Increase In Response Gain Research Articles

Subcortical coding of predictable and unsupervised sound-context associations

Our environment is made of a myriad of stimuli present in combinations often patterned in predictable ways. For example, there is a strong association between where we are and the sounds we hear. Like many environmental patterns, sound-context associations are learned implicitly, in an unsupervised manner, and are highly informative and predictive of normality. Yet, we know little about where and how unsupervised sound-context associations are coded in the brain. Here we measured plasticity in the auditory midbrain of mice living over days in an enriched task-less environment in which entering a context triggered sound with different degrees of predictability. Plasticity in the auditory midbrain, a hub of auditory input and multimodal feedback, developed over days and reflected learning of contextual information in a manner that depended on the predictability of the sound-context association and not on reinforcement. Plasticity manifested as an increase in response gain and tuning shift that correlated with a general increase in neuronal frequency discrimination. Thus, the auditory midbrain is sensitive to unsupervised predictable sound-context associations, revealing a subcortical engagement in the detection of contextual sounds. By increasing frequency resolution, this detection might facilitate the processing of behaviorally relevant foreground information described to occur in cortical auditory structures.

Feature-Based Attention Multiplicatively Scales the fMRI-BOLD Contrast-Response Function.

fMRI plays a key role in the study of attention. However, there remains a puzzling discrepancy between attention effects measured with fMRI and with electrophysiological methods. While electrophysiological studies find that attention increases sensory gain, amplifying stimulus-evoked neural responses by multiplicatively scaling the contrast-response function (CRF), fMRI appears to be insensitive to these multiplicative effects. Instead, fMRI studies typically find that attention produces an additive baseline shift in the BOLD signal. These findings suggest that attentional effects measured with fMRI reflect top-down inputs to visual cortex, rather than the modulation of sensory gain. If true, this drastically limits what fMRI can tell us about how attention improves sensory coding. Here, we examined whether fMRI is sensitive to multiplicative effects of attention using a feature-based attention paradigm designed to preclude any possible additive effects. We measured BOLD activity evoked by a probe stimulus in one visual hemifield while participants (6 male, 6 female) attended to the probe orientation (attended condition), or to an orthogonal orientation (unattended condition), in the other hemifield. To measure CRFs in visual areas V1-V3, we parametrically varied the contrast of the probe stimulus. In all three areas, feature-based attention increased contrast gain, improving sensitivity by shifting CRFs toward lower contrasts. In V2 and V3, we also found an increase in response gain, an increase in the responsivity of the CRF, that was greatest at inner eccentricities. These results provide clear evidence that the fMRI-BOLD signal is sensitive to multiplicative effects of attention.SIGNIFICANCE STATEMENT fMRI plays a central role in the study of attention because it allows researchers to precisely and noninvasively characterize the effects of attention throughout the brain. Electrophysiological studies have shown that attention increases sensory gain, amplifying stimulus-evoked neural responses. However, a growing body of work suggests that the BOLD signal that is measured with fMRI is not sensitive to these multiplicative effects of attention, calling into question what we can learn from fMRI about how attention improves sensory codes. Here, using a feature-based attention paradigm, we provide evidence that the BOLD signal can pick up multiplicative effects of attention.

Covert Attention Increases the Gain of Stimulus-Evoked Population Codes.

