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This report is written by MaltSci based on the latest literature and research findings

How does neurodevelopment shape brain function? ​

Abstract ​

Neurodevelopment is a complex and dynamic process that lays the foundation for brain function throughout an individual's life. It encompasses critical stages such as neurogenesis, synaptogenesis, and myelination, which collectively shape the brain's structural and functional architecture. Understanding how neurodevelopment influences brain function is vital for elucidating the mechanisms underlying cognitive processes, emotional regulation, and behavioral responses. The interplay between intrinsic genetic programs and extrinsic environmental cues is crucial during these developmental stages, determining the trajectory of brain growth and maturation. Recent advances in neuroimaging and molecular biology have begun to unravel these intricate relationships, providing insights into how deviations in neurodevelopment can lead to a spectrum of neurodevelopmental disorders, such as autism spectrum disorders (ASDs) and attention deficit hyperactivity disorder (ADHD). Current research highlights the significance of both genetic predispositions and environmental influences on brain development. Studies utilizing twin MRI analyses have demonstrated that while global brain morphology and network organization are highly heritable, environmental factors significantly mediate brain network differentiation. Additionally, the immune system has emerged as a crucial player in neurodevelopment, influencing neuronal and glial cell proliferation, differentiation, and function. This interplay underscores the need for a holistic approach to studying neurodevelopment. The organization of this review is structured to provide a comprehensive overview of the relationship between neurodevelopment and brain function. We explore stages of neurodevelopment, genetic and environmental influences, brain plasticity, critical periods, neurodevelopmental disorders, and implications for intervention and treatment. By synthesizing current research findings, this review aims to provide a nuanced understanding of how neurodevelopment shapes brain function and the consequences of disruptions in these processes.

Outline ​

This report will discuss the following questions.

  • 1 Introduction
  • 2 Stages of Neurodevelopment
    • 2.1 Early Neurogenesis
    • 2.2 Synaptogenesis and Pruning
    • 2.3 Myelination
  • 3 Genetic and Environmental Influences
    • 3.1 Genetic Factors in Neurodevelopment
    • 3.2 Environmental Impacts: Nutrition, Toxins, and Experiences
  • 4 Brain Plasticity and Critical Periods
    • 4.1 Mechanisms of Brain Plasticity
    • 4.2 Critical Periods in Development
  • 5 Neurodevelopmental Disorders
    • 5.1 Autism Spectrum Disorders
    • 5.2 Attention Deficit Hyperactivity Disorder (ADHD)
    • 5.3 Schizophrenia and Other Disorders
  • 6 Implications for Intervention and Treatment
    • 6.1 Early Intervention Strategies
    • 6.2 Therapeutic Approaches for Neurodevelopmental Disorders
  • 7 Conclusion

1 Introduction ​

Neurodevelopment is a complex and dynamic process that lays the foundation for brain function throughout an individual's life. It encompasses a series of critical stages, including neurogenesis, synaptogenesis, and myelination, which collectively shape the brain's structural and functional architecture. Understanding how neurodevelopment influences brain function is vital for elucidating the mechanisms underlying cognitive processes, emotional regulation, and behavioral responses. The interplay between intrinsic genetic programs and extrinsic environmental cues is crucial during these developmental stages, as they determine the trajectory of brain growth and maturation. Recent advances in neuroimaging and molecular biology have begun to unravel these intricate relationships, providing insights into how deviations in neurodevelopment can lead to a spectrum of neurodevelopmental disorders, such as autism spectrum disorders (ASDs) and attention deficit hyperactivity disorder (ADHD) [1].

The significance of this research extends beyond academic interest; it holds profound implications for public health and education. Neurodevelopmental disorders affect approximately 15% of children and adolescents worldwide, contributing to significant societal burdens [1]. A deeper understanding of the neurodevelopmental processes can inform early intervention strategies and therapeutic approaches, ultimately improving outcomes for affected individuals. The integration of genetic, environmental, and neurobiological perspectives is essential to construct a comprehensive framework that addresses the multifaceted nature of neurodevelopment and its associated disorders [2][3].

Current research highlights the importance of both genetic predispositions and environmental influences on brain development. Studies utilizing twin MRI analyses have demonstrated that while global brain morphology and network organization are highly heritable, environmental factors significantly mediate brain network differentiation [4]. Furthermore, the immune system has emerged as a crucial player in neurodevelopment, influencing neuronal and glial cell proliferation, differentiation, and function [5][6]. This interplay between genetic and environmental factors underscores the need for a holistic approach to studying neurodevelopment.

