presents neuropsychological test summary scores for the control and patient groups for each of the broad cognitive domains sampled: intelligence, memory, working memory, and executive function. For each domain, MANCOVAs (covarying for education) revealed a significant overall multivariate effect for group. As can be seen in , patients with schizophrenia generally scored within the low-average range (80–89) on measures of intelligence and memory, and control participants scored, as expected, in the average range (90–109).
Neuropsychological Summary Scores for the Entire Sample and the DTI Subset of Patients With Schizophrenia and Control Participants
On the WAIS–III Full Scale, Verbal, and Performance IQs, MANCOVAs revealed a highly significant effect for group, F(1, 79) = 24.51, p < .001, but no significant interaction involving scale type (Verbal or Performance IQ). The patient group scored lower on both Verbal IQ (M = 86.20, SD = 12.73) and Performance IQ (M = 81.46, SD = 10.47) summary measures than did the control group (M = 109.28, SD = 12.86, and M = 103.33, SD = 14.98, respectively). For the WAIS–III index scores, MANCOVAs revealed a significant effect for group, F(1, 76) = 27.46, p < .001, but did not reveal a significant Group × Index Score interaction.
A similar pattern of findings emerged on the WMS–III index measures of memory. MANCOVAs revealed a highly significant group effect for measures of Immediate Recall, F(1, 73) = 8.95, p < .01, and Delayed Recall, F(1, 73) = 12.50, p = .001, but there was no interaction involving either modality of presentation (auditory or visual) or time interval (immediate or delayed). The patient group scored lower on both Auditory Immediate Memory (M = 81.09, SD = 20.42) and Visual Immediate Memory (M = 81.12, SD = 18.50) than did the control group (M = 105.86, SD = 13.64, and M = 99.83, SD = 16.12, respectively). Likewise, for Delayed Recall, the patient group scored lower on both Auditory Delayed Memory (M = 84.53, SD = 18.92) and Visual Delayed Memory (M = 82.74, SD = 19.89) than did the control group (M = 107.86, SD = 11.13, and M = 103.10, SD = 15.97, respectively). Thus, on these summary measures of intelligence and memory, patients with schizophrenia showed clear evidence of reduced levels of performance, as reflected by the highly significant group effects observed even when controlling for group differences in education. However, they did not show evidence of a distinct profile on either the memory or intelligence summary measures.
On the WCST, a measure of executive function, a MANCOVA focusing on the dependent measures of Categories Completed, Perseverative Errors, and Nonperseverative Errors revealed a highly significant group effect, F(2, 124) = 7.75, p = .001. The patient group completed fewer categories and made more perseverative and nonperseverative errors than did the control group. In addition, the patient group showed evidence of a different pattern of WCST performance from that of the control group, as reflected by the highly significant Group × WCST Response Measure interaction, F(2, 124) = 8.40, p < .001. The nature of this interaction indicated that the patient group showed evidence of a disproportionate amount of perseverative errors. However, the groups also differed significantly in overall total responses (p < .001), with the patient group requiring more responses (M = 119.21, SD = 17.44) than the control group (M = 96.73, SD = 23.27). Because error rates could have been confounded by these group differences in total WCST responses (i.e., more responses and higher likelihood of errors), a second MANCOVA with total WCST responses as the covariate was performed. The MANCOVA results again demonstrated a significant group effect, F(2, 140) = 3.58, p < .05, and the interaction remained significant even when controlling for group differences in total WCST responses, F(2, 140) = 4.49, p < .05. These analyses indicated that reduced numbers of categories achieved might be attributed to perseverative errors in the patient group.
