Anatomy of the Corpus Callosum Reveals Its Function

The Journal of Neuroscience, February 13, 2008 • 28(7):1535–1536 • 1535

Journal Club

Editor’s Note: These short critical reviews of recent papers in the Journal, written exclusively by graduate students or postdoctoral fellows, are intended to summarize the important findings of the paper and provide additional insight and comentary. For more information on the format and purpose of the Journal Club, please see http://www.jneurosci.org/misc/ifa_features.shtml.

Eric Mooshagian Department of Psychology, University of California, Los Angeles, California 90095-1563 Review of Wahl et al. (http://www.jneurosci.org/cgi/content/full/27/45/12132)

The corpus callosum (CC) comprises ax- views of the CC. In contrast, a few recent amining callosal topography, suggesting a ons connecting the cortices of the two ce- studies have used diffusion tensor imag- more posterior crossing of CMFs (for dis- rebral hemispheres and is the principal ing (DTI) methods to re-evaluate callosal cussion, see Wahl et al., 2007). In addi- white matter fiber bundle in the brain. As topography (for discussion, see Wahl et tion, the present study goes beyond a recently as the mid 20th century, the CC al., 2007). These methods challenge the demonstration of topography by reveal- was thought to serve no other purpose conventional partitioning schemes used ing, for the first time, a clear somatotopy than preventing the two hemispheres to divide the CC into functionally signifi- of CMFs; hand fibers were situated ventral from collapsing on one another (Bogen, cant regions (Witelson, 1989). and anterior to foot fibers, and lip fibers, 1979). This cynical view was attributable In their recent article published in The for the one subject in which they were vi- to the failure of the Van Wagenen/Ake- Journal of Neuroscience, Wahl et al. (2007) sualized successfully, were localized ante- laitis split-brain surgery to reveal strong revisit the issue of CC topography using rior to the hand fibers [Wahl et al. (2007), disconnection symptoms. The work of functional MRI (fMRI) and DTI to assess their Figs. 2b (http://www.jneurosci.org/ Myers and Sperry (1958) in the 1950s callosal motor fiber (CMF) microstruc- cgi/content/full/27/45/12132/F2), 4 (http:// changed this by definitively confirming ture in vivo. Their participants performed www.jneurosci.org/cgi/content/full/27/45/ the functional role of the CC in the inter- a simple, visually guided motor task that 12132/F4)]. hemispheric transfer of visual informa- included alternating blocks of pursing Next, the authors extended this imag- tion in animals. Since then, the structure lips, flexing left-hand fingers, right-hand ing approach using a paired-pulse trans- and function of the CC have remained fingers, left toes, and right toes, and a rest cranial magnetic stimulation (TMS) topics of continuous investigation (Zaidel condition, all while being scanned. DTI paradigm to assess the functional connec- and Iacoboni, 2003). In particular, re- analysis allows one to quantify the magni- tivity between the primary (M1) hand ar- searchers have asked how callosal struc- tude and direction of water diffusion (i.e., eas of each cerebral hemisphere, thereby ture relates to callosal function (i.e., hemi- fractional anisotropy). Because diffusion measuring interhemispheric inhibition. spheric specialization and interaction). of water molecules is hindered by the ax- The paired-pulse TMS approach involves One pioneering study of callosal mor- onal membrane and myelin sheath, the measuring the effect of a conditioning phology relied on light microscopy of molecules disperse primarily in the direc- pulse on the motor-evoked potential postmortem specimens to look at callosal tion of the fiber tract, thus allowing one to (MEP) elicited by a second, test pulse. The structure and fiber composition (Aboitiz infer the overall orientation of white mat- conditioning pulse was given over the left et al., 1992), but most anatomical studies ter fibers. M1, and the test pulse was given over the of humans have relied on structural magnetic resonance imaging (MRI) mor- The results of this study revealed a to- right M1. The intensity of the condition- phometry of midsagittal cross-section pographic organization of CMFs in the ing pulse varied between 100 and 150% of CC. Whereas previous anatomical studies individuals’ resting motor threshold, in suggested that CMFs cross primarily 10% intervals. Interhemispheric inhibi- Received Dec. 7, 2007; revised Jan. 7, 2008; accepted Jan. 10, 2008. I thank Teresa Esch and Eran Zaidel and the members of his laboratory through the anterior midbody of the CC, tion threshold was measured as the per- for constructive comments and discussion on a previous draft of this Wahl et al. (2007) found that CMFs cross centage of maximum stimulator output manuscript. through the posterior body and isthmus required for a 25 or 50% inhibition. The Correspondence should be addressed to Eric Mooshagian, Department [Wahl et al. (2007), their Fig. 2b (http:// authors found a positive correlation be- ofPsychology,UniversityofCalifornia,LosAngeles,Box951563,LosAnge- www.jneurosci.org/cgi/content/full/27/ tween fractional anisotropy of hand les, CA 90095-1563. E-mail: [email protected]. DOI:10.1523/JNEUROSCI.5426-07.2008 45/12132/F2)]. These results are in agree- CMFs and the magnitude of interhemi- Copyright©2008SocietyforNeuroscience 