The organization of this review is structured to provide a comprehensive overview of the relationship between neurodevelopment and brain function. We will first explore the stages of neurodevelopment, detailing early neurogenesis, synaptogenesis, and myelination. Next, we will examine the genetic and environmental influences that shape brain development, focusing on genetic factors and the impacts of nutrition, toxins, and early experiences. The discussion will then shift to brain plasticity and critical periods, emphasizing how experiences during these sensitive windows can have lasting effects on brain function. Following this, we will address neurodevelopmental disorders, including ASDs, ADHD, and schizophrenia, highlighting their underlying mechanisms and clinical implications. Finally, we will consider the implications for intervention and treatment, discussing early intervention strategies and therapeutic approaches tailored for neurodevelopmental disorders.

By synthesizing current research findings, this review aims to provide a nuanced understanding of how neurodevelopment shapes brain function and the consequences of disruptions in these processes. This exploration not only contributes to our knowledge of normative brain function but also emphasizes the critical need for continued research in this vital area of neuroscience.

2 Stages of Neurodevelopment ​

2.1 Early Neurogenesis ​

Neurodevelopment plays a crucial role in shaping brain function through a series of intricate processes that begin shortly after conception and continue into adolescence. Early neurogenesis, characterized by the proliferation and differentiation of neural stem cells (NSCs) into various cell types, is foundational for establishing the architecture and functionality of the nervous system. This process is tightly regulated by genetic programs and influenced by environmental factors, which can have lasting effects on brain development and function throughout an individual's lifespan.

During early neurogenesis, a complex interplay of cellular processes occurs, including neurogenesis, synaptogenesis, and the maturation of synaptic circuits. The differentiation of neurogenic cells into neurons, astrocytes, and oligodendrocytes is critical for forming the functional networks required for brain activity. Notably, the role of neurotransmitters is pivotal during this phase, as they regulate various developmental processes. For example, neurotransmitters influence neurogenesis and synaptic maturation, which are essential for the formation of neural circuits that underlie cognitive functions and behaviors. Research indicates that disturbances in neurotransmitter signaling during these early stages can lead to neurodevelopmental disorders such as autism and attention deficit hyperactivity disorder (ADHD) [7].

Additionally, the ubiquitin-proteasome system (UPS) and autophagy are integral to the remodeling of the proteome during brain development. These systems facilitate the selective degradation of proteins, allowing for the proper maturation of neurons and the formation of synapses. Malfunctions in UPS components during the early stages of neurogenesis can lead to aberrant brain development and are linked to various neurodevelopmental disorders [8].

Microglia, the brain's resident immune cells, also play a significant role during early brain development. They are involved in shaping neural circuits by responding to environmental cues and exhibiting diverse functional states that can influence neurodevelopment. Their activity during the prenatal and early postnatal periods is crucial for the establishment of proper neural connections, and dysregulation of microglial function has been associated with neurodevelopmental and neurodegenerative disorders [9].

The development of the brain is further influenced by epigenetic modifications and environmental factors, such as maternal immune activation, which can impact neurogenesis and contribute to the variability observed in brain development across species, including differences between humans and rodents [3]. The intricate nature of these processes underscores the importance of early neurodevelopment in establishing the functional architecture of the brain, which ultimately shapes cognitive abilities and behaviors.

In summary, early neurogenesis is a critical stage in brain development that sets the foundation for future brain function. It involves a complex interplay of genetic and environmental factors, neurotransmitter signaling, and cellular interactions, all of which contribute to the proper formation of neural circuits and the prevention of neurodevelopmental disorders. Understanding these mechanisms provides valuable insights into the etiology of various cognitive and behavioral disorders, emphasizing the need for early interventions in at-risk populations.

2.2 Synaptogenesis and Pruning ​

Neurodevelopment is a complex and dynamic process that significantly shapes brain function through various stages, particularly during synaptogenesis and synaptic pruning. These stages are critical for establishing functional neural circuits and ensuring efficient brain operation.

Synaptogenesis refers to the formation of synapses between neurons, which is a foundational aspect of neural connectivity. During early brain development, there is a rapid increase in synaptic connections as neurons establish communication pathways. This process is influenced by both intrinsic genetic programs and extrinsic factors such as environmental stimuli and experiences. As synapses form, they undergo refinement through a process known as synaptic pruning, which is essential for eliminating unnecessary or weak connections. This pruning is largely mediated by glial cells, particularly microglia and astrocytes, which help to maintain synaptic homeostasis and enhance the efficiency of neural circuits [10][11].

The timing of synaptogenesis and pruning is crucial, as these processes occur in specific developmental windows. For instance, the critical periods of synaptic pruning coincide with significant cognitive milestones and behavioral developments. Alterations in the balance of synaptogenesis and pruning can lead to neurodevelopmental disorders. For example, excessive or insufficient synaptic pruning has been linked to conditions such as autism spectrum disorder and schizophrenia, suggesting that dysregulation during these stages can have profound long-term consequences for brain function [12][13].

