Strategic Processing and Episodic Memory Impairment in Obsessive Compulsive Disorder

Strategic Processing and Episodic Memory Impairment in Obsessive Compulsive Disorder
[Articles]
Savage, Cary R.1,2,3; Deckersbach, Thilo1,2; Wilhelm, Sabine1,2; Rauch, Scott L.1,2; Baer, Lee1,2; Reid, Tracey1,2; Jenike, Michael A.1,2
1Department of Psychiatry, Massachusetts General Hospital
2Department of Psychiatry, Harvard Medical School
3Correspondence concerning this article should be addressed to Cary R. Savage, Department of Psychiatry, 149-9102, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, Massachusetts 02129-2060. Electronic mail may be sent to savage@psych.mgh.harvard.edu.
This research was presented, in part, to the Society for Neuroscience, Los Angeles, November 1998. Support was provided by the David Judah Research Fund and Grants MH01230 and MH01215 from the National Institutes of Health. We thank Ulrike Buhlmann, Iris Nellisen, and David Mataix-Cols for their work on this project.
Received Date: January 13, 1999; Revised Date: May 24, 1999; Accepted Date: May 24, 1999
Abstract
There is evidence that nonverbal memory problems in obsessive compulsive disorder (OCD) are mediated by impaired strategic processing. Although many studies have found verbal memory to be normal in OCD, these studies did not use tests designed to stress organizational strategies. This study examined verbal and nonverbal memory performance in 33 OCD patients and 30 normal control participants with the Rey–Osterrieth Complex Figure Test and the California Verbal Learning Test. OCD patients were impaired on verbal and nonverbal measures of organizational strategy and free recall. Multiple regression modeling indicated that free recall problems in OCD were mediated by impaired organizational strategies used during learning trials. Therefore, verbal and nonverbal episodic memory deficits in OCD are affected by impaired strategic processing. Results are consistent with neurobiological models proposing frontal-striatal system dysfunction in OCD.
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Obsessive compulsive disorder (OCD) is characterized by intrusive thoughts and stereotyped behaviors that are severe enough to interfere with daily functioning and cause significant distress (American Psychiatric Association, 1994). There is substantial evidence that OCD is associated with distinct patterns of brain dysfunction and cognitive impairment. There is also reason to believe that cognitive deficits may contribute to many of the characteristic symptoms of OCD, such as chronic doubt, repetitive checking, rumination, behavioral inflexibility, and ritualistic behavior. However, until recently, it has been difficult to link these sets of findings together.
Functional neuroimaging methods, such as positron emission tomography and functional magnetic resonance imaging, have been used to identify neural systems involved in OCD. These studies have provided consistent evidence of prefrontal, especially orbital prefrontal, and striatal dysfunction in OCD patients during resting states and during induced states of symptom provocation and cognitive activation (Rauch & Baxter, 1998). In addition, abnormal metabolic activity in the orbital prefrontal cortex and caudate nuclei is attenuated following successful treatment with serotonergic reuptake inhibitors (Baxter et al., 1992; Benkelfat et al., 1990; Schwartz et al., 1996; Swedo et al., 1992) and behavior therapy (Baxter et al., 1992; Schwartz et al., 1996).
Further evidence of frontal-striatal dysfunction comes from studies noting an association between OCD or OCD-like behavior and neurologic disorders, such as Tourette syndrome, postencephalitic and idiopathic Parkinson's disease (PD), Huntington's disease (HD), Sydenham's chorea, and cases with focal prefrontal and striatal lesions (Berthier, Kulisevsky, Gironell, & Heras, 1996; Coffey, Jones, & Shapiro, 1998; Cummings & Cunningham, 1992; Daniele et al., 1997; Donovan & Barry, 1994; Weilburg et al., 1989). These findings, taken together, have led investigators to propose frontal-striatal models of OCD (Rauch, Whalen, Dougherty, & Jenike, 1998; Schwartz, 1997) because the implicated regions (i.e., prefrontal cortex and striatum) are components of distributed frontal-striatal neural systems (Alexander, Crutcher, & DeLong, 1990).
Neuropsychological investigations are also beginning to associate OCD with distinct patterns of cognitive impairment. Although results of early studies were frequently inconsistent, recent studies have identified problems in memory (Boone, Ananth, Philpott, Kaur, & Djenderedjian, 1991; Christensen, Kim, Dysken, & Hoover, 1992; Cohen et al., 1996; Dirson, Bouvard, Cottraux, & Martin, 1995; Savage et al., 1996, 1999; Zielinski, Taylor, & Juzwin, 1991), visuospatial skills (Aronowitz et al., 1994; Behar et al., 1984; Boone et al., 1991; Cohen et al., 1996; Head, Bolton, & Hymas, 1989; Hollander et al., 1993), and selected executive functions (Abbruzzese, Bellodi, Ferri, & Scarone,1995; Abbruzzese, Ferri, & Scarone, 1995, 1997; Aronowitz et al., 1994; Head et al., 1989; Malloy, 1987; Nelson, Early, & Haller, 1993; Purcell, Maruff, Kyrios, & Pantelis, 1998a, 1998b; Veale, Sahakian, Owen, & Marks, 1996; Zielinski et al., 1991).
Although memory abnormalities are among the most consistent findings in the OCD literature, they have been difficult to link definitively to frontal-striatal system function. Studies of neurologic patients with frontal lobe lesions or with disorders affecting frontal-striatal function (e.g., PD and HD) provide insights into the contribution of frontal-striatal systems to memory (Shimamura, 1995; Shimamura, Janowsky, & Squire,1991). Findings in these groups point to abnormalities in the strategic aspects of memory, which are closely tied to executive functioning (Bondi, Kaszniak, Bayles, & Vance, 1993; Buytenhuijs et al., 1994; Gabrieli, Singh, Stebbins, & Goetz, 1996; Gershberg & Shimamura, 1995; Incisa Della Rocchetta & Milner, 1993; Pillon, Deweer, Agid, & Dubois, 1993; Pillon et al., 1998; Savage, 1997). For instance, these patients have difficulty using semantic and perceptual organizational attributes of stimuli (e.g., categorical similarities between words in a list) when encoding and retrieving new episodic memories. Impaired use of organizational strategies leads to slower learning rates and disproportionate impairment in free recall when compared with conditions in which organizational structure is externally provided, such as in category-cued recall and recognition. However, the ability to store information, once learned, is preserved. This pattern of memory impairment can be distinguished from that associated with medial temporal dysfunction, in which the ability to store new memories is primarily affected (Squire, 1992).
