This article reviews the major paradigm shifts that have occurred in the area of the application of clinical and experimental neuropsychology to epilepsy and epilepsy surgery since the founding of the International Neuropsychological Society. The five paradigm shifts discussed include: 1) The neurobiology of cognitive disorders in epilepsy – expanding the landscape of syndrome-specific neuropsychological impairment; 2) pathways to comorbidities: bidirectional relationships and their clinical implications; 3) discovering quality of life: The concept, its quantification and applicability; 4) outcomes of epilepsy surgery: challenging conventional wisdom; and 5) Iatrogenic effects of treatment: cognitive and behavioral effects of antiepilepsy drugs. For each area we characterize the status of knowledge, the key developments that have occurred, and how they have altered our understanding of the epilepsies and their management. We conclude with a brief overview of where we believe the field will be headed in the next decade which includes changes in assessment paradigms, moving from characterization of comorbidities to interventions; increasing development of new measures, terminology and classification; increasing interest in neurodegenerative proteins; transitioning from clinical seizure features to modifiable risk factors; and neurobehavioral phenotypes. Overall, enormous progress has been made over the lifespan of the INS with promise of ongoing improvements in understanding of the cognitive and behavioral complications of the epilepsies and their treatment. (JINS, 2017, 23, 791–805)

Clinicians are accustomed to interpreting diagnostic test scores in terms of sensitivity and specificity. Many clinicians also appreciate that sensitivity and specificity need to be interpreted in terms of local base rates (i.e., pretest probability). However, most neuropsychological tests contain a wide range of scores. Important diagnostic information may be sacrificed when valid test scores are reduced to the simple dichotomy of “positive” or “negative” diagnosis that underlies sensitivity and specificity analysis. The purpose of this study is to provide an introduction to multiple-level likelihood ratios, a method for preserving the information in a wider range of scores. These statistics are first described using a hypothetical example of dementia screening, then with patient data from an epilepsy surgery sample. Multiple-level likelihood ratios have several advantages over sensitivity and specificity analysis because they are applied across a wider range of diagnostic scores, and generalize to settings with different base rates. We suggest that the diagnostic validity of many psychological tests may be underestimated by relying solely on traditional dichotomous sensitivity and specificity analysis. (JINS, 2009, 15, 769–776.)

We examined the sensitivity of the Rey Auditory Verbal Learning Test (AVLT), California Verbal Learning Test (CVLT), Boston Naming Test (BNT), and Multilingual Aphasia Examination Visual Naming subtest (MAE VN) to lateralized temporal lobe epilepsy (TLE) in patients who subsequently underwent anterior temporal lobectomy. For the AVLT (n = 189), left TLE patients performed more poorly than their right TLE counterparts [left TLE = 42.9 (10.6), right TLE = 47.7 (9.9); p < .002 (Cohen's d = .47)]. Although statistically significant, the CVLT group difference (n = 212) was of a smaller magnitude [left LTE = 40.7 (11.1), right TLE = 43.8 (9.9); (p < .03, Cohen's d = .29)] than the AVLT. Group differences were also present for both measures of confrontation naming ability [BNT: left LTE = 43.1 (8.9), right TLE = 48.1 (8.9); p < .001 (Cohen's d = .56); MAE VN: left TLE = 42.2, right TLE = 45.6, p = .02 (Cohen's d = .36)]. When these data were modeled in independent logistic regression analyses, the AVLT and BNT both significantly predicted side of seizure focus, although the positive likelihood ratios were modest. In the subset of 108 patients receiving both BNT and AVLT, the AVLT was the only significant predictor of seizure laterality, suggesting individual patient variability regarding whether naming or memory testing may be more sensitive to lateralized TLE. (JINS, 2008, 14, 394–400.)

Reliable neuropsychological markers of right temporal integrity have proven elusive. Specifically it is unclear whether figural and spatial aspects of visual memory are differentially affected by right temporal lobe epilepsy (TLE) and subsequent resection. To investigate this we used the modified Rey Complex Figure (RCF) scoring system devised by Brier et al. (1996) to obtain separate indices of figural and spatial memory in TLE surgery candidates. We extended on their study by examining presurgical performance and change following right and left temporal lobectomy (RATL, n = 38, LATL, n = 42) in individuals from a cross-institutional sample with and without hippocampal sclerosis (HS+/HS−). Contrary to expectation neither figural nor spatial RCF recall were differentially sensitive to RTLE, right HS, or subsequent resection. Presurgically, laterality effects on both figural and spatial memory indices were not found although HS− individuals significantly outperformed HS+ individuals on both measures. Following surgery the largest decrements in both figural and spatial recall were observed among LATL HS− participants. We concluded that RCF recall is a poor marker of right temporal lobe function and suggest it may be a “surrogate” measure of left temporal lobe function possibly due to the verbalizability of many of its components. (JINS, 2007, 13, 664–671.)

