Sensory Neurophysiology Research Articles

A note on estimating absolute cytosolic Ca2+ concentration in sensory neurons using a single wavelength Ca2+ indicator.

Ca2+ imaging is frequently used in the investigation of sensory neuronal function and nociception. In vitro imaging of acutely dissociated sensory neurons using membrane-permeant fluorescent Ca2+ indicators remains the most common approach to study Ca2+ signalling in sensory neurons. Fluo4 is a popular choice of single-wavelength indicator due to its brightness, high affinity for Ca2+ and ease of use. However, unlike ratiometric indicators, the emission intensity from single-wavelength indicators can be affected by indicator concentration, optical path length, excitation intensity and detector efficiency. As such, without careful calibration, it can be difficult to draw inferences from differences in the magnitude of Ca2+ transients recorded using Fluo4. Here, we show that a method scarcely used in sensory neurophysiology - first proposed by Maravall and colleagues (2000) - can provide reliable estimates of absolute cytosolic Ca2+ concentration ([Ca2+]cyt) in acutely dissociated sensory neurons using Fluo4. This method is straightforward to implement; is applicable to any high-affinity single-wavelength Ca2+ indicator with a large dynamic range; and provides estimates of [Ca2+]cyt in line with other methods, including ratiometric imaging. Use of this method will improve the granularity of sensory neuron Ca2+ imaging data obtained with Fluo4.

The perception of affective and discriminative touch in blind individuals

Enhanced tactile acuity in blindness is among the most widely reported results of neuroplasticity following prolonged visual deprivation. However, tactile submodalities other than discriminative touch are profoundly understudied in blind individuals. Here, we examined the influence of blindness on two tactile submodalities, affective and discriminative touch, the former being vital for social functioning and emotional processing. We tested 36 blind individuals and 36 age- and sex-matched sighted volunteers. In Experiment 1, we measured the perception of affective tactile signals by asking participants to rate the pleasantness of touch delivered on the palm (nonhairy skin, sparsely innervated with C tactile [CT] fibers) or the forearm (hairy skin, densely innervated with CT fibers) in a CT-optimal versus a CT-nonoptimal manner using a paradigm grounded in studies on tactile sensory neurophysiology. In Experiment 2, we implemented a classic task assessing discriminative touch abilities, the grating orientation task. We found that blind individuals rated the touch as more pleasant when delivered on the palm than on the forearm, while the opposite pattern was observed for sighted participants, who rated stimulation on the forearm as more pleasant than stimulation on the palm. We also replicated the previous findings showing enhanced discriminative tactile acuity in blind individuals. Altogether, our results suggest that blind individuals might experience affective touch differently than sighted individuals, with relatively greater pleasantness perceived on the palm. These results provide a broader insight into somatosensory perception in blind individuals, for the first time taking into consideration the socioemotional aspect of touch.

A Critical Review of the Deviance Detection Theory of Mismatch Negativity

Mismatch negativity (MMN) is a component of the difference waveform derived from passive auditory oddball stimulation. Since its inception in 1978, this has become one of the most popular event-related potential techniques, with over two-thousand published studies using this method. This is a testament to the ingenuity and commitment of generations of researchers engaging in basic, clinical and animal research. Despite this intensive effort, high-level descriptions of the mechanisms theorized to underpin mismatch negativity have scarcely changed over the past four decades. The prevailing deviance detection theory posits that MMN reflects inattentive detection of difference between repetitive standard and infrequent deviant stimuli due to a mismatch between the unexpected deviant and a memory representation of the standard. Evidence for these mechanisms is inconclusive, and a plausible alternative sensory processing theory considers fundamental principles of sensory neurophysiology to be the primary source of differences between standard and deviant responses evoked during passive oddball stimulation. By frequently being restated without appropriate methods to exclude alternatives, the potentially flawed deviance detection theory has remained largely dominant, which could lead some researchers and clinicians to assume its veracity implicitly. It is important to have a more comprehensive understanding of the source(s) of MMN generation before its widespread application as a clinical biomarker. This review evaluates issues of validity concerning the prevailing theoretical account of mismatch negativity and the passive auditory oddball paradigm, highlighting several limitations regarding its interpretation and clinical application.