0270-6474/08/281535-02$15.00/0 ment with other previous DTI studies ex- spheric inhibition measured physiologi- 1536 • J. Neurosci., February 13, 2008 • 28(7):1535–1536 Mooshagian • Journal Club cally [Wahl et al. (2007), their Fig. 5a subjects and take into account differences raphy and somatotopy relate to asymmet- (http://www.jneurosci.org/cgi/content/ in individual anatomy, which show signif- rical callosal transfer. full/27/45/12132/F5)] and a negative cor- icant variation [Wahl et al. (2007), their In summary, Wahl et al. (2007) dem- relation between fractional anisotropy of Fig. 3 (http://www.jneurosci.org/cgi/con- onstrate that novel MRI and TMS tech- hand CMFs with threshold intensity tent/full/27/45/12132/F3)]. Specifically, niques can be effectively combined to in- [Wahl et al. (2007), their Fig. 5b (http:// data of the sort presented by Wahl et al. vestigate the link between structure and www.jneurosci.org/cgi/content/full/27/ (2007) allow one to partition the CC into function in vivo in human subjects. Their 45/12132/F5)]. Fractional anisotropy of functionally meaningful regions. More- results suggest that the role of the CC in foot CMFs did not correlate with either over, the promise of the techniques de- interhemispheric integration, as it relates the magnitude or the threshold intensity scribed in their study is that they can relate to structure, should be re-examined in of interhemispheric inhibition [Wahl et individual variations in brain structure to light of the new approaches to studying al. (2007), their Fig. 5c,d (http://www. individual differences in behavior. the morphometry and morphology of the jneurosci.org/cgi/content/full/27/45/ The paired-pulse TMS approach to CC. It will be useful in future experiments 12132/F5)]. In short, the results demon- linking the observed microstructure to to reconsider the relationship between in- strate that the microstructure (measured function is not without its limitations, dividual callosal anatomy and behavioral by fractional anisotropy) of callosal fibers however; it seems best suited to studying laterality measures (Clarke and Zaidel, predicts their function (measured by in- CMFs, as it was used in this study. It is not 1994). terhemispheric inhibition). clear how TMS can be easily implemented Heretofore, the relationship between to demonstrate connectivity for fibers References CC morphometry and hemispheric spe- Aboitiz F, Scheibel AB, Fisher RS, Zaidel E (1992) subserving other functions (e.g., auditory cialization has been explored by correlat- Fiber composition of the human corpus callo- or visual). For example, the phosphenes ing the midsagittal callosal area with per- sum. Brain Res 598:143–153. evoked by TMS over visual cortical re- Bogen JE (1979) The callosal syndromes. In: formance on behavioral laterality tests gions are subjective, and they do not pro- Clinical neuropsychology (Heilman KM, (Clarke and Zaidel, 1994). These studies vide a convenient, quantifiable measure as Valenstein E, eds), pp 308–359. New York: have relied on partitioning schemes that Oxford UP. obtain regions based on fractions of the do MEPs for TMS over motor regions. Clarke JM, Zaidel E (1994) Anatomical- longest rostral-caudal CC length (Witel- The work by Wahl et al. (2007) leaves a behavioral relationships: corpus callosum son, 1989). Thus, researchers inferred the few open questions. For example, they morphometry and hemispheric specialization. Behav Brain Res 64:185–202. function of a callosal region and, in turn, only look at homotopic cortical regions; their DTI analysis was constrained such Myers RE, Sperry RW (1958) Interhemispheric the fibers within the region, from behav- communication through the corpus callosum: ior (Clarke and Zaidel, 1994). In their that heterotopic connections were not mnemonic carry-over between the hemi- study, Wahl et al. (2007) used DTI to vi- considered. It would also be useful to ap- spheres. AMA Arch Neurol Psychiatry sualize, on an individual basis, where ply the same DTI analysis approach to vi- 80:298–303. CMFs cross in the CC. The authors sug- sualization of heterotopic callosal fibers Wahl M, Lauterbach-Soon B, Hattingen E, Jung P, Singer O, Volz S, Klein JC, Steinmetz H, Zi- gest that their approach may provide a (e.g., those between premotor or supple- mentary motor and primary motor corti- emann U (2007) Human motor corpus cal- useful way to better understand the func- losum: topography, somatotopy, and link be- tional relevance of fiber pathways in the ces) and determine whether these fibers tween microstructure and function. human brain. Indeed, the combined use share the same somatotopy observed in J Neurosci 27:12132–12138. of fractional anisotropy with TMS, partic- their study. Furthermore, Wahl et al. Witelson SF (1989) Hand and sex differences in ularly the paired-pulse design, offers a (2007) only considered left-to-right inter- the isthmus and genu of the human corpus powerful new approach to examining the hemispheric inhibition, although asym- callosum. A postmortem morphological study. Brain 112:799–835. link between structure and function of metry in callosal transfer has been docu- Zaidel E, Iacoboni M, eds (2003) The parallel callosal fibers. Moreover, it is now possi- mented (Zaidel and Iacoboni, 2003). brain: the cognitive neuroscience of the cor- ble to go past gross morphometry across Thus, it remains to be seen how CC topog- pus callosum. Cambridge, MA: MIT.