Yevgeniy B. Sirotin

Spatiotemporal precision and hemodynamic mechanism of optical point spreads in alert primates

In functional brain imaging there is controversy over which hemodynamic signal best represents neural activity. Intrinsic signal optical imaging (ISOI) suggests that the best signal is the early darkening observed at wavelengths absorbed preferentially by deoxyhemoglobin (HbR). It is assumed that this darkening or “initial dip” reports local conversion of oxyhemoglobin (HbO) to HbR, i.e., oxygen consumption caused by local neural activity, thus giving the most specific measure of such activity. The blood volume signal, by contrast, is believed to be more delayed and less specific. Here, we used multiwavelength ISOI to simultaneously map oxygenation and blood volume [i.e., total hemoglobin (HbT)] in primary visual cortex (V1) of the alert macaque. We found that the hemodynamic “point spread,” i.e., impulse response to a minimal visual stimulus, was as rapid and retinotopically specific when imaged by using blood volume as when using the initial dip. Quantitative separation of the imaged signal into HbR, HbO, and HbT showed, moreover, that the initial dip was dominated by a fast local increase in HbT, with no increase in HbR. We found only a delayed HbR decrease that was broader in retinotopic spread than HbO or HbT. Further, we show that the multiphasic time course of typical ISOI signals and the strength of the initial dip may reflect the temporal interplay of monophasic HbO, HbR, and HbT signals. Characterizing the hemodynamic response is important for understanding neurovascular coupling and elucidating the physiological basis of imaging techniques such as fMRI.

The neuroimaging signal is a linear sum of neurally distinct stimulus- and task-related components

Neuroimaging (for example, functional magnetic resonance imaging) signals are taken as a uniform proxy for local neural activity. By simultaneously recording electrode and neuroimaging (intrinsic optical imaging) signals in alert, task-engaged macaque visual cortex, we recently observed a large anticipatory trial-related neuroimaging signal that was poorly related to local spiking or field potentials. We used these same techniques to study the interactions of this trial-related signal with stimulus-evoked responses over the full range of stimulus intensities, including total darkness. We found that the two signals could be separated, and added linearly over this full range. The stimulus-evoked component was related linearly to local spiking and, consequently, could be used to obtain precise and reliable estimates of local neural activity. The trial-related signal likely has a distinct neural mechanism, however, and failure to account for it properly could lead to substantial errors when estimating local neural spiking from the neuroimaging signal.

Rodent ultrasonic vocalizations are bound to active sniffing behavior

During rodent active behavior, multiple orofacial sensorimotor behaviors, including sniffing and whisking, display rhythmicity in the theta range (~5–10 Hz). During specific behaviors, these rhythmic patterns interlock, such that execution of individual motor programs becomes dependent on the state of the others. Here we performed simultaneous recordings of the respiratory cycle and ultrasonic vocalization emission by adult rats and mice in social settings. We used automated analysis to examine the relationship between breathing patterns and vocalization over long time periods. Rat ultrasonic vocalizations (USVs, “50 kHz”) were emitted within stretches of active sniffing (5–10 Hz) and were largely absent during periods of passive breathing (1–4 Hz). Because ultrasound was tightly linked to the exhalation phase, the sniffing cycle segmented vocal production into discrete calls and imposed its theta rhythmicity on their timing. In turn, calls briefly prolonged exhalations, causing an immediate drop in sniffing rate. Similar results were obtained in mice. Our results show that ultrasonic vocalizations are an integral part of the rhythmic orofacial behavioral ensemble. This complex behavioral program is thus involved not only in active sensing but also in the temporal structuring of social communication signals. Many other social signals of mammals, including monkey calls and human speech, show structure in the theta range. Our work points to a mechanism for such structuring in rodent ultrasonic vocalizations.

Stimulus-related neuroimaging in task-engaged subjects is best predicted by concurrent spiking.

