Daniel I. Brooks

Optogenetic and Electrical Microstimulation Systematically Bias Visuospatial Choice in Primates

Optogenetics is a recently developed method in which neurons are genetically modified to express membrane proteins sensitive to light, enabling precisely targeted control of neural activity [1-3]. The temporal and spatial precision afforded by neural stimulation by light holds promise as a powerful alternative to current methods of neural control, which rely predominantly on electrical and pharmacological methods, in both research and clinical settings [4, 5]. Although the optogenetic approach has been widely used in rodent and other small animal models to study neural circuitry [6-8], its functional application in primate models has proven more difficult. In contrast to the relatively large literature on the effects of cortical electrical microstimulation in perceptual and decision-making tasks [9-13], previous studies of optogenetic stimulation in primates have not demonstrated its utility in similar paradigms [14-18]. In this study, we directly compare the effects of optogenetic activation and electrical microstimulation in the lateral intraparietal area during a visuospatial discrimination task. We observed significant and predictable biases in visual attention in response to both forms of stimulation that are consistent with the experimental modulation of a visual salience map. Our results demonstrate the power of optogenetics as a viable alternative to electrical microstimulation for the precise dissection of the cortical pathways of high-level processes in the primate brain.

The Nesting of Search Contexts Within Natural Scenes: Evidence From Contextual Cuing

In a contextual cuing paradigm, we examined how memory for the spatial structure of a natural scene guides visual search. Participants searched through arrays of objects that were embedded within depictions of real-world scenes. If a repeated search array was associated with a single scene during study, then array repetition produced significant contextual cuing. However, expression of that learning was dependent on instantiating the original scene in which the learning occurred: Contextual cuing was disrupted when the repeated array was transferred to a different scene. Such scene-specific learning was not absolute, however. Under conditions of high scene variability, repeated search array were learned independently of the scene background. These data suggest that when a consistent environmental structure is available, spatial representations supporting visual search are organized hierarchically, with memory for functional subregions of an environment nested within a representation of the larger scene.

Generalized auditory same-different discrimination by pigeons.

Three pigeons were trained in a successive same/different (S/D) procedure using compound auditory stimuli (pitch/timbre combinations). Using a go/no-go procedure, pigeons successfully learned to discriminate between sequences of either all same (AAAA...or BBBB...) or all different (ABCD...) sequences consisting of 12 sounds. Both pitch and timbre were subsequently established as controlling dimensions. Transfer tests with novel stimuli revealed a generalized basis for the discrimination (novel pitch/timbre combinations, novel pitches, novel instruments, and complex natural & man-made sounds). These results indicate for the first time that pigeons can learn generalized same/different discriminations in a nondominant modality. When combined with earlier visual results, they support a qualitative similarity among birds and primates in their capacity to judge this type of fundamental stimulus relation across different modalities.

Same/different discrimination learning with trial-unique stimuli.

A long-standing issue in same/different discrimination learning concerns the possible role of individual stimulus memory through repeated presentation. The aim of eliminating any effect of repetition prompted us to devise a new method for generating trial-unique stimuli. These stimuli were arrays of 16 mosaics, each containing 16 cells, which could be filled with 16 possible luminance levels. In Experiment 1, we successfully trained 4 pigeons with these trial-unique stimuli in a two-alternative forced choice same/different discrimination task to 80% correct-choice performance. We later conducted two tests that explored the nature of this discrimination and suggested that pigeons compared the mosaics in the arrays on the basis of their spatial configurations, not on the basis of lower level perceptual properties. In Experiment 2, college students responded similarly to the same sequence of training and testing. Our results suggest that pigeons and people may use similar mechanisms in relational discrimination learning.

Modified toolbox for optogenetics in the nonhuman primate

Abstract. Attracted by the appealing advantages of optogenetics, many nonhuman primate labs are attempting to incorporate this technique in their experiments. Despite some reported successes by a few groups, many still find it difficult to develop a reliable way to transduce cells in the monkey brain and subsequently monitor light-induced neuronal activity. Here, we describe a methodology that we have developed and successfully deployed on a regular basis with multiple monkeys. All devices and accessories are easy to obtain and results using these have been proven to be highly replicable. We developed the “in-chair” viral injection system and used tapered and thinner fibers for optical stimulation, which significantly improved the efficacy and reduced tissue damage. With these methods, we have successfully transduced cells in multiple monkeys in both deep and shallow cortical areas. We could reliably obtain neural modulation for months after injection, and no light-induced artifacts were observed during recordings. Further experiments using these methods have shown that optogenetic stimulation can be used to bias spatial attention in a visual choice discrimination task in a way comparable to electrical microstimulation, which demonstrates the potential use of our methods in both fundamental research and clinical applications.