Moreover, recent studies have highlighted the role of the immune system, particularly the complement cascade, in synaptic pruning. Complement proteins opsonize excess synapses, marking them for elimination by microglia. This process is essential for refining neural circuits and is thought to be involved in the pathogenesis of various neurodevelopmental disorders [14]. Understanding these mechanisms is vital, as they may provide insights into potential therapeutic targets for addressing developmental brain disorders [13].

In summary, the processes of synaptogenesis and synaptic pruning during neurodevelopment are pivotal for shaping brain function. They ensure the establishment of effective neural circuits, influence cognitive and behavioral outcomes, and are closely linked to the risk of developing neurodevelopmental disorders. The intricate balance between forming new synapses and pruning away the unnecessary ones is essential for the maturation of the brain and the optimization of its functions throughout an individual's lifespan.

2.3 Myelination ​

Neurodevelopment is a complex process that shapes brain function through various stages, one of the most critical being myelination. Myelination is the formation of a myelin sheath around neuronal axons, which is essential for efficient electrical signal conduction and rapid communication between neurons. This process is particularly dynamic during early life, with significant implications for cognitive and behavioral outcomes.

Myelination begins shortly after birth and continues throughout childhood and into early adulthood. The most rapid phase of myelination occurs during the first few years of life, coinciding with a dramatic increase in cognitive abilities. Studies have shown that the nutritional composition of early life diets, particularly the differences between breast milk and formula, can significantly influence myelination and cognitive outcomes. For instance, research indicates that children who are exclusively breastfed exhibit improved myelination and enhanced cognitive abilities compared to those who are formula-fed, with differences persisting into later childhood despite controlling for socioeconomic factors (Deoni et al., 2018) [15].

The role of myelination extends beyond mere structural development; it also influences functional outcomes such as learning and memory. Neuronal activity plays a vital role in regulating myelination processes. Oligodendrocyte precursor cells, which differentiate into myelinating oligodendrocytes, are influenced by neuronal activity, highlighting the adaptive nature of myelination. This relationship indicates that experiences during critical developmental periods can sculpt brain structure and function, suggesting that myelination is not just a passive process but one that is actively shaped by environmental and experiential factors (Taylor & Monje, 2023) [16].

Moreover, the interaction between myelination and neuronal remodeling is crucial for proper circuit function. Research has shown that ongoing axonal remodeling can delay myelination onset, indicating a complex interplay between these two processes. Specifically, local axon remodeling has been shown to influence the timing of myelination, suggesting that the two processes must be finely coordinated for optimal brain function (Wang et al., 2021) [17].

The consequences of disrupted myelination can be profound, leading to cognitive impairments and neurodevelopmental disorders. Alterations in myelination trajectories have been associated with conditions such as schizophrenia, where dysregulation of myelination contributes to the cognitive and functional impairments observed in affected individuals (Bartzokis, 2002) [18]. Furthermore, the developmental trajectories of myelination correlate with cognitive abilities, indicating that variations in myelination can significantly influence individual differences in cognitive function (O'Muircheartaigh et al., 2014) [19].

In summary, myelination is a critical stage of neurodevelopment that significantly shapes brain function. It facilitates rapid neuronal communication, supports cognitive development, and is influenced by both intrinsic and extrinsic factors. Understanding the nuances of myelination and its relationship with neuronal activity and environmental influences is essential for comprehending how brain function develops and how disruptions in these processes can lead to neurodevelopmental disorders.

3 Genetic and Environmental Influences ​

3.1 Genetic Factors in Neurodevelopment ​

Neurodevelopment is a complex process influenced by both genetic and environmental factors, which collectively shape brain function and cognitive abilities. Genetic mutations and environmental factors dynamically influence gene expression and developmental trajectories at the neural, cognitive, and behavioral levels. This interplay is evident across different periods of neurocognitive development, including early childhood, adolescence, and adulthood, where variations in socioeconomic status and stress have been shown to affect brain function significantly. Furthermore, allelic differences among individuals can explain why some respond to interventions while others do not, indicating a nuanced relationship between genetics and environmental influences in neurodevelopmental outcomes (Karmiloff-Smith et al., 2014) [20].

Recent advancements in genetics and genomics have unveiled numerous genomic loci associated with neuroanatomical and neurobehavioral phenotypes. Research has highlighted genetic changes in both protein-coding and noncoding regions that impact brain development and evolution, offering insights into neurological and neuropsychiatric disorders, such as autism and schizophrenia (Bae et al., 2015) [21]. The complexity of genetic influences on brain development is further underscored by findings that suggest genetic factors contribute significantly to the heritability of various cognitive functions and brain structures during childhood and adolescence. For instance, a study involving pediatric twins demonstrated that genetic influences on brain anatomy are high, particularly for regions associated with complex reasoning abilities, which become increasingly heritable with maturation (Lenroot & Giedd, 2008) [22].