Covert spatial attention has a variety of effects on the responses of individual neurons. However, relatively little is known about the net effect of these changes on sensory population codes, even though perception ultimately depends on population activity. Here, we measured the EEG in human observers (male and female), and isolated stimulus-evoked activity that was phase-locked to the onset of attended and ignored visual stimuli. Using an encoding model, we reconstructed spatially selective population tuning functions from the pattern of stimulus-evoked activity across the scalp. Our EEG-based approach allowed us to measure very early visually evoked responses occurring ∼100 ms after stimulus onset. In Experiment 1, we found that covert attention increased the amplitude of spatially tuned population responses at this early stage of sensory processing. In Experiment 2, we parametrically varied stimulus contrast to test how this effect scaled with stimulus contrast. We found that the effect of attention on the amplitude of spatially tuned responses increased with stimulus contrast, and was well described by an increase in response gain (i.e., a multiplicative scaling of the population response). Together, our results show that attention increases the gain of spatial population codes during the first wave of visual processing.SIGNIFICANCE STATEMENT We know relatively little about how attention improves population codes, even though perception is thought to critically depend on population activity. In this study, we used an encoding-model approach to test how attention modulates the spatial tuning of stimulus-evoked population responses measured with EEG. We found that attention multiplicatively scales the amplitude of spatially tuned population responses. Furthermore, this effect was present within 100 ms of stimulus onset. Thus, our results show that attention improves spatial population codes by increasing their gain at this early stage of processing.

Hidden Hearing Loss Impacts the Neural Representation of Speech in Background Noise

SummaryMany individuals with seemingly normal hearing abilities struggle to understand speech in noisy backgrounds. To understand why this might be the case, we investigated the neural representation of speech in the auditory midbrain of gerbils with “hidden hearing loss” through noise exposure that increased hearing thresholds only temporarily. In noise-exposed animals, we observed significantly increased neural responses to speech stimuli, with a more pronounced increase at moderate than at high sound intensities. Noise exposure reduced discriminability of neural responses to speech in background noise at high sound intensities, with impairment most severe for tokens with relatively greater spectral energy in the noise-exposure frequency range (2–4 kHz). At moderate sound intensities, discriminability was surprisingly improved, which was unrelated to spectral content. A model combining damage to high-threshold auditory nerve fibers with increased response gain of central auditory neurons reproduced these effects, demonstrating that a specific combination of peripheral damage and central compensation could explain listening difficulties despite normal hearing thresholds.

Representation of Haltere Oscillations and Integration with Visual Inputs in the Fly Central Complex.

The reduced hindwings of flies, known as halteres, are specialized mechanosensory organs that detect body rotations during flight. Primary afferents of the haltere encode its oscillation frequency linearly over a wide bandwidth and with precise phase-dependent spiking. However, it is not currently known whether information from haltere primary afferent neurons is sent to higher brain centers where sensory information about body position could be used in decision making, or whether precise spike timing is useful beyond the peripheral circuits that drive wing movements. We show that in cells in the central brain, the timing and rates of neural spiking can be modulated by sensory input from experimental haltere movements (driven by a servomotor). Using multichannel extracellular recording in restrained flesh flies (Sarcophaga bullata of both sexes), we examined responses of central complex cells to a range of haltere oscillation frequencies alone, and in combination with visual motion speeds and directions. Haltere-responsive units fell into multiple response classes, including those responding to any haltere motion and others with firing rates linearly related to the haltere frequency. Cells with multisensory responses showed higher firing rates than the sum of the unisensory responses at higher haltere frequencies. They also maintained visual properties, such as directional selectivity, while increasing response gain nonlinearly with haltere frequency. Although haltere inputs have been described extensively in the context of rapid locomotion control, we find haltere sensory information in a brain region known to be involved in slower, higher-order behaviors, such as navigation.SIGNIFICANCE STATEMENT Many animals use vision for navigation; however, these cues must be interpreted in the context of the body's position. In mammalian brains, hippocampal cells combine visual and vestibular information to encode head direction. A region of the arthropod brain, known as the central complex (CX), similarly encodes heading information, but it is unknown whether proprioceptive information is integrated here as well. We show that CX neurons respond to input from halteres, specialized proprioceptors in flies that detect body rotations. These neurons also respond to visual input, providing one of the few examples of multiple sensory modalities represented in individual CX cells. Haltere stimulation modifies neural responses to visual signals, providing a mechanism for integrating vision with proprioception.

