Biology subjects

D'Esposito, M.

Publications and source records attributed to D'Esposito, M..

28 records · Page 2Linked to original sources

bioRxiv2020

An MRI protocol for anatomical and functional evaluation of the California sea lion brain

We describe a research MRI protocol for in vivo evaluation of pinniped brains using standard human clinical MRI hardware and pulse sequences. Our intended application is to study development of California sea lions (Zalophus californianus) exposed in utero to domoic acid (DOM) produced by harmful algae blooms in the coastal Pacific Ocean. In cases where the fetus survives to birth, exposure to the toxin in utero could result in developmental abnormalities leading to neurological and behavioral deficits. Prior studies on sea lions naturally exposed to DOM as adults have demonstrated hippocampal atrophy and altered mesial temporal connectivity. This MRI protocol is therefore intended to depict the hippocampal formation as the primary region of interest, and to provide longitudinal measures of brain functional and structural connectivity as well as quantitative anatomical evaluations. Scan quality and utility are assessed by comparison with prior studies in live and post mortem sea lion brains. We include the first determination of cerebral blood flow mapping using MRI, and also the first fiber tractography using diffusion-weighted imaging from a live sea lion brain. The protocol also facilitates screening for common neurological pathologies, including tumors, trauma and hemorrhages. We believe the protocol would be suitable for any pinniped that can fit inside a human MRI scanner.

neuroscience↗

bioRxiv2020

Differential Contributions of Static and Time-Varying Functional Connectivity to Human Behavior

Measures of human brain functional connectivity acquired during the resting-state track critical aspects of behavior. Recently, fluctuations in resting-state functional connectivity patterns - typically averaged across in traditional analyses - have been considered for their potential neuroscientific relevance. There exists a lack of research on the differences between traditional "static" measures of functional connectivity and newly-considered "time-varying" measures as they relate to human behavior. Using functional magnetic resonance imagining (fMRI) data collected at rest, and a battery of behavioral measures collected outside the scanner, we determined the degree to which each modality captures aspects of personality and cognitive ability. Measures of time-varying functional connectivity were derived by fitting a Hidden Markov Model. To determine behavioral relationships, static and time-varying connectivity measures were submitted separately to canonical correlation analysis. A single relationship between static functional connectivity and behavior existed, defined by measures of personality and stable behavioral features. However, two relationships were found when using time-varying measures. The first relationship was similar to the static case. The second relationship was unique, defined by measures reflecting trialwise behavioral variability. Our findings suggest that time-varying measures of functional connectivity are capable of capturing unique aspects of behavior to which static measures are insensitive. Author SummaryCorrelated patterns of brain activity measured in the absence of any prescribed task show meaningful temporal fluctuations. However, the manner by which such fluctuations track aspects of human behavior remains unresolved. The current report takes a data-driven approach to characterize how time-varying patterns of human brain functional connectivity differ from traditional static measures in their ability to track aspects of personality and cognitive ability. We determine that time-varying patterns of functional connectivity not only track similar aspects of behavior as do static measures, but also unique behavioral qualities as well, specifically those that reflect behavioral variability. These results highlight the importance and relevance of examining time-varying measures of functional connectivity.

neuroscience↗

bioRxiv2020

Pupil-linked arousal biases evidence accumulation towards desirable percepts during perceptual decision-making

People are biased towards seeing outcomes they are motivated to see. The arousal system coordinates the bodys response to motivationally significant events, and is well positioned to regulate motivational effects on sensory perception. However, it remains unclear whether arousal would enhance or reduce motivational biases. Here we measured pupil dilation as a measure of arousal while participants performed a visual categorization task. We used monetary bonuses to motivate participants to see one category over another. Even though the reward-maximizing strategy was to perform the task accurately, participants were more likely to report seeing the motivationally desirable category. Furthermore, higher arousal levels were associated with making motivationally biased responses. Analyses using computational models suggest that arousal enhanced motivational effects by biasing evidence accumulation in favor of motivationally desirable percepts. These results suggest heightened arousal biases people towards what they want to see and away from an objective representation of the environment. Statement of RelevanceWhen confronted with an event of motivational significance (e.g., an opportunity to earn a huge reward), people often experience a strong arousal response that includes increased sweating, faster heart-rate and larger pupils. Does this arousal response help individuals make more accurate decisions, or does it instead bias and impair decision-making? This work examines the effects of arousal on how people decide what they see when they are motivated to see a particular outcome. We found that heightened arousal, as measured by larger pupils, was associated with a bias in how participants accumulated sensory evidence to make their decisions. As a result, participants became more likely to report seeing an ambiguous visual image as the interpretation they were motivated to see. Our results suggest that arousal biases perceptual judgments towards desirable percepts, and that modulating arousal levels could be a promising approach in reducing motivational biases in decision-making.