The implicit goal of functional magnetic resonance imaging is to infer local neural activity. There is considerable debate, however, as to whether imaging correlates most linearly with local spiking or some local field potential (LFP) measurement. Through simultaneous neuroimaging (intrinsic-signal optical imaging) and electrode recordings from alert, task-engaged macaque monkeys, we showed previously that local electrophysiology correlates with only a specific stimulus-related imaging component. Here we show that this stimulus-related component—obtained by subtracting a substantial task-related component—is particularly linear with local spiking over a comprehensive range of response strengths. Matches to concurrent LFP measurements are, to varying degrees, poorer. As a control, we also tried matching the full imaging signal to local electrophysiology without subtracting task-related components. These control matches were consistently worse; they were, however, slightly better for gamma LFP than spiking, potentially resolving discrepancies between our findings and earlier reports favoring LFP.

Rapid triggering of vocalizations following social interactions

Summary Social interactions are multifaceted, composed of interlinked sensory-motor behaviors. The individual significance of each of these correlated components cannot be established without observing the full behavior. Recently, Wesson [1] concluded that rats display their submissive status by lowering sniff rate following face-to-face encounters with a dominant conspecific. How rats can perceive such changes in sniff rate is unclear. We recorded sniffing and vocal production of rats during social interactions. Face-to-face encounters with a dominant rat immediately elicited 22 kHz alarm calls in the submissive. The large drop in sniff rate observed in submissive rats was caused by the prolonged exhalations needed to produce these calls. We propose that, while submissive rats do lower sniffing rates around face-to-face encounters, dominant rats need not directly perceive this change, but may instead attend to the salient 22 kHz alarm calls.

Neural Coding of Perceived Odor Intensity

Abstract Stimulus intensity is a fundamental perceptual feature in all sensory systems. In olfaction, perceived odor intensity depends on at least two variables: odor concentration; and duration of the odor exposure or adaptation. To examine how neural activity at early stages of the olfactory system represents features relevant to intensity perception, we studied the responses of mitral/tufted cells (MTCs) while manipulating odor concentration and exposure duration. Temporal profiles of MTC responses to odors changed both as a function of concentration and with adaptation. However, despite the complexity of these responses, adaptation and concentration dependencies behaved similarly. These similarities were visualized by principal component analysis of average population responses and were quantified by discriminant analysis in a trial-by-trial manner. The qualitative functional dependencies of neuronal responses paralleled psychophysics results in humans. We suggest that temporal patterns of MTC responses in the olfactory bulb contribute to an internal perceptual variable: odor intensity.

Single Scale for Odor Intensity in Rat Olfaction

Humans and laboratory animals are thought to discriminate sensory objects using elemental perceptual features computed by neural circuits in the brain. However, it is often difficult to identify the perceptual features that animals use to make specific comparisons. In olfaction, changes in the concentration of a given odor lead to discriminable changes in both its perceived quality and intensity. Humans use perceived intensity to compare quantities of different odors. Here we establish that laboratory rats also use perceived intensity to compare concentrations of different odors and reveal the perceptual organization of this elemental feature. We first trained rats to classify concentrations of single odors as high or low. When subsequently classifying concentrations of two odors presented on different trials of the same session, rats made errors consistent with using a single intensity criterion for both odors. This allowed us to investigate the relative perceived intensity of different odor pairs. Odor intensity was not only a function of concentration, but varied also with molecular weight and exposure time. These findings demonstrate the role of perceived intensity as an elemental perceptual feature of odors in rat olfaction.

What could underlie the trial-related signal? A response to the commentaries by Drs. Kleinschmidt and Muller, and Drs. Handwerker and Bandettini.

Here we address two recent commentaries on our finding of an anticipatory trial-related signal that could not be predicted by concurrent electrode recordings. In addition, we offer a broad discussion regarding what our findings do and do not say about local neural activity underlying imaging signals.

Reply to Uludağ: fMRI “initial dip” reflects increase in oxygenated hemoglobin

We thank Uludag (1) for the thoughtful letter about our paper (2) and for drawing our attention to …

Zooming in on mouse vision

An examination of the micro-organization of visual cortex using two-photon calcium imaging provides a new level of insight into retinotopic maps, finding that retinotopy is scrambled on fine scales in mouse primary visual cortex.