Systemic Nicotine Increases Gain and Narrows Receptive Fields in A1 via Integrated Cortical and Subcortical Actions.

Nicotine enhances sensory and cognitive processing via actions at nicotinic acetylcholine receptors (nAChRs), yet the precise circuit- and systems-level mechanisms remain unclear. In sensory cortex, nicotinic modulation of receptive fields (RFs) provides a model to probe mechanisms by which nAChRs regulate cortical circuits. Here, we examine RF modulation in mouse primary auditory cortex (A1) using a novel electrophysiological approach: current-source density (CSD) analysis of responses to tone-in-notched-noise (TINN) acoustic stimuli. TINN stimuli consist of a tone at the characteristic frequency (CF) of the recording site embedded within a white noise stimulus filtered to create a spectral “notch” of variable width centered on CF. Systemic nicotine (2.1 mg/kg) enhanced responses to the CF tone and to narrow-notch stimuli, yet reduced the response to wider-notch stimuli, indicating increased response gain within a narrowed RF. Subsequent manipulations showed that modulation of cortical RFs by systemic nicotine reflected effects at several levels in the auditory pathway: nicotine suppressed responses in the auditory midbrain and thalamus, with suppression increasing with spectral distance from CF so that RFs became narrower, and facilitated responses in the thalamocortical pathway, while nicotinic actions within A1 further contributed to both suppression and facilitation. Thus, multiple effects of systemic nicotine integrate along the ascending auditory pathway. These actions at nAChRs in cortical and subcortical circuits, which mimic effects of auditory attention, likely contribute to nicotinic enhancement of sensory and cognitive processing.

Asymmetric effects of activating and inactivating cortical interneurons.

Bidirectional manipulations - activation and inactivation - are widely used to identify the functions supported by specific cortical interneuron types. Implicit in much of this work is the notion that tonic activation and inactivation will both produce valid, internally consistent insights into interneurons' computational roles. Here, using single-unit recordings in auditory cortex of awake mice, we show that this may not generally hold true. Optogenetically manipulating somatostatin-positive (Sst+) or parvalbumin-positive (Pvalb+) interneurons while recording tone-responses showed that Sst+ inactivation increased response gain, while Pvalb+ inactivation weakened tuning and decreased information transfer, implying that these neurons support delineable computational functions. But activating Sst+ and Pvalb+ interneurons revealed no such differences. We used a simple network model to understand this asymmetry, and showed how relatively small changes in key parameters, such as spontaneous activity or strength of the light manipulation, determined whether activation and inactivation would produce consistent or paradoxical conclusions regarding interneurons' computational functions.

The role of inhibition and excitation in visual attention

The natural world contains more information than our brain has the capacity to process. We make use of selective attention to filter this information ‐ enhance the relevant and suppress the distracting. While the behavioral improvements due to attention are easy to quantify experimentally, the neural circuits that give rise to these improvements remain unclear. In the visual system, modulation of neural activity due to attention is ubiquitous in measurements ranging from scalp electroencephalography to extracellular recordings from single neurons. A number of recent models of attention have proposed that inhibition may play a key role in modulating the computational abilities of neural networks at the locus of attention. While the fundamental importance of inhibition in the nervous system has been known since Sherrington's work at the turn of the 20th century, the mechanisms by which inhibition and excitation interact in service of neural computation are not well understood. Computations in cortex take place in networks of noisy neurons, and modulation of that noise likely plays an important role in attention. Recent models of cortical networks, employing balanced excitation and inhibition, are able to control the level of noise in the system. One prediction from such a model is that the attended state may be mediated be the activity of inhibitory neurons which serve to both modulate the noise in the network while simultaneously increasing response gain. While such a model is easy to implement, it is difficult to test in awake, behaving animals because extracellular recordings are blind to the cell class of the recorded neuron. We developed a novel method of probabilistically classifying neurons based on multiple aspects of their waveform shape that correspond to known differences between cell classes. Using this method, we were able to achieve a high degree of certainty of the classification of 95% of recorded V4 neurons in two rhesus macaque monkeys performing a demanding spatial attention task. We found that inhibitory neurons had stronger effects of attention than excitatory neurons in three key measures: (1) firing rate modulation; (2) decorrelation of their pairwise spiking response; and (3) the match of their response profile to the task's temporal demands. These results suggest that inhibitory neurons are indeed the recipients of a shared signal during the attentive state, and that this signal leads to a decrease in correlation in the rest of the population. Our results thus provide a network‐level account for the role of inhibition in attention.Support or Funding InformationNIH Grants EY023456, EY018894, EY022928, EY008098 and DA023428