Altered Neural Oscillations During Multisensory Integration in Adolescents with Fetal Alcohol Spectrum Disorder.

Children with fetal alcohol spectrum disorder (FASD), who were exposed to alcohol in utero, display a broad range of sensory, cognitive, and behavioral deficits, which are broadly theorized to be rooted in altered brain function and structure. Based on the role of neural oscillations in multisensory integration from past studies, we hypothesized that adolescents with FASD would show a decrease in oscillatory power during event-related gamma oscillatory activity (30 to 100Hz), when compared to typically developing healthy controls (HC), and that such decrease in oscillatory power would predict behavioral performance. We measured sensory neurophysiology using magnetoencephalography (MEG) during passive auditory, somatosensory, and multisensory (synchronous) stimulation in 19 adolescents (12 to 21years) with FASD and 23 age- and gender-matched HC. We employed a cross-hemisphere multisensory paradigm to assess interhemispheric connectivity deficits in children with FASD. Time-frequency analysis of MEG data revealed a significant decrease in gamma oscillatory power for both unisensory and multisensory conditions in the FASD group relative to HC, based on permutation testing of significant group differences. Greater beta oscillatory power (15 to 30Hz) was also noted in the FASD group compared to HC in both unisensory and multisensory conditions. Regression analysis revealed greater predictive power of multisensory oscillations from unisensory oscillations in the FASD group compared to the HC group. Furthermore, multisensory oscillatory power, for both groups, predicted performance on the Intra-Extradimensional Set Shift Task and the Cambridge Gambling Task. Altered oscillatory power in the FASD group may reflect a restricted ability to process somatosensory and multisensory stimuli during day-to-day interactions. These alterations in neural oscillations may be associated with the neurobehavioral deficits experienced by adolescents with FASD and may carry over to adulthood.

Understanding spike-triggered covariance using Wiener theory for receptive field identification

Receptive field identification is a vital problem in sensory neurophysiology and vision. Much research has been done in identifying the receptive fields of nonlinear neurons whose firing rate is determined by the nonlinear interactions of a small number of linear filters. Despite more advanced methods that have been proposed, spike-triggered covariance (STC) continues to be the most widely used method in such situations due to its simplicity and intuitiveness. Although the connection between STC and Wiener/Volterra kernels has often been mentioned in the literature, this relationship has never been explicitly derived. Here we derive this relationship and show that the STC matrix is actually a modified version of the second-order Wiener kernel, which incorporates the input autocorrelation and mixes first- and second-order dynamics. It is then shown how, with little modification of the STC method, the Wiener kernels may be obtained and, from them, the principal dynamic modes, a set of compact and efficient linear filters that essentially combine the spike-triggered average and STC matrix and generalize to systems with both continuous and point-process outputs. Finally, using Wiener theory, we show how these obtained filters may be corrected when they were estimated using correlated inputs. Our correction technique is shown to be superior to those commonly used in the literature for both correlated Gaussian images and natural images.

Chapter 7 - New perspectives on the auditory cortex: learning and memory

Primary ("early") sensory cortices have been viewed as stimulus analyzers devoid of function in learning, memory, and cognition. However, studies combining sensory neurophysiology and learning protocols have revealed that associative learning systematically modifies the encoding of stimulus dimensions in the primary auditory cortex (A1) to accentuate behaviorally important sounds. This "representational plasticity" (RP) is manifest at different levels. The sensitivity and selectivity of signal tones increase near threshold, tuning above threshold shifts toward the frequency of acoustic signals, and their area of representation can increase within the tonotopic map of A1. The magnitude of area gain encodes the level of behavioral stimulus importance and serves as a substrate of memory strength. RP has the same characteristics as behavioral memory: it is associative, specific, develops rapidly, consolidates, and can last indefinitely. Pairing tone with stimulation of the cholinergic nucleus basalis induces RP and implants specific behavioral memory, while directly increasing the representational area of a tone in A1 produces matching behavioral memory. Thus, RP satisfies key criteria for serving as a substrate of auditory memory. The findings suggest a basis for posttraumatic stress disorder in abnormally augmented cortical representations and emphasize the need for a new model of the cerebral cortex.