Moreover, early environmental influences, such as adverse experiences, can have lasting effects on brain structure and function through epigenetic modifications. Evidence indicates that experiences during critical developmental periods can permanently alter brain connectivity and volume, particularly in regions such as the amygdala and hippocampus, which are crucial for emotional regulation and memory (Miguel et al., 2019) [23]. The interaction between genetic predispositions and environmental factors, including diet and parental care quality, further illustrates the multifaceted nature of neurodevelopment. For example, polymorphisms in genes related to neurotrophic factors can moderate the impact of adverse environmental conditions on child neurodevelopment, suggesting that genetic variations play a role in determining susceptibility to negative environmental influences (Miguel et al., 2019) [23].

The understanding of genetic influences on cognitive development is essential for elucidating the biological mechanisms governing both typical and atypical maturation. Studies have shown that neurocognitive measures are significantly heritable and that genetic variance in general cognitive ability increases from childhood to early adulthood, highlighting the importance of genetic factors in cognitive maturation (Mollon et al., 2021) [24]. Furthermore, genetic contributions to brain criticality—a state that optimizes information processing—have been shown to correlate with cognitive functions, suggesting that genetic influences extend beyond structural aspects to functional dynamics within the brain (Xin et al., 2025) [25].

In summary, neurodevelopment is shaped by a complex interplay of genetic and environmental factors that influence brain function and cognitive abilities. Genetic variations contribute significantly to the heritability of brain structures and cognitive functions, while environmental experiences, particularly during sensitive developmental periods, can modify these genetic influences and lead to long-term changes in brain architecture and function. Understanding these interactions is crucial for developing targeted interventions aimed at supporting optimal neurodevelopment and addressing neurodevelopmental disorders.

3.2 Environmental Impacts: Nutrition, Toxins, and Experiences ​

Neurodevelopment is a complex process influenced by both genetic and environmental factors, significantly shaping brain function throughout early life. The interplay between these factors can lead to profound changes in brain structure and function, with implications for cognitive and mental health outcomes.

Environmental influences, particularly during critical periods such as prenatal and early postnatal stages, play a crucial role in shaping neurodevelopment. Adverse experiences, such as poor nutrition, exposure to toxins, and negative social interactions, can have lasting effects on brain morphology and functionality. For instance, it has been shown that socioeconomic background can profoundly affect structural and functional brain development, particularly in areas associated with language and executive function. These effects are mediated by various factors, including diet, quality of parental care, and exposure to prenatal toxins [26].

Nutrition is one of the most critical environmental factors affecting brain development. Early life nutrition has been shown to influence the brain's plasticity and overall function. Nutritional deficits can disrupt critical periods of brain development, leading to long-term cognitive impairments. Specific nutrients are essential for the opening and closing of sensitive periods in brain regions, highlighting the need for adequate nutrition during these times [27]. Conversely, positive early life experiences, such as enriched environments and proper nutrition, can reverse some detrimental effects of adversity and promote healthy neurodevelopment [23].

Toxic exposures, such as maternal alcohol consumption during pregnancy, can lead to neurodevelopmental disturbances that are associated with psychiatric disorders. The interplay between environmental toxins and genetic predispositions can exacerbate vulnerabilities, further complicating the neurodevelopmental landscape [28]. For example, epigenetic modifications resulting from adverse environmental conditions can lead to persistent changes in brain development, influencing susceptibility to mental health disorders later in life [29].

Moreover, experiences such as maltreatment or institutionalized care can alter the development of the "social brain," contributing to negative mental health outcomes. Such alterations may be partially reversible through early intervention programs, emphasizing the importance of supportive environments during sensitive developmental windows [26].

In summary, neurodevelopment shapes brain function through a dynamic interplay of genetic and environmental influences. Adverse environmental factors, including nutrition, toxins, and early life experiences, can significantly impact brain structure and function, leading to long-term consequences for cognitive and emotional health. Understanding these influences is crucial for developing effective interventions to support healthy brain development and mitigate the risks associated with adverse experiences.

4 Brain Plasticity and Critical Periods ​

4.1 Mechanisms of Brain Plasticity ​

Neurodevelopment plays a crucial role in shaping brain function through the mechanisms of brain plasticity, which refers to the brain's ability to change and adapt in response to experiences and environmental influences. This plasticity is particularly pronounced during critical periods of development, where the brain exhibits heightened sensitivity to external stimuli, leading to significant structural and functional changes.

One intrinsic feature of the developing brain is its high susceptibility to environmental influences, known as plasticity. This plasticity can be viewed as a double-edged sword, especially in populations such as preterm infants. On one hand, the high plasticity of rapidly developing neural tissue makes the preterm brain more vulnerable to injuries resulting from adverse events like inflammation, hypoxia, and ischemia. On the other hand, this same plasticity provides a mechanism through which positive experiences can help normalize neurological development in these infants (DeMaster et al., 2019) [30].

