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Todd, R.

Publications and source records attributed to Todd, R..

4 recordsLinked to original sources

Cross-state stability and maturational similarity of the social brain connectome in children and adolescents

The intra-individual stability of functional connectivity (FC) across two or more scans and the inter-individual similarity of FC patterns relative to peers capture developmental variability in functional brain organization. Despite their different referents, these measures are strongly coupled at the whole brain level; however, it remains unclear whether this relationship emerges in development, whether it extends to the social brain, and whether it differs by sex. Based on the importance of social development in this age range, we hypothesized that known developmental relationships and sex-specific effects would be more pronounced in the social brain relative to the whole brain. Using a large psychiatrically enriched sample of 769 youth ages 6-21 (female N = 327, mean age = 12.27 years), we computed FC during rest and movie-watching scans and quantified stability across scans as well as similarity to mature subjects (n=36) within each condition. We then tested whether sex-dependent age relationships were captured by these measures or by the strength of their coupling. Our results showed that cross-state stability and maturational similarity are strongly coupled in development, and that this coupling is enhanced in the social brain relative to the whole brain. Furthermore, the strength of stability-similarity coupling increased as a function of age in females, while males showed the opposite effect. When assessing relationships between age and each FC measure independently, no individual effects were significant after FDR correction. However, our multivariate age-prediction models fared much better, demonstrating that edgewise stability and maturational similarity measures can capture spatially heterogeneous developmental effects that are lost when collapsing across edges. Together, these results support the emerging idea that the degree of FC stability across scans is related to how closely an individuals functional architecture aligns to a shared template. Here, we newly show that this stability-similarity coupling is stronger in the social brain and varies with age in sex-specific ways. Future longitudinal work is needed to establish whether these cross-sectional relationships also characterize within-person developmental change.

neuroscience↗

An iterative design approach to development of an ex-vivo normothermic multivisceral perfusion platform

Challenges in normothermic machine perfusion (NMP) remain, particularly concerning the duration for which individual organs can be safely preserved. We hypothesize that optimal preservation can be achieved by perfusing organs together in a multivisceral block. Therefore, our aim was to establish a platform for ex vivo multivisceral organ perfusion. Multivisceral grafts containing the liver, kidneys, pancreas, spleen and intestine were obtained from Yorkshire pigs. Three generation (gen) setups were tested during the iterative design process, and minor changes were made throughout. Gen1 (n=4) used a custom-designed single perfusion circuit. Gen2 (n=3) employed a dual perfusion circuit. Gen3 (n=4) featured a single perfusion circuit with an optimized basin and reservoir. Grafts underwent NMP using an autologous blood-based perfusate, while hemostatic parameters and function were assessed. With each iteration, aortic flow improved, resistance decreased, urine output increased, oxygen consumption rose, perfusate lactate levels dropped, and pH stability improved. Cellular injury trended lower in Gen3. Histological evaluation demonstrated minimal differences in Gen2 and 3. We demonstrate the feasibility of abdominal multivisceral NMP for up to 8 hours. Adequate arterial flow, stable perfusate pH, and high oxygen consumption in setup 3 indicate organ viability. Multivisceral perfusion may serve as a platform for long-term NMP.

physiology↗

Lateralization of autonomic activity in response to limb-specific threat

In times of stress or danger, the autonomic nervous system (ANS) signals the fight or flight response. A canonical function of ANS activity is to globally mobilize metabolic resources, preparing the organism to respond to threat. Yet a body of research has demonstrated that, rather than displaying a homogenous pattern across the body, autonomic responses to arousing events -- as measured through changes in electrodermal activity (EDA) -- can differ between right and left body locations. Surprisingly, the metabolic function of such ANS asymmetry has not been investigated. In the current study, we investigated whether asymmetric autonomic responses could be induced through limb-specific aversive stimulation. Participants were given mild electric stimulation to either the left or right arm while EDA was monitored bilaterally. Across participants, a strong ipsilateral EDA response bias was observed, with increased EDA response in the hand adjacent to the stimulation. This effect was observable in over 50% of individual subjects. These results demonstrate that autonomic output is more complex than canonical interpretations suggest. We suggest that, in stressful situations, autonomic outputs can prepare either the whole-body fight or flight response, or a simply a limb-localized flick, which can effectively neutralize the threat while minimizing global resource consumption. These findings provide insight into the evolutionary pathway of neural systems processing general arousal by linking observed asymmetry in the peripheral arousal response to a historical leveraging of neural structures organized to mediate responses to localized threat.

neuroscience↗

Hedonic representations in primary somatosensory cortices; Pain but not pleasure?

Emotion is typically understood to be an internal subjective experience originating in the brain. Yet in the somatosensory system hedonic information is coded by mechanoreceptors at the point of sensory contact before it reaches the central nervous system. It remains unknown, however, how these distinct peripheral channels for tactile hedonic information contribute to representations of interoceptive states relative to exteroceptive experience. In this fMRI study we applied representational similarity analyses with pattern component modeling, a technique that deconstructs representational states into a weighted set of distinct predefined constructs, to dissociate how discriminatory vs. hedonic tactile information, carried by A- and C-/CT-fibers respectively, contributes to population code representations in the human brain. Results demonstrated that information about appetitive and aversive tactile sensation is represented separately from non-hedonic tactile information across cortical structures. Specifically, although hedonic touch originates as a peripheral signal, labeled at the point of contact, representations in somatosensory cortices are guided by experiences of non-hedonic touch, By contrast, representations in regions associated with interoception and affect encode signals of hedonic touch. This provides evidence of complex tactile encoding that involves both external-exteroceptive and internal-interoceptive dimensions. Importantly, hedonic touch contributes to representations of internal state as well as those of externally generated stimulation.

neuroscience↗