Auditory Cortex Represents Both Pitch Judgments and the Corresponding Acoustic Cues

SummaryThe neural processing of sensory stimuli involves a transformation of physical stimulus parameters into perceptual features, and elucidating where and how this transformation occurs is one of the ultimate aims of sensory neurophysiology. Recent studies have shown that the firing of neurons in early sensory cortex can be modulated by multisensory interactions [1–5], motor behavior [1, 3, 6, 7], and reward feedback [1, 8, 9], but it remains unclear whether neural activity is more closely tied to perception, as indicated by behavioral choice, or to the physical properties of the stimulus. We investigated which of these properties are predominantly represented in auditory cortex by recording local field potentials (LFPs) and multiunit spiking activity in ferrets while they discriminated the pitch of artificial vowels. We found that auditory cortical activity is informative both about the fundamental frequency (F0) of a target sound and also about the pitch that the animals appear to perceive given their behavioral responses. Surprisingly, although the stimulus F0 was well represented at the onset of the target sound, neural activity throughout auditory cortex frequently predicted the reported pitch better than the target F0.

Adaptive stimulus optimization for sensory systems neuroscience.

In this paper, we review several lines of recent work aimed at developing practical methods for adaptive on-line stimulus generation for sensory neurophysiology. We consider various experimental paradigms where on-line stimulus optimization is utilized, including the classical optimal stimulus paradigm where the goal of experiments is to identify a stimulus which maximizes neural responses, the iso-response paradigm which finds sets of stimuli giving rise to constant responses, and the system identification paradigm where the experimental goal is to estimate and possibly compare sensory processing models. We discuss various theoretical and practical aspects of adaptive firing rate optimization, including optimization with stimulus space constraints, firing rate adaptation, and possible network constraints on the optimal stimulus. We consider the problem of system identification, and show how accurate estimation of non-linear models can be highly dependent on the stimulus set used to probe the network. We suggest that optimizing stimuli for accurate model estimation may make it possible to successfully identify non-linear models which are otherwise intractable, and summarize several recent studies of this type. Finally, we present a two-stage stimulus design procedure which combines the dual goals of model estimation and model comparison and may be especially useful for system identification experiments where the appropriate model is unknown beforehand. We propose that fast, on-line stimulus optimization enabled by increasing computer power can make it practical to move sensory neuroscience away from a descriptive paradigm and toward a new paradigm of real-time model estimation and comparison.

Analytical methods for the geometric optics of thermal vision illustrated with four species of pitvipers

The pitviper facial pit is a pinhole camera-like sensory organ consisting of a flask-shaped cavity divided into two chambers by a suspended membrane. Neurophysiological studies and simplified optical models suggest that facial pits detect thermal radiation and form an image that is combined with visual input in the optic tectum to form a single multispectral image. External pit anatomy varies markedly among taxonomic groups. However, optical function depends on unknown internal anatomy. Therefore, we developed methods for relating anatomy to optical performance. To illustrate, we constructed detailed anatomical models of the internal anatomy of the facial pits of four individuals of four pitviper species using X-ray tomography sections of fresh material. We used these models to define the point spread function, i.e. the distribution of radiation from a point source over the pit membrane, for each species. We then used optical physics, heat transfer physics and computational image processing to define the thermal image formed on the pit membrane for each species. Our computed pit membrane images are consistent with behavioral observations if the sensitivity of membrane receptors equals the most sensitive (ca. 0.001°C) laboratory estimates. Vignetting (variation in optical aperture size with view angle) and differences between body and environmental temperatures can create temperature variation across the membrane that greatly exceeds image temperature contrasts, potentially impairing imaging. Spread functions plotted versus source point azimuth and elevation show distinct patterns that suggest new research directions into the relationships among the optical anatomy, ecology, behavior and sensory neurophysiology of pitvipers.