On the Structure of Neuronal Population Activity under Fluctuations in Attentional State.

Covert attention is one of the most widely studied examples of top-down modulation of neural activity in the visual system. Recent studies argue that attention improves behavioral performance by shaping of the noise distribution to suppress shared variability rather than by increasing response gain. Our work shows, however, that latent, trial-to-trial fluctuations of the focus and strength of attention lead to shared variability that is highly consistent with known experimental observations. Interestingly, fluctuations in the strength of attention do not affect coding performance. As a consequence, the experimentally observed changes in response variability may not be a mechanism of attention, but rather a side effect of attentional allocation strategies in different behavioral contexts.

Feature expectation heightens visual sensitivity during fine orientation discrimination.

Attending to a stimulus enhances the sensitivity of perceptual decisions. However, it remains unclear how perceptual sensitivity varies according to whether a feature is expected or unexpected. Here, observers made fine discrimination judgments about the orientation of visual gratings embedded in low spatial-frequency noise, and psychophysical reverse correlation was used to estimate decision 'kernels' that revealed how visual features influenced choices. Orthogonal cues alerted subjects to which of two spatial locations was likely to be probed (spatial attention cue) and which of two oriented gratings was likely to occur (feature expectation cue). When an expected (relative to unexpected) feature occurred, decision kernels shifted away from the category boundary, allowing observers to capitalize on more informative, "off-channel" stimulus features. By contrast, the spatial attention cue had a multiplicative influence on decision kernels, consistent with an increase in response gain. Feature expectation thus heightens sensitivity to the most informative visual features, independent of selective attention.

Crosstalk opposing view: Fear of falling does not influence vestibular-evoked balance responses.

Crosstalk opposing view: Fear of falling does not influence vestibular-evoked balance responses.

Cholinergic Inputs from Basal Forebrain Add an Excitatory Bias to Odor Coding in the Olfactory Bulb

Cholinergic modulation of central circuits is associated with active sensation, attention, and learning, yet the neural circuits and temporal dynamics underlying cholinergic effects on sensory processing remain unclear. Understanding the effects of cholinergic modulation on particular circuits is complicated by the widespread projections of cholinergic neurons to telencephalic structures that themselves are highly interconnected. Here we examined how cholinergic projections from basal forebrain to the olfactory bulb (OB) modulate output from the first stage of sensory processing in the mouse olfactory system. By optogenetically activating their axons directly in the OB, we found that cholinergic projections from basal forebrain regulate OB output by increasing the spike output of presumptive mitral/tufted cells. Cholinergic stimulation increased mitral/tufted cell spiking in the absence of inhalation-driven sensory input and further increased spiking responses to inhalation of odorless air and to odorants. This modulation was rapid and transient, was dependent on local cholinergic signaling in the OB, and differed from modulation by optogenetic activation of cholinergic neurons in basal forebrain, which led to a mixture of mitral/tufted cell excitation and suppression. Finally, bulbar cholinergic enhancement of mitral/tufted cell odorant responses was robust and occurred independent of the strength or even polarity of the odorant-evoked response, indicating that cholinergic modulation adds an excitatory bias to mitral/tufted cells as opposed to increasing response gain or sharpening response spectra. These results are consistent with a role for the basal forebrain cholinergic system in dynamically regulating the sensitivity to or salience of odors during active sensing of the olfactory environment.

