bioRxiv Subject Collection: Neuroscience's Journal
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Tuesday, February 6th, 2024
| Time |
Event |
| 11:45a |
The role of prospective contingency in the control of behavior and dopamine signals during associative learning
Associative learning depends on contingency, the degree to which a stimulus predicts an outcome. Despite its importance, the neural mechanisms linking contingency to behavior remain elusive. Here we examined the dopamine activity in the ventral striatum -- a signal implicated in associative learning -- in a Pavlovian contingency degradation task in mice. We show that both anticipatory licking and dopamine responses to a conditioned stimulus decreased when additional rewards were delivered uncued, but remained unchanged if additional rewards were cued. These results conflict with contingency-based accounts using a traditional definition of contingency or a novel causal learning model (ANCCR), but can be explained by temporal difference (TD) learning models equipped with an appropriate inter-trial-interval (ITI) state representation. Recurrent neural networks trained within a TD framework develop state representations like our best 'handcrafted' model. Our findings suggest that the TD error can be a measure that describes both contingency and dopaminergic activity. | | 11:45a |
Examining the relationship between psychosocial adversity and inhibitory control: an fMRI study of children growing up in extreme poverty
Exposure to psychosocial adversity (PA) is associated with poor behavioral, physical, and mental health outcomes in adulthood. Growing evidence suggests that deficits in executive functions may in part moderate these outcomes, with inhibitory control as an example of such a putative moderator. However, much of the literature examining the development of inhibitory control has been based on children in higher resource environments, and little is known how growing up in a low resource setting might exacerbate the link between inhibitory control and health outcomes. In this context we collected fMRI data during a Go/No-Go inhibitory control task and PA variables for 68 children 5 to 7 years of age living in Dhaka, Bangladesh, an area with a high prevalence of PA. The children's mothers completed behavioral questionnaires to assess the child's PA and their own PA. Whole-brain activation underlying inhibitory control was examined using the No-Go versus Go contrast, and associations with PA variables were assessed using whole-brain regressions. Childhood neglect was associated with weaker activation in the right posterior cingulate, whereas greater family conflict, economic stress, and maternal PA factors were associated with greater activation in the left medial frontal gyrus, right superior and middle frontal gyrus, and left cingulate gyrus. These data suggest that neural networks supporting inhibitory control processes may vary as a function of exposure to different types of PA, particularly between those related to threat and deprivation. Furthermore, increased activation in children with greater PA may serve as a compensatory mechanism, allowing them to maintain similar behavioral task performance. | | 11:45a |
A Functional and Non-Homuncular Representation of the Larynx in the Primary Motor Cortex of Mice, a Vocal Non-Learner
Vocalization is a complex behavior ranging from fully innate to advanced vocal learning. Vocal learning species possess a vocal primary motor cortex (M1) region that makes direct projections to brainstem vocal motor neurons, which are thought to facilitate learning and fine modulation of vocalizations. Surprisingly, a similar, albeit sparse, direct projection from M1 was found in mice. Mice produce ultrasonic vocalizations (USV) which appear to be mostly innate. Modulation of these USVs is impacted by lesions to this M1 region, but genetic ablation of the cortex leads to few, if any, changes to USVs. It remained unclear whether M1 has any control over the vocal organ in a vocal non-learning species. In the current study, we found that stimulation in different parts of M1 in mice can generate contractions in laryngeal and jaw muscles, with different latencies suggestive of both direct and indirect projections to brainstem vocal motor neurons. Viral tracing reveals both single- and double-labeled populations of cortical neurons that simultaneously innervate laryngeal, jaw, and forelimb motor circuits. Chemical lesions reveal that an anterolateral orofacial region of M1 regulates the number of syllables in vocal sequences. Our results provide evidence that M1 in a vocal non-learner has some influence on vocal musculature, consistent with the continuum hypothesis of vocal learning. They also reveal that the representations of muscles for different behaviors across mouse M1 are more intermixed than previously considered. We discuss how these results impact hypotheses on the evolution of cortical vocal control and motor cortex organization. | | 11:45a |
Distinct dynamics and intrinsic properties in ventral tegmental area populations mediate reward association and motivation
Ventral tegmental area (VTA) dopamine neurons regulate reward-related associative learning and reward-driven motivated behaviors, but how these processes are coordinated by distinct VTA neuronal subpopulations remains unresolved. Here we examine the neural correlates of reward-related prediction-error, action, cue, and outcome encoding as well as effort exertion and reward anticipation during reward-seeking behaviors. We compare the contribution of two primarily dopaminergic and largely non-overlapping VTA subpopulations, all VTA dopamine neurons, and VTA GABAergic neurons of the mouse midbrain to these processes. The dopamine subpopulation that projects to the nucleus accumbens (NAc) core preferentially encodes prediction-error and reward-predictive cues. In contrast, the dopamine subpopulation that projects to the NAc shell preferentially encodes goal-directed actions and reflects relative reward anticipation. VTA GABA neuron activity strongly contrasts VTA dopamine population activity and preferentially encodes reward outcome and retrieval. Electrophysiology, targeted optogenetics, and whole-brain input mapping reveal heterogeneity among VTA dopamine subpopulations. Our results demonstrate that VTA subpopulations carry distinct reward-related learning and motivation signals and reveal a striking pattern of functional heterogeneity among projection-defined VTA dopamine neuron populations. | | 11:45a |
