Behavioral Neuroscience publications

Purpose: In anesthesia research and clinical practice, the level of consciousness is often assessed by stimulating subjects and observing their responses. It is possible that such stimulation alters the very state of consciousness being assessed. Whether this phenomenon is accompanied by specific cortical activities remains unknown. Here, we tested the effects of behavioral assessments on neuronal activity in the rat primary auditory cortex (A1) and perirhinal cortex (PrC). Methods: Neuronal spiking activity was recorded from microwire arrays targeting A1 and/or PrC in rats (n = 9), whilst presenting 40 Hz click-trains and gradually increasing infusion rates of propofol, remifentanil, ketamine or dexmedetomidine. We assessed righting reflex, pain withdrawal, whisking reflex, and corneal reflex every 12 minutes (every 360 auditory trials). We searched for significant changes in baseline firing rate and stimulus-evoked activities (where present) due to the behavioral assessments, by comparing 4 min intervals before and after the behavioral tests. Results: Out of 1004 units in 20 sessions, we found significantly elevated activity (p < 0.01) following behavioral tests in 32% and 20% of A1 auditory-responsive units and 8.6% and 5.3% of auditory-unresponsive units under propofol and dexmedetomidine, respectively, but not under remifentanil or ketamine. A higher proportion of units modulated their firing following behavioral tests in A1 compared to PrC, with median gains ranging from +0.23 to +1.06, depending on the specific response feature. Conclusion: Behavioral testing increases ongoing firing rate and responses to sounds in some cortical neurons. This increase is more prevalent in A1 than in PrC, mirroring clinical observations that patients exhibit basic responses under sedation, while complex processing, such as memory encoding, is impaired. The degree of neuronal modulation due to behavioral testing varies between anesthetic agents, mirroring their clinical phenotypes.

Flexible behavior requires decision-making that integrates both perceptual and mnemonic-related information. While the dorsal premotor cortex (PMd) is known to support perceptual decision-making, its contributions to decisions based on mnemonic information for motor planning remain underexplored. Here, we investigate local field potential (LFP) oscillations in the PMd of monkeys performing a transitive inference task requiring the formation and retrieval of mnemonic representations of an arbitrarily defined rank order among perceptual items. The difficulty of this operation depends on the distance of the items in the mnemonic representation. We tested the hypothesis that this symbolic distance (SD) systematically modulates PMd oscillatory activity in a frequency-specific manner during decisions that combine perceptual identification with mnemonic retrieval. Consistent with this hypothesis, PMd exhibited local and reliable SD-dependent changes across low (Theta, Alpha, Beta) and high-Gamma (h-Gamma) frequency bands, and related to behavioral performance. These findings provide evidence that the PMd integrates perceptual and mnemonic information through coordinated modulations of oscillatory activity, extending its role beyond perceptual mapping to support abstract, memory-guided decisions.

Flexible behaviour requires decision-making that integrates both perceptual and mnemonic-related information. While the dorsal premotor cortex (PMd) is known to support decision-making based on perceptual computations, its contributions to decisions based on mnemonic information for motor planning are underexplored. Here, investigating local field potential (LFP) oscillations in PMd of monkeys performing a transitive inference task required the formation and retrieval of mnemonic representations of an arbitrarily defined rank order among perceptual items. Our results highlight that a dynamic interplay between lower frequencies (Theta, Alpha, Beta) and high-Gamma oscillatory activity of LFP reflects a mechanism for accessing and manipulating memory-related information underlying decision-making. These findings provide evidence that the PMd plays a role in multiplexing both perceptual and mnemonic information, extending its competence beyond the association of perceptual input with motor decisions.

