Dynamics of cortical contrast adaptation predict perception of signals in noise.

Neurons throughout the sensory pathway adapt their responses depending on the statistical structure of the sensory environment. Contrast gain control is a form of adaptation in the auditory cortex, but it is unclear whether the dynamics of gain control reflect efficient adaptation, and whether they shape behavioral perception. Here, we trained mice to detect a target presented in background noise shortly after a change in the contrast of the background. The observed changes in cortical gain and behavioral detection followed the dynamics of a normative model of efficient contrast gain control; specifically, target detection and sensitivity improved slowly in low contrast, but degraded rapidly in high contrast. Auditory cortex was required for this task, and cortical responses were not only similarly affected by contrast but predicted variability in behavioral performance. Combined, our results demonstrate that dynamic gain adaptation supports efficient coding in auditory cortex and predicts the perception of sounds in noise.

Environmental dynamics shape perceptual decision bias.

To interpret the sensory environment, the brain combines ambiguous sensory measurements with knowledge that reflects context-specific prior experience. But environmental contexts can change abruptly and unpredictably, resulting in uncertainty about the current context. Here we address two questions: how should context-specific prior knowledge optimally guide the interpretation of sensory stimuli in changing environments, and do human decision-making strategies resemble this optimum? We probe these questions with a task in which subjects report the orientation of ambiguous visual stimuli that were drawn from three dynamically switching distributions, representing different environmental contexts. We derive predictions for an ideal Bayesian observer that leverages knowledge about the statistical structure of the task to maximize decision accuracy, including knowledge about the dynamics of the environment. We show that its decisions are biased by the dynamically changing task context. The magnitude of this decision bias depends on the observer's continually evolving belief about the current context. The model therefore not only predicts that decision bias will grow as the context is indicated more reliably, but also as the stability of the environment increases, and as the number of trials since the last context switch grows. Analysis of human choice data validates all three predictions, suggesting that the brain leverages knowledge of the statistical structure of environmental change when interpreting ambiguous sensory signals.

Panoramic visual statistics shape retina-wide organization of receptive fields.

Statistics of natural scenes are not uniform-their structure varies dramatically from ground to sky. It remains unknown whether these nonuniformities are reflected in the large-scale organization of the early visual system and what benefits such adaptations would confer. Here, by relying on the efficient coding hypothesis, we predict that changes in the structure of receptive fields across visual space increase the efficiency of sensory coding. Using the mouse (Mus musculus) as a model species, we show that receptive fields of retinal ganglion cells change their shape along the dorsoventral retinal axis, with a marked surround asymmetry at the visual horizon, in agreement with our predictions. Our work demonstrates that, according to principles of efficient coding, the panoramic structure of natural scenes is exploited by the retina across space and cell types.

Efficient coding theory of dynamic attentional modulation.

Activity of sensory neurons is driven not only by external stimuli but also by feedback signals from higher brain areas. Attention is one particularly important internal signal whose presumed role is to modulate sensory representations such that they only encode information currently relevant to the organism at minimal cost. This hypothesis has, however, not yet been expressed in a normative computational framework. Here, by building on normative principles of probabilistic inference and efficient coding, we developed a model of dynamic population coding in the visual cortex. By continuously adapting the sensory code to changing demands of the perceptual observer, an attention-like modulation emerges. This modulation can dramatically reduce the amount of neural activity without deteriorating the accuracy of task-specific inferences. Our results suggest that a range of seemingly disparate cortical phenomena such as intrinsic gain modulation, attention-related tuning modulation, and response variability could be manifestations of the same underlying principles, which combine efficient sensory coding with optimal probabilistic inference in dynamic environments.

Efficient and adaptive sensory codes.

The ability to adapt to changes in stimulus statistics is a hallmark of sensory systems. Here, we developed a theoretical framework that can account for the dynamics of adaptation from an information processing perspective. We use this framework to optimize and analyze adaptive sensory codes, and we show that codes optimized for stationary environments can suffer from prolonged periods of poor performance when the environment changes. To mitigate the adversarial effects of these environmental changes, sensory systems must navigate tradeoffs between the ability to accurately encode incoming stimuli and the ability to rapidly detect and adapt to changes in the distribution of these stimuli. We derive families of codes that balance these objectives, and we demonstrate their close match to experimentally observed neural dynamics during mean and variance adaptation. Our results provide a unifying perspective on adaptation across a range of sensory systems, environments, and sensory tasks.

Statistical analysis and optimality of neural systems.

Normative theories and statistical inference provide complementary approaches for the study of biological systems. A normative theory postulates that organisms have adapted to efficiently solve essential tasks and proceeds to mathematically work out testable consequences of such optimality; parameters that maximize the hypothesized organismal function can be derived ab initio, without reference to experimental data. In contrast, statistical inference focuses on the efficient utilization of data to learn model parameters, without reference to any a priori notion of biological function. Traditionally, these two approaches were developed independently and applied separately. Here, we unify them in a coherent Bayesian framework that embeds a normative theory into a family of maximum-entropy "optimization priors." This family defines a smooth interpolation between a data-rich inference regime and a data-limited prediction regime. Using three neuroscience datasets, we demonstrate that our framework allows one to address fundamental challenges relating to inference in high-dimensional, biological problems.

