Table 4.

Main takeaways for the pre-clinical sections and associated clinical relevance.

Coding	Physiology		Epilepsy
	Preclinical	Clinical	Preclinical	Clinical
Rate	• Place cells fire when an animal visits a specific place field • Time cells fire at specific times in a task called time fields and they can be time locked to an external stimulus • Grid cells provide activity-based maps of speed and direction in a certain environment and fire in different locations in an environment • Place and grid cells map are part of the greater hippocampal cognitive map • Inputs from the entorhinal cortex are important for hippocampal rate coding in the formation of the spatial memory and cognitive map • Selective disruption of the theta rhythm power correlated with spatial component of the non-verbal correlates of episodic-like memory task	• Time cells fire at specific times in a task called time fields and they can be time locked to an external stimulus • Inputs from the entorhinal cortex are important for hippocampal rate coding in the formation of the spatial memory and cognitive map	• Place cell misfiring • Loss of accurate spatial navigation • Lesioning the hippocampus results in loss of spatial memory • Lesioning the lateral entorhinal cortex impairs the hippocampal rate remapping upon changing the configuration of the environment • Time and grid cells deficits	• Time cells firing deficits • Disruption of entorhinal cortex inputs • Spatial memory deficits
Temporal	• The rate of populations of neuronal firing is also modulated in time • Temporal modulation is manifested as burst firing with bursts occurring at theta frequency in the hippocampus • Theta modulation is important for phase precession, phase preference and hippocampal replay • Phase precession is important for information processing. • Theta-phase precession could be an indication of item-context associations • Selective disruption of theta coordination across CA1 and the DG correlated with temporal component of the non-verbal correlates of episodic-like memory task	• The rate of populations of neuronal firing is also modulated in time • Neurons in the hippocampus and entorhinal cortex fire for space and time • Time cells exhibited theta-phase precession during memory encoding • Time cells activity correlates with the use of temporal location during retrieval phase of free recall task	• Loss of phase precession • Temporal modulation deficits • Item-context association deficits	• Loss of time modulation of neuronal firings • Theta-phase precession deficits • Temporal location alteration in free recall task
Population	• Neurons are functionally connected into a network • Population coding increases robustness of network function • Place cell populations will respond when the animal goes into the field • Dentate gyrus (DG) and its projection to CA3 underlie the pattern separation process • Working memory in the prefrontal cortex depends on population coding	• Pattern separation involves posterior occipitotemporal cortex (OTC) and the hippocampus • Dentate gyrus (DG) and its projection to CA3 underlie the pattern separation process • Working memory in the prefrontal cortex depends on population coding • BOLD signal on fMRI decreases during the delay phase of image-sequence matching task in humans • BOLD signal re-emerge during the image presentation phase of image-sequence matching task • Working memory information is maintained in the collective synaptic weights of populations of neurons in the PFC.	• Loss of functional connections • Decreased robustness of network function • Loss of place cells firing accuracy • DG aberrant CA3 influences • Working memory deficits	• Early stage TLE patients experience functional connectivity deficits in the ipsilateral hemisphere and interhemispheric connections • Patients with generalized epilepsy have an increase in the interhemispheric connectivity but reduced functional connectivity • Decreased cluster coefficient within the DMN underlies the language impairment in patients with generalized epilepsy without focal brain damage • Reduced DMN activity suppression can alter the balance between activated and deactivated neural networks and disturb cognitive function • Hub nodes in TLE patients were mainly located in the limbic and temporal association cortices instead of being evenly distributed between different lobes • Memory impairments are present in patients who don't show a lesion with MRI