Computational modeling of tinnitus development

Animal models and human neuroimaging studies have shown that tinnitus is generated through pathologically altered spontaneous activity of neurons in the central auditory system. Sensorineural hearing loss has been identified as an important trigger for the development of these aberrant patterns of neuronal activity, but the functional mechanisms that underlie this process have not yet been pinpointed. Using computational models, we have investigated which neuronal plasticity mechanisms could account for the development of neuronal correlates of tinnitus after hearing loss. We could show that a model based on the principle of activity stabilization through homeostatic plasticity can explain the development of neuronal hyperactivity as observed in animal studies. Moreover, the model’s predictions of tinnitus frequencies from the audiograms of patients with noise-induced hearing loss and tonal tinnitus are close to the observed tinnitus pitch. The model thus proposes a specific mechanism for how plasticity in the central auditory system could lead to the development of tinnitus after cochlear damage. The model also predicts that central auditory structures may show increased response gain, which could explain why tinnitus and hyperacusis often occur together. Moreover, the homeostasis model is consistent with recent experimental findings from tinnitus patients with normal audiograms, and it explains why auditory deprivation through an earplug can lead to the occurrence of phantom sounds.

Feature-based attention enhances performance by increasing response gain

Covert spatial attention can increase contrast sensitivity either by changes in contrast gain or by changes in response gain, depending on the size of the attention field and the size of the stimulus (Herrmann et al., 2010), as predicted by the normalization model of attention (Reynolds & Heeger, 2009). For feature-based attention, unlike spatial attention, the model predicts only changes in response gain, regardless of whether the featural extent of the attention field is small or large. To test this prediction, we measured the contrast dependence of feature-based attention. Observers performed an orientation-discrimination task on a spatial array of grating patches. The spatial locations of the gratings were varied randomly so that observers could not attend to specific locations. Feature-based attention was manipulated with a 75% valid and 25% invalid pre-cue, and the featural extent of the attention field was manipulated by introducing uncertainty about the upcoming grating orientation. Performance accuracy was better for valid than for invalid pre-cues, consistent with a change in response gain, when the featural extent of the attention field was small (low uncertainty) or when it was large (high uncertainty) relative to the featural extent of the stimulus. These results for feature-based attention clearly differ from results of analogous experiments with spatial attention, yet both support key predictions of the normalization model of attention.

Multiple Adaptable Mechanisms Early in the Primate Visual Pathway

We describe experiments that isolate and characterize multiple adaptable mechanisms that influence responses of orientation-selective neurons in primary visual cortex (V1) of anesthetized macaque (Macaca fascicularis). The results suggest that three adaptable stages of machinery shape neural responses in V1: a broadly tuned early stage and a spatio-temporally tuned later stage, both of which provide excitatory input, and a normalization pool that is also broadly tuned. The early stage and the normalization pool are revealed by adapting gratings that themselves fail to evoke a response from the neuron: either low temporal frequency gratings at the null orientation or gratings of any orientation drifting at high temporal frequencies. When effective, adapting stimuli that altered the sensitivity of these two mechanisms caused reductions of contrast gain and often brought about a paradoxical increase in response gain due to a relatively greater desensitization of the normalization pool. The tuned mechanism is desensitized only by stimuli well matched to a neuron's receptive field. We could thus infer desensitization of the tuned mechanism by comparing effects obtained with adapting gratings of preferred and null orientation modulated at low temporal frequencies.

