Memory Functions Six to Nine Months After Electroconvulsive Therapy Larry
R.
Squire, PhD, Paul
M. Chace
\s=b\ Memory functions after electroconvulsive therapy (ECT) assessed in 38 former patients who had received bilateral treatment, right unilateral treatment, or hospitalization without ECT six to nine months previously. Results of six different tests of delayed retention and remote memory provided no evidence for persisting memory impairment. Nevertheless, persons who had received bilateral ECT rated their memory as impaired significantly (P < .05) more often than did persons in the other follow-up groups. Although considerable effort was made to maximize the sensitivity of the memory tests, it is possible that, long after ECT, some impairment of memory remained that was not were
tention intervals as long as 30 minutes to assess recovery of memory long after ECT. In one report, retention of nonverbal material across a 30-minute delay was still be¬ low the before-ECT levels two to three months after treatment.16 In the other, the capacity to retain material over a three-hour interval recovered between one week and one month after ECT.21 However, the clinical rele¬ vance of this finding may be limited, since the aver¬ age number of treatments (5.3) was 25% to 50% less than the number typically used to relieve depressive
detected
by these tests. Alternatively, it is hypothesized that the impairment of recent and remote memory initially associated
symptoms.3·10·22·23 According
with bilateral ECT could cause some persons to become more alert to subsequent memory failures and then to underestimate their memory abilities. (Arch Gen Psychiatry 32:1557-1564, 1975)
ing reversible, we know of no systematic, long-term stud¬ ."2" ies that demonstrate this conclusively. The present study investigated memory functions six to nine months after ECT. To maximize test sensitivity, one-day and two-week intervals were interposed between learning and retention, and assessments of memory func¬ tions were made with six different tests of new learning and remote memory capacity. In addition, self-ratings of memory function were obtained from all subjects.
Sincetherapy (ECT)
its introduction in 1938,1 electroconvulsive has been used to treat a number of psychiatric disorders and is currently considered to be one of the most effective treatments for depressive illness.2·3 Impairment of memory associated with ECT has been well documented46 and is believed an undesirable side-ef¬ fect of treatment not required for therapeutic benefit.79 It is apparent that memory functions begin to improve after treatment is completed and recovery of memory functions is generally believed to be complete within a few weeks. For example, paired-associate learning scores returned to or exceeded the levels before ECT between ten and 30 days after the final treatment,10 and the ability to recall words ten minutes after learning had returned to the lev¬ els before ECT within three weeks.8 Nevertheless, isolated clinical reports of memory impairment long after ECT re¬ cur.11-13 Moreover, in a few instances, deficits in new learn¬ ing capacity or remote memory have been reported within 2 to 14 weeks after a course of ECT,111417 and only one of these studies" used later tests to demonstrate that the deficit was reversible. Memory tests having long delays between learning and retention appear to be considerably more sensitive to am¬ nesia than tests having short delays between learning and retention.1820 Thus, patients learning new material a few hours after ECT exhibited almost normal retention 30 minutes later but exhibited marked impairment 24 hours after learning.18 Only two studies have used learning-reAccepted
for publication July 28, 1975. From the departments of psychiatry, University of California School of Medicine, La Jolla (Dr Squire) and the Veterans Administration Hospital, San Diego, Calif (Dr Squire and Mr Chace). Reprint requests to the Department of Psychiatry, Veterans Administration Hospital, 3350 La Jolla Village Dr, San Diego, CA 92161 (Dr
Squire).
to one textbook, "Although most clinicians consider ECT's effect on mental function¬ .
.
SUBJECTS AND METHODS The subjects of the follow-up study had been patients
at a pri¬ psychiatric hospital six to nine months prior to testing (mean, 6.8 months). Three groups of subjects, all exhibiting symp¬ toms of depression, were constructed from records of consecutive admissions during that period (Table 1). The specific diagnoses as recorded on admission by the various psychiatrists were depres¬ sive neurosis (19), primary affective disorder (9), involutional melancholia (4), schizophrenic, depressed (3), and manic depres¬ sive (3). Subjects with neurological disorders, schizophrenia with¬ out depression, or with depression secondary to alcoholism or drug abuse were excluded. The length of hospitalization was 15 to 67 days (mean, 30.2 days). The first group (A) were persons who had vate
received
a course
of five
or more
bilateral ECT treatments. Of 24
selected, 17 could be located and 16 of these agreed to persons participate in the study. The second group (B) were persons who had received a course of five or more right unilateral ECT treat¬ ments. Each of these individuals had been judged by their psychi¬ atrists to be strongly right-handed. None of the subjects in this group had a history of bilateral ECT. Of 15 persons so selected, 14 could be located, 12 agreed to participate, and ten completed test¬ ing. The third group (C) were persons who did not receive ECT during their hospitalization and who had no prior history of ECT. Of 16 persons selected, 16 could be located, 14 agreed to partici¬ pate, and 12 completed testing. None of the 26 persons in groups A and had received ECT within six months prior to their last ad¬ mission; four had received ECT 6 months to 2% years prior to their last admission; two had received ECT more than 2% years prior to their last admission; 20 had never received ECT before. A group of inpatients was also included for comparative purposes (Table 1 [group D]), who at the time of testing were undergoing a pre¬ scribed course of bilateral ECT at the same psychiatric hospital. so
