Neuronal Population Responses Research Articles

Electrophysiological Responses in the Ventral Temporal Cortex During Reading of Numerals and Calculation.

Recent evidence suggests that specific neuronal populations in the ventral temporal cortex show larger electrophysiological responses to visual numerals compared with morphologically similar stimuli. This study investigates how these responses change from simple reading of numerals to the active use of numerals in an arithmetic context. We recorded high-frequency broadband (HFB) signals, a reliable measure for local neuronal population activity, while 10 epilepsy patients implanted with subdural electrodes performed separate numeral reading and calculation tasks. We found that calculation increased activity in the posterior inferior temporal gyrus (ITG) with a factor of approximately 1.5 over the first 500 ms of calculation, whereas no such increase was noted for reading numerals without calculation or reading and judging memory statements. In a second experiment conducted in 2 of the same subjects, we show that HFB responses increase in a systematic manner when the single numerals were presented successively in a calculation context: The HFB response in the ITG, to the second and third numerals (i.e., b and c in a + b = c), was approximately 1.5 times larger than the responses to the first numeral (a). These results provide electrophysiological evidence for modulation of local neuronal population responses to visual stimuli based on increasing task demands.

Simple Learned Weighted Sums of Inferior Temporal Neuronal Firing Rates Accurately Predict Human Core Object Recognition Performance.

To go beyond qualitative models of the biological substrate of object recognition, we ask: can a single ventral stream neuronal linking hypothesis quantitatively account for core object recognition performance over a broad range of tasks? We measured human performance in 64 object recognition tests using thousands of challenging images that explore shape similarity and identity preserving object variation. We then used multielectrode arrays to measure neuronal population responses to those same images in visual areas V4 and inferior temporal (IT) cortex of monkeys and simulated V1 population responses. We tested leading candidate linking hypotheses and control hypotheses, each postulating how ventral stream neuronal responses underlie object recognition behavior. Specifically, for each hypothesis, we computed the predicted performance on the 64 tests and compared it with the measured pattern of human performance. All tested hypotheses based on low- and mid-level visually evoked activity (pixels, V1, and V4) were very poor predictors of the human behavioral pattern. However, simple learned weighted sums of distributed average IT firing rates exactly predicted the behavioral pattern. More elaborate linking hypotheses relying on IT trial-by-trial correlational structure, finer IT temporal codes, or ones that strictly respect the known spatial substructures of IT ("face patches") did not improve predictive power. Although these results do not reject those more elaborate hypotheses, they suggest a simple, sufficient quantitative model: each object recognition task is learned from the spatially distributed mean firing rates (100 ms) of ∼60,000 IT neurons and is executed as a simple weighted sum of those firing rates. Significance statement: We sought to go beyond qualitative models of visual object recognition and determine whether a single neuronal linking hypothesis can quantitatively account for core object recognition behavior. To achieve this, we designed a database of images for evaluating object recognition performance. We used multielectrode arrays to characterize hundreds of neurons in the visual ventral stream of nonhuman primates and measured the object recognition performance of >100 human observers. Remarkably, we found that simple learned weighted sums of firing rates of neurons in monkey inferior temporal (IT) cortex accurately predicted human performance. Although previous work led us to expect that IT would outperform V4, we were surprised by the quantitative precision with which simple IT-based linking hypotheses accounted for human behavior.

Impact of membrane bistability on dynamical response of neuronal populations.

Neurons in many brain areas can develop a pronounced depolarized state of membrane potential (up state) in addition to the normal hyperpolarized state near the resting potential. The influence of the up state on signal encoding, however, is not well investigated. Here we construct a one-dimensional bistable neuron model and calculate the linear dynamical response to noisy oscillatory inputs analytically. We find that with the appearance of an up state, the transmission function is enhanced by the emergence of a local maximum at some optimal frequency and the phase lag relative to the input signal is reduced. We characterize the dependence of the enhancement of frequency response on intrinsic dynamics and on the occupancy of the up state.

A Specific Component of the Evoked Potential Mirrors Phasic Dopamine Neuron Activity during Conditioning.

