Biology subjects

Larsen, B.

Publications and source records attributed to Larsen, B..

43 records · Page 3Linked to original sources

bioRxiv2020

Dopamine-related striatal neurophysiology is associated with specialization of frontostriatal reward circuitry through adolescence

Characterizing developmental changes in frontostriatal circuitry is critical to our understanding of adolescent development and can clarify neurobiological mechanisms underlying increased reward sensitivity and sensation seeking, and the emergence of psychopathology during this period. However, the role of striatal neurobiology in the development of frontostriatal circuitry through human adolescence remains largely unknown. We combine longitudinal MR-based assessments of striatal tissue-iron as a correlate of dopamine-related neurobiology with functional magnetic resonance imaging indices of resting-state and reward-state connectivity to investigate the contribution of dopaminergic processes to developmental changes in frontostriatal circuitry. Connectivity between the nucleus accumbens and ventral anterior cingulate, subgenual cingulate, and orbitofrontal cortices decreased through adolescence into adulthood. Nucleus accumbens tissue-iron mediated age-related changes and was associated with variability in connectivity. Our results provide evidence that developmental changes in dopamine-related striatal properties contribute to specialization of frontostriatal circuitry, potentially underlying changes in sensation seeking and reward sensitivity into adulthood.

neuroscience↗

bioRxiv2020

Striatal dopamine supports reward reactivity and learning: A simultaneous PET/fMRI study

Converging evidence from both human neuroimaging and animal studies has supported a model of mesolimbic processing in computing prediction errors, which form the basis of reward learning behaviors. However, direct evidence demonstrating how human dopamine signaling in the basal ganglia contributes to learning has been hampered by limitations of individual imaging modalities. Here, we present data from a large (N=81, 18-30 year olds), multi-modal neuroimaging study using simultaneously acquired task fMRI, affording temporal resolution of reward system function, and PET imaging with [11C]Raclopride (RAC) assessing striatal D2/3 receptor binding. Results indicated that task-related dopamine release in the ventral striatum, measured as a change in RAC binding, was greater among those who demonstrated successful reward learning on a probabilistic map learning task. This learning response was specific to the ventral striatum and was not present in fMRI BOLD reward response activation. This provides support for considering task-related DA release in ventral striatum as a key signal for translating reward outcomes into a learning signal, rather the representing the reward outcome in isolation. These data provide novel, human in vivo evidence that dopaminergic function may support reward reactivity as well as reward learning as distinct processes.

neuroscience↗

bioRxiv2019

Convergent neural representations of acute nociceptive pain in healthy volunteers: A large-scale fMRI meta-analysis

Characterizing a reliable, pain-related neural signature is critical for translational applications. Many prior fMRI studies have examined acute pain-related brain activation in healthy participants. However, synthesizing these data to identify convergent patterns of activation can be challenging due to the heterogeneity of experimental designs and samples. To address this challenge, we conducted a comprehensive meta-analysis of fMRI studies of stimulus-induced pain in healthy participants. Following pre-registration, two independent reviewers evaluated 4,927 abstracts returned from a search of 8 databases, with 222 fMRI experiments meeting inclusion criteria. We analyzed these experiments using Activation Likelihood Estimation with rigorous type I error control (voxel height p < 0.001, cluster p < 0.05 FWE-corrected) and found a convergent, largely bilateral pattern of pain-related activation in the secondary somatosensory cortex, insula, midcingulate cortex, and thalamus. Notably, these regions were consistently recruited regardless of stimulation technique, location of induction, and participant sex. These findings suggest a highly-conserved core set of pain-related brain areas, encouraging applications as a biomarker for novel therapeutics targeting acute pain.\n\nHIGHLIGHTSO_LIPain stimulation recruits a core set of pain-related brain regions.\nC_LIO_LIThis core set includes thalamus, SII, insula and mid-cingulate cortex.\nC_LIO_LIThese regions were recruited regardless of stimulus modality and stimulus location.\nC_LI

neuroscience↗

bioRxiv2019

Development of structure-function coupling in human brain networks during youth

The protracted development of structural and functional brain connectivity within distributed association networks coincides with improvements in higher-order cognitive processes such as working memory. However, it remains unclear how white matter architecture develops during youth to directly support coordinated neural activity. Here, we characterize the development of structure-function coupling using diffusion-weighted imaging and n-back fMRI data in a sample of 727 individuals (ages 8-23 years). We found that spatial variability in structure-function coupling aligned with cortical hierarchies of functional specialization and evolutionary expansion. Furthermore, hierarchy-dependent age effects on structure-function coupling localized to transmodal cortex in both cross-sectional data and a subset of participants with longitudinal data (n=294). Moreover, structure-function coupling in rostrolateral prefrontal cortex was associated with executive performance, and partially mediated age-related improvements in executive function. Together, these findings delineate a critical dimension of adolescent brain development, whereby the coupling between structural and functional connectivity remodels to support functional specialization and cognition.

