Electrophysiological responses to appetitive and consummatory behavior in the rostral nucleus tractus solitarius in awake, unrestrained rats.

As the intermediate nucleus in the brainstem receiving information from the tongue and transmitting information upstream, the rostral portion of the nucleus tractus solitarius (rNTS) is most often described as a "taste relay". Although recent evidence implicates the NTS in a broad neural circuit involved in regulating ingestion, there is little information about how cells in this structure respond when an animal is eating solid food. Here, single cells in the rNTS were recorded in awake, unrestrained rats as they explored and ate solid foods (Eating paradigm) chosen to correspond to the basic taste qualities: milk chocolate for sweet, salted peanuts for salty, Granny Smith apples for sour and broccoli for bitter. A subset of cells was also recorded as the animal licked exemplars of the five basic taste qualities: sucrose, NaCl, citric acid, quinine and MSG (Lick paradigm). Results showed that most cells were excited by exploration of a food-filled well, sometimes responding prior to contact with the food. In contrast, cells that were excited by food well exploration became significantly less active while the animal was eating the food. Most cells were broadly tuned across foods, and those cells that were recorded in both the Lick and Eating paradigms showed little correspondence in their tuning across paradigms. The preponderance of robust responses to the appetitive versus the consummatory phase of ingestion suggests that multimodal convergence onto cells in the rNTS may be used in decision making about ingestion.

The Geometry of Low- and High-Level Perceptual Spaces.

Low-level features are typically continuous (e.g., the gamut between two colors), but semantic information is often categorical (there is no corresponding gradient between dog and turtle) and hierarchical (animals live in land, water, or air). To determine the impact of these differences on cognitive representations, we characterized the geometry of perceptual spaces of five domains: a domain dominated by semantic information (animal names presented as words), a domain dominated by low-level features (colored textures), and three intermediate domains (animal images, lightly texturized animal images that were easy to recognize, and heavily texturized animal images that were difficult to recognize). Each domain had 37 stimuli derived from the same animal names. From 13 participants (9F), we gathered similarity judgments in each domain via an efficient psychophysical ranking paradigm. We then built geometric models of each domain for each participant, in which distances between stimuli accounted for participants' similarity judgments and intrinsic uncertainty. Remarkably, the five domains had similar global properties: each required 5-7 dimensions, and a modest amount of spherical curvature provided the best fit. However, the arrangement of the stimuli within these embeddings depended on the level of semantic information: dendrograms derived from semantic domains (word, image, and lightly texturized images) were more "tree-like" than those from feature-dominated domains (heavily texturized images and textures). Thus, the perceptual spaces of domains along this feature-dominated to semantic-dominated gradient shift to a tree-like organization when semantic information dominates, while retaining a similar global geometry.

Local texture statistics augment the power spectrum in modeling radiographic judgments of breast density.

Purpose: Anatomical "noise" is an important limitation of full-field digital mammography. Understanding its impact on clinical judgments is made difficult by the complexity of breast parenchyma, which results in image texture not fully captured by the power spectrum. While the number of possible parameters for characterizing anatomical noise is quite large, a specific set of local texture statistics has been shown to be visually salient, and human sensitivity to these statistics corresponds to their informativeness in natural scenes. Approach: We evaluate these local texture statistics in addition to standard power-spectral measures to determine whether they have additional explanatory value for radiologists' breast density judgments. We analyzed an image database consisting of 111 disease-free mammographic screening exams (4 views each) acquired at the University of Pittsburgh Medical Center. Each exam had a breast density score assigned by the examining radiologist. Power-spectral descriptors and local image statistics were extracted from images of breast parenchyma. Model-selection criteria and accuracy were used to assess the explanatory and predictive value of local image statistics for breast density judgments. Results: The model selection criteria show that adding local texture statistics to descriptors of the power spectra produce better explanatory and predictive models of radiologists' judgments of breast density. Thus, local texture statistics capture, in some form, non-Gaussian aspects of texture that radiologists are using. Conclusions: Since these local texture statistics are expected to be impacted by imaging factors like modality, dose, and image processing, they suggest avenues for understanding and optimizing observer performance.

Thalamic deep brain stimulation in traumatic brain injury: a phase 1, randomized feasibility study.

