Epileptic baboons have lower numbers of neurons in specific areas of cortex

Abstract

Epilepsy is characterized by recurrent seizure activity that can induce pathological reorganization and alter normal function in neocortical networks. In the present study, we determined the numbers of cells and neurons across the complete extent of the cortex for two epileptic baboons with naturally occurring seizures and two baboons without epilepsy. Overall, the two epileptic baboons had a 37% average reduction in the number of cortical neurons compared with the two nonepileptic baboons. The loss of neurons was variable across cortical areas, with the most pronounced loss in the primary motor cortex, especially in lateral primary motor cortex, representing the hand and face. Less-pronounced reductions of neurons were found in other parts of the frontal cortex and in somatosensory cortex, but no reduction was apparent in the primary visual cortex and little in other visual areas. The results provide clear evidence that epilepsy in the baboon is associated with considerable reduction in the numbers of cortical neurons, especially in frontal areas of the cortex related to motor functions. Whether or not the reduction of neurons is a cause or an effect of seizures needs further investigation.

Keywords: neuronal density; plasticity; primates.

Fig. 1.

Cell and neuron density maps from a normal baboon (case 09-27) and an epileptic baboon (case 11-45). The normal cell (A) and neuron (A′) distribution in baboons shows a general caudal-to-rostral decrease in cells and neurons across the cortical sheet, with the highest cell and neuron densities located within primary sensory areas, which is consistent with findings from other primates. Epileptic baboons have consistently lower cell (B) and neuron (B′) densities relative to control. Neuron reduction appears to be regional specific with the most neuron loss observed in cortex rostral to the central sulcus, including M1.

Fig. 2.

Neuron density versus the anterior-posterior dimension was plotted for each case. All flattened hemispheres were dissected into tissue pieces, and each piece was assigned an anterior-posterior coordinate by generating centroid measures. Normal neuron distribution (A and B) is shown to follow the caudal-to-rostral decrease in cortical neuron density that is typical of primates. Epileptic baboons show a reduction of neurons within this distribution, particularly in cortex rostral to the central sulcus (C and D).

Fig. 3.

Histograms of neuron density in M1. Movement representation boundaries within M1 were estimated and dissected as described by Young et al. (16), and neuron densities by surface area were plotted for each case. There is neuron reduction within M1 of epileptic baboons relative to normal baboons. Lateral M1, which contains the face and hand representations, was the most neuron dense M1 region in normal baboons. In epileptic baboons, there is a substantial reduction of neurons in M1 in both cases, with the hand movement representation being the least neuron dense region of motor cortex.