Impaired task-dependent cerebral cortex oxygenation in Glut1 deficiency

Neuronal activation increases regional glucose utilization and requires coordinated increases in tissue oxygenation. While glucose uptake is regulated by cell type-specific transporter expression, oxygen diffuses more broadly across brain tissue, linking cerebral blood flow to measurable changes in oxygenation using functional near-infrared spectroscopy (fNIRS). In glucose transporter type 1 deficiency (G1D), reduced brain glucose and glycogen levels suggest limited substrate availability to support neural activity.

Individuals with G1D and age-matched controls underwent fNIRS while performing standardized cognitive tasks. Task-evoked changes in oxygenated and deoxygenated hemoglobin were recorded to quantify cortical activation and regional oxygenation responses.

We hypothesized that task-dependent metabolic responses are constrained in G1D. Consistent with this hypothesis, fNIRS measurements demonstrated reduced cortical oxygenation responses in individuals with G1D compared with controls.

These findings support an altered neuroenergetic response to neural activation in G1D, in which cognitive performance is preserved despite limited substrate availability and attenuated oxygenation responses, consistent with adaptive or compensatory mechanisms.