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The Neuropsychological Syndrome of Agenesis of the Corpus Callosum

Published online by Cambridge University Press:  29 January 2019

Warren S. Brown*
Affiliation:
Fuller Graduate School of Psychology, Travis Research Institute, Pasadena, California
Lynn K. Paul
Affiliation:
California Institute of Technology, Division of Humanities and Social Sciences, Pasadena, California
*
Correspondence and reprint requests to: Warren S. Brown, Fuller Graduate School of Psychology 180 N. Oakland Avenue, Pasadena, CA 91101. E-mail: wsbrown@fuller.edu
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Abstract

Background: Agenesis of the corpus callosum (AgCC) involves congenital absence of all or part of the corpus callosum. Because the disorder can only be firmly diagnosed via neuroradiology, it has a short research history, and only recently has the cognitive syndrome become clear. Purpose: Our purpose is to review the primary deficits in AgCC that constitute the core syndrome. Conclusions: The cores syndrome includes: (1) reduced interhemispheric transfer of sensory-motor information; (2) reduced cognitive processing speed; and (3) deficits in complex reasoning and novel problem-solving. These domains do not appear to reflect different neuroanatomical abnormalities, but rather different domains of expression of reduced interhemispheric communication from callosal absence. Implications: These core deficits are expressed across various domains of cognitive, behavioral, and social functioning. The impact of these deficits varies across development and may be moderated by individual factors such as co-occurrence of other neurodevelopmental conditions, general intellectual capacity, and environmental support. (JINS, 2019, 25, 324–330)

Type
Short Review
Copyright
Copyright © The International Neuropsychological Society 2019 

INTRODUCTION

This study describes what we believe to be the core syndrome of agenesis of the corpus callosum (AgCC) as displayed in adults who have few, if any, other neurological abnormalities, and have grossly intact general intelligence. Although AgCC was previously thought to be exceedingly rare, increased clinical use of neuroimaging has resulted in higher detection rates in relatively normally functioning individuals. Studies conducted with this larger pool of patients are providing greater understanding of the role of the corpus callosum in cognition and behavior. The accumulating data also provides families and clinicians with more nuanced insights into the patterns of cognitive capacities that influence learning, daily behaviors, and developmental progression of individuals with AgCC.

AgCC is a congenital brain malformation defined by anatomy (complete or partial absence of the corpus callosum), and not defined by behavior abnormalities (as in autism). AgCC occurs due to disruption of neural development during the 7th to 20th embryonic weeks (Edwards, Sherr, Barkovich, & Richards, Reference Edwards, Sherr, Barkovich and Richards2014). The most recent evidence indicates that AgCC occurs in at least 1 in 4000 births, making it one of the more commonly occurring congenital brain disorders (Glass, Shaw, Ma, & Sherr, Reference Glass, Shaw, Ma and Sherr2008; Guillem, Fabre, Cans, Robert-Gnansia, & Jouk, Reference Guillem, Fabre, Cans, Robert-Gnansia and Jouk2003; Wang, Huang, & Yeh, Reference Wang, Huang and Yeh2004).

AgCC is often associated with a broader syndrome of brain malformation related to known toxic-metabolic conditions or genetic causes, but in 55–70% of AgCC cases the cause is unknown (Bedeschi et al., Reference Bedeschi, Bonaglia, Grasso, Pellegri, Garghentino, Battaglia and Borgatti2006; Schell-Apacik et al., Reference Schell-Apacik, Wagner, Bihler, Ertl-Wagner, Heinrich, Klopocki and von Voss2008; Tang et al., Reference Tang, Bartha, Norton, Barkovich, Sherr and Glenn2009). When part of broader neurodevelopmental syndromes or accompanied by other congenital brain malformations, the cognitive and behavioral impact of these other conditions would likely obscure the moderate to mild deficiencies directly related to callosal absence. To identify the specific contributions of the corpus callosum to higher cognitive abilities, this review describes the AgCC syndrome as it appears in individuals without any (or only very minor) other brain or body dysmorphology. These individuals typically have normal-range IQs and appear neurologically “asymptomatic” (i.e., lack of symptoms apparent in diagnostic procedures typically used in clinical neurology). In most of these individuals AgCC is discovered through routine prenatal sonogram or neuroimaging motivated by unrelated issues. In these cases, AgCC is likely to be the primary contributor to the cognitive outcome; thus, we refer to these individuals as having “Primary AgCC.”

Although they have a common primary neurological finding, individuals with Primary AgCC are somewhat heterogeneous with respect to other minor structural brain abnormalities, some of which appear to be secondary to the callosal dysgenesis (e.g., colpocephaly, Probst bundles) and some of which may or may not be related to the callosum (e.g., minor areas of heterotopia, interhemispheric cysts, interhemispheric lipoma). The group also varies with regard to amount of residual callosal connection (complete versus partial), and most likely varies at the molecular and synaptic level. To minimize the negative influence of concomitant neurological abnormalities, this review focuses on individuals with a full scale IQ above 80. Heterogeneity notwithstanding, we present what we believe to be the core syndrome that results in the mild to moderate cognitive and psychosocial deficits in Primary AgCC.

Finally, since the corpus callosum in neurotypical children is undergoing significant myelinization and functional development into the teenage years (Giedd et al., Reference Giedd, Castellanos, Casey, Kozuch, King, Hamburger and Rapoport1994; Yakovlev, Lecours, & Minkovski, Reference Yakovlev, Lecours and Minkovski1967), the neuropsychological and psychosocial outcomes of AgCC seem to “emerge” as their peers increase reliance on callosal connectivity. Thus, our commentary focuses on studies of older adolescents and adults.

