Based on the overall “impaired” versus “non-impaired” classification described above, we ended up with 30 subjects in the impaired group and 87 in the non-impaired group (see ). The two groups were not statistically different on any of the demographic parameters (per t-tests for Age (t(115) = 1.94, p = 0.06), Education (t(115) = 0.76, p = 0.45), and Chronicity (t(115) = 0.15, p = 0.88); per Chi Square tests for Sex (X2 = 0.04, p = 0.85) and Handedness (X2 = 0.09, p = 0.77)). The range for Chronicity was also similar between the two groups.
The results of the effective coverage maps (ECMs) are shown in , broken down for the overall impaired group and for the two subgroups with specific error types. The maps differ slightly as statistical power does not depend only on lesion coverage (i.e., the number of subjects with a lesion at a given voxel), but also on the proportion of subjects counted as having a deficit in the sample, which varies across error types. In total, there were 64 subjects with left hemisphere lesions and 53 subjects with right hemisphere lesions, and it can be seen that at the selected threshold, effective coverage is adequate in the convexities of both hemispheres, and in the underlying white matter. However, there are some brain regions that are not covered adequately for any conclusions to be reached, and it is important to note that we simply cannot comment on these regions, one way or another, vis-à-vis their potential importance for CDT performance. Those regions include the mesial cortices of both hemispheres, and the very anterior prefrontal (mainly polar) cortices of both hemispheres. Some subcortical structures are not covered sufficiently to yield reliable conclusions, either.
Figure 1 Effective Coverage Maps (ECMs) for the Clock Drawing Test. The ECMs show regions of the brain, in red, where significant effects of lesion-deficit relationships could be found at a threshold of P < 0.05 (uncorrected), if lesion-deficit relationships (more ...)
Neuroanatomical correlates of impaired CDT performance
The thresholded PM3 map for the 30 impaired subjects versus the 87 non-impaired subjects is shown in . The map shows that subjects who were impaired were clustered in two groups: (1) Subjects with lesions overlapping in the right hemisphere, with foci in the right parietal cortices (mostly in the supramarginal gyrus), the middle and superior temporal cortices, the frontal operculum, and the insula and underlying subcortical structures (including anterior basal ganglia); and (2) Subjects with lesions overlapping in the left inferior frontal-parietal opercular cortices, with foci in the inferior frontal gyrus, the lower sector of the precentral and postcentral gyri, the anterior sector of the supramarginal gyrus, and the insula and underlying basal ganglia.
Figure 2 Lesion-deficit relationships for the Clock Drawing Test. The Maps show regions of the brain, in red, where significant effects of lesion-deficit relationship were found at a threshold of P < 0.05 (uncorrected). Three series of maps are shown: (more ...)
Error pattern analysis
We conducted analyses in which the neuroanatomical correlates of CDT performances were analyzed with an eye to the types of qualitative error patterns produced by subjects in the impaired group (given the emphasis on qualitative scoring approaches in previous studies, as presented in the Introduction). A researcher blind to the lesions of the subjects (E.P.M.V.) classified CDT error types, using the methods suggested by Freedman et al. (1994)
. Of the 30 subjects with impaired CDT performance, it turned out that there were two predominant error patterns that characterized most of them (24/30): (1) impaired spatial organization, usually together with impaired number placement and/or omission of numbers (n = 11); and (2) impaired time (hand) setting, in the context of a relatively well drawn clock that had all the numbers in approximately the correct spatial locations (n = 13) (see for examples). (The remaining 6 subjects had various “other” types of errors, such as missing hands, distorted clock outlines, and mixed patterns that could not be readily classified into either of these error pattern types.) Following Freedman et al. (1994
; see also Fischer & Loring, 2004
), these two error patterns can be interpreted as impaired spatial analysis and spatial planning for the first type, and impaired linguistic and/or numeric processing in the second case, e.g., impaired comprehension of the time specifics in the clock drawing instructions.
