Little is known about the development of the human entorhinal cortex (EC), a major hub in a widespread network for learning and memory, spatial navigation, high‐order processing of object information, multimodal integration, attention and awareness, emotion, motivation, and perception of time. We analyzed a series of 20 fetal and two adult human brains using Nissl stain, acetylcholinesterase (AChE) histochemistry, and immunocytochemistry for myelin basic protein (MBP), neuronal nuclei antigen (NeuN), a pan‐axonal neurofilament marker, and synaptophysin, as well as postmortem 3T MRI. In comparison with other parts of the cerebral cortex, the cytoarchitectural differentiation of the EC begins remarkably early, in the 10th week of gestation (w.g.). The differentiation occurs in a superficial magnocellular layer in the deep part of the marginal zone, accompanied by cortical plate (CP) condensation and multilayering of the deep part of CP. These processes last until the 13–14th w.g. At 14 w.g., the superficial lamina dissecans (LD) is visible, which divides the CP into the lamina principalis externa (LPE) and interna (LPI). Simultaneously, the rostral LPE separates into vertical cell‐dense islands, whereas in the LPI, the deep LD emerges as a clear acellular layer. In the 16th w.g., the LPE remodels into vertical cell‐dense and cell‐sparse zones with a caudorostral gradient. At 20 w.g., NeuN immunoreactivity is most pronounced in the islands of layer II cells, whereas migration and differentiation inside‐out gradients are seen simultaneously in both the upper (LPE) and the lower (LPI) pyramidal layers. At this stage, the EC adopts for the first time an adult‐like cytoarchitectural organization, the superficial LD becomes discernible by 3T MRI, MBP‐expressing oligodendrocytes first appear in the fimbria and the perforant path (PP) penetrates the subiculum to reach its molecular layer and travels along through the Cornu Ammonis fields to reach the suprapyramidal blade of the dentate gyrus, whereas the entorhinal‐dentate branch perforates the hippocampal sulcus about 2–3 weeks later. The first AChE reactivity appears as longitudinal stripes at 23 w.g. in layers I and II of the rostrolateral EC and then also as AChE‐positive in‐growing fibers in islands of superficial layer III and layer II neurons. At 40 w.g., myelination of the PP starts as patchy MBP‐immunoreactive oligodendrocytes and their processes. Our results refute the possibility of an inside‐out pattern of the EC development and support the key role of layer II prospective stellate cells in the EC lamination. As the early cytoarchitectural differentiation of the EC is paralleled by the neurochemical development, these developmental milestones in EC structure and connectivity have implications for understanding its normal function, including its puzzling modular organization and potential contribution to consciousness content (awareness), as well as for its insufficiently explored deficits in developmental, psychiatric, and degenerative brain disorders.

Early regional patterning and laminar position of cortical projection neurons is determined by activation and deactivation of transcriptional factors (TFs) and RNA binding proteins (RBPs) that regulate spatiotemporal framework of neurogenetic processes (proliferation, migration, aggregation, postmigratory differentiation, molecular identity acquisition, axonal growth, dendritic development, and synaptogenesis) within transient cellular compartments. Deep-layer projection neurons (DPN), subplate (SPN), and Cajal–Retzius neurons (CRN) are early-born cells involved in the establishment of basic laminar and regional cortical architecture; nonetheless, laminar dynamics of their molecular transcriptional markers remain underexplored. Here we aimed to analyze laminar dynamics of DPN markers, i.e., transcription factors TBR1, CTIP2, TLE4, SOX5, and RBP CELF1 on histological serial sections of the human frontal cortex between 7.5–15 postconceptional weeks (PCW) in reference to transient proliferative, migratory, and postmigratory compartments. The subtle signs of regional patterning were seen during the late preplate phase in the pattern of sublaminar organization of TBR1+/Reelin+ CRN and TBR1+ pioneering SPN. During the cortical plate (CP)-formation phase, TBR1+ neurons became radially aligned, forming continuity from a well-developed subventricular zone to CP showing clear lateral to medial regional gradients. The most prominent regional patterning was seen during the subplate formation phase (around 13 PCW) when a unique feature of the orbitobasal frontal cortex displays a “double plate” pattern. In other portions of the frontal cortex (lateral, dorsal, medial) deep portion of CP becomes loose and composed of TBR1+, CTIP2+, TLE4+, and CELF1+ neurons of layer six and later-born SPN, which later become constituents of the expanded SP (around 15 PCW). Overall, TFs and RBPs mark characteristic regional laminar dynamics of DPN, SPN, and CRN subpopulations during remarkably early fetal phases of the highly ordered association cortex development.