Midbrain dopamine (DA) neurons are thought to be a critical node in the circuitry that mediates reward learning. DA neurons receive diverse inputs from regions distributed throughout the neuraxis from frontal neocortex to the mesencephalon. While a great deal is known about changes in the activity of individual DA neurons during learning, much less is known about the functional changes in the microcircuits in which DA neurons are embedded. Here we used local field potentials recorded from the midbrain of behaving mice to show that the midbrain evoked potential (mEP) faithfully reflects the temporal and spatial structure of the phasic response of midbrain neuron populations during conditioning. By comparing the mEP to simultaneously recorded single units, we identified specific components of the mEP that corresponded to phasic DA and non-DA responses to salient stimuli. The DA component of the mEP emerged with the acquisition of a conditioned stimulus, was extinguished following changes in reinforcement contingency, and could be inhibited by pharmacological manipulations that attenuate the phasic responses of DA neurons. In contrast to single-unit recordings, the mEP permitted relatively dense sampling of the midbrain circuit during conditioning and thus could be used to reveal the spatiotemporal structure of multiple intermingled midbrain circuits. Finally, the mEP response was stable for months and thus provides a new approach to study long-term changes in the organization of ventral midbrain microcircuits during learning. Significance statement: Neurons that synthesize and release the neurotransmitter dopamine play a critical role in voluntary reward-seeking behavior. Much of our insight into the function of dopamine neurons comes from recordings of individual cells in behaving animals; however, it is notoriously difficult to record from dopamine neurons due to their sparsity and depth, as well as the presence of intermingled non-dopaminergic neurons. Here we show that much of the information that can be learned from recordings of individual dopamine and non-dopamine neurons is also revealed by changes in specific components of the local field potential. This technique provides an accessible measurement that could prove critical to our burgeoning understanding of the molecular, functional, and anatomical diversity of neuron populations in the midbrain.

Caudate neuronal recording in freely behaving animals following acute and chronic dose response methylphenidate exposure

The misuse and abuse of the psychostimulant, methylphenidate (MPD) the drug of choice in the treatment of attention deficit hyperactivity disorder (ADHD) has seen a sharp uprising in recent years among both youth and adults for its cognitive enhancing effects and for recreational purposes. This uprise in illicit use has lead to many questions concerning the long-term consequences of MPD exposure. The objective of this study was to record animal behavior concomitantly with the caudate nucleus (CN) neuronal activity following acute and repetitive (chronic) dose response exposure to methylphenidate (MPD). A saline control and three MPD dose (0.6, 2.5, and 10.0mg/kg) groups were used.Behaviorally, the same MPD dose in some animals following chronic MPD exposure elicited behavioral sensitization and other animals elicited behavioral tolerance. Based on this finding, the CN neuronal population recorded from animals expressing behavioral sensitization was also evaluated separately from CN neurons recorded from animals expressing behavioral tolerance to chronic MPD exposure, respectively.Significant differences in CN neuronal population responses between the behaviorally sensitized and the behaviorally tolerant animals were observed for the 2.5 and 10.0mg/kg MPD exposed groups. For 2.5mg/kg MPD, behaviorally sensitized animals responded by decreasing their firing rates while behaviorally tolerant animals showed mainly an increase in their firing rates. The CN neuronal responses recorded from the behaviorally sensitized animals following 10.0mg/kg MPD responded by increasing their firing rates whereas the CN neuronal recordings from the behaviorally tolerant animals showed that approximately half decreased their firing rates in response to 10.0mg/kg MPD exposure. The comparison of percentage change in neuronal firing rates showed that the behaviorally tolerant animals trended to exhibit increases in their neuronal firing rates at ED1 following initial MPD exposure and oppositely at ED10 MPD rechallenge. While the behaviorally sensitized animals in general increased in their percentage change of firing rats were observed following acute 10.0mg/kg MPD and the behaviorally sensitized 10.0mg/kg MPD animals and a robust increase in neuronal firing rates at ED1 and ED10 rechallenge.These results suggest the need to first individually analyze animal behavioral activity, and then to evaluate the neuronal responses to the drug based on the animals behavioral response to chronic MPD exposure.