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Table
1.—Subject Characteristics* Verbal IQ, Wechsler Adult
No. of Patients
Age
6-9 mo after Bilateral ECT.j group A
16
45.1 ±3.1
Unilateral ECT, group
10
42.2 ±4.6
No ECT, group C
12
45.5 ±3.0
Group
Depression Scale,
Score
Zung Depression Rating
Raw Score
No. of Treatments
12.6 ±0.5
105.2 ±3.2
47.7 ±3.5
28.4 ±2.4
10.1 ±1.0
(9-16)
(80-129)
(26-73)
(17-24)
6F
12.6 ±0.9
100.1 ±3.7
47.8 ±4.6
28.0 ±3.9
(10-20)
(91-128)
(30-70)
(12-50)
11 F
12.1 ±0.6
106.6 ±3.3
52.4 ± 3.6
29.8 ±2.0
(8-16)
(95-125)
(34-71)
(20-43)
12.3 ±0.5
102.5 ±3.1
59.3 ±2.8
31.3 ±2.2
(10-16)
(93-118)
(39-80)
(14-44)
Intelligence
Sex
Years of Education
14 F
(30-71 )
(28-64)
(33-68)
6-10 hr after Fifth bilateral ECT, group D
15
44.2 ±2.7
11 F
(26-62)
(5-17) 9.2 ±1.0
(5-15)
Values are expressed as mean ± SE; ranges are shown in parentheses. t ECT signifies electroconvulsive therapy. X MMPI signifies Minnesota Multiphasic Personality Inventory. *
Electroconvulsive
Therapy
Electroconvulsive therapy was administered three times a week alternate days following medication with atropine, methohexital sodium, and succinylcholine. For bilateral treatment (300 to 500 milliamperes, 2 to 3 seconds), electrode placement was tempo¬ ral-parietal. For right unilateral treatment (pulsed current at an average intensity of 14 to 15 milliamperes, for 14 seconds), elec¬ trode placement followed the method described by D'Elia.25 In all cases, the attending physician reported that the current produced a well-modified grand mal seizure. Decisions concerning the choice and number of treatments and the prescription of drugs in addi¬ tion to ECT were made by the individual psychiatrists. Since the patients' psychiatrists first learned about and approved of this study at the time of the follow-up, their judgments concerning the administration of ECT were based strictly on clinical criteria. on
Tests
Subjects in the three follow-up groups (A, B, and C) were visited
three occasions at their homes. The interval between the first was one day and the interval between the first and third visits was 13 to 18 days (mean, 14.9 days). This spacing of visits meant that retention tests for material learned during the first visit could be scheduled at three different learning-retention inter¬ vals-no delay, one day, and approximately two weeks. Inpatients receiving ECT (group D) were seen on two occasions—in the after¬ noon, six to ten hours after the fifth ECT treatment, and the next morning, 16 to 19 hours later. In this way, retention tests for ma¬ terial learned during the first visit could be given both immedi¬ ately and the next day. Patients receiving ECT were not tested on a third occasion because in most cases additional treatments were prescribed. Except for the two-week retention tests (tests 1-4) and the two-week incidental learning test (test 5), the inpatients took the same tests as the follow-up subjects. All follow-up subjects also took the verbal portion of the Wechsler Adult Intelligence Scale (WAIS) on the first visit. On the second visit follow-up sub¬ jects took the Zung Self-Rating Scale for Depression26 and the De¬ pression Scale of the Minnesota Multiphasic Personality Inven¬ tory (MMPI).27 Inpatients took the WAIS one hour after their sixth treatment and the two depression scales six to ten hours af¬ ter their fifth treatment. on
two visits
Test 1 :
Recognition of 32 Items on an eight-item test described previously.18
Test 1 was based The test consisted of 32 items, eight in each of the following four categories: pictures of common objects, 5.1x4.4-cm photographs from a high school yearbook, nonsense line drawings, and common words. For learning, subjects saw 32 items, three seconds for each
item, in the order of eight objects, eight faces, eight drawings, and eight words. The order of items within each category was al¬ ways the same. For each group of eight items, these instructions were repeated: "Look at these pictures and try to remember them
for later on so that you might be able to pick them out from a group." For the objects and the words, patients were also asked to name the items aloud. Immediately after seeing each group of eight items, subjects were tested for retention. Subjects saw eight sets of three items. Each set of three included one of the eight items just seen and two new (incorrect) items. The order in which the correct items were seen during the retention test was differ¬ ent from the order in which they were seen during original learn¬ ing. For each group of three items, patients were asked to point to the item they had seen before and to indicate their confidence on a 1 to 4 scale, with "4" representing high confidence, "1" represent¬
ing low confidence, and
"2" or "3" representing intermediate con¬ fidence. In this way, an "immediate retention score" was obtained for all 32 items. Delayed retention tests were given one day later and approxi¬ mately two weeks later. Procedures for the two delayed tests (forced choice, three alternatives, with confidence ratings) were identical to the procedure used for testing immediate retention, except that different incorrect items were used on every retention test. The correct items appeared in a different order in all three retention tests, and the score for each retention test was the num¬ ber of correctly identified items out of 32.