The utility of the WMS–III in detecting lateralized impairment was examined in a large sample of patients with temporal lobe epilepsy. Methods of analysis included evaluation of group means on the various indexes and subtest scores, the use of ROC curves, and an examination of Auditory–Visual Index discrepancy scores. In addition, performance on immediate and delayed indexes in the auditory and the visual modality was compared within each group. Of the WMS–III scores, the Auditory–Visual Delayed Index difference score appeared most sensitive to side of temporal dysfunction, although patient classification rates were not within an acceptable range to have clinical utility. The ability to predict laterality based on statistically significant index score differences was particularly weak for those with left temporal dysfunction. The use of unusually large discrepancies led to improved prediction, however, the rarity of such scores in this population limits their usefulness. Although the utility of the WMS–III in detecting laterality may be limited in preoperative cases, the WMS–III may still hold considerable promise as a measure of memory in documenting baseline performance and in detecting those that may be at risk following surgery. (JINS, 2001, 7, 881–891.)

In a previous study, we demonstrated that unilateral cerebral lesions produce hypometric limb movements of the contralateral arm and hemispatial (i.e., directional) hypometria for movements towards contralateral hemispace. In the present study, we investigated 10 patients with right cerebral lesions and 25 healthy controls using a task to uncouple deficits in sensory perceptual systems and motor-action output systems on directional hypometria. This task required participants, with their eyes closed, to reproduce lateral and medial horizontal displacements (15–27 cm) with each arm. Each participant was seated at a waist high table and had their hand placed at an origin point aligned with the axillary fold on the same side. Their hand was moved by the investigator from the origin point to a target point and brought back to the point of origin (input displacement). The participant was then asked to return their hand to either the same target point or to an equidistant target point in the opposite direction. Healthy dextral participants were significantly more hypometric with their right arm, but patients with right cerebral lesions exhibited an opposite pattern with overall left arm hypometria. In addition, patients were significantly more hypometric for movements when output displacements were toward left hemispace. No effect was found for direction of sensory input. The results suggest that the directional hypometria is predominantly produced by hemispatial output deficits. (JINS, 2000, 6, 71–75.)

In a descriptive analysis of 158 patients with temporal lobe epilepsy, Taylor (1969) reported that the age of first seizure varied systematically as a function of laterality and sex. We conducted inferential analyses of Taylor's original data which (1) provided support for his proposal of disproportionate left hemisphere vulnerability to seizure onset in early life, but (2) failed to provide evidence of sex differences in age of onset of unilateral seizures. Examination of these effects in a larger sample of 844 patients drawn from the Bozeman Epilepsy Consortium provided some additional support for findings from the inferential analysis. Specifically, the left hemisphere appeared more vulnerable to seizure onset in childhood, this increased vulnerability extending to about age 5 years. Age of onset of seizures was not different when males and females were compared. Thus, reanalysis of Taylor's original data as well as examination of data from a larger, more contemporary sample suggest that seizure onset varies as a function of laterality, but not sex. (JINS, 1997, 3, 428–434.)

The construct of nonverbal memory, as assessed by figural reproduction tests, has recently been questioned by a number of investigators. The purpose of this study was to reexamine this construct and its relationship to right temporal lobe dysfunction. Figural reproduction test scores were examined in 757 epilepsy surgery candidates obtained from 8 epilepsy centers participating in the Bozeman Epilepsy Consortium. All participants exhibited unequivocal evidence of left (LTL) or right (RTL) temporal lobe epilepsy observed in ictal and interictal EEG recordings. All subjects also had IQ scores exceeding 70, right-hand preference, and left hemisphere language dominance confirmed by intracarotid sodium amytal testing. Comparisons of LTL and RTL groups showed no significant differences in scores on the Visual Reproduction subtests from the Wechsler Memory Scale (WMS) or Wechsler Memory Scale–Revised (WMS–R) or on the copy and delayed recall conditions of the Rey–Osterrieth Complex Figure Test (ROCFT). Significant differences were observed among centers on WMS and ROCFT scores, which are likely to be a result of variations in administration and/or scoring procedures. The lack of significant differences between LTL and RTL groups in this large sample raise questions about the nature of nonverbal memory and its relationship to right temporal lobe dysfunction. (JINS, 1997, 3, 435–443.)