Past events

Retinal degenerative diseases lead to blindness due to loss of the “image capturing” photoreceptors, while neurons in the “image-processing” inner retinal layers are relatively well preserved. Information can be reintroduced into the visual system using electrical stimulation of the surviving inner retinal neurons. Some electronic retinal prosthetic systems have been already approved for clinical use, but they provide low resolution and involve very difficult implantation procedures. We developed a photovoltaic subretinal prosthesis which converts light into pulsed electric current, stimulating the nearby inner retinal neurons. Visual information is projected onto the retina from video goggles using pulsed nearinfrared (~880nm) light. This design avoids the use of bulky electronics and wiring, thereby greatly reducing the surgical complexity. Optical activation of the photovoltaic pixels allows scaling the implants to thousands of electrodes. In preclinical studies, we found that prosthetic vision with subretinal implants preserves many features of natural vision, including flicker fusion at high frequencies (>20 Hz), adaptation to static images, antagonistic center-surround organization and nonlinear summation of subunits in receptive fields, providing high spatial resolution. Results of the clinical trial with our implants (PRIMA, Pixium Vision) having 100µm pixels, as well as preclinical measurements with 75 and 55µm pixels, confirm that spatial resolution of prosthetic vision can reach the sampling density limit. For a broad acceptance of this technology by patients who lost central vision due to age-related macular degeneration, visual acuity should exceed 20/100, which requires pixels smaller than 25µm. I will describe the fundamental limitations in electro-neural interfaces and 3-dimensional configurations which should enable such a high spatial resolution. Ease of implantation of these wireless arrays, combined with high resolution opens the door to highly functional restoration of sight.

Driven by recent technological advancements, behavior and brain activity can now be measured at an unprecedented resolution and scale. This “big-data” revolution is akin to a similar revolution in biology. In biology, the wealth of data allowed systems-biologists to uncover the underlying design principles that are shared among biological systems. In my studies, I apply design principles from systems-biology to cognitive phenomena. In my talk I will demonstrate this approach in regard to creative search. Using a novel paradigm, I discovered that people’s search exhibits exploration and exploitation durations that were highly correlated along a line between quick-to-discover/quick-to-drop and slow-to-discover/slow-to-drop strategies. To explain this behavior, I focused on the property of scale invariance, which allows sensory systems to adapt to environmental signals spanning orders of magnitude. For example, bacteria search for nutrients, by responding to relative changes in nutrient concentration rather than absolute levels, via a sensory mechanism termed fold change detection (FCD). Scale invariance is prevalent in cognition, yet the specific mechanisms are mostly unknown. I found that an FCD model best describes creative search dynamics and further predicts robustness to variations in meaning perception, in agreement with behavioral data. These findings suggest FCD as a specific mechanism for scale invariant search, connecting sensory processes of cells and cognitive processes in human. I will end with a broader perspective and outline the benefits of the search for computational design principles of cognition.

In many tasks, such as mazes or social interactions, effective decision making typically requires enumerating the expected outcomes of candidate actions over a series of subsequent events. Because of the computational complexity of such evaluation, it is believed that human and animal brains use a range of shortcuts to simplify or approximate it. I review behavioral and neural evidence that humans rationally trade off exact and approximate evaluation in such sequential decision making. This research offers a new perspective on healthy behaviors, like habits, and pathological ones, like compulsion, which are both viewed as approximate evaluations that fail to incorporate experiences relevant to a decision and instead rely on inappropriate or out-of-date evaluations. I also present new theoretical and experimental work that aims to address the positive counterpart to such neglect: which particular events are considered, in which circumstances, to support choice. This brings the reach of the framework to many new phenomena, including pre-computation for future choices, nonlocal activity in the hippocampal place system, consolidation during sleep, and a new range of disordered symptoms such as craving, hallucinations, and rumination.

The excitability of the apical tuft of layer 5 pyramidal neurons is thought to play a crucial role in behavioral performance and synaptic plasticity. We show that the excitability of the apical tuft is sensitive to adrenergic neuromodulation. Using two-photon dendritic Ca2+ imaging and in vivo whole-cell and extracellular recordings in awake mice, we show that application of the a2A-adrenoceptor agonist guanfacine increases the probability of dendritic Ca2+ events in the tuft and lowers the threshold for dendritic Ca2+ spikes. We further show that these effects are likely to be mediated by the dendritic current Ih. Modulation of Ih in a realistic compartmental model controlled both the generation and magnitude of dendritic calcium spikes in the apical tuft. These findings suggest that adrenergic neuromodulation may affect cognitive processes such as sensory integration, attention, and working memory by regulating the sensitivity of layer 5 pyramidal neurons to top-down inputs.