Susan E. Boehnke

On the importance of the transient visual response in the superior colliculus

A salient event in the environment can initiate a complex orienting response that includes a shift in gaze. The midbrain superior colliculus (SC) contains the appropriate circuitry to generate and distribute a signal of the priority of this event, and co-ordinate the orienting response. The magnitude and timing of the short-latency transient visual response in the SC, when combined with cortical inputs signaling stimulus relevance and expectation, influences the type and latency of the orienting response. This signal in the SC is distributed to higher cortical areas to influence visual processing, to the reinforcement learning system to influence future actions, and to premotor circuits, including neck and shoulder muscles, to influence immediate action.

Free viewing of dynamic stimuli by humans and monkeys

Due to extensive homologies, monkeys provide a sophisticated animal model of human visual attention. However, for electrophysiological recording in behaving animals simplified stimuli and controlled eye position are traditionally used. To validate monkeys as a model for human attention during realistic free viewing, we contrasted human (n = 5) and monkey (n = 5) gaze behavior using 115 natural and artificial video clips. Monkeys exhibited broader ranges of saccadic endpoints and amplitudes and showed differences in fixation and intersaccadic intervals. We compared tendencies of both species to gaze toward scene elements with similar low-level visual attributes using two computational models--luminance contrast and saliency. Saliency was more predictive of both human and monkey gaze, predicting human saccades better than monkey saccades overall. Quantifying interobserver gaze consistency revealed that while humans were highly consistent, monkeys were more heterogeneous and were best predicted by the saliency model. To address these discrepancies, we further analyzed high-interest gaze targets--those locations simultaneously chosen by at least two monkeys. These were on average very similar to human gaze targets, both in terms of specific locations and saliency values. Although substantial quantitative differences were revealed, strong similarities existed between both species, especially when focusing analysis onto high-interest targets.

Color-Related Signals in the Primate Superior Colliculus

Color is important for segmenting objects from backgrounds, which can in turn facilitate visual search in complex scenes. However, brain areas involved in orienting the eyes toward colored stimuli in our environment are not believed to have access to color information. Here, we show that neurons in the intermediate layers of the monkey superior colliculus (SC), a critical structure for the production of saccadic eye movements, can respond to isoluminant color stimuli with the same magnitude as a maximum contrast luminance stimulus. In contrast, neurons from the superficial SC layers showed little color-related activity. Crucially, visual onset latencies were 30–35 ms longer for color, implying that luminance and chrominance information reach the SC through distinct pathways and that the observed color-related activity is not the result of residual luminance signals. Furthermore, these differences in visual onset latency translated directly into differences in saccadic reaction time. The results demonstrate that the saccadic system can signal the presence of chromatic stimuli only one stage from the brainstem premotor circuitry that drives the eyes.

Alzheimer's Disease-Like Pathology Induced by Amyloid-β Oligomers in Nonhuman Primates

Alzheimers disease (AD) is a devastating neurodegenerative disorder and a major medical problem. Here, we have investigated the impact of amyloid-β (Aβ) oligomers, AD-related neurotoxins, in the brains of rats and adult nonhuman primates (cynomolgus macaques). Soluble Aβ oligomers are known to accumulate in the brains of AD patients and correlate with disease-associated cognitive dysfunction. When injected into the lateral ventricle of rats and macaques, Aβ oligomers diffused into the brain and accumulated in several regions associated with memory and cognitive functions. Cardinal features of AD pathology, including synapse loss, tau hyperphosphorylation, astrocyte and microglial activation, were observed in regions of the macaque brain where Aβ oligomers were abundantly detected. Most importantly, oligomer injections induced AD-type neurofibrillary tangle formation in the macaque brain. These outcomes were specifically associated with Aβ oligomers, as fibrillar amyloid deposits were not detected in oligomer-injected brains. Human and macaque brains share significant similarities in terms of overall architecture and functional networks. Thus, generation of a macaque model of AD that links Aβ oligomers to tau and synaptic pathology has the potential to greatly advance our understanding of mechanisms centrally implicated in AD pathogenesis. Furthermore, development of disease-modifying therapeutics for AD has been hampered by the difficulty in translating therapies that work in rodents to humans. This new approach may be a highly relevant nonhuman primate model for testing therapeutic interventions for AD.

Microstimulation of the Monkey Superior Colliculus Induces Pupil Dilation Without Evoking Saccades

The orienting reflex is initiated by a salient stimulus and facilitates quick, appropriate action. It involves a rapid shift of the eyes, head, and attention and other physiological responses such as changes in heart rate and transient pupil dilation. The SC is a critical structure in the midbrain that selects incoming stimuli based on saliency and relevance to coordinate orienting behaviors, particularly gaze shifts, but its causal role in pupil dilation remains poorly understood in mammals. Here, we examined the role of the primate SC in the control of pupil dynamics. While requiring monkeys to keep their gaze fixed, we delivered weak electrical microstimulation to the SC, so that saccadic eye movements were not evoked. Pupil size increased transiently after microstimulation of the intermediate SC layers (SCi) and the size of evoked pupil dilation was larger on a dim versus bright background. In contrast, microstimulation of the superficial SC layers did not cause pupil dilation. Thus, the SCi is directly involved not only in shifts of gaze and attention, but also in pupil dilation as part of the orienting reflex, and the function of pupil dilation may be related to increasing visual sensitivity. The shared neural mechanisms suggest that pupil dilation may be associated with covert attention.

