The retinae as windows to the brain: An oscillatory vision

Project Information

OscillatoryVision

Grant agreement ID: 640448

DOI

10.3030/640448

Project closed

EC signature date 13 November 2015

Start date 1 March 2016

End date 31 March 2022

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 499 850,00

EU contribution

€ 1 499 850,00

Coordinated by

AARHUS UNIVERSITET
Denmark

Periodic Reporting for period 4 - OscillatoryVision (The retinae as windows to the brain: An oscillatory vision)

Reporting period: 2020-09-01 to 2022-03-31

Summary of the context and overall objectives of the project

Several sophisticated image processing circuits have been discovered in animal retina, many of which manifest massive neural synchrony. A major insight is that this type of synchrony often translates to high-frequency activity on a macroscopic level, but electroretinography (ERG) has not been tapped to examine this potential in humans. Bolstered by our compelling results combining ERG with magnetoencephalography (MEG), this project aimed to address several open questions with respect to human visual processing:

1) Could variable retinal timing be linked to intrinsic image properties and pass on phase variance downstream to visual cortex? Our preliminary data with suggested that the retina responds to moving gratings and natural imagery with non-phase-locked high gamma oscillations (>65 Hz) just like visual cortex. However, when stimuli were designed with equal contrast and luminance relative to baseline, we could no longer detect ERG modulations, even with time-frequency analysis techniques. We now plan to devise new approaches to this question in follow-up studies.

2) Do retinal gamma band responses, both evoked and induced, directly drive some cortical gamma responses? We found that they indeed do in the context of light flashes and light onset and offset (Westner et al., 2019).

3) Several kinds of motion have now been shown to elicit massive synchrony in mammalian retina circuits. Does this also result in activity measurable with electroretinography in humans? We discovered that motion onset indeed elicits low-frequency phase synchrony (Alves et al., 2022).

4) Do efferent pathways to the retina exist in humans? We attempted to address this by investigating whether a retinal analog of cortical resting alpha waves could be measured, with inconclusive results. We next attempted to directly drive retinal activity by stimulating visual cortex with transcranial magnetic stimulation, but electroretinogram signals appeared to be explained by small blink or saccade artifacts rather than true retinal responses.

While some of the above questions remain unresolved despite our investigations, we found evidence supporting our overarching hypothesis that the interaction of measurable neural oscillations between the retina and cortex plays a key role in the human visual system. The results, taken together, furthermore advance our understanding of neural synchrony in the human nervous system, including population activity in the retina in addition to the population activity of cortical pyramidal cells that are the traditional focus of MEG and EEG research.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

ERG responses were examined with respect to the corresponding responses of thalamus and visual cortex, as reconstructed with MEG. We implemented a novel neuroimaging strategy, combining beamforming with the Hilbert transform to examine high-frequency response in bands ranging from 55 Hz to 145 Hz. The first cortical responses appear at 27 ms at ~115 Hz, lagging the corresponding retinal oscillatory potential by 8 ms.

Some studies suggest that the processing of dark stimuli may occur more quickly by taking advantage of greater neural resources in the visual system. In a second experiment, longer light pulses of about half a second were employed. In the cortex but not in the retina, high frequency responses occurred more quickly with transitions from light to dark compared to transitions from dark to light (Figure 1). Interestingly, while dark-to-light transitions involved a wide range of frequencies (55-195 Hz in the retina, and 55-145 Hz in the cortex), light-to-dark transitions were restricted to the 75-95 Hz frequency band in both retina and cortex (Westner et al., 2019).

We next investigated how perception of visual motion may begin in the retina. Experiments measured retinal and cortical responses to expanding and contracting annular gratings. Motion onset elicited low-frequency phase synchrony in the electroretinogram, demonstrating for the first time that human retinal oscillations respond to motion stimuli (Alves, 2022).

We demonstrated that OPMs can capture the same activity without even touching the participant (Figure 2), opening up retinal measurements to OPM-MEG labs that are rapidly proliferating with the potential to serve as an alternative diagnostic in eye clinic patients (Westner et al., 2021). In a subsequent investigation, we furthermore found that OPMs can also detect high-frequency oscillations in the retina up to 150 Hz (Lubell et al., in prep).

We have also made significant strides in contributing to open source software for MEG/EEG analysis, particularly MEG/EEG source reconstruction methods in MNE-Python, a rapidly growing open source toolbox (https://mne.tools). This included several beamformer variants, including the Hilbert beamformer method developed in our group to reconstruct amplitude and phase information across frequency bands. We have found it is particularly well-suited to high gamma band responses (75-150 Hz).

We furthermore developed a new method for removing electrical interference from our MEG/EEG recordings (Leske & Dalal, 2019). We contributed our method to a leading open source toolbox, FieldTrip (fieldtriptoolbox.org) for the immediate benefit of the MEG/EEG community.

We also developed approaches to improve MEG/EEG acquisition, including design of a camera array and associated software for photogrammetric reconstruction of research participants’ heads together with MEG/EEG sensor positions (Clausner et al., 2017). This involved the construction of a geodesic dome that simultaneously photographs the head from multiple angles while the volunteer wears either an EEG cap or MEG fiducial markers. The software, Janus3D (https://janus3d.github.io/janus3D_toolbox/) then derives the positions of the MEG/EEG sensors relative to the volunteer’s head and matches it to their MRI. This ultimately increases the accuracy of MEG/EEG source activity and its correspondence with an individual’s brain anatomy

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

We have initiated a line of research investigating how retinal and cortical dynamics interact. The results of our experiments suggest that many high-frequency responses of visual cortex may indeed be driven by retinal activity. We have also discovered that stimulus motion elicits phase synchrony in the electroretinogram, providing evidence that motion processing begins in the human retina.

Measuring ERG together with MEG thereby provides a more informative measure of information processing at each stage of the visual pathway. It may furthermore constitute a potential strategy to uncover disturbances of the visual pathway in disease, not only in disorders of vision but also as a diagnostic of systemic abnormalities relevant to many neurological and psychiatric disorders.

We have furthermore made improvements to MEG/EEG methodology that can equally benefit the technique at large, namely, improved removal of powerline interference, localization of sensors with a camera array, and implementation of novel brain source mapping algorithms in the leading open source Python toolbox for MEG/EEG analysis. During the project period, optically pumped magnetometer arrays for MEG emerged and appear poised to become the basis for next-generation MEG. We demonstrated that this technology can also comfortably measure human retinal activity, providing a contactless alternative to the traditional electroretinogram.

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