CORE SYNDROME OF PRIMARY AgCC

The aim of this study is to briefly sketch the core syndrome of Primary AgCC (i.e., deficits specifically related to callosal absence), which in turn contributes to more specific neuropsychological and psychosocial deficits in AgCC. The following sections will offer evidence from published literature (including much of our own research) demonstrating that Primary AgCC is associated with a core syndrome involving: (1) reduced interhemispheric transfer of sensory-motor information; (2) increased cognitive processing time; (3) deficient processing of complex information and unfamiliar tasks, and amplified vulnerability to increases in cognitive demands.

These three domains of dysfunction are not independent. Reduced interhemispheric interactions likely contribute to slower processing time and difficulty in complex problem-solving, which are themselves inter-related. These core deficits contribute to many other specific deficiencies we describe briefly (see Figure 1).

Fig. 1 Agenesis of the corpus callosum, core syndrome, and specific deficits.

DIMINISHED INTERHEMISPHERIC INTEGRATION OF SENSORY-MOTOR INFORMATION

The current understanding of callosal function came primarily from studying individuals who had a surgical commissurotomy, severing all of the cerebral commissures as a treatment for epilepsy. Commissurotomy and AgCC both involve a lack of callosal connections between hemispheres, but they are distinguished by (1) the presence of the other cerebral commissures in most cases of AgCC (e.g., anterior commissure is present in all cases of AgCC we describe), and (2) by the point in development at which the hemispheres are disconnected. Early investigations of interhemispheric transfer and integration of sensory and motor information in AgCC discovered that congenital absence of callosal connections does not cause a full “disconnection syndrome” as is seen following commissurotomy (Bogen & Frederiks, Reference Bogen and Frederiks1985; Sperry, Reference Sperry1968; Sperry, Gazzaniga, Bogen, Vinken, & Bruyn, Reference Sperry, Gazzaniga, Bogen, Vinken and Bruyn1969).

Unlike commissurotomy, limitations of interhemispheric transfer in AgCC are contingent upon the complexity of information being transferred. Numerous studies have shown that individuals with AgCC are capable of interhemispheric integration of easily encoded visual and tactile information (e.g., Brown, Jeeves, Dietrich, & Burnison, Reference Brown, Jeeves, Dietrich and Burnison1999; Chiarello, Reference Chiarello1980; Jeeves & Ettlinger, Reference Jeeves and Ettlinger1965; Lassonde, Sauerwein, Chicoine, & Geoffroy, Reference Lassonde, Sauerwein, Chicoine and Geoffroy1991; Saul & Sperry, Reference Saul and Sperry1968). However, diminished interhemispheric transfer in AgCC is evident in studies requiring transfer of more complex (and less familiar) information (e.g., Brown et al., Reference Brown, Jeeves, Dietrich and Burnison1999; Bryden & Zurif, Reference Bryden and Zurif1970; Buchanan, Waterhouse, & West, Reference Buchanan, Waterhouse and West1980; Geffen, Nilsson, Quinn, & Teng, Reference Geffen, Nilsson, Quinn and Teng1985; Jeeves, Reference Jeeves1979).

A study by Brown et al. (Reference Brown, Jeeves, Dietrich and Burnison1999) illustrated key differences in interhemispheric transfer of sensory information in individuals with AgCC and individuals with commissurotomy through the use of two tachistoscopic bilateral visual field matching tasks (letters and dot-patterns). As predicted by studies of the “disconnection syndrome,” the two commissurotomy patients in this study could not match bilateral presentations of either letters or dot-patterns above the level of chance. In contrast, participants with AgCC performed as well as neurotypical controls when matching two bilaterally and simultaneously flashed letters, with their limitations in interhemispheric transfer only becoming evident in impaired bilateral visual field matching of the less familiar and less easily encoded random dot patterns.

The mediating effect of encoding complexity on interhemispheric transfer in AgCC has also been demonstrated in studies of tactual-spatial information transfer using the Tactual Performance Test (Dunn, Paul, Schieffer, & Brown, Reference Dunn, Paul, Schieffer and Brown2000; Sauerwein & Lassonde, Reference Sauerwein and Lassonde1994; Sauerwein, Lassonde, Cardu, & Geoffroy, Reference Sauerwein, Lassonde, Cardu and Geoffroy1981), Finger Localization Test (Dunn et al., Reference Dunn, Paul, Schieffer and Brown2000; Geffen et al., Reference Geffen, Nilsson, Quinn and Teng1985; Sauerwein & Lassonde, Reference Sauerwein and Lassonde1994), and tactual recognition (Jeeves & Silver, Reference Jeeves and Silver1988). As with visual transfer, individuals with AgCC exhibited intact performance at the lowest levels of sensory-motor difficulty, with significant declines in performance occurring as tasks requiring transfer of more complex (less easily encoded) information.

Finally, limitations in interhemispheric transmission also interfere with fine motor coordination of the two hands in individuals with AgCC (Jeeves, Silver, & Jacobson, Reference Jeeves, Silver and Jacobson1988; Jeeves, Silver, & Milner, Reference Jeeves, Silver and Milner1988), as well as in individuals with surgical transection of either the anterior or posterior callosum (Eliassen, Baynes, & Gazzaniga, Reference Eliassen, Baynes and Gazzaniga2000; Preilowski, Reference Preilowski1972). Using the Bimanual Coordination Test (BCT), a test based on an Etch-a-Sketch toy (Brown, Reference Brown1991), we found that bimanual motor coordination was slower and less accurate in adults with AgCC than in neurotypical adults (Mueller, Marion, Paul, & Brown, Reference Mueller, Marion, Paul and Brown2009), but performance of adults with AgCC was similar to that of neurotypical children for whom the corpus callosum was not yet fully developed (Marion, Kilian, Naramor, & Brown, Reference Marion, Kilian, Naramor and Brown2003). Notably, even in neurotypical adults, poor structural integrity of motor connections via the corpus callosum becomes more strongly associated with poor bimanual coordination performance as task complexity increases (Gooijers et al., Reference Gooijers, Caeyenberghs, Sisti, Geurts, Heitger, Leemans and Swinnen2013).

