Periodic Reporting for period 2 - HYPERSTIM (High-dimensional electrical stimulation for visual prosthesis)
Reporting period: 2023-11-01 to 2025-04-30
At present, there is virtually no treatment for patients who have lost vision. One possibility is to insert small electrodes in the visual cortex and directly stimulate the brain cells that are responsible for vision in a pattern derived from a camera image. However, current approaches face strong limitations due to the low number of electrodes that can be inserted. To achieve a genuine breakthrough, we will have to insert more than 1000 electrodes in the brain. Moreover, to achieve a sufficiently high resolution for blind patients we will have to apply electrical stimulation using sophisticated stimulation protocols. Our objective is to achieve a resolution of artificial vision that is at least 20 times higher than the number of electrodes that are physically present.
The main achievements in the first year of the project can be summarized as follows:
- succesful fabricaton of thin, flexible electrode arrays for recording and microstimulation
- implantation of several hundred electrodes in visual cortex of nonhuman primates
- first calcium imaging experiments using thin flexible electrode arrays in mice
- recordings of neural activity in visual cortex of nonhuman primates for several months up to 2.5 years
- demonstration of the effect of epicranial transcranial direct current stimulation (EDCS) on neural activity
- a computational model of the mouse visual cortex allowing simulations of the effect of a high number of stimulation patterns
- reliable decoding of orientation based on the recordings in visual cortex of NHPs
- induction of phosphenes by microstimulation in visual cortex
- charting fMRI activations caused by microstimulation in visual cortex
The main achievements in the second reporting period can be summarized as follows:
- First evidence for different neural activation patterns with current steering in calcium imaging experiments in mouse brain slices, anesthetized mice and awake monkey experiments
- Demonstration of increased visual selectivity and shifts in the orientation tuning caused by epicranial direct current stimulation in monkeys
- Ventral and dorsal stream functional activations caused by microstimulation in V1 in monkeys
- Excellent biocompatibility of flexible Revision electrodes demonstrated in histological analysis of monkey visual cortex
- A computational model of monkey visual cortex including higher visual areas and layers
- Decoding of different neural activation patterns in V4 by current steering in V1 in monkeys
- succesful fabricaton of thin, flexible electrode arrays for recording and microstimulation
- implantation of several hundred electrodes in visual cortex of nonhuman primates
- first calcium imaging experiments using thin flexible electrode arrays in mice
- recordings of neural activity in visual cortex of nonhuman primates for several months up to 2.5 years
- demonstration of the effect of epicranial transcranial direct current stimulation (EDCS) on neural activity
- a computational model of the mouse visual cortex allowing simulations of the effect of a high number of stimulation patterns
- reliable decoding of orientation based on the recordings in visual cortex of NHPs
- induction of phosphenes by microstimulation in visual cortex
- charting fMRI activations caused by microstimulation in visual cortex
The main achievements in the second reporting period can be summarized as follows:
- First evidence for different neural activation patterns with current steering in calcium imaging experiments in mouse brain slices, anesthetized mice and awake monkey experiments
- Demonstration of increased visual selectivity and shifts in the orientation tuning caused by epicranial direct current stimulation in monkeys
- Ventral and dorsal stream functional activations caused by microstimulation in V1 in monkeys
- Excellent biocompatibility of flexible Revision electrodes demonstrated in histological analysis of monkey visual cortex
- A computational model of monkey visual cortex including higher visual areas and layers
- Decoding of different neural activation patterns in V4 by current steering in V1 in monkeys
The application of epicranial Direct Curent Stimulation (EDCS) may be beneficial for a cortical visual prostheses since we observed major changes in neuronal excitability. However, we did not yet test the effect of EDCS on the threshold for inducing phosphenes nor on the fMRI activations. If we observe a positive effect we will start a patent search investigation.
The possibility to measure functional activations caused by microstimulation is another significant advantage over other electrode arrays.
RP2:
The demonstration of different neural activation patterns in primary visual cortex and in higher visual areas by current steering using different animal models is a crucial finding for our goal to increase the resolution of electrical stimulation beyond the number of electrodes inserted into the brain. We cannot assess the quality of the perceptual effects of V1 microstimulation in animal models, but showing different activation patterns represents objective evidence in favor of our hypothesis that advanced stimulation patterns can increase the resolution of brain stimulation in blind patients.
Using microstimulation during functional Magnetic Resonance Imaging (fMRI), we could also demonstrate that V1 electrical stimulation can activate higher ventral stream visual areas, but also dorsal stream areas combined with deactivations in the ventral stream. These findings are important to interpret the differences in evoked phosphenes observed in blind patients.
The possibility to measure functional activations caused by microstimulation is another significant advantage over other electrode arrays.
RP2:
The demonstration of different neural activation patterns in primary visual cortex and in higher visual areas by current steering using different animal models is a crucial finding for our goal to increase the resolution of electrical stimulation beyond the number of electrodes inserted into the brain. We cannot assess the quality of the perceptual effects of V1 microstimulation in animal models, but showing different activation patterns represents objective evidence in favor of our hypothesis that advanced stimulation patterns can increase the resolution of brain stimulation in blind patients.
Using microstimulation during functional Magnetic Resonance Imaging (fMRI), we could also demonstrate that V1 electrical stimulation can activate higher ventral stream visual areas, but also dorsal stream areas combined with deactivations in the ventral stream. These findings are important to interpret the differences in evoked phosphenes observed in blind patients.