Animacy perception, the ability to discern living from non-living entities, is crucial for survival and social interaction, as it includes recognizing abstract concepts such as movement, purpose, and intentions. This process involves interpreting cues that may suggest the intentions or actions of others. It engages the temporal cortex (TC), particularly the superior temporal sulcus (STS) and the adjacent region of the inferior temporal cortex (ITC), as well as the dorsomedial prefrontal cortex (dmPFC). However, it remains unclear how animacy is dynamically encoded over time in these brain areas and whether its processing is distributed or localized. In this study, we addressed these questions by employing a symbolic categorization task involving animate and inanimate objects using natural movie stimuli. Simultaneously, electrocorticography were conducted in both the TC and dmPFC. Time-frequency analysis revealed region-specific frequency representations throughout the observation of the movies. Spatial searchlight decoding analysis demonstrated that animacy processing is represented in a distributed manner. Regions encoding animacy information were found to be dispersed across the fundus and lip of the STS, as well as in the ITC. Next, we examined whether these dispersed regions form functional networks. Independent component analysis revealed that the spatial distribution of the component with the most significant animacy information corresponded with the dispersed regions identified by the spatial decoding analysis. Furthermore, Granger causality analysis indicated that these regions exhibit frequency-specific directional functional connectivity, with a general trend of causal influence from the ITC to STS across multiple frequency bands. Notably, a prominent feedback flow in the alpha band from the ITC to both the ventral bank and fundus of the STS was identified. These findings suggest a distributed and functionally interconnected neural substrate for animacy processing across the STS and ITC.

Before selecting a saccadic target, we often acquire partial information about the location of the forthcoming target and preselect a region of visual space even before the target becomes visible. To determine whether the supplementary eye field (SEF) represents information signifying the potential target space, we examined neuronal activity in the SEF of monkeys performing a behavioral task designed to isolate the process of visuospatial preselection under uncertainty from the process of selecting a specified location. Our data showed that the activity of SEF neurons represented information about the potential target space instructed by symbolic cues. Increased activity of visuospatially selective SEF neurons encoded the potential target space, which could be a mechanism facilitating subsequent selection of an appropriate target. Furthermore, electrical stimulation of the SEF during the preselection period disrupted subsequent target selection. These results demonstrate that the SEF contributes to the preselection of potential target spaces based on partial information.

The claustrum has been linked to attention and sleep. We hypothesized that this reflects a shared function, determining responsiveness to stimuli, which spans the axis of engagement. To test this hypothesis, we recorded claustrum population dynamics from male mice during both sleep and an attentional task (‘ENGAGE’). Heightened activity in claustrum neurons projecting to the anterior cingulate cortex (ACCp) corresponded to reduced sensory responsiveness during sleep. Similarly, in the ENGAGE task, heightened ACCp activity correlated with disengagement and behavioral lapses, while low ACCp activity correlated with hyper-engagement and impulsive errors. Chemogenetic elevation of ACCp activity reduced both awakenings during sleep and impulsive errors in the ENGAGE task. Furthermore, mice employing an exploration strategy in the task showed a stronger correlation between ACCp activity and performance compared to mice employing an exploitation strategy which reduced task complexity. Our results implicate ACCp claustrum neurons in restricting engagement during sleep and goal-directed behavior.

Objective . Therapeutic brain stimulation is conventionally delivered using constant-frequency stimulation pulses. Several recent clinical studies have explored how unconventional and irregular temporal stimulation patterns could enable better therapy. However, it is challenging to understand which irregular patterns are most effective for different therapeutic applications given the massively high-dimensional parameter space. Approach . Here we applied many irregular stimulation patterns in a single neural circuit to demonstrate how they can enable new dimensions of neural control compared to conventional stimulation, to guide future exploration of novel stimulation patterns in translational settings. We optogenetically excited the septohippocampal circuit with constant-frequency, nested pulse, sinusoidal, and randomized stimulation waveforms, systematically varying their amplitude and frequency parameters. Main results. We first found equal entrainment of hippocampal oscillations: all waveforms provided similar gamma-power increase, whereas no parameters increased theta-band power above baseline (despite the mechanistic role of the medial septum in driving hippocampal theta oscillations). We then compared each of the effects of each waveform on high-dimensional multi-band activity states using dimensionality reduction methods. Strikingly, we found that conventional stimulation drove predominantly ‘artificial’ (different from behavioral activity) effects, whereas all irregular waveforms induced activity patterns that more closely resembled behavioral activity. Significance . Our findings suggest that irregular stimulation patterns are not useful when the desired mechanism is to suppress or enhance a single frequency band. However, novel stimulation patterns may provide the greatest benefit for neural control applications where entraining a particular mixture of bands (e.g. if they are associated with different symptoms) or behaviorally-relevant activity is desired.

