Biology subjects

Olson, I. R.

Publications and source records attributed to Olson, I. R..

15 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

Altered Dopamine-Linked Striatal Hemodynamic Latency in Early Psychosis

Key Points Question: Is striatal hemodynamic latency, a novel indirect correlate of dopamine physiology, altered in individuals with early psychosis? Findings: In this cross-sectional study of 105 individuals with early psychosis and 55 healthy comparison participants, early psychosis was associated with significantly lower striatal hemodynamic latency. Differences were observed in the dorsal striatum (caudate and putamen), whereas ventral striatal (nucleus accumbens) latency did not significantly differ between groups. Meaning: These findings support further evaluation of striatal hemodynamic latency as a noninvasive, indirect marker of dopamine-linked physiology in early psychosis. Abstract Importance: Psychosis is strongly associated with striatal dopamine dysfunction, but noninvasive measures that capture variation in dopamine remain limited. Hemodynamic latency, which quantifies the timing of low-frequency blood oxygen level-dependent (BOLD) fluctuations, may provide a way to indirectly probe dopamine dysfunction in psychosis. Objective: To determine whether striatal hemodynamic latency differs between individuals with early psychosis (EP) and healthy control (HC) participants and whether latency is associated with positive or negative symptom severity. Design: Cross-sectional analysis of resting-state functional magnetic resonance imaging (fMRI) data from the Human Connectome Project (HCP)-EP dataset. Setting: Multisite study at 4 sites using 3T Siemens Prisma MRI scanners. Participants: 105 individuals with EP and 55 HC participants with usable resting-state fMRI and hemodynamic latency data. Exposure: EP status. Main Outcomes and Measures: Voxel-wise hemodynamic latency was estimated using RapidTide and summarized within 6 striatal regions: nucleus accumbens core and shell, anterior and posterior caudate and putamen. Group differences were evaluated using linear mixed-effects models accounting for region and subject-level random effects and controlling for age, sex, and mean framewise displacement. Positive symptoms were measured using the Positive and Negative Syndrome Scale positive subscale; negative symptoms using the Clinical Assessment Interview for Negative Symptoms. Associations with symptoms were assessed using nested linear regressions within the EP group. Results: Latency was significantly lower in the dorsal than ventral striatum in HC and EP, with a greater difference in EP (b=-119.46 ms, SE=52.16, p=.022). Follow-up six-subregion models found significant main effects of group F(1,156.55)=7.79, p=.006, and region F(5,2760)=187.99; p< .001, but no group-by-region interaction F(5,2760)=1.74; p=.121. Region-specific contrasts showed lower latency in EP in the anterior caudate (p=.014), posterior caudate (p<.001), anterior putamen (p=.007), and posterior putamen (p=.029), but not NAc core or shell. Striatal latency was not significantly associated with positive or negative symptom severity among participants with EP. Conclusions and Relevance: EP was associated with broadly reduced striatal hemodynamic latency, with the strongest differences in the caudate and putamen. Altered striatal latency in psychosis warrants further evaluation as a noninvasive indirect marker of striatal pathophysiology linked to dopamine.

neuroscience↗

bioRxiv2026

A Tripartite Map of the Ventromedial Prefrontal Cortex

The ventromedial prefrontal cortex (VMPFC) has been repeatedly implicated in affect, valuation, and social cognition, yet how these diverse functions are organized within a single cortical territory has remained unresolved. Here, we integrate large-scale meta-analysis, individual-level task fMRI, artificial neural-network encoding models, and multimodal connectivity analyses to reveal the internal functional architecture of the human VMPFC. Across four complementary studies, we identify a robust tripartite organization along the anterior-posterior axis, comprising posterior affective, middle valuation, and anterior social functional motifs. Connectivity fingerprinting demonstrates that each motif is preferentially embedded within distinct large-scale brain networks, providing a mechanistic account of VMPFC functional specialization. This organization is reproducible at the level of individual subjects, generalizes to naturalistic stimuli, extends across development, and shows cross-species correspondence with non-human primates and multiple neurobiological markers. Together, these findings resolve a long-standing organizational question and establish a biologically grounded framework for interpreting VMPFC function.