Black-Capped Chickadee (Poecile atricapillus) and Human (Homo sapiens) Chord Discrimination

Human music perception is related both to musical experience and the physical properties of sound. Examining the processing of music by nonhuman animals has been generally neglected. We tested both black-capped chickadees and humans in a chord discrimination task that replicates and extends prior research with pigeons. We found that chickadees and humans, in common with pigeons, showed similar patterns of discrimination across manipulations of the 3rd and 5th notes of the triadic chords. For all species (chickadee and humans here, pigeons previously), chords with half-step alterations in the 5th note were easier to discriminate than half-step manipulations of the 3rd note, which is likely due to the sensory consonance of these chords. There were differences among species in terms of the fine discrimination of the chords within this larger pattern of results. Further, the ability to relearn the chords when transposed to a new root differed across species. Our results provide new comparative data suggesting some similarities in chord perception that span a wide range of species, from pigeons (nonvocal learners) to songbirds and humans (vocal learners).

Scene-based contextual cueing in pigeons.

Repeated pairings of a particular visual context with a specific location of a target stimulus facilitate target search in humans. We explored an animal model of such contextual cueing. Pigeons had to peck a target, which could appear in 1 of 4 locations on color photographs of real-world scenes. On half of the trials, each of 4 scenes was consistently paired with 1 of 4 possible target locations; on the other half of the trials, each of 4 different scenes was randomly paired with the same 4 possible target locations. In Experiments 1 and 2, pigeons exhibited robust contextual cueing when the context preceded the target by 1 s to 8 s, with reaction times to the target being shorter on predictive-scene trials than on random-scene trials. Pigeons also responded more frequently during the delay on predictive-scene trials than on random-scene trials; indeed, during the delay on predictive-scene trials, pigeons predominately pecked toward the location of the upcoming target, suggesting that attentional guidance contributes to contextual cueing. In Experiment 3, involving left-right and top-bottom scene reversals, pigeons exhibited stronger control by global than by local scene cues. These results attest to the robustness and associative basis of contextual cueing in pigeons.

Dynamic cue use in pigeon mid-session reversal

The systematic anticipation and preservation errors produced by pigeons around the reversal point in midsession reversal (MSR) learning experiments suggest that an internal time estimation cue, instead of a more efficient external cue provided by reinforcement, controls behavior over the course of a session. The current experiments examined the role and effectiveness of other external cues in the MSR task. In Experiment 1, providing differential outcomes based on response key location produced fewer errors prior to, but not after, the reversal as compared with a non-differential outcomes condition. Experiment 2a used alternating differentially colored ITIs (cued sessions) or dark ITIs (un-cued sessions) during each half of the session. The ITI cues improved switch efficiency both prior to and after the reversal. Experiment 2b introduced probe trials around the reversal, testing ITI color cues added to un-cued sessions or removed from cued sessions. Results showed control by the ITI cues when they were available and control by the time-based cue when they were unavailable. This suggests both cues were being simultaneously processed when available and that the cues could also independently provide sufficient information about future reinforcement. In Experiment 2c, ITI cues were inserted as probe trials in the opposite half of the session (miscues). The closer such miscue trials were to the reversal, the more the ITI cues exerted control over behavior. Together, these results indicate that as the utility of internal temporal cues is reduced, the use of external visual cues increases. These results have implications for the way in which cues dynamically shift in controlling behavior over time based on their relative rates of utility, and are discussed in light of an occasion setting perspective.

Monitoring same/different discrimination behavior in time and space: Finding differences and anticipatory discrimination behavior

Discrimination behavior in a standard, two-alternative forced choice same/different task is usually measured by the pigeon’s pecking one or the other of two arbitrary report areas. We found that pigeons make anticipatory, discriminative responses to the visual display during the stimulus observing period prior to the availability of the report areas; the spatial distribution of these anticipatory discriminative responses strongly correlated with the upcoming choice response. These anticipatory pecks provide evidence that the process of discrimination occurs well before the moment of choice and that key aspects of this process can be revealed by looking at the distribution of observing responses. We also manipulated the variability of the displayed items to study the nature of these anticipatory responses; again, the spatial distribution of responding during the stimulus observing period strongly correlated with the upcoming choice response. The distribution of these prechoice pecks supports the theory that pigeons search for differences in the displayed items. If differences are found, then pigeons prepare to report “different”; if not, then they report “same.”

The interaction between global and local scene features in contextual cueing

With local and global contexts clearly segregated, and with the target appearing only in the local array, the present method provided a strong test of our hypothesis that the two sources of information are integrated. During the training block, we found contextual cueing when subjects searched in repeated arrays (global and local predictive), suggesting that participants were sensitive to the spatial regularity in either global scene, th l l b th driven primarily by memory for local elements near the target location (Olson & Chun, 2002). In contrast, studies using real-world scene stimuli have found that contextual cueing is driven primarily by memory for global scene features (Brockmole et al., 2006). Participants completed a training session of 24 blocks of 16 trials. Within a block, each of the 16 global scene items appeared once. Training e oca array or o .