Development of the Ontogenetic Self-Regulation Clock

Abstract

To date, there is no overarching proposition for the ontogenetic-neurobiological basis of self-regulation. This paper suggests that the balanced self-regulatory reaction of the fetus, newborn and infant is based on a complex mechanism starting from early brainstem development and continuing to progressive control of the cortex over the brainstem. It is suggested that this balance occurs through the synchronous reactivity between the sympathetic and parasympathetic systems, both which originate from the brainstem. The paper presents an evidence-based approach in which molecular excitation-inhibition balance, interchanges between excitatory and inhibitory roles of neurotransmitters as well as cardiovascular and white matter development across gestational ages, are shown to create sympathetic-parasympathetic synchrony, including the postnatal development of electroencephalogram waves and vagal tone. These occur in developmental milestones detectable in the same time windows (sensitive periods of development) within a convergent systematic progress. This ontogenetic stepwise process is termed "the self-regulation clock" and suggest that this clock is located in the largest connection between the brainstem and the cortex, the corticospinal tract. This novel evidence-based new theory paves the way towards more accurate hypotheses and complex studies of self-regulation and its biological basis, as well as pointing to time windows for interventions in preterm infants. The paper also describes the developing indirect signaling between the suprachiasmatic nucleus and the corticospinal tract. Finally, the paper proposes novel hypotheses for molecular, structural and functional investigation of the "clock" circuitry, including its associations with other biological clocks. This complex circuitry is suggested to be responsible for the developing self-regulatory functions and their neurobehavioral correlates.

Keywords: EEG; autonomic nervous system; corticospinal tract; excitation-inhibition; heart rate variability; self-regulation; white matter.

Figure 1

The interplay between the neurobehavioral subsystems through excitation-inhibition of each other while faced with environmental inputs and return to balance following achievement of a developmental task.

Figure 2

The imbalance and lack of synchrony in ANS functioning of the preterm infant compared to the optimal range. The ascending arrow describes conditions of over-arousal and sympathetic control. The descending arrow describes conditions of parasympathetic control up to shut-down. The other arrows describe the progress of the process in overloaded vs. under-stimulated conditions.

Figure 3

Step-response (text in yellow) acquisition of a developmental task running from zero (pre acquisition status) to one (acquired capacity, e.g., the first breath, the first step, the first word). The interplay between subsystems is a continuous process which is enhanced at an age-appropriate acquisition of any developmental task. The figure describes the process of a special pattern of interplay within the subsystems at such a momentary point of acquisition up to the return to a new balance and to advanced interplay of excitation-inhibition between all subsystems. The purple arrows represent the step-response. The other arrows represent the flow of the process.

Figure 4

The stepwise stages of heart rate development and the timing of its coupling with fetal sleep states and behavior.

Figure 5

The stepwise developmental progress of the self-regulation clock from conception to postnatal life.

Figure 6

The origin of cortical control over the brainstem by which the CST develops to become the location of the self-regulation clock.