Biology subjects

Murty, V. P.

Publications and source records attributed to Murty, V. P..

12 recordsLinked to original sources

bioRxiv2026

Mapping Mesolimbic Dopamine Projections to Subcortical Circuits Underlying Adaptive Behavior: A Human 7T Diffusion Tractography Atlas

The mesolimbic dopamine system supports broad aspects of adaptive behavior including salience, learning, memory, and decision making, yet the structural organization supporting these functions remains incompletely mapped in humans. Using high-resolution 7T diffusion magnetic resonance imaging (up to N=173), we reconstructed seven bilateral ventral tegmental area (VTA)-subcortical pathways spanning direct mesolimbic projections and the hippocampus-VTA (HPC-VTA) loop regulatory circuit. Projection-endpoint analyses revealed long-axis and subfield organization of VTA-hippocampal pathways and superior-inferior VTA-nucleus accumbens (NAc) topography. Consistent with the HPC-VTA loop framework, neurite density covaried across mesolimbic pathways but not the arcuate fasciculus, demonstrating circuit-level organization. Nodewise analyses identified localized associations between pathway microstructure and delay discounting across VTA-hippocampal, VTA-NAc, and VTA-amygdala pathways. Together, these findings parse the human mesolimbic system into distinct pathways supporting adaptive behavior. The probabilistic atlas, MesoConnect, is freely available with tutorials to facilitate reconstruction and investigation of circuits in independent datasets.

neuroscience↗

bioRxiv2026

The hippocampus and cortical memory networks have an inflection point in middle childhood

Decades of developmental memory research has mainly reported linear and protracted changes in both human hippocampal function and connectivity between the hippocampus and cortex. While foundational, very few studies have interrogated the reliability of hippocampal signals across age, and how this coincides with (or diverges from) age-related changes in connectivity to broader cortical networks supporting multiple memory systems. Here, utilizing movie-watching fMRI data in children 3 to 12 years and adults, we assessed hippocampal response stability using an inter-subject functional correlation (ISFC) approach, and then measured functional connectivity between the hippocampus and the Posterior Medial (PM) - Anterior Temporal (AT) cortical memory networks proposed to support episodic-like (PM) and semantic-like (AT) memory respectively. Results showed that hippocampal responses are stable in the youngest children, but bifurcate in 7 year olds, with half the subjects correlating most highly with younger and half with older age groups. Likewise, we found that while functional connectivity within the AT network is stable across development, connections between the anterior hippocampus and this network did not reach adult levels until around 7 years. Thus, while brain networks supporting semantic memory may be in place early, interactions with the hippocampus may not develop until after middle childhood, with an inflection point around 7 years of age.

neuroscience↗

bioRxiv2026

Social Motivation and Hippocampal-Cortical Structural Development in Adolescent Girls

Adolescence is a fundamental developmental period marked by dramatic socio-affective and physiological changes, including shifts in social behavior and maturation of underlying brain architecture. In girls, this period coincides with the onset of the pubertal transition, which fundamentally influences motivated social behavior and neurodevelopment. The present study examines age- and pubertal maturation-related changes in social motivational goals and hippocampal and motivation-related cortical structural development in adolescent girls (n=154) across five timepoints. Social motivational goals showed substantial variability of each subdomain across age and pubertal development. Specifically, all social goals showed linear increases across age and pubertal stage, whereas goals centered around developing social competency increased non-linearly across age. Our neurodevelopmental findings align with established research, revealing volumetric increases of the hippocampus, and cortical thinning of the medial orbitofrontal cortex (mOFC) and rostral anterior cingulate cortex (rACC) across age and pubertal stages. Collectively, these results highlight simultaneous change in endorsement and prioritization of different social motivational goals across adolescence, and they underscore the simultaneous shifts in structural development in regions supporting social motivation and broader socio-affective development. This research highlights the importance of fostering positive social experiences during this critical developmental stage, with implications for adolescent well-being and social development.