Neural dynamics for landmark orientation and angular path integration.

SummaryMany animals navigate using a combination of visual landmarks and path integration. In mammalian brains, head direction cells integrate these two streams of information by representing an animal's heading relative to landmarks, yet maintaining their directional tuning in darkness based on self-motion cues. Here we use two-photon calcium imaging in head-fixed flies walking on a ball in a virtual reality arena to demonstrate that landmark-based orientation and angular path integration are combined in the population responses of neurons whose dendrites tile the ellipsoid body — a toroidal structure in the center of the fly brain. The population encodes the fly's azimuth relative to its environment, tracking visual landmarks when available and relying on self-motion cues in darkness. When both visual and self-motion cues are absent, a representation of the animal's orientation is maintained in this network through persistent activity — a potential substrate for short-term memory. Several features of the population dynamics of these neurons and their circular anatomical arrangement are suggestive of ring attractors — network structures proposed to support the function of navigational brain circuits.

The Key Role of Calcium in the Mechanism of Deprivation Potentiation of Population Responses of Neurons in Hippocampal Field CA1

In vitro studies on living rat hippocampus slices addressed the role of Ca2+ in the mechanism of deprivation potentiation of population responses (pop spikes) of neurons in field CA1 induced by prolonged (60 min) interruption of low-frequency test stimulation of Schaffer collaterals. Two phases were seen in deprivation potentiation, with presumptively different origins: an initial short-lived “peak” (about 12 min) and a longer-lasting “plateau” (more than 1 h). The experiments reported here showed that the presence of a penetrating Ca2+ chelator (BAPTA-AM), decreasing the Ca2+ concentration in the solution, and depletion of the intracellular calcium depot (presence of thapsigargin/cyclopiazonic acid in the solution) led to reductions in the transient phase and blockade of the longer-lasting phase of deprivation potentiation. These studies thus demonstrate the key roles of both extracellular and stored intracellular calcium in the mechanism of development of deprivation potentiation.

Low attention impairs optimal incorporation of prior knowledge in perceptual decisions.

When visual attention is directed away from a stimulus, neural processing is weak and strength and precision of sensory data decreases. From a computational perspective, in such situations observers should give more weight to prior expectations in order to behave optimally during a discrimination task. Here we test a signal detection theoretic model that counter-intuitively predicts subjects will do just the opposite in a discrimination task with two stimuli, one attended and one unattended: when subjects are probed to discriminate the unattended stimulus, they rely less on prior information about the probed stimulus' identity. The model is in part inspired by recent findings that attention reduces trial-by-trial variability of the neuronal population response and that they use a common criterion for attended and unattended trials. In five different visual discrimination experiments, when attention was directed away from the target stimulus, subjects did not adjust their response bias in reaction to a change in stimulus presentation frequency despite being fully informed and despite the presence of performance feedback and monetary and social incentives. This indicates that subjects did not rely more on the priors under conditions of inattention as would be predicted by a Bayes-optimal observer model. These results inform and constrain future models of Bayesian inference in the human brain.

Effects of luminance contrast on the color selectivity of neurons in the macaque area v4 and inferior temporal cortex.

Appearance of a color stimulus is significantly affected by the contrast between its luminance and the luminance of the background. In the present study, we used stimuli evenly distributed on the CIE-xy chromaticity diagram to examine how luminance contrast affects neural representation of color in V4 and the anterior inferior temporal (AITC) and posterior inferior temporal (PITC) color areas (Banno et al., 2011). The activities of single neurons were recorded from monkeys performing a visual fixation task, and the effects of luminance contrast on the color selectivity of individual neurons and their population responses were systematically examined by comparing responses to color stimuli that were brighter or darker than the background. We found that the effects of luminance contrast differed considerably across V4 and the PITC and AITC. In both V4 and the PITC, the effects of luminance contrast on the population responses of color-selective neurons depended on color. In V4, the size of the effect was largest for blue and cyan, whereas in the PITC, the effect gradually increased as the saturation of the color stimulus was reduced, and was especially large with neutral colors (white, gray, black). The pattern observed in the PITC resembles the effect of luminance contrast on color appearance, suggesting PITC neurons are closely involved in the formation of the perceived appearance of color. By contrast, the color selectivities of AITC neurons were little affected by luminance contrast, indicating that hue and saturation of color stimuli are represented independently of luminance contrast in the AITC.

