Interhemispheric connectivity dynamics of brain activity indused by cortical spreading depolarization in rats

Abstract

Growing experimental and clinical evidence indicates the crucial role of network dysfunction in neurological disorders’ pathogenesis, including migraine, one of the most prevalent chronic brain diseases. Episodic headache attacks, frequently unilateral, accompanied by an aura, are associated with migraine. Migraine aura is a neurological condition characterized by the temporary development of unilateral sensory, motor, and/or speech disturbances. The symptoms are thought to indicate transient cerebral dysfunction in the cerebral cortex resulting from cortical spreading depolarization (SD), a wave of strong cellular depolarization that gradually spreads through the cortex at a rate of 3–5 mm/min. Electrophysiologically, the cortical SD wave is revealed by a high-amplitude slow negative shift in the extracellular potential and temporary suppression of the electrical activity of the cortex (EEG depression). The change in extracellular potential is associated with strong neuroglial depolarization and disruption of local ion homeostasis, which lasts for 1–2 min in healthy neuronal tissue. The SD results in a momentary suppression of the spontaneous electrical activity within the cortex, which is preceded by a brief excitation of the neurons. The neurological symptoms of the aura suggest a unilateral impairment of interhemispheric interactions during the early phase of a migraine attack. Our study investigated the effect of unilateral SD (a probable pathophysiological mechanism of migraine aura) on interhemispheric functional communication in freely behaving rats using local field potentials of the visual and motor cortex. Two methods were used to examine connectivity: mutual information function, computed using the method proposed in [1], and phase synchronization, calculated through the method [2], for four frequency bands: delta (1–4 Hz), theta (4–10 Hz), beta (10–25 Hz), and gamma (25–50 Hz). This was done by performing calculations on non-overlapping twenty-second intervals. Functional connectivity evolution was analyzed using local field potential records collected from homotopic points of the motor and visual cortex of two hemispheres in freely moving rats after inducing a single unilateral cortical SD in the somatosensory cortex. Cortical SD caused a significant wide-band decline (3–4 times) in interhemispheric functional connectivity in both the visual and motor cortex areas. Following the depolarization wave, the functional decoupling of the hemispheres began and progressively intensified, concluding by 5 min after the induction of the cortical SD wave. The network impairment displayed region- and frequency-specific features, with greater prominence observed in the visual cortex than in the motor cortex. The decline in functional connectivity was concurrent with abnormal animal behavior and aberrant activity in the ipsilateral cortex that appeared after the SD wave had ended. The study indicated that unilateral SD leads to a reversible decline in the functional interhemispheric connectivity in the awake animal cortex. Given the crucial role of synchronizing cortical oscillations for processing sensory information and integrating sensorimotor functions, the intracortical functional interactions disruption resulting from a unilateral SD wave, which we discovered in our present study, could contribute to the neuropathological mechanisms of migraine aura and sensory processing dysfunction during a migraine attack.