Evoked Frontal and Parietal Field Potential Signatures of Target Detection and Response Inhibition in Rats Performing an Equiprobable Auditory Go/No-Go Task.

To characterize the rat as a potential model of frontal-parietal auditory processing during sustained attention, target detection, and response inhibition, we recorded field potentials (FPs) at multiple sites in medial-dorsal frontal and posterior parietal cortex simultaneously while rats performed an equiprobable auditory go/no-go discrimination task. Event-related potentials (ERPs) were calculated by averaging tone-triggered FPs across hit, miss, false alarm (FA), and correct rejection (CR) trials separately for each recording session, and five peak amplitudes (termed N1, P2, N2, P3E, and P3L) were extracted from the individual-session ERPs. Comparing peak amplitudes across different trials types indicated a statistically significant amplification of the P2 peak on hit trials that accompanies detection of the target tone prior to the behavioral go response. This result appears analogous to human ERP phenomena during auditory target discrimination. Conversely, the rat P3 responses were not associated with target detection as in the human ERP literature. Likewise, we did not observe the "no-go N2" or "no-go P3" responses reported in the human literature in association with response inhibition, which might reflect differences in task context or a difference in auditory processing between rats and humans. We also present analyses of stimulus-induced spectral power and interarea coherence to characterize oscillatory synchronization which may contribute to ERPs, and discuss possible error-related processing at the N2, P3E, and P3L peaks.

An Instructor's Guide to (Some of) the Most Amazing Papers in Neuroscience.

Although textbooks are still assigned in many undergraduate science courses, it is now not uncommon, even in some of the earliest courses in the curriculum, to supplement texts with primary source readings from the scientific literature. Not only does reading these articles help students develop an understanding of specific course content, it also helps foster an ability to engage with the discipline the way its practitioners do. One challenge with this approach, however, is that it can be difficult for instructors to select appropriate readings on topics outside of their areas of expertise as would be required in a survey course, for example. Here we present a subset of the papers that were offered in response to a request for the "most amazing papers in neuroscience" that appeared on the listserv of the Faculty for Undergraduate Neuroscience (FUN). Each contributor was subsequently asked to describe briefly the content of their recommended papers, their pedagogical value, and the audiences for which these papers are best suited. Our goal is to provide readers with sufficient information to decide whether such articles might be useful in their own classes. It is not our intention that any article within this collection will provide the final word on an area of investigation, nor that this collection will provide the final word for the discipline as a whole. Rather, this article is a collection of papers that have proven themselves valuable in the hands of these particular educators. Indeed, it is our hope that this collection represents the inaugural offering of what will become a regular feature in this journal, so that we can continue to benefit from the diverse expertise of the FUN community.

Role of medio-dorsal frontal and posterior parietal neurons during auditory detection performance in rats.

To further characterize the role of frontal and parietal cortices in rat cognition, we recorded action potentials simultaneously from multiple sites in the medio-dorsal frontal cortex and posterior parietal cortex of rats while they performed a two-choice auditory detection task. We quantified neural correlates of task performance, including response movements, perception of a target tone, and the differentiation between stimuli with distinct features (different pitches or durations). A minority of units--15% in frontal cortex, 23% in parietal cortex--significantly distinguished hit trials (successful detections, response movement to the right) from correct rejection trials (correct leftward response to the absence of the target tone). Estimating the contribution of movement-related activity to these responses suggested that more than half of these units were likely signaling correct perception of the auditory target, rather than merely movement direction. In addition, we found a smaller and mostly not overlapping population of units that differentiated stimuli based on task-irrelevant details. The detection-related spiking responses we observed suggest that correlates of perception in the rat are sparsely represented among neurons in the rat's frontal-parietal network, without being concentrated preferentially in frontal or parietal areas.

Prestimulus frontal-parietal coherence predicts auditory detection performance in rats.

Electrophysiology in primates has implicated long-range neural coherence as a potential mechanism for enhancing sensory detection. To test whether local synchronization and long-range neural coherence support detection performance in rats, we recorded local field potentials (LFPs) in frontal and parietal cortex while rats performed an auditory detection task. We observed significantly elevated power at multiple low frequencies (<15 Hz) preceding the target beep when the animal failed to respond to the signal (misses), in both frontal and parietal cortex. In terms of long-range coherence, we observed significantly more frontal-parietal coherence in the beta band (15-30 Hz) before the signal on misses compared with hits. This effect persisted after regressing away linear trends in the coherence values during a session, showing that the excess frontal-parietal beta coherence prior to misses cannot be explained by slow motivational changes during a session. In addition, a trend toward higher low-frequency (<15 Hz) coherence prior to miss trials compared with hits became highly significant when we rereferenced the LFPs to the mean voltage on each recording array, suggesting that the results are specific to our frontal and parietal areas. These results do not support a role for long-range frontal-parietal coherence or local synchronization in facilitating the detection of external stimuli. Rather, they extend to long-range frontal-parietal coherence previous findings that correlate local synchronization of low-frequency (<15 Hz) oscillations with inattention to external stimuli and synchronization of beta rhythms (15-30 Hz) with voluntary or involuntary prolongation of the current cognitive or motor state.

