NDC neurobiological model: neural and behavioural biomarkers of critically injury-sensitive neuroplasticity in the first 100 days

The cortical subplate is a behavioural biomarker of the critically neuroplastic and injury-sensitive first 100 days of life

Neural network development activity peaks between the last three months in-utero and the first three months post-birth, spanning from the beginning of cortical subplate diminution until the subplate disappears as permanent circuitries in the primary motor, somatosensory, and visual cortex take over.

Until then, sensory-motor information continues to be relayed through subplate neurons, which sculpt permanent cortical templates. Cortical subplate neurons are known to be selectively sensitive to injury, and very early sensory-motor defects due to subplate neuronal injury have been implicated in neurodevelopmental disorders, including Autism Spectrum Disorder.1-3

From 10 weeks post-conception, the brainstem and spinal cord central pattern generator initiates general movements. These disappear by three to 5 months post-birth, as fidgety movements and goal directed, affect-driven movements of the limbs emerge and the cortical subplate disappears.

The groundbreaking Dutch Professor of Developmental Neurology, Minja Hadders-Algra, notes that the emergence, blooming, and eventual disappearance of general movements coincides temporally with the emergence, dominance, and disappearance of subplate synaptic activity. She hypothesises that general movement complexity and variability are modulated by the cortical subplate and mediated by subplate motor efferents. In her model, abnormal general movements result from lesions in either the subplate or in subplate motor efferent connections within the periventricular white matter.3-6

Monoaminergic exuberance is a neurohormonal biomarker of the critically neuroplastic and injury-sensitive first 100 days of life

Significantly, at the time of birth and in the middle of the period of peak neural network development, noradrenergic alpha 2 receptors and glutamatergic N-methyl-D-aspartate receptors are temporarily overexpressed, with high serotonergic innervation and dopaminergic turnover. [JUST THINK: HIGH LEVELS OF NEUROHORMONES RELATED TO STRESS AND EMOTIONS.]

Professor Hadders-Algra hypothesises that monoaminergic exuberance from birth until three months of age is associated with increased neural excitability, including of motor neurons. She speculates that monoaminergic exuberance offers evolutionary advantage, and is expressed in the writhing character of general movements. This over-expression resolves as the permanent cortical circuitries take over from the subplate. 3-6

The crying diathesis (or tendency) is a behavioural biomarker of the critically neuroplastic and injury-sensitive first 100 days of life

Behaviorally, persistence of the cortical subplate and increased monoaminergic excitability correspond post-birth with the infant crying diathesis.

The crying diathesis (or tendency) can be viewed, then, as a behavioral biomarker, and the cortical subplate as a neural biomarker, of the critically injury-sensitive neuroplasticity of an infant’s first 100 days of life.

Stress response settings in early life may impact upon psychological attachment style and mental health life-long

Neural templates for emotional and stress regulation are laid down in the cortical subplate and cortex, and in subcortical structures such as the basal ganglia and the amygdala, during the developmentally critical first 100 days post-birth. These templates form the basis for secure psychological attachment and mental health life-long.

The NDC models draw on the Greenspan Affect Diathesis model to hypothesize that chronic sympathetic nervous system and hypothalamic-pituitary-adrenal axis (SNS-HPA) hyperarousal has monoaminergic impacts on the brainstem and cortical subplate during the critical window of monoaminergic excitability and injury-sensitive neuroplasticity, and is a key physiological mechanism disrupting capacity for attention on developmental tasks, mediating atypical developmental cascades.7-13

Although genetic susceptibility to long-term HPA axis dysregulation varies, painful perceptual experiences in very early life, including fear or chronic stress (experienced physiologically as chronic SNS-HPA hyperarousal), risk lifetime changes in SNS-HPA axis settings and dopaminergic, serotonergic, or noradrenergic circuitries. The HPA axis does not return to its ‘unstressed’ state, normal patterns of cortisol release fail to emerge, and behaviorally, infants show difficulty moving out of hyper-aroused or hypo-aroused states.

Stress also increases the permeability of the blood brain barrier, allowing penetration of pro-inflammatory cytokines. The immune dysregulation associated with chronic stress and increased allostatic load has widespread effect on physiological systems underlying developmental processes and mental and physical health, including on growth, metabolism, immunity, and cognition.12, 14, 15

Executive functions and the development of sustained intention, including joint or shared attention, are particularly sensitive to stress. In 12 month old neurotypical infants, those with high autonomic reactivity to stressors show short attention durations, and those with lower autonomic reactivity show longer attention durations.16

In older children diagnosed with Autism Spectrum Disorder (ASD) or Attention Deficit Hyperactivity Disorder (ADHD), stress triggers worsened signs and symptoms, impairing the capacity to achieve developmental tasks, which further upregulates the stress response, perpetuating multi-directional developmental cascades.

The NDC neurobiological model proposes that the same chronic SNS-HPA hyperarousal known to impact negatively on capacity to perform developmental tasks in the older child similarly impedes an infant’s capacity to perform the vital motor and sensory-motor developmental tasks of very early life. Most infants are resilient and will have no long-term effects, but this is of concern for those infants who are genetically or psychosocially vulnerable.

References

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