REDUCED SPEED OF COGNITIVE PROCESSING

Speed is a fundamental feature of all cognitive processes. Consequently, slow processing speed may interfere with abilities in multiple domains. Processing speed is highly vulnerable to disruptions in white matter connectivity, particularly the CC (Kourtidou et al., Reference Kourtidou, McCauley, Bigler, Traipe, Wu, Chu and Wilde2013; Mathias et al., Reference Mathias, Bigler, Jones, Bowden, Barrett-Woodbridge, Brown and Taylor2004; Solmaz et al., Reference Solmaz, Tunc, Parker, Whyte, Hart, Rabinowitz and Verma2017; Ubukata et al., Reference Ubukata, Ueda, Sugihara, Yassin, Aso, Fukuyama and Murai2016). Studies described in the previous section offer clear evidence of slowed sensory and motor reaction times in individuals with AgCC. Slow processing speed is also evident in other cognitive tests. For example, in a sample of 32 adults with complete AgCC, we found that WAIS-III processing speed index scores were significantly lower on average than verbal, perceptual, and working memory indices (Erickson, Young, Paul, & Brown, Reference Erickson, Young, Paul and Brown2013).

Slow processing speed was also implicated in a study of cognitive inhibition in adults with AgCC. On the Color-Word subtest of the Delis-Kaplan Executive Function System, we found deficient cognitive inhibition and flexibility in adults with AgCC compared to age- and IQ-matched controls, but regression analyses indicated that these differences in cognitive control were primarily the consequence of slowed processing speed (Marco et al., Reference Marco, Harrell, Brown, Hill, Jeremy, Kramer and Paul2012). Thus, processing speed limitations may have wide-ranging implications for cognition and behavior in AgCC. However, as found in studies of callosal damage in traumatic brain injury, impairments in processing speed are exacerbated on tasks with greater information processing demands (Mathias et al., Reference Mathias, Bigler, Jones, Bowden, Barrett-Woodbridge, Brown and Taylor2004).

DIFFICULTY WITH COMPLEX PROCESSING

Psychometric research in neurotypical adults has demonstrated that interhemispheric resources are recruited to assist with cognitively complex tasks (Koivisto, Reference Koivisto2000; Reuter-Lorenz, Stanczak, & Miller, Reference Reuter-Lorenz, Stanczak and Miller1999; Weissman & Banich, Reference Weissman and Banich2000) and simple tasks that are unfamiliar / unpracticed (Norman et al., Reference Norman, Jeeves, Milne and Ludwig1992). However, the benefit of interhemispheric processing decreases with practice (Cherbuin & Brinkman, Reference Cherbuin and Brinkman2005; Maertens & Pollmann, Reference Maertens and Pollmann2005; Weissman & Compton, Reference Weissman and Compton2003). In keeping with this finding, adults with Primary AgCC display amplified vulnerability to increases in cognitive demands, resulting in impaired reasoning, concept formation, and novel complex problem-solving, (i.e., deficits in fluid intelligence). By contrast, they do not have deficits in over-learned cognitive processes (i.e., crystallized intelligence), as supported by relatively normal (or even elevated) performance on most verbal and spatial portions of standardized intelligence scales (Erickson et al., Reference Erickson, Young, Paul and Brown2013) and on tests of basic academic skills such as single-word reading, spelling, and math calculation (Young, Erickson, Paul, & Brown, Reference Young, Erickson, Paul and Brown2013).

Impairments in abstract reasoning (Brown & Paul, Reference Brown and Paul2000; David, Wacharasindhu, & Lishman, Reference David, Wacharasindhu and Lishman1993; Gott & Saul, Reference Gott and Saul1978), concept formation (Fischer, Ryan, & Dobyns, Reference Fischer, Ryan and Dobyns1992; Imamura, Yamadori, Shiga, Sahara, & Abiko, Reference Imamura, Yamadori, Shiga, Sahara and Abiko1994), problem-solving (Brown, Anderson, Symington, & Paul, Reference Brown, Anderson, Symington and Paul2012; Schieffer, Paul, & Brown, Reference Schieffer, Paul and Brown2000), and generalization (Solursh, Margulies, Ashem, & Stasiak, Reference Solursh, Margulies, Ashem and Stasiak1965) have all been observed in patients with AgCC. Such deficiencies are particularly evident as task complexity increases (Schieffer, Paul, & Brown, Reference Schieffer, Paul and Brown2000). For example, on the simplified (color) version of the Raven’s Progressive Matrices Tests (Raven, Reference Raven1960, Reference Raven1965) performance of adults with AgCC was consistent with individual Full-Scale IQ (FSIQ) scores, but performance was impaired relative to FSIQ on the more complex Standard Progressive Matrices (Schieffer, Paul, & Brown, Reference Schieffer, Paul and Brown2000). The benefits of practice in Primary AgCC are supported by patterns of academic achievement in a sample of adults who performed within average range on basic mathematic calculations (a skill practiced throughout school), but exhibited significant deficits on math reasoning (Wechsler Individual Achievement Test-II; Hanna, Reference Hanna2018).

