Asymmetric neural entrainment at resonance frequencies underlies unilateral spatial neglect

Abstract

Unilateral spatial neglect (USN) is a common consequence of right-hemisphere stroke, traditionally attributed to structural lesions and dysfunctional attention networks. However, the brain is fundamentally a rhythmic and dynamical system, and how disrupted neural synchronization underlies USN remains unknown. We recorded steady-state visual evoked potentials (SSVEPs; 3 - 30 Hz flicker) in stroke patients with USN, without USN, and healthy controls. Only the USN group exhibited significant hemispheric asymmetry at 9 Hz, driven by exaggerated responses in the intact hemisphere rather than suppression in the lesioned hemisphere. This effect appeared only during stimulation, not at rest, indicating its specificity to sensory processing. The enhanced 9 Hz entrainment in the intact hemisphere was accompanied by increased phase-amplitude coupling (PAC) between alpha phase and gamma amplitude, reflecting systematic coordination of high-frequency activity. Transfer entropy analysis further revealed increased feedforward information flow from the right visual to the left frontal cortex, highlighting large-scale asymmetry. To explore the mechanism underlying this frequency-specific bias, we implemented a coupled-oscillator model. The model showed that the hemispheric asymmetry arises from resonance between intrinsic alpha rhythms and external input, amplified by asymmetric right-to-left interhemispheric coupling. These findings suggest that USN arises from a selective impairment of alpha-band synchrony capacity. This study offers a novel framework conceptualizing USN as a disorder of disrupted oscillatory dynamics underlying spatial attention, and points toward frequency-specific neuromodulatory intervention as a potential therapeutic approach. Significant statementThe brain behaves as a metronome-like oscillator ensemble. When a rhythmic flicker--a cortical "tuning fork" matching the visual systems intrinsic alpha frequency--is applied, it serves as a probe that visualizes the brains internal state. Under normal conditions, neuronal oscillations in both hemispheres are moderately entrained at this frequency. In unilateral spatial neglect (USN), this resonance displays a distinctive asymmetry: the intact hemisphere becomes over-amplified, whereas the lesioned hemisphere shows no enhancement. A coupled-oscillator model shows that asymmetric interhemispheric coupling selectively boosts this intrinsic alpha resonance unilaterally. This biased resonance reflects a destabilization of the dynamic coordination of attention networks, offering a novel mechanistic view of spatial neglect in USN and pointing toward frequency-specific neuromodulation as a promising therapeutic strategy.