Differential forgetting in patients with temporal lobe dysfunction

Archrves o/Clmrcal Newops.vcholog~. Vol 3. PP. 351-358. 1988 CopyrIght Prmted ,n the USA. All nghts reserved

0887.6177i88 $3 00 f .oO E 1988 Natronal Academy of Neuropsycholognts

Differential Forgetting in Patients with Temporal Lobe Dysfunction Roy C. Martin,

David W. Loring, Kimford J. Meador, and Gregory Medical

P. Lee

College of Georgia

Delayed recall performance was investigated in 13 patrents wrth temporal lobe eprlepsy (TLE) and 13 healthy age-matched controls who were matched on a patrwise basis for initial learning on the Selective Remrndmg test. TLE patients performed significantly worse on the 30-minute delqved recall condition despite equivalent mitial continuous long-term retrieval scores. These data suggest that TLE patients forget at dtsproportionately rapid rates as compared to healthy controls desprte equivalent initial learning. Consequently, delayed recall may increase group discrimination when mitial learning levels are similar.

Patients with temporal lobe dysfunction reportedly forget information more quickly than other patient populations. In an early report, Huppert and Piercy (1979) examined forgetting in H.M. (the famous patient who underwent bilateral hippocampal resection), Korsakoff patients, and healthy controls on a picture recognition task. The rate of forgetting was greatest in H.M., with similar forgetting rates seen in Korsakoff patients and controls at intervals of up to one week. However, Freed, Corkin, and Cohen (1987) criticized Huppert and Piercy’s (1979) failure to control for differences in initial learning ability. When initial learning differences were eliminated, H.M. performed more poorly at 24 hours. However, H.M. and controls performed similarly following a one-week delay. Huppert and Piercy’s (1979) data also suggest that differences for rates of forgetting previously learned material can improve sensitivity in clinical This study was supported in part by NIA K08 AGO03 14 awarded to K.J.M. This paper was presented in part at the Annual meeting of the American Psychological Association, Atlanta, GA, August 1988. We thank Patricia A. Downs for her assistance with manuscript preparation. Requests for reprints should be sent to Roy C. Martin, Department of Neurology, Medical College of Georgia, Augusta, GA 30912-3275. 351

352

R. C. Martin et al.

assessment by isolating specific memory impairments in pathologically distinct clinical populations. For example, Hart, Kwentus, Taylor, and Harkins (1987) suggest that a rate of forgetting paradigm may be useful in differential diagnosis of early dementia of the Alzheimer’s type (DAT) and depression. The memory impairment associated with DAT is due, in part, to degeneration of a basal forebrain cholinergic system which projects directly to the neocortex and hippocampus (Coyle, Price, & DeLong, 1983). Further, specific cellular pathologies (e.g., neurofibrillary tangles) have been observed in hippocampal projection neurons of DAT patients. The resultant functional isolation of the hippocampal formation also contributes to the memory impairment (Hyman, Van Hoesen, Damasio, & Barnes, 1984). However, reports on forgetting rates in DAT patients have been inconsistent. For example, Kopelman (1985), equating for initial learning, and Becker, Boller, Saxon, and McGonigle-Gibson (1987), without initial learning matched, report similar forgetting rates in DAT patients compared to patients with Korsakoff disease and healthy controls. In contrast, Hart et al. (1987) noted that DAT patients forget information at a disproportionately rapid rate as compared to controls, despite comparable initial learning. Memory studies of patients with temporal lobe epilepsy (TLE) have similarly produced inconsistent results. Some investigators observe comparable memory performance in TLE patients, generalized seizure patients, and healthy controls (Mayeux, Brandt, Rosen, & Benson, 1980; Stevens, Milstein, & Goldstein, 1972), whereas others have reported disproportionately rapid loss from memory within TLE populations (Delaney, Rosen, Mattson, & Novelly, 1980; Glowinski, 1973; Hermann, Wyler, Richey, & Rea, 1987; Mungas, Ehlers, Walton, & McCutchen, 1985). Methodological discrepancies (e.g., stimulus presentation, type of recall, and patient inclusion criteria) among these studies make it difficult to derive firm conclusions. Techniques that adjust for initial stimulus exposure do not equate for learning ability but rather compensate for learning differences by affording one group a longer period for acquisition. In the present study we matched initial learning on the selective reminding test on a pairwise basis for the two groups. In this way, we minimized the methodological concerns to which an adjusting stimulus exposure technique seemed vulnerable (i.e., Huppert & Piercy, 1979). Further, differences inherent in subject variable research (e.g., medication effects) are mitigated against by insuring that equivalent initial learning levels are present. We examined delayed recall in patients with TLE and healthy agematched controls who were matched on a pairwise basis for initial Selective Reminding learning. We hypothesized that despite comparable initial learning, patients with TLE would forget newly learned information more rapidly than healthy controls.