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bioRxiv2024

Synergistic Neural Circuits for Novelty and Goal-Directed Behavior

The ability to adapt to a dynamic world relies on detecting, learning, and responding to environmental changes. The detection of novelty serves as a critical indicator of such changes, priming mechanisms to detect and respond to goal-relevant information. However, neural regions that support novelty detection (hippocampus) and goal-directed behavior (dopaminergic midbrain [VTA] and prefrontal cortex [PFC]) have yet to be described as a sequential process that unfolds over time. Using a forward-prediction functional magnetic resonance imaging (fMRI) model, we explored interactions between the hippocampus, VTA, and PFC in humans performing a novelty-imbued target-detection task. Hippocampal novelty activation predicted subsequent VTA target activation, enhancing readiness to detect goal-relevant information. Concurrently, goal-directed PFC activation modulated VTA target activation, refining focus on behaviorally significant cues. These circuits function both synergistically and independently, promoting subsequent hippocampal activity during target trials. This work provides new insights into how distributed circuits coordinate to optimize adaptive behavior. Significance StatementSurviving in dynamic environments requires coordinated neural mechanisms to detect, learn from, and respond to change. However, neural regions that support novelty detection and goal-oriented behavior have yet to be described as a sequential process that unfolds over time. Using a novel forward-prediction functional magnetic resonance imaging (fMRI) model, we show that hippocampal activation during novelty predicts ventral tegmental area (VTA) readiness to process goal-relevant information. Concurrently, goal-directed prefrontal cortex activity modulates VTA responses, sharpening focus on behaviorally significant cues. Furthermore, these synergistic and independent circuits enhance hippocampal sensitivity for future adaptive responses, offering novel insights into integration of brain mechanisms critical for learning, motivation, and executive function.

neuroscience↗

bioRxiv2024

Differential representations for affective and informative components of reward in the striatum and hippocampus

Receipt of a reward is composed of affective and informative components, which are often intertwined in most reward-processing and decision-making tasks. Our previous work allowed us to identify regions that were more strongly engaged for the affective and informative components of reward upon receipt (Smith et al., 2016) and showed that the ventral striatum responds to both affective and informative components of reward processing. However, the limited spatial resolution and coarse analytical approaches made it hard to understand how these different components of reward were represented in the brain, wherein similar engagement may not necessitate similar representations. In our current study, we used high-resolution functional magnetic resonance imaging (voxel size: 1.75 mm3) and representational similarity analysis to investigate the representation of affective and informative components of reward receipt in the striatum and the hippocampus, another region that is sensitive to reward information. We found a differential representation of affective and informative components of reward receipt in the striatum and the hippocampus, with no difference in representation between the two structures. However, in the dorsal striatum, we found that representations were stronger for affective rather than the informative components of reward receipt. Finally, we observed that the ventral striatum was sensitive to the predictiveness of information, such that across-run pattern similarity in the ventral striatum increased with the predictiveness of information. In sum, our results provide evidence of how affective and informative components of rewards are represented in the striatum and the hippocampus, potentially indicating a differential coding schema for the dorsal and the ventral striatum.

neuroscience↗

bioRxiv2023

Connecting self-report and instrumental behavior during incubation of food craving in humans.

Incubation of craving is a phenomenon describing the intensification of craving for a reward over extended periods of abstinence from reinforcement. Animal models employ instrumental markers of craving to reward cues to examine incubation, while homologous human paradigms often rely on subjective self-reports. Here, we characterize a novel human paradigm that showed strong positive relationships between self-reports and instrumental markers of craving. Further, both measures expressed non-linear relationships with time since last consumption, which parallels homologous animal paradigms of incubation of craving.

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bioRxiv2023

In Vivo Structural Connectivity of the Reward System Along the Hippocampal Long-Axis

Recent work has identified a critical role for the hippocampus in reward-sensitive behaviors, including motivated memory, reinforcement learning, and decision-making. Animal histology and human functional neuroimaging have shown that brain regions involved in reward processing and motivation are more interconnected with the ventral/anterior hippocampus. However, direct evidence examining gradients of structural connectivity between reward regions and the hippocampus in humans is lacking. The present study used diffusion MRI and probabilistic tractography to quantify the structural connectivity of the hippocampus with key reward processing regions in vivo. Using a large sample of subjects (N=628) from the human connectome dMRI data release, we found that connectivity profiles with the hippocampus varied widely between different regions of the reward circuit. While the dopaminergic midbrain (VTA) showed stronger connectivity with the anterior versus posterior hippocampus, the vmPFC showed stronger connectivity with the posterior hippocampus. The nucleus accumbens (NAc) showed a more homogeneous connectivity profile along the hippocampal long-axis. This is the first study to generate a probabilistic atlas of the hippocampal structural connectivity with reward-related networks, which is essential to investigating how these circuits contribute to normative adaptive behavior and maladaptive behaviors in psychiatric illness. These findings describe nuanced structural connectivity that sets the foundation to better understand how the hippocampus influences reward-guided behavior in humans.