Developmental plasticity allows individuals to modify and adapt to contextual and experiential influences throughout their lifespan. The reciprocal interactions between behavioral and neuronal plasticity are vital in regulating neurobehavioral development. Evidence suggests that the dopaminergic system plays a significant role in modulating this plasticity, influencing both associative memory and the functional organization of cognitive processes (Li et al., 2006) [31].

In the context of cognitive aging, the brain retains the capacity for both neuronal and cognitive plasticity. Neuronal plasticity encompasses changes at the neuron level, such as neurogenesis and synaptogenesis, while cognitive plasticity refers to adaptive changes in cognitive patterns. Successful cognitive aging is thought to require interactions between these two forms of plasticity, suggesting that learning and environmental factors can stimulate neural plasticity, thereby enhancing cognitive functions (Greenwood & Parasuraman, 2010) [32].

Furthermore, the timing of brain injury relative to the expected course of neurodevelopment significantly impacts recovery outcomes. Studies indicate that injuries occurring during critical developmental windows can have lasting effects, potentially leading to diminished cognitive functions such as attention, memory, and reasoning skills in individuals born preterm (Luciana, 2003) [33]. This highlights the importance of understanding both genetic and experiential factors that contribute to neurodevelopment and subsequent brain function.

Recent research also emphasizes the role of non-coding RNAs in brain plasticity, linking molecular changes to the potential for recovery following neurological damage. This suggests that a deeper understanding of the mechanisms underlying brain plasticity can inform therapeutic strategies aimed at enhancing recovery and improving quality of life for individuals with neurological disorders (Statsenko et al., 2025) [34].

In summary, neurodevelopment shapes brain function through mechanisms of plasticity that are particularly influential during critical periods. The interplay of genetic, environmental, and experiential factors drives these processes, ultimately determining cognitive outcomes and the capacity for recovery following injury. Understanding these mechanisms is essential for developing interventions that support optimal brain development and function across the lifespan.

4.2 Critical Periods in Development ​

Neurodevelopment plays a crucial role in shaping brain function through periods of heightened plasticity known as critical periods. These critical periods are developmental epochs during which the nervous system exhibits increased sensitivity to specific environmental stimuli, which are essential for proper circuit organization and learning. Mechanistic studies have demonstrated that critical periods are characterized by exuberant brain plasticity in early development, with constraints imposed as the brain matures. The closure of these critical periods can limit the brain's ability to adapt, even when optimal conditions are restored, making the identification of manipulations that can reopen critical periods a priority in translational neuroscience [35].

During critical periods, synaptic plasticity, particularly long-term depression and potentiation, is essential for the refinement of neural connections that underlie cognitive functions such as perception, language, and social behavior. For instance, the developmental regulation of oxytocin-mediated synaptic plasticity in the nucleus accumbens establishes a critical period for social reward learning. A single dose of (+/-)-3,4-methylendioxymethamphetamine (MDMA) has been shown to reopen this critical period, indicating that neurochemical interventions can influence developmental trajectories [35].

Research has identified various factors that regulate the timing and duration of critical periods, including genetic, environmental, and epigenetic influences. For example, the maturation of parvalbumin-positive inhibitory neurons is critical for establishing the temporal dynamics of critical periods, influencing the plasticity of neural circuits [36]. Moreover, genetic factors, such as the SYNGAP1 gene, have been linked to the maturation rates of excitatory synapses and the duration of critical-period synaptic plasticity, suggesting that genetic control can influence cognitive abilities and developmental outcomes [37].

Furthermore, glial cells, which comprise a significant portion of the brain, also play a role in modulating critical period timing. These cells can provide signals that influence the plasticity of neural circuits, particularly during these specialized windows of development [38]. The understanding of how glial cells interact with neurons to regulate critical periods is essential for unraveling the complexities of neurodevelopment and its implications for neurodevelopmental disorders.

In summary, critical periods are integral to neurodevelopment, as they dictate the timing of plasticity that shapes brain function. Environmental experiences during these periods lead to sustained changes in neural circuitry and behavior, underscoring the importance of these developmental windows in both typical and atypical brain development [39]. Understanding the mechanisms that govern critical periods can provide insights into potential interventions for neurodevelopmental disorders and inform strategies for promoting healthy brain development [40].

5 Neurodevelopmental Disorders ​

5.1 Autism Spectrum Disorders ​

Neurodevelopment is a complex and tightly regulated process that is crucial for the formation, maturation, and functional specialization of the nervous system. It encompasses several critical stages, including cellular proliferation, differentiation, migration, synaptogenesis, and synaptic pruning, all of which establish the foundation for cognitive, behavioral, and emotional functions. The interplay between metabolic processes and neurodevelopment is significant, as metabolism provides the energy and substrates necessary for various biosynthetic and signaling activities essential for brain development (He et al., 2025) [2].