Simultaneous top-down modulation of the primary somatosensory cortex and thalamic nuclei during active tactile discrimination.

The rat somatosensory system contains multiple thalamocortical loops (TCLs) that altogether process, in fundamentally different ways, tactile stimuli delivered passively or actively sampled. To elucidate potential top-down mechanisms that govern TCL processing in awake, behaving animals, we simultaneously recorded neuronal ensemble activity across multiple cortical and thalamic areas while rats performed an active aperture discrimination task. Single neurons located in the primary somatosensory cortex (S1), the ventroposterior medial, and the posterior medial thalamic nuclei of the trigeminal somatosensory pathways exhibited prominent anticipatory firing modulations before the whiskers touching the aperture edges. This cortical and thalamic anticipatory firing could not be explained by whisker movements or whisker stimulation, because neither trigeminal ganglion sensory-evoked responses nor EMG activity were detected during the same period. Both thalamic and S1 anticipatory activity were predictive of the animal's discrimination accuracy. Inactivation of the primary motor cortex (M1) with muscimol affected anticipatory patterns in S1 and the thalamus, and impaired the ability to predict the animal's performance accuracy based on thalamocortical anticipatory activity. These findings suggest that neural processing in TCLs is launched in anticipation of whisker contact with objects, depends on top-down effects generated in part by M1 activity, and cannot be explained by the classical feedforward model of the rat trigeminal system.

Color tuning in alert macaque V1 assessed with fMRI and single-unit recording shows a bias toward daylight colors.

Colors defined by the two intermediate directions in color space, "orange-cyan" and "lime-magenta," elicit the same spatiotemporal average response from the two cardinal chromatic channels in the lateral geniculate nucleus (LGN). While we found LGN functional magnetic resonance imaging (fMRI) responses to these pairs of colors were statistically indistinguishable, primary visual cortex (V1) fMRI responses were stronger to orange-cyan. Moreover, linear combinations of single-cell responses to cone-isolating stimuli of V1 cone-opponent cells also yielded stronger predicted responses to orange-cyan over lime-magenta, suggesting these neurons underlie the fMRI result. These observations are consistent with the hypothesis that V1 recombines LGN signals into "higher-order" mechanisms tuned to noncardinal color directions. In light of work showing that natural images and daylight samples are biased toward orange-cyan, our findings further suggest that V1 is adapted to daylight. V1, especially double-opponent cells, may function to extract spatial information from color boundaries correlated with scene-structure cues, such as shadows lit by ambient blue sky juxtaposed with surfaces reflecting sunshine.

Deviance detection by a P3-like response in rat posterior parietal cortex.

To better understand sensory processing in frontal and parietal cortex of the rat, and to further assess the rat as a model of human frontal-parietal processing, we recorded local field potentials (LFPs) from microelectrode arrays implanted in medio-dorsal frontal, and posterior parietal cortex of awake rats as they were presented with a succession of frequent "standard" tones and infrequent "oddball" tones. Extending previous results from surface recordings we found, after controlling for the frequencies of the standard and oddball tones, that rat frontal and parietal-evoked LFPs (eLFPs) exhibit significantly larger N1 (~40 ms latency), P2 (~100 ms), N2 (~160 ms), P3E (~200-240 ms), and P3L (~300-500 ms) amplitudes after an oddball tone. These neural oddball effects could contribute to the automatic allocation of attention to rare stimuli. To determine whether these enhanced responses to rare stimuli could be accounted for in terms of stimulus-specific neural adaptation (SSA), we also recorded during single-tone control sessions involving frequent standard, or infrequent oddball beeps alone. We compared the difference between rare-tone and frequent-tone response amplitudes in the two-tone context (oddball effect) or single-tone context which isolates the contribution of SSA (SSA effect). An analysis of variance (ANOVA) revealed a significant main effect of tone context on rare-tone response enhancements, showing that the rare-tone enhancements were stronger in the two-tone context than the single-tone context. This difference between tone contexts was greatest at the early P3E peak (200-240 ms post-beep) in parietal cortex, suggesting true deviance detection by this evoked response component, which cannot be accounted for in terms of simple models of SSA.