Converging evidence indicates that impairments in executive function and information-processing speed limit quality of life and social reentry after moderate-to-severe traumatic brain injury (msTBI). These deficits reflect dysfunction of frontostriatal networks for which the central lateral (CL) nucleus of the thalamus is a critical node. The primary objective of this feasibility study was to test the safety and efficacy of deep brain stimulation within the CL and the associated medial dorsal tegmental (CL/DTTm) tract.Six participants with msTBI, who were between 3 and 18 years post-injury, underwent surgery with electrode placement guided by imaging and subject-specific biophysical modeling to predict activation of the CL/DTTm tract. The primary efficacy measure was improvement in executive control indexed by processing speed on part B of the trail-making test.All six participants were safely implanted. Five participants completed the study and one was withdrawn for protocol non-compliance. Processing speed on part B of the trail-making test improved 15% to 52% from baseline, exceeding the 10% benchmark for improvement in all five cases.CL/DTTm deep brain stimulation can be safely applied and may improve executive control in patients with msTBI who are in the chronic phase of recovery.ClinicalTrials.gov identifier: NCT02881151 .

Ordinal Characterization of Similarity Judgments.

Characterizing judgments of similarity within a perceptual or semantic domain, and making inferences about the underlying structure of this domain from these judgments, has an increasingly important role in cognitive and systems neuroscience. We present a new framework for this purpose that makes very limited assumptions about how perceptual distances are converted into similarity judgments. The approach starts from a dataset of empirical judgments of relative similarities: the fraction of times that a subject chooses one of two comparison stimuli to be more similar to a reference stimulus. These empirical judgments provide Bayesian estimates of underling choice probabilities. From these estimates, we derive three indices that characterize the set of judgments, measuring consistency with a symmetric dis-similarity, consistency with an ultrametric space, and consistency with an additive tree. We illustrate this approach with example psychophysical datasets of dis-similarity judgments in several visual domains and provide code that implements the analyses.

Poster Session: Oculomotor influences on retinal input signals in myopia.

Studies of emmetropization have traditionally focused on the spatial characteristics of visual input signals. Yet the input to the retina is not a two-dimensional pattern but a temporally-varying luminance flow. The temporal structure of this flow is predominately determined by eye movements, as the human eyes move incessantly. Even when fixating on a single point, a persistent motion known as ocular drift reformats the luminance flow in a way that counterbalances the spectra of natural scenes. It is established that emmetropes are highly sensitive to these luminance modulations. However, their visual consequences in myopia and hyperopia are unknown. Here, we first review how the temporal-frequency distribution of retinal input signals varies with the amount of ocular drift. We then use a detailed optical/geometrical model of the eye to study how the eye movements jointly shape retinal input as a function of refraction. We show that, within the temporal range of sensitivity of the retina, the spatial frequency distribution of the input signals conveys signed information about defocus. Specifically, for a given degree of defocus, myopic retinas experience more power from low spatial frequency stimuli than hyperopic retinas. These redistribution of input power may have a consequence during eye growth supporting the proposal that eye movements should be taken into consideration in the process of emmetropization.

Application of a Hermite-based measure of non-Gaussianity to normality tests and independent component analysis.

In the analysis of neural data, measures of non-Gaussianity are generally applied in two ways: as tests of normality for validating model assumptions and as Independent Component Analysis (ICA) contrast functions for separating non-Gaussian signals. Consequently, there is a wide range of methods for both applications, but they all have trade-offs. We propose a new strategy that, in contrast to previous methods, directly approximates the shape of a distribution via Hermite functions. Applicability as a normality test was evaluated via its sensitivity to non-Gaussianity for three families of distributions that deviate from a Gaussian distribution in different ways (modes, tails, and asymmetry). Applicability as an ICA contrast function was evaluated through its ability to extract non-Gaussian signals in simple multi-dimensional distributions, and to remove artifacts from simulated electroencephalographic datasets. The measure has advantages as a normality test and, for ICA, for heavy-tailed and asymmetric distributions with small sample sizes. For other distributions and large datasets, it performs comparably to existing methods. Compared to standard normality tests, the new method performs better for certain types of distributions. Compared to contrast functions of a standard ICA package, the new method has advantages but its utility for ICA is more limited. This highlights that even though both applications-normality tests and ICA-require a measure of deviation from normality, strategies that are advantageous in one application may not be advantageous in the other. Here, the new method has broad merits as a normality test but only limited advantages for ICA.

