Image Processing: How the Retina Detects the Direction of Image Motion

In the retina, the beautifully symmetrical ‘starburst’ amacrine cells interact with each other in a way that creates asymmetrical responses to moving images at their dendritic tips. This computation, occurring in a retinal interneuron, is a foundation of the directional signals transmitted by the retina to the brain

Response of Mouse Visual Cortical Neurons to Electric Stimulation of the Retina

Retinal prostheses strive to restore vision to the blind by electrically stimulating the neurons that survive the disease process. Clinical effectiveness has been limited however, and much ongoing effort is devoted toward the development of improved stimulation strategies, especially ones that better replicate physiological patterns of neural signaling. Here, to better understand the potential effectiveness of different stimulation strategies, we explore the responses of neurons in the primary visual cortex to electric stimulation of the retina. A 16-channel implantable microprobe was used to record single unit activities in vivo from each layer of the mouse visual cortex. Layers were identified by electrode depth as well as spontaneous rate. Cell types were classified as excitatory or inhibitory based on their spike waveform and as ON, OFF, or ON-OFF based on the polarity of their light response. After classification, electric stimulation was delivered via a wire electrode placed on the surface of cornea (extraocularly) and responses were recorded from the cortex contralateral to the stimulated eye. Responses to electric stimulation were highly similar across cell types and layers. Responses (spike counts) increased as a function of the amplitude of stimulation, and although there was some variance across cells, the sensitivity to amplitude was largely similar across all cell types. Suppression of responses was observed for pulse rates ≥3 pulses per second (PPS) but did not originate in the retina as RGC responses remained stable to rates up to 5 PPS. Low-frequency sinusoids delivered to the retina replicated the out-of-phase responses that occur naturally in ON vs. OFF RGCs. Intriguingly, out-of-phase signaling persisted in V1 neurons, suggesting key aspects of neural signaling are preserved during transmission along visual pathways. Our results describe an approach to evaluate responses of cortical neurons to electric stimulation of the retina. By examining the responses of single cells, we were able to show that some retinal stimulation strategies can indeed better match the neural signaling patterns used by the healthy visual system. Because cortical signaling is better correlated to psychophysical percepts, the ability to evaluate which strategies produce physiological-like cortical responses may help to facilitate better clinical outcomes

Mediating Retinal Ganglion Cell Spike Rates Using High-Frequency Electrical Stimulation

Recent retinal studies have directed more attention to sophisticated stimulation strategies based on high-frequency (>1.0 kHz) electrical stimulation (HFS). In these studies, each retinal ganglion cell (RGC) type demonstrated a characteristic stimulus-strength-dependent response to HFS, offering the intriguing possibility of focally targeting retinal neurons to provide useful visual information by retinal prosthetics. Ionic mechanisms are known to affect the responses of electrogenic cells during electrical stimulation. However, how these mechanisms affect RGC responses is not well understood at present, particularly when applying HFS. Here, we investigate this issue via an in silico model of the RGC. We calibrate and validate the model using an in vitro retinal preparation. An RGC model based on accurate biophysics and realistic representation of cell morphology, was used to investigate how RGCs respond to HFS. The model was able to closely replicate the stimulus-strength-dependent suppression of RGC action potentials observed experimentally. Our results suggest that spike inhibition during HFS is due to local membrane hyperpolarization caused by outward membrane currents near the stimulus electrode. In addition, the extent of HFS-induced inhibition can be largely altered by the intrinsic properties of the inward sodium current. Finally, stimulus-strength-dependent suppression can be modulated by a wide range of stimulation frequencies, under generalized electrode placement conditions. In vitro experiments verified the computational modeling data. This modeling and experimental approach can be extended to further our understanding on the effects of novel stimulus strategies by simulating RGC stimulus-response profiles over a wider range of stimulation frequencies and electrode locations than have previously been explored

Key features of palliative care service delivery to Indigenous peoples in Australia, New Zealand, Canada and the United States: A comprehensive review