Key metabolic pathways, such as glycolysis, lipid metabolism, and amino acid metabolism, support essential neurodevelopmental processes including cell proliferation, myelination, and neurotransmitter synthesis. Dysregulation of these metabolic processes has been linked to various neurodevelopmental disorders, including Autism Spectrum Disorders (ASDs), intellectual disabilities, and epilepsy. For instance, alterations during neurogenesis have been implicated in the development of neurodevelopmental cognitive disorders, highlighting the importance of metabolic stability during brain development (Ijomone et al., 2025) [41].

Furthermore, neurotransmitters play a pivotal role in brain development and the emergence of neurodevelopmental disorders. The dopaminergic system, which begins to express receptors early in development and matures through adolescence, is critical for the stabilization and integration of neural circuits. Disruptions in dopaminergic signaling have been implicated in the pathogenesis of disorders such as autism, schizophrenia, and attention deficit hyperactivity disorder (Ijomone et al., 2025) [41].

Neurotrophins, particularly brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), are also crucial for neurodevelopment, influencing neurogenesis, synaptic plasticity, and neuronal survival. Dysregulation in neurotrophin signaling pathways has been associated with core features of ASDs and other neurodevelopmental disorders, indicating their potential as biomarkers and therapeutic targets (Panvino et al., 2025) [42].

Moreover, neurodevelopmental disorders, which affect approximately 15% of children and adolescents globally, manifest as cognitive, behavioral, or motor impairments. The increasing diagnoses of profound autism and attention deficit hyperactivity disorder in the USA highlight the pressing need to understand the origins and mechanisms underlying these conditions. Comprehensive studies of the developing human brain, alongside those of model organisms, are revealing novel developmental cell populations and conserved patterns of cell genesis, migration, and maturation. These insights are essential for unraveling the mechanisms of brain function and disease vulnerability (Nowakowski et al., 2025) [1].

In conclusion, neurodevelopment shapes brain function through a multifaceted interplay of metabolic processes, neurotransmitter systems, and neurotrophic factors. The disruption of these intricate systems can lead to neurodevelopmental disorders such as ASDs, emphasizing the need for further research to elucidate the underlying mechanisms and to develop innovative therapeutic strategies aimed at enhancing brain health and function.

5.2 Attention Deficit Hyperactivity Disorder (ADHD) ​

Neurodevelopment plays a crucial role in shaping brain function, particularly in the context of neurodevelopmental disorders such as Attention Deficit Hyperactivity Disorder (ADHD). ADHD is characterized by persistent patterns of inattention, hyperactivity, and impulsivity, which manifest due to complex neurodevelopmental processes. Recent findings suggest that specific processes related to brain developmental disorganization can create a vulnerable background that increases sensitivity to stress stimuli from the psychosocial environment, thereby exacerbating ADHD symptoms [43].

In ADHD, the psychopathological processes are linked to mechanisms of disturbed inhibitory functions, leading to incongruent neural interactions, often referred to as "neural interference." This phenomenon arises from the integration or disintegration of primitive functions and higher cognitive processes, which can result in increased sensitivity to stress and the manifestation of various cognitive and affective disturbances, including anxiety and depression [43].

Furthermore, neurodevelopmental alterations in ADHD are reflected in the structural and functional connectivity of the brain. Studies using functional MRI have shown that ADHD symptoms are associated with significant changes in the modular structure of intrinsic brain networks. These changes involve altered connections between and within functional brain networks, which are critical for cognitive functioning. Specifically, ADHD has been linked to abnormal small-world properties in both functional and structural brain networks, characterized by higher local clustering and lower global integrity. This suggests a disorder-related shift of network topology toward regular configurations, impacting attentional and motor functions [44].

Longitudinal studies have also highlighted the differences in brain development trajectories between children with ADHD and their typically developing peers. These studies indicate that while therapeutic interventions, such as psychostimulants, can normalize many measures of brain anatomy and function, the developmental course of ADHD may differ significantly among individuals [45]. This developmental perspective emphasizes the importance of understanding ADHD not only as a set of behavioral symptoms but also as a condition deeply rooted in neurobiological and neurodevelopmental processes.

Additionally, emerging research has pointed to the role of neuroinflammation and dopamine dysfunction in the etiology of ADHD. Inflammation and disruptions in dopaminergic signaling pathways can contribute to the behavioral and cognitive profiles observed in ADHD. For instance, studies have indicated that microglial alterations and excitatory/inhibitory (E/I) imbalance in specific brain regions, such as the anterior cingulate cortex and hippocampus, are associated with ADHD symptoms [46]. This highlights the interplay between neurodevelopmental changes and the underlying neurochemical environments that shape brain function in ADHD.