Test 2: Recall of
a
Paragraph
A short paragraph from the Guild Memory Test28 was read to the subject, with the instruction "When I am finished I want you to tell me as much of it as you can remember." Immediately there¬ after, subjects were asked to "begin at the beginning and tell me everything you can remember of what I read." On both the second and third visits recall was again tested by saying "Do you remem¬ ber the story I read to you yesterday (or two weeks ago)? Please start at the beginning and tell me everything you can remember about it." The story was divided into 20 segments, and the score on this test was the number of segments recalled.
Test 3:
Drawing
of a Complex Geometric From Memory
Figure
Subjects were asked to copy the Rey-Osterrieth figure,29 taking to include all line segments. On the second visit, without fore¬ warning, subjects were asked to reproduce this figure from mem¬ ory. On the third visit, subjects were asked once again to repro¬ duce the figure from memory. The drawings from memory were scored after the method described by Osterrieth,28 which involves giving points for each properly positioned line segment. The maxcare
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after a correct or incorrect response. One day and approximately two weeks later, retention was tested in a similar fashion by going through the eight cards four times. The score on this test was the number of correct responses in each set of eight cards.
32
S 28
Learning Test It seemed possible that performance in formal learning tests might misrepresent the memory abilities of subjects, since these Test 5: Incidental
O 24
challenged the subjects to pay attention and to try to re¬ member under highly structured conditions. To evaluate the abil¬ ity of these subjects to remember material to which their atten¬ tion was not explicitly directed, and which was not learned as part of a formal test, an incidental learning test was included. Thus, on the third visit, subjects were asked to recall all the tests that had been given on the second visit two weeks before, and to recall the order in which the tests had been given. The order of tests on the second visit had been Remote Memory Test (test 6), Zung Rating Scale, Depression Scale of MMPI, and 24-hour retests of tests 1, 2, 3, and 4. In addition, subjects were asked to answer questions about the appearance of the examiner during the first two visits. The questions involved the color and type of his tie, the pen in his left pocket, and the blue identification badge above his pocket. The examiner always appeared in the same way during the first two visits and did not exhibit any of the relevant features (tie, pen, badge) during the third visit. Points were given for each detail re¬ called. The maximum score on this test was 24—15 points for ques¬ tions dealing with the tests and nine points for questions dealing with the examiner's appearance. tests
íáCL
W20
*—a
Bilateral
LU
•—·
Unilateral
"
16
— 0--0
No
No ECT
Group D 2 Weeks
1
Day
Delay
LEARNING-RETENTION INTERVAL Fig 1 .—Score on a 32-item recognition memory test administered six to nine months after bilateral, right unilateral, or no electro¬ convulsive therapy (ECT). A separate group was also tested six to ten hours after fifth bilateral treatment.
-a
8
-·
^
o---d
< O
0--0
UJ cc
Test 6: Remote
Bilateral
Memory
for Television
Programs
The construction of this test has been described in detail previ¬ ously.30 It asked subjects to recognize the names of television pro¬ grams that were broadcast nationally for only one season from 1957 to 1972. It was designed to permit an equivalent sampling of events from different time periods. Each question asked "Which of the following was a television show?" and the correct answer was presented along with three incorrect answers, selected ran¬ domly from a list of fabricated titles. The order of questions was random with respect to the time periods that they covered. This test was given to inpatients (group D) one hour rather than six to ten hours after the fifth ECT treatment.
Unilateral No ECT
Group D
Subjective Evaluation of Memory Functions
O HI
C/>
1
No
"
Delay Day LEARNING -RETENTION INTERVAL 2.—Recall of short
Fig paragraph learned six to nine months after bilateral, right unilateral, or no electroconvulsive therapy (ECT). A separate group was also tested six to ten hours after fifth bilat¬ eral treatment. ¡mum
score was
42
points.
Test 4: Paired-Associate
Learning
Test
Subjects saw eight 7.6x6.4-cm cards, one at a time, each bear¬ ing the picture of an animal on one side and a capital letter on the other. For each card, subjects saw the picture and then the letter were told to try to remember which letter went with each pic¬ ture. The set of eight animals was then shown three more times, each time in a different order, and subjects attempted to name the
and
letter
on
During the first visit, subjects were questioned at length as to how they judged their memory to be functioning. From written summaries of these conversations, subjects were scored either " " + (perceived impairment of memory) or "0" (no perceived im¬ pairment of memory). Subjects receiving a + score complained of current learning problems or of difficulty in recalling familiar material. Subjects were questioned separately about their recall for the time of hospitalization, and subjects with complaints lim¬ ited to the period of hospitalization did not receive a " + score. Subjects receiving a "0" score reported no memory problems or problems only in remembering the period of hospitalization.
the back of each card. The correct
answer was
displayed
"
"
Statistical Procedures To evaluate differences between groups, the data for each mem¬ ory test were submitted to an analysis of variance with repeated measures on one factor." Further comparisons between and with¬ in groups were accomplished by analyses of main effects and by orthogonal comparisons. The performance of patients in group D was compared to each of the follow-up groups by the method of Dunnett31 for the comparison of several means with a control. Es¬ timates of correlation were made with the Spearman rank correla¬ tion coefficients.32
RESULTS The groups tested several months after
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hospitalization
(groups A, , and C) did not differ from each other on any objective memory tests (tests 1 through 6). By con¬ trast, patients tested shortly after their fifth ECT treat¬ ment (group D) performed more poorly on each memory test than any of the other groups. As shown in Table 1, the four groups studied were closely matched on a number of characteristics. The inpatients in group D tested after five bilateral treatments obtained somewhat higher de¬ pression ratings than the other three groups, but did not significantly differ from them (Zung Scale, P>.05; MMPI Depression Scale, P>.3).