Detection of static and dynamic changes in interaural correlation

This study examines the relation between a static and a dynamic measure of interaural correlation discrimination: (1) the just noticeable difference (JND) in interaural correlation and (2) the minimum detectable duration of a fixed interaural correlation change embedded within a single noise-burst of a given reference correlation. For the first task, JNDs were obtained from reference interaural correlations of + 1, -1, and from 0 interaural correlation in either the positive or negative direction. For the dynamic task, duration thresholds were obtained for a brief target noise of +1, -1, and 0 interaural correlation embedded in reference marker noise of +1, -1, and 0 interaural correlation. Performance with a reference interaural correlation of +1 was significantly better than with a reference correlation of -1. Similarly, when the reference noise was interaurally uncorrelated, discrimination was significantly better for a target correlation change towards +1 than towards -1. Thus, for both static and dynamic tasks, interaural correlation discrimination in the positive range was significantly better than in the negative range. Using the two measures, the length of a binaural temporal window was estimated. Its equivalent rectangular duration (ERD) was approximately 86 ms and independent of the interaural correlation configuration.

Azimuthal tuning of human perceptual channels for sound location

Human sound localization is acute for frontal locations, but relatively poor in the lateral hemifields. Previous studies in man have not, however, provided evidence on the tuning of the perceptual channels for auditory space that subserve this pattern of acuity. The spatial tuning of perceptual channels used in human azimuthal sound localization was determined using a between-channel auditory temporal gap detection paradigm. In this paradigm, gap thresholds are low when the markers bounding the silent period (gap) activate the same perceptual channel but are elevated when the two markers activate different channels. To determine the tuning of spatial channels, gap thresholds were obtained in an anechoic room with white noise markers coming from each combination of 12 leading marker locations and 18 trailing marker locations throughout the full 360 degrees of azimuth in the horizontal plane through the interaural axis. Gap thresholds remained low (2-4 ms) for all combinations of leading and trailing markers between 30 degrees and 150 degrees in both lateral hemifields. When the leading marker was located deep in one hemifield, and the trailing marker was in the opposite hemifield, gap thresholds rose to 8-16 ms. For leading marker locations at 30 degrees from the midline, gap thresholds were low for all trailing marker locations in the ipsilateral hemifield and locations near the midline in the contralateral hemifield, and were elevated (6-8 ms) only near the contralateral pole. Finally, for leading marker locations at 0 degree or 180 degrees, gap thresholds were low for any trailing location within 30 degrees of the midline at the front or back, and thresholds were elevated for trailing locations at the lateral poles. These data are accountable in terms of two broadly tuned perceptual channels, occupying the left and right auditory hemifields, respectively, each extending 30 degrees across the midline. These channels have widths and locations similar to the spatial receptive fields previously described for central auditory neurons in animals. The data suggest a model of spatial acuity based on the rates of activation of two spatially overlapping channels, rather than the selective activation of members of a large population of finely tuned channels.

Linking visual response properties in the superior colliculus to saccade behavior

Here we examined the influence of the visual response in the superior colliculus (SC) (an oculomotor control structure integrating sensory, motor and cognitive signals) on the development of the motor command that drives saccadic eye movements in monkeys. We varied stimulus luminance to alter the timing and magnitude of visual responses in the SC and examined how these changes correlated with resulting saccade behavior. Increasing target luminance resulted in multiple modulations of the visual response, including increased magnitude and decreased response onset latency. These signal modulations correlated strongly with changes in saccade latency and metrics, indicating that these signal properties carry through to the neural computations that determine when, where and how fast the eyes will move. Thus, components of the earliest part of the visual response in the SC provide important building blocks for the neural basis of the sensory–motor transformation, highlighting a critical link between the properties of the visual response and saccade behavior.

Visual adaptation and novelty responses in the superior colliculus

The brain’s ability to ignore repeating, often redundant, information while enhancing novel information processing is paramount to survival. When stimuli are repeatedly presented, the response of visually sensitive neurons decreases in magnitude, that is, neurons adapt or habituate, although the mechanism is not yet known. We monitored the activity of visual neurons in the superior colliculus (SC) of rhesus monkeys who actively fixated while repeated visual events were presented. We dissociated adaptation from habituation as mechanisms of the response decrement by using a Bayesian model of adaptation, and by employing a paradigm including rare trials that included an oddball stimulus that was either brighter or dimmer. If the mechanism is adaptation, response recovery should be seen only for the brighter stimulus; if the mechanism is habituation, response recovery (‘dishabituation’) should be seen for both the brighter and dimmer stimuli. We observed a reduction in the magnitude of the initial transient response and an increase in response onset latency with stimulus repetition for all visually responsive neurons in the SC. Response decrement was successfully captured by the adaptation model, which also predicted the effects of presentation rate and rare luminance changes. However, in a subset of neurons with sustained activity in response to visual stimuli, a novelty signal akin to dishabituation was observed late in the visual response profile for both brighter and dimmer stimuli, and was not captured by the model. This suggests that SC neurons integrate both rapidly discounted information about repeating stimuli and novelty information about oddball events, to support efficient selection in a cluttered dynamic world.

The relation between auditory temporal interval processing and sequential stream segregation examined with stimulus laterality differences

In this study, we examine the effects of laterality differences between noise bursts on two objective measures of temporal interval processing (gap detection and temporal asymmetry detection) and one subjective measure of temporal organization (stream segregation). Noise bursts were lateralized by presentation to different ears or dichotic presentation with oppositely signed interaural level (ILD) or time (ITD) differences. Objective thresholds were strongly affected by ear-of-entry differences, were moderately affected by ILD differences, but were unaffected by ITD differences. Subjectively, A and B streams segregated well on the basis of ear-of-entry or ILD differences but segregated poorly on the basis of ITD differences. These results suggest that perceptual segregation may be driven more effectively by differential activation of the two ears (peripheral channeling) than by differences in perceived laterality.