Neural signatures of opioid-induced risk-taking behavior in the prelimbic prefrontal cortex
Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed a novel approach-avoidance conflict model using a modified conditioned place preference paradigm to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision making. Upon establishment of morphine conditioned place preference, rats underwent a subsequent conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline control group avoided the cat odor side, the morphine group maintained preference for the paired side despite the presence of cat odor. K-means clustering identified two subsets of morphine-treated rats that exhibited either persistent drug seeking (Risk-Takers) or increased avoidance (Risk-Avoiders) during conflict. Single-unit recordings from the prelimbic cortex (PL) revealed decreased neuronal firing rates upon acute morphine exposure in both Risk-Takers and Risk-Avoiders, but this firing rate suppression was absent after repeated administration. Risk-Avoiders also displayed distinct post-morphine excitation in PL which persisted across conditioning. During the preference test, subpopulations of PL neurons in all groups were either excited or inhibited when rats entered the paired side. Interestingly, while this inhibitory signal was lost during the subsequent conflict test in both saline and Risk-Avoider groups, these inhibitory responses persisted in Risk-Takers. Our results suggest that loss of PL inhibition after opioid conditioning is associated with the formation of contextual reward memory. Furthermore, persistent PL inhibitory signaling in the drug associated context during conflict may underlie increased risk taking following opioid exposure. | | 11:45a |
Intact Somatosensory Temporal Sensitivity in Adults on the Autism Spectrum: A High-Density Electrophysiological Mapping Study Using the Mismatch Negativity (MMN) Sensory Memory Paradigm.
Atypical reactivity to somatosensory inputs is common in autism spectrum disorder and carries considerable impact on downstream social communication and quality of life. While behavioral and survey work have established differences in the perception of somatosensory information, little has been done to elucidate the underlying neurophysiological processes that drive these characteristics. Here, we implemented a duration-based somatosensory mismatch negativity paradigm to examine the role of temporal sensitivity and sensory memory in the processing of vibrotactile information in autistic (n=30) and neurotypical (n=30) adults. To capture the variability in responses between groups across a range of duration discrepancies, we compared the electrophysiological responses to frequent standard vibrations (100 ms) and four infrequent deviant vibrations (115, 130, 145, and 160 ms). The same stimuli were used in a follow-up behavioral task to determine active detection of the infrequent vibrations. We found no differences between the two groups with regard to discrimination between standard and deviant vibrations, demonstrating comparable neurologic and behavioral temporal somatosensory perception. However, exploratory analyses yielded subtle differences in amplitude at the N1 and P220 time points. Together, these results indicate that the temporal mechanisms of somatosensory discrimination are conserved in adults on the autism spectrum, though more general somatosensory processing may be affected. We discuss these findings in the broader context of the MMN literature in autism, as well as the potential role of cortical maturity in somatosensory mechanisms. | | 11:45a |
The dimensionality of neural coding for cognitive control is gradually transformed within the lateral prefrontal cortex
Implementing cognitive control relies on neural representations that are inherently high-dimensional and distribute across multiple subregions in the prefrontal cortex (PFC). Traditional approaches tackle prefrontal representations by reducing them into a unidimensional measure (univariate amplitude) or using them to distinguish a limited number of alternatives (pattern classification). By contrast, representational similarity analysis (RSA) enables flexibly formulating various hypotheses about informational contents underlying the neural codes, explicitly comparing hypotheses, and examining the representational alignment between brain regions. Here, we used a multifaceted paradigm wherein the difficulty of cognitive control was manipulated separately for five cognitive tasks. We used RSA to unveil representational contents, measure the representational alignment between regions, and quantify representational generality vs. specificity. We found a graded transition in the lateral PFC: The dorsocaudal PFC was tuned to the information about behavioural effort, preferentially connected with the parietal cortex, and representationally generalisable across domains. The ventrorostral PFC was tuned to the abstract structure of tasks, preferentially connected with the temporal cortex, and representationally specific. The middle PFC (interposed between dorsocaudal and ventrorostral PFC) was tuned to individual task-sets, ranked in the middle in terms of connectivity and generalisability. Furthermore, whether a region was dimensionally rich or thin co-varied with its functional profile: Low dimensionality (only gist) in the dorsocaudal PFC dovetailed with better generality, whereas high dimensionality (gist plus details) in the ventrorostral PFC corresponded with better ability to encode subtleties. Our findings, collectively, demonstrate how cognitive control is decomposed into distinct facets that transition steadily along prefrontal subregions. | | 11:45a |
Featural and spatial interference with functionally active and passive items in working memory
We hypothesised that functionally active and passive states in working memory might be related to different neural mechanisms. Memoranda in active states might be maintained by persistent neural firing, whereas memoranda in passive states might be maintained through short-term synaptic plasticity. We reasoned that this might make these items differentially susceptible to interference during maintenance, and that passive items in particular might be more robust. To test this hypothesis, we gave our participants a working memory task in which one item was prioritised (active) by always probing it first, while the other item was deprioritised (passive) by always probing it second. In three experiments, we presented an interfering task during memory maintenance, in which the stimuli matched either the feature dimension of the memory items (colour or orientation), their spatial location, or both. We found that both active and passive memory items were affected by interference, to a similar extent, with overall performance being closely matched. However, we observed a qualitative difference in the nature of their representations. Specifically, featural interference seemed to produce reduced precision for active items, whereas it resulted in higher guess rates for passive items. The existence of this qualitative difference suggests that functionally active and passive working memory states may indeed map onto different neural mechanisms, even though on average they seem to be equally robust to interference. | | 3:17p |
Depression Attenuates Caudate and Dorsolateral Prefrontal Cortex Alpha and Beta Power Response to Reward
Depression is a prevalent psychiatric condition and a common comorbidity across neurological disorders. Common symptoms include anhedonia, negative emotional biases, and cognitive dysfunction. Beta (15-30 Hz) neural oscillations have been shown to increase during reward-based learning within fronto-striatal reward networks. Corticostriatal beta oscillations have also been implicated in cognitive functions including working memory. However, the relationship between beta oscillations and depression remains unknown. Using intracranial recordings, we aimed to investigate how depression modulates the spectral power of neural oscillations in corticostriatal structures during reward feedback in a working memory task. Thirty movement disorder patients undergoing awake deep brain stimulation surgery with electrode trajectories traversing the caudate or dorsolateral prefrontal cortex (DLPFC) participated in this study. We recorded local field potential data intraoperatively as subjects completed a 2-back verbal working memory task where they identified whether a word matched the word presented two trials prior. Subjects received reward in the form of visual feedback for correct answers. Word stimuli had either a positive, negative, or neutral emotional valence. Subjects completed the Beck Depression Inventory-II preoperatively, and we used a cut-off score of 14 to identify patients with depression. We found that caudate and DLPFC power increased in the alpha (8-15 Hz) and beta range during reward feedback and that this increase was significantly greater for subjects without depression compared to depressed subjects. In non-depressed patients, positive feedback stimuli evoked significantly higher beta power in the caudate during reward compared to neutral and negative stimuli. In depressed patients, emotional valence did not affect reward-related spectral power. We additionally found that anti-depressant medications (ADMs) generally blunted alpha and beta reward signaling processes in the DLPFC. This blunting effect on reward-related alpha power in the DLPFC, however, was reversed in depressed patients, indicating that the effects of ADMs on reward signaling processes may depend on whether a patient is exhibiting depression symptoms. Our findings suggest that depression suppresses the alpha and beta power response to both reward and emotional stimuli during working memory, indicating power attenuation in these frequency bands may contribute to emotional and cognitive depression symptoms. | | 3:17p |
The Brain Tells a Story: Unveiling Distinct Representations of Semantic Content in Speech, Objects, and Stories in the Human Brain with Large Language Models
In recent studies, researchers have utilized Large Language Models (LLMs) to investigate semantic representation within the brain. However, in many of these studies, the researchers often examined various semantic information contents separately, such as speech content, objects in scenes, and background stories. To quantitatively evaluate the contribution of various semantic contents in the brain, we recorded brain activity using functional magnetic resonance imaging (fMRI) while participants watched a total of 8.3 hours of videos of dramas or movies. Importantly, we densely annotated these videos at multiple semantic levels related to video contents, which allowed us to extract latent representations of LLMs for a range of semantic contents. We show that LLMs explain human brain activity more accurately than traditional language models, particularly for the high-level background story. Additionally, we show that distinct brain regions correspond to different semantic contents, thereby underscoring the importance of simultaneously modeling various levels of semantic contents. We will make our fMRI dataset publicly available for future research as a biological metric of the alignment between LLMs and humans. |
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