Differential

Forgetting

353

METHOD

Subjects We analyzed preoperative neuropsychological data from 13 patients who had undergone subsequent unilateral anterior temporal lobectomy. Of the 13 TLE patients who had lateralized epileptiform discharges, seven had left temporal seizure onset and six patients had right temporal seizure onset. Laterality of seizure onset determination was based upon multiple ictal EEG recordings from scalp, sphenoidal, and/or intracranial depth electrodes. With the exception of one left TLE patient who displayed mixed language dominance and mixed handedness, all patients were right handed and left hemisphere language dominant by Intracarotid Sodium Amytal testing (Loring & Lee, 1988). In addition, neuropsychological data from 13 control subjects were also examined. Control subjects were patients referred for neuropsychological assessment who had no evidence of cerebral dysfunction, with normal neurological exam and neuropsychological test performance in all patients. When present, CT, EEG, and MRI were also within normal limits. Material The Selective Reminding test (Buschke, 1973; Buschke & Fuld, 1974) was used to assess verbal learning and memory. The Selective Reminding Test has been shown to be a useful measure for the retention and recall of verbal material in a variety of clinical populations, such as, alcoholic Korsakoffs syndrome (Buschke &.Fuld, 1974), dementia of the Alzheimer’s type (Fuld, Katzman, Davies, & Terry, 1982; Kaye, Sitaram, Weingartner, Ebert, Smallberg, & Gillin, 1982), traumatic brain injury (Levitt, Benton, & Grossman, 1982), and patients with TLE (Loring, Lee, Martin, & Meador, 1988). Each patient was read a list of 12 nonrelated words (Form 2; Hannay & Levin, 1985). Subjects were instructed to recall as many of the words as possible, in any order. On the second trial, subjects were read only those words not recalled after the initial presentation. Subsequent trials followed the same administration procedure; only those words that had not been recalled from the previous trial were read. Two consecutive trials without error was our discontinuation criterion. Long-term storage is correct recall of a word on two or more consecutive trials. Continuous long-term retrieval (CLTR), that is, the ability to consistently retrieve a word that had entered operationally defined long-term storage, was our matching variable. By matching subjects from two clinically different populations, we recognize the potential for selection bias for patients from extreme positions on their respective normal curves (Meehl, 1975). However, patient’s learning

R. C. Martin et al.

354

scores selected from both groups represented a wide range of performance variability. Performances were considered equivalent when CLTR differed by no more than five points. We then compared the number of words freely recalled following a thirty minute delay and used this measure as our dependent variable. RESULTS As shown in Table 1, patients in both groups did not differ in terms of FSIQ, VIQ. or PIQ. TLE and controls were similar in age and education. The TLE and control groups were nearly identical on CLTR, our matching variable [97.7(26.3) vs. 97.1(25.0), respectively]. This means CLTR performance level is within the normal range of variation (Hannay & Levin, 1985). A statistically significant difference was present for delayed recall [9.7(1.8) vs. 11.2(1.1); t(24)=2.64, p< .015]. We contrasted delayed recall with performance on the final trial since both measures have a common range (O-12) in order to provide a visual estimate of forgetting rate in the two patient groups. As can be seen in Figure 1, similar final trial performance levels were present whereas the TLE group forgot more quickly than controls. We also investigated the possibility of differential forgetting rates based upon laterality of seizure onset. No statistical difference between delayed recall scores for left and right TLE patients was present [10.4(1.6) vs. 8.8(1.4), respectively].

TABLE 1 Demographic Characteristics Variable

TLE

Control

34.7 7.2

36.9 10.8

12.5 2.4

12.6 3.1

9 4

9 4

88.1 8.1

96.0 14.0

87.8 6.9

97.4 13.5

90.4 9.7

97.9 13.9

As Mean (yr)

SD Education Mean (yr) SD

Sex Female Male FSIQ Mean SD

vlQ Mean SD

P1Q Mean SD

355

Differential Forgetting 12-

11.5 * u 2

Il.

ii v ~10.5 % &

*

10.

n

3

0

Control TLE patients

9.5.

t 91

LAST

DELAY

TRIAL FIGURE 1.