Given these findings and evidence of frontal-striatal system dysfunction in OCD, it is likely that impaired use of organizational strategies may also contribute to memory dysfunction in patients with OCD (Savage, 1998). We recently examined this question using the Rey–Osterrieth Complex Figure Test (RCFT; Osterrieth, 1944) in matched groups of unmedicated OCD patients and healthy controls (Savage et al., 1999). We found that OCD patients were impaired in their use of organizational strategies when copying the figure, and they recalled less on both immediate and delayed testing. Retention rates from immediate to delayed recall were normal. Multiple regression modeling indicated that group differences in immediate recall were statistically mediated by copy organizational strategies. Thus, there is evidence that nonverbal episodic memory problems in OCD are mediated by impaired organizational strategies.
This initial finding involved nonverbal memory only. Most previous neuropsychological studies have found that verbal memory is normal in OCD (Boone et al., 1991; Christensen et al., 1992; Dirson et al., 1995; Savage et al., 1996; Zielinski et al., 1991). However, this finding would not be predicted from studies of patients with frontal-striatal lesions. One possible explanation is that OCD affects predominantly right-hemisphere functions, which selectively disrupt nonverbal abilities (e.g., Christensen et al., 1992). An alternative explanation for the preponderance of nonverbal findings in OCD is that nonverbal stimuli place greater demands on strategic processing because of their more abstract nature, inherent unfamiliarity, and greater complexity. OCD participants with comparatively mild cognitive impairment might have problems only on these more organizationally challenging nonverbal tests. Consequently, in the current study, we sought to examine performance of OCD participants on a verbal test designed more specifically to stress organizational processes.
The California Verbal Learning Test (CVLT; Delis, Kramer, Kaplan, & Ober, 1987) is well suited to this question. In the CVLT, participants are presented with a list of 16 words containing an imbedded semantic structure (four categories, containing four words each). The degree to which participants actively impose semantic organizational strategies can be evaluated in relation to learning and memory performance. Tests like the CVLT, containing semantically related word groups, have been used in frontal-striatal disorders to document impairment of strategic organizational processes and the impact on free recall (Buytenhuijs et al., 1994; Gershberg & Shimamura, 1995; Pillon et al., 1993).
To our knowledge, the CVLT has been used in three previous investigations of OCD. Two of the three studies found reduced free recall in OCD (Deckersbach, Otto, Savage, Baer, & Jenike, in press(1999z); Martin et al., 1993). The other study (Zielinski et al., 1991) reported more intrusive errors among OCD patients on free-recall measures. Thus, all three studies indicated some degree of difficulty in free recall. None of these prior studies examined the contribution of organizational strategies to OCD-related differences in free recall. Deckersbach et al. (in press) administered the RCFT and CVLT to a group of OCD patients and compared performance with published norms. OCD patients were clinically impaired on strategy and free recall scores on both the RCFT and CVLT. Organizational strategy scores were also strongly correlated with free recall. However, the absence of a matched control group precluded formal analysis of the effects of organizational strategies on recall.
The current study set out to evaluate the mediating effects of organizational strategies on both verbal and nonverbal episodic memory in OCD, by using the RCFT and CVLT. Our goals were (a) to replicate the original finding that nonverbal memory problems on the RCFT are mediated by impaired organizational strategies (Savage et al., 1999) in independent samples of OCD participants and healthy matched controls, (b) to extend findings in OCD to verbal memory by evaluating the effects of organizational strategies on verbal free recall using the CVLT, and (c) to examine other CVLT characteristics previously associated with frontal-striatal dysfunction, including disproportionate performance improvement with category cues and recognition trials.
Method
Participants
Study participants were 33 patients meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM–IV, American Psychiatric Association, 1994) criteria for OCD and 30 matched healthy control participants. Patients were recruited through the Obsessive Compulsive Disorders Clinic and Research Unit of the Massachusetts General Hospital, and controls were recruited through bulletin board notices within the hospital. Diagnoses of OCD participants and status of healthy controls were determined by the Structured Clinical Interview for DSM–IV (SCID; First, Spitzer, Gibbon, & Williams, 1995), conducted by trained interviewers. All clinical diagnoses were confirmed by a clinical psychologist or a psychiatrist. Among OCD participants, 18 had one comorbid Axis I diagnosis, although OCD was considered to be the primary diagnosis in all cases. Comorbid conditions included major depression (2), dysthymia (2), panic disorder (10), substance abuse (1), Tourette syndrome (1), and body dysmorphic disorder (2). In addition, 22 of the OCD participants were taking selective serotonin reuptake inhibitor (SSRI) medications. To evaluate potential effects of comorbid diagnoses, data were first analyzed with the entire OCD group and then with the 18 comorbidly diagnosed patients excluded. Exclusion criteria for healthy control participants were history of prescribed psychotropic medication, current or past substance dependence, current or past psychiatric disorder, and current or past neurologic disorder or other significant medical illness. All controls received a SCID interview to verify their normal status. All participants were right- handed according to the Edinburgh Handedness Inventory (Oldfield, 1971) and provided written consent prior to participation.
Participants completed the Yale–Brown Obsessive Compulsive Scale (Goodman et al., 1989) and the Beck Depression Inventory (Beck, Ward, Mendelson, Mock, & Erbaugh, 1961). Verbal intellectual functioning was estimated with the Vocabulary subtest of the Shipley Institute of Living Scale (Zachary,1991). Patients and control participants were matched for gender, handedness, age, education, and estimated verbal intelligence. Table 1 summarizes the demographic data and clinical characteristics of the sample.

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Table 1 Demographic and Clinical Characteristics of the Sample
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Procedure and Materials
Neuropsychological tests were administered and scored by trained examiners. The entire battery was administered in one session, and the order of individual tests was counterbalanced. Encoding and recall conditions of the two memory tests (RCFT, CVLT) were never overlapping.
RCFT.
The RCFT (Osterrieth, 1944) provides measures of construction ability (copy) and nonverbal immediate free recall (immediate recall). In addition, the RCFT can be used to examine organizational strategies used during the copy condition. In this study, participants were instructed to copy the complex figure using colored pencils that were changed every 15 s to permit analysis of organizational strategies. If participants were completing a major feature at the end of 15 s, they were allowed to complete that feature before the pencil was switched. Immediately following copy, without intervening distraction, participants were instructed to draw everything they remembered of the figure.
Construction accuracy was calculated by using a scoring system developed by Denman (1984), in which 24 segments of the figure were evaluated using criteria such as sector location, line angles (measured with a protractor), line length (measured with a ruler), and line number. This scoring method was chosen on the basis of its objectivity, reliability, and focus on figure details rather than global attributes, which might otherwise artificially inflate correlations with copy organization. There are three identified criteria for each segment, each assigned 1 point, resulting in a range of scores from 0 to 72. The criteria for each segment are not hierarchically organized; therefore, participants can receive credit for some but not other criteria within each component. The focus of scoring is on the participant's ability to construct and recall visual details rather than on skill in drawing or how the components are organized. Thus, participants are not penalized on construction accuracy scores for poor organization.