neuroscience↗

bioRxiv2026

Prenatal Maternal Inflammation Is Associated with Altered Offspring Mesolimbic White Matter Circuitry Observed in Late Midlife

BackgroundExposure to prenatal maternal inflammation (PNMI) has been linked to neurodevelopmental alterations in human offspring. Preclinical studies suggest that PNMI disrupts reward circuitry, particularly within mesolimbic circuits. However, the effects of PNMI on mesolimbic circuits (i.e, ventral tegmental area (VTA) projections to the hippocampus (VTA-H) and limbic striatum (VTA-LS)) in humans are not yet known. MethodsData for PNMI biomarkers [interleukin (IL)-6, IL-8, IL-1 receptor antagonist (IL-1ra), soluble TNF receptor-II (sTNF-RII)] from first trimester (T1) and second trimester (T2) maternal sera, and offspring MRI brain scans in late midlife (aged 57-63 years), were available for 89 mother-offspring dyads. Probabilistic tractography delineated bilateral VTA-H and VTA-LS tracts. Macrostructural tract measures were examined using hierarchical linear regressions. Microstructural integrity was assessed using neurite orientation dispersion and density imaging, and permutation-based cluster analyses. ResultsHigher T2 IL-1ra was associated with increased macrostructure (left VTA-H tract), whereas higher T2 sTNF-RII was associated with reduced macrostructure (right VTA-H and VTA-LS tracts) and higher T2 IL-8 (bilateral VTA-LS tracts). Microstructurally, higher T2 IL-6 was associated with increased neurite density (distal cluster, right VTA-H tract), while higher T1 IL-8 was associated with reduced neurite density (near the hippocampus in the left VTA-H tract, near the VTA in bilateral VTA-LS tracts). ConclusionsPNMI was associated with altered mesolimbic reward circuitry in offspring. This suggests that prenatal inflammation may contribute to affective and motivational disorders in offspring via alterations in mesolimbic circuitry.

neuroscience↗

bioRxiv2025

The Cerebellum and Striatum in Reward Processing: Caring About Being Right vs. Caring About Reward

Emerging evidence indicates the cerebellum contributes to cognitive functions including social reward processing, yet its specific role relative to established reward regions like the ventral striatum remains undefined. We hypothesized the cerebellum would respond equivalently to both positive and negative social rewards. This prediction is grounded in classical findings that the cerebellum operates via supervised learning mechanisms that rely on error signals rather than traditional reward-based reinforcement. Using fMRI, we examined adolescents and young adults during a social prediction task where participants forecasted others opinions of them and received accuracy feedback. Findings reveal that both the ventral striatum and a subregion of the posterior cerebellum (Crus I and II) were sensitive to social rewards. However, unlike the ventral striatum, the cerebellum exhibited a more uniform response to feedback, treating correct predictions about being liked and disliked in a similar manner. No age-related differences were observed. These findings suggest the cerebellum processes social rewards distinctly from the ventral striatum, likely reflecting its computational emphasis on prediction errors rather than reward valence. This functional distinction advances our understanding of cerebellar contributions to social cognition and learning mechanisms.

neuroscience↗

bioRxiv2024

Decreased hippocampal neurite density in middle-aged/aging adults following prenatal exposure to higher levels of maternal inflammation