Sensory Neurophysiology: Motion Vision during Motor Action

Sensory Neurophysiology: Motion Vision during Motor Action

Auditory Influences in V1 of Mice Induced by Varying Anesthesia Level

Anesthesia affects cortical response properties and induces changes in functional network connectivity. Many studies in sensory neurophysiology do not explicitly differentiate between anesthetic states and possibly underestimate the effect of anesthetic level on cortical response properties. To investigate this question, we performed simultaneous multisite recordings in V1 of C57bl/6 mice under continuously changing inspiratory isoflurane concentration from low to high dosage. During the continuous change of anesthesia level we presented visual and auditory stimuli. At all levels of anesthesia, visual stimulation evoked responses in V1. However, during light anesthesia auditory stimulation slightly suppressed ongoing LFP activity in V1. With increasing anesthesia levels this suppression vanished, and at a specific point a discrete change in sensory responsiveness of V1 to auditory stimulation appeared. At this discrete point auditory suppression was reversed into auditory induced activation of V1. This transition in properties was coincident with the appearance of burst-suppression. The responses during burst suppression state had long latency and resembled spontaneous bursts. This presumably unspecific auditory effect in V1 disappeared as soon as isoflurane concentration level dropped below a certain level. The results demonstrate that in the extreme case heteromodal effects can be induced by varying anesthesia level.

Sensory Neurophysiology: Motion Vision during Motor Action

Summary A recent study identifies mechanisms of state-dependent modulation of visual processing, using a comprehensive approach of electrophysiology in the behaving animal, pharmacology and computational modelling.

Automating the design of informative sequences of sensory stimuli

Adaptive stimulus design methods can potentially improve the efficiency of sensory neurophysiology experiments significantly; however, designing optimal stimulus sequences in real time remains a serious technical challenge. Here we describe two approximate methods for generating informative stimulus sequences: the first approach provides a fast method for scoring the informativeness of a batch of specific potential stimulus sequences, while the second method attempts to compute an optimal stimulus distribution from which the experimenter may easily sample. We apply these methods to single-neuron spike train data recorded from the auditory midbrain of zebra finches, and demonstrate that the resulting stimulus sequences do in fact provide more information about neuronal tuning in a shorter amount of time than do more standard experimental designs.

Identifiability of nonlinear receptive field models from sensory neurophysiology data

Identifiability of nonlinear receptive field models from sensory neurophysiology data

Effects of attention on perceptual direction tuning curves in the human visual system

In sensory neurophysiology, reverse correlation analyses have advanced our understanding of the spatio-temporal structure of receptive fields (RFs) and the tuning properties of individual neurons. Here, we used a psychophysical variant of the motion reverse correlation technique to investigate how visual selective attention influences human perceptual tuning curves for direction of motion. Direction tuning functions were computed by reverse correlating speeded target-present responses of human observers with a random sequence of brief, fully coherent motion impulses. We found that attention enhanced the amplitude of perceptual tuning curves for direction of motion, while tuning width remained unaffected. Furthermore, the full direction tuning profile across time could be well fitted by a separable model of direction and temporal tuning. Attention enhanced both the direction tuning and its temporal profile, without shifts or changes in shape. Thus, attention exerts a multiplicative effect on human perceptual tuning curves for direction of motion. An analysis of second-order correlations revealed a boost in the likelihood of responses to the target direction when it was followed by a motion impulse in the opposite direction. This perceptual effect might be mediated by biphasic neurons that are preferentially activated by a rapid succession of opposite motion directions.

Associative representational plasticity in the auditory cortex: A synthesis of two disciplines

Historically, sensory systems have been largely ignored as potential loci of information storage in the neurobiology of learning and memory. They continued to be relegated to the role of "sensory analyzers" despite consistent findings of associatively induced enhancement of responses in primary sensory cortices to behaviorally important signal stimuli, such as conditioned stimuli (CS), during classical conditioning. This disregard may have been promoted by the fact that the brain was interrogated using only one or two stimuli, e.g., a CS(+) sometimes with a CS(-), providing little insight into the specificity of neural plasticity. This review describes a novel approach that synthesizes the basic experimental designs of the experimental psychology of learning with that of sensory neurophysiology. By probing the brain with a large stimulus set before and after learning, this unified method has revealed that associative processes produce highly specific changes in the receptive fields of cells in the primary auditory cortex (A1). This associative representational plasticity (ARP) selectively facilitates responses to tonal CSs at the expense of other frequencies, producing tuning shifts toward and to the CS and expanded representation of CS frequencies in the tonotopic map of A1. ARPs have the major characteristics of associative memory: They are highly specific, discriminative, rapidly acquired, exhibit consolidation over hours and days, and can be retained indefinitely. Evidence to date suggests that ARPs encode the level of acquired behavioral importance of stimuli. The nucleus basalis cholinergic system is sufficient both for the induction of ARPs and the induction of specific auditory memory. Investigation of ARPs has attracted workers with diverse backgrounds, often resulting in behavioral approaches that yield data that are difficult to interpret. The advantages of studying associative representational plasticity are emphasized, as is the need for greater behavioral sophistication.

