Our cohort of children, adolescents, and adults with isolated AgCC and FSIQ ≥ 80 performed significantly worse than matched controls in timed tasks of cognitive inhibition and flexibility. However, in analyses that also considered processing speed conditions, committed errors, and age, the group differences in executive tasks disappeared. Measures of processing speed explained most of the variance in executive test performance across groups, and in turn we found that group membership explained a significant amount of the variance on the processing speed tasks. Thus while individuals with agenesis of the corpus callosum showed real deficits on tasks of executive function, this impairment appeared to be primarily a consequence of slow cognitive processing.
Understanding the mechanism of the executive function deficits is crucial to crafting effective education programs. We begin our discussion by exploring the implication of slowed processing speed in this population. In the field of neuro-psychology, the term processing speed refers to the rate at which mental activities are performed (Lezak, Howieson, & Loring, 2004
). It is a fundamental feature of all cognitive processes, and in multi-step complex tasks, the rate-limiting impact of processing speed impairment becomes most evident. Because processing speed can be impacted by disruption of any neural system, slow processing speed is a common concern for individuals with brain injury and brain malformations (Beauchamp et al., 2011
; Jeeves, Ludwig, Moes, & Norman, 2001
). In AgCC, we posit that the absence of interhemispheric callosal connections might introduce a capacity limitation to the overall processing system, which then leads to concomitant deficits in higher order tasks such as response inhibition and switching.
Clearly, it is impossible to isolate overall processing speed using a single behavioral measure. Response generation introduces at least one additional cognitive process. For example, verbal responses in CWIT involve visual, linguistic and oral-motor systems, while grapho-motor responses on TMT involve visual and fine-motor systems. By measuring processing speed in these two different response modalities, we are able to more confidently generalize the similar findings on these measures to the shared construct of processing speed.
In summary, we see evidence for processing speed related deficits of executive function in tasks that involve both speaking and writing.
On the CWIT, the AgCC group exhibited significantly poorer performance than controls on the conditions that require cognitive inhibition and flexibility. The small to medium effect sizes on these comparisons indicate that group differences would remain (and possibly become stronger) in larger groups. Although response inhibition performance was more strongly related to scores on a test of linguistically mediated processing speed (Color Naming) than to group, we found a significant group difference on that processing speed task. This group difference in processing speed also had a small to medium effect size. This indicates that individuals with callosal agenesis and intact IQ are likely to exhibit deficits in response inhibition as a secondary consequence of their fundamental impairment in processing speed.
Similarly, performance on the inhibition-switching condition was more strongly correlated with performance on the inhibition task and with errors, than it was with group. Although the AgCC group made significantly more errors on this task, the small effect size suggests that this difference is not as robust as the group difference on inhibition. The CWIT findings were further supported by the TMT results. On the TMT, individuals with AgCC exhibited poorer performance than controls on the test of cognitive flexibility. This group difference had a small effect size and as with the CWIT executive function tasks, statistically significant group differences on the TMT executive task disappeared when controlling for processing speed scores. Most of the variance on the executive task was explained by Letter Sequencing performance and once again, the AgCC group was significantly slower than controls on the explanatory processing speed component.
Since the TMT processing speed measures require graphomotor activity in addition to higher-order cognition, it is important to note that the AgCC group did not show impaired performance on the motor-only subtest. Thus their lowered processing speed scores were not simply a product of impaired motor dexterity or motor speed. Previous studies concur that while individuals with both AgCC and corpus callosotomy show impairment in bimanual motor coordination, they are not deficient in simple unimanual response speed (Mueller et al., 2009
). The AgCC group’s pattern of intact motor performance with impaired performance on letter sequencing adds support to the hypothesis that slowed cognitive processing speed is a rate-limiting factor, which may not be notable during a simple motor task but becomes significantly evident on tasks that require interaction of multiple neural systems.
While individuals with AgCC commit more errors in general, the error score was only found to contribute to executive function in the CWIT-IS condition. This may reflect the additive cognitive demands of the inhibition and switching task. Furthermore, there is no evidence that the slow speed noted on all baseline and executive measures was due to excessive caution.
Processing speed deficits in AgCC likely result from an overall paucity of long-range connections, specifically the interhemispheric connections subserved by the corpus callosum in a typical brain. While individuals with AgCC do not experience the complete disconnection syndrome manifest by individuals with surgical callosotomy, they do exhibit diminished interhemispheric transfer of complex sensory information and learning (Paul et al., 2007
). It is speculated that the limited amount of interhemispheric transfer evident in AgCC is mediated by smaller interhemispheric commissures such as the anterior commissure. However, these much smaller commissures cannot compensate fully for the absence of ~ 200 million interhemispheric callosal axons in complete AgCC. There is now evidence from other developmental disorders indicating that reduced callosal connectivity, particularly in the splenium, is correlated with impairments in interhemispheric transfer, processing speed during complex tasks, visual-spatial processing, attention, motor coordination, and social skills (Paul, 2011
If slowed processing speed is a product of reduced callosal connectivity, it would follow that the degree of disconnection would mediate this cognitive performance. We did not find significant differences between the pAgCC and cAgCC groups on the executive test conditions of the CWIT or TMT, and the effect size of these contrasts was quite small. Although the test of trends did indicate that the pAgCC group performed at an intermediate level between cAgCC and HC (). In this study, the partial group performance was more similar to the complete agenesis group than to the controls. The finding of a trend offers limited support to the hypothesis that degree of callosal connectivity mediates the observed cognitive deficits. Since partial AgCC is characterized by considerable variability in the pattern of interhemispheric connectivity of the remaining callosal fibers, the cognitive outcome is also likely to be variable (Wahl et al., 2009
). Quantification of residual callosal connections in our pAgCC sample was beyond the scope of this study. However, it may be informative in future studies to correlate cognitive performance with the area and degree of residual callosal connectivity in the pAgCC subjects as assessed with MRI and DTI techniques. It is possible that the area and extent of the remnant connection will predict processing speed and abilities in particular cognitive domains.
