Structural Organization of the Corpus Callosum Predicts Attentional Shifts after Continuous Theta Burst Stimulation

Abstract

Repetitive transcranial magnetic stimulation (rTMS) applied over the right posterior parietal cortex (PPC) in healthy participants has been shown to trigger a significant rightward shift in the spatial allocation of visual attention, temporarily mimicking spatial deficits observed in neglect. In contrast, rTMS applied over the left PPC triggers a weaker or null attentional shift. However, large interindividual differences in responses to rTMS have been reported. Studies measuring changes in brain activation suggest that the effects of rTMS may depend on both interhemispheric and intrahemispheric interactions between cortical loci controlling visual attention. Here, we investigated whether variability in the structural organization of human white matter pathways subserving visual attention, as assessed by diffusion magnetic resonance imaging and tractography, could explain interindividual differences in the effects of rTMS. Most participants showed a rightward shift in the allocation of spatial attention after rTMS over the right intraparietal sulcus (IPS), but the size of this effect varied largely across participants. Conversely, rTMS over the left IPS resulted in strikingly opposed individual responses, with some participants responding with rightward and some with leftward attentional shifts. We demonstrate that microstructural and macrostructural variability within the corpus callosum, consistent with differential effects on cross-hemispheric interactions, predicts both the extent and the direction of the response to rTMS. Together, our findings suggest that the corpus callosum may have a dual inhibitory and excitatory function in maintaining the interhemispheric dynamics that underlie the allocation of spatial attention.

Significance statement: The posterior parietal cortex (PPC) controls allocation of attention across left versus right visual fields. Damage to this area results in neglect, characterized by a lack of spatial awareness of the side of space contralateral to the brain injury. Transcranial magnetic stimulation over the PPC is used to study cognitive mechanisms of spatial attention and to examine the potential of this technique to treat neglect. However, large individual differences in behavioral responses to stimulation have been reported. We demonstrate that the variability in the structural organization of the corpus callosum accounts for these differences. Our findings suggest novel dual mechanism of the corpus callosum function in spatial attention and have broader implications for the use of stimulation in neglect rehabilitation.

Keywords: TMS; corpus callosum; diffusion tractography; individual differences; neglect; spatial attention.

Figure 1.

Study design. A, Participants performed a free visual exploration task (example of a visual picture display with a visual scanpath) while their eye movements were recorded. The cumulative fixation duration (i.e., the sum of the duration of all fixations) on the left and the right screen half was computed for each participant during each testing session at two time points (pre and post stimulation). B, Schematic representation of the three testing sessions for each participant (counterbalanced order): with cTBS over the right IPS (left), with cTBS over the left IPS (central), and with sham stimulation over the right IPS (right). Gray rectangles represent blocks of the free visual exploration task before (Pre) and after (Post) stimulation application. Bolt symbols represent stimulation: real cTBS (solid symbols) and sham stimulation (dotted symbol). C, Location and delineation of regions of interest (ROIs) used in spherical deconvolution tractography (see Materials and Methods section for full details).

Figure 2.

A, Initial spatial bias (i.e., at time point pre; percentage cumulative fixation duration) across testing sessions in individual participants (left) and at a group level (right). Negative values indicate a leftward bias; positive values indicate a rightward bias. Bars indicate the SEM. B, Mean percentage cumulative fixation time at a group level on the right and the left screen halves, pre and post stimulation, in the condition with cTBS over the left IPS (left), cTBS over the right IPS (central), and sham stimulation over the right IPS (right). Error bars indicate SEM. Asterisks denote significant post hoc tests (**p < 0.01).

Figure 3.

A, Individual bias spatial shifts (post − pre percentage cumulative fixation durations on the right screen half) after cTBS over the left IPS (left), after cTBS over the right IPS (central), and after sham stimulation (right). Positive values indicate a rightward shift; negative values indicate a leftward shift. B, Mean normalized spatial bias shift (calculated as follows: post minus pre spatial bias shift divided by the absolute value of the difference between post minus pre sham condition) after cTBS over the left IPS and cTBS over the right IPS. Positive values indicate a rightward shift; negative values indicate a leftward shift. Error bars indicate SEM.

Figure 4.

Results of TBSS analyses. A, Higher FA in the corpus callosum was associated with stronger leftward shifts in attention after stimulation over the left IPS. B, Higher FA in the corpus callosum was associated with stronger leftward shifts in attention after cTBS over the left IPS after controlling for the effect of handedness (continuous variable). All results are presented after correction for multiple comparisons (p < 0.05). Results are displayed on the FSL FA template in the standard MNI space with given X, Y, and Z coordinates. L, Left; R, right. Only parts of the TBSS skeleton where significant effects (p < 0.05) were found are shown. The colors depict p-values.

Figure 5.

Results of TBSS group analyses. Higher FA in the corpus callosum in participants with leftward versus rightward attentional shifts after cTBS over the left IPS (presented in red-yellow; A) and with “typical” versus “atypical” overall responses to cTBS as predicted by Kinsbourne's (1987, 1993) model (i.e., a rightward attentional shift after cTBS over the right IPS cTBS, and a leftward attentional shift after cTBS over the left IPS; presented in blue-light blue; B). All results are presented after correction for multiple comparisons (p < 0.05). The results are displayed on the FSL FA template in the standard MNI space with given X, Y, and Z coordinates. L, Left; R, right. Only parts of the TBSS skeleton where significant effects (p < 0.05) were found are shown. The colors depict p-values.

Figure 6.

Results of spherical deconvolution tractography. A, Examples of spherical deconvolution tractography reconstruction of the entire corpus callosum (top) and of different callosal parts: orbitofrontal (blue), prefrontal/frontal (green), parietal (yellow), temporal (red), and occipital (orange). B, Correlations between HMOA measures within the corpus callosum and the effect of cTBS over the left IPS (i.e., normalized shift in the allocation of spatial attention/normalized spatial bias shift). C, Correlations between normalized volume of the corpus callosum and the effect of cTBS over the right IPS (i.e., normalized shift in the allocation of spatial attention/normalized spatial bias shift). Negative values indicate leftward and positive rightward shift in the allocation of spatial attention after cTBS. *Correlation is significant after correction for multiple comparisons (FDR-corrected p-values).

Figure 7.

Dual inhibitory and excitatory model of callosal function in spatial attention. A, Inhibitory model. cTBS applied over the left IPS in participants with a high FA/HMOA index triggers a leftward attentional shift because the inhibitory stimulation is applied to regions already inhibited by the right dominant hemisphere (left panel). In participants with a low FA/HMOA index, there is a weak reciprocal inhibition of the two hemispheres across the respective attentional networks. cTBS over the left IPS thus triggers compensatory activation of other cortical areas within the left hemisphere (red cross), with the result that spatial attention is directed to the contralateral (right) visual field (right panel). B, Excitatory model. In participants with a large corpus callosum (large volume), cTBS applied over the right IPS results in smaller rightward attentional shifts. This is due to the fact that, whereas this stimulation triggers some inhibition of the right hemisphere, there is also high interhemispheric connectivity, causing rebalancing activation across both hemispheres (left panel). In participants with a smaller corpus callosum (small volume), cTBS over the right IPS results in larger rightward attentional shifts due to stimulation triggering inhibition within the dominant right hemisphere and the smaller corpus callosum being less efficient in rebalancing activation across both hemispheres (right panel). C, Dual model. The “typical” responses to cTBS can in turn be better accounted for not by a purely inhibitory model (as originally proposed by Kinsbourne, 1977, 1987, 1993), but rather by a dual inhibitory and excitatory model of callosal function, differentially maintaining right hemispheric dominance in spatial attention.