Cognitive influences on fixational eye movements.

We perceive the world based on visual information acquired via oculomotor control,1 an activity intertwined with ongoing cognitive processes.2,3,4 Cognitive influences have been primarily studied in the context of macroscopic movements, like saccades and smooth pursuits. However, our eyes are never still, even during periods of fixation. One of the fixational eye movements, ocular drifts, shifts the stimulus over hundreds of receptors on the retina, a motion that has been argued to enhance the processing of spatial detail by translating spatial into temporal information.5 Despite their apparent randomness, ocular drifts are under neural control.6,7,8 However little is known about the control of drift beyond the brainstem circuitry of the vestibulo-ocular reflex.9,10 Here, we investigated the cognitive control of ocular drifts with a letter discrimination task. The experiment was designed to reveal open-loop effects, i.e., cognitive oculomotor control driven by specific prior knowledge of the task, independent of incoming sensory information. Open-loop influences were isolated by randomly presenting pure noise fields (no letters) while subjects engaged in discriminating specific letter pairs. Our results show open-loop control of drift direction in human observers.

Low-level language processing in brain-injured patients.

Assessing cognitive function-especially language processing-in severely brain-injured patients is critical for prognostication, care, and development of communication devices (e.g. brain-computer interfaces). In patients with diminished motor function, language processing has been probed using EEG measures of command-following in motor imagery tasks. While such tests eliminate the need for motor response, they require sustained attention. However, passive listening tasks, with an EEG response measure can reduce both motor and attentional demands. These considerations motivated the development of two assays of low-level language processing-identification of differential phoneme-class responses and tracking of the natural speech envelope. This cross-sectional study looks at a cohort of 26 severely brain-injured patient subjects and 10 healthy controls. Patients' level of function was assessed via the coma recovery scale-revised at the bedside. Patients were also tested for command-following via EEG and/or MRI assays of motor imagery. For the present investigation, EEG was recorded while presenting a 148 s audio clip of Alice in Wonderland. Time-locked EEG responses to phoneme classes were extracted and compared to determine a differential phoneme-class response. Tracking of the natural speech envelope was assessed from the same recordings by cross-correlating the EEG response with the speech envelope. In healthy controls, the dynamics of the two measures were temporally similar but spatially different: a central parieto-occipital component of differential phoneme-class response was absent in the natural speech envelope response. The differential phoneme-class response was present in all patient subjects, including the six classified as vegetative state/unresponsive wakefulness syndrome by behavioural assessment. However, patient subjects with evidence of language processing either by behavioural assessment or motor imagery tests had an early bilateral response in the first 50 ms that was lacking in patient subjects without any evidence of language processing. The natural speech envelope tracking response was also present in all patient subjects and responses in the first 100 ms distinguished patient subjects with evidence of language processing. Specifically, patient subjects with evidence of language processing had a more global response in the first 100 ms whereas those without evidence of language processing had a frontopolar response in that period. In summary, we developed two passive EEG-based methods to probe low-level language processing in severely brain-injured patients. In our cohort, both assays showed a difference between patient subjects with evidence of command-following and those with no evidence of command-following: a more prominent early bilateral response component.

Discrimination of textures with spatial correlations and multiple gray levels.

Analysis of visual texture is important for many key steps in early vision. We study visual sensitivity to image statistics in three families of textures that include multiple gray levels and correlations in two spatial dimensions. Sensitivities to positive and negative correlations are approximately independent of correlation sign, and signals from different kinds of correlations combine quadratically. We build a computational model, fully constrained by prior studies of sensitivity to uncorrelated textures and black-and-white textures with spatial correlations. The model accounts for many features of the new data, including sign-independence, quadratic combination, and the dependence on gray-level distribution.

Inferring visual space from ultra-fine extra-retinal knowledge of gaze position.

It has long been debated how humans resolve fine details and perceive a stable visual world despite the incessant fixational motion of their eyes. Current theories assume these processes to rely solely on the visual input to the retina, without contributions from motor and/or proprioceptive sources. Here we show that contrary to this widespread assumption, the visual system has access to high-resolution extra-retinal knowledge of fixational eye motion and uses it to deduce spatial relations. Building on recent advances in gaze-contingent display control, we created a spatial discrimination task in which the stimulus configuration was entirely determined by oculomotor activity. Our results show that humans correctly infer geometrical relations in the absence of spatial information on the retina and accurately combine high-resolution extraretinal monitoring of gaze displacement with retinal signals. These findings reveal a sensory-motor strategy for encoding space, in which fine oculomotor knowledge is used to interpret the fixational input to the retina.