The task demands in this study did not specifically challenge interhemispheric transfer of sensory information (i.e., stimuli were presented to both visual fields), thus we suggest that the processing speed deficits observed in our AgCC sample result from diminished sharing and coordination of processing load within and between hemispheres. CWIT performance for individuals with AgCC may have been additionally impacted by diminished functioning of the
anterior cingulate cortex, a region reported to show reduced volume in AgCC (Nakata et al., 2009
). In typical subjects, the anterior cingulate is recruited heavily during color-word inhibition (Pardo, Pardo, Janer, & Raichle, 1990
). It is possible that a slight weakness in anterior cingulate function in AgCC may be one of several factors which limit performance on tasks involving response inhibition.
This study applied group statistics and identified a clear pattern of deficient AgCC cohort performance relative to controls on both the CWIT and TMT; however, to apply this information within the context of clinical neuropsychology, it is also important to examine group and individual performance relative to published norms. As a group, the AgCC subjects’ mean scores were in low average range for CWIT completion times and average range for TMT completion times. There was notable variability at an individual level. If our subject groups were representative of the normative population, we would expect that approximately 5% of each group would score in the borderline-impaired range on each condition. This was, in fact, the case for our control group, with only one condition eliciting a slightly higher-than-expected percentage of borderline-impaired scores: 7.1% of controls scored at or below 5th percentile on CWIT Inhibition/Switching. In striking contrast, the percentage of the AgCC group that scored in borderline-impaired range was notably elevated on all subtests except TMT Motor Sequencing (5.5%). On the TMT completion times, 19.4% of the AgCC group scored at or below 5th percentile on Number Sequencing, and ~ 17% fell in that range on Visual Search, Letter Sequencing, and Number-Letter Switching. The percentage of AgCC subjects scoring in impaired range wasmore notable for the CWIT completion time, with 25% impaired on Color Naming, 31.5% on Word Reading, 38.9% on Inhibition, and 41.7% on Inhibition-Switching task. Thus, it appears that the pattern of weaknesses we described at a group level is likely to appear in individual neuropsychological evaluations. However, this also shows us that it may be difficult for clinicians and educators doing evaluations to identify these subtle but real deficits in processing speed: deficits which have considerable impact on daily living skills and academics.
While this study provides the most comprehensive examination to date of inhibition, cognitive flexibility, and processing speed in AgCC, participants were limited to those with general cognition in the typical range. Results cannot necessarily be extrapolated to individuals with lower cognitive abilities or those with additional anatomic differences or intractable epilepsy. To ascertain how generalized or specific this finding might be, it would be informative to examine a broader range of the AgCC population and also to explore inhibition and cognitive flexibility using tasks without processing speed demands and that are not mediated by language or motor ability. Finally, the findings of this study regarding processing speed leave open the question of processing speed in other task domains, as well as the possibility of deficits in other aspects of executive function not addressed using the CWIT and TMT. Future studies assessing processing speed, such as simple and choice reaction times, will serve to better understand this populations’ deficit and inform remediation approaches. In addition, to parse out the contributions of particular cortical regions and the role of inter- and intrahemispheric transfer, future studies will need to measure and control for interhermispheric transfer time within a functional imaging assessment.
In summary, this study suggests that executive deficits result from primary cognitive impairment in individuals with AgCC as well as from profound cognitive slowing. These findings yield exciting treatment implication as processing speed deficits in other conditions (e.g., traumatic brain disorder, multiple sclerosis, aging, and schizophrenia) are now being approached through pharmacologic interventions (Parry, Scott, Palace, Smith, & Matthews, 2003
; Sawyer, Mauro, & Ohlinger, 2008
; Tenovuo, 2005
; Whyte, et al., 1997
). Computer brain training methods are beginning to show promising results for individuals with schizophrenia and speed of processing interventions are showing lasting benefits in aging adults (Fisher, Holland, Subramaniam, & Vinogradov, 2010
; Grynszpan et al., 2010
; Wolinsky et al., 2010
). The simplest intervention, allowing children to have additional time to understand presented material and produce responses is an adaptation that can easily be implemented and will likely benefit learning, group engagement, and frustration-related behavior.
Individuals with AgCC provide an important cohort for future processing speed investigations. In addition to treatment trials, research directions should include the characterization and correlation of the degree of agenesis and connectivity of remaining fibers in the pAgCC group using morphometric MRI and DTI techniques. This study focused on dissecting the role of processing speed with respect to inhibition control and cognitive flexibility; however, there are clearly other areas of challenge (e.g., social ability and success) that must be investigated to gain a fuller understanding of the needs for this group.