neuroscience↗

bioRxiv2020

A new sulcal landmark identifying anatomical and functional gradients in human lateral prefrontal cortex

Understanding the relationship between neuroanatomy and function in portions of human cortex that are expanded compared to other mammals such as lateral prefrontal cortex (LPFC) is of major interest in systems and cognitive neuroscience. When considering neuroanatomical-functional relationships in LPFC, shallow indentations in cortex known as tertiary sulci have been largely ignored. Here, by implementing a multi-modal approach and manually defining 936 neuroanatomical structures in 72 hemispheres (males and females), we show that a subset of these overlooked tertiary sulci serve as a meso-scale link between microstructural (myelin content) and functional (network connectivity) properties of human LPFC in individuals. For example, the posterior middle frontal sulcus (pmfs) is a tertiary sulcus with three components that differ in their myelin content, resting state connectivity profiles, and engagement across meta-analyses of 83 cognitive tasks. Further, generating microstructural profiles of myelin content across cortical depths for each pmfs component and the surrounding middle frontal gyrus (MFG) shows that both gyral and sulcal components of the MFG have greater myelin content in deeper compared to superficial layers and that the myelin content in superficial layers of the gyral components is greater than sulcal components. These findings support a classic, yet largely unconsidered theory that tertiary sulci may serve as landmarks in association cortices, as well as a modern cognitive neuroscience theory proposing a functional hierarchy in LPFC. As there is a growing need for computational tools that automatically define tertiary sulci throughout cortex, we share pmfs probabilistic sulcal maps with the field. Significance statementLateral prefrontal cortex (LPFC) is critical for higher-order cognitive control and goal-directed behavior and is disproportionately expanded in the human brain. However, relationships between fine-scale neuroanatomical structures largely specific to hominoid cortex and functional properties of LPFC remain elusive. Here, we show that these structures, which have been largely neglected throughout history, surprisingly serve as markers for anatomical and functional organization in human LPFC. These findings have theoretical, methodological, developmental, and evolutionary implications for improved understanding of neuroanatomical-functional relationships not only in LPFC, but also in association cortices more broadly. Finally, these findings ignite new questions regarding how morphological features of these neglected neuroanatomical structures contribute to functions of association cortices that are critical for human-specific aspects of cognition.

neuroscience↗

bioRxiv2020

Dissociable neural systems support the learning and transfer of hierarchical control structure

Humans can draw insight from previous experiences in order to quickly adapt to novel environments that share a common underlying structure. Here we combine functional imaging and computational modeling to identify the neural systems that support the discovery and transfer of hierarchical task structure. Human subjects completed multiple blocks of a reinforcement learning task that contained a global hierarchical structure governing stimulus-response action mapping. First, behavioral and computational evidence showed that humans successfully discover and transfer the hierarchical rule structure embedded within the task. Next, analysis of fMRI BOLD data revealed activity across a frontal-parietal network that was specifically associated with the discovery of this embedded structure. Finally, activity throughout a cingulo-opercular network and in caudal frontal cortex supported the transfer and implementation of this discovered structure. Together, these results reveal a division of labor in which dissociable neural systems support the learning and transfer of abstract control structures.

neuroscience↗

bioRxiv2019

The drift diffusion model as the choice rule in inter-temporal and risky choice: a case study in medial orbitofrontal cortex lesion patients and controls.

Sequential sampling models such as the drift diffusion model have a long tradition in research on perceptual decision-making, but mounting evidence suggests that these models can account for response time distributions that arise during reinforcement learning and value-based decision-making. Building on this previous work, we implemented the drift diffusion model as the choice rule in inter-temporal choice (temporal discounting) and risky choice (probability discounting) using a hierarchical Bayesian estimation scheme. We validated our approach in data from nine patients with focal lesions to the ventromedial prefrontal cortex / medial orbitofrontal cortex (vmPFC/mOFC) and nineteen age- and education-matched controls. Choice model parameters estimated via standard softmax action selection were reliably reproduced using the drift diffusion model as the choice rule, both for temporal discounting and risky choice. Model comparison revealed that, for both tasks, the data were best accounted for by a variant of the drift diffusion model including a non-linear mapping from value-differences to trial-wise drift rates. Posterior predictive checks of the winning models revealed a reasonably good fit to individual participants reaction time distributions. We then applied this modeling framework and 1) reproduced our previous results regarding temporal discounting in vmPFC/mOFC patients and 2) showed in a previously unpublished data set on risky choice that vmPFC/mOFC patients exhibit increased risk-taking relative to controls. Analyses of diffusion model parameters revealed that vmPFC/mOFC damage abolished neither value sensitivity nor asymptote of the drift rate. Rather, it substantially increased non-decision times and reduced response caution during risky choice. Our results highlight that novel insights can be gained from applying sequential sampling models in studies of inter-temporal and risky decision-making in cognitive neuroscience.

