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Mesial temporal lobe epilepsy: Large-scale changes of network oscillations?

Mesial temporal lobe epilepsy (MTLE) is the most common form of focal epilepsies in adults and frequently resistant to anti-epileptic medication. It is characterized by recurrent seizures, pathological restructuring of the hippocampal formation and is often accompanied by cognitive deficits, in particular by impairments of spatial navigation and memory. Changes in a certain type of oscillatory network activity are being discussed as a possible cause of these memory deficits, which in turn were seen in connection with structural changes in the hippocampus. New studies by PhD student Antje Kilias and co-workers from the Bernstein Center Freiburg, the Dept. of Microsystems Engineering, University of Freiburg and the Freiburg University Medical Center, however, suggest other conclusions.

Mesial temporal lobe epilepsy: Large-scale changes of network oscillations?

Epileptic animals (gray line) show a reduced theta frequency when running at the same speed as control animals (white line).

In rodent MTLE models, memory deficits are associated with changes of a particular type of oscillatory network activity, the theta rhythm (5 – 12 Hz). Since in healthy humans and rodents theta oscillations are tightly coupled to navigation and spatial memory, impairments of these oscillations have been proposed as a potential cause for memory deficits in MTLE. At the same time, memory deficits have been correlated with cell loss and reorganization in the hippocampus.



Structural changes, however, are typically stronger in one of the two hippocampi and vary along the extent of the hippocampus. This raised the question whether the hippocampal damage actually causes the changes in theta rhythm and whether the degree of change depends on the severity of the restructuring.



To investigate this, Antje Kilias and colleagues used an MTLE mouse model that reproduces focal hippocampal sclerosis. Although the network structure suffers only local damage, the frequency of the theta rhythm was dramatically decreased throughout the hippocampal formation of these mice. This frequency reduction was independent of the rate of epileptic activity or the extent of tissue reorganization.



This indicates that the slow-down of the theta rhythm more likely arises from epilepsy-associated changes in other brain structures involved in theta generation. Irrespective of the origin of the theta slowdown, this dramatic decrease in frequency has the potential to account for cognitive and memory deficits. The findings of Antje Kilias and her co-workers have now been published in “Hippocampus”.



Original publication

Kilias, A.; Haeussler, U.; Heining, K.; Froriep, U.; Haas, C. & Egert, U. (2018) Theta frequency decreases throughout the hippocampal formation in a focal epilepsy model. Hippocampus; [Epub ahead of print] [DOI]



Contact

Antje Kilias

Bernstein Center Freiburg

University of Freiburg

Hansastr. 9a

79104 Freiburg

and 

University of Freiburg

Biomicrotechnology, Dept. of Microsystems Engineering

Faculty of Engineering

Georges-Köhler-Allee 102

79110 Freiburg

Tel.: +49 (0)761 203 7523

E-mail: kilias@bcf.uni-freiburg.de

 

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