Changes in White Matter Microstructure Impact Cognition by Disrupting the Ability of Neural Assemblies to Synchronize

Abstract

Cognition is compromised by white matter (WM) injury but the neurophysiological alterations linking them remain unclear. We hypothesized that reduced neural synchronization caused by disruption of neural signal propagation is involved. To test this, we evaluated group differences in: diffusion tensor WM microstructure measures within the optic radiations, primary visual area (V1), and cuneus; neural phase synchrony to a visual attention cue during visual-motor task; and reaction time to a response cue during the same task between 26 pediatric patients (17/9: male/female) treated with cranial radiation treatment for a brain tumor (12.67 ± 2.76 years), and 26 healthy children (16/10: male/female; 12.01 ± 3.9 years). We corroborated our findings using a corticocortical computational model representing perturbed signal conduction from myelin. Patients show delayed reaction time, WM compromise, and reduced phase synchrony during visual attention compared with healthy children. Notably, using partial least-squares-path modeling we found that WM insult within the optic radiations, V1, and cuneus is a strong predictor of the slower reaction times via disruption of neural synchrony in visual cortex. Observed changes in synchronization were reproduced in a computational model of WM injury. These findings provide new evidence linking cognition with WM via the reliance of neural synchronization on propagation of neural signals. By comparing brain tumor patients to healthy children, we establish that changes in the microstructure of the optic radiations and neural synchrony during visual attention predict reaction time. Furthermore, by testing the directionality of these links through statistical modeling and verifying our findings with computational modeling, we infer a causal relationship, namely that changes in white matter microstructure impact cognition in part by disturbing the ability of neural assemblies to synchronize. Together, our human imaging data and computer simulations show a fundamental connection between WM microstructure and neural synchronization that is critical for cognitive processing.

White matter plasticity and maturation in human cognition

“…Our current experimental and computational findings, as well as past work (Bells et al, ), show a fundamental connection between white matter microstructure and neural synchronization that appears critical for cognitive processing. Although studies comparing patients and healthy cohorts are essential in delineating such a connection, our patient based cross‐sectional studies ultimately do not provide evidence of the role of myelin plasticity in neural communication and cognition.…”

“…Damage to myelin and axons alters conduction velocities and decreases temporal synchrony within neural ensembles by increasing the variance in conduction velocity, resulting in impaired neural function (Bells et al, ; Fields, ; Nunez et al, ; Pajevic et al, ). In past DTI work, decreased FA in pediatric MS patients was associated with increased connectivity within the resting state visual network (Akbar et al, ).…”

“…These individual pulses where set to a duration of 10 ms. In the spirit of previous work from the authors (Bells et al, ), inputs were delivered with timings statistics that reflect myelin integrity. Specifically, the conduction timings τ k were sampled from a gamma distributionΓ( α , θ ), whose order α was increased to represent myelin damage (reflecting more variable conduction velocities).…”

“…Injury to myelin may cause disruption in timing of neural signaling that maintains oscillatory neural activity within and between neural coalitions (Bells et al, ; Nunez et al, ; Pajevic et al, ). Hence, comparing children with white matter injury to typically developing children on measures of white matter, neural communication, and cognition is a useful means to address how white matter may mediate cognitive function.…”

Disrupted network connectivity in pediatric brain tumor survivors is a signature of injury

“…Specifically, we have shown that children treated for PBT display abnormal neural activation compared to typically developing children that predicts impaired cognitive function (Dockstader et al, ; Dockstader, Wang, Bouffet, & Mabbott, ). Indeed white matter injury may have its impact on cognition via influence on neural communication (Bells et al, ). Consequently, the cognitive deficits observed in PBT survivors may result from tumor and treatment‐related changes in neural synchrony between different brain regions.…”