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Initial experiences with Direct Imaging of Neuronal Activity (DIANA) in humans
Shota Hodono1, Reuben Rideaux2,3, Timo van Kerkoerle4
1Centre for Advanced Imaging, The University of Queensland, Brisbane, Australia.
Abstract:
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.
Insights
Researchers attempted Direct Imaging of Neuronal Activity (DIANA) in humans, a method with high spatiotemporal specificity in mice. Human trials showed inconsistent signals, suggesting artifacts, and failed to detect clear neuronal activity, necessitating further research.
Area of Science:
- Neuroimaging
- Magnetic Resonance Imaging (MRI)
- Human Brain Activity
Background:
- Functional MRI (fMRI) infers brain activity from hemodynamic responses, limiting spatiotemporal specificity.
- Direct Imaging of Neuronal Activity (DIANA) in mice shows high spatiotemporal specificity, correlating MRI signals with electrical activity.
Purpose of the Study:
- To investigate the feasibility of applying the DIANA method for human brain activity detection.
- To explore DIANA's potential for higher spatiotemporal resolution compared to conventional fMRI.
Main Methods:
- Tested five experimental paradigms in humans using DIANA with varying stimuli (flickering noise, naturalistic images), durations (50-200 ms), and resolutions (2x2x5 mm³, 1x1x5 mm³).
- Defined regions of interest (ROIs) using Blood Oxygen Level Dependent (BOLD) fMRI (EPI, FLASH) and T1-weighted anatomical scans.
- Analyzed signal changes in response to stimuli across single subjects and small groups (n=1, n=3).
Main Results:
- Initial paradigms showed ambiguous signals resembling activity, but lacked correlation with stimulus duration changes or were comparable to white matter fluctuations.
- A small, delayed signal increase was observed in one paradigm but was significantly smaller than expected and confounded by noise.
- Higher resolution imaging and naturalistic stimuli did not yield clear functional signals, with subject strain potentially impacting data quality.
Conclusions:
- Direct Imaging of Neuronal Activity (DIANA) in humans did not yield clear, reproducible functional signals in this study.
- Artifacts and signal confounds pose significant challenges, requiring careful interpretation and methodological improvements.
- Future research should focus on optimizing DIANA sequences, stimulus designs, and validating signals with simultaneous electrophysiological recordings.