ASSOCIATED COGNITIVE AND PSYCHOSOCIAL DEFICIENCIES

These three core cognitive deficiencies impact a wider range of cognitive and psychosocial functioning. Adults with AgCC have difficulties encoding verbal and visual information in memory and spontaneously retrieving newly learned information (Erickson, Paul, & Brown, Reference Erickson, Paul and Brown2014; Paul, Erickson, Hartman, & Brown, Reference Paul, Erickson, Hartman and Brown2016), adequately understanding non-literal and complex language (Brown, Paul, Symington, & Dietrich, Reference Brown, Paul, Symington and Dietrich2005; Brown, Symington, Van Lancker-Sidtis, Dietrich, & Paul, Reference Brown, Symington, VanLancker, Dietrich and Paul2005; Paul, Van Lancker-Sidtis, Schieffer, Dietrich, & Brown, Reference Paul, Van Lancker-Sidtis, Schieffer, Dietrich and Brown2003; Rehmel, Brown, & Paul, Reference Rehmel, Brown and Paul2016), exerting cognitive inhibition and flexibility (Marco et al., Reference Marco, Harrell, Brown, Hill, Jeremy, Kramer and Paul2012), formulating strategies (Brown et al., Reference Brown, Anderson, Symington and Paul2012), and effectively applying imagination and creativity (Paul, Schieffer, & Brown, Reference Paul, Schieffer and Brown2004; Young et al., in press).

In addition, these core cognitive deficits negatively impact social and emotional cognition, resulting in difficulty reasoning abstractly about emotions in social context (Anderson, Paul, & Brown, Reference Anderson, Paul and Brown2017; Paul et al., Reference Paul, Lautzenhiser, Brown, Hart, Neumann, Spezio and Adolphs2006); expressing emotions in words (Pazienza, Brown, & Paul, Reference Pazienza, Brown and Paul2011); interpreting sarcasm and understanding subtle aspects of social interactions (Symington, Paul, Symington, Ono, & Brown, Reference Symington, Paul, Symington, Ono and Brown2010); recognizing emotion in faces (Bridgman et al., Reference Bridgman, Brown, Spezio, Leonard, Adolphs and Paul2014); imagining and inferring the mental, emotional, and social functioning of others (Kang, Paul, Castelli, & Brown, Reference Kang, Paul, Castelli and Brown2009; Turk, Brown, Symington, & Paul, Reference Turk, Brown, Symingtion and Paul2010); and awareness of functional deficits (Kaplan, Brown, Adolphs, & Paul, Reference Kaplan, Brown, Adolphs and Paul2012; Mangum, Reference Mangum2018; Miller, Su, Paul, & Brown, Reference Miller, Su, Paul and Brown2018). Although they appear to be secondary products of diminished interhemispheric interactions, slowed processing time, and deficient complex problem-solving, these associated cognitive and social deficits may result in functionally significant impairments in adaptive skills needed in daily life (Mangum, Reference Mangum2018; Miller et al, Reference Miller, Su, Paul and Brown2018) and reciprocal social communication (Paul, Corsello, Kennedy, & Adolphs, Reference Paul, Corsello, Kennedy and Adolphs2014).

MODERATING FACTORS

Expression of these core deficits will vary across the lifespan, as a consequence of neuroanatomic variations and concomitant conditions, and in relation to individual traits and context. We offer brief comments on each of these influences.

Since the corpus callosum in neurotypical children is undergoing significant myelinization and functional development into the teenage years (Giedd et al., Reference Giedd, Castellanos, Casey, Kozuch, King, Hamburger and Rapoport1994; Yakovlev et al., Reference Yakovlev, Lecours and Minkovski1967), the core deficits of AgCC described above may not become pronounced relative to peers before late childhood (Paul et al., Reference Paul, Brown, Adolphs, Tyszka, Richards, Mukherjee and Sherr2007). Consistent with this, we found that processing speed and problem-solving scores were consistent with FSIQ in younger children with Primary AgCC, but fell significantly below FSIQ in an older sample (over 13 years; Schieffer, Paul, Schilmoeller, & Brown, Reference Schieffer, Paul, Schilmoeller and Brown2000). Nonetheless, older children with AgCC may fall behind their peers when tasks are sufficiently complex (Garrels et al., Reference Garrels, Paul, Schieffer, Florendo, Fox, Turk and Brown2001) or novel (Young et al., Reference Young, Erickson, Paul and Brown2013) for their developmental level. Thus, tasks that can be mastered through practice, such as reading and arithmetic, are more likely to be impaired in children with AgCC than in adults. In contrast, tasks such as social interaction and complex problem-solving become increasingly complex in adolescence and remain complex and somewhat novel throughout life, posing an ongoing challenge to individuals with AgCC (e.g., Kang et al., Reference Kang, Paul, Castelli and Brown2009; Turk et al., Reference Turk, Brown, Symingtion and Paul2010; Mangum, Reference Mangum2018; Miller et al., Reference Miller, Su, Paul and Brown2018).

It is reasonable to expect that the impact of AgCC would vary in relation to degree of callosal absence, with partial AgCC resulting in less severe manifestations of these deficiencies than complete AgCC. However, although most of the research cited in this study focused on complete AgCC, studies that included persons with partial AgCC found their performances were distributed among the results of individuals with complete. While the explanation for this is not yet clear, it is possible that outcomes in partial AgCC are impacted by individual variations in how the remaining callosal interhemispheric connections are organized (Wahl et al., Reference Wahl, Strominger, Jeremy, Barkovich, Wakahiro, Sherr and Mukherjee2009).

Up to 45% of individuals with AgCC have a known chromosomal abnormality or recognizable genetic syndrome, often resulting in additional neuropathology and/or medical conditions (i.e., not Primary ACC). The nature and severity of these additional conditions will influence expression of the core deficits from AgCC and at the extreme may render the core deficits functionally irrelevant in daily life.

Finally, there is inherent variations between individuals, as well as environmental influences. For example, although general intelligence did not account for the core deficits described herein, general intelligence or specific skill sets may modulate an individual’s complexity threshold and markedly impact an individuals’ daily adaptive functioning.