neuroscience↗

bioRxiv2019

Individual Variation in Control Network Topography Supports Executive Function in Youth

The spatial distribution of large-scale functional networks on the anatomic cortex differs between individuals, and is particularly variable in networks responsible for executive function. However, it remains unknown how this functional topography evolves in development and supports cognition. Capitalizing upon advances in machine learning and a large sample of youth (n=693, ages 8-23y) imaged with 27 minutes of high-quality fMRI data, we delineate how functional topography evolves during youth. We found that the functional topography of association networks is refined with age, allowing accurate prediction of an unseen individuals brain maturity. Furthermore, the cortical representation of executive networks predicts individual differences in executive function. Finally, variability of functional topography is associated with fundamental properties of brain organization including evolutionary expansion, cortical myelination, and cerebral blood flow. Our results emphasize the importance of considering both the plasticity and diversity of functional neuroanatomy during development, and suggest advances in personalized therapeutics.

neuroscience↗

bioRxiv2018

Systematic Characterization of RhoGEF/RhoGAP Regulatory Proteins Reveals Organization Principles of Rho GTPase Signaling

Rho GTPases control cell morphogenesis and thus fundamental processes in all eukaryotes. They are regulated by 145 RhoGEF and RhoGAP multi-domain proteins in humans. How the Rho signaling system is organized to generate localized responses in cells and prevent their spreading is not understood. Here, we systematically characterized the substrate specificities, localization and interactome of the RhoGEFs/RhoGAPs and revealed their critical role in contextualizing and spatially delimiting Rho signaling. They localize to multiple compartments providing positional information, are extensively interconnected to jointly coordinate their signaling networks and are widely autoinhibited to remain sensitive to local activation. RhoGAPs exhibit lower substrate specificity than RhoGEFs and may contribute to preserving Rho activity gradients. Our approach led us to uncover a multi-RhoGEF complex downstream of G-protein-coupled receptors controlling a Cdc42/RhoA crosstalk. The spatial organization of Rho signaling thus differs from other small GTPases and expands the repertoire of mechanisms governing localized signaling activity.

cell biology↗

bioRxiv2017

Modality-Independent Coding Of Concepts In Prefrontal Cortex

Natural environments convey information through multiple sensory modalities, all of which contribute to peoples percepts. Although it has been shown that visual or auditory content of scene categories can be decoded from brain activity, it remains unclear where and how humans integrate different sensory inputs and represent scene information beyond a specific sensory modality domain. To address this question, we investigated how categories of scene images and sounds are represented in several brain regions. A mixed gender group of healthy human subjects participated the present study, where their brain activity was measured with fMRI while viewing images or listening to sounds of different places. We found that both visual and auditory scene categories can be decoded not only from modality-specific areas, but also from several brain regions in the temporal, parietal, and prefrontal cortex. Intriguingly, only in the prefrontal cortex, but not in any other regions, categories of scene images and sounds appear to be represented in similar activation patterns, suggesting that scene representations in the prefrontal cortex are modality-independent. Furthermore, the error patterns of neural decoders indicate that category-specific neural activity patterns in the middle and superior frontal gyri are tightly linked to categorization behavior. Our findings demonstrate that complex scene information is represented at an abstract level in the prefrontal cortex, regardless of the sensory modality of the stimulus.\n\nStatement of SignificanceOur experience in daily life requires the integration of multiple sensory inputs such as images, sounds, or scents from the environment. Here, for the first time, we investigated where and how in the brain information about the natural environment from multiple senses is merged to form modality-independent representations of scene categories. We show direct decoding of scene categories across sensory modalities from patterns of neural activity in the prefrontal cortex. We also conclusively tie these neural representations to human categorization behavior based on the errors from the neural decoder and behavior. Our findings suggest that the prefrontal cortex is a central hub for integrating sensory information and computing modality-independent representations of scene categories.

neuroscience↗