Neuropathophysiology of functional gastrointestinal disorders

The investigative evidence and emerging concepts in neurogastroenterology implicate dysfunctions at the levels of the enteric and central nervous systems as underlying causes of the prominent symptoms of many of the functional gastrointestinal disorders. Neurogastroenterological research aims for improved understanding of the physiology and pathophysiology of the digestive subsystems from which the arrays of functional symptoms emerge. The key subsystems for defecation-related symptoms and visceral hyper-sensitivity are the intestinal secretory glands, the musculature and the nervous system that controls and integrates their activity. Abdominal pain and discomfort arising from these systems adds the dimension of sensory neurophysiology. This review details current concepts for the underlying pathophysiology in terms of the physiology of intestinal secretion, motility, nervous control, sensing function, immuno-neural communication and the brain-gut axis.

COMPLETE FUNCTIONAL CHARACTERIZATION OF SENSORY NEURONS BY SYSTEM IDENTIFICATION

System identification is a growing approach to sensory neurophysiology that facilitates the development of quantitative functional models of sensory processing. This approach provides a clear set of guidelines for combining experimental data with other knowledge about sensory function to obtain a description that optimally predicts the way that neurons process sensory information. This prediction paradigm provides an objective method for evaluating and comparing computational models. In this chapter we review many of the system identification algorithms that have been used in sensory neurophysiology, and we show how they can be viewed as variants of a single statistical inference problem. We then review many of the practical issues that arise when applying these methods to neurophysiological experiments: stimulus selection, behavioral control, model visualization, and validation. Finally we discuss several problems to which system identification has been applied recently, including one important long-term goal of sensory neuroscience: developing models of sensory systems that accurately predict neuronal responses under completely natural conditions.

Behavioral guides for sensory neurophysiology

The study of natural behavior is important for understanding the coding schemes of sensory systems. The jamming avoidance response of the weakly electric fish Eigenmannia is an excellent example of a bottom-up approach, in which behavioral analyses guided neurophysiological studies. These studies started from the electroreceptive sense organs to the motor output consisting of pacemaker neurons. Going in the opposite direction, from the central nervous system to lower centers, is the characteristic of the top-down approach. Although this approach is perhaps more difficult than the bottom-up approach, it was successfully employed in the neuroethological analysis of sound localization in the barn owl. In the latter studies, high-order neurons selective for complex natural stimuli led to the discovery of neural pathways and networks responsible for the genesis of the stimulus selectivity. Comparison of Eigenmannia and barn owls, and their neural systems, has revealed similarities in network designs, such as parallel pathways and their convergence to produce stimulus selectivity necessary for detection of natural stimuli.

Neuropathophysiology of irritable bowel syndrome.

Widespread symptoms associated with the irritable bowel syndrome (IBS) are abnormal defecation and abdominal pain, both of which can be exacerbated by psychogenic stress. Disordered defecation may present as diarrhea or constipation. A subgroup of IBS patients alternate from one to the other over time. Urgency to stool often accompanies the diarrheal-state, and patients with the constipation-predominant form of IBS report straining and the feeling of incomplete evacuation. Basic scientific research aims for improved understanding of the physiology and pathophysiology of the digestive systems from which the arrays of IBS symptoms emerge. The key systems for the defecation-related symptoms are the intestinal secretory glands, the musculature, and the nervous system that controls and integrates their activity. Abdominal pain and discomfort arising from these systems adds the dimension of sensory neurophysiology. This review details current concepts of the underlying pathophysiology in terms of the physiology of intestinal secretion, motility, nervous control, sensing function, immuno-neural communication, and the brain-gut axis.