CONCLUSION

Research has accumulated over the past 2 decades allowing for the description of a pattern of deficits characteristic of AgCC. We have argued for a core syndrome associated with callosal absence in AgCC involving reduced interhemispheric transfer of sensory-motor information, slowed cognitive processing speed, and deficits in complex reasoning and novel problem-solving. However, because these cognitive deficiencies are typically mild to moderate, they are often not easily recognized. It is our hope that a better description of the cognitive and psychosocial impact of AgCC will increase the likelihood of a diagnostic MRI in these high-functioning cases, as well as provide more complete information and helpful guidance to patients and their families regarding the likely consequences of this congenital brain disorder.

ACKNOWLEDGMENTS

The authors of this study declare that they have no conflicts of interest with respect to the writing of this study or the information contained. The writing of this study was also not supported by grant funding.

References

REFERENCES

Anderson, L. B., Paul, L. K., & Brown, W. S. (2017). Emotional intelligence in agenesis of the corpus callosum. Archives of Clinical Neuropsychology, 32(3), 267279. doi:10.1093/arclin/acx001 Google Scholar
Bedeschi, M. F., Bonaglia, M. C., Grasso, R., Pellegri, A., Garghentino, R. R., Battaglia, M. A., . . . Borgatti, R. (2006). Agenesis of the corpus callosum: clinical and genetic study in 63 young patients. Pediatric Neurology, 34(3), 186193. doi:10.1016/j.pediatrneurol.2005.08.008 Google Scholar
Bogen, J., & Frederiks, J. (1985). Split-brain syndromes. Handbook of clinical neurology (Vol. 45, pp. 99–106). Amsterdam, Netherlands: Elsevier Science Publishing Co.Google Scholar
Bridgman, M. W., Brown, W. S., Spezio, M. L., Leonard, M. K., Adolphs, R., & Paul, L. K. (2014). Facial emotion recognition in agenesis of the corpus callosum. Journal of Neurodevelopmental Disorders, 6, 32. doi:10.1186/1866-1955-6-32 Google Scholar
Brown, W. S. (1991). The Bimanual Coordination Test: Version 1. The Travis Research Institute Papers.Google Scholar
Brown, W. S., Anderson, L. B., Symington, M. F., & Paul, L. K. (2012). Decision-making in individuals with agenesis of the corpus callosum: Expectancy-valence in the Iowa Gambling Task. Archives of Clinical Neuropsychology, 27(5), 532544. doi:10.1093/arclin/acs052 Google Scholar
Brown, W. S., Jeeves, M. A., Dietrich, R., & Burnison, D. S. (1999). Bilateral field advantage and evoked potential interhemispheric transmission in commissurotomy and callosal agenesis. Neuropsychologia, 37(10), 11651180.Google Scholar
Brown, W. S., & Paul, L. K. (2000). Cognitive and psychosocial deficits in agenesis of the corpus callosum with normal intelligence. Cognitive Neuropsychiatry, 5(2), 135157.Google Scholar
Brown, W. S., Paul, L. K., Symington, M., & Dietrich, R. (2005). Comprehension of humor in primary agenesis of the corpus callosum. Neuropsychologia, 43, 906916.Google Scholar
Brown, W. S., Symington, M., VanLancker, D., Dietrich, R. & Paul, L. K. (2005). Paralinguistic processing in children with callosal agenesis: Emergence of neurolinguistic deficits. Brain and Language, 93, 135139. doi:10.1016/j.neuropsychologia.2004.09.008 Google Scholar
Bryden, M. P., & Zurif, E. B. (1970). Dichotic listening performance in a case of agenesis of the corpus callosum. Neuropsychologia, 8(3), 371377.Google Scholar
Buchanan, D. C., Waterhouse, G. J., & West, S. C. Jr. (1980). A proposed neurophysiological basis of alexithymia. Psychotherapy and Psychosomatics, 34, 248255.Google Scholar
Cherbuin, N., & Brinkman, C. (2005). Practice makes two hemispheres almost perfect. Cognitive Brain Research, 24(3), 413422.Google Scholar
Chiarello, C. (1980). A house divided? Cognitive functioning with callosal agenesis. Brain and Language, 11, 128158.Google Scholar
David, A. S., Wacharasindhu, A., & Lishman, W. A. (1993). Severe psychiatric disturbance and abnormalities of the corpus callosum: review and case series. Journal of Neurology, Neurosurgery, and Psychiatry, 56, 8593.Google Scholar
Dunn, C., Paul, L., Schieffer, B., & Brown, W. (2000). Spatial tactile interhemispheric transfer and task complexity in agenesis of the corpus callosum [Abstract]. Presented at the Twenty-Eighth Annual International Neuropsychological Society Conference: February 9–12, 2000 Denver, Colorado. Journal of the International Neuropsychological Society, 6(2), 165.Google Scholar
Edwards, T. J., Sherr, E. H., Barkovich, A. J., & Richards, L. J. (2014). Clinical, genetic and imaging findings identify new causes for corpus callosum development syndromes. Brain, 137, 15791613. doi:10.1093/brain/awt358 Google Scholar
Eliassen, J. C., Baynes, K., & Gazzaniga, M. S. (2000). Anterior and posterior callosal contributions to simultaneous bimanual movements of the hands and fingers. Brain, 123(Pt 12), 25012511.Google Scholar
Erickson, R. L., Paul, L. K., & Brown, W. S. (2014). Verbal learning and memory in agenesis of the corpus callosum. Neuropsychologia, 60, 121130. doi:10.1016/j.neuropsychologia.2014.06.003 Google Scholar