DISCUSSION

The results of the present study demonstrate that temporal lobe dysfunction in TLE contributes to more rapid forgetting of verbal material. TLE patients were found to forget information more rapidly than healthy controls despite equivalent initial learning performance. These findings are consistent with previous studies (e.g., Delaney et al., 1980; Glowinski, 1973, Mungas et al., 1985) that examined retention over delayed intervals on learning tasks in TLE patients. However, unlike previous research, our patient groups were matched on a pairwise basis for initial verbal learning. These results support Huppert and Piercy’s (1979) conclusion that temporal lobe dysfunction contributes to rapid forgetting of newly learned information. Our analysis comparing forgetting rates between left and right TLE patients revealed no significant group difference, contrary to reports demonstrating greater verbal memory deficits associated with left TLE (e.g., Delaney et al., 1980; Hermann et al., 1987). This is unlikely due to relatively small sample sizes since delayed recall was superior for left as compared to right TLE patients. In addition, CLTR performance was in the normal range for our TLE sample. The total immediate memory by both left and right TLE patients reported by Hermann et al. (1987), in contrast, is in the impaired range as defined by being at least two standard deviations below the age means for each sex as presented in the California Verbal Learning Test Manual (Delis, Kramer, Kaplan, & Ober, 1987). Although immediate memory for prose passages by patients in the Delaney et al. (1980) study

356

R. C. Martin

et al.

appears to be in the normal range, with relatively greater loss of information over time, the task demands for prose passage retention and word list acquisition differ substantially. Further, TLE patients in both the Hermann et al. (1987) and Delaney et al. (1980) reports performed significantly more poorly than their respective control groups. Therefore, generalizing from our sample to other TLE populations that were either administered different type verbal memory tests (e.g., prose passage recall; Delaney et al., 1980) or presented with impaired verbal memory performance (Hermann et al., 1987) must be made with a great deal of caution. Finally, lO/ 13 TLE patients in the present report required implantation of depth electrodes to precisely determine side of seizure onset, suggesting some degree of bilateral dysfunction. Although the habitual seizures were determined to originate primarily from a single temporal lobe, multiple ictal recordings from scalp/sphenoidal leads were unable to identify clearly a unilateral seizure onset. These results substantiate Russell’s (1975) contention that delayed recall adds valuable information for delineating specific memory impairment. Further, Russell (1975) presented data, using the Wechsler Memory Scale (WMS), that the inclusion of a 30-minute delay recall measure more accurately predicted organic diagnosis for brain damaged patients. Additionally, factor analytic research of the Wechsler Memory Scale has revealed a principal factor loading of Visual Reproduction on a visual-perceptual-motor factor, whereas delayed reproduction loads principally on the memory component (Larrabee, Kane, Schuck, & Francis, 1985). Consequently, in the revision of the WMS, a delay is included as part of the standardized battery (Wechsler, 1987). The decision to match patients on verbal learning scores was based in part on pragmatic considerations. We felt that Huppert and Piercy’s (1979) method of adjusting initial stimulus exposure was not appropriate for equating initial learning in a clinical setting. The matching paradigm eliminates the need to spend clinical time equating for task learning (i.e., longer stimulus exposure time) prior to data analysis. Gauging from the present study, TLE patients are an excellent population for pairwise matching with healthy controls based upon comparable demographic variables and verbal learning scores. That is, many patients with TLE do not display such severe memory deficits that matching with healthy controls would be impossible. We believe that CLTR is an appropriate variable for initial learning; CLTR is reportedly a sensitive measure of verbal memory impairment in patients suffering closed-head injury or DAT (Larrabee, Trahan, & Levin, 1986). The matching paradigm used in this study isolated the delayed memory measure by controlling for unequal learning abilities. This methodological approach demonstrates the potential clinical utility of delayed recall in group discrimination, particularly when initial learning levels are comparable. These data indicate that inclusion of a delayed recall component may

Differential Forgetting

357

increase the discriminating power of the test when examining patients with relatively subtle temporal lobe dysfunction. Further research employing a larger sample size on other tests of verbal memory will be necessary to determine the robustness of our findings.

REFERENCES Becker, J. T., Boiler, F., Saxon, J., & McGonigle-Gibson, K. L. (1987). Normal rates of forgetting of verbal material and non-verbal material in Alzheimer’s disease. Cortex, 23, 59-72. Buschke, H. (1973). Stages of retrieval in verbal learning. Journal of Verbal Behavior, 12, 543550.

