The neurobiology of cognitive disorders in temporal lobe epilepsy

Abstract

Cognitive impairment, particularly memory disruption, is a major complicating feature of epilepsy. This Review will begin with a focus on the problem of memory impairment in temporal lobe epilepsy (TLE). We present a brief overview of anatomical substrates of memory disorders in TLE, followed by a discussion of how our understanding of these disorders has been improved by studying the outcomes of anterior temporal lobectomy. The clinical efforts made to predict which patients are at greatest risk of experiencing adverse cognitive outcomes following epilepsy surgery are also considered. Finally, we examine the vastly changing view of TLE, including findings demonstrating that anatomical abnormalities extend far outside the temporal lobe, and that cognitive impairments extend beyond memory function. Linkage between these distributed cognitive and anatomical abnormalities point to a new understanding of the anatomical architecture of cognitive impairment in epilepsy. Clarifying the origin of these cognitive and anatomical abnormalities, their progression over time and, most importantly, methods for protecting cognitive and brain health in epilepsy, present a challenge to neurologists.

Figure 1

Variability in verbal memory change following left and right anterior temporal lobectomy. Preoperative to postoperative changes in verbal learning performance (total words recalled on California Verbal Learning Test) in 100 patients who underwent left or right anterior temporal lobectomy. The dependent variable is the number of words recalled from a 16-item word list across five learning trials. Abbreviation: ATL, anterior temporal lobectomy.

Figure 2

Verbal memory change following left anterior temporal lobectomy in relation to hippocampal pathology. Resection of left hippocampus with no or minimal sclerosis results in significant preoperative to postoperative decline in trial-to-trial learning. Long-delay recall is ≈35% lower compared with preoperative performance. Resection of left hippocampus with significant hippocampal sclerosis has a minimal effect on postoperative trial-to-trial learning compared to preoperative performance. All patients were confirmed to be left hemisphere speech dominant by the Wada test. Abbreviation: CVLT, California Verbal Learning Test.

Figure 3

Change in the serial position curve following left anterior temporal lobectomy as a function of left hippocampal pathology. a | Resection of left hippocampus with no or minimal sclerosis results in significant preoperative to postoperative alteration of the serial position curve with decreased recall of primacy and middle portions of the list. b | Resection of left hippocampus with notable hippocampal Sclerosis has no effect on the serial position curve. The data are derived from the patient’s free recall of a supraspan word list.

Figure 4

Reduced gray matter thickness and white matter integrity in left MTLE. a | Mean percent reduction in cortical thickness as a percentage of control average. Red areas in the bilateral in the frontal poles, frontal operculum, orbitalfrontal, lateral temporal and occipital regions, and the right angular gyrus and primary sensorimotor cortex surroundings the central sulcus denote ≤30% decrease in thickness, on average, compared with corresponding areas in controls. b | Significance of these changes shown as a map of P values. c | Reductions in white matter integrity, measured by decreased fractional anisotropy, were evident in mesial and lateral temporal lobe, limbic system and extratemporal lobe regions, particularly ipsilateral to the side of seizure onset. Yellow and dark red regions indicate white matter tracts with decreased fractional anisotropy. Green regions indicate areas not notably different from controls. Only left MTLE patients are presented here, although similar gray and white matter abnormalities—albeit to a lesser degree—were evident in right MTLE. Parts a and b are modified, with permission from Oxford University Press © Lin, J. J. et al. Cereb. Cortex 17, 2007–2018 (2007). Part c is modified with permission from Elsevier Ltd © Focke, N. K. et al. Neuroimage 40, 728–737 (2008). Abbreviation: MTLE, mesial temporal lobe epilepsy.