Hand movements are associated with modulations of neuronal activity across several interconnected cortical areas, including the primary motor cortex (M1) and the dorsal and ventral premotor cortices (PMd and PMv). Local field potentials (LFPs) provide a link between neuronal discharges and synaptic inputs. Our current understanding of how LFPs vary in M1, PMd, and PMv during contralateral and ipsilateral movements is incomplete. To help reveal unique features in the pattern of modulations, we simultaneously recorded LFPs in these areas in two macaque monkeys performing reach and grasp movements with either the right or left hand. The greatest effector-dependent differences were seen in M1, at low (≤13 Hz) and γ frequencies. In premotor areas, differences related to hand use were only present in low frequencies. PMv exhibited the greatest increase in low frequencies during instruction cues and the smallest effector-dependent modulation during movement execution. In PMd, δ oscillations were greater during contralateral reach and grasp, and β activity increased during contralateral grasp. In contrast, β oscillations decreased in M1 and PMv. These results suggest that while M1 primarily exhibits effector-specific LFP activity, premotor areas compute more effector-independent aspects of the task requirements, particularly during movement preparation for PMv and production for PMd. The generation of precise hand movements likely relies on the combination of complementary information contained in the unique pattern of neural modulations contained in each cortical area. Accordingly, integrating LFPs from premotor areas and M1 could enhance the performance and robustness of brain-machine interfaces.

Natural scene responses in the primary visual cortex are modulated simultaneously by attention and by contextual signals about scene statistics stored across the connectivity of the visual processing hierarchy. We hypothesized that attentional and contextual signals interact in V1 in a manner that primarily benefits the representation of natural stimuli, rich in high-order statistical structure. Recording from two macaques engaged in a spatial attention task, we found that attention enhanced the decodability of stimulus identity from population responses evoked by natural scenes, but not by synthetic stimuli lacking higher-order statistical regularities. Population analysis revealed that neuronal responses converged to a low-dimensional subspace only for natural stimuli. Critically, we determined that the attentional enhancement in stimulus decodability was captured by the natural-scene subspace, indicating an alignment between the attentional and natural stimulus variance. These results suggest that attentional and contextual signals interact in V1 in a manner optimized for natural vision.

Progress in understanding brain–viscera interoceptive signaling is hindered by a dearth of implantable devices suitable for probing both brain and peripheral organ neurophysiology during behavior. Here we describe multifunctional neural interfaces that combine the scalability and mechanical versatility of thermally drawn polymer-based fibers with the sophistication of microelectronic chips for organs as diverse as the brain and the gut. Our approach uses meters-long continuous fibers that can integrate light sources, electrodes, thermal sensors and microfluidic channels in a miniature footprint. Paired with custom-fabricated control modules, the fibers wirelessly deliver light for optogenetics and transfer data for physiological recording. We validate this technology by modulating the mesolimbic reward pathway in the mouse brain. We then apply the fibers in the anatomically challenging intestinal lumen and demonstrate wireless control of sensory epithelial cells that guide feeding behaviors. Finally, we show that optogenetic stimulation of vagal afferents from the intestinal lumen is sufficient to evoke a reward phenotype in untethered mice.

During visual search, it is important to reduce the interference of distracting objects in the scene. The neuronal responses elicited by the search target stimulus are typically enhanced. However, it is equally important to suppress the representations of distracting stimuli, especially if they are salient and capture attention. We trained monkeys to make an eye movement to a unique “pop-out” shape stimulus among an array of distracting stimuli. One of these distractors had a salient color that varied across trials and differed from the color of the other stimuli, causing it to also pop-out. The monkeys were able to select the pop-out shape target with high accuracy and actively avoided the pop-out color distractor. This behavioral pattern was reflected in the activity of neurons in area V4. Responses to the shape targets were enhanced, while the activity evoked by the pop-out color distractor was only briefly enhanced, directly followed by a sustained period of pronounced suppression. These behavioral and neuronal results demonstrate a cortical selection mechanism that rapidly inverts a pop-out signal to “pop-in” for an entire feature dimension thereby facilitating goal-directed visual search in the presence of salient distractors.

The common marmoset has emerged as a key model in neuroscience. Marmosets are small in size, show great potential for genetic modification and exhibit complex behaviors. Thus, it is necessary to develop technology that enables monitoring and manipulation of the underlying neural circuits. Here, we describe a novel approach to record and optogenetically manipulate neural activity in awake, behaving marmosets. Our design utilizes a light-weight, 3D printed titanium chamber that can house several high-density silicon probes for semi-chronic recordings, while enabling simultaneous optogenetic stimulation. We demonstrate the application of our method in male marmosets by recording multi- and single-unit data from areas V1 and V6 with 192 channels simultaneously, and show that optogenetic activation of excitatory neurons in area V6 can influence behavior in a detection task. This method may enable future studies to investigate the neural basis of perception and behavior in the marmoset.