In animal models, exposure to heightened maternal inflammation in utero is associated with altered offspring hippocampal development, including reduced dendritic arborization and density. However, the effects of prenatal maternal inflammation (PNMI) on offspring hippocampal microstructure in humans remains unclear. Here, we examined the relationship between exposure to PNMI and neurite density in the hippocampus and its subfields among offspring during late middle age. Participants included 72 mother-offspring dyads from the Child Health and Development Studies (CHDS) cohort. Data for four inflammatory biomarkers (IL-6, IL-8, IL-1 receptor antagonist [IL-1RA], and soluble TNF receptor-II [sTNF-RII]) were available from first and second trimester maternal sera. Neurite density in the offspring hippocampus and its subfields was estimated using microstructural modeling of offsprings diffusion-weighted Magnetic Resonance Imaging data (mean age of offspring at imaging = 59 years; 51% male). We estimated the relationship between each biomarker and region-of-interests neurite density. Higher first trimester maternal IL-1RA and IL-6 levels were associated with lower offspring hippocampal neurite density. These relationships were specific to the CA3, CA4, dentate gyrus, and subiculum subfields. In addition, higher second trimester IL-6 was associated with lower subiculum neurite density. Our findings reveal that exposure to heightened prenatal levels of maternal inflammation is linked to altered offspring hippocampal microstructure in late middle age, which could have implications for memory decreases during this period and may be relevant for understanding risk of aging-related cognitive changes. Significance StatementThe contribution of prenatal maternal inflammation (PNMI) to offspring brain microstructure in later life is well established in animal models but poorly understood in humans. Our study discovered long-lasting impacts of elevated PNMI during early mid-gestation on the structural integrity of the hippocampus in offspring during late middle age. Our findings underscore the potential role of prenatal insults in aging-related neurological and cognitive decline, as the observed degradation in hippocampal microstructure is present over half a century following exposure.

immunology↗

bioRxiv2023

Cerebellum-Midbrain Reward Circuitry in Humans: an in vivo dissection

Emerging research in non-human animals implicates cerebellar projections to the ventral tegmental area (VTA) in appetitive behaviors, but these circuits have not been characterized in humans. Here, we mapped cerebello-VTA white-matter connectivity in humans using probabilistic tractography on diffusion imaging data from the Human Connectome Project. We uncovered the topographical organization of these connections by separately tracking from parcels of cerebellar lobule VI, crus I/II, vermis, paravermis, and cerebrocerebellum. Results revealed that connections from the cerebellum to the VTA predominantly originate in the right hemisphere, interposed nucleus, and paravermal cortex, and terminate mostly ipsilaterally. Paravermal crus I sends the most connections to the VTA compared to other lobules. We discovered a medial-to-lateral gradient of connectivity, such that the medial cerebellum has the highest connectivity with the VTA. Individual differences in microstructure were associated with measures of negative affect and social functioning. By splitting the tracts into quarters, we found that the socio-affective effects were driven by the third quarter of the tract, corresponding to the point at which the fibers leave the deep nuclei. Taken together, we produced detailed maps of cerebello-VTA structural connectivity for the first time in humans and established their relevance for trait differences in socio-affective regulation.

neuroscience↗

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.

neuroscience↗

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.

neuroscience↗

bioRxiv2022

Language and the cerebellum: structural connectivity to the eloquent brain

Neurobiological models of receptive language have focused on the left-hemisphere perisylvian cortex with the assumption that the cerebellum supports peri-linguistic cognitive processes such as verbal working memory. The goal of this study was to identify language-sensitive regions of the cerebellum then map the structural connectivity profile of these regions. Functional imaging data and diffusion-weighted imaging data from the Human Connectome Project (HCP) were analyzed. We found that (a) working memory, motor activity, and language comprehension activated partially overlapping but mostly unique subregions of the cerebellum; (b) the linguistic portion of the cerebello-thalamo-cortical circuit was more extensive than the linguistic portion of the cortico-ponto-cerebellar tract; (c) there was a frontal-lobe bias in the connectivity from the cerebellum to the cerebrum; (d) there was some degree of specificity; and (e) for some cerebellar tracts, individual differences in picture identification ability covaried with fractional anisotropy metrics. These findings yield insights into the structural connectivity of the cerebellum as relates to the uniquely human process of language comprehension.