Organizational strategy was evaluated with a quantitative method developed and described in detail by Savage et al. (1999). To score organization, five configural elements of the figure were identified (base rectangle, two diagonals, vertical midline, horizontal midline, vertex of the triangle on right), and the participant received points for constructing each as an unfragmented unit. The order of construction and drawing accuracy were not considered in this score. The base rectangle was assigned 2 points, with all other elements receiving 1 point, resulting in a possible score of 0 to 6 points. As in other systems, the base rectangle was more heavily weighted to reflect its importance to the fundamental organization of the figure (Akshoomoff & Stiles, 1995; Shorr, Delis, & Massman, 1992). To obtain scoring reliability measures, copy organization was rescored by a second trained examiner. Interrater reliability measures for copy organization in this cohort were very high, r(61) = .96, p < .0001.
CVLT.
The CVLT (Delis et al., 1987) consists of a list of 16 shopping items read to participants in five study trials, with free recall after each trial. The list contains an imbedded semantic structure, in which words can be grouped into one of four categories (e.g., fruits, tools). Participants are not informed of this structure, and the list is presented so that a given word is never followed by another word from the same category. An interference list is then administered and recalled immediately after the fifth study trial. Short- and long-delay (20-min) free and category-cued recall of the original list are subsequently assessed, followed by a recognition test.
Recognition discriminability scores were calculated to measure participants' ability to discriminate between items of the original list and a set of distractors. This score was calculated nonparametrically, as outlined in the CVLT manual (Delis et al., 1987). Verbal organizational strategies were quantified with a semantic clustering score that measured the degree to which participants grouped words into semantic categories during recall in the five learning trials. Participants received points for recalling words from the same category in succession. This score was corrected for the overall number of words recollected, as the likelihood of receiving semantic clustering points by chance increases with the number of words recalled (Delis et al., 1987).
For the purposes of this study, we were interested in the following CVLT measures: Trial 1 free recall, Trial 5 free recall, short-delay free and cued recall, long-delay free and cued recall, semantic clustering (Trials 1–5), and long-delay recognition discriminability. In addition, we calculated four contrast measures to evaluate retention rates and how much participants benefited from retrieval aids. The formulas were as follows: For percentage recall, Trial 5 to short delay = short delay/Trial 5 × 100; for percentage recall, short delay to long delay = long delay/short delay × 100; for percentage improvement, free recall to cued recall = (cued recall - free recall)/free recall × 100; and for percentage improvement, free recall to recognition = (recognition hits - free recall)/free recall × 100.
Statistical Analysis
RCFT and CVLT means were first evaluated in one-way and mixed-model analyses of variance (ANOVAs). We predicted that when compared with controls, the OCD group would use less systematic organizational strategies, learn significantly less during encoding, demonstrate normal retention rates over long and short delays, and show disproportionate improvement when provided with retrieval aids on delayed recall, in the form of cued recall and recognition.
Following these analyses, we tested the hypothesis that differences in free recall would be mediated by strategies used during learning, separately for the RCFT and CVLT. These mediation hypotheses were tested through multiple regression, in two 3-variable path models (Land, 1969) that used procedures identical to those from Savage et al. (1999). In this analytical approach, the causal ordering is established a priori, and a multiple regression equation is computed conditional on the model. In these analyses, group (OCD = 1, control = 0) was the independent variable, RCFT and CVLT free-recall measures were the dependent variables, and RCFT and CVLT strategy measures (copy organization, semantic clustering) were the hypothesized mediators. Baron and Kenny (1986) have formalized procedures for establishing statistical mediation. These steps are described in detail in Savage et al. (1999). We predicted that the mediated models would be supported in both verbal and nonverbal tests.
Results
RCFT
Mean RCFT accuracy, percentage recall rates, and copy organization scores are presented in Table 2. RCFT accuracy scores were evaluated using a two-variable (Group × Condition) mixed-model ANOVA, with repeated measures on condition. Analyses indicated a significant main effect for group, F(1, 60) = 7.62, p = .008, as well as a significant Group × Condition interaction, F(1,60) = 8.00, p = .006. Post hoc analyses indicated that OCD patients and controls did not differ in copy performance, t(60) = 1.26, p = .21, but OCD participants recalled less than controls on immediate recall, t(60) = 2.96, p = .004. Mean percentage recall rates (immediate recall/copy × 100) were also compared with ANOVAs (see Table 2), revealing that the OCD group recalled significantly less from copy than the control group, F(1, 60) = 8.88, p = .009. Finally, OCD patients obtained lower copy organization scores in comparison with controls (see Table 2), t(60) = 2.33, p = .02.

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Table 2 Summary of RCFT and CVLT Means and Significance Tests in OCD Patients and Healthy Controls
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CVLT
CVLT means are presented in Table 2 and are subdivided into the following categories: general learning and memory, retention over a delay, strategic processing, and response to retrieval aids. In addition, the means for Recall Trials 1–5; List B recall; short-delay free and cued recall; and long-delay free recall, cued recall, and recognition are illustrated in Figure 1. On general learning and memory measures (see Table 2), a two-variable (group, condition) mixed-model ANOVA revealed a main effect for group, F(1, 61) = 8.75, p = .004, with no Group × Condition interaction, F(1, 183) = 1.24, p = .30. Thus, OCD participants showed difficulties recalling information across the general learning and memory measures. However, OCD patients did not show abnormal retention rates over a delay, as measured by percentage recall from Trial 5 to short delay, t(61) = -0.80, p = .43. Although there was a significant group difference on percentage recall from short delay to long delay, t(61) = 1.97, p = .05, this reflected improvement in performance among controls (107%) rather than abnormal forgetting in OCD patients (101%). Thus, there are no indications of impaired retention rates in our OCD group. Examination of strategic processing (see Table 2) revealed that OCD patients used semantic clustering strategies less than controls, t(61) = 2.15, p = .03, but did not differ in the use of serial clustering, t(61) = 0.95, p = .34. Finally, analyses of response to retrieval aids (see Table 2) indicated that although impaired on long-delay free recall (p = .009), OCD participants obtained similar scores on recognition discriminability, t(61) = 1.54, p = .13. In addition, the OCD group showed disproportionate improvement from free recall to cued recall, t(61) = -2.02, p = .04, and from free recall to recognition hits, t(61) = -2.83, p = .006.

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Figure 1. Summary of the primary California Verbal Learning Test (CVLT; Delis, Kramer, Kaplan, & Ober, 1987) scores. Error bars represent standard error of the mean. Obsessive compulsive disorder (OCD) patients performed worse overall than control participants on free-recall measures, including learning trials (Trials 1–5) and delayed recall measures (short delay [SD], long delay [LD]). OCD patients also improved disproportionately on long-delay measures when provided with additional structure in the form of category cues and recognition (Recog) trials.
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Results of these initial analyses of the RCFT and CVLT indicate that the OCD group differed from the healthy control group in the following ways: (a) OCD participants used less systematic organizational strategies, (b) OCD participants learned significantly less information during encoding, as expressed on immediate free recall, (c) OCD participants did not have difficulty storing verbal information over short and long delays, and (d) OCD participants showed disproportionate improvement in comparison with controls on CVLT measures of cued recall and recognition after a 20-min delay, with recognition performance at normal levels after a long delay.
Path Models
Our a priori hypothesis was that both verbal and nonverbal memory problems in OCD would be mediated by poor organizational strategies during encoding. On the basis of the results just described, we selected RCFT percentage recall and CVLT long-delay free-recall scores as dependent variables. These measures were considered to be the most statistically robust and representative of group differences in free recall for each test. The mediation hypothesis was then evaluated in three-variable path models, separately for the RCFT and CVLT.
RCFT.
Path modeling results for the RCFT are presented following the steps outlined in Baron and Kenny (1986). In the simple regression analyses, group had a direct effect on the hypothesized mediator, copy organization ([beta] = -.29, p = .02), and on the dependent variable, percentage recall from copy ([beta] = -.36, p = .004). In the multiple regression equation, copy organization continued to have a strong direct effect on percentage recall ([beta] = .64, p < .0001), but the direct effect of group was reduced in absolute size and dropped to a statistical trend ([beta] = -.17, p = .07). When comparing the direct and mediated models, the mediated model provided significantly greater explanatory power ([DELTA]R2= .37, p < .0001). Thus, group differences in RCFT recall are expressed primarily along an indirect path through the effects of group on organizational strategies.
CVLT.
In the simple regression analyses, group had a direct effect on the hypothesized mediator, semantic clustering ([beta] = -.27, p = .03), and on the dependent variable, long-delay free recall ([beta] = -.33, p = .009). In the multiple regression equation, semantic clustering continued to have a strong direct effect on percentage recall ([beta] = .68, p < .0001), but the direct effect of group was reduced in absolute size and significance ([beta] = -.15, p = .11). When comparing the direct and mediated models, the mediated model provided significantly greater explanatory power ([DELTA]R2= .42, p < .0001). As with the RCFT, group differences in verbal recall are expressed primarily through the indirect effects of group on strategies.
Figure 2 illustrates these results for the RCFT and CVLT as path diagrams representing direct and mediated models, with standard coefficients ([beta]) and significance levels listed for each link. In the direct model, group differences in nonverbal and verbal free recall are expressed directly, as reflected in the significant correlation between group and immediate percentage recall (RCFT, [beta] = -.36, p = .004; CVLT, [beta] = -.33, p = .009). This model accounts for 13% of the variance in RCFT free recall and for 11% in CVLT free recall. In the mediated model, group effects on free recall are expressed indirectly, through the effects of group on strategic processing and strategic processing on free recall (i.e., strategic processing mediates group differences in free recall). The direct effects of group in the mediated model are reduced in absolute size and significance. In addition, the mediated model provides significantly greater explanatory power, with total explained variance of 50% for the RCFT and 53% for the CVLT ([DELTA]R2 = .37 and .42, respectively, p < .0001). The size and significance of the indirect effect of group through strategic processing can be calculated by multiplying the two standard coefficients (Cohen & Cohen, 1983). This indirect path is statistically significant in both the RCFT (-.29 × .64 = -.19, p < .01) and CVLT (-.27 × .68 = -.18, p < .01) models. The hypothesized mediated models provide the best fit to the obtained data sets for both the RCFT and CVLT.

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Figure 2. Two alternate path models explaining group differences in free-recall memory on the Rey–Osterrieth Complex Figure Test (RCFT; Osterrieth,1944) and California Verbal Learning Test (CVLT; Delis et al.,1987). The top portion presents a direct model, in which the effects of group are expressed directly in differences in nonverbal and verbal free recall (percentage retention on the RCFT; long-delay free recall on the CVLT); the bottom portion presents a mediated model, in which the effects of group on free recall are expressed indirectly, through the influence of strategic processing during encoding (copy organization for the RCFT; Trial 1–5 semantic clustering for the CVLT). Regression analyses supported the mediated model.
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Effects of comorbid diagnoses.
As noted previously, 18 of the 33 OCD participants had one comorbid Axis I diagnosis. To evaluate the potential effects of comorbidity, we excluded these 18 participants and reanalyzed data with the 15 remaining participants who had OCD as their only diagnosis. For RCFT, simple regression group on organization, [beta] = -.41, p = .006; and group on percentage recall, [beta] = -.48, p = .001. For RCFT, multiple regression on percentage recall, organization, [beta] = .60, p < .0001; group, [beta] = -.24, p = .05; and [DELTA]R2 = .30, p < .0001. For CVLT, simple regression, group on clustering, [beta] = -.34, p = .02; and group on long-delay recall, [beta] = -.35, p = .02. For CVLT, multiple regression on long-delay recall, clustering, [beta] = .70, p < .0001; group, [beta] = -.12, p = .28; and [DELTA]R2 = .43, p < .0001. Therefore, these path models were nearly statistically identical to those in the total OCD group, and comorbidity does not appear to have contributed to the significance of our current results. This interpretation is further strengthened by the fact that the RCFT data replicated our original finding in an independent group of 20 OCD patients without comorbid diagnoses and off all psychotropic medication (Savage et al., 1999).
The validity of our mediated model is dependent on the variables selected and their causal ordering. The causal ordering has face validity, however, because there is only one possible logical ordering for these variables: Group -> Strategic Processing -> Free Recall (see Cohen & Cohen, 1983). However, the effects of group, although significantly reduced in absolute size and significance, are not eliminated entirely in the mediated model. In addition, power limitations necessitate caution because of the potential for Type II error when determining the residual effects of group. There are undoubtedly other unmeasured influences on RCFT and CVLT performance that we have not considered here. Nonetheless, the current models fit the obtained data sets and are both clinically and theoretically relevant.