Hippocampal theta and gamma rhythms are hypothesized to play a role in the physiology of higher cognition. Prior research has reported that an offset in theta cycles between the entorhinal cortex, CA3, and CA1 regions promotes independence of population activity across the hippocampus. In line with this idea, it has recently been observed that CA1 pyramidal cells can establish and maintain coordinated place cell activity intrinsically, with minimal reliance on afferent input. Counter to these observations is the contemporary hypothesis that CA1 neuron activity is driven by a gamma oscillation arising from the medial entorhinal cortex (MEC) that relays information by providing precisely timed synchrony between MEC and CA1. Reinvestigating this in rats during appetitive track running, we found that theta is the dominant frequency of cross-frequency coupling between the MEC and hippocampus, with hippocampal gamma largely independent of entorhinal gamma.

After a briefly presented visual stimulus disappears, observers retain a detailed representation of this stimulus for a short period of time. This sensory storage is called iconic memory. We measured iconic memory in the perception of monkeys and its neuronal correlates in the primary visual cortex (area V1). We determined how many milliseconds extra viewing time iconic memory is worth and how it decays by varying the duration of a brief stimulus and the timing of a mask. The V1 activity that persists after the disappearance of a stimulus predicted accuracy, with a time course resembling the worth and decay of iconic memory. Finally, we examined how iconic memory interacts with attention. A cue presented after the stimulus disappears boosts attentional influences pertaining to a relevant part of the stimulus but only if it appears before iconic memory decayed. Our results relate iconic memory to neuronal activity in early visual cortex.

The marmoset has emerged as a promising primate model system, in particular for visual neuroscience. Many common experimental paradigms rely on head fixation and an extended period of eye fixation during the presentation of salient visual stimuli. Both of these behavioral requirements can be challenging for marmosets. Here, we present two methodological developments, each addressing one of these difficulties. First, we show that it is possible to use a standard eye-tracking system without head fixation to assess visual behavior in the marmoset. Eye-tracking quality from head-free animals is sufficient to obtain precise psychometric functions from a visual acuity task. Second, we introduce a novel method for efficient receptive field (RF) mapping that does not rely on moving stimuli but uses fast flashing annuli and wedges. We present data recorded during head-fixation in areas V1 and V6 and show that RF locations are readily obtained within a short period of recording time. Thus, the methodological advancements presented in this work will contribute to establish the marmoset as a valuable model in neuroscience.

Anxiety disorders involve distorted perception of the world including increased saliency of stress-associated cues. However, plasticity in the initial sensory regions of the brain following a fearful experience has never been examined. The cochlear nucleus (CN) is the first station in the central auditory system, with heterogeneous collections of neurons that not only project to but also receive projections from cortico-limbic regions, suggesting a potential for experience-dependent plasticity. Using wireless neural recordings in freely behaving rats, we demonstrate for the first time that neural gain in the CN is significantly altered by fear conditioning to auditory sequences. Specifically, the ventral subnuclei significantly increased firing rate to the conditioned tone sequence, while the dorsal subnuclei significantly decreased firing rate during the conditioning session overall. These findings suggest subregion-specific changes in the balance of inhibition and excitation in the CN as a result of conditioning experience. Heart rate was measured as the conditioned response (CR), which showed that while pre-conditioned stimulus (CS) responding did not change across baseline and conditioning sessions, significant changes in heart rate were observed to the tone sequence followed by shock. Heart-rate findings support acquisition of conditioned fear. Taken together, the present study presents first evidence for potential experience-dependent changes in auditory perception that involve novel plasticity within the first site of processing auditory information in the brain.

A major frontier in neuroscience is to find neural correlates of perception, learning, decision making, and a variety of other types of behavior. In the last decades, modern devices allow simultaneous recordings of different operant responses and the electrical activity of large neuronal populations. However, the commercially available instruments for studying operant conditioning are expensive, and the design of low-cost chambers has emerged as an appealing alternative to resource-limited laboratories engaged in animal behavior. In this article, we provide a full description of a platform that records the operant behavior and synchronizes it with the electrophysiological activity. The programming of this platform is open source, flexible, and adaptable to a wide range of operant conditioning tasks. We also show results of operant conditioning experiments with freely moving rats with simultaneous electrophysiological recordings.

