Biology subjects

Berry, A. S.

Publications and source records attributed to Berry, A. S..

7 recordsLinked to original sources

bioRxiv2026

Dopamine Compensates for Amyloid-Induced Default Mode Network Dysfunction to Support Learning

Throughout the preclinical phase of Alzheimers disease (AD) {beta}-amyloid (A{beta}) accumulates preferentially within the default mode network (DMN), yet the functional and behavioural consequences of this pathological burden remain poorly understood. Using task-based fMRI combined with A{beta}, tau, and dopamine PET in cognitively normal older adults, we show that A{beta} burden impairs learning independent of tau, but this learning performance is recovered with higher dorsolateral striatal dopamine synthesis capacity. Investigating the neural mechanisms that support this learning, we observe that A{beta} positive individuals show attenuated DMN activity to error related feedback, a metric that relates to poorer learning. When estimating the effective connectivity during feedback, computational modelling reveals that A{beta} induces dis-inhibition of the DMN during error processing. Critically, dopamine synthesis capacity in the dorsolateral striatum rebalances effective connectivity between the DMN and frontostriatal network, thereby opposing A{beta} related disruption. These findings establish a systems-level framework in which A{beta} impairs learning by disrupting dynamic DMN modulation during feedback, a disruption for which dopaminergic function can partially compensate. This suggests that learning in the presence of A{beta} may be subserved by dopamine-dependent network rebalancing, a candidate mechanism of cognitive resilience to support learning in preclinical AD.

neuroscience↗

bioRxiv2025

Age-Related Changes in Curiosity: The Influence of Locus Coeruleus on Information-Seeking Behavior

Curiosity enhances learning and memory and has been linked to the locus coeruleus (LC), which undergoes age-related decline. To examine how aging affects curiosity and information-seeking, we developed the Photographic Art Storytelling Task. Participants (sixty-eight young and sixty-five older adults) viewed photographs, rated their curiosity, and later read stories associated with selected images. The stories were deliberately constructed to be either interesting or boring, functioning as rewards that elicited prediction errors. Participants reappraised their curiosity, allowing us to separate intrinsic motivation from story-driven reward influences. Associations between performance and both pupil diameter and MRI measures of LC integrity supported a role of LC in curiosity regulation. Aging was associated with greater reliance on novelty-driven (initial) curiosity and a shift away from prediction error-related information-seeking. Both age groups showed curiosity-driven memory enhancement, with older adults exhibiting youth-like effects, suggesting a role for intrinsic motivation in preserving cognitive function in aging.

neuroscience↗

bioRxiv2025

Temporal fMRI Dynamics Map Dopamine Physiology

Spatial variations in dopamine function are linked to cognition and substance use disorders but are challenging to characterize with current methods. Because dopamine influences blood vessel dilation, we hypothesized that hemodynamic latency, which reflects BOLD signal timing, could serve as an indirect marker of dopamine physiology. Across four datasets, we found a topography of hemodynamic latencies that precisely distinguished the nucleus accumbens, a dopaminergic region implicated in motivation and substance abuse, from other striatal regions. Using PET, genetics, and pharmacology, we found that hemodynamic latencies are robustly related to dopamine function and dopamine-linked behavior. In individuals with cocaine use disorder, we observed a spatial gradient of altered hemodynamic latencies in the striatum. This pattern independently predicted nicotine use, revealing a conserved physiological profile associated with addictive substance use. Hemodynamic latencies map regional, individual, and pathological differences linked to dopamine, opening new avenues for indirectly assessing the role of dopamine in healthy cognition and disease.

neuroscience↗

bioRxiv2024

A dopaminergic basis of behavioral control

Both goal-directed and automatic processes shape human behavior, but these processes often conflict. Behavioral control is the decision about which process guides behavior. Despite the importance of behavioral control for adaptive decision-making, its neural mechanisms remain unclear. