J Epilepsy 1991;4 139-148 © 1991 Demos Publications

Predictors of Neuropsychological Change Following Anterior Temporal Lobectomy: Role of Regression Toward

the Mean

1"3'4"6Bruce P. Hermann, "4'6Allen R. Wyler, 2Roger VanderZwagg, 7Robert K. LeBailly, 7Steve Whitman, 5Grant Somes, and 1Julianna Ward

The purpose of this investigation was to identify the determinants of changes in visual-spatial, language, and memory function following anterior temporal lobec- tomy (ATL). Demographic (age, education, and IQ), epilepsy (age at onset), and surgical variables (laterality of resection and surgical outcome) were examined for their ability to predict postoperative changes in neuropsychological function. Particular interest was focused on the ability of an additional variable, initial level of performance, to predict postoperative cognitive change. This latter variable reflected the effects of a statistical artifact (regression toward the mean). The pre- dictive ability of these variables was examined in three data sets involving over- lapping groups of patients who underwent dominant or nondominant ATL. Re- sults indicated that initial level of performance was the most powerful predictor of postoperative cognitive change on measures of cortical ability (visual-spatial and language function), whereas laterality of resection was not a significant predictor of postoperative cognitive decline. With regard to postoperative changes in memory function, initial level of performance remained a significant predictor. However, laterality of resection was also a consistent and significant predictor of postoperative impairments in memory ability. These results suggest that regres- sion toward the mean exerts a significant effect on pre- to postoperative neuro- psychological evaluations and needs to be taken into consideration in research with groups of patients as well as when interpreting the results of test findings from individual patients. Key Words: Anterior temporal lobectomy--Outcome-- Neuropsychology.

While it is generally agreed that anterior temporal lobectomy (ATL) is an effective treatment for intrac- table seizures of temporal lobe origin (1), many de-

Received December 2, 1990; accepted March 18, 1991. From the lEpiCare Center and 2Division of Health Ser-

vices Research, Baptist Memorial Hospital, Departments of 3psychiatry, 4Neurosurgery, and SBiostatistics, University of Tennesee, Memphis, and the 6Semmes-Murphey Clinic, Memphis, TN, and 7Center for Urban Affairs and Policy Re- search, Northwestern University, Evanston, IL, U.S.A.

Address correspondence and reprint requests to Dr. B. Hermann at EpiCare Center, 910 Madison Avenue, Mem- phis, TN 38103, U.S.A.

tails concerning the neuropsychological morbidity associated with the procedure remain to be clarified. This issue could be most directly addressed by pro- spective neuropsychological investigations that com- pare surgical patients to matched groups of unop- erated individuals with comparably severe epilepsy. Unfortunately, such studies are very few in number (2). Further, while findings based on group data pro- vide information regarding the general neuropsy- chological risks and benefits associated with ATL, considerable concern continues to center on the prediction of cognitive risk/benefit and neuropsy- chological outcome for individual patients (3-5).

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However , determining the neuropsychological ef- fects of epilepsy surgery in individual patients is dif- ficult. The basic paradigm requires that the patient be assessed both pre- and postoperatively so as not to confuse long-standing preoperative deficits with the effects of surgery. As will be discussed, use of a test- retest paradigm is associated with several methodo- logical and interpretive difficulties.

Along with other centers, we have been attempt- ing to identify the neuropsychological sequelae of ATL. In the course of these efforts, we have identi- fied a significant source of variability in pre- to post- operative neuropsychological performance that ap- pears to be attributable to the use of a test-retest paradigm. This effect, regression toward the mean, can take the form of either postoperative test score im- provements or declines and could easily be misinter- preted as an outcome of surgical intervention. One of the ways in which regression toward the mean is manifested is by the tendency of patients with ex- treme scores to score closer to the overall group mean upon retesting (6-9). That is, a patient who scored well above the mean on a neuropsychological test preoperatively may score lower (closer to the mean) at postoperative testing merely because of this statis- tical effect. A drop in performance thus does not necessarily reflect an adverse effect of surgery. Con- versely, a patient who scored poorly at the preoper- ative assessment may score considerably higher at the second evaluation and the gain in performance does not necessarily reflect a positive effect of surgery. The magnitude of the regression effect varies as a function of the extremity of the patient's (initial) score from the group mean, the magnitude of the error component compared to the true effect, and the cor- relation between the pre- and postoperative meas- urements (6). Before determining the neurobehav- ioral effects of surgery in general, or the effects of other variables of interest in particular (e.g., laterality of resection), the variability due to regression toward the mean needs to be determined and controlled.