neuroscience↗

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

The Backbone Network of Dynamic FunctionalConnectivity

1.Temporal networks have become increasingly pervasive in many real-world applications, including the functional connectivity analysis of spatially separated regions of the brain. A major challenge in analysis of such networks is the identification of noise confounds, which introduce temporal ties that are non-essential, or links that are formed by chance due to local properties of the nodes. Several approaches have been suggested in the past for static networks or temporal networks with binary weights for extracting significant ties whose likelihood cannot be reduced to the local properties of the nodes. In this work, we propose a data-driven procedure to reveal the irreducible ties in dynamic functional connectivity of resting state fRMI data with continuous weights. This framework includes a null model that estimates the latent characteristics of the distributions of temporal links through optimization, followed by a statistical test to filter the links whose formation can be reduced to the activities and local properties of their interacting nodes. We demonstrate the benefits of this approach by applying it to a resting state fMRI dataset, and provide further discussion on various aspects and advantages of it.

neuroscience↗

bioRxiv2021

The social cerebellum: A large-scale investigation of functional and structural specificity and connectivity

The cerebellum has been traditionally disregarded in relation to non-motor functions, but recent findings indicate it may be involved in language, affective processing, and social functions. Mentalizing is the ability to infer mental states of others and this skill relies on a distributed network of brain regions. Here, we leveraged large-scale multimodal neuroimaging data to elucidate the structural and functional role of the cerebellum in mentalizing. We used functional activations to determine whether the cerebellum has a domain-general or domain-specific functional role, and effective connectivity and probabilistic tractography to map the cerebello-cerebral mentalizing network. We found that the cerebellum is organized in a domain-specific way and that there is a left cerebellar effective and structural lateralization, with more and stronger effective connections from the left cerebellar hemisphere to the right cerebral mentalizing areas, and greater cerebello-thalamo-cortical (CTC) and cortico-ponto-cerebellar (CPC) streamline counts from and to the left cerebellum. Our study provides novel insights to the network organization of the cerebellum, an overlooked brain structure, and mentalizing, one of humans most essential abilities to navigate the social world.

neuroscience↗

bioRxiv2020

A Large-Scale Structural and Functional Connectome of Social Mentalizing

Humans have a remarkable ability to infer the mind of others. This mentalizing skill relies on a distributed network of brain regions but how these regions connect and interact is not well understood. Here we leveraged large-scale multimodal neuroimaging data to elucidate the connectome-level organization and brain-wide mechanisms of mentalizing processing. Key features of the mentalizing connectome have been delineated in exquisite detail and its relationship with the default mode network has been extensively scrutinized. Our study demonstrates that mentalizing processing unfolds across functionally heterogeneous regions with highly structured fiber tracts and unique hierarchical functional architecture, which make it distinguishable from the default mode network and other social brain networks.

neuroscience↗

bioRxiv2017

White Matter and Social Cognition

There is a growing consensus that social cognition and behavior emerge from interactions across distributed regions of the \"social brain\". Social neuroscience has traditionally focused its attention on functional response properties of these gray matter networks and neglected the vital role of white matter (WM) connections in establishing such networks and their functions. In this article, we conduct a comprehensive review of prior research on structural connectivity in social neuroscience and highlight the importance of this literature in clarifying brain mechanisms of social cognition. We pay particular attention to the research on three key social processes: face processing, embodied cognition, and theory of mind, and their respective underlying neural networks. To fully identify and characterize the anatomical architecture of these networks, we further implement probabilistic tractography on a large sample of diffusion-weighted imaging data. The combination of an in-depth literature review and the empirical investigation gives us an unprecedented, well-defined landscape of WM pathways underlying major social brain networks. Finally, we discuss current problems in the field, outline suggestions for best practice in diffusion imaging data collection and analysis, and offer new directions for future research.\n\nAbbreviations

neuroscience↗