Feature-based attention enhances performance by increasing response gain

Covert spatial attention can increase contrast sensitivity either by changes in contrast gain or by changes in response gain, depending on the size of the attention field and the size of the stimulus (Herrmann et al., 2010), as predicted by the normalization model of attention (Reynolds & Heeger, 2009). For feature-based attention, unlike spatial attention, the model predicts only changes in response gain, regardless of whether the featural extent of the attention field is small or large. To test this prediction, we measured the contrast dependence of feature-based attention. Observers performed an orientation-discrimination task on a spatial array of grating patches. The spatial locations of the gratings were varied randomly so that observers could not attend to specific locations. Feature-based attention was manipulated with a 75% valid and 25% invalid pre-cue, and the featural extent of the attention field was manipulated by introducing uncertainty about the upcoming grating orientation. Performance accuracy was better for valid than for invalid pre-cues, consistent with a change in response gain, when the featural extent of the attention field was small (low uncertainty) or when it was large (high uncertainty) relative to the featural extent of the stimulus. These results for feature-based attention clearly differ from results of analogous experiments with spatial attention, yet both support key predictions of the normalization model of attention.

In memoriam Robert B. Barlow, Jr

It is with great sadness that we mark the loss of Dr Robert (Bob) Barlow, a pioneering investigator into the neural basis of visual behavior. Bob had a passion for vision research that was vibrant and engaging. He would surely have remained scientifically active and productive for years to come,

Entrainment of Neuronal Oscillations as a Mechanism of Attentional Selection

Whereas gamma-band neuronal oscillations clearly appear integral to visual attention, the role of lower-frequency oscillations is still being debated. Mounting evidence indicates that a key functional property of these oscillations is the rhythmic shifting of excitability in local neuronal ensembles. Here, we show that when attended stimuli are in a rhythmic stream, delta-band oscillations in the primary visual cortex entrain to the rhythm of the stream, resulting in increased response gain for task-relevant events and decreased reaction times. Because of hierarchical cross-frequency coupling, delta phase also determines momentary power in higher-frequency activity. These instrumental functions of low-frequency oscillations support a conceptual framework that integrates numerous earlier findings.

Brain state and contrast sensitivity in the awake visual thalamus

Neuronal responses to visual stimuli depend on both the nature of the stimulus and brain state. Here we examined the contrast sensitivity of visual thalamic neurons as awake rabbits shifted between alert and nonalert states. We found that despite a large increase in response gain with alertness, contrast sensitivity remained nearly constant. This accurate scaling might be achieved through a balanced increase in excitation and inhibition with alertness.

Independent Controls of Attentional Influences in Primary and Secondary Somatosensory Cortex

The neuronal mechanisms underlying enhanced perception of tactile stimuli with directed attention were investigated using single-unit recordings from primary (S1, n = 53) and secondary (S2, n = 50) somatosensory cortex in macaque monkeys. Neuronal responses to textures scanned under the digit tips (spatial periods, SP, of 2, 3.7 or 4.7 mm) were recorded while attention was directed either to discriminating a change in texture or to the reward and also in a neutral no-task condition. Cell discharge was quantified in three periods of the trials: salient Delta texture (directed attention), postreward, and static (both cases, attention directed to the reward). S1 texture- and non-texture-sensitive cells, as well as S2 non-texture-sensitive cells, showed a modest enhancement of discharge during the salient Delta texture period (approximately 25%) but no change in response gain, consistent with an additive increase in neuronal responsiveness with directed attention. In contrast, S2 texture-related cells showed a larger enhancement with directed attention to salient inputs (82%) and increased response gain, suggesting that directed attention produces a multiplicative increase in S2 responsiveness. During the postreward period, and also in no-task testing, S1 texture-sensitive cells preserved their sensitivity to SP. In contrast, S2 texture-, but not non-texture-, sensitive cells showed a marked suppression of discharge and decreased gain after the discrimination response. Together, the results support the notion that S2 discharge reflects stimulus parameters in relation to ongoing behavioral demands. The results also support the existence of two independent attentional mechanisms in somatosensory cortex, one generalized (S1 and S2), and the other focused on S2 texture-related cells.