Buschke, H., & Fuld, P. A. (1974). Evaluating storage, retention, and retrieval in disordered memory and learning. Neurology, 24, 1019-1025. Coyle, J., Price, D., & DeLong, M. (1983). Alzheimer’s disease: A disorder of cortical cholinergic innervation. Science, 219, 1184-l 190. Delaney, R. C., Rosen, A. J., Mattson, R. H., & Novelly, R. A. (1980). Memory function in focal epilepsy: A comparison of non-surgical, unilateral temporal lobe and frontal lobe samples. Cortex, 16, 103-l 17. Delis, D. C., Kramer, J. H., Kaplan, E., & Ober, B. A. (1987). The Munualfor the California Verbal Leurning Test. San Antonio, TX: The Psychological Corporation. Freed, D. M., Corkin, S., & Cohen, N. J. (1987). Forgetting H. M.: A second look. Neuropsychologia,

25, 461-471.

Fuld, P. A., Katzman, R., Davies, P., & Terry, R. D. (1982). Intrusions as a sign of Alzheimer dementia: Chemical and pathological verification. Annals of Neurology, 11, 155-159. Glowinski, H. (1973). Cognitive deficits in temporal lobe epilepsy. The JournaIof Nervous ond Mental

Disease,

157, 129-137.

Hannay, H. J., & Levin, H. S. (1985). Selective reminding test: An examination of the eqmvalence of four forms. Journal of Clinical and Experimental Neuropsychology, 7, 25 l-263. Hart, R. P., Kwentus, J. A., Taylor, J. R.. & Harkins, S. W. (1987). Rate of forgetting m dementia and depression. Journal of Consulting and Clinical Psychology, 55, 101-105. Hermann, B. P., Wyler, A. R., Richey, E. T., & Rea, J. M. (1987). Memory function and verbal learning ability in patients with complex partial seizures of temporal lobe origin. Eprlepsra, 28, 547-554. Huppert, F. A., & Piercy, M. (1979). Normal and abnormal forgetting in organic amnesia: Effect of locus of lesion. Cortex, IS, 385-390. Hyman, B. T., Van Hoesen, G. W., Damasio, G. R., & Barnes, C. L. (1984). Alzheimer’s dtsease: Cell-specific pathology isolates the hippocampal formation. Scrence, 225, 11681170. Kaye, W. H., Sitaram, N., Weingartner, J. C., Ebert, M. H., Smallberg, S., & Gillin, J. C. (1982). Modest facilitation of memory in dementia with combined lecithin and anticholinesterase treatment. Biological Psychiutry, 17, 275-280. Kopelman, M. D. (1985). Rates of forgetting Alzheimer-typed dementia and Korsakoffs Syndrome. Neuropsychologia, 23, 623-638. Larrabee, G. J., Kane, R. L., Schuck, J. R., & Francis, D. J. (1985). Construct validity of various memory testing procedures. Journal of Clinical and Experimental Neuropsychology, 7.497-504.

Larrabee, G. J., Trahan, D. E., & Levin H. S. (1986). Normative data for the verbal selective reminding test. Journal of Clinical und Experimental Neuropsychology, 7, 641 (Abstract).

358

R. C. Martin et al.

Levitt, G. S., Benton, A. L., & Grossman, R. G. (1982). Neurobehavioral consequences of closed head injury. New York: Oxford Universtty Press. Loring, D. W., & Lee, G. P. (1988). The neuropsychological evaluation. In K. J. Meador (Ed.)., Surgrcal freatment of epilepsy (Course Syllabus, available from American Academy of Neurology [2221 University Avenue S.E., Suite 335, Minneapolis, Minnesota 554141). Loring, D. W., Lee, G. P., Martin, R. C., & Meador, K. J. (1988). Material specific learning m patients with partial complex seizures of temporal lobe origin: Convergent validation of memory constructs. Journal of Epilepsy, 1, 53-59. Mayeux, R., Brandt, J., Rosen, J., Benson, D. F. (1980). lnterictal memory and language impairment in temporal lobe epilepsy. Neurology, 30, 120-125. Meehl. P. E. (1975). Nuisance variables and the ex post facto design. In M. Radner & S. Winokur (Eds.), Analyses of theories and methods of physrcs and psychology. Minneapolis: University of Minnesota Press. Mungas, D., Ehlers, C., Walton, N., & McCutchen, C. B. (1985). Verbal learning differences in epileptic patients with left and right temporal lobe foci. Eplepsla, 26, 340-345. Russell, E. W. (1975). A multiple scoring method for assessment of complex memory functions. Journal of Consulting and Clinical Psychology, 43, 800-809. Stevens, J., Milstein, V., & Goldstein, S. (1972). Psychometric test performance in relation to the psychopathology of epilepsy. Archives of General Psychiatry, 26, 532-538. Wechsler, D. (1987). Wechsler Memory Scale-Revised. San Antonio, TX: Harcourt Brace Jovanovich.