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Background: Intracortical microstimulation (ICMS) is an emerging approach to restore sensation to people with neurological injury or disease. Biomimetic microstimulation, or stimulus trains that mimic neural activity in the brain through encoding of onset and offset transients, could improve the utility of ICMS for brain-computer interface (BCI) applications, but how biomimetic microstimulation affects neural activation is not understood. Current “biomimetic” ICMS trains aim to reproduce the strong onset and offset transients evoked in the brain by sensory input through dynamic modulation of stimulus parameters. Stimulus induced depression of neural activity (decreases in evoked intensity over time) is also a potential barrier to clinical implementation of sensory feedback, and dynamic microstimulation may reduce this effect. Objective: We evaluated how bio-inspired ICMS trains with dynamic modulation of amplitude and/or frequency change the calcium response, spatial distribution, and depression of neurons in the somatosensory and visual cortices. Methods: Calcium responses of neurons were measured in Layer 2/3 of visual and somatosensory cortices of anesthetized GCaMP6s mice in response to ICMS trains with fixed amplitude and frequency (Fixed) and three dynamic ICMS trains that increased the stimulation intensity during the onset and offset of stimulation by modulating the amplitude (DynAmp), frequency (DynFreq), or amplitude and frequency (DynBoth). ICMS was provided for either 1-s with 4-s breaks (Short) or for 30-s with 15-s breaks (Long). Results: DynAmp and DynBoth trains evoked distinct onset and offset transients in recruited neural populations, while DynFreq trains evoked population activity similar to Fixed trains. Individual neurons had heterogeneous responses primarily based on how quickly they depressed to ICMS, where neurons farther from the electrode depressed faster and a small subpopulation (1–5%) were modulated by DynFreq trains. Neurons that depressed to Short trains were also more likely to depress to Long trains, but Long trains induced more depression overall due to the increased stimulation length. Increasing the amplitude during the hold phase resulted in an increase in recruitment and intensity which resulted in more depression and reduced offset responses. Dynamic amplitude modulation reduced stimulation induced depression by 14.6 ± 0.3% for Short and 36.1 ± 0.6% for Long trains. Ideal observers were 0.031 ± 0.009 s faster for onset detection and 1.33 ± 0.21 s faster for offset detection with dynamic amplitude encoding. Conclusions: Dynamic amplitude modulation evokes distinct onset and offset transients, reduces depression of neural calcium activity, and decreases total charge injection for sensory feedback in BCIs by lowering recruitment of neurons during long maintained periods of ICMS. In contrast, dynamic frequency modulation evokes distinct onset and offset transients in a small subpopulation of neurons but also reduces depression in recruited neurons by reducing the rate of activation.
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Activation and depression of neural and hemodynamic responses induced by the intracortical microstimulation and visual stimulation in the mouse visual cortex
Abstract Objective. Intracortical microstimulation (ICMS) can be an effective method for restoring sensory perception in contemporary brain–machine interfaces. However, the mechanisms underlying better control of neuronal responses remain poorly understood, as well as the relationship between neuronal activity and other concomitant phenomena occurring around the stimulation site.Approach. Different microstimulation frequencies were investigatedin vivoon Thy1-GCaMP6s mice using widefield and two-photon imaging to evaluate the evoked excitatory neural responses across multiple spatial scales as well as the induced hemodynamic responses. Specifically, we quantified stimulation-induced neuronal activation and depression in the mouse visual cortex and measured hemodynamic oxyhemoglobin and deoxyhemoglobin signals using mesoscopic-scale widefield imaging.Main results. Our calcium imaging findings revealed a preference for lower-frequency stimulation in driving stronger neuronal activation. A depressive response following the neural activation preferred a slightly higher frequency stimulation compared to the activation. Hemodynamic signals exhibited a comparable spatial spread to neural calcium signals. Oxyhemoglobin concentration around the stimulation site remained elevated during the post-activation (depression) period. Somatic and neuropil calcium responses measured by two-photon microscopy showed similar dependence on stimulation parameters, although the magnitudes measured in soma was greater than in neuropil. Furthermore, higher-frequency stimulation induced a more pronounced activation in soma compared to neuropil, while depression was predominantly induced in soma irrespective of stimulation frequencies.Significance. These results suggest that the mechanism underlying depression differs from activation, requiring ample oxygen supply, and affecting neurons. Our findings provide a novel understanding of evoked excitatory neuronal activity induced by ICMS and offer insights into neuro-devices that utilize both activation and depression phenomena to achieve desired neural responses.
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- Award ID(s):
- 1943906
- PAR ID:
- 10499632
- Publisher / Repository:
- IOP Publishing
- Date Published:
- Journal Name:
- Journal of Neural Engineering
- Volume:
- 21
- Issue:
- 2
- ISSN:
- 1741-2560
- Format(s):
- Medium: X Size: Article No. 026033
- Size(s):
- Article No. 026033
- Sponsoring Org:
- National Science Foundation
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