Table 2.—Average Confidence Rating Each Group for Test 1
of the
Test 1:
Recognition
of 32 Items
Figure 1 indicates the performance of all four groups on the recognition memory test. The effect of learning-reten¬ tion interval was significant (F [2,70] 54.9, < .01), indi¬ cating that retention scores did decline in successive retention tests. However, subjects who had received bilat¬ eral ECT, unilateral ECT, or no ECT did not differ from each other (F [2,35] 0.12, P>.3). Unilateral ECT affects verbal memory less than bilat¬ eral ECT, but can markedly affect memory for nonverbal material.16 31 To determine if subjects who had received unilateral ECT (group B) might exhibit a selective impair¬ ment of memory for the nonverbal items of this test, scores for the nonverbal items (nonsense drawings and faces) were analyzed separately. Scores on these items did not differ among groups (F [2,35] 1.68, P>.3), and the three groups did not vary by more than 1.6 points at any retention interval. On the immediate retention test, the patients in group D scored somewhat lower than the other groups, but this difference fell short of significance (t [49] 1.1 to 2.1, P>.05). One day after learning, however, patients in group D remembered an average of only 17.2 items out of 32, compared to 27.0, 28.5, and 28.0 for groups A, B, and C, respectively (t [49] 7.5 to 8.7, < .01). =
=
=
Confidence
Ratings
In addition to obtaining similar scores on this test, sub¬ jects in the three follow-up groups expressed a similar amount of confidence in their responses. Each subject was
assigned one score for each retention session, represent¬ ing his average confidence rating for the 32 responses made during the session. Table 2 indicates the average confidence ratings given by groups A, B, and C for re¬ sponses during the immediate, one-day, and two-week re¬ tention tests. The confidence ratings employed by each group were not measurably different at any learning re¬ tention interval (F [2,105] < 0.6, P>.3). However, patients in group D employed comparatively low confidence rat¬ ings. Their average confidence rating during the one-day retention session was significantly lower than the corre¬ sponding confidence ratings employed by each of the other groups (t [49] 5.0 to 5.4, < .01). Another way to compare the use of confidence ratings is to ask how well subjects discriminated items they judged to be correct from items they judged to be incorrect. An estimate of this discriminative ability (d') is given by cal¬ culating for each group a type II receiver operating char¬ acteristic (ROC) curve.34 The calculated values for d' were =
Used
by
Learning-Retention Interval Group Bilateral ECT Unilateral ECT NoECT Group D *
Values
expressed
_
are
No Delay 3.76±.06 3.75 ±.07 3.73±.07 3.57±.07
1 Day 3.40 ±.14 3.32 ± .14 3.35±.13 2.21 ±.17
as mean ±
2 Wk 3.00 ±.15 2.99 ±.14 3.16 ± .14
SE.
quite similar—1.19, 1.28, and 1.21 for groups A, B, and C, respectively. The value of d' for group D was also similar (1.25), indicating that patients in this group applied confi¬ dence ratings according to the same criteria as the other groups. Test 2: Recall of
a
Paragraph
Figure 2 indicates that the three follow-up groups were quite similar in their ability to recall a short paragraph at
various delays after original learning. Performance de¬ clined significantly between the immediate-retention test and the one-day test (F [1,70] 72,6, < .01) and between the one-day test and the two-week test (F [1,70] 7.3, < .01), but there was no effect of prior treatment on re¬ call at any learning-retention interval (F [2,105] .07 to 0.8, P>.3). By contrast, patients in group D had great dif¬ ficulty retaining information about the paragraph. They scored about as well as the other groups on immediate re¬ tention (t [49] =0.8, P>.3), but only two of the 15 patients could recall any part of the paragraph a day later (i [49] 2.0 to 3.0; < .05 when P>2.1). =
=
=
=
=
=
(1-4)
*
Test 3:
Drawing
of a Complex Geometric from Memory
Figure
Figure 3 presents scores at one day and two weeks after learning for the follow-up subjects and at one day after learning for patients in group D. From one day to two weeks after learning, performance on this memory task significantly declined (F [1,35] 37.9, < .01); however, performance declined at about the same rate in each of the follow-up groups, and there was no measurable differ¬ ence between groups at either learning-retention interval (F [2,70] 0.5 to 0.6, P>.3). The control group (group C) =
=
scored somewhat below the other two groups, but this dif¬ ference did not approach significance (F [1,35] 1,2, P>.3, orthogonal comparisons). Patients in group D were greatly impaired in their ability to reproduce the figure from memory the day after learning, and scored signifi¬ cantly below each of the other three groups (t [49] 3.7 to =
=
4.9,
R.