This paper will present a method to assess pre- versus postoperative netiropsychological change that facilitates detection of regression toward the mean. This method will be demonstrated on multiple mea- sures of visual-spatial ability using 109 patients who underwent ATL. Similar effects in the language do- main will be demonstrated via a reanalysis of data on a smaller and overlapping group of 64 ATL patients who underwent assessment with a standardized apha- sia battery (10). After examining performance on these tests of cortical function, a similar reanalysis will be carried out on a measure of mesial temporal ability (memory) using 61 ATL patients (11). Analysis of the

140 J EPILEPSY, VOL. 4, NO. 3, 1991

similarities and differences among these three data sets will be shown to have some implications for understanding the neuropsychological morbidity associated with ATL.

Study 1: Visual-Spatial Function

Subjects

The subjects were 109 nonretarded (WAIS-R FSIQ >69) patients who underwent partial resection of the dominant (n = 50) or nondominant (n = 59) anterior temporal lobe. Table 1 provides information on the demographic and seizure-related characteristics of the two groups.

Procedure

For all three studies represented in this paper, pa- tients underwent continuous inpatient closed-circuit video/EEG recording of spontaneous seizures first using scalp, and then invasive, EEG procedures. The patients underwent magnetic resonance imaging, complete neuropsychological assessment, psychi- atric evaluation, social service interview, and bilateral intracarotid sodium amytal testing in order to deter- mine cerebral dominance for speech (12-14).

Preoperative neuropsychological assessment was typically carried out 2-3 months prior to surgery (during inpatient scalp electrode monitoring), and then again as close as possible to the 6-month post- operative clinic visit. Therefore, there was usually an 8-9 month interval between assessments.

Surgical Procedure

Patients' surgery was conducted using general en- dotrachael anesthesia. The anterior temporal tip was amputated down to the ventricle and then hippo-

Table 1. Subject characteristics (Study 1)

Nondominant Dominant ATL (n = 59) a ATL (n = 50) a

Age (years) 31.2 (16-63) 30.1 (16-52) Education (years) 12.2 (7-19) 12.3 (7-18) Gender 33 F, 26 M 29 F, 21 M Age at onset (years) 16.3 (1-56) 10.3 (1-39) Full-Scale IQ 90.3 (73-117) 87.6 (71-124) Outcome 39 SF, 20 NSF b 28 SF, 22 NSF

aRanges are provided in parentheses. bSF, totally seizure-free; NSF, not totally seizure-free

(auras only or greater than 75% reduction in seizure fre- quency).

PREDICTORS OF NEUROPSYCHOLOGICAL CHANGE FOLLOWING ATL

Table 2. Predictors of change on visuospatial measures (Study 1)

Test R 2 p Significant predictors

Form Discrimination 0.35 (0.001

Facial Recognition 0.22 (0.001

Line Orientation 0.29 (0.001

Hooper Test 0.38 (0.001

Initial performance (B = -0.58) Education (B = 0.31)

Initial performance (B = -0.47)

Initial performance (B = -0.55) Education (B = 0.17)

Initial performance (B = -0.58) Age (B = -0.22)

campus was taken as a separate specimen for patho- logical examination. The hippocampus and parahip- pocampal gyrus were resected to the posterior margin ofthe cerebral peduncle. Conservative lateral temporal resections were carried out, and the mean resections are specified in the individual tables. This resection is similar to that previously described by Spencer et al. (15) except that the superior temporal gyrus was removed in our patients. All cortical dis- section was done using the operative microscope for visualization.

Neuropsychological Measures

Measures of visual-perceptual and visual-spatial ability were administered, and, for the purposes of this investigation, results from the following four tests were examined: Visual Form Discrimination Test (a measure of visual alertness and visual form discrim- ination) (16); Hooper Visual Organization Test (a test of visual closure/gestalt perception) (17); Facial Rec- ognition Test (a test of the ability to match unfamiliar faces) (16); and Judgment of Line Orientation Test (a measure of visual-spatial perception) (16). Age, edu- cation, and/or gender corrections were made as spe- cified in the test manuals.

Data Analysis

Pre- to postoperative difference scores were com- puted for each patient on each neuropsychological test. These difference scores served as the dependent or criterion measure. The proportion of variance in the change scores that is attributable to the effects of regression toward the mean can be identified by using the patients' initial level of performance (i.e., preop- erative test score) as a predictor of the difference score (6,8). If initial level of performance is significantly inversely correlated with pre- to postoperative differ- ence scores, then regression toward the mean is sig-

nificant. Usually regression toward the mean is treated as a nuisance variable and is controlled for prior to examining the effects of the primary variables of interest. Here the attempt is to determine whether regression toward the mean exerts a significant effect in the evaluation of cognitive outcome and to assess its relative explanatory value compared to other variables.

The additional independent or predictor variables for each test included laterality of ATL (dominant versus nondominant), chronological age, years of education, age at onset of epilepsy, and surgical out- come (seizure-free/not seizure-free). The ratio of subjects to predictor variables was approximately 10:1, a favorable ratio. For all three data sets, the identical predictor variables were used, and the data were analyzed by stepwise regression.

Results

Table 2 provides a summary of the regression anal- yses, including the standardized beta weights for the significant predictor variables. All four regression analyses were highly statistically significant (p < 0.001), accounting for between 22% and 38% of the variance in the difference scores (Multiple Rs varying between 0.47 and 0.62). For every test examined, the most powerful predictor of postoperative neuropsy- chological change was the patients' initial (preop- erative) level of performance. The amount of post- operative neuropsychological change was dependent on how well (or poorly) the patient performed pre- operatively.

Some additional predictors of postoperative neu- ropsychological change were identified. Education was a significant predictor of postoperative cognitive change for two tests (Visual Form Discrimination and Facial Recognition). Increasing years of education was associated with postoperative improvements on these measures. In addition, increasing chronologic-

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al age was a significant predictor of postoperative cognitive decline for one test (Hooper Visual Or- ganization). Interestingly, in no case did the laterality of ATL serve as a significant predictor of postopera- tive test score change, i.e., patients who underwent nondominant ATL did not exhibit more postoperative loss on these tests as a result of surgery.

Inspection of scatterplots of difference scores for the neuropsychological tests similarly reflected the effects of regression toward the mean. For instance, on the Visual Form Discrimination Test the preop- erative mean score was 29. Thirty-six patients scored below the mean preoperatively. Twenty-nine of the 36 showed postoperative gains, whereas only seven showed postoperative losses. Thirty-two patients scored above the mean preoperatively. Twenty-three of the 32 patients showed postoperative declines, whereas only 9 showed postoperative gains. The remaining patients either scored at the mean pre- operatively or showed a difference score of 0.

Finally, a comparison was made of the overall pre- versus postoperative mean scores on each test. There were significant (p <(0.01) postoperative mean score increases on the Hooper Visual Organization Test (mean gain, 1.0 point; range, - 9 to +7) and the Judg- ment of Line Orientation Test (mean gain, 0.95 point; range, - 7 to +11). A significant (p < 0.01) overall decline was seen on the Facial Recognition Test (mean loss, 1.2 points; range, - 1 3 to +8). No overall change was found on the Visual Form Discrimination Test.

Study 2: Language Funct ion

The purpose of this study was to determine the ability of the same demographic, epilepsy, and sur- gical variables to predict postoperative alterations in language function. As before, initial level of perfor- mance was an additional predictor variable. A stan- dardized aphasia battery was administered to all pa- tients, and the primary interest was to determine the predictors of postoperative language change and identify any similarities in outcome compared to Study 1. These patients were the subject of an in- dependent report on language outcome following ATL (10), and their data were reanalyzed here in order to determine the effects of regression to the mean on the aphasia battery.

Subjects

Subjects consisted of 64 consecutive nonretarded (FSIQ > 69) patients who underwent partial resection of the dominant (n = 29) or nondominant (n = 35) anterior temporal lobe. As in Study 1, all patients

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Table 3. Subject characteristics (Study 2)

Dominant Nondominant temporal temporal (n = 29) a (n = 35) a

Age (years) 25 (16-48) 26 (17-49) Education (years) 12 (7-18) 12 (7-19) Gender 12 M, 17F 19 M, 16 F Age at onset (years) ~ 4 (1-39) 13 (1-36) Full-Scale IQ 84 (71-124) 85 (73-117) Outcome 13 SF, 14 NSF 19 SF, 16 NSF Amount resected (cm) c 4.25 (3.4-4.7) 4.5 (3.5-5.5)

°Tabled values for continuous variables are medians with the range in parentheses.

bp <~ 0.01 using Wilcoxin Rank Sum Test. Cp < 0.05 using Wilcoxin Rank Sum Test.

underwent a bilateral intracarotid sodium amytal test to determine cerebral dominance for speech.

The demographic and seizure-related characteris- tics of the patients are listed in Table 3. The dominant temporal lobe group had a significantly earlier me- dian age at onset (p <(0.01) ;and concomitantly longer duration of epilepsy (p <~ 0.05), and underwent less resection of the lateral temporal lobe (p <~ 0.05) com- pared to the nondominant temporal lobe group. None of the other between-group comparisons were significant.

Neuropsychological Measures

The Multilingual Aphasia Examination (MAE) was used to assess language ability (18). The MAE is a specialized language battery designed to evaluate the presence, severity, and qualitative aspects of lan- guage disorder. Seven subtests were administered that assessed the following abilities: visual confronta- tion naming (Visual Naming), repetition (Sentence Repetition), oral associative fluency (Controlled Oral Word Association), spelling of individual words (Oral Spelling), complex receptive language comprehen- sion (Token Test), and aural and reading comprehen- sion of simple words and phrases (Aural Compre- hension, Reading Comprehension).

Raw scores for each subtest were corrected for age and education where appropriate as indicated in the test manual.

Data Analyses

As in Study 1, for each subtest each patient's pre- minus postoperative raw score difference was calcu- lated. The same demographic, epilepsy, and surgical variables were examined as to their ability to predict

PREDICTORS OF NEUROPSYCHOLOGICAL CHANGE FOLLOWING ATL

Table 4. Predictors of language change (Study 2)

Subtest R 2 p Significant predictors

Visual Naming 0.195 0.002 Full-Scale IQ (B = 0.26)

Sentence Repetition 0.35 <0.001 Initial performance (B = -0.48)

Associative Verbal Fluency 0.38 <0.001 Initial performance (B = -0.56) Age at onset (B = -0.27)

Oral Spelling 0.35 <0.001 Initial performance (B = -0.43)

Token Test 0.34 <0.001 Initial performance (B = -0.49)

Aural Comprehension 0.22 <0.001 Initial performance (B = -0.26)

Reading Comprehension 0.34 <0.001 Initial performance (B = -0.31)

postoperative alterations in language performance. Initial level of performance also served as a predictor in order to determine the role played by regression toward the mean in pre- to postoperative perfor- mance change.

