Entorhinal Cortex

The Five Senses and Beyond: The Encyclopedia of Perception - Jennifer L. Hellier 2017

Entorhinal Cortex

The entorhinal cortex (EC), where “ento” means interior and “rhino” means nose, is an area of the brain that is located in the medial temporal lobe and functions as a hub in a widespread network for memory and navigation (the sense of direction). This is the main interface between the hippocampus and neocortex. The EC-hippocampus system plays a role in declarative memories including but not limited to memory formation, memory consolidation, and memory optimization during sleep. The EC stretches dorsolaterally and is located at the rostral (closer to the nose) end of the temporal lobe. Divided into medial and lateral regions, there are three bands that each have their own distinct properties and connectivity that run perpendicular across the whole area.


Brodmann areas were originally described by German anatomist Korbinian Brodmann (1868—1918). He became interested in neuroscience due to the influence of Alois Alzheimer (1864—1915), another German scientist after whom Alzheimer’s disease is named. Brodmann used a histological method known as the Nissl staining method to examine the structure and organization of cells in different regions of the brain. Brodmann applied this stain to very thin sections of brain specimens that he had acquired. This allowed him to visualize the structure and organization of cells, which is often referred to as their cytoarchitecture. Brodmann published his original cortical maps in 1909 and described the layout of the brains of humans, monkeys, and other organisms. Though Brodmann’s original cortical maps labeled 52 individual areas, several of them are found only in nonhuman primates and thus there are fewer areas in the human brain.

The EC is also named Brodmann area 28. Interest in this area arose around the turn of the 19th century when Santiago Ramón y Cajal (1852—1934) described a peculiar part of the posterior temporal cortex, which was strongly connected to the hippocampal formation. Ramon y Cajal suggested that the physiological significance of the latter structure would relate to that of the EC. He assumed that the EC was part of the olfactory system; however, in the late 1950s, Scoville and Milner speculated that the hippocampus was a main player in conscious memory processes in humans. Now, it is well accepted that the EC is part of a strongly interconnected set of cortical areas that together form the parahippocampal region, which is closely related to the hippocampal formation.


The EC is normally the first area affected by Alzheimer’s disease, which accounts for 60—70 percent of all cases of dementia. Alzheimer’s is a chronic neurodegenerative disease that typically starts slowly and worsens over time. A recent study by López and colleagues (2014) showed there are differences in the volume of the left EC between patients with progressing and stable mild cognitive impairment. They also found the volume inversely correlates with the level of alpha band phase synchronization between the right anterior cingulate and temporo-occipital regions.

The EC is also associated with temporal lobe epilepsy and schizophrenia. In epilepsy, layer III of the EC shows degeneration, while in schizophrenia the EC has a general miswiring and decreased volume. In 2012, Suthana and collaborators implanted intracranial depth electrodes in seven epileptic patients to identify seizure-onset zones for subsequent epilepsy surgery. All subjects completed a spatial learning task during which they learned destinations within virtual environments. The researchers found that when entorhinal stimulation was applied while the subjects learned locations of landmarks, their subsequent memory of these locations was enhanced and they reached these landmarks more quickly and by shorter routes. They also found that direct hippocampal stimulation was not effective. Suthana et al. (2012) concluded that stimulation of the EC enhanced memory of spatial information when applied during learning.

Renee Johnson

See also: Cerebral Cortex; Limbic System; Seizures

Further Reading

Hafting, Torkel, Marianne Fyhn, Sturla Molden, May-Britt Moser, & Edvard I. Moser. (2005). Microstructure of a spatial map in the entorhinal cortex. Nature, 436, 801—806.

López, María Eugenía, Ricardo Bruña, Sara Aurtenetxe, José Ángel Pineda-Pardo, Alberto Marcos, Juan Arrazola, … Fernando Maestú. (2014). Alpha-band hypersynchronization in progressive mild cognitive impairment: A magnetoencephalography study. Journal of Neuroscience, 34(44), 14551—14559. Retrieved from http://www.jneurosci.org/content/34/44/14551

Suthana, Nanthia, Zulfi Haneef, John Stern, Roy Mukamel, Eric Behnke, Barbara Knowlton, & Itzhak Fried. (2012). Memory enhancement and deep-brain stimulation of the entorhinal area. New England Journal of Medicine, 366, 502—510. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMoa1107212