Squire, PhD, Paul
M. Chace
\s=b\ Memory functions after electroconvulsive therapy (ECT) assessed in 38 former patients who had received bilateral treatment, right unilateral treatment, or hospitalization without ECT six to nine months previously. Results of six different tests of delayed retention and remote memory provided no evidence for persisting memory impairment. Nevertheless, persons who had received bilateral ECT rated their memory as impaired significantly (P < .05) more often than did persons in the other follow-up groups. Although considerable effort was made to maximize the sensitivity of the memory tests, it is possible that, long after ECT, some impairment of memory remained that was not were
tention intervals as long as 30 minutes to assess recovery of memory long after ECT. In one report, retention of nonverbal material across a 30-minute delay was still be¬ low the before-ECT levels two to three months after treatment.16 In the other, the capacity to retain material over a three-hour interval recovered between one week and one month after ECT.21 However, the clinical rele¬ vance of this finding may be limited, since the aver¬ age number of treatments (5.3) was 25% to 50% less than the number typically used to relieve depressive
detected
by these tests. Alternatively, it is hypothesized that the impairment of recent and remote memory initially associated
symptoms.3·10·22·23 According
with bilateral ECT could cause some persons to become more alert to subsequent memory failures and then to underestimate their memory abilities. (Arch Gen Psychiatry 32:1557-1564, 1975)
ing reversible, we know of no systematic, long-term stud¬ ."2" ies that demonstrate this conclusively. The present study investigated memory functions six to nine months after ECT. To maximize test sensitivity, one-day and two-week intervals were interposed between learning and retention, and assessments of memory func¬ tions were made with six different tests of new learning and remote memory capacity. In addition, self-ratings of memory function were obtained from all subjects.
Sincetherapy (ECT)
its introduction in 1938,1 electroconvulsive has been used to treat a number of psychiatric disorders and is currently considered to be one of the most effective treatments for depressive illness.2·3 Impairment of memory associated with ECT has been well documented46 and is believed an undesirable side-ef¬ fect of treatment not required for therapeutic benefit.79 It is apparent that memory functions begin to improve after treatment is completed and recovery of memory functions is generally believed to be complete within a few weeks. For example, paired-associate learning scores returned to or exceeded the levels before ECT between ten and 30 days after the final treatment,10 and the ability to recall words ten minutes after learning had returned to the lev¬ els before ECT within three weeks.8 Nevertheless, isolated clinical reports of memory impairment long after ECT re¬ cur.11-13 Moreover, in a few instances, deficits in new learn¬ ing capacity or remote memory have been reported within 2 to 14 weeks after a course of ECT,111417 and only one of these studies" used later tests to demonstrate that the deficit was reversible. Memory tests having long delays between learning and retention appear to be considerably more sensitive to am¬ nesia than tests having short delays between learning and retention.1820 Thus, patients learning new material a few hours after ECT exhibited almost normal retention 30 minutes later but exhibited marked impairment 24 hours after learning.18 Only two studies have used learning-reAccepted
for publication July 28, 1975. From the departments of psychiatry, University of California School of Medicine, La Jolla (Dr Squire) and the Veterans Administration Hospital, San Diego, Calif (Dr Squire and Mr Chace). Reprint requests to the Department of Psychiatry, Veterans Administration Hospital, 3350 La Jolla Village Dr, San Diego, CA 92161 (Dr
Squire).
to one textbook, "Although most clinicians consider ECT's effect on mental function¬ .
.
SUBJECTS AND METHODS The subjects of the follow-up study had been patients
at a pri¬ psychiatric hospital six to nine months prior to testing (mean, 6.8 months). Three groups of subjects, all exhibiting symp¬ toms of depression, were constructed from records of consecutive admissions during that period (Table 1). The specific diagnoses as recorded on admission by the various psychiatrists were depres¬ sive neurosis (19), primary affective disorder (9), involutional melancholia (4), schizophrenic, depressed (3), and manic depres¬ sive (3). Subjects with neurological disorders, schizophrenia with¬ out depression, or with depression secondary to alcoholism or drug abuse were excluded. The length of hospitalization was 15 to 67 days (mean, 30.2 days). The first group (A) were persons who had vate
received
a course
of five
or more
bilateral ECT treatments. Of 24
selected, 17 could be located and 16 of these agreed to persons participate in the study. The second group (B) were persons who had received a course of five or more right unilateral ECT treat¬ ments. Each of these individuals had been judged by their psychi¬ atrists to be strongly right-handed. None of the subjects in this group had a history of bilateral ECT. Of 15 persons so selected, 14 could be located, 12 agreed to participate, and ten completed test¬ ing. The third group (C) were persons who did not receive ECT during their hospitalization and who had no prior history of ECT. Of 16 persons selected, 16 could be located, 14 agreed to partici¬ pate, and 12 completed testing. None of the 26 persons in groups A and had received ECT within six months prior to their last ad¬ mission; four had received ECT 6 months to 2% years prior to their last admission; two had received ECT more than 2% years prior to their last admission; 20 had never received ECT before. A group of inpatients was also included for comparative purposes (Table 1 [group D]), who at the time of testing were undergoing a pre¬ scribed course of bilateral ECT at the same psychiatric hospital. so