Discussion
OCD patients in this study showed impaired free recall on both verbal and nonverbal memory tests. Specifically, they used less systematic organizational strategies during encoding trials, and they learned significantly less, as expressed on immediate free recall measures. Although impaired on verbal delayed free recall, OCD patients did not have additional difficulty storing information over short or long delays. In addition, a series of regression analyses demonstrated that free recall problems in OCD were mediated by impaired organizational strategies used during learning trials. Thus, these OCD patients were primarily impaired in strategic processing, which then had secondary effects on immediate and delayed free recall. These findings are consistent with neurobiological models hypothesizing the importance of frontal-striatal system dysfunction in OCD. The current study also found evidence of other memory problems characteristic of frontal-striatal dysfunction. Specifically, OCD participants showed disproportionate improvement in comparison with controls on measures of verbal cued recall and recognition, and delayed verbal recognition performance was at normal levels.
Current findings may be influenced by the presence of comorbid conditions in a significant proportion of the OCD group (18/33) or by the fact that many patients were medicated (22/33). Data from this study and previous work help to address these issues. First, the path models in the current study were supported equally in the total group of 33 OCD patients and in the subgroup of 15 without any comorbid conditions, indicating that comorbidity did not account for significance in the whole group. This study does not directly address the potential effects of SSRIs; however, parallel findings in unmedicated OCD groups (Deckersbach et al., in press; Savage et al., 1999) suggest that medication status alone cannot account for group differences. Current data must still be interpreted with some caution because parallel findings support the absence of medication effects but do not completely exclude the possibility. It is also important to note that all patients in the current study met full diagnostic criteria for OCD at the time of testing, regardless of treatment status. Taken together, results speak to the robustness and generalizability of these findings in OCD groups. Consistent patterns of results have now been demonstrated in three independent samples of OCD patients—two with pure OCD off all medications and one with various comorbid disorders and medication status. Nonetheless, additional studies are needed to document the potential cognitive effects of SSRI medication and comorbidity.
Findings from the RCFT replicate earlier findings (Savage et al., 1999) in independent samples of OCD patients and control participants. OCD participants from both studies had difficulty using organizational strategies when copying the RCFT figure and this influenced how much they later recalled. The current study also extends these findings to verbal memory. As noted earlier, numerous studies have found verbal memory in OCD to be normal; however, most of these studies used lists of unrelated words. To our knowledge, only three previous studies used semantically related word lists (all of these used the CVLT), and all three showed abnormal free recall in OCD (Deckersbach et al., in press(1999z); Martin et al., 1993; Zielinski et al., 1991). Current findings indicate that verbal memory abnormalities in OCD may only emerge on tests containing some degree of semantic structure, which can be exploited by normal participants to improve learning and recall. Taken together, neuropsychological investigations of OCD indicate that patients are most likely to have memory problems on strategic memory tests (Gabrieli, 1998), which tap into organized and effortful encoding and retrieval operations—these processes are not necessarily modality specific.
This study also examined performance characteristics previously associated with frontal-striatal dysfunction. OCD patients were impaired in comparison with control participants on almost all verbal and nonverbal measures of free recall. For instance, on the CVLT, they showed equivalently impaired free recall on short-term (Trials 1–5) and long-term measures, indicating that free recall is consistently affected throughout immediate learning trials and delayed memory. Their performance improved disproportionately when they were given increased structure in the form of category cues and recognition trials. In fact, long-delay recognition performance was normal. Impaired recall with normal recognition has previously been found in OCD with nonverbal stimuli (Savage et al., 1996). Combined findings from these studies indicate that memory problems in OCD are most pronounced in conditions of free recall; this may reflect the lack of structure provided in free-recall tests, as compared with cued recall and recognition.
Normal participants benefit from structure by spontaneously grouping stimuli according to their shared semantic or perceptual features. Structure, as used here, could apply to either verbal or nonverbal stimuli. For example, word lists can be subdivided into groups of words with shared semantic features (e.g., categories), whereas complex designs can be broken down into simpler units that are perceptually meaningful (e.g., squares, triangles, diagonals). OCD participants do not appear to spontaneously detect or apply organizational structure as a means of improving encoding and retrieval to the same degree as control participants. However, results from the CVLT indicate that they can use semantic structure if their attention is directed to it by providing category cues at the time of retrieval. Therefore, one important feature of these tests is that the underlying structure is latent.
As noted earlier, strategic processes of memory are closely related to executive functioning. There is evidence from Savage et al. (1999) that organizational impairment on the RCFT is related to a type of executive dysfunction affecting the ability to shift mental set. RCFT copy organization was correlated with measures of mental and spatial set-shifting ability but not with other measures of executive function. In addition, qualitative analyses of organization showed that both OCD patients and controls frequently initiated RCFT construction with a detail; however, the controls quickly shifted to major organizational features, whereas OCD participants continued using a detail-oriented approach.
Evidence for executive dysfunction in OCD is also provided from other published studies, especially those examining strategic processing using working-memory tests. Veale et al. (1996) used the Tower of London test (Shallice, 1982) to show that OCD participants had delays generating alternate strategies following initially incorrect responses, which they attributed to difficulty shifting mental set. Purcell et al. (1998a, 1998b) found that OCD patients experienced difficulties on measures of spatial working memory. They concluded that their OCD group had executive function deficits that specifically affected the ability to organize and execute strategies, especially in the absence of external structure.
Grachev et al. (1998) conducted a morphometric magnetic resonance imaging study of OCD patients and matched controls using recently developed cortical parcellation techniques that subdivide the cortex into 48 separate units, paralleling functional boundaries (i.e., Brodmann areas). They found gray matter volumes to be significantly increased in the OCD group in regions of the right prefrontal cortex, especially the right inferior frontal and right midfrontal regions that correspond to Brodmann's Areas 44, 45, 46,6, 8, and 9 (Rademacher, Galaburda, Kennedy, Filipek, & Caviness, 1992). Furthermore, these increases were negatively correlated with immediate recall scores on the RCFT, indicating that poorer nonverbal memory performance was associated with greater abnormalities in right prefrontal gray matter volumes. This is interesting because these right prefrontal regions have been implicated in strategic episodic retrieval processes in functional neuroimaging studies of normal participants (e.g., Buckner et al., 1998; Rugg et al., 1998; Wagner, Desmond, Glover, & Gabrieli, 1998).