In summary, neurodevelopment shapes brain function through a complex interplay of structural and functional connectivity, neurochemical signaling, and environmental influences. ADHD exemplifies how disruptions in these processes can lead to significant cognitive, behavioral, and emotional challenges, necessitating a comprehensive understanding of its neurodevelopmental underpinnings to inform effective interventions and treatments.

5.3 Schizophrenia and Other Disorders ​

Neurodevelopment plays a crucial role in shaping brain function, particularly in the context of neurodevelopmental disorders such as schizophrenia. The neurodevelopmental hypothesis posits that disruptions in early brain development contribute significantly to the onset of schizophrenia and other related disorders. This hypothesis is supported by a wealth of evidence indicating that both genetic and environmental factors during critical periods of brain development can lead to long-lasting alterations in brain structure and function.

Research indicates that schizophrenia is characterized by abnormalities that arise during early brain development, which can manifest as structural changes in the brain even before the onset of clinical symptoms. For instance, studies have shown that structural brain changes are apparent premorbidly, particularly in the frontal and cingulate regions, and these changes correlate with neuropsychological deficits in executive function [47]. Furthermore, the timing of these structural changes suggests that an early neurodevelopmental insult may interact with subsequent brain maturation processes, leading to further neurodevelopmental alterations [47].

Genomic insights into schizophrenia have revealed that genetic risk factors associated with the disorder are dynamic and context-dependent, with their effects varying across different stages of neurodevelopment [48]. This dynamic interplay suggests that genetic predispositions can lead to atypical neurodevelopmental trajectories, which may culminate in the manifestation of schizophrenia symptoms in early adulthood. For example, the neurodevelopmental model emphasizes that disturbances occurring during fetal, childhood, or adolescent periods can significantly impact cognitive functions such as memory and executive function, which are critical for adaptive behavior [49].

The relationship between neurodevelopment and cognitive impairment in schizophrenia is complex. Cognitive deficits often seen in individuals with schizophrenia may originate from neurodevelopmental abnormalities, which lead to a slower trajectory of cognitive development rather than a continuous decline in function [50]. This suggests that neurodevelopmental disturbances can establish a foundation for later cognitive challenges, influenced by both genetic factors and environmental exposures, such as prenatal stress or infections [51].

Additionally, the neurodevelopmental hypothesis has implications for understanding the timing and nature of therapeutic interventions. It posits that early identification of individuals at risk and intervention during critical developmental windows—such as pre- and perinatal stages—may be more effective than focusing solely on treatment during adolescence or adulthood [48]. This proactive approach aligns with the idea that addressing neurodevelopmental perturbations early may help in altering the trajectory of brain development and mitigate the risk of developing schizophrenia.

In summary, neurodevelopment shapes brain function through a complex interplay of genetic and environmental factors that influence brain structure and cognitive abilities. The implications of this understanding extend to both the etiology of schizophrenia and potential therapeutic strategies, highlighting the importance of early intervention in managing neurodevelopmental disorders.

6 Implications for Intervention and Treatment ​

6.1 Early Intervention Strategies ​

Neurodevelopment plays a critical role in shaping brain function, particularly during the early stages of life when the brain undergoes significant changes. The developing brain is highly plastic, meaning it can adapt to environmental influences, which can either promote healthy development or lead to impairments if adverse conditions are present. This plasticity underscores the importance of early intervention strategies aimed at enhancing neurodevelopmental outcomes, especially for infants at risk of disorders.

Research has demonstrated that neurodevelopmental disorders affect various domains, including motor, cognitive, language, learning, and behavioral development, with lifelong consequences (Cioni et al., 2016). Early identification of infants at risk for these disorders is crucial, as it allows for timely intervention programs that can modify the natural history of the disorders. Interventions initiated in the first weeks or months of life have been shown to have a positive impact on developmental outcomes, particularly in preterm infants (Cioni et al., 2016; Lea et al., 2017).

A significant body of evidence suggests that environmental factors and experiences can influence brain development, thus improving outcomes for at-risk infants (Cioni et al., 2016). The complexity of the brain's sensitivity to environmental stimuli highlights the potential clinical effects of early interventions. For instance, enriched environments can foster positive neurodevelopmental changes in both human and animal models (Cioni et al., 2016).

In terms of pharmacological interventions, the timing of drug administration during critical developmental windows can optimize long-term therapeutic effects. Andersen and Navalta (2011) propose that a deeper understanding of neurodevelopment can lead to improved treatments that intervene early in the progression of disorders, potentially preventing the manifestation of symptoms. However, the use of psychotropic agents during sensitive periods also carries risks of harmful delayed consequences, necessitating a careful consideration of treatment strategies (Andersen & Navalta, 2011).