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Table
1.—Subject Characteristics* Verbal IQ, Wechsler Adult
No. of Patients
Age
6-9 mo after Bilateral ECT.j group A
16
45.1 ±3.1
Unilateral ECT, group
10
42.2 ±4.6
No ECT, group C
12
45.5 ±3.0
Group
Depression Scale,
Score
Zung Depression Rating
Raw Score
No. of Treatments
12.6 ±0.5
105.2 ±3.2
47.7 ±3.5
28.4 ±2.4
10.1 ±1.0
(9-16)
(80-129)
(26-73)
(17-24)
6F
12.6 ±0.9
100.1 ±3.7
47.8 ±4.6
28.0 ±3.9
(10-20)
(91-128)
(30-70)
(12-50)
11 F
12.1 ±0.6
106.6 ±3.3
52.4 ± 3.6
29.8 ±2.0
(8-16)
(95-125)
(34-71)
(20-43)
12.3 ±0.5
102.5 ±3.1
59.3 ±2.8
31.3 ±2.2
(10-16)
(93-118)
(39-80)
(14-44)
Intelligence
Sex
Years of Education
14 F
(30-71 )
(28-64)
(33-68)
6-10 hr after Fifth bilateral ECT, group D
15
44.2 ±2.7
11 F
(26-62)
(5-17) 9.2 ±1.0
(5-15)
Values are expressed as mean ± SE; ranges are shown in parentheses. t ECT signifies electroconvulsive therapy. X MMPI signifies Minnesota Multiphasic Personality Inventory. *
Electroconvulsive
Therapy
Electroconvulsive therapy was administered three times a week alternate days following medication with atropine, methohexital sodium, and succinylcholine. For bilateral treatment (300 to 500 milliamperes, 2 to 3 seconds), electrode placement was tempo¬ ral-parietal. For right unilateral treatment (pulsed current at an average intensity of 14 to 15 milliamperes, for 14 seconds), elec¬ trode placement followed the method described by D'Elia.25 In all cases, the attending physician reported that the current produced a well-modified grand mal seizure. Decisions concerning the choice and number of treatments and the prescription of drugs in addi¬ tion to ECT were made by the individual psychiatrists. Since the patients' psychiatrists first learned about and approved of this study at the time of the follow-up, their judgments concerning the administration of ECT were based strictly on clinical criteria. on
Tests
Subjects in the three follow-up groups (A, B, and C) were visited
three occasions at their homes. The interval between the first was one day and the interval between the first and third visits was 13 to 18 days (mean, 14.9 days). This spacing of visits meant that retention tests for material learned during the first visit could be scheduled at three different learning-retention inter¬ vals-no delay, one day, and approximately two weeks. Inpatients receiving ECT (group D) were seen on two occasions—in the after¬ noon, six to ten hours after the fifth ECT treatment, and the next morning, 16 to 19 hours later. In this way, retention tests for ma¬ terial learned during the first visit could be given both immedi¬ ately and the next day. Patients receiving ECT were not tested on a third occasion because in most cases additional treatments were prescribed. Except for the two-week retention tests (tests 1-4) and the two-week incidental learning test (test 5), the inpatients took the same tests as the follow-up subjects. All follow-up subjects also took the verbal portion of the Wechsler Adult Intelligence Scale (WAIS) on the first visit. On the second visit follow-up sub¬ jects took the Zung Self-Rating Scale for Depression26 and the De¬ pression Scale of the Minnesota Multiphasic Personality Inven¬ tory (MMPI).27 Inpatients took the WAIS one hour after their sixth treatment and the two depression scales six to ten hours af¬ ter their fifth treatment. on
two visits
Test 1 :
Recognition of 32 Items on an eight-item test described previously.18
Test 1 was based The test consisted of 32 items, eight in each of the following four categories: pictures of common objects, 5.1x4.4-cm photographs from a high school yearbook, nonsense line drawings, and common words. For learning, subjects saw 32 items, three seconds for each
item, in the order of eight objects, eight faces, eight drawings, and eight words. The order of items within each category was al¬ ways the same. For each group of eight items, these instructions were repeated: "Look at these pictures and try to remember them
for later on so that you might be able to pick them out from a group." For the objects and the words, patients were also asked to name the items aloud. Immediately after seeing each group of eight items, subjects were tested for retention. Subjects saw eight sets of three items. Each set of three included one of the eight items just seen and two new (incorrect) items. The order in which the correct items were seen during the retention test was differ¬ ent from the order in which they were seen during original learn¬ ing. For each group of three items, patients were asked to point to the item they had seen before and to indicate their confidence on a 1 to 4 scale, with "4" representing high confidence, "1" represent¬
ing low confidence, and
"2" or "3" representing intermediate con¬ fidence. In this way, an "immediate retention score" was obtained for all 32 items. Delayed retention tests were given one day later and approxi¬ mately two weeks later. Procedures for the two delayed tests (forced choice, three alternatives, with confidence ratings) were identical to the procedure used for testing immediate retention, except that different incorrect items were used on every retention test. The correct items appeared in a different order in all three retention tests, and the score for each retention test was the num¬ ber of correctly identified items out of 32.
