Effective connectivity between homologous cortices mediated by the corpus callosum: An axono-cortical evoked potentials study

Abstract

Objective: To demonstrate the role of the corpus callosum in interhemispheric effective connectivity and investigate the distribution of the connectivity originating from it using axono-cortical evoked potentials.

Methods: A 14-year-old girl with drug-resistant focal epilepsy underwent total callosotomy. Intraoperatively, we placed four subdural strip electrode contacts on the corpus callosum and eight on each hemisphere. We applied single-pulse electrical stimulation to eight pairs of contacts placed on the corpus callosum and cerebral cortex, recording axono-cortical, cortico-axonal, and cortico-cortical evoked potentials. Propagation latencies and anatomical distributions were determined based on the first negative deflection within 10-50 ms.

Results: Stimulation of the rostral to the anterior midbody elicited responses in bilateral anterior premotor cortices. The anterior to posterior midbody stimulation elicited responses in more posterior premotor cortices. The sum of latencies from the corpus callosum to each hemisphere (23.5 + 21.75 = 45.25 ms) approximated the interhemispheric neural propagation latency (44.5 ms). No significant responses were observed within the corpus callosum.

Conclusion: The corpus callosum mediated effective connectivity between homologous cortices aligned along the anterior-posterior axis, consistent with known structural connectivity.

Significance: This study provides the first direct neurophysiological evidence of the contribution of the corpus callosum to interhemispheric effective connectivity, highlighting its structural-functional correspondence and limitations in generating local field potentials.

Keywords: Axono-cortical evoked potentials; Corpus callosum; Effective connectivity; Electrocorticography; Functional brain mapping; Intracranial electroencephalography; Structural connectivity.

Fig. 1

Magnetic resonance imaging findings and anatomical locations of subdural electrode contacts. (A) T1-weighted axial images. The bilateral temporal, occipital, and parietal lobes showed reduced gyration, cerebral cortical thickening, and subcortical band heterotopia. (B) The green spheres denote the locations of subdural electrode contact sites. Contacts were labeled sequentially from the ventral side: C1–C4 for the corpus callosum, R1–R8 for the right hemisphere cortex, and L1–L8 for the left hemisphere cortex.

Fig. 2

Example of axono-cortical evoked potentials (ACEPs). The figure shows z-score–normalized waveforms of ACEPs evoked by stimulation of the C3–C4 electrode contacts located on the anterior–posterior midbody of the corpus callosum. Colored circles on the central cortical surface indicate the locations of electrode contacts. In each waveform plot, the black vertical line represents the time of stimulation (0 ms), the red line indicates 10 ms, and the blue line indicates 50 ms. Stimulation was delivered at the magenta-colored contacts (C3 and C4), and significant N1 components exceeding a z-score of 5 between 10 and 50 ms after stimulation were observed at the red contacts (L3, L4, R3, and R4), which were located on the premotor cortices.

Fig. 3

Summary of axono-cortical and cortico-cortical evoked potentials. C1–C4 are electrode contacts placed on the corpus callosum; R1–R8 and L1–L8 are contacts placed on the cerebral cortices of the right and left hemispheres, respectively. The green arrows indicate effective connectivity from the corpus callosum to both hemispheres. The blue arrows denote effective connectivity from the left hemisphere to the right hemisphere. The red arrows represent effective connectivity from the right hemisphere to the left hemisphere. The arrow thickness reflects the latency of evoked potentials, with thick arrows representing short latencies. CC: Corpus callosum.