Functional MRI (fMRI) has been widely used to study activity patterns in the human brain. It infers neuronal activity from the associated hemodynamic response, which fundamentally limits its spatiotemporal specificity. In mice, the Direct Imaging of Neuronal Activity (DIANA) method revealed MRI signals that correlated with extracellular electric activity, showing high spatiotemporal specificity. In this work, we attempted DIANA in humans. Five experimental paradigms were tested, exploring different stimulus types (flickering noise patterns, and naturalistic images), stimulus durations (50-200 ms), and imaging resolution (2 × 2 × 5 mm³ and 1 × 1 × 5 mm³). Regions of interest (ROI) were derived from Blood Oxygen Level Dependent (BOLD) fMRI acquisitions (both EPI and FLASH based) and T1-weighted anatomical scans. In Paradigm I (n = 1), using flickering noise patterns, signals were detected that resembled possible functional activity from a small ROI. However, changes in stimulus duration did not lead to corresponding signal changes (Paradigm II; n = 1). Therefore, care should be taken not to mistake artifacts for neuronal activity. In Paradigm III (n = 3), when averaged across multiple subjects, a ~200 ms long 0.02% signal increase was observed ~100 ms after the stimulus onset (10x smaller than the expected signal). However, white matter control ROIs showed similarly large signal fluctuations. In Paradigm IV (n = 3), naturalistic image stimuli were used, but did not reveal signs of a potential functional signal. To reduce partial voluming effects and improve ROI definition, in Paradigm V (n = 3), we acquired data with higher resolution (1 × 1 × 5 mm³) using naturalistic images. However, no sign of activation was found. It is important to note that repetitive experiments with short interstimulus intervals were found to be strenuous for the subjects, which likely impacted data quality. To obtain better data, improvements in sequence and stimulus designs are needed to maximize the DIANA signal and minimize confounds. However, without a clear understanding of DIANA's biophysical underpinnings it is difficult to do so. Therefore, it may be more effective to first investigate DIANA signals with simultaneously recorded electrophysiological signals in more controlled settings, e.g., in anesthetized mice.

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