The cingulate gyrus, as a prominent part of the human limbic lobe, is involved in the integration and regulation of complex emotional, executive, motivational, and cognitive functions, attributed to several functional regions along the anteroposterior axis. In contrast to increasing knowledge of cingulate function in the adult brain, our knowledge of cingulate development is based primarily on classical neuroembryological studies. We aimed to reveal the laminar and cellular development of the various cingulate regions during the critical period from 7.5 to 15 postconceptional weeks (PCW) before the formation of Brodmann type arealization, employing diverse molecular markers on serial histological sections of postmortem human fetal brains. The study was performed by analysis of: (1) deep projection neuron (DPN) markers laminar dynamics, (2) all transient laminar compartments, and (3) characteristic subplate (SP) formation-expansion phase. We found that DPN markers labeling an incipient cortical plate (CP) were the first sign of regional differentiation of the dorsal isocortical and ventral mesocortical belt. Remarkably, increased width of the fibrillar marginal zone (MZ) towards the limbus, in parallel with the narrowing of CP containing DPN, as well as the diminishment of subventricular zone (SVZ) were reliable landmarks of early mesocortical differentiation. Finally, the SP formation pattern was shown to be a crucial event in the isocortical cingulate portion, given that the mesocortical belt is characterized by an incomplete CP delamination and absence of SP expansion. In conclusion, laminar DPN markers dynamics, together with the SVZ size and mode of SP formation indicate regional belt-like cingulate cortex differentiation before the corpus callosum expansion and several months before Brodmann type arealization.

Human neurodevelopment is characterised by the appearance, development and disappearance or transformation of various transient structures that underlie the establishment of connectivity within and between future cortical and subcortical areas. Examples of transient structures in the forebrain (amongst many others) include the subpial granular layer and the subplate zone. We have previously characterised the precise spatiotemporal dynamics of microglia in the human telencephalon. Here, we describe the diversity of microglial morphologies in the subpial granular layer and the subplate zone. Where possible, we couple the predominant morphological phenotype with functional characterisations to infer tentative roles for microglia in a changing neurodevelopmental landscape. We interpret these findings within the context of relevant morphogenetic and neurogenetic events in humans. Due to the unique genetic, molecular and anatomical features of the human brain and because many human neurological and psychiatric diseases have their origins during development, these structures deserve special attention.

Art therapy is one of the non-pharmacological treatment modalities for many diseases, including neurological and psychiatric disorders. Adrian Hill started art therapy in the 1940s. Parkinson`s disease is one of the progressive neurodegenerative diseases characterized by various motor and non-motor symptoms. As patients with Parkinson`s disease often report low quality of life despite improving their motor symptoms, complementary therapy may reduce their difficulties. Music and dance therapy, clay manipulation therapy, and tai chi training have promising results. There is also art therapy for one of the most common causes of dementia worldwide, Alzheimer`s disease. In addition to standard pharmacological treatment for Alzheimer`s disease e.g. cholinesterase inhibitors, music and visual arts therapy are evolving. This article presented some of the art therapy methods used in the most common neurodegenerative disorders, Parkinson`s and Alzheimer`s. In addition, we also presented some of the limitations of those studies. Some of the limitations are as follows: small sample size, relatively short duration of therapy sessions, and the fact that it is doubtful that art therapy could improve symptoms and cognitive abilities of people with advanced forms of neurodegenerative disorders.