Test 2: Recall of
a
Paragraph
A short paragraph from the Guild Memory Test28 was read to the subject, with the instruction "When I am finished I want you to tell me as much of it as you can remember." Immediately there¬ after, subjects were asked to "begin at the beginning and tell me everything you can remember of what I read." On both the second and third visits recall was again tested by saying "Do you remem¬ ber the story I read to you yesterday (or two weeks ago)? Please start at the beginning and tell me everything you can remember about it." The story was divided into 20 segments, and the score on this test was the number of segments recalled.
Test 3:
Drawing
of a Complex Geometric From Memory
Figure
Subjects were asked to copy the Rey-Osterrieth figure,29 taking to include all line segments. On the second visit, without fore¬ warning, subjects were asked to reproduce this figure from mem¬ ory. On the third visit, subjects were asked once again to repro¬ duce the figure from memory. The drawings from memory were scored after the method described by Osterrieth,28 which involves giving points for each properly positioned line segment. The maxcare
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after a correct or incorrect response. One day and approximately two weeks later, retention was tested in a similar fashion by going through the eight cards four times. The score on this test was the number of correct responses in each set of eight cards.
32
S 28
Learning Test It seemed possible that performance in formal learning tests might misrepresent the memory abilities of subjects, since these Test 5: Incidental
O 24
challenged the subjects to pay attention and to try to re¬ member under highly structured conditions. To evaluate the abil¬ ity of these subjects to remember material to which their atten¬ tion was not explicitly directed, and which was not learned as part of a formal test, an incidental learning test was included. Thus, on the third visit, subjects were asked to recall all the tests that had been given on the second visit two weeks before, and to recall the order in which the tests had been given. The order of tests on the second visit had been Remote Memory Test (test 6), Zung Rating Scale, Depression Scale of MMPI, and 24-hour retests of tests 1, 2, 3, and 4. In addition, subjects were asked to answer questions about the appearance of the examiner during the first two visits. The questions involved the color and type of his tie, the pen in his left pocket, and the blue identification badge above his pocket. The examiner always appeared in the same way during the first two visits and did not exhibit any of the relevant features (tie, pen, badge) during the third visit. Points were given for each detail re¬ called. The maximum score on this test was 24—15 points for ques¬ tions dealing with the tests and nine points for questions dealing with the examiner's appearance. tests
íáCL
W20
*—a
Bilateral
LU
•—·
Unilateral
"
16
— 0--0
No
No ECT
Group D 2 Weeks
1
Day
Delay
LEARNING-RETENTION INTERVAL Fig 1 .—Score on a 32-item recognition memory test administered six to nine months after bilateral, right unilateral, or no electro¬ convulsive therapy (ECT). A separate group was also tested six to ten hours after fifth bilateral treatment.
-a
8
-·
^
o---d
< O
0--0
UJ cc
Test 6: Remote
Bilateral
Memory
for Television
Programs
The construction of this test has been described in detail previ¬ ously.30 It asked subjects to recognize the names of television pro¬ grams that were broadcast nationally for only one season from 1957 to 1972. It was designed to permit an equivalent sampling of events from different time periods. Each question asked "Which of the following was a television show?" and the correct answer was presented along with three incorrect answers, selected ran¬ domly from a list of fabricated titles. The order of questions was random with respect to the time periods that they covered. This test was given to inpatients (group D) one hour rather than six to ten hours after the fifth ECT treatment.
Unilateral No ECT
Group D
Subjective Evaluation of Memory Functions
O HI
C/>
1
No
"
Delay Day LEARNING -RETENTION INTERVAL 2.—Recall of short
Fig paragraph learned six to nine months after bilateral, right unilateral, or no electroconvulsive therapy (ECT). A separate group was also tested six to ten hours after fifth bilat¬ eral treatment. ¡mum
score was
42
points.
Test 4: Paired-Associate
Learning
Test
Subjects saw eight 7.6x6.4-cm cards, one at a time, each bear¬ ing the picture of an animal on one side and a capital letter on the other. For each card, subjects saw the picture and then the letter were told to try to remember which letter went with each pic¬ ture. The set of eight animals was then shown three more times, each time in a different order, and subjects attempted to name the
and
letter
on
During the first visit, subjects were questioned at length as to how they judged their memory to be functioning. From written summaries of these conversations, subjects were scored either " " + (perceived impairment of memory) or "0" (no perceived im¬ pairment of memory). Subjects receiving a + score complained of current learning problems or of difficulty in recalling familiar material. Subjects were questioned separately about their recall for the time of hospitalization, and subjects with complaints lim¬ ited to the period of hospitalization did not receive a " + score. Subjects receiving a "0" score reported no memory problems or problems only in remembering the period of hospitalization.
the back of each card. The correct
answer was
displayed
"
"
Statistical Procedures To evaluate differences between groups, the data for each mem¬ ory test were submitted to an analysis of variance with repeated measures on one factor." Further comparisons between and with¬ in groups were accomplished by analyses of main effects and by orthogonal comparisons. The performance of patients in group D was compared to each of the follow-up groups by the method of Dunnett31 for the comparison of several means with a control. Es¬ timates of correlation were made with the Spearman rank correla¬ tion coefficients.32
RESULTS The groups tested several months after
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hospitalization
(groups A, , and C) did not differ from each other on any objective memory tests (tests 1 through 6). By con¬ trast, patients tested shortly after their fifth ECT treat¬ ment (group D) performed more poorly on each memory test than any of the other groups. As shown in Table 1, the four groups studied were closely matched on a number of characteristics. The inpatients in group D tested after five bilateral treatments obtained somewhat higher de¬ pression ratings than the other three groups, but did not significantly differ from them (Zung Scale, P>.05; MMPI Depression Scale, P>.3).