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bioRxiv2022

Awake Hippocampal-Cortical Co-reactivation Is Associated with Forgetting

Systems consolidation theories posit that consolidation occurs primarily through a coordinated communication between hippocampus and neocortex (McClelland and OReilly 1995; Kumaran et al., 2016; Moscovitch and Gilboa, 2022). Recent sleep studies in rodents have shown that hippocampus and visual cortex replay the same information at temporal proximity ("co-replay") (Ji & Wilson, 2007; Lansink et al., 2009; Wierzynski et al., 2009; Peyrache et al., 2009). We developed a novel TR-based co-reactivation (TRCR) analysis method to study hippocampal-cortical co-replays in humans using functional MRI. Thirty-six young adults completed an image (face or scene)-location paired associate encoding task in the scanner, which were preceded and followed by resting state scans. We identified post-encoding rest TRs (+/- 1) that showed neural reactivation of each image-location trials in both hippocampus (HPC) and category-selective cortex (fusiform face area, FFA). This allowed us to characterize temporally proximal coordinated reactivations ("co-reactivations") between HPC and FFA. Moreover, we found that increased HPC-FFA co-reactivations were associated with incorrectly recognized trials after a 1-week delay (p = 0.004). Finally, we found that these HPC-FFA co-reactivations were also associated with trials that were initially correctly recognized immediately after encoding but were later forgotten in 1-day (p = 0.043) and 1-week delay period (p = 0.031). We discuss these results from a trace transformation perspective (Winocur and Moscovitch, 2011; Sekeres et al., 2018) and speculate that HPC-FFA co-reactivations may be integrating related events, at the expense of disrupting event-specific details, hence leading to forgetting.

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bioRxiv2022

Midbrain-Hippocampus Structural Integrity Selectively Predicts Motivated Memory Encoding

Motivation is a powerful driver of learning and memory. Functional MRI studies show that interactions between the dopaminergic midbrain (SN/VTA), hippocampus, and nucleus accumbens (NAc) are critical for motivated memory encoding. However, it is not known if these effects are transient and purely functional, or if individual differences in the structure of this circuit underlie motivated memory encoding. To quantify individual differences in structure, diffusion-weighted MRI and probabilistic tractography were used to quantify SN/VTA-striatum and SN/VTA-hippocampus pathways associated with motivated memory encoding in humans. Participants completed a motivated source memory paradigm. During encoding, words were randomly assigned to one of three conditions: reward ($1.00), control ($0.00), or punishment (-$1.00). During retrieval, participants were asked to retrieve item and source information of the previously studied words and were rewarded or penalized according to their performance. Source memory for words assigned to both reward and punishment conditions was greater than control words, while there were no differences in item memory based on value. Anatomically, probabilistic tractography results revealed a heterogeneous, topological arrangement of the SN/VTA. Tract density measures of SN/VTA-hippocampus pathways were positively correlated with individual differences in reward and punishment modulated memory performance, while density of SN/VTA-striatum pathways showed no association. This novel finding suggests that pathways emerging from the human SV/VTA are anatomically separable and functionally heterogeneous. Individual differences in structural connectivity of the dopaminergic hippocampus-VTA loop are selectively associated with motivated memory encoding. Significance StatementFunctional MRI studies show that interactions between the dopaminergic midbrain (SN/VTA), hippocampus, and nucleus accumbens (NAc) are critical for motivated memory encoding. This has led to competing theories that posit either SN/VTA-NAc reward prediction errors or SN/VTA-hippocampus signals underlie motivated memory encoding. Additionally, it is not known if these effects are transient and purely functional, or if individual differences in the structure of these circuits underlie motivated memory encoding. Using diffusion-weighted MRI and probabilistic tractography, we show that tract density measures of SN/VTA-hippocampus pathways are positively correlated with motivated memory performance, while density of SN/VTA-striatum pathways show no association. This finding suggests that anatomical individual differences of the dopaminergic hippocampus-VTA loop are selectively associated with motivated memory encoding.

