Pain and Consciousness in Infants

FIGURE 11-1 Maturation of thalamocortical connections and somatosensory-evoked potentials. In early preterm infants (<24 gestational weeks) the neurons from the sensory organs terminate in the subplate (the waiting zone) (A). After 24 weeks they start to make connections in the cortical layer (B) and reach the final destination at term (C). This is also reflected by the patterns of spontaneous activity transients and somatosensory-evoked potentials. (Original figure by Vanhatalo modified by Lagercrantz [16].)

Spontaneous Brain Activity

Low-frequency intrinsic spontaneous brain activity is evident in the human electroencephalogram (EEG), when no external stimulation is taking place. In adults, this spontaneous resting activity corresponds to the uncensored thinking related to random episodic memory, retrieving past experiences, reflecting on current experience, and planning for the future. Resting-state networks, that is, the default mode network that includes temporal, parietal, and anterior prefrontal cortices begin to develop early, and have been identified in preterm and full-term infants. This spontaneous resting state activity has been proposed to correspond to “the stream of consciousness” (see reference [16]).

Evoked Activity

In adults, cortical networks activated during pain involve thalamus, posterior and anterior insulae, secondary somatosensory cortex, anterior cingulate cortex, and the periaqueductal gray matter [5]. Moreover, this large network is comprised of multiple interacting pain matrices. These imaging studies reveal a complex network of responsive regional brain activity that underlies the multidimensional nature of pain in the mature human. Characterization of pain networks in infants has received little attention so far. Importantly, magnetic resonance imaging (MRI) of children born very prematurely at age 11–16 years, during quantitative testing of sensory thresholds, revealed that adolescents born preterm showed significantly greater BOLD signal than full-term controls in the primary somatosensory cortex, anterior cingulate cortex, and insula [13]. In that study, the exaggerated brain response was pain-specific and was not observed during nonpainful warmth stimulation. Clearly experiential factors in the individual’s life course and environmental context that inform the full complex multidimensional experience of the adolescent or adult have not yet emerged in the early developing human. Yet, differences in threshold to temperature in micropremies compared to full-term adolescents at this age have been largely accounted for by exposure to neonatal surgery, rather than prematurity per se. Therefore, a lot remains to be learned about the potential for long-term changes to pain processing in this population.

Recently Hartley and Slater [12] summarized the literature on nociceptive-evoked brain activity in newborn infants. Using near-infrared spectroscopy (NIRS), studies have shown increases in hemoglobin oxygen concentration over central regions following acute noxious stimulation. EEG recordings in full-term infants show a specific localized somatosensory response to noxious stimulation, but not to tactile stimulation; thus, these responses are nociceptive-specific. In contrast, in preterm newborns before 35 weeks gestation, both tactile- and noxious stimuli-evoked nonspecific delta brush activity widespread throughout the cortex [8, 12]. In preterms, this lack of a mature localized response, with diffuse activation across the cortex, suggests increased vulnerability to external stimulation. As Hartley and Slater conclude, since cortical activation is a fundamental component of pain processing well-established in adults, observations that even the very preterm newborns manifest cortical responses to noxious stimuli is of clear importance. In summary, evidence of evoked activity suggests that infants process pain.

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