Fetal development of functional thalamocortical and cortico–cortical connectivity

Abstract

Measuring and understanding functional fetal brain development in utero is critical for the study of the developmental foundations of our cognitive abilities, possible early detection of disorders, and their prevention. Thalamocortical connections are an intricate component of shaping the cortical layout, but so far, only ex-vivo studies provide evidence of how axons enter the sub-plate and cortex during this highly dynamic phase. Evidence for normal in-utero development of the functional thalamocortical connectome in humans is missing. Here, we modeled fetal functional thalamocortical connectome development using in-utero functional magnetic resonance imaging in fetuses observed from 19th to 40th weeks of gestation (GW). We observed a peak increase of thalamocortical functional connectivity strength between 29th and 31st GW, right before axons establish synapses in the cortex. The cortico–cortical connectivity increases in a similar time window, and exhibits significant functional laterality in temporal-superior, -medial, and -inferior areas. Homologous regions exhibit overall similar mirrored connectivity profiles, but this similarity decreases during gestation giving way to a more diverse cortical interconnectedness. Our results complement the understanding of structural development of the human connectome and may serve as the basis for the investigation of disease and deviations from a normal developmental trajectory of connectivity development.

Fetal development of the human amygdala

“…The fibers are a component of the network involved in the higher cognitive functions attributed to the prefrontal cortex of primates (Barbas, 2000): decision‐making and reward‐related learning (Hunt & Hayden, 2017; Martino et al., 2006; Morrison & Salzman, 2010; Rudebeck & Murray, 2014), as well as social and emotional behaviors (Berboth & Morawetz, 2021; Noonan et al., 2014; Weiskrantz, 1956). The processes of myelination described previously indicate that the amygdala's structural connectivity has matured, whereas the overall brain developmental processes at term involve primarily the formation of corticocortical associative pathways (Kostović et al., 2021), which therefore provides a framework for interhemispheric synchronization (Taymourtash et al., 2022). Supporting the strong correlation between structural and functional connectivity, these functional networks form early in brain development and continue to strengthen during the postnatal period (Oldham et al., 2022; van den Heuvel & Thomason, 2016).…”

Quantifying myelin density in the feline auditory cortex

“…As a general principle, myelination ascends along a hierarchical order of increasing functional complexity (Yakovlev & Lecours 1967), and axons in regions that are myelinated early are also myelinated more rapidly and more completely (Stadelmann et al 2019). Since core regions of auditory cortex are the principal targets of thalamocortical afferents that form the earliest cortical circuitry (Yakovlev & Lecours 1967;Taymourtash et al 2023), it stands to reason they would be most densely myelinated. Table 1.…”

“…As a general principle, myelination ascends along a hierarchical order of increasing functional complexity (Yakovlev & Lecours 1967), and axons in regions that are myelinated early are also myelinated more rapidly and more completely (Stadelmann et al 2019). Since core regions of auditory cortex are the principal targets of thalamocortical afferents that form the earliest cortical circuitry (Yakovlev & Lecours 1967;Taymourtash et al 2023), it stands to reason they would be most densely myelinated. Lomber et al 2010), and auditory field of the anterior ectosylvian sulcus (fAES; Meredith et al 2011) take on visual functions following profound, early-onset hearing loss; however, evidence for functional reorganization of core feline auditory regions remains contested (Stewart and Starr 1970;Rebillard et al 1977;Kral et al 2003).…”

Exome-wide analysis implicates rare protein-altering variants in human handedness

“…Population-level asymmetries of anatomy and function arise in the human brain during fetal development (8)(9)(10)(11)(12)(13), and right-lateralized predominance of arm movements has been reported already at ten weeks of gestational age (14). The early appearance of these asymmetries indicates a genetically regulated program of left-right axis development in the central nervous system (1,(15)(16)(17)(18).…”