Tight coupling between oxygen consumption and oxygen delivery through the vascular system is essential to proper brain function. Previous studies have shown mild hypoxia, defined as the physiological state on which arterial blood oxygen saturation (Y) ranges between 80-85%, causes a reduced extension of BOLD, cerebral blood flow (CBF) and cerebral blood volume (CBV) activated areas during a visual stimulation.^1-6 The amplitude of BOLD signal is also reduced, however the amplitude of CBF and CBV evoked responses in the active areas is unaltered. Overall, it remains unclear if smaller neuronal populations are recruited during hypoxia, in which case the energetic cost of activation is expected to be also reduced, or whether mild-hypoxia mainly results in a different neurovascular coupling, in which case the functional energy demands should remain unchanged. The present study aims at quantifying the effect of mild hypoxia on functional energy metabolism as measured by stimulus-induced changes in metabolite levels using functional spectroscopy (fMRS) at 7T.Data from 6 subjects (males, 26±6 years) were acquired using a 7T/90cm Agilent magnet interfaced to Siemens console. End-tidal CO₂ (PetCO₂) and O₂ (PetO₂) were controlled using a prospective feed-forward gas delivery system (RespirAct, Thornhill Inc). Subjects were fitted with a special breathing mask and individual “baseline” PetCO₂ ­was measured. Two gas conditions were defined based on the targeted PetO₂: normoxia (100 mmHg) and hypoxia (45 mmHg). During both study conditions PetCO₂ was held constant to each individual’s initial baseline value. Subject’s heart rate (HR) and Y were monitored using a pulse oximeter. Subject’s targeted respiratory rate was 10 bpm, cued by an auditory metronome. Spectra were acquired with semi-LASER (TR=5 s, TE=26 ms, 32 scans/spectra) from a 2x2x2 cm³ voxel positioned in the occipital cortex during a 10 min-long fMRS paradigm (REST-STIM), repeated for each gas condition. The stimulus consisted of radial red and black checkerboards flickering at 8 Hz, whereas the rest condition was a black screen. In order to minimize possible quantification bias induced by linewidth changes, spectra linewidths were matched to the broadest linewidth corresponding to hypoxia REST by using the linewidth measured on creatine peak at 3 ppm.⁷ The resulting line-matched spectra were quantified with LCModel. In order to estimate the BOLD effect, unsuppressed water signals were also acquired from the voxel during a brief 1-min stimulation paradigm in both gas conditions. Statistical significance of changes was inferred by two-tailed paired t-test. The mean difference of PetCO₂ in between normoxia and hypoxia was 0.8±2.4% from the normoxia value, which demonstrates the excellent PetCO₂ control achieved during both gas conditions. HR and Y changed from 67±6 bpm and 98.5±0.7% during normoxia to 81±8 bpm to 82.2±1.1% during hypoxia, respectively. The functional water peaks revealed a smaller BOLD effect during hypoxia in comparison to normoxia (0.19±0.24 Hz vs 0.48±0.37 Hz, p=0.01, Fig. 1), in agreement with previous MRI findings.^1-6 Spectra were artifact-free during the entire experiment, while the linewidth of creatine increased significantly in hypoxia as compared to normoxia (11.2±0.7 to 12.5±0.6 Hz, Fig. 2). Typical functional changes in metabolite concentrations⁷ were observed for both gas conditions. In particular, glutamate (Glu) and lactate (Lac) levels increased during stimulation as compared to rest, whereas aspartate (Asp) and glucose (Glc) decreased (Fig. 3). Within the limited number of participants studied so far, concentration changes during stimulation vs. rest in normoxia were not different from changes during hypoxia. This finding, if confirmed in a larger cohort of subjects, would suggest similar functional energetic demands, and therefore similar neuronal population recruitment, during normoxia and mild hypoxia.Our preliminary fMRS findings suggest that the reduced oxygen availability during mild hypoxia does not affect the energetic demands of the activated cortex. Together with findings from MRI studies^1-6, this observation suggests that mild hypoxia induces an altered neurovascular coupling, but does not result in smaller neuronal recruitment during visual activation. We are currently acquiring data on a larger cohort of subjects to confirm the findings of this pilot study.