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bioRxiv2022

Agency as a Bridge to Form Associative Memories

The perception of agency occurs when individuals feel their decisions exert control over their environment. While agency can increase memory for items, most real-life situations are more complex. The decisions we make not only affect the item we act upon, but all the other items in direct proximity of our decisions. Here, we examined how an individuals agency to influence a situation affects their ability to learn associations between items that occur prior to and after making a decision. In our paradigm, participants were told they were playing a game show where they had to help a trial unique contestant choose between three doors. On agency trials, participants were allowed to pick any door they wanted. On forced-choice trials, participants were instructed to select a door that was highlighted. They then saw the outcome, a prize that was behind the selected door. Across two studies, participants show enhanced memory for contestants they saw in agency vs forced-choice trials. Memory benefits also extended to contestant - door and door - prize associations in both studies. Study 2 found this effect in the contestant - prize association. Notably, we found that agency also shaped the representation of memories such that they were stored as integrated sequences rather than individual relational pairs. Together, these data suggest agency over a situation leads to enhanced memory for all items in that situation. This enhanced binding for items may be occurring by the formation of causal links when an individual has agency over their learning environment.

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bioRxiv2021

Distinct Alterations in Cerebellar Connectivity with Substantia Nigra and Ventral Tegmental Area in Parkinsons Disease

In Parkinsons disease (PD), neurodegeneration of dopaminergic neurons occurs in the midbrain, specifically targeting the substantia nigra (SN), while leaving the ventral tegmental area (VTA) relatively spared in early phases of the disease. Although the SN and VTA are known to be functionally dissociable in healthy adults, it remains unclear how this dissociation is altered in PD. To examine this issue, we performed a whole-brain analysis to compare functional connectivity in PD to healthy adults using resting-state functional magnetic resonance imaging (rs-fMRI) data compiled from three independent datasets. Our analysis showed that across the sample, the SN had greater connectivity with the precuneus, anterior cingulate gyrus, and areas of the occipital cortex, partially replicating our previous work in healthy young adults. Notably, we also found that, in PD, VTA-right cerebellum connectivity was higher than SN-right cerebellum connectivity, whereas the opposite trend occurred in healthy controls. This double dissociation may reflect a compensatory role of the cerebellum in PD and could provide a potential target for future study and treatment.

neuroscience↗

bioRxiv2021

Novelty-related engagement of VTA and anterior hippocampus propagate changes in cortical network plasticity at different scales

The detection of novelty indicates changes in the environment and the need to update existing representations. In response to novelty, interactions across the ventral tegmental area (VTA)-hippocampal circuit support experience-dependent plasticity in the hippocampus. While theories have broadly suggested plasticity-related changes are also instantiated in the cortex, research has also shown evidence for functional heterogeneity in cortical networks. It therefore remains unclear how the hippocampal-VTA circuit engages cortical networks, and whether novelty targets specific cortical regions or diffuse, large-scale cortical networks. To adjudicate the role of the VTA and hippocampus in cortical network plasticity, we used human functional magnetic resonance imaging (fMRI) to compare resting state functional coupling before and following exposure to novel scene images. Functional coupling between right anterior hippocampus and VTA was enhanced following novelty exposure. However, we also found evidence for a double dissociation, with anterior hippocampus and VTA showing distinct patterns of post-novelty functional coupling enhancements, targeting task-relevant regions versus large-scale networks, respectively. Further, significant correlations between these networks and the novelty-related plasticity in the anterior hippocampal-VTA functional network suggest the central hippocampal-VTA network may facilitate the interactions with the cortex. These findings support an extended model of novelty-induced plasticity, in which novelty elicits plasticity-related changes in both local and global cortical networks. Significance StatementNovelty detection is critical for adaptive behavior, signaling the need to update existing representations. By engaging the bi-directional hippocampal-VTA circuit, novelty has been shown to induce plasticity-related changes in the hippocampus. However, it remains an open question how novelty targets such plasticity-related changes in cortical networks. We show that anterior hippocampus and VTA target cortical networks at different spatial scales, with respective enhancements in post-novelty functional coupling with a task-relevant cortical region and a large-scale memory network. The results presented here support an extended model of novelty-related plasticity, in which engaging the anterior hippocampal-VTA circuit through novelty exposure propagates cortical plasticity through hippocampal and VTA functional pathways at distinct scales, targeting specific or diffuse cortical networks.

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