Erickson, R. L., Young, C., Paul, L. K., & Brown, W. S. (2013). WAIS-III index scores in individuals with agenesis of the corpus callosum [Abstract]. Presented at the Forty First Annual Meeting International Neuropsychological Society February 6–9, 2013 Waikoloa, Hawaii. Journal of the International Neuropsychological Society, 19(S1), 224.Google Scholar
Fischer, M., Ryan, S. B., & Dobyns, W. B. (1992). Mechanisms of interhemispheric transfer and patterns of cognitive function in acallosal patients of normal intelligence. Archives of Neurology, 49(3), 271277.Google Scholar
Garrels, S. R., Paul, L. K., Schieffer, B. M., Florendo, E. V., Fox, M. M., Turk, A. A., & Brown, W. S. (2001). Abstract problem solving in children with callosal agenesis [Abstract]. Presented at the Twenty-Ninth Annual International Neuropsychological Society Conference, February 14–17, 2001 Chicago, Illinois. Journal of the International Neuropsychological Society, 7(2), 258.Google Scholar
Geffen, G., Nilsson, J., Quinn, K., & Teng, E. L. (1985). The effects of lesions of the corpus callosum on finger localization. Neuropsychologia, 23, 497514.Google Scholar
Giedd, J. N., Castellanos, F. X., Casey, B. J., Kozuch, P., King, A. C., Hamburger, S. D., & Rapoport, J. L. (1994). Quantitative morphology of the corpus callosum in attention deficit hyperactivity disorder. American Journal of Psychiatry, 151(5), 665669.Google Scholar
Glass, H., Shaw, G., Ma, C., & Sherr, E. H. (2008). Agenesis of the corpus callosum in California 1983-2003: a population-based study. American Journal of Medical Genetics, 146A(19), 24952500. doi:10.1002/ajmg.a.32418 Google Scholar
Gooijers, J., Caeyenberghs, K., Sisti, H. M., Geurts, M., Heitger, M. H., Leemans, A., & Swinnen, S. P. (2013). Diffusion tensor imaging metrics of the corpus callosum in relation to bimanual coordination: effect of task complexity and sensory feedback. Human Brain Mapping, 34(1), 241245. doi:10.1002/hbm.21429 Google Scholar
Gott, P. S., & Saul, R. E. (1978). Agenesis of the corpus callosum: Limits of functional compensation. Neurology, 28(12), 12721279.Google Scholar
Guillem, P., Fabre, B., Cans, C., Robert-Gnansia, E., & Jouk, P. S. (2003). Trends in elective terminations of pregnancy between 1989 and 2000 in a French county (the Isère). Prenatal Diagnosis, 23(11), 877883. doi:10.1002/pd.711 Google Scholar
Hanna, S. D. (2018). Academic functioning in individuals with agenesis of the corpus callosum (Unpublished doctoral dissertation). Fuller Graduate School of Psychology, Pasadena, California.Google Scholar
Imamura, T., Yamadori, A., Shiga, Y., Sahara, M., & Abiko, H. (1994). Is disturbed transfer of learning in callosal agenesis due to a disconnection syndrome? Behavioural Neurology, 7, 4348.Google Scholar
Jeeves, M. A. (1979). Some limits to interhemispheric integration in cases of callosal agenesis and partial commissurotomy. In I. S. Russell, M. W. Van Hof, & G. Berlucchi (Eds.), Structure and function of the cerebral commissures (pp. 449474). London: McMillan.Google Scholar
Jeeves, M. A., & Ettlinger, E. G. (1965). Psychological studies of the three cases of congenital agenesis of the corpus callosum. Functions of the Corpus Callosum: CIBA Foundations Study Groups (Vol. 20, pp. 7394).Google Scholar
Jeeves, M. A., & Silver, P. H. (1988). Interhemispheric transfer of spatial tactile information in callosal agenesis and partial commissurotomy. Cortex, 24, 601604.Google Scholar
Jeeves, M. A., Silver, P. H., & Jacobson, I. (1988). Bimanual co-ordination in callosal agenesis and partial commissurotomy. Neuropsychologia, 26, 833850.Google Scholar
Jeeves, M. A., Silver, P. H., & Milner, A. D. (1988). Role of the corpus callosum in the development of a bimanual skills. Developmental Neuropsychology, 4, 305323.Google Scholar
Kang, K. H., Paul, L. K., Castelli, F., & Brown, W. S. (2009). Theory of mind in agenesis of the corpus callosum compared to high functioning autism [Abstract]. Poster presented at the Thirty-Seventh Annual Meeting International Neuropsychological Society: February 11–14, 2009 Atlanta, Georgia. Journal of the International Neuropsychological Society, 15(S1), 168. doi:10.1017/S1355617709090420 Google Scholar
Kaplan, J. M., Brown, W. S., Adolphs, R., & Paul, L. K. (2012). Psychological profile in agenesis of the corpus callosum [Abstract]. Poster presented at the Society for Neuroscience Annual Meeting: October 13–17, 2012 New Orleans, Louisiana. 198.19.Google Scholar
Kourtidou, P., McCauley, S. R., Bigler, E. D., Traipe, E., Wu, T. C., Chu, Z. D., . . . Wilde, E. A. (2013). Centrum semiovale and corpus callosum integrity in relation to information processing speed in patients with severe traumatic brain injury. Journal of Head Trauma Rehabilitation, 28(6), 433441. doi:10.1097/HTR.0b013e3182585d06 Google Scholar
Koivisto, M. (2000). Interhemispheric interaction in semantic categorization of pictures. Cognitive Brain Research, 9(1), 4551. PII: S0926-6410(99)00042-7.Google Scholar
Lassonde, M., Sauerwein, H., Chicoine, A. J., & Geoffroy, G. (1991). Absence of disconnexion syndrome in callosal agenesis and early callosotomy: brain reorganization or lack of structural specificity during ontogeny? Neuropsychologia, 29(6), 481495.Google Scholar