neuroscience↗

bioRxiv2018

Single-cell whole-brain imaging and network analysis provide evidence of the three-stage hypothesis of addiction

Three main theories of the neurobiology of addiction have been proposed: (1) incentive salience mediated by a brainstem-striatal network, (2) habit mediated by a cortico-striato-thalamic network, and (3) hedonic allostasis mediated by an extended amygdala network. Efforts have been made to reconcile these theories within a three-stage model, but the relevance of each theory remains controversial. We tested the validity of each theory with a single dataset using unbiased single-cell whole-brain imaging and data-driven analyses of neuronal activity in a mouse model of alcohol use disorder. Abstinence in alcohol dependent mice decreased brain modularity and resulted in clustering of brain regions that correspond to each stage of the three-stage theory of addiction. Furthermore, we identified several brain regions whose activity highly predicted addiction-like behaviors and \"hub\" regions that may drive neural activation during abstinence. These results validate the three-stage theory of addiction and identify potential target regions for future study.

neuroscience↗

bioRxiv2017

Serial dependence is absent at the time of perception but increases in visual working memory

Recent experiments have shown that visual cognition blends current visual input with that from the recent past to guide ongoing decision making. This serial dependence is tuned to the similarity between consecutive stimuli and appears to exploit the temporal autocorrelation normally present in visual scenes to promote perceptual stability. While these benefits have been assumed, evidence that serial dependence directly alters stimulus perception has been limited. In the present study, we parametrically vary the delay between stimulus and response in a spatial delayed response task to explore the trajectory of serial dependence from the moment of perception into post-perceptual visual working memory. We find that behavioral responses made immediately after viewing a stimulus show evidence of adaptation, but not attractive serial dependence. Only as the memory period lengthens is a blending of past and present information apparent in behavior, reaching its maximum with a memory delay of six seconds. These results dovetail with other recent findings to bolster the interpretation that serial dependence is a phenomenon of mnemonic rather than perceptual processes. We also demonstrate that when leading mathematical models of visual working memory are adjusted to account for this trial-history effect, their fit to behavioral data is substantially improved.

animal behavior and cognition↗

bioRxiv2017

Fronto-Parietal Interactions With Task-Evoked Functional Connectivity During Cognitive Control

Flexible interaction between brain regions enables neural systems to transfer and process information adaptively for goal-directed behaviors. In the current study, we investigated neural substrates that interact with task-evoked functional connectivity during cognitive control. We conducted a human fMRI study where participants selectively attended to a category of visual stimuli in the presence of competing distractors from another stimulus category. To study flexible interactions between brain regions, we performed a dynamic functional connectivity analysis to estimate temporal changes in connectivity strength between brain regions under different levels of cognitive control. Consistent with theoretical predictions, we found that cognitive control selectively enhances functional connectivity for prioritizing the processing of task-relevant information. By regressing temporal changes in connectivity strength against activity patterns elsewhere in the brain, we localized frontal and parietal regions that potentially provide top-down biasing signals for influencing, or reading information out from, task-evoked functional connectivity. Our results suggest that in addition to modulating local activity, fronto-parietal regions could also exert top-down biasing signals to influence functional connectivity between distributed brain regions.

neuroscience↗

bioRxiv2017

Causal Evidence for Lateral Prefrontal Cortex Dynamics Supporting Cognitive Control

The lateral prefrontal cortex (LPFC) is essential for higher-level cognition, but how interactions among LPFC areas support cognitive control has remained elusive. In previous work, dynamic causal modeling (DCM) of fMRI data revealed that demands on cognitive control elicited a convergence of influences towards mid LPFC. We proposed that these findings reflect the integration of abstract, rostral and concrete, caudal influences to inform context-appropriate action. Here, we provide a causal test of this model using continuous theta-burst transcranial magnetic stimulation (cTBS). cTBS was applied to caudal, mid, or rostral LPFC, as well as a control site in counterbalanced sessions. In most cases, behavioral modulations resulting from cTBS could be predicted based upon the direction of influences within the previously estimated DCM. However, inconsistent with our DCM, we found that cTBS to caudal LPFC impaired cognitive control processes presumed to involve rostral LPFC. Revising the original DCM with a pathway from caudal LPFC to rostral LPFC significantly improved the fitted DCM and accounted for the observed behavioral findings. These data provide causal evidence for LPFC dynamics supporting cognitive control and demonstrate the utility of combining DCM with causal manipulations to create, test, and refine models of cognition.

neuroscience↗