Geometry of spiking patterns in early visual cortex: a topological data analytic approach.

In the brain, spiking patterns live in a high-dimensional space of neurons and time. Thus, determining the intrinsic structure of this space presents a theoretical and experimental challenge. To address this challenge, we introduce a new framework for applying topological data analysis (TDA) to spike train data and use it to determine the geometry of spiking patterns in the visual cortex. Key to our approach is a parametrized family of distances based on the timing of spikes that quantifies the dissimilarity between neuronal responses. We applied TDA to visually driven single-unit and multiple single-unit spiking activity in macaque V1 and V2. TDA across timescales reveals a common geometry for spiking patterns in V1 and V2 which, among simple models, is most similar to that of a low-dimensional space endowed with Euclidean or hyperbolic geometry with modest curvature. Remarkably, the inferred geometry depends on timescale and is clearest for the timescales that are important for encoding contrast, orientation and spatial correlations.

Functional recursion of orientation cues in figure-ground separation.

Visual texture is an important cue to figure-ground organization. While processing of texture differences is a prerequisite for the use of this cue to extract figure-ground organization, these stages are distinct processes. One potential indicator of this distinction is the possibility that texture statistics play a different role in the figure vs. in the ground. To determine whether this is the case, we probed figure-ground processing with a family of local image statistics that specified textures that varied in the strength and spatial scale of structure, and the extent to which features are oriented. For image statistics that generated approximately isotropic textures, the threshold for identification of figure-ground structure was determined by the difference in correlation strength in figure vs. ground, independent of whether the correlations were present in figure, ground, or both. However, for image statistics with strong orientation content, thresholds were up to two times higher for correlations in the ground, vs. the figure. This held equally for texture-defined objects with convex or concave boundaries, indicating that these threshold differences are driven by border ownership, not boundary shape. Similar threshold differences were found for presentation times ranging from 125 to 500 ms. These findings identify a qualitative difference in how texture is used for figure-ground analysis, vs. texture discrimination. Additionally, it reveals a functional recursion: texture differences are needed to identify tentative boundaries and consequent scene organization into figure and ground, but then scene organization modifies sensitivity to texture differences according to the figure-ground assignment.

Electrophysiological correlates of thalamocortical function in acute severe traumatic brain injury.

Tools assaying the neural networks that modulate consciousness may facilitate tracking of recovery after acute severe brain injury. The ABCD framework classifies resting-state EEG into categories reflecting levels of thalamocortical network function that correlate with outcome in post-cardiac arrest coma. In this longitudinal cohort study, we applied the ABCD framework to 20 patients with acute severe traumatic brain injury requiring intensive care (12 of whom were also studied at ≥6-months post-injury) and 16 healthy controls. We tested four hypotheses: 1) EEG ABCD classifications are spatially heterogeneous and temporally variable; 2) ABCD classifications improve longitudinally, commensurate with the degree of behavioral recovery; 3) ABCD classifications correlate with behavioral level of consciousness; and 4) the Coma Recovery Scale-Revised arousal facilitation protocol yields improved ABCD classifications. Channel-level EEG power spectra were classified based on spectral peaks within pre-defined frequency bands: 'A' = no peaks above delta (<4 Hz) range (complete thalamocortical disruption); 'B' = theta (4-8 Hz) peak (severe thalamocortical disruption); 'C' = theta and beta (13-24 Hz) peaks (moderate thalamocortical disruption); or 'D' = alpha (8-13 Hz) and beta peaks (normal thalamocortical function). Acutely, 95% of patients demonstrated 'D' signals in at least one channel but exhibited within-session temporal variability and spatial heterogeneity in the proportion of different channel-level ABCD classifications. By contrast, healthy participants and patients at follow-up consistently demonstrated signals corresponding to intact thalamocortical network function. Patients demonstrated longitudinal improvement in ABCD classifications (p < .05) and ABCD classification distinguished patients with and without command-following in the subacute-to-chronic phase of recovery (p < .01). In patients studied acutely, ABCD classifications improved after the Coma Recovery Scale-Revised arousal facilitation protocol (p < .05) but did not correspond with behavioral level of consciousness. These findings support the use of the ABCD framework to characterize channel-level EEG dynamics and track fluctuations in functional thalamocortical network integrity in spatial detail.

