Dynamic network structure of INAUGURAL ARTICLE interhemispheric coordination Karl W. Dorona, Danielle S. Bassettb,c, and Michael S. Gazzanigaa,c,1 Departments of aPsychological and Brain Sciences and bPhysics, and cSage Center for the Study of the Mind, University of California, Santa Barbara, CA 93106 This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected in 2011. Contributed by Michael S. Gazzaniga, September 21, 2012 (sent for review August 5, 2012) Fifty years ago Gazzaniga and coworkers published a seminal arti- in animals were used to characterize the spatial and temporal cle that discussed the separate roles of the cerebral hemispheres in properties of interhemispheric cross-talk between homologous humans. Today, the study of interhemispheric communication is regions of visual cortex. Subsequent studies further demonstrated facilitated by a battery of novel data analysis techniques drawn that functional coherence, as measured by oscillatory synchroni- from across disciplinary boundaries, including dynamic systems the- zation, is mediated by corticocortical connections passing through ory and network theory. These techniques enable the characteriza- the corpus callosum. This interhemispheric communication tion of dynamic changes in the brain’s functional connectivity, facilitates the binding of features within and between the visual fi thereby providing an unprecedented means of decoding interhemi- hemi elds (12). spheric communication. Here, we illustrate the use of these techni- Complementing examination of the functional role of the cor- ques to examine interhemispheric coordination in healthy human pus callosum, anatomical studies demonstrated that the callosum participants performing a split visual field experiment in which can be divided along its anteroposterior axis into regions with distinct projection topographies (13). These regions differ in terms they process lexical stimuli. We find that interhemispheric coordi- of their axon density, their size, and the myelination of projections. nation is greater when lexical information is introduced to the right Such variations in callosal microstructure relate to the type of in- hemisphere and must subsequently be transferred to the left hemi- formation being transferred within a given callosal region (14, 15). sphere for language processing than when it is directly introduced Large, heavily myelinated fibers allow for rapid interhemispheric fi NEUROSCIENCE to the language-dominant (left) hemisphere. Further, we nd that integration of primary sensory-motor information, whereas finer, fi putative functional modules de ned by coherent interhemispheric less myelinated fibers allow for intrahemispheric consolidation of coordination come online in a transient manner, highlighting the more complex multimodal information before interhemispheric underlying dynamic nature of brain communication. Our work illus- communication. Conceivably, smaller fibers that delay inter- trates that recently developed dynamic, network-based analysis hemispheric communication might reduce interference from con- techniques can provide novel and previously unapproachable flicting signals and allow for the segregated processing of in- insights into the role of interhemispheric coordination in cognition. formation within task-specialized hemispheres. PHYSICS community detection | network dynamics | split-brain | Neuroimaging and Network Theory temporal network | neural oscillations The relatively recent development of a host of novel noninvasive neuroimaging techniques has facilitated the examination of in- he field of split-brain research began several decades ago with terhemispheric connectivity at a much larger spatial scale than Tthe use of a drastic surgical solution for intractable epilepsy was previously possible. Functional [functional MRI, EEG, and (1–3): the severing of the corpus callosum. This procedure sig- magnetoencephalography (MEG)] and structural [MRI and nificantly decreased the connectivity between the hemispheres, diffusion tensor imaging (DTI)] neuroimaging methods can be thereby irrevocably altering interhemispheric communication. used to examine the functional and structural connectivity be- Although a few interhemispheric pathways remained through tween hemispheres, respectively. Noninvasive diffusion imaging fi subcortical structures and the anterior commissure, examination of the intact brain has identi ed the strength and density of in- fi of callosal function using split visual field experiments clearly terhemispheric communication bers in beautiful detail, poten- demonstrated its role in interhemispheric communication (2). tially providing us with unique information about the targets and The callosal projection plays a particularly crucial role in a vari- function of callosal projections. Studies combining DTI and ety of sensory-motor integrative functions of the two hemi- behavioral measures have demonstrated a relationship between spheres (4), shows changes with age, and demonstrates the callosal microstructure and task performance under a range of – potential for dynamic changes with training (5). In fact, experi- cognitive and perceptual conditions (16 18). Indeed, individual ments in patients with severance of the callosum revealed that it differences in callosal organization might profoundly affect the subserves a large range of behaviors and cognitive functions that information integration between the hemispheres (2, 19). underlie the varied workings of the mind. Collectively, these neuroimaging techniques have underscored Interhemispheric communication has been studied using two the large-scale interconnectedness of the human brain in general basic approaches. The first uses behavioral experiments to examine and the unique connection pathways mediated by the corpus cal- cognitive phenotypes, and the second uses neuroscientificexperi- losum in particular. Recent advances in mathematics, sociology, ments to examine brain phenotypes. Split-brain research initially and physics have provided a means to characterize such connec- focused on the former: Patients demonstrated striking behavioral tion patterns quantitatively as networks in which nodes represent phenotypes that provided clues regarding the underlying mechanics of brain communication. For example, although most perceptual processing appears to be isolated in each hemisphere following Author contributions: K.W.D. designed research; K.W.D. performed research; D.S.B. con- surgery, some attentional and emotional mechanisms initiated in tributed new reagents/analytic tools; K.W.D. and D.S.B. analyzed data; and K.W.D., D.S.B., one hemisphere can still be communicated to the other, cortically and M.S.G. wrote the paper. disconnected, hemisphere (6). The authors declare no conflict of interest. Complementing behavioral experiments, neuroscientific stud- Freely available online through the PNAS open access option. ies provided measurements of both functional and anatomical 1To whom correspondence should be addressed. E-mail: [email protected]. properties of the callosal body (7–11). For example, to understand This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. the functional role of the callosum, electrophysiological recordings 1073/pnas.1216402109/-/DCSupplemental. www.pnas.org/cgi/doi/10.1073/pnas.1216402109 PNAS Early Edition | 1of8 Downloaded by guest on September 28, 2021 brain regions and edges represent connections between those frequency activity. At an even larger scale, low-frequency brain regions (20–29). Network science provides a novel and potentially rhythms might enable the dynamic evolution of whole-brain net- critical framework in which to understand interhemispheric com- works at behavioral time scales (41, 42). munication at the scale of large interconnected areas. Taken together, these results suggest that successful in- In this paper, we illustrate the potential of combining non- terhemispheric transfer of the information necessary to perform invasive neuroimaging techniques with new analytical methods our split visual field experiment accurately depends on a combi- derived from network theory to provide insight into the mecha- nation of oscillatory activity in multiple frequency bands and nisms underlying interhemispheric communication. Using a split across distributed networks of brain areas. visual field experiment, we examine brain activity measured using MEG in healthy subjects processing lexical stimuli. By determining Dynamic Network Construction the correlated oscillatory activity between sensors over short time An exhaustive assessment of frequency-specific communication intervals, we quantify the dynamic evolution of interhemispheric patterns is outside the scope of the present study. Instead, we focus connectivity during task processing. We conclude by suggesting on a frequency band that has been shown to facilitate spatial at- that the application of dynamic network theory to neuroimaging tention and enable information transfer between the cerebral data might be important for the future of brain research in a hemispheres (43, 44): the low-frequency amplitude envelope of world where split-brain patients are no longer available to science. α-band activity. The amplitude envelope correlation (AEC) (45) between pairs of MEG sensors can be used to examine whole-brain Split Visual Field Experiment coordination potentially associated with information transfer. An Here, we focus on an important