Results

Table 4 presents the results of the analyses, includ- ing the standardized beta weights for the significant predictor variables. All seven regression analyses were highly statistically significant (p < 0.01), ac- counting for between 22 and 38% of the variance in the difference scores (Multiple Rs ranging from 0.47 to 0.62). For six of the seven MAE subtests, the most powerful predictor of postoperative language change was the patients' initial (preoperative) level of per- formance. Patients who scored above the mean pre- operatively tended to score lower postoperatively, whereas patients who scored below the mean pre- operatively tended to score higher (better) post- operati,)ely.

Full-Scale IQ was a significant predictor of post- operative Visual Naming scores, with higher IQ scores associated with better postoperative Visual Naming scores. On the measure of oral fluency, age at onset was an additional predictor with older age at onset associated with lower postoperative fluency scores.

Finally, an overall comparison of the pre- to post- operative scores was made, and only one significant (p < 0.05) difference was found. There was a sig- nificantly higher postoperative Token Test score. Inspection of Token Test performance change as a function of the laterality of the resection revealed increased Token Test scores in the patients who underwent dominant ATL.

In summary, the results involving language func- tion were comparable to the findings involving

visual-spatial ability, i.e., the patients' initial level of performance was the most frequent and powerful predictor of postoperative neuropsychological change, suggesting the strong presence of regression toward the mean. Laterality of resection was not a predictor of declining postoperative test scores.

Study 3: Memory Function

The purpose of this final investigation was to deter- mine the predictors of postoperative alterations in verbal memory function. It has been our experience, consistent with the reports of others (19), that the mesial temporal region is the most frequent site of seizure onset in patients with intractable nonlesional complex partial seizures. In that the mesial temporal region, therefore, represents the primary target of resection at our center, and given the known rela- tionship between this region and memory ability (13,20-23), one might reasonably expect to find pre- dictors of postoperative memory change other than regression to the mean. For instance, an effect of laterality of resection is most often noted for measures of verbal learning and verbal recall ability, and less often for measures of nonverbal (visual) material (e.g., 24). We therefore examined pre- and post- operative performance on a measure of verbal learn- ing and recall ability [California Verbal Learning Test (CVLT)] (25). A subset of these patients is the sub- ject of an independent report on memory outcome following ATL (11), and the data were reanalyzed here to investigate the effects of regression toward the mean on memory performance.

Subjects The subject pool consisted of 61 nonretarded

(FSIQ > 69) patients with medically resistant com- plex partial seizures of temporal lobe origin. Char-

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Table 5. Subject characteristics (Study 3)

Dominant Nondominant temporal temporal (n = 29) a (n = 32) °

Age (years) 29.8 (14-52) 32.6 (16-63) Education (years) 12.4 (8-16) 12.1 (7-16) Gender 17 F, 12 M 19 F, 13 M Age at onset (years) 11.7 (1-34) 17.4 (1-56) Outcome 13 SF, 16 NSF 19 SF, 13 NSF Amount of resection

(cm) 4.5 (3.4-5.5) 4.8 (3.8-6.5)

°Standard deviations are given in parentheses.

acteristics of patients who underwent dominant (n = 29) or nondominant (n = 32) ATL are shown in Table 5.

Procedure

All subjects were administered the CVLT (25). This test consists of five learning trials of a 16-word target list composed of four words from four different se- mantic categories. The CVLT yields measures of re- call, recognition, learning characteristics, and error types.

The target list was read aloud to the examinee at the rate of one word per second. After each trial, the examinee was instructed to freely recall as many words as possible in any order. This procedure was carried out for five trials. A similarly constructed in- terference list was then presented for one learning trial. Following free recall of the interference list the examinee was asked to recall as many words as pos- sible from the list that had been presented five times (short delay free recall). This was followed by short delay cued recall of the target list during which the examinee was cued with the four category names and was asked to recall as many words as possible. Fol- lowing a 20-min delay, during which time other tasks were administered, there was assessment of long de- lay free recall, long delay cued recall, and recogni- tion memory. Recognition was assessed with a yes / no paradigm, with 28 distracters mixed in with 16 tar- gets (25). The CVLT protocols were analyzed by the standard computer software.