Table 2.—Average Confidence Rating Each Group for Test 1
of the
Test 1:
Recognition
of 32 Items
Figure 1 indicates the performance of all four groups on the recognition memory test. The effect of learning-reten¬ tion interval was significant (F [2,70] 54.9, < .01), indi¬ cating that retention scores did decline in successive retention tests. However, subjects who had received bilat¬ eral ECT, unilateral ECT, or no ECT did not differ from each other (F [2,35] 0.12, P>.3). Unilateral ECT affects verbal memory less than bilat¬ eral ECT, but can markedly affect memory for nonverbal material.16 31 To determine if subjects who had received unilateral ECT (group B) might exhibit a selective impair¬ ment of memory for the nonverbal items of this test, scores for the nonverbal items (nonsense drawings and faces) were analyzed separately. Scores on these items did not differ among groups (F [2,35] 1.68, P>.3), and the three groups did not vary by more than 1.6 points at any retention interval. On the immediate retention test, the patients in group D scored somewhat lower than the other groups, but this difference fell short of significance (t [49] 1.1 to 2.1, P>.05). One day after learning, however, patients in group D remembered an average of only 17.2 items out of 32, compared to 27.0, 28.5, and 28.0 for groups A, B, and C, respectively (t [49] 7.5 to 8.7, < .01). =
=
=
Confidence
Ratings
In addition to obtaining similar scores on this test, sub¬ jects in the three follow-up groups expressed a similar amount of confidence in their responses. Each subject was
assigned one score for each retention session, represent¬ ing his average confidence rating for the 32 responses made during the session. Table 2 indicates the average confidence ratings given by groups A, B, and C for re¬ sponses during the immediate, one-day, and two-week re¬ tention tests. The confidence ratings employed by each group were not measurably different at any learning re¬ tention interval (F [2,105] < 0.6, P>.3). However, patients in group D employed comparatively low confidence rat¬ ings. Their average confidence rating during the one-day retention session was significantly lower than the corre¬ sponding confidence ratings employed by each of the other groups (t [49] 5.0 to 5.4, < .01). Another way to compare the use of confidence ratings is to ask how well subjects discriminated items they judged to be correct from items they judged to be incorrect. An estimate of this discriminative ability (d') is given by cal¬ culating for each group a type II receiver operating char¬ acteristic (ROC) curve.34 The calculated values for d' were =
Used
by
Learning-Retention Interval Group Bilateral ECT Unilateral ECT NoECT Group D *
Values
expressed
_
are
No Delay 3.76±.06 3.75 ±.07 3.73±.07 3.57±.07
1 Day 3.40 ±.14 3.32 ± .14 3.35±.13 2.21 ±.17
as mean ±
2 Wk 3.00 ±.15 2.99 ±.14 3.16 ± .14
SE.
quite similar—1.19, 1.28, and 1.21 for groups A, B, and C, respectively. The value of d' for group D was also similar (1.25), indicating that patients in this group applied confi¬ dence ratings according to the same criteria as the other groups. Test 2: Recall of
a
Paragraph
Figure 2 indicates that the three follow-up groups were quite similar in their ability to recall a short paragraph at
various delays after original learning. Performance de¬ clined significantly between the immediate-retention test and the one-day test (F [1,70] 72,6, < .01) and between the one-day test and the two-week test (F [1,70] 7.3, < .01), but there was no effect of prior treatment on re¬ call at any learning-retention interval (F [2,105] .07 to 0.8, P>.3). By contrast, patients in group D had great dif¬ ficulty retaining information about the paragraph. They scored about as well as the other groups on immediate re¬ tention (t [49] =0.8, P>.3), but only two of the 15 patients could recall any part of the paragraph a day later (i [49] 2.0 to 3.0; < .05 when P>2.1). =
=
=
=
=
=
(1-4)
*
Test 3:
Drawing
of a Complex Geometric from Memory
Figure
Figure 3 presents scores at one day and two weeks after learning for the follow-up subjects and at one day after learning for patients in group D. From one day to two weeks after learning, performance on this memory task significantly declined (F [1,35] 37.9, < .01); however, performance declined at about the same rate in each of the follow-up groups, and there was no measurable differ¬ ence between groups at either learning-retention interval (F [2,70] 0.5 to 0.6, P>.3). The control group (group C) =
=
scored somewhat below the other two groups, but this dif¬ ference did not approach significance (F [1,35] 1,2, P>.3, orthogonal comparisons). Patients in group D were greatly impaired in their ability to reproduce the figure from memory the day after learning, and scored signifi¬ cantly below each of the other three groups (t [49] 3.7 to =
=
4.9,