Face inversion decreased information about facial identity and expression in face-responsive neurons in macaque area TE.

To investigate the effect of face inversion and thatcherization (eye inversion) on temporal processing stages of facial information, single neuron activities in the temporal cortex (area TE) of two rhesus monkeys were recorded. Test stimuli were colored pictures of monkey faces (four with four different expressions), human faces (three with four different expressions), and geometric shapes. Modifications were made in each face-picture, and its four variations were used as stimuli: upright original, inverted original, upright thatcherized, and inverted thatcherized faces. A total of 119 neurons responded to at least one of the upright original facial stimuli. A majority of the neurons (71%) showed activity modulations depending on upright and inverted presentations, and a lesser number of neurons (13%) showed activity modulations depending on original and thatcherized face conditions. In the case of face inversion, information about the fine category (facial identity and expression) decreased, whereas information about the global category (monkey vs human vs shape) was retained for both the original and thatcherized faces. Principal component analysis on the neuronal population responses revealed that the global categorization occurred regardless of the face inversion and that the inverted faces were represented near the upright faces in the principal component analysis space. By contrast, the face inversion decreased the ability to represent human facial identity and monkey facial expression. Thus, the neuronal population represented inverted faces as faces but failed to represent the identity and expression of the inverted faces, indicating that the neuronal representation in area TE cause the perceptual effect of face inversion.

From neuronal populations to behavior: a computational journey.

Cognitive behaviors originate in the responses of neuronal populations. We have a reasonable understanding of how the activity of a single neuron can be related to a specific behavior. However, it is still unclear how more complex behaviors are inferred from the responses of neuronal populations. This is a particularly timely problem because multi-neuronal recording techniques have recently become increasingly available, simultaneously spurring advances in the analysis of neuronal population data. These developments are, however, constrained by the challenges of combining theoretical and experimental approaches because both approaches have their unique set of constraints. A solution to this problem is to design computational models that are either derived or inspired by cortical computations.

Development of a neural circuit in the superior colliculus

The superior colliculus is important for orientation behaviors, in which visuomotor transformation is performed by the pathway from the superficial layer (SGS) to the intermediate layers (SGI). The opposite pathway (from the SGI to the SGS) also exists, raising the possibility of a feedback circuit, although it could be either negative (inhibitory) or positive (excitatory). In this study, we focused on the development of the feedback circuit. We used optical imaging methods that can measure neuronal population responses directly, as the orientation behaviors are determined by large population activities of superior colliculus neurons. We examined the postnatal development of the propagation pattern of neuronal excitation from the SGI to the SGS using a GABAA receptor antagonist. The optical response propagated within the SGI, but not to the SGS in infant mice that have not opened their eyes. In contrast, in young mice after eye opening, the optical response propagated initially in the SGI and then to the SGS. The GABAA receptor antagonist increased the optical response in the SGS in young mice, as well as that in the SGI in infant mice. Together, these results suggest that axons of SGI neurons terminate to the SGS during development after eye opening.

Nucleus accumbens neuronal activity correlates to the animal's behavioral response to acute and chronic methylphenidate