Data Analyses

The CVLT yields a large number of dependent measures (eight recall measures, seven indices re- garding learning characteristics, four concerning recall errors, four recognition, and five contrast mea-

144 J EPILEPSY, VOL. 4, NO. 3, 1991

sures). A total of 10 indices were selected for analy- sis. They represented indices of overall learning (total words recalled), delayed recall (short delay free recall and short delay cued recall), learning style (semantic clustering and serial clustering), other qualitative as- pects of recall (percent recall middle and percent recall recency), and error characteristics (cued re- call intrusion errors and free recall intrusion errors). In this manner, several different aspects of verbal learning and recall could be sampled.

Difference scores were computed for each patient on the above CVLT indices. Stepwise regression was computed entering the same predictor variables in- corporated in Studies 1 and 2: initial level of per- formance, laterality of resection (dominant versus nondominant temporal lobe), age at onset, chrono- logical age, years of education, Full-Scale IQ, and surgical outcome (seizure-free versus not seizure- free).

Results

The results are shown in Table 6. In summary, the multiple regression analyses accounted for between 10% and 46% of the variance in the pre- and post- operative difference scores (Multiple Rs between 0.32 and 0.68). Initial level of performance was significant for all but one CVLT index (free recall intrusions). Laterality of resection was significant for all 10 CVLT indices. The effect of initial level of performance indi- cated that above-average preoperative CVLT per- formance was associated with postoperative declines, whereas below-average preoperative performance was associated with postoperative improvements. The laterality of resection effect revealed that left temporal lobectomy was associated with greater post- operative performance declines, and /or fight tem- poral lobectomy was associated with improved post- operative performance on all the CVLT indices (see ref. 11 for a more detailed presentation of these find- ings).

Chronological age was significant on two CVLT indices (total words recalled and short delayed free recall), with increasing chronological age associated with greater postoperative declines in memory per- formance. Finally, education was a significant predic- tor on two CVLT indices (total words recalled and trial 5), with increasing years of education associated with increased postoperative memory performance. None of the other predictor variables was associated with postoperative alterations in memory performance.

When mean pre- versus postoperative scores were examined, only one CVLT index was significant (p 0.05). There were significantly more total free recall

PREDICTORS OF NEUROPSYCHOLOGICAL CHANGE FOLLOWING ATL

Table 6. Predictors of memory change (Study 3)

CVLT index R 2 Predictors

Total Words Recalled 0.40

Trial 5 0.39

Short Delay Free Recall 0.37

Short Delay Cued Recall 0.37

Semantic Clustering 0.16

Serial Clustering 0.33

Percent Correct Middle 0.46

Percent Correct Recency 0.36

Free Recall Intrusions 0.10

Cued Recall Intrusions 0.14

Initial performance (B = -0.60) Laterality of resection (B = -0.50) Age (B = -0.30) Education (B = -0.27)

Initial performance (B = -0.66) Laterality of resection (B = -0.38) Education (B = -0.26)

Initial performance (B = -0.53) Laterality of resection (B = -0.50) Age (B = -0.23)

Initial performance (B = -0.51) Laterality of resection (B = -0.51)

Laterality of resection (B = -0.35) Initial performance (B = -0.31)

Initial performance (B = -0.50) Laterality of resection (B = 0.25)

Initial performance (B = -0.58) Laterality of resection (B = -0.49)

Laterality of resection (B = -0.47) Initial performance (B = -0.46)

Laterality of resection (B = 0.32)

Initial performance (B = -0.28) Laterality of resection (B = 0.27)

intrusions postoperatively (mean change, +1.4 in- trusions; range, - 8 to +19).

Discussion

We will first review the findings from the three data sets and discuss their implications. Second, the issue of regression toward the mean will be examined in closer detail. Finally, some of the methodological problems inherent in this investigation will be reviewed.