Ecological origins of perceptual grouping principles in the auditory system.

Events and objects in the world must be inferred from sensory signals to support behavior. Because sensory measurements are temporally and spatially local, the estimation of an object or event can be viewed as the grouping of these measurements into representations of their common causes. Perceptual grouping is believed to reflect internalized regularities of the natural environment, yet grouping cues have traditionally been identified using informal observation and investigated using artificial stimuli. The relationship of grouping to natural signal statistics has thus remained unclear, and additional or alternative cues remain possible. Here, we develop a general methodology for relating grouping to natural sensory signals and apply it to derive auditory grouping cues from natural sounds. We first learned local spectrotemporal features from natural sounds and measured their co-occurrence statistics. We then learned a small set of stimulus properties that could predict the measured feature co-occurrences. The resulting cues included established grouping cues, such as harmonic frequency relationships and temporal coincidence, but also revealed previously unappreciated grouping principles. Human perceptual grouping was predicted by natural feature co-occurrence, with humans relying on the derived grouping cues in proportion to their informativity about co-occurrence in natural sounds. The results suggest that auditory grouping is adapted to natural stimulus statistics, show how these statistics can reveal previously unappreciated grouping phenomena, and provide a framework for studying grouping in natural signals.

Adaptive coding for dynamic sensory inference.

Behavior relies on the ability of sensory systems to infer properties of the environment from incoming stimuli. The accuracy of inference depends on the fidelity with which behaviorally relevant properties of stimuli are encoded in neural responses. High-fidelity encodings can be metabolically costly, but low-fidelity encodings can cause errors in inference. Here, we discuss general principles that underlie the tradeoff between encoding cost and inference error. We then derive adaptive encoding schemes that dynamically navigate this tradeoff. These optimal encodings tend to increase the fidelity of the neural representation following a change in the stimulus distribution, and reduce fidelity for stimuli that originate from a known distribution. We predict dynamical signatures of such encoding schemes and demonstrate how known phenomena, such as burst coding and firing rate adaptation, can be understood as hallmarks of optimal coding for accurate inference.

Learning Midlevel Auditory Codes from Natural Sound Statistics.

Interaction with the world requires an organism to transform sensory signals into representations in which behaviorally meaningful properties of the environment are made explicit. These representations are derived through cascades of neuronal processing stages in which neurons at each stage recode the output of preceding stages. Explanations of sensory coding may thus involve understanding how low-level patterns are combined into more complex structures. To gain insight into such midlevel representations for sound, we designed a hierarchical generative model of natural sounds that learns combinations of spectrotemporal features from natural stimulus statistics. In the first layer, the model forms a sparse convolutional code of spectrograms using a dictionary of learned spectrotemporal kernels. To generalize from specific kernel activation patterns, the second layer encodes patterns of time-varying magnitude of multiple first-layer coefficients. When trained on corpora of speech and environmental sounds, some second-layer units learned to group similar spectrotemporal features. Others instantiate opponency between distinct sets of features. Such groupings might be instantiated by neurons in the auditory cortex, providing a hypothesis for midlevel neuronal computation.

The opponent channel population code of sound location is an efficient representation of natural binaural sounds.

In mammalian auditory cortex, sound source position is represented by a population of broadly tuned neurons whose firing is modulated by sounds located at all positions surrounding the animal. Peaks of their tuning curves are concentrated at lateral position, while their slopes are steepest at the interaural midline, allowing for the maximum localization accuracy in that area. These experimental observations contradict initial assumptions that the auditory space is represented as a topographic cortical map. It has been suggested that a "panoramic" code has evolved to match specific demands of the sound localization task. This work provides evidence suggesting that properties of spatial auditory neurons identified experimentally follow from a general design principle- learning a sparse, efficient representation of natural stimuli. Natural binaural sounds were recorded and served as input to a hierarchical sparse-coding model. In the first layer, left and right ear sounds were separately encoded by a population of complex-valued basis functions which separated phase and amplitude. Both parameters are known to carry information relevant for spatial hearing. Monaural input converged in the second layer, which learned a joint representation of amplitude and interaural phase difference. Spatial selectivity of each second-layer unit was measured by exposing the model to natural sound sources recorded at different positions. Obtained tuning curves match well tuning characteristics of neurons in the mammalian auditory cortex. This study connects neuronal coding of the auditory space with natural stimulus statistics and generates new experimental predictions. Moreover, results presented here suggest that cortical regions with seemingly different functions may implement the same computational strategy-efficient coding.

Statistics of natural binaural sounds.

