Hemispheric asymmetry, modular variability and age-related changes in the human entorhinal cortex

doi:10.1016/j.neuroscience.2004.09.040

Neuroscience

Volume 130, Issue 4, 2005, Pages 911-925

https://doi.org/10.1016/j.neuroscience.2004.09.040 Get rights and content

Abstract

The verrucae areae entorhinalis (VAE) are a characteristic feature of the human brain that occupy the anterior and posterolateral parts of the parahippocampal gyri and correspond to the islands of layer II neurons. We analyzed VAE in 60 neurologically normal subjects ranging from 23 to 85 years of age using a casting method. In 10 of these subjects the total number of neurons in the entorhinal islands was estimated stereologically using the optical fractionator. The number and surface area of VAE were higher in the left hemisphere compared with the right, and this leftward asymmetry was highly significant. Regression analysis showed a negative correlation between average VAE area and age in both hemispheres, representing a rate loss of about 800 μm² per year. The estimated number of neurons obtained with the optical fractionator showed no significant difference between the left and the right hemisphere (468,000±144,000 vs. 405,000±117,000). There was a highly significant negative correlation between neuron numbers and age in both sides. In addition, clusters of small, undifferentiated layer II neurons (‘heterotopias’) were frequently observed in the rostral part of the entorhinal cortex in young and elderly adults.

Layer II entorhinal neurons are among the first to show neurofibrillary changes during normal aging. The present data confirm the occurrence of age-related neuron loss in the entorhinal cortex. Considering the consistent projections from ipsilateral auditory association areas that, together with Broca’s motor-speech area (Brodmann areas 44 and 45), show leftward asymmetry from early infancy (such as Brodmann area 22, planum temporale, and area 52 in the long insular gyrus), we speculate that functional lateralization of the human entorhinal cortex may be associated with specialization for memory processing related to language. Due to the dependence of hippocampal formation on entorhinal projections, this finding is also consistent with the greater capacity of the left hippocampus for verbal episodic memory.

Section snippets

Experimental procedures

The brains of 60 normal individuals, between the ages of 23 and 85 (25 women and 35 men) were obtained between 1976 and 1987 from the Departments of Forensic Medicine at the University Medical School Zagreb and the University Medical School Pristina during routine autopsies in accordance with the law and under the control of the Ethical Committee of the Zagreb Medical School. Only subjects with no neuropsychiatric illnesses and no neurologic evidence of vascular or neurodegenerative lesions

Results

Both the rhinal and collateral sulci were fully present in all of the investigated hemispheres. No macroscopically noticeable differences in the major sulcal patterns were observed between the right and left hemispheres, and between genders. In eight out of 120 hemispheres, the entorhinal cortex extended significantly into the medial bank of the collateral fissure so that VAE located in this part of entorhinal cortex could not reliably be imprinted on the casts. In these cases, the number of

Discussion

The present findings show that determination of the number and area of VAE on casts of the ambient and parahippocampal gyri, and area and number of neurons in entorhinal islands provide us with quantitative parameters about the modular organization of the entorhinal cortex in a large sample of human brains. The number and area of VAE are substantially higher in the left than in the right hemisphere, indicating an anatomical asymmetry of the entorhinal cortex. This finding is in a general

Acknowledgments

Supported by Croatian Ministry of Science and Technology, grant no. 0108–258 to G.S., and by NIH grants AG02219 and AG05138 (to P.R.H.). The authors thank Zdenka Cmuk, Danica Budinscak and Bozica Popovic for excellent technical assistance.

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Hemispheric asymmetry, modular variability and age-related changes in the human entorhinal cortex

Abstract

Section snippets

Experimental procedures

Results

Discussion

Acknowledgments

Brain Res

Schizophr Res

Neurosci Lett

Brain Res Rev

Biol Psychiatry

Neuropsychologia

Anat Anzeiger

Neuron

Brain Res Rev

Neuroscience

Exp Neurol

Brain Cogn

Distorted distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in temporal lobe of schizophrenics implies anomalous cortical development

Arch Gen Psychiatry

Broca’s region revisitedcytoarchitecture and intersubject variability

J Comp Neurol

Broca’s regioncytoarchitectonic asymmetry and developmental changes

J Comp Neurol

Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia

Arch Gen Psychiatry

“Modular” cytoarchitectonic organization of the human entorhinal cortex

Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of elderly patientsa quantitative evaluation of a one-year autopsy population from a geriatric hospital

Cereb Cortex

Zur Pigmentarchitektonik der Grosshirnrinde des MenschenI

Regio entorhinalis. Z Zellforsch

Neuropathological stageing of Alzheimer-related changes

Acta Neuropathol

The human entorhinal cortexnormal morphology and lamina-specific pathology in various diseases

Neurosci Res

Perte de la paroleramollisement chronique et destruction partielle du lobe antérieur gauche du cerveau

Bull Soc Anthropol (Paris)

Sur la faculté du langage articulé

Bull Soc Anthropol (Paris)

Vergleichende Lokalisationslehre der Groβ hirnrinde

Stereologic analysis of neurofibrillary tangle formation in prefrontal cortex area 9 in aging and Alzheimer’s disease

Neuroscience

SPECT of the brain in childhood autismevidence for a lack of normal hemispheric asymmetry

Dev Med Child Neurol

The neural basis of language

Annu Rev Neurosci

Atrophy rates of entorhinal cortex in AD and normal aging

Neurology

A cortical-hippocampal system for declarative memory

Nat Rev Neurosci

Symmetry and asymmetry in the human posterior thalamus: I. Cytoarchitectonic analysis in normal persons

Arch Neurol

Inferior parietal lobuledivergent architectonic asymmetries in the human brain

Arch Neurol

Entorhinal cortex disruption causes memory deficit in early Alzheimer’s disease as shown by PET

Neuroreport

Right-left asymmetry in anterior speech region

Arch Neurol

Level of sustained entorhinal activity at study correlates with subsequent cued-recall performancea fMRI study with high acquisition rate

Hippocampus

Developmental dyslexiafour consecutive patients with cortical anomalies

Ann Neurol

Multi-level analysis of cortical neuroanatomy in Williams syndrome

J Cogn Neurosci

Interhemispheric asymmetries of the modular structure in the human temporal cortex

Science

Asymmetry of chimpanzee planum temporalehumanlike pattern of Wernicke’s brain language area homolog

Science

Human brainleft-right asymmetries in temporal speech region

Science

Cerebral cortex pathology in aging and Alzheimer’s diseasea quantitative survey of large hospital-based geriatric and psychiatric cohorts

Brain Res Rev

Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer’s disease

J Neurosci