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.
Highlights
There are sparse data on the stepwise process of autonomic nervous system (ANS) maturation and its coupling with cortical development
It is important to note that these processes are not antagonistic and they work in a developing synergy in healthy fetuses similar to their synergic action in inflammation (e.g., [127,128])
This paper suggests that ANS synchrony represents the biological basis for the developing self-regulatory functions, here termed the self-regulation clock
Summary
There are sparse data on the stepwise process of autonomic nervous system (ANS) maturation and its coupling with cortical development. It is further suggested that cortical coupling with the ANS is essential for brain inhibition-excitation balance within the developing organism and that the synchrony is resulting in required molecular and biochemical delicate conditions for accomplishing the interplay between the sympathetic and parasympathetic systems Another suggestion is that ANS synchrony is achieved following cell migration from the brainstem to the cortex and the crucial interchange of neurotransmitters affecting proliferation, differentiation and the onset of myelination processes, and is intensified at the time window of mid-gestation through the first two years of life. This time window has been identified as a period of excitation-inhibition development, which results in a mature balance and parallels the neurobehavioral conceptualization of self-regulation. The current postulates are based on neuroanatomical, neurochemical, electroencephalogram (EEG) and Magnetic Resonance Imaging (MRI) data as well as on vagal tone measures, cardiovascular development and connectivity with the maturing cortex
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