Maertens, M., & Pollmann, S. (2005). Interhemispheric resource sharing: Decreasing benefit with increasing processing efficiency. Brain and Cognition, 58(2), 183192. doi:10.1016/j.bandc.2004.11.002 Google Scholar
Mangum, R. (2018). Self-understanding of executive function in individuals with agenesis of the corpus callosum. (Unpublished doctoral dissertation). Fuller Graduate School of Psychology, Pasadena, California.Google Scholar
Marco, E. J., Harrell, K. M., Brown, W. S., Hill, S. S., Jeremy, R. J., Kramer, J. H., . . . Paul, L. K. (2012). Processing speed delays contribute to executive function deficits in individuals with agenesis of the corpus callosum. Journal of the International Neuropsychological Society, 18(3), 521529. doi:10.1017/s1355617712000045 Google Scholar
Marion, S. D., Kilian, S. C., Naramor, T. L., & Brown, W. S. (2003). Normal development of bimanual coordination: Visuomotor and interhemispheric contributions. Developmental Neuropsychology, 23(3), 399421. doi:10.1207/s15326942dn2303_6 Google Scholar
Mathias, J. L., Bigler, E. D., Jones, N. R., Bowden, S. C., Barrett-Woodbridge, M., Brown, G. C., & Taylor, D. J. (2004) Neuropsychological and information processing performance and its relationship to white matter changes following moderate and severe traumatic brain injury: A preliminary study, Applied Neuropsychology, 11(3), 134152. doi:10.1207/s15324826an1103_2 Google Scholar
Miller, J. S., Su, J. J., Paul, L. K., & Brown, W. S. (2018). Adaptive behavior in agenesis of the corpus callosum: Self and informant reports. [Abstract]. Presented at the Forty First Annual Meeting International Neuropsychological Society February 14–17, 2018 Washington, DC. Journal of the International Neuropsychological Society, 24(S1), 195.Google Scholar
Mueller, K. L. O., Marion, S. D., Paul, L. K., & Brown, W. S. (2009). Bimanual motor coordination in agenesis of the corpus callosum. Behavioral Neuroscience, 123(5), 10001011. doi:10.1037/a0016868 Google Scholar
Norman, W., Jeeves, M. A., Milne, A., & Ludwig, T. (1992). Hemispheric interactions: the bilateral advantage and task difficulty. Cortex, 28(4), 623642.Google Scholar
Paul, L. K., Brown, W. S., Adolphs, R., Tyszka, J. M., Richards, L. J., Mukherjee, P., & Sherr, E. H. (2007). Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity. Nature Reviews Neuroscience, 8(4), 287299. doi:10.1038/nrn2107 Google Scholar
Paul, L. K., Corsello, C., Kennedy, D. P., & Adolphs, R. (2014). Agenesis of the corpus callosum and autism: a comprehensive comparison. Brain, 137, 18131829. doi:10.1093/brain/awu070 Google Scholar
Paul, L. K., Erickson, R. L., Hartman, J. A., & Brown, W. S. (2016). Learning and memory in individuals with agenesis of the corpus callosum. Neuropsychologia, 86, 183192. doi:10.1016/j.neuropsychologia.2016.04.013 Google Scholar
Paul, L. K., Lautzenhiser, A., Brown, W. S., Hart, A., Neumann, D., Spezio, M., & Adolphs, R. (2006). Emotional arousal in agenesis of the corpus callosum. International Journal of Psychophysiology, 61(1), 4756. doi:10.1016/j.ijpsycho.2005.10.017 Google Scholar
Paul, L. K., Schieffer, B., & Brown, W. S. (2004). Social processing deficits in agenesis of the corpus callosum: narratives from the Thematic Appreciation Test. Archives of Clinical Neuropsychology, 19(2), 215225. doi:10.1016/S0887-6177(03)00024-6 Google Scholar
Paul, L. K., Van Lancker-Sidtis, D., Schieffer, B., Dietrich, R., & Brown, W. S. (2003). Communicative deficits in agenesis of the corpus callosum: nonliteral language and affective prosody. Brain and Language, 85(2), 313324. doi:10.1016/s0093- 934x(03)00062-2 Google Scholar
Pazienza, S. R., Brown, W. S., & Paul, L. K. (2011). Emotional expressiveness and somatization in agenesis of the corpus callosum. [Abstract]. Poster presented at the Thirty-Ninth Annual Meeting International Neuropsychological Society: February 2–5, 2011 Boston, Massachusetts USA. Journal of the International Neuropsychological Society, 17(S1), 2. doi:10.1017/S1355617711000415 Google Scholar
Preilowski, B. F. (1972). Possible contribution of the anterior forebrain commissures to bilateral motor coordination. Neuropsychologia, 10(3), 267277.Google Scholar
Raven, J. C. (1960). Guide to the standard progressive matrices. London: H.K. Lewis.Google Scholar
Raven, J. C. (1965). Guide to using the colored progressive matrices. London: H.K. Lewis.Google Scholar
Rehmel, J. L., Brown, W. S., & Paul, L. K. (2016). Proverb comprehension in individuals with agenesis of the corpus callosum. Brain and Language, 160, 2129. doi:10.1016/j.bandl.2016.07.00 1 Google Scholar
Reuter-Lorenz, P. A., Stanczak, L., & Miller, A. C. (1999). Neural recruitment and cognitive aging: Two hemispheres are better than one, especially as you age. Psychological Science, 10(6), 494500.Google Scholar
Sauerwein, H. C., & Lassonde, M. (1994). Cognitive and sensori-motor functioning in the absence of the corpus callosum: neuropsychological studies in callosal agenesis and callosotomized patients. Behavioural Brain Research, 64(1-2), 229240.Google Scholar