also presents neuropsychological test scores for the subset of participants who completed DTI studies. As can be seen in , the subset of DTI patients with schizophrenia showed similarly reduced scores to those of the larger group for the WAIS–III summary measures of Full Scale IQ (M = 82.85, SD = 12.54), Verbal IQ (M = 84.33, SD = 14.65), and Performance IQ (M = 81.83, SD = 10.32), as well as for the WAIS–III index scores of Verbal Comprehension (M = 87.62, SD = 14.81), Perceptual Organization (M = 87.92, SD = 13.74), Working Memory (M = 85.69, SD = 14.66), and Processing Speed (M = 77.92, SD = 9.42). For the WMS–III summary measures, the DTI patients with schizophrenia also showed similarly reduced scores for Immediate (M = 73.09, SD = 22.05) and Delayed (M = 76.45, SD = 20.63) memory quotients as well as for Auditory Immediate Memory (M = 77.82, SD = 27.44), Visual Immediate Memory (M = 73.18, SD = 21.93), Auditory Delayed Memory (M = 80.82, SD = 25.21), Visual Delayed Memory (M = 76.18, SD = 23.96), and Working Memory (M = 87.40, SD = 14.62). Likewise, they exhibited means similar to those of the larger patient sample for WCST number of Categories Completed (M = 4.21, SD = 1.67), number of Perseverative Errors (M = 25.00, SD = 17.03), and number of Nonperseverative Errors (M = 16.50, SD = 8.23).
presents Pearson product–moment correlations for DTI measures of UF and neuropsychological tests of learning and memory, as indexed by the WMS–III. Among patients with schizophrenia but not control participants, reduced left UF fractional anisotropy correlated significantly and positively with reduced scores on the following WMS–III indexes: Immediate Memory (r = .712, p = .021), Auditory Immediate Memory (r = .680, p = .030), General–Delayed Memory (r = .792, p = .006), and Delayed Auditory Recognition (r = .764, p = .01). For the WCST, reduced left CB area correlated significantly with increased number of Nonperseverative Errors (r =−.637, p = .014) among patients but not control participants. These correlations remained significant even when controlling for total brain size, as assessed by intracranial content. Thus, among the patient group, DTI-derived UF and CB measures correlated with performance on different neuropsychological measures. Scatter plots of these significant correlations are presented in .
Pearson Correlations of WMS–III (n = 10) and WCST (n = 14) Scores for DTI-Derived Measures of the Uncinate Fasciculus and Cingulate Bundle Among Patients With Schizophrenia
Figure 3 Scatter plots of Pearson product–moment correlations of Wechsler Memory Scale—Third Edition (WMS–III) and Wisconsin Card Sorting Test (WCST) scores and diffusion-tensor-imaging derived measures of the left uncinate fasciculus and (more ...)
We next tested whether the significant correlations found only in the patient sample might reflect statistical evidence of a double dissociation between the left UF and declarative–episodic memory, on one hand, and the left CB and executive function, on the other hand. We entered both brain regions as predictors in a hierarchical regression analysis, first with WMS–III General Memory index and then with WCST Nonperseverative Errors as the dependent variable. For the WMS–III General Memory index, the left UF produced a significant R2 change of .652, F(2, 7) = 6.92, p = .022, in contrast to the nonsignificant R2 change of .014, F(1, 8) = 0.11, p = .747, accounted for by the left CB. Left UF and WMS–III General Memory index revealed a partial correlation value of .813 and a semipartial correlation value of .807, as compared with values of −.321 and −.196 for left CB and WMS–III General Memory index. These values indicated that the left UF uniquely accounted for 66% and 65% of the variance in WMS–III General Memory index scores. Further analyses demonstrated that only the left UF, β = .687, t(8) = 3.04, p = .019, contributed significantly to the WMS–III General Memory index.
By contrast, for WCST Nonperseverative Errors, the left CB produced a nearly significant R2 change of .370, F(2, 10) = 3.91, p = .056, in contrast to the nonsignificant R2 change of .069, F(1, 11) < 1, p > .35, accounted for by the left UF. Left CB and WCST Nonperseverative Errors revealed a partial correlation value of −.630 and a semipartial value of −.608, in comparison with values of .368 and .297 for left UF and WCST Nonperseverative Errors. These values indicated that the left CB uniquely accounted for 40% and 36% of the variance in WCST Nonperseverative Error scores. Likewise, the left CB, β = −.609, t(10) = −2.57, p = .028, but not the left UF, contributed significantly to WCST Nonperseverative Errors.
Finally, Pearson product–moment correlations revealed significant relationships between performance on other neuropsychological measures and UF fractional anisotropy values among the patient sample. Reduced right UF fractional anisotropy values correlated significantly with lower scores on the WMS–III Working Memory index (r = .803, p = .009) as well as on the WAIS–III measures of general intelligence (r = .640, p = .025), verbal intelligence (r = .638, p = .026), and verbal comprehension (r = .586, p = .045).