Findings from this study and others indicate that when presented with complex ambiguous situations, OCD patients may tend to make the following strategic processing errors: They focus on details without appreciating the larger perceptual or semantic context, and they have difficulty shifting mental set, which makes it difficult for them to try alternative, more adaptive, strategies. These characteristics negatively impact their ability to encode and retrieve new episodic memories. These strategic memory processes are closely related to executive functioning, and their disturbance is consistent with frontal-striatal models of OCD (e.g., Rauch et al., 1998). Lesions affecting frontal systems have also been tied to other aspects of episodic memory that may be relevant to OCD: source memory, or the ability to distinguish one episode from another, and metamemory, or the ability to accurately evaluate and predict one's own memory performance (Shimamura, 1995; Shimamura et al., 1991). These memory characteristics should also be evaluated in studies of OCD.
Although current findings are consistent with frontal-striatal dysfunction, some caution is warranted in drawing neuroanatomically based conclusions from our data. Performance on a cognitive test is only an indirect measure of brain function. Furthermore, the underlying neuropathology in psychiatric disorders such as OCD is not a gross lesion per se but rather subtle morphological abnormalities and disrupted function in widely distributed neural systems. More specific inferences might be made on the basis of results of functional imaging studies, particularly those using cognitive activation paradigms (e.g., Rauch et al., 1997). Our findings indicate that these studies might specifically examine strategic processes engaged during the encoding and retrieval of episodic memories.
The current study indicates that strategic processes underlie abnormalities in verbal and nonverbal episodic memory in OCD. It is possible that disruptions of episodic memory contribute to the clinical symptoms of OCD, such as chronic doubt and repetitive behaviors. For example, some OCD patients may have incomplete or fragmented memory representations of critical episodes that are difficult to differentiate (e.g., “Did I lock the door?” “Was it this time or some other time?” “How can I be sure?”). Episodic memory abnormalities might thereby contribute to vicious cycles that maintain and compound obsessions and compulsions (Savage,1998). It is of note that OCD patients benefited when provided with additional structure in the form of category cues. Improved performance with the imposition of structure has also been noted by other investigators (e.g., Purcell et al., 1998b). On the basis of these findings, we are currently investigating the effectiveness of cognitive retraining approaches for OCD, in which patients are taught to use more effective encoding and retrieval strategies. Such studies are needed to more directly examine the relationships between cognitive deficits and clinical symptoms in OCD.
References
Abbruzzese, M., Bellodi, L., Ferri, S., & Scarone, S. (1995). Frontal lobe dysfunction in schizophrenia and obsessive-compulsive disorder: A neuropsychological study. Brain and Cognition, 27, 202–212. [Context Link]
Abbruzzese, M., Ferri, S., & Scarone, S. (1995). Wisconsin Card Sorting Test performance in obsessive-compulsive disorder: No evidence for involvement of dorsolateral prefrontal cortex. Psychiatry Research, 58, 37–43. Bibliographic Links [Context Link]
Abbruzzese, M., Ferri, S., & Scarone, S. (1997). The selective breakdown of frontal functions in patients with obsessive-compulsive disorder and in patients with schizophrenia: A double dissociation experimental finding. Neuropsychologia, 35, 907–912. Bibliographic Links [Context Link]
Akshoomoff, N. A., & Stiles, J. (1995). Developmental trends in visuospatial analysis and planning: I. Copying a complex figure. Neuropsychology, 9, 364–377. Ovid Full Text [Context Link]
Alexander, G. E., Crutcher, M. D., & DeLong, M. R. (1990). Basal ganglia-thalamocortical circuits: Parallel substrates for motor, oculomotor, “prefrontal” and “limbic” functions. Progress in Brain Research, 85, 119–146. [Context Link]
American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: Author. [Context Link]
Aronowitz, B. R., Hollander, E., DeCaria, C., Cohen, L., Saoud, J. B., & Stein, D. (1994). Neuropsychology of obsessive-compulsive disorder: Preliminary findings. Neuropsychiatry, Neuropsychology, and Behavioral Neurology, 7, 81–86. [Context Link]
Baron, R. M., & Kenny, D. A. (1986). The moderator–mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations. Journal of Personality and Social Psychology, 51, 1173–1182. Ovid Full Text [Context Link]
Baxter, L. R., Schwartz, J. M., Bergman, K. S., Szuba, M. P., Guze, B. H., Mazziotta, J. C., Alazraki, A., Selin, C. E., Ferng, H. K., & Munford, P. (1992). Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Archives of General Psychiatry, 49, 681–689. Bibliographic Links [Context Link]
Beck, A. T., Ward, C. H., Mendelson, M., Mock, J., & Erbaugh, J. (1961). An inventory for measuring depression. Archives of General Psychiatry, 4, 561–571. Bibliographic Links [Context Link]
Behar, D., Rapoport, J. L., Berg, C. J., Denckla, M. B., Mann, L., Cox, C., Fedio, P., Zahn, T., & Wolfman, M. G. (1984). Computerized tomography and neuropsychological test measures in adolescents with obsessive-compulsive disorder. American Journal of Psychiatry, 141, 363–368. Bibliographic Links [Context Link]
Benkelfat, C., Nordahl, T. E., Semple, W. E., King, C., Murphy, D. L., & Cohen, R. M. (1990). Local cerebral glucose metabolic rates in obsessive-compulsive disorder. Archives of General Psychiatry, 47, 840–848. [Context Link]
Berthier, M. L., Kulisevsky, J., Gironell, A., & Heras, J. A. (1996). Obsessive-compulsive disorder associated with brain lesions: Clinical phenomenology, cognitive function, and anatomic correlates. Neurology, 47, 353–361. Buy Now Bibliographic Links [Context Link]
Bondi, M. W., Kaszniak, A. W., Bayles, K. A., & Vance, K. T. (1993). Contributions of frontal system dysfunction to memory and perceptual abilities in Parkinson's disease. Neuropsychology, 7, 89–102. Ovid Full Text [Context Link]