Background: Indigenous peoples in developed countries have reduced life expectancies, particularly from chronic diseases. The lack of access to and take up of palliative care services of Indigenous peoples is an ongoing concern. Objectives: To examine and learn from published studies on provision of culturally safe palliative care service delivery to Indigenous people in Australia, New Zealand (NZ), Canada and the United States of America (USA); and to compare Indigenous peoples’ preferences, needs, opportunities and barriers to palliative care. Methods: A comprehensive search of multiple databases was undertaken. Articles were included if they were published in English from 2000 onwards and related to palliative care service delivery for Indigenous populations; papers could use quantitative or qualitative approaches. Common themes were identified using thematic synthesis. Studies were evaluated using Daly’s hierarchy of evidence-for-practice in qualitative research. Results: Of 522 articles screened, 39 were eligible for inclusion. Despite diversity in Indigenous peoples’ experiences across countries, some commonalities were noted in the preferences for palliative care of Indigenous people: to die close to or at home; involvement of family; and the integration of cultural practices. Barriers identified included inaccessibility, affordability, lack of awareness of services, perceptions of palliative care, and inappropriate services. Identified models attempted to address these gaps by adopting the following strategies: community engagement and ownership; flexibility in approach; continuing education and training; a whole-of-service approach; and local partnerships among multiple agencies. Better engagement with Indigenous clients, an increase in number of palliative care patients, improved outcomes, and understanding about palliative care by patients and their families were identified as positive achievements. Conclusions: The results provide a comprehensive overview of identified effective practices with regards to palliative care delivered to Indigenous populations to guide future program developments in this field. Further research is required to explore the palliative care needs and experiences of Indigenous people living in urban areas

Temporal properties of network-mediated responses to repetitive stimuli are dependent upon retinal ganglion cell type

OBJECTIVE: To provide artificially-elicited vision that is temporally dynamic, retinal prosthetic devices will need to repeatedly stimulate retinal neurons. However, given the diversity of physiological types of retinal ganglion cells (RGCs) as well as the heterogeneity of their responses to electric stimulation, temporal properties of RGC responses have not been adequately investigated. Here, we explored the cell type dependence of network-mediated RGC responses to repetitive electric stimulation at various stimulation rates. APPROACH: We examined responses of ON and OFF types of RGCs in the rabbit retinal explant to five consecutive stimuli with varying inter-stimulus intervals (10-1000 ms). Each stimulus was a 4 ms long monophasic sinusoidal cathodal current, which was applied epiretinally via a conical electrode. Spiking activity of targeted RGCs was recorded using a cell-attached patch electrode. MAIN RESULTS: ON and OFF cells had distinct responses to repetitive stimuli. Consistent with earlier studies, OFF cells always generated reduced responses to subsequent stimuli compared to responses to the first stimulus. In contrast, a new stimulus to ON cells suppressed all pending/ongoing responses from previous stimuli and initiated its own response that was remarkably similar to the response from a single stimulus in isolation. This previously unreported \u27reset\u27 behavior was observed exclusively and consistently in ON cells. These contrasts between ON and OFF cells created a range of stimulation rates (4-7 Hz) that maximized the ratio of the responses arising in ON versus OFF cells. SIGNIFICANCE: Previous clinical testing reported that subjects perceive bright phosphenes (ON responses) and also prefer stimulation rates of 5-7 Hz. Our results suggest that responses of ON cells are weak at high rates of stimulation (\u3e ∼7 Hz) due to the reset while responses of OFF cells are strong at low rates (\u3c ∼4 Hz) due to reduced desensitization, both reducing the ratio of ON to OFF responses. In combination with previous results indicating that responses in ON cells more closely match physiological patterns (Im and Fried 2015 J. Physiol. 593 3577-96), our results offer a potential reason for the user preference of intermediate rates (5-7 Hz)

Directionally selective retinal ganglion cells suppress luminance responses during natural viewing

The ON-OFF directionally selective cells of the retina respond preferentially to movement in a preferred direction, but under laboratory conditions they are also sensitive to changes in the luminance of the stationary stimulus. If the response of these neurons contains information about both direction and luminance downstream neurons are faced with the challenge of extracting the motion component, a computation that may be difficult under certain viewing conditions. Here, we show that during natural viewing the response to luminance is suppressed, leaving a relatively pure motion signal that gets transmitted to the brain

High frequency electric stimulation of retinal neurons elicits physiological signaling patterns