Moreover, specific interventions have been identified as effective in promoting neurodevelopmental outcomes. Hadders-Algra (2011) emphasizes that coaching parents appears to be an effective intervention strategy. It is also noted that while the understanding of brain plasticity is still evolving, interventions focused on reducing stress before term age and stimulating development after term age may yield positive results. Additionally, opportunities for infants to explore their capabilities through self-produced motor activities may enhance developmental outcomes (Hadders-Algra, 2011).

In the context of congenital heart disease (CHD), neurodevelopmental impairment is a common long-term morbidity. Ortinau et al. (2022) highlight the necessity of preventing brain injury and treating long-term neurological sequelae in this high-risk population. The focus has shifted towards understanding the prenatal, genetic, and environmental contributions to impaired neurodevelopment, advocating for comprehensive cardiac neurodevelopmental care that includes developmental care and parental support.

Overall, early intervention strategies that leverage the brain's plasticity and address both biological and environmental factors are vital for optimizing neurodevelopmental outcomes. This multifaceted approach, combining pharmacological, behavioral, and environmental interventions, holds promise for improving the quality of life for children at risk of neurodevelopmental disorders. Future research should continue to explore innovative strategies and refine existing interventions to enhance their efficacy and accessibility in clinical practice.

6.2 Therapeutic Approaches for Neurodevelopmental Disorders ​

Neurodevelopment is a complex and tightly regulated process that is essential for the formation, maturation, and functional specialization of the nervous system. It encompasses critical stages, including cellular proliferation, differentiation, migration, synaptogenesis, and synaptic pruning, which collectively establish the foundation for cognitive, behavioral, and emotional functions. The interplay between various metabolic pathways and neurodevelopment is crucial, as these pathways provide the necessary energy and substrates for biosynthesis, signaling, and cellular activities essential for brain development (He et al. 2025) [2].

Neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and intellectual disabilities, can significantly impact cognitive, behavioral, and social functioning. The origins of these disorders are multifactorial, involving genetic, environmental, and neurobiological factors. Early intervention is critical, as timely identification of infants at risk for NDDs can facilitate interventions that positively modify the natural history of these disorders (Cioni et al. 2016) [52]. It is recognized that gene abnormalities or congenital brain lesions are not the sole determinants of neurodevelopmental outcomes; environmental factors and experiences can significantly influence brain development and improve outcomes in at-risk infants (Cioni et al. 2016) [52].

Recent studies have begun to explore the role of neuroimmune interactions in neurodevelopment, highlighting that immune cells and molecules can influence neurodevelopment beyond the context of overt inflammation. This shift in understanding suggests that deviations in normal neuroimmune activities may contribute to the pathogenesis of neurodevelopmental disorders (Monet & Quan 2023) [6]. Furthermore, neurotrophins, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), play critical roles in brain development by influencing neurogenesis, synaptic plasticity, and neuronal survival. Dysregulation of neurotrophin signaling pathways has been associated with core features of NDDs, indicating their potential as biomarkers and therapeutic targets (Panvino et al. 2025) [42].

The therapeutic landscape for NDDs is evolving, with innovative approaches being explored. For instance, serious games (SGs) have emerged as promising digital therapeutic interventions for managing neurobehavioral and cognitive disturbances in children with NDDs. These interactive video games can help improve adaptive, cognitive, and motor skills while addressing behavioral problems associated with these disorders (Vacca et al. 2023) [53]. Additionally, there is increasing interest in the development of polymeric nanocarriers for nose-to-brain drug delivery, which could enhance the treatment of neurodevelopmental conditions by bypassing the blood-brain barrier and increasing the bioavailability of therapeutic agents in the brain (Awad et al. 2023) [54].

In summary, neurodevelopment shapes brain function through a multifaceted interplay of genetic, environmental, metabolic, and neuroimmune factors. Understanding these mechanisms is critical for developing effective interventions and treatments for neurodevelopmental disorders. Future research should continue to explore these interactions and refine therapeutic approaches to improve outcomes for affected individuals.

7 Conclusion ​

Neurodevelopment is a multifaceted process that shapes brain function through various stages, including neurogenesis, synaptogenesis, myelination, and critical periods of plasticity. The interplay between genetic predispositions and environmental influences is crucial in determining the trajectory of brain development and function. Recent advancements in research highlight the importance of early intervention strategies for neurodevelopmental disorders, which affect a significant percentage of children globally. These disorders, including autism spectrum disorders (ASDs) and attention deficit hyperactivity disorder (ADHD), underscore the necessity for a comprehensive understanding of the neurodevelopmental processes to inform effective therapeutic approaches. Future research should focus on elucidating the intricate mechanisms involved in neurodevelopment, exploring the potential for interventions that can mitigate the impact of adverse environmental factors, and promoting healthy brain development through innovative strategies that leverage the brain's inherent plasticity. By integrating genetic, environmental, and neurobiological perspectives, we can enhance our understanding of neurodevelopment and improve outcomes for individuals at risk of neurodevelopmental disorders.

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