Predictors of Postoperative Neuropsychological Change

Across all three data sets the most consistent and powerful predictor of postoperative neuropsycho- logical change was the patients' initial level of perfor- mance. It was a significant predictor for all 4 of the visual-perceptual and visual-spatial tests, 6 of the 7 aphasia battery subtests, and 9 of the 10 memory in- dices. The effect of initial level of performance was negative in all instances, indicating that patients who scored above average preoperatively tended to score

lower (closer to the overall mean) postoperatively, whereas patients who scored below-average pre- operatively tended to score better postoperatively. This relationship between initial level of performance and change scores indicates the presence of regres- sion toward the mean (6,8).

Particularly interesting was the dichotomy in re- sults between the language and visual-spatial tests relative to the measures of memory function. For the language and visual-spatial tests, laterality of resec- tion never predicted postoperative declines in cog- nitive function. Conversely, laterality of temporal lobe resection was a significant predictor of post- operative change for all 10 memory indices, indicat- ing that surgery had a direct effect on the direction and degree of postoperative alterations in memory ability. Measures of language ability and visual-per- ception and visual-spatial ability are largely (but not exclusively) tests of cortical function, and it is therefore interesting that a statistical phenomenon, and not laterality of resection, appeared to be the major de- terminant of postoperative test score changes on these measures.

One might argue that an effect of laterality of lesion

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B. P. ~ ET AL.

was not detected because the language and visual- spatial tests that were utilized are insensitive to im- pairments or losses in cortical function. An alterna- tive explanation is that the standard lateral temporal lobe resections in the Memphis series are conserva- tive and do not impinge upon the cortical regions thought to mediate these particular abilities. Further, as will be discussed, resection of mesial temporal struc- tures, structures known to mediate memory function, revealed consistent surgical effects. Therefore, we do not think that our results are due to insensitivity of the neuropsychological measures that were used.

As noted, the major target of resection was the mesial temporal lobe, including parahippocampal gyms, amygdala, and hippocampus. There is a large literature that describes the contribution of these structures to memory function, as well as their ma- terial-specificity (13,20-23). Resection of these struc- tures would, a priori, be expected to result in detect- able alterations in memory ability, which should co-vary to some degree with parameters of the sur- gical intervention (e.g., laterality of resection and degree of hippocampal resection). Although an ef- fect of initial level of performance was noted on the majority of the CVLT indices, a significant indepen- dent effect of surgical intervention was also noted (laterality of resection). Typically, patients who underwent left (dominant) temporal resection showed poorer postoperative verbal learning and memory performance, and/or patients who under- went right (nondominant) temporal resection showed no change or improvement.

In summary, these findings suggest that with a conservative resection of the lateral temporal lobe the neuropsychological morbidity associated with the laterality ATL may be largely limited to the area of memory function as the majority of test-retest alter- ations that were noted on tests of cortical ability (lan- guage and visual-spatial ability) appeared to primar- ily reflect the effects of a statistical phenomenon. Comparable analyses on additional tests of language and visual-spatial abilities (e.g., the WAIS-R), as well as memory function (e.g., the Wechsler Memory Scale), would address the generalizability of these findings.

Regression Toward the Mean

In research designed to measure behavioral change over time, regression toward the mean has been rec- ognized as a potential major confounding variable (6,9). As has been reviewed elsewhere (9), failure to account for regression toward the mean has been

146 ] EPILEPSY, VOL. 4, NO. 3, 1991

identified as a significant problem in many different areas of research including education, human devel- opment and aging, business, and behavior genetics (6,26-29). Regression toward the mean (or median) has also been identified as a methodological con- founder in treatment studies of epilepsy (30).

In studies of the type presented here, involving the measurement of behavior on two separate occasions, regression toward the mean is expected (9). Explana- tions of the regression effect are usually couched in terms of measurement error (6,9), a type of error well known in the field of psychometrics (31). Less than perfect correlation between test and retest, another common situation in psychometrics, also facilitates this effect (6,9). Further detailed discussions and explanations of the regression toward the mean ef- fect are available elsewhere (6,8,9,32).