Acute and chronic methylphenidate (MPD) exposure was recorded simultaneously for the rat's locomotor activity and the nucleus accumbens (NAc) neuronal activity. The evaluation of the neuronal events was based on the animal's behavior response to chronic MPD administration: 1) Animals exhibiting behavioral sensitization, 2) Animals exhibiting behavioral tolerance. The experiment lasted for 10days with four groups of animals; saline, 0.6, 2.5, and 10.0mg/kg MPD. For the main behavioral findings, about half of the animals exhibited behavioral sensitization or behavioral tolerance to 0.6, 2.5, and/or 10mg/kg MPD respectively. Three hundred and forty one NAc neuronal units were evaluated. Approximately 80% of NAc units responded to 0.6, 2.5, and 10.0mg/kg MPD. When the neuronal activity was analyzed based on the animals' behavioral response to chronic MPD exposure, significant differences were seen between the neuronal population responses recorded from animals that expressed behavioral sensitization when compared to the NAc neuronal responses recorded from animals exhibiting behavioral tolerance. Three types of neurophysiological sensitization and neurophysiological tolerance can be recognized following chronic MPD administration to the neuronal populations.Collectively, these findings show that the same dose of chronic MPD can elicit either behavioral tolerance or behavioral sensitization. Differential statistical analyses were used to verify our hypothesis that the neuronal activity recorded from animals exhibiting behavioral sensitization will respond differently to MPD compared to those animals exhibiting behavioral tolerance, thus, suggesting that it is essential to record the animal's behavior concomitantly with neuronal recordings.

Optogenetic stimulation of the auditory pathway

Auditory prostheses can partially restore speech comprehension when hearing fails. Sound coding with current prostheses is based on electrical stimulation of auditory neurons and has limited frequency resolution due to broad current spread within the cochlea. In contrast, optical stimulation can be spatially confined, which may improve frequency resolution. Here, we used animal models to characterize optogenetic stimulation, which is the optical stimulation of neurons genetically engineered to express the light-gated ion channel channelrhodopsin-2 (ChR2). Optogenetic stimulation of spiral ganglion neurons (SGNs) activated the auditory pathway, as demonstrated by recordings of single neuron and neuronal population responses. Furthermore, optogenetic stimulation of SGNs restored auditory activity in deaf mice. Approximation of the spatial spread of cochlear excitation by recording local field potentials (LFPs) in the inferior colliculus in response to suprathreshold optical, acoustic, and electrical stimuli indicated that optogenetic stimulation achieves better frequency resolution than monopolar electrical stimulation. Virus-mediated expression of a ChR2 variant with greater light sensitivity in SGNs reduced the amount of light required for responses and allowed neuronal spiking following stimulation up to 60 Hz. Our study demonstrates a strategy for optogenetic stimulation of the auditory pathway in rodents and lays the groundwork for future applications of cochlear optogenetics in auditory research and prosthetics.

Population Decoding in Rat Barrel Cortex: Optimizing the Linear Readout of Correlated Population Responses

Sensory information is encoded in the response of neuronal populations. How might this information be decoded by downstream neurons? Here we analyzed the responses of simultaneously recorded barrel cortex neurons to sinusoidal vibrations of varying amplitudes preceded by three adapting stimuli of 0, 6 and 12 µm in amplitude. Using the framework of signal detection theory, we quantified the performance of a linear decoder which sums the responses of neurons after applying an optimum set of weights. Optimum weights were found by the analytical solution that maximized the average signal-to-noise ratio based on Fisher linear discriminant analysis. This provided a biologically plausible decoder that took into account the neuronal variability, covariability, and signal correlations. The optimal decoder achieved consistent improvement in discrimination performance over simple pooling. Decorrelating neuronal responses by trial shuffling revealed that, unlike pooling, the performance of the optimal decoder was minimally affected by noise correlation. In the non-adapted state, noise correlation enhanced the performance of the optimal decoder for some populations. Under adaptation, however, noise correlation always degraded the performance of the optimal decoder. Nonetheless, sensory adaptation improved the performance of the optimal decoder mainly by increasing signal correlation more than noise correlation. Adaptation induced little systematic change in the relative direction of signal and noise. Thus, a decoder which was optimized under the non-adapted state generalized well across states of adaptation.

Neural Representation of Orientation Relative to Gravity in the Macaque Cerebellum

A fundamental challenge for maintaining spatial orientation and interacting with the world is knowledge of our orientation relative to gravity, i.e., head tilt. Sensing gravity is complicated because of Einstein's equivalence principle, in which gravitational and translational accelerations are physically indistinguishable. Theory has proposed that this ambiguity is solved by tracking head tilt through multisensory integration. Here we identify a group of Purkinje cells in the caudal cerebellar vermis with responses that reflect an estimate of head tilt. These tilt-selective cells are complementary to translation-selective Purkinje cells, such that their population activities sum to the net gravitoinertial acceleration encoded by the otolith organs, as predicted by theory. These findings reflect the remarkable ability of the cerebellum for neural computation and provide quantitative evidence for a neural representation of gravity, whose calculation relies on long-postulated theoretical concepts such as internal models and Bayesian priors.