A common cause of impaired spatial organization in drawing tests is left-sided neglect, and it is relevant to ask whether this was a common finding in our sample of 11 participants with impaired spatial organization types of errors. In looking through the impaired clocks in this group, it seemed that there could have been subtle signs of neglect in some of the performances, but these were not unequivocal and really could not be rated reliably as spatial neglect. This is not surprising, given that our participants were studied in the chronic epoch, when major spatial neglect has typically dissipated (we return to this point in the Discussion). Also, to give a sense of the range of impaired CDT performances in our sample, has examples of the “best” and the “worst” clocks from participants in the impaired group (as judged by an expert blind to the current study hypotheses).
Examples of “best” (A) and “worst” (B) impaired Clock Drawing Test performances from the sample of 30 participants with impaired clock drawing tests.
Using these different error patterns as a grouping variable, we analyzed the lesion commonalities in the subjects who comprised the two groups. This revealed the following results, depicted in the PM3 maps in :
- The first error pattern—the impaired spatial organization and number placement pattern—was much more frequent in subjects with right hemisphere lesions. In fact, all but one of the 11 subjects who produced this error type had right hemisphere lesions (). The PM3 map in indicates that the main areas of lesion overlap in these subjects were in the inferior frontal gyrus, with some effects in the middle frontal gyrus and in the ventral perirolandic region. There were also overlaps in the temporal lobe (mainly in the superior temporal gyrus), in the ventral occipitotemporal cortex (encompassing the posterior fusiform gyrus), and in the pericalcarine cortex. Also, there is significant lesion overlap in the insula, and in the anterior basal ganglia and white matter underneath the frontoparietal operculum.
Clock Drawing Test error types and associated lesion sites.
- The second error pattern—the time setting error pattern—was much more frequent in subjects with left hemisphere lesions. Specifically, 11 of the 13 subjects who produced this error type had left hemisphere lesions (). The PM3 map in indicates that the main areas of lesion overlap in these subjects were in the inferior frontal gyrus, the ventral perirolandic region (with extensions along the postcentral gyrus), the anterior supramarginal gyrus, the insula, and the superior temporal gyrus.
Other neuropsychological test performances
It was of interest to compare the two impaired CDT subgroups and the non-impaired group on several other tests, in order to analyze possible causes behind and other correlates of the error patterns. Specifically, adjuvant neuropsychological tests were chosen in order to ascertain whether the differences between CDT performances were accompanied by differences in other cognitive domains, such as intellectual functioning, language, visuospatial performance, and working memory, and to help substantiate our impression of why the different impaired CDT subgroups had failed the Clock Drawing Test. The data are presented in , and the groups were compared statistically with MANOVA. The groups did not differ on most of the WAIS-III scores, including overall Verbal IQ (p = 0.05), Performance IQ (p = 0.15), and the Digit Span subtest score (p = 0.38). However, the Impaired Time Setting group demonstrated lower performances on several language-related tests: Controlled Oral Word Association (COWA, F(2,108) = 9.79, p = 0.000, partial eta squared = 0.15; post-hoc analysis indicated that the Impaired Time Setting group was statistically different from the Non-impaired group (p = 0.000, 95% Confidence Interval for Difference = 6.4 to 24.5, Bonferroni adjusted)); Token Test (F(2,108) = 21.25, p = 0.000, partial eta squared = 0.28; post-hoc analysis indicated that the Impaired Time Setting group was statistically different from the Impaired Spatial Organization Group (p = 0.000, 95% Confidence Interval for Difference = 5.6 to 22.2, Bonferroni adjusted) and from the Non-impaired group, p = 0.000, 95% Confidence Interval for Difference = 10.1 to 22.1, Bonferroni adjusted)); Boston Naming Test (F(2,108) = 24.40, p = 0.000, partial eta squared = 0.31; post-hoc analysis indicated that the Impaired Time Setting group was statistically different from the Impaired Spatial Organization group (p = 0.000, 95% Confidence Interval for Difference = 13.9 to 34.9, Bonferroni adjusted) and from the Non-impaired group (p = 0.000, 95% Confidence Interval for Difference = 13.6 to 28.8, Bonferroni adjusted)). Subjects in the Impaired Spatial Organization group, by contrast, did not demonstrate defects on the language-related measures. Interestingly, though, the Impaired Spatial Organization group had lower scores on visuoconstruction and visuospatial tests, and the differences were statistically significant for the Block Design subtest from the WAIS-III (F(2,108) = 4.59, p = 0.012, partial eta squared = 0.08; post-hoc analysis indicated that the Impaired Spatial Organization group was statistically different from the Non-impaired group (p = 0.021, 95% Confidence Interval for Difference = 0.3 to 4.6, Bonferroni adjusted) and for the Facial Discrimination Test (F(2,108) = 3.70, p = 0.028, partial eta squared = 0.06; post-hoc analysis indicated that the Impaired Spatial Organization group was marginally different from the Non-impaired group (p = 0.068, 95% Confidence Interval for Difference = 0.2 to −6.8, Bonferroni adjusted). The groups were not statistically different on the Judgment of Line Orientation Test (p = 0.16).