A Psychophysics Paradigm for the Collection and Analysis of Similarity Judgments.

Similarity judgments are commonly used to study mental representations and their neural correlates. This approach has been used to characterize perceptual spaces in many domains: colors, objects, images, words, and sounds. Ideally, one might want to compare estimates of perceived similarity between all pairs of stimuli, but this is often impractical. For example, if one asks a subject to compare the similarity of two items with the similarity of two other items, the number of comparisons grows with the fourth power of the stimulus set size. An alternative strategy is to ask a subject to rate similarities of isolated pairs, e.g., on a Likert scale. This is much more efficient (the number of ratings grows quadratically with set size rather than quartically), but these ratings tend to be unstable and have limited resolution, and the approach also assumes that there are no context effects. Here, a novel ranking paradigm for efficient collection of similarity judgments is presented, along with an analysis pipeline (software provided) that tests whether Euclidean distance models account for the data. Typical trials consist of eight stimuli around a central reference stimulus: the subject ranks stimuli in order of their similarity to the reference. By judicious selection of combinations of stimuli used in each trial, the approach has internal controls for consistency and context effects. The approach was validated for stimuli drawn from Euclidean spaces of up to five dimensions. The approach is illustrated with an experiment measuring similarities among 37 words. Each trial yields the results of 28 pairwise comparisons of the form, "Was A more similar to the reference than B was to the reference?" While directly comparing all pairs of pairs of stimuli would have required 221445 trials, this design enables reconstruction of the perceptual space from 5994 such comparisons obtained from 222 trials.

Enhancing GABAergic Tone in the Rostral Nucleus of the Solitary Tract Reconfigures Sensorimotor Neural Activity.

Recent work has shown that most cells in the rostral, gustatory portion of the nucleus tractus solitarius (rNTS) in awake, freely licking rats show lick-related firing. However, the relationship between taste-related and lick-related activity in rNTS remains unclear. Here, we tested whether GABA-derived inhibitory activity regulates the balance of lick- and taste-driven neuronal activity. Combinatorial viral tools were used to restrict the expression of channelrhodopsin 2-enhanced yellow fluorescent protein to GAD1+ GABAergic neurons. Viral infusions were bilateral in rNTS. A fiber-optic fiber attached to a bundle of drivable microwires was later implanted into the rNTS. After recovery, water-deprived rats were presented with taste stimuli in an experimental chamber. Trials were five consecutive taste licks [NaCl, KCl, NH4Cl, sucrose, monosodium glutamate/inosine-5'-monophosphate, citric acid, quinine, or artificial saliva (AS)] separated by five AS rinse licks on a variable ratio 5 schedule. Each taste lick triggered a 1 s train of laser light (25 Hz; 473 nm; 8-10 mW) in a random half of the trials. In all, 113 cells were recorded in the rNTS, 50 cells responded to one or more taste stimuli without GABA enhancement. Selective changes in response magnitude (spike count) within cells shifted across-unit patterns but preserved interstimulus relationships. Cells where enhanced GABAergic tone increased lick coherence conveyed more information distinguishing basic taste qualities and different salts than other cells. In addition, GABA activation significantly amplified the amount of information that discriminated palatable versus unpalatable tastants. By dynamically regulating lick coherence and remodeling the across-unit response patterns to taste, enhancing GABAergic tone in rNTS reconfigures the neural activity reflecting sensation and movement.

Visual Search for Circumscribed Interests in Autism Is Similar to That of Neurotypical Individuals.

Intense interests are a core symptom of autism spectrum disorders (ASD) and can be all-encompassing for affected individuals. This observation raises the hypothesis that intense interests in ASD are related to pervasive changes in visual processing for objects within that category, including visual search. We assayed visual processing with two novel tasks, targeting category search and exemplar search. For each task, three kinds of stimuli were used: faces, houses, and images personalized to each participant's interest. 25 children and adults with ASD were compared to 25 neurotypical (NT) children and adults. We found no differences in either visual search task between ASD and NT controls for interests. Thus, pervasive alterations in perception are not likely to account for ASD behavioral symptoms.