Complex Population Response of Dorsal Putamen Neurons Predicts the Ability to Learn

Day-to-day variability in performance is a common experience. We investigated its neural correlate by studying learning behavior of monkeys in a two-alternative forced choice task, the two-armed bandit task. We found substantial session-to-session variability in the monkeys’ learning behavior. Recording the activity of single dorsal putamen neurons we uncovered a dual function of this structure. It has been previously shown that a population of neurons in the DLP exhibits firing activity sensitive to the reward value of chosen actions. Here, we identify putative medium spiny neurons in the dorsal putamen that are cue-selective and whose activity builds up with learning. Remarkably we show that session-to-session changes in the size of this population and in the intensity with which this population encodes cue-selectivity is correlated with session-to-session changes in the ability to learn the task. Moreover, at the population level, dorsal putamen activity in the very beginning of the session is correlated with the performance at the end of the session, thus predicting whether the monkey will have a "good" or "bad" learning day. These results provide important insights on the neural basis of inter-temporal performance variability.

Signal-To-Noise-Optimal scaling of heterogenous population codes

Similarity measures for neuronal population responses that are based on scalar products can be little informative if the neurons have different firing statistics. Based on signal-to-noise optimality, this paper derives positive weighting factors for the individual neurons' response rates in a heterogeneous neuronal population. The weights only depend on empirical statistics. If firing follows Poisson statistics, the weights can be interpreted as mutual information per spike. The scaling is shown to improve linear separability and clustering as compared to unscaled inputs.

Linking neural mass signals and spike train statistics through point process and linear systems theory

The relation between neural mass signals, like local field potentials (LFP) or electro-encephalograms (EEG), and the spiking activity of neurons in a network is still poorly understood. Recently, linear temporal filters have been used to map multi-unit activity (MUA) to LFP signals recorded at the same electrode [1]. Similar kernels have been previously identified relating simulated network activity to the human EEG [2]. However, currently there are no theoretical/computational models to explain the form of these filters that map MUA to LFP or EEG. Here we studied the relation between MUA and LFP in a minimal network model of the neocortex. Using simplified statistical models of neurons [3,4], the firing rate response of neuronal populations to time-dependent inputs can be characterized as that of a high pass filter. At the same time, the LFP recorded in the neocortex can be interpreted as a measure of the summated synaptic input to the population of nearby neurons [5], filtered by the neuronal membranes and the recurrent network [6]. Combining these various filter operations, we arrive at the forward model (LFP to MUA) of a band-pass filter, which can be inverted to predict the LFP from the MUA. Our results explain the form of the experimentally obtained kernels [1] and provide insight into the encoding of a stimulus by local neuronal populations. Furthermore, our theory explains characteristic properties of the neocortical LFP, solely based on effective neuronal refractoriness, membrane filtering and recurrent connectivity.

Decoding the motion aftereffect in human visual cortex

In the motion aftereffect (MAE), adapting to a moving stimulus causes a subsequently presented stationary stimulus to appear to move in the opposite direction. Recently, the neural basis of the motion aftereffect has received considerable interest, and a number of brain areas have been implicated in the generation of the illusory motion. Here, we use functional magnetic resonance imaging in combination with multivariate pattern classification to directly compare the neural activity evoked during the observation of both real and illusory motions. We show that the perceived illusory motion is not encoded in the same way as real motion in the same direction. Instead, suppression of the adapted direction of motion results in a shift of the population response of motion sensitive neurons in area MT+, resulting in activation patterns that are in fact more similar to real motion in orthogonal, rather than opposite directions. Although robust motion selectivity was observed in visual areas V1, V2, V3, and V4, this MAE-specific modulation of the population response was only observed in area MT+. Implications for our understanding of the motion aftereffect, and models of motion perception in general, are discussed.