It is important to note that, although the effect of regression toward the mean plays a role in pre- to postsurgical test performance, we do not suggest that it is the sole determinant of performance change. Although this investigation demonstrated that re- gression toward the mean was almost always statis- tically significant, we could not determine whether these surgical patients showed more (or less) regres- sion, or cognitive change, than would an unoperated epilepsy control group. It is simply suggested that regression toward the mean is an effect that needs to be taken into consideration, or controlled for, in fu- ture studies and is a particularly relevant issue when assessing individual patients following surgery. Not to control for initial level of performance may invite spurious findings. To investigate this point, we re-ran our analyses of difference scores without using initial level of performance as a predictor. In the majority of cases, different predictors of postoperative change were obtained and the regression analyses accounted for substantially less variance.

Chelune et al. (3) recently considered whether re- gression toward the mean influenced pre- to post- operative cognitive findings in their subjects. They hypothesized that regression toward the mean im- plied that there should be a significant decrease in the range of test-score variability at postoperative assess- ment. They found only a very few such instances and suggested that the results of their tests of homosce- dasticity of variance argued against regression toward the mean as an explanation of their findings. How- ever, homoscedasticity of variance is not among the defining features of regression to the mean. In order to investigate this further, we carried out a computer simulation and generated random numbers for 2,000 "subjects," specifying that the scores be distributed normally. A second set of random numbers (nor-

PREDICTORS OF NEUROPSYCHOLOGICAL CHANGE FOLLOWING ATL

mally distributed) was generated for these 2,000 sub- jects and difference scores were computed. The mean difference score was 0, and regression toward the mean was significant (the correlation of initial score to difference score was -0 .64; p <~ 0.001). The variance in the second distribution was identical to the first. A comparable result was obtained when a uniform distribution of scores was used. Therefore, regres- sion toward the mean can occur when the variances of the distributions of pre- and postoperative test scores do not change.

Further Considerations

The mean scores on some tests did show a signifi- cant improvemen t (e.g., Hooper , 1 point gain; Line Orientation, 0.95 point gain), or decline (Face Rec- ognition, 1.2 point loss; CVLT free recall intrusions, 1.4 intrusion gain). While these are statistically sig- nificant postoperat ive changes, the clinical signifi- cance of such small psychometric alterations remain unclear. Test score increases could reflect real cog- nitive improvements secondary to improved seizure control, or merely practice effects attributable to previous experience with the test materials. Compar- ison to an unopera ted epilepsy control group is needed in order to determine which of these possibil- ities is correct.

In a speculative vein, it appears as if a dynamic process may be taking place from pre- to postopera- tive assessments. The overall (group) distribution of scores on a particular test may shift to a statistically significant but clinically modest degree, and this overall change might reflect actual improvements , practice effects, or real decline. Compar ison to ap- propriate controls would determine which of these alternatives, or others, is correct. Within the context of this general distribution shift, several factors de- termine the nature and degree of an individual's test score change (e.g., regression to the mean, age, later- ality of resection). The influences that are operating will depend on the neural systems responsible for mediat ion of that particular task (cortical versus mesial temporal) , the degree to which the surgical resection invades those systems, and characteris- tics of the patients (e.g., age). Because surgical centers vary in the amount of lateral and medial tissue that is resected, different neuropsychological outcomes may be associated with different surgical techniques.

Finally, we have been investigating pre /pos topera- tive cognitive changes by examining one test at a time. It may be that a broader investigation of the overall pattern of test score increases or declines may be less subject to the effects of statistical artifacts and

more reflective of actual alterations in cognitive func- tion. More sophisticated mathematical modeling may be valuable in this regard. At the present time, how- ever, the results of this investigation suggest that regression toward the mean is a significant contrib- utor to pre/postoperat ive test score change and needs to be considered in order to accurately determine the neurobehavioral effects of ATL.

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