The effectiveness of retinal prosthetics will depend on their ability to elicit patterns of neural activity that can be recognized by the visual cortex. While conventional short-duration pulses activate retinal neurons effectively, many nearby neurons are thought to respond similarly to a given pulse train a situation that is non-physiological. Use of pulse trains delivered at rates > 1000 pulses per second (PPS) in cochlear prosthetics help to avoid phase-locked responses but have not been evaluated in the retina; here, we explored the response to trains of 2000 PPS. We found that ganglion cells respond robustly to these stimuli but that the properties of the response were highly sensitive to stimulus amplitude. At low amplitudes the response patterns were burst-like while at higher amplitudes elicited spikes had intervals that were more uniform. Because burst responses were insensitive to synaptic blockers, our results suggest that they arise from direct activation. This was surprising because previous studies indicated that burst responses arise only through indirect activation. Thus, our results suggest multiple mechanisms of burst creation may exist. Further, histograms of interspike intervals revealed that the response properties were different in different types of ganglion cells. While further testing is needed, the ability to create different patterns of activity in different types of ganglion cells raises the possibility that more natural spike patterns can be created. ? 2011 IEEE.EI

Electric stimulus duration alters network-mediated responses depending on retinal ganglion cell type

OBJECTIVE: To improve the quality of artificial vision that arises from retinal prostheses, it is important to bring electrically-elicited neural activity more in line with the physiological signaling patterns that arise normally in the healthy retina. Our previous study reported that indirect activation produces a closer match to physiological responses in ON retinal ganglion cells (RGCs) than in OFF cells (Im and Fried 2015 J. Physiol. 593 3677-96). This suggests that a preferential activation of ON RGCs would shape the overall retinal response closer to natural signaling. Recently, we found that changes to the rate at which stimulation was delivered could bias responses towards a stronger ON component (Im and Fried 2016a J. Neural Eng. 13 025002), raising the possibility that changes to other stimulus parameters can similarly bias towards stronger ON responses. Here, we explore the effects of changing stimulus duration on the responses in ON and OFF types of brisk transient (BT) and brisk sustained (BS) RGCs. APPROACH: We used cell-attached patch clamp to record RGC spiking in the isolated rabbit retina. Targeted RGCs were first classified as ON or OFF type by their light responses, and further sub-classified as BT or BS types by their responses to both light and electric stimuli. Spiking in targeted RGCs was recorded in response to electric pulses with durations varying from 5 to100 ms. Stimulus amplitude was adjusted at each duration to hold total charge constant for all experiments. MAIN RESULTS: We found that varying stimulus durations modulated responses differentially for ON versus OFF cells: in ON cells, spike counts decreased significantly with increasing stimulus duration while in OFF cells the changes were more modest. The maximum ratio of ON versus OFF responses occurred at a duration of ~10 ms. The difference in response strength for BT versus BS cells was much larger in ON cells than in OFF cells. SIGNIFICANCE: The stimulation rates preferred by subjects during clinical trials are similar to the rates that maximize the ON/OFF response ratio in in vitro testing (Im and Fried 2016a J. Neural Eng. 13 025002). Here, we determine the stimulus duration that produces the strongest bias towards ON responses and speculate that it will further enhance clinical effectiveness

Implantable microcoils for intracortical magnetic stimulation

Neural prostheses that stimulate the neocortex have the potential to treat a wide range of neurological disorders. However, the efficacy of electrode-based implants remains limited, with persistent challenges that include an inability to create precise patterns of neural activity as well as difficulties in maintaining response consistency over time. These problems arise from fundamental limitations of electrodes as well as their susceptibility to implantation and have proven difficult to overcome. Magnetic stimulation can address many of these limitations, but coils small enough to be implanted into the cortex were not thought strong enough to activate neurons. We describe a new microcoil design and demonstrate its effectiveness for both activating cortical neurons and driving behavioral responses. The stimulation of cortical pyramidal neurons in brain slices in vitro was reliable and could be confined to spatially narrow regions (<60 μm). The spatially asymmetric fields arising from the coil helped to avoid the simultaneous activation of passing axons. In vivo implantation was safe and resulted in consistent and predictable behavioral responses. The high permeability of magnetic fields to biological substances may yield another important advantage because it suggests that encapsulation and other adverse effects of implantation will not diminish coil performance over time, as happens to electrodes. These findings suggest that a coil-based implant might be a useful alternative to existing electrode-based devices. The enhanced selectivity of microcoil-based magnetic stimulation will be especially useful for visual prostheses as well as for many brain-computer interface applications that require precise activation of the cortex