Boone, K. B., Ananth, J., Philpott, L., Kaur, A., & Djenderedjian, A. (1991). Neuropsychological characteristics of nondepressed adults with obsessive-compulsive disorder. Neuropsychiatry, Neuropsychology, and Behavioral Neurology, 4, 96–109. [Context Link]
Buckner, R. L., Koutstaal, W., Schacter, D. L., Dale, A. M., Rotte, M., & Rosen, B. R. (1998). Functional-anatomic study of episodic retrieval: II. Selective averaging of event-related fMRI trials to test the retrieval success hypothesis. Neuroimage, 7, 163–175. Bibliographic Links [Context Link]
Buytenhuijs, E. L., Berger, H. J. C., Van Spaendonck, K. P. M., Horstink, M. W. I. M., Borm, G. E., & Cools, A. R. (1994). Memory and learning strategies in patients with Parkinson's disease. Neuropsychologia, 32, 335–342. Bibliographic Links [Context Link]
Christensen, K. J., Kim, S. W., Dysken, M. W., & Hoover, K. M. (1992). Neuropsychological performance in obsessive-compulsive disorder. Biological Psychiatry, 31, 4–18. Bibliographic Links [Context Link]
Coffey, B. J., Jones, J., & Shapiro, S. (1998). Tourette's disorder and obsessive-compulsive disorder: Clinical similarities and differences. In M. A. Jenike, L. Baer, & W. E. Minichiello (Eds), Obsessive-compulsive disorders: Practical management (3rd ed., pp. 143–161). St Louis, MO: Mosby. [Context Link]
Cohen, J., & Cohen, P. (1983). Applied regression/correlation analysis for the behavioral sciences (2nd ed.). Hillsdale, NJ: Erlbaum. [Context Link]
Cohen, L. J., Hollander, E., DeCaria, C. M., Stein, D. J., Simeon, D., Liebowitz, M. R., & Aronowitz, B. R. (1996). Specificity of neuropsychological impairment in obsessive-compulsive disorder: A comparison with social phobic and normal control subjects. Journal of Neuropsychiatry and Clinical Neuroscience, 8, 82–85. [Context Link]
Cummings, J. L., & Cunningham, K. (1992). Obsessive-compulsive disorder in Huntington's disease. Biological Psychiatry, 31, 263–270. Bibliographic Links [Context Link]
Daniele, A., Bartolomeo, P., Cassetta, E., Bentivoglio, A. R., Gainotti, G., Albanese, A., & Partolomeo, B. (1997). Obsessive-compulsive behaviour and cognitive impairment in a Parkinsonian patient after left putaminal lesion. Journal of Neurology, Neurosurgery, and Psychiatry, 62, 288–302. [Context Link]
Deckersbach, T., Otto, M. W., Savage, C. R., Baer, L., & Jenike, M. A. (in press). The relationship between semantic organization and memory in obsessive-compulsive disorder. Psychotherapy and Psychosomatics. [Context Link]
Delis, D. C., Kramer, J. H., Kaplan, E., & Ober, B. A. (1987). California Verbal Learning Test: Manual. San Antonio, TX: Psychological Corporation. [Context Link]
Denman, S. B. (1984). Denman Neuropsychology Memory Scale. Charleston, SC: S. B. Denman. [Context Link]
Dirson, S., Bouvard, M., Cottraux, J., & Martin, R. (1995). Visual memory impairment in patients with obsessive-compulsive disorder: A controlled study. Psychotherapy and Psychosomatics, 63, 22–31. Bibliographic Links [Context Link]
Donovan, N., & Barry, J. J. (1994). Compulsive symptoms associated with frontal lobe injury. American Journal of Psychiatry, 151, 618 [Context Link]
First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (1995). Structured clinical interview for DSM-IV Axis I Disorders—Patient edition (SCID–I/D, Version 2.0). New York: Biometrics Research Department, New York Psychiatric Institute. [Context Link]
Gabrieli, J. D. E. (1998). Cognitive neuroscience of human memory. Annual Review of Psychology, 49, 87–115. Bibliographic Links [Context Link]
Gabrieli, J. D. E., Singh, J., Stebbins, G. T., & Goetz, C. G. (1996). Reduced working memory span in Parkinson's disease: Evidence for the role of a frontostriatal system in working and strategic memory. Neuropsychology, 10, 322–332. Ovid Full Text [Context Link]
Gershberg, F. B., & Shimamura, A. P. (1995). Impaired use of organizational strategies in free recall following frontal lobe damage. Neuropsychologia, 13, 1305–1333. [Context Link]
Goodman, W. K., Price, L. H., Rasmussen, S. A., Mazure, C., Fleischman, R. L., Hill, C. L., Heninger, G. R., & Charney, D. S. (1989). The Yale–Brown Obsessive Compulsive Scale, I: Development, use, and reliability. Archives of General Psychiatry, 46, 1006–1011. [Context Link]
Grachev, I. D., Breiter, H. C., Rauch, S. L., Savage, C. R., Baer, L., Shera, D. M., Kennedy, D. N., Makris, N., Caviness, V. S., & Jenike, M. A. (1998). Structural abnormalities of frontal neocortex in obsessive-compulsive disorder. Archives of General Psychiatry, 55, 181–182. [Context Link]
Head, D., Bolton, D., & Hymas, N. (1989). Deficit in cognitive shifting ability in patients with obsessive-compulsive disorders. Biological Psychiatry, 25, 929–937. Bibliographic Links [Context Link]
Hollander, E., Cohen, L., Richards, M., Mullen, L., DeCaria, C., & Stern, Y. (1993). A pilot study of the neuropsychology of obsessive-compulsive disorder and Parkinson's disease: Basal ganglia disorders. Journal of Neuropsychiatry and Clinical Neuroscience, 5, 104–106. [Context Link]
Incisa Della Rocchetta, A., & Milner, B. (1993). Strategic search and retrieval inhibition: The role of the frontal lobes. Neuropsychologia, 31, 503–524. Bibliographic Links [Context Link]
Land, K. C. (1969). Principles of path analysis. In E. Borgatta (Ed.), Sociological methodology 1969 (pp. 3–37). San Francisco: Jossey-Bass. [Context Link]
Malloy, P. (1987). Frontal lobe dysfunction in obsessive-compulsive disorder. In E. Perecmam (Ed.), The frontal lobes revisited (pp. 207–223). New York: IRBN Press. [Context Link]
Martin, A., Pigott, T. A., Lalonde, F. M., Dalton, I., Dubbert, B., & Murphy, D. L. (1993). Lack of evidence for Huntington's disease-like cognitive dysfunction in obsessive-compulsive disorder. Biological Psychiatry, 33, 345–353. Bibliographic Links [Context Link]
Nelson, E., Early, T. S., & Haller, J. W. (1993). Visual attention in obsessive-compulsive disorder. Psychiatry Research, 49, 183–196. Bibliographic Links [Context Link]
Oldfield, R. C. (1971). The assessment and analysis of handedness: The Edinburgh Inventory. Neuropsychologia, 9, 97–113. Bibliographic Links [Context Link]
