Layers of the Brain
The human brain cortex consists of a six-layered structure in the neocortex (which comprises 90% of the cerebral cortical surface), while the evolutionarily older archicortex and paleocortex contain only three layers 1.
Neocortex (Isocortex) - Six Layers
The neocortex is organized as a compact ribbon of grey matter with the following architecture 1:
- Occupies 90% of the overall cerebral cortical surface
- Thickness ranges from 1 to 4.5 mm (thinner in sulcal depths, thicker at gyral crowns)
- Six distinct layers with specific cellular compositions and functions
Layer-Specific Characteristics
The six layers demonstrate distinct patterns 2, 3:
- Supragranular layers (Layers II-III): Contain the highest synaptic density and maximal receptor concentrations for most neurotransmitter systems
- Layer 4 (Granular layer): Primary termination site for feedforward projections
- Infragranular layers: Origin of feedback projections, associated with alpha-beta band synchronization
Important functional distinction: Feedforward signaling originates predominantly from supragranular layers and terminates in layer 4 (associated with gamma-band synchronization), while feedback projections originate from infragranular layers and terminate outside layer 4 (associated with alpha-beta band synchronization) 4.
Allocortex - Three Layers
The evolutionarily older cortical structures have a simpler organization 1:
- Archicortex: Hippocampal formation and related structures (3 layers)
- Paleocortex: Olfactory cortex (3 layers)
- Periallocortex: Presubiculum, parasubiculum, and entorhinal cortex
The entorhinal cortex shows a peculiar laminar organization that largely deviates from all other cortical areas 2.
Developmental Layers
During early brain development, distinct transient layers form 5, 6:
- Marginal zone: Outermost layer after cortical plate formation
- Cortical plate (CP): Appears at 7 postconceptional weeks
- Presubplate (pSP): Forms when cortical plate splits the preexisting preplate
- Intermediate zone (IZ): Deeper layer containing migrating neurons
Critical developmental note: The cortical plate first appears at 7 postconceptional weeks and splits the preplate into marginal zone and presubplate, with neurons migrating outward from stem cells near the neural tube center to form the six-layered cortex 5, 6.
Clinical Imaging Considerations
The cortical-subcortical interface should always appear smooth and sharply delineated on imaging 1. The appearance varies with age:
- Newborns to 6 months: Cortex is hypointense on T2, hyperintense on T1 (infantile pattern)
- 8-12 months: "Isointense pattern" period with blurred boundaries due to myelination
- After 18 months: Adult pattern with cortex hypointense on T1, hyperintense on T2/FLAIR
Common pitfall: Cortical thickness measurements on MRI should not be used as strict cut-off values, as thickness varies with age, myelination status, gender, head size, and cortical area 1.