Evidence suggests that the pathophysiology associated with epileptic susceptibility may disturb the functional connectivity of neural circuits and compromise the brain functions, even when seizures are absent. Although memory impairment is a common comorbidity found in patients with epilepsy, it is still unclear whether more caudal structures may play a role in cognitive deficits, particularly in those cases where there is no evidence of hippocampal sclerosis. This work used a genetically selected rat strain for seizure susceptibility (Wistar audiogenic rat, WAR) and distinct behavioral (motor and memory-related tasks) and electrophysiological (inferior colliculus, IC) approaches to access acoustic primary integrative network properties. The IC neural assemblies' response was evaluated by auditory transient (focusing on bottom-up processing) and steady-state evoked response (ASSR, centering on feedforward and feedback forces over neural circuitry). The results show that WAR displayed no disturbance in motor performance or hippocampus-dependent memory tasks. Nonetheless, WAR animals exhibited significative impairment for auditory fear conditioning (AFC) along with no indicative of IC plastic changes between the pre-conditioning and test phases (ASSR coherence analysis). Furthermore, WAR's IC response to transient stimuli presented shorter latency and higher amplitude compared with Wistar; and the ASSR analysis showed similar results for WAR and Wistar animals under subthreshold dose of pentylenetetrazol (pro-convulsive drug) for seizure-induction. Our work demonstrated alterations at WAR IC neural network processing, which may explain the associated disturbance on AFC memory.

Humans and other animals effortlessly identify natural sounds and categorize them into behaviorally relevant categories. Yet, the acoustic features and neural transformations that enable sound recognition and the formation of perceptual categories are largely unknown. Here, using multichannel neural recordings in the auditory midbrain of unanesthetized female rabbits, we first demonstrate that neural ensemble activity in the auditory midbrain displays highly structured correlations that vary with distinct natural sound stimuli. These stimulus-driven correlations can be used to accurately identify individual sounds using single-response trials, even when the sounds do not differ in their spectral content. Combining neural recordings and an auditory model, we then show how correlations between frequency-organized auditory channels can contribute to discrimination of not just individual sounds but sound categories. For both the model and neural data, spectral and temporal correlations achieved similar categorization performance and appear to contribute equally. Moreover, both the neural and model classifiers achieve their best task performance when they accumulate evidence over a time frame of approximately 1-2 seconds, mirroring human perceptual trends. These results together suggest that time-frequency correlations in sounds may be reflected in the correlations between auditory midbrain ensembles and that these correlations may play an important role in the identification and categorization of natural sounds.

Local field potential (LFP) oscillations are primarily shaped by the superposition of postsynaptic currents. Hippocampal LFP oscillations in the 25- to 50-Hz range (“slow γ”) are proposed to support memory retrieval independent of other frequencies. However, θ harmonics extend up to 48 Hz, necessitating a study to determine whether these oscillations are fundamentally the same. We compared the spectral analysis methods of wavelet, ensemble empirical-mode decomposition (EEMD), and Fourier transform. EEMD, as previously applied, failed to account for the θ harmonics. Depending on analytical parameters selected, wavelet may convolve over high-order θ harmonics due to the variable time-frequency atoms, creating the appearance of a broad 25- to 50-Hz rhythm. As an illustration of this issue, wavelet and EEMD depicted slow γ in a synthetic dataset that only contained θ and its harmonics. Oscillatory transience cannot explain the difference in approaches as Fourier decomposition identifies ripples triggered to epochs of high-power, 120- to 250-Hz events. When Fourier is applied to high power, 25- to 50-Hz events, only θ harmonics are resolved. This analysis challenges the identification of the slow γ rhythm as a unique fundamental hippocampal oscillation. While there may be instances in which slow γ is present in the rat hippocampus, the analysis presented here shows that unless care is exerted in the application of EEMD and wavelet techniques, the results may be misleading, in this case misrepresenting θ harmonics. Moreover, it is necessary to reconsider the characteristics that define a fundamental hippocampal oscillation as well as theories based on multiple independent γ bands.