance in four full-term infants. The shadowed areas mark the time interval in which the PC analyses were conducted.

Figure 2

Both Time-Locked Touch and Noxious Lance of the Heel Trigger a Neuronal Burst (A) Example is shown here of a neuronal burst recorded from the temporal region in a preterm infant (34 weeks gestational age [GA]) following time-locked touch of the heel. (B) Example is shown here of a neuronal burst recorded from the temporal region in a different preterm infant (34 weeks GA) following time-locked noxious heel lance. The area shadowed in orange highlights the neuronal burst. Significant changes in signal energy from baseline are delineated by the dashed lines.

Figure 3

Relationship between Response Type, Nonspecific Neuronal Burst, or Modality-Specific Potentials, Evoked by Tactile and Noxious Stimulation, with Gestational Age Age dependence of the occurrence and topographical distribution of tactile (A), nociceptive-specific potentials (B), and nonspecific neuronal bursts (C and D) following tactile or noxious stimulation of the heel. The occurrence of each type of activity is shown on a week-by-week basis (circles) together with the generalized linear model (GLM) fitted to the data (solid lines) and 90% confidence intervals (dashed lines). An example of each response is illustrated in the inset; the dashed lines represent the time of stimulation and the scale bars represent 100 μV (vertical) and 500 ms (horizontal). At the bottom of the figure, the transition from the neuronal bursts to the modality-specific potentials is described as the significance of the difference between the respective occurrences. Touch and noxious lance were more likely to evoke a tactile and nociceptive-specific potential than a neuronal burst from approximately 35–37 weeks GA.