Osterrieth, P. A. (1944). Le test de copie d'une figure complex: Contribution à l'étude de la perception et de la memoire [The test of copying a complex figure: A contribution to the study of perception and memory]. Archives de Psychologie, 30, 286–350. [Context Link]
Pillon, B., Deweer, B., Agid, Y., & Dubois, B. (1993). Explicit memory in Alzheimer's, Huntington's, and Parkinson's diseases. Archives of Neurology, 50, 374–379. [Context Link]
Pillon, B., Deweer, B., Vidailhet, M., Bonnet, A. M., Hahn-Barma, V., & Dubois, B. (1998). Is impaired memory for spatial location in Parkinson's disease domain specific or dependent on “strategic” processes? Neuropsychologia, 36, 1–9. Bibliographic Links [Context Link]
Purcell, R., Maruff, P., Kyrios, M., & Pantelis, C. (1998a). Cognitive deficits in obsessive-compulsive disorder on tests of frontal-striatal function. Biological Psychiatry, 43, 348–357. Bibliographic Links [Context Link]
Purcell, R., Maruff, P., Kyrios, M., & Pantelis, C. (1998b). Neuropsychological deficits in obsessive-compulsive disorder: A comparison with unipolar depression, panic disorder, and normal controls. Archives of General Psychiatry, 55, 415–423. Bibliographic Links [Context Link]
Rademacher, J., Galaburda, A. M., Kennedy, D. N., Filipek, P. A., & Caviness, V. S. (1992). Human cerebral cortex: Localization, parcellation, and morphometry with magnetic resonance imaging. Journal of Cognitive Neuroscience, 4, 352–374. [Context Link]
Rauch, S. L., & Baxter, L. R. (1998). Neuroimaging in obsessive-compulsive disorder and related disorders. In M. A. Jenike, L. Baer, & W. E. Minichiello (Eds.), Obsessive-compulsive disorders: Practical management (3rd ed., pp. 289–317). St. Louis, MO: Mosby. [Context Link]
Rauch, S. L., Savage, C. R., Alpert, N. M., Dougherty, D., Kendrick, A., Curran, T., Brown, H. D., Manzo, P., Fischman, A. J., & Jenike, M. A. (1997). Probing striatal function in obsessive-compulsive disorder: A PET study of implicit sequence learning. Journal of Neuropsychiatry and Clinical Neuroscience, 9, 568–573. [Context Link]
Rauch, S. L., Whalen, P. J., Dougherty, D., & Jenike, M. A. (1998). Neurobiologic models of obsessive-compulsive disorder. In M. A. Jenike, L. Baer, & W. E. Minichiello (Eds.), Obsessive-compulsive disorders: Practical management (3rd ed., pp. 222–253). St. Louis, MO: Mosby. [Context Link]
Rugg, M. D., Fletcher, P. C., Allan, K., Frith, C. D., Frackowiak, R. S. J., & Dolan, R. J. (1998). Neural correlates of memory retrieval during recognition memory and cued recall. Neuroimage, 8, 262–273. Bibliographic Links [Context Link]
Savage, C. R. (1997). Neuropsychology of subcortical dementias. Psychiatric Clinics of North America, 20, 911–931. [Context Link]
Savage, C. R. (1998). Neuropsychology of OCD: Research findings and treatment implications. In M. A. Jenike, L. Baer, & W. E. Minichiello (Eds.), Obsessive-compulsive disorders: Practical management (3rd ed., pp. 254–275). St. Louis, MO: Mosby. [Context Link]
Savage, C. R., Baer, L., Keuthen, N. J., Brown, H. D., Rauch, S. L., & Jenike, M. A. (1999). Organizational strategies mediate nonverbal memory impairment in obsessive-compulsive disorder. Biological Psychiatry, 45, 905–916. Bibliographic Links [Context Link]
Savage, C. R., Keuthen, N. J., Jenike, M. A., Brown, H. D., Baer, L., Kendrick, A. D., Miguel, E. C., Rauch, S. L., & Albert, M. S. (1996). Recall and recognition memory in obsessive-compulsive disorder. Journal of Neuropsychiatry and Clinical Neuroscience, 8, 99–103. [Context Link]
Schwartz, J. M. (1997). Obsessive-compulsive disorder. Science & Medicine, 4(2), 14–23. [Context Link]
Schwartz, J. M., Stoessel, P. W., Baxter, L. R., Martin, K. M., & Phelps, M. E. (1996). Systematic changes in cerebral glucose metabolic rate after successful behavior modification. Archives of General Psychiatry, 53, 109 Bibliographic Links [Context Link]
Shallice, T. (1982). Specific impairments of planning. Philosophical transactions of the Royal Society of London. Biological Sciences, 298, 199–209. [Context Link]
Shimamura, A. P. (1995). Memory and frontal lobe function. In M. S. Gazzaniga (Ed.), The cognitive neurosciences (pp. 803–813). Cambridge, MA: MIT Press. [Context Link]
Shimamura, A. P., Janowsky, J. S., & Squire, L. R. (1991). What is the role of frontal lobe damage in memory disorders? In H. S. Levin, H. M. Eisenberg, & A. L. Benton (Eds.), Frontal lobe function and dysfunction (pp. 173–195). New York: Oxford University Press. [Context Link]
Shorr, J. S., Delis, D. C., & Massman, P. J. (1992). Memory for the Rey–Osterrieth figure: Perceptual clustering, encoding, and storage. Neuropsychology, 6, 43–50. Ovid Full Text [Context Link]
Squire, L. R. (1992). Memory and the hippocampus: A synthesis from findings with rats, monkeys, and humans. Psychological Review, 99, 195–231. Ovid Full Text [Context Link]
Swedo, S. E., Pietrini, P., Leonard, H. L., Schapiro, M. B., Rettew, D. C., Goldberger, E. L., Rapoport, S. I., Rapoport, J. L., & Grady, C. L. (1992). Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder: Revisualization during pharmacotherapy. Archives of General Psychiatry, 49, 690–694. Bibliographic Links [Context Link]
Veale, D. M., Sahakian, B. J., Owen, A. M., & Marks, I. M. (1996). Specific cognitive deficits in tests sensitive to frontal lobe dysfunction in obsessive-compulsive disorder. Psychological Medicine, 26, 1261–1269. Buy Now [Context Link]
Wagner, A. D., Desmond, J. E., Glover, G. H., & Gabrieli, J. D. E. (1998). Prefrontal cortex and recognition memory: Functional MRI evidence for context-dependent retrieval. Brain, 121, 1985–2002. Bibliographic Links [Context Link]
Weilburg, J. B., Mesulam, M. M., Weintraub, S., Bmonnano, F., Jenike, M. A., & Stakes, J. W. (1989). Focal striatal abnormalities in a patient with obsessive-compulsive disorder. Archives of Neurology, 46, 233–235. [Context Link]
Zachary, R. A. (1991). Shipley Institute of Living Scale: Revised manual. Los Angeles: Western Psychological Services. [Context Link]
Zielinski, C. M., Taylor, M. A., & Juzwin, K. R. (1991). Neuropsychological deficits in obsessive-compulsive disorder. Neuropsychiatry, Neuropsychology, and Behavioral Neurology, 4, 110–126. [Context Link]
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