Binaural sound localization is usually considered a discrimination task, where interaural phase (IPD) and level (ILD) disparities at narrowly tuned frequency channels are utilized to identify a position of a sound source. In natural conditions however, binaural circuits are exposed to a stimulation by sound waves originating from multiple, often moving and overlapping sources. Therefore statistics of binaural cues depend on acoustic properties and the spatial configuration of the environment. Distribution of cues encountered naturally and their dependence on physical properties of an auditory scene have not been studied before. In the present work we analyzed statistics of naturally encountered binaural sounds. We performed binaural recordings of three auditory scenes with varying spatial configuration and analyzed empirical cue distributions from each scene. We have found that certain properties such as the spread of IPD distributions as well as an overall shape of ILD distributions do not vary strongly between different auditory scenes. Moreover, we found that ILD distributions vary much weaker across frequency channels and IPDs often attain much higher values, than can be predicted from head filtering properties. In order to understand the complexity of the binaural hearing task in the natural environment, sound waveforms were analyzed by performing Independent Component Analysis (ICA). Properties of learned basis functions indicate that in natural conditions soundwaves in each ear are predominantly generated by independent sources. This implies that the real-world sound localization must rely on mechanisms more complex than a mere cue extraction.

Position of acoustic stimulus modulates visual α activity.

It has been repeatedly shown that a unimodal stimulus can modulate oscillatory activity of multiple cortical areas already at early stages of sensory processing. In this way, an influence can be exerted on the response to a subsequent sensory input. Even though this fact is now well established, it is still not clear whether cortical sensory areas are informed about spatial positions of objects of modality other than their preferred one. Here, we test the hypothesis of whether oscillatory activity of the human visual cortex depends on the position of a unimodal auditory object. We recorded electroencephalogram while presenting sounds in an acoustic free-field either at the center of the visual field or at lateral positions. Using independent component analysis, we identified three cortical sources located in the visual cortex, showing stimulus position-specific oscillatory responses. The most pronounced effect was an immediate α (8-12 Hz) power decrease over the entire occipital lobe when the stimulus originated from the center of the binocular visual field. Following a lateral stimulation, the amplitude of α activity decreased slightly over contralateral visual areas, while at the same time a weak α synchronization was observed in corresponding ipsilateral areas. Thus, even in the absence of visual stimuli, the visual cortex is differentially activated depending on the position of an acoustic sound source. Our results show that the visual cortex receives information about the position of auditory stimuli within the visual field.

Efficient coding of spectrotemporal binaural sounds leads to emergence of the auditory space representation.

To date a number of studies have shown that receptive field shapes of early sensory neurons can be reproduced by optimizing coding efficiency of natural stimulus ensembles. A still unresolved question is whether the efficient coding hypothesis explains formation of neurons which explicitly represent environmental features of different functional importance. This paper proposes that the spatial selectivity of higher auditory neurons emerges as a direct consequence of learning efficient codes for natural binaural sounds. Firstly, it is demonstrated that a linear efficient coding transform-Independent Component Analysis (ICA) trained on spectrograms of naturalistic simulated binaural sounds extracts spatial information present in the signal. A simple hierarchical ICA extension allowing for decoding of sound position is proposed. Furthermore, it is shown that units revealing spatial selectivity can be learned from a binaural recording of a natural auditory scene. In both cases a relatively small subpopulation of learned spectrogram features suffices to perform accurate sound localization. Representation of the auditory space is therefore learned in a purely unsupervised way by maximizing the coding efficiency and without any task-specific constraints. This results imply that efficient coding is a useful strategy for learning structures which allow for making behaviorally vital inferences about the environment.

Novel drug-regulated transcriptional networks in brain reveal pharmacological properties of psychotropic drugs.

BACKGROUND: Despite their widespread use, the biological mechanisms underlying the efficacy of psychotropic drugs are still incompletely known; improved understanding of these is essential for development of novel more effective drugs and rational design of therapy. Given the large number of psychotropic drugs available and their differential pharmacological effects, it would be important to establish specific predictors of response to various classes of drugs. RESULTS: To identify the molecular mechanisms that may initiate therapeutic effects, whole-genome expression profiling (using 324 Illumina Mouse WG-6 microarrays) of drug-induced alterations in the mouse brain was undertaken, with a focus on the time-course (1, 2, 4 and 8 h) of gene expression changes produced by eighteen major psychotropic drugs: antidepressants, antipsychotics, anxiolytics, psychostimulants and opioids. The resulting database is freely accessible at http://www.genes2mind.org. Bioinformatics approaches led to the identification of three main drug-responsive genomic networks and indicated neurobiological pathways that mediate the alterations in transcription. Each tested psychotropic drug was characterized by a unique gene network expression profile related to its neuropharmacological properties. Functional links that connect expression of the networks to the development of neuronal adaptations (MAPK signaling pathway), control of brain metabolism (adipocytokine pathway), and organization of cell projections (mTOR pathway) were found. CONCLUSIONS: The comparison of gene expression alterations between various drugs opened a new means to classify the different psychoactive compounds and to predict their cellular targets; this is well exemplified in the case of tianeptine, an antidepressant with unknown mechanisms of action. This work represents the first proof-of-concept study of a molecular classification of psychoactive drugs.