Comparison of CDT subgroups on IQ and other neuropsychological variables (means, standard deviations in parentheses).
Overall, the findings support the notion that the CDT defects in the Impaired Time Setting group tended to be related to deficits in language processing (consistent with previous interpretations of this type of error pattern, e.g., Fischer & Loring, 2004
), whereas CDT defects in the Impaired Spatial Organization group tended to be related to visuoconstructional and visuospatial processing defects. These findings are perhaps not surprising, but they help give a broader picture in which the nature of CDT performance impairments and specific error types in our patients can be situated.
The right parietal region and CDT performance
As indicated in the Introduction, there has been historically a strong emphasis on the CDT being related to right parietal function. Thus, it was of interest to explore in more detail the nature of lesion-deficit relationships for the CDT and the right parietal region in the current sample of patients.
To begin with, in the error analysis presented above, it appeared that neither spatial organization impairments nor time setting impairments were associated with significant lesion-deficit relationships in the right parietal cortex, contrasting with the effect in the right parietal cortex found for overall impairments irrespective of error type (compare 2b and 2c with 2a). As it turned out, the right parietal effects indeed did not appear to be specific to error types: among the 8 subjects with CDT impairments and lesions that involved the right parietal region, 4 had impairments in spatial organization (3 for spatial organization per se and 1 for number placement), 2 had impairments in time setting, and 2 had other types of impairments (see ).
We explored the relationship between CDT performance and the right parietal region in more depth, taking both a brain-to-behavior approach and a behavior-to-brain approach. In the brain-to-behavior case, we investigated the extent to which right parietal damage was predictive of CDT defects in our sample. An anatomical ROI comprising the supramarginal gyrus and angular gyrus was delineated on our reference brain. To have what we considered “substantial” right parietal damage, a lesion had to encompass at least 40% of the supramarginal gyrus or angular gyrus. Considering all such lesions, the likelihood of having defective CDT performance following substantial right parietal damage was 50%. Also, the odds of having a CDT deficit following substantial right parietal damage was 3.4 times greater than the odds of a CDT deficit following damage anywhere else in the brain (sampled in our study).
In the behavior-to-brain case, we investigated the question of whether subjects presenting with deficits on the CDT would turn out to have a right parietal lesion. In our dataset, the likelihood of having substantial right parietal damage (as defined above) when presenting with a deficit on the CDT was 17.9%, as only 17.9% of the entire set of subjects with CDT deficits had right parietal lesions. This means that the proportion of lesions elsewhere in the brain when presenting a CDT deficit has to be larger than that, which indicates that CDT deficits per se are not a good predictor of right parietal lesions. To put the formulation in terms of an odds ratio (following the standard definition of odds: p/(1-p) for a given proportion p), the odds of having substantial right parietal damage when presenting with a deficit on the CDT were 38.3 times smaller than the odds of having damage elsewhere in the brain (as sampled in our study) when presenting a CDT deficit.
To summarize, we found overall a significant lesion-deficit relationship between impaired CDT performance and right parietal damage, but this relationship was not specific to error type. Also, our data suggest that having right parietal damage substantially raises the odds of performing defectively on the CDT, but having impaired CDT performance is not especially predictive of right parietal damage.