Changes in S1 neural responses during tactile discrimination learning.

In freely moving rats that are actively performing a discrimination task, single-unit responses in primary somatosensory cortex (S1) are strikingly different from responses to comparable tactile stimuli in immobile rats. For example, in the active discrimination context prestimulus response modulations are common, responses are longer in duration and more likely to be inhibited. To determine whether these differences emerge as rats learned a whisker-dependent discrimination task, we recorded single-unit S1 activity while rats learned to discriminate aperture-widths using their whiskers. Even before discrimination training began, S1 responses in freely moving rats showed many of the signatures of active responses, such as increased duration of response and prestimulus response modulations. As rats subsequently learned the discrimination task, single unit responses changed: more cortical units responded to the stimuli, neuronal sensory responses grew in duration, and individual neurons better predicted aperture-width. In summary, the operant behavioral context changes S1 tactile responses even in the absence of tactile discrimination, whereas subsequent width discrimination learning refines the S1 representation of aperture-width.

Heterogeneous integration of bilateral whisker signals by neurons in primary somatosensory cortex of awake rats.

Bilateral single-unit recordings in primary somatosensory cortex (S1) of anesthetized rats have revealed substantial cross talk between cortical hemispheres, suggesting the possibility that behaviorally relevant bilateral integration could occur in S1. To determine the extent of bilateral neural responses in awake animals, we recorded S1 multi- and single-unit activity in head-immobilized rats while stimulating groups of 4 whiskers from the same column on both sides of the head. Results from these experiments confirm the widespread presence of single units responding to tactile stimuli on either side of the face in S1 of awake animals. Quantification of bilateral integration by multiunits revealed both facilitative and suppressive integration of bilateral inputs. Varying the interval between left and right whisker stimuli between 0 and 120 ms showed the temporal integration of bilateral stimuli to be dominated on average by suppression at intervals around 30 ms, in agreement with comparable recordings in anesthetized animals. Contrary to the anesthetized data, in the awake animals we observed a high level of heterogeneity of bilateral responses and a strong interaction between synchronous bilateral stimuli. The results challenge the traditional conception of highly segregated hemispheric processing channels in the rat S1 cortex, and support the hypothesis that callosal cross-projections between the two hemispheres mediate rats' known ability to integrate bilateral whisker signals.

Layer-specific somatosensory cortical activation during active tactile discrimination.

Ensemble neuronal activity was recorded in each layer of the whisker area of the primary somatosensory cortex (SI) while rats performed a whisker-dependent tactile discrimination task. Comparison of this activity with SI activity evoked by similar passive whisker stimulation revealed fundamental differences in tactile signal processing during active and passive stimulation. Moreover, significant layer-specific functional differences in SI activity were observed during active discrimination. These differences could not be explained solely by variations in ascending thalamocortical input to SI. Instead, these results suggest that top-down influences during active discrimination may alter the overall functional nature of SI as well as layer-specific mechanisms of tactile processing.

Behavioral detection of tactile stimuli during 7-12 Hz cortical oscillations in awake rats.

Prominent 7-12 Hz oscillations in the primary somatosensory cortex (S1) of awake but immobile rats might represent a seizure-like state in which neuronal burst firing renders animals unresponsive to incoming tactile stimuli; others have proposed that these oscillations are analogous to human mu rhythm. To test whether rats can respond to tactile stimuli during 7-12 Hz oscillatory activity, we trained head-immobilized awake animals to indicate whether they could detect the occurrence of transient whisker deflections while we recorded local field potentials (LFPs) from microelectrode arrays implanted bilaterally in the S1 whisker representation area. They responded rapidly and reliably, suggesting that this brain rhythm represents normal physiological activity that does not preclude perception.

Hyperscanning: simultaneous fMRI during linked social interactions.

"Plain question and plain answer make the shortest road out of most perplexities." Mark Twain-Life on the Mississippi. A new methodology for the measurement of the neural substrates of human social interaction is described. This technology, termed "Hyperscan," embodies both the hardware and the software necessary to link magnetic resonance scanners through the internet. Hyperscanning allows for the performance of human behavioral experiments in which participants can interact with each other while functional MRI is acquired in synchrony with the behavioral interactions. Data are presented from a simple game of deception between pairs of subjects. Because people may interact both asymmetrically and asynchronously, both the design and the analysis must accommodate this added complexity. Several potential approaches are described.