NDC neurobiological model: link between unsettled infant behaviour in the first months of life with suboptimal developmental outcomes

The interaction between genetic predisposition and environmental factors is mediated by the epigenome

An individual’s complex genetic susceptibility to a neurodevelopmental disorder is impacted by a myriad of environmental factors in intra-uterine and early life, which alter epigenomic regulation and phenotype expression.3-8

A developmental disorder is best conceptualised, applying a dynamic systems or complexity science framework, as a spectrum disorder of connectome development, that is, of the neural wiring of the brain, in which one or more feedback loops amplify small variations in early development.

Initial lesions trigger a ‘butterfly effect’ of unpredictable cascades of structural and functional imbalances in the global neuronal workspace, which dynamically interact with and impact upon the infant’s social and non-social environmental experiences, amplifying feedback loops and affecting behaviors, cognition, and social communication long-term.9

The initial lesions which cause feedback loop disruptions may be structural, either genomic or due to injury; or functional, for example, from changes in the monoaminergic system. Variable phenotypic expressions emerge out of the compensations of the child’s neural networks in response to very early lesions, as myriad feedback loops in the complex adaptive system of the global neuronal workspace compensate for deficiencies and maintain the best possible functional stability. This may occur at the expense of, or with unusual development of and compensation by, higher order cognitive functions like memory, attention and executive functions. The heterogeneity of certain neurodevelopmental disorders reflect the multiple different disturbances that can occur along any one of multiple pathways. Dysregulation in any one neural or physiological pathway causes a cascade of events culminating in a cluster of symptoms.9

At the cellular level, feedback loop imbalances sculpt neuron morphology and synaptogenesis and alter synaptic transmissions by excitatory or inhibitory neurons. By the time a child is diagnosed with Autism Spectrum Disorder, for example, neuroanatomic patterns of excessive short-range connections and weakened long-range connections have emerged in vulnerable parts of the brain, including in parts of the prefrontal cortex associated with attention, social interaction, emotions, and executive control, and in a decreased density of axons below limbic cortices such as the anterior cingulate cortex.10-14

Applying the NDC lens to provide explanatory mechanisms for the link between two neurodevelopmental disorders and cry-fuss problems in early life

An individual’s complex genetic susceptibility to a neurodevelopmental disorder is known to be impacted by a myriad of environmental factors in intra-uterine and early life, which alter epigenomic regulation and phenotype expression.1-6

This article is concerned with two neurodevelopmental disorders, Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). Each is linked with excessive crying or regulatory problems in early life.

It's often assumed that the unsettled infant behaviour was, in hindsight, an early manifestation of genetically determined neurodivergence. However, it's critical to consider the very large amounts of research demonstrating the complex interplay between genetic predisposition and environmental factors, which is mediated by the epigenome.

Each of the two neurodevelopmental disorders considered here are best conceptualised, applying a dynamic systems or complexity science framework, as a spectrum disorder of connectome development, that is, of the neural wiring of the brain, in which one or more feedback loops amplify small variations in early development.

Initial lesions trigger a ‘butterfly effect’ of unpredictable cascades of structural and functional imbalances in the global neuronal workspace, which dynamically interact with and impact upon the infant’s social and non-social environmental experiences, amplifying feedback loops and affecting behaviors, cognition, and social communication long-term.7

ASD and developmental trajectories

In ASD, the initial lesions which cause feedback loop disruptions may be structural, either genomic or due to injury; or functional, for example, from changes in the monoaminergic system. Variable phenotypic expressions emerge out of the compensations of the child’s neural networks in response to very early lesions, as myriad feedback loops in the complex adaptive system of the global neuronal workspace compensate for deficiencies and maintain the best possible functional stability.

This may occur at the expense of, or with neurodivergent development of and compensation by, higher order cognitive functions like memory, attention and executive functions. The heterogeneity of ASD may reflect the multiple different disturbances that can occur along any one of multiple pathways. Dysregulation in any one neural or physiological pathway causes a cascade of events culminating in a cluster of symptoms.7

At the cellular level, feedback loop imbalances sculpt neuron morphology and synaptogenesis and alter synaptic transmissions by excitatory or inhibitory neurons. By the time a child is diagnosed with ASD, for example, neuroanatomic patterns of exuberant short-range connections and fewer long-range connections have emerged in vulnerable parts of the brain, including in parts of the prefrontal cortex associated with attention, social interaction, emotions, and executive control, and in a decreased density of axons below limbic cortices such as the anterior cingulate cortex.8-12

Multiple developmental cascades across various systems typically occur in response to very early, foundational structural or functional neural lesions

Comorbidity of ASD and ADHD with other medical disorders, including neurodevelopmental, psychiatric, and physical disorders, is common, further supporting the hypothesis that impaired neural and physiological developmental cascades occur in response to very early structural or functional neural lesions. Resultant neural and physiological morbidities then interact with co-occurring behavioral morbidities.13

This article is adapted from an article I published in 2019.

References

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14. Douglas PS. Pre-emptive intervention for Autism Spectrum Disorder: theoretical foundations and clinical translation. Frontiers in Integrative Neuroscience. 2019;13(66):doi.org/10.3389/fnint.2019.00066.