Sauerwein, H. C., Lassonde, M., Cardu, B., & Geoffroy, G. (1981). Interhemispheric integration of sensory and motor functions in callosal agenesis. Neuropsychologia, 19, 445454.Google Scholar
Saul, R. E., & Sperry, R. W. (1968). Absence of commissurotomy symptoms with agenesis of the corpus callosum. Neurology, 18, 307.Google Scholar
Schell-Apacik, C. C., Wagner, K., Bihler, M., Ertl-Wagner, B., Heinrich, U., Klopocki, E., . . . von Voss, H. (2008). Agenesis and dysgenesis of the corpus callosum: clinical, genetic and neuroimaging findings in a series of 41 patients. American Journal of Medical Genetics, 146A(19), 25012511. doi:10.1002/ajmg.a.32476 Google Scholar
Schieffer, B., Paul, L. K., & Brown, W. S. (2000). Deficits in complex concept formation in agenesis of the corpus callosum [Abstract]. Poster presented at the Twenty-Eighth Annual International Neuropsychological Society Conference: February 9–12, 2000 Denver, Colorado . Journal of the International Neuropsychological Society, 6(2), 164.Google Scholar
Schieffer, B., Paul, L. K., Schilmoeller, K., & Brown, W. S. (2000). Components of intelligence and basic achievement in agenesis of the corpus callosum [Abstract]. Poster presented at the Twenty-Eighth Annual International Neuropsychological Society Conference: February 9–12, 2000 Denver, Colorado. Journal of the International Neuropsychological Society, 6(2), 164.Google Scholar
Solmaz, B., Tunc, B., Parker, D., Whyte, J., Hart, T., Rabinowitz, A., . . . Verma, R. (2017). Assessing connectivity related injury burden in diffuse traumatic brain injury. Human Brain Mapping, 38(6), 29132922. doi:10.1002/hbm.23561 Google Scholar
Solursh, L. P., Margulies, A. I., Ashem, B., & Stasiak, E. A. (1965). The relationships of agenesis of the corpus callosum to perception and learning. Journal of Nervous and Mental Disease, 141(2), 180189.Google Scholar
Sperry, R. W. (1968). Hemisphere deconnection and unity in conscious awareness. American Psychologist, 23(10), 723733.Google Scholar
Sperry, R. W., Gazzaniga, M., Bogen, J., Vinken, P. J., & Bruyn, G. W. (1969). Interhemispheric relationships: the neocortical commissures; syndromes of hemisphere disconnection. Handbook of Clinical Neurology, 4, 273290).Google Scholar
Symington, S. H., Paul, L. K., Symington, M. F., Ono, M., & Brown, W. S. (2010). Social cognition in individuals with agenesis of the corpus callosum. Social Neuroscience, 5(3), 296308. doi:10.1080/17470910903462419 Google Scholar
Tang, P. H., Bartha, A. I., Norton, M. E., Barkovich, A. J., Sherr, E. H., & Glenn, O. A. (2009). Agenesis of the corpus callosum: an MR imaging analysis of associated abnormalities in the fetus. AJNR American Journal of Neuroradiology, 30(2), 257263. doi:10.3174/ajnr.A1331Google Scholar
Turk, A., Brown, W. S., Symingtion, M., & Paul, L. K. (2010). Social narratives in agenesis of the corpus callosum: linguistic analysis of the Thematic Apperception Test. Neuropsychologia, 48, 4350. doi:10.1016/j.neuropsychologia.2009.08.009 Google Scholar
Ubukata, S., Ueda, K., Sugihara, G., Yassin, W., Aso, T., Fukuyama, H., & Murai, T. (2016). Corpus callosum pathology as a potential surrogate marker of cognitive impairment in diffuse axonal injury. Journal of Neuropsychiatry and Clinical Neuroscience, 28(2), 97103. doi:10.1176/appi.neuropsych.15070159 Google Scholar
Wahl, M., Strominger, Z., Jeremy, R. J., Barkovich, A. J., Wakahiro, I., Sherr, E. H., & Mukherjee, P. (2009). Variability of homotopic and heterotopic callosal connectivity in partial agenesis of the corpus callosum: a 3T diffusion tensor imaging and q-ball tractography study. AJNR American Journal of Neuroradiology, 30(2), 282289. doi:10.3174/ajnr.A1361 Google Scholar
Wang, L. W., Huang, C. C., & Yeh, T. F. (2004). Major brain lesions detected on sonographic screening of apparently normal term neonates. Neuroradiology, 46(5), 368373. doi:10.1007/s00234-003-1160-4 Google Scholar
Weissman, D. H., & Banich, M. T. (2000). The cerebral hemispherescooperate to perform complex but not simple tasks. Neuropsychology, 14(1), 4159.Google Scholar
Weissman, D. H., & Compton, R. J. (2003). Practice makes a hemisphere perfect: The advantage of interhemispheric recruitment is eliminated with practice. Laterality: Asymmetries of Body, Brain, and Cognition, 8(4), 361375.Google Scholar
Yakovlev, P. I., Lecours, A., & Minkovski, A. (1967). The myelogenetic cycles of regional maturation of the brain. Regional Development of the Brain in Early Life (pp. 365).Google Scholar
Young, C. M., Erickson, R. L., Paul, L. K., & Brown, W. S. (2013). Academic achievement in children and adults with agenesis of the corpus callosum. Poster presented at the Forty First Annual Meeting International Neuropsychological Society February 6–9, 2013 Waikoloa, Hawaii. Journal of the International Neuropsychological Society, 19(S1), 44. doi:10.1017/S1355617713000362 Google Scholar
Young, C. M., Folsom, R. C., Paul, L. K., Su, J., Mangum, R., & Brown, W. S. (in press). Awareness of consequences in agenesis of the corpus callosum: semantic analysis of responses.Google Scholar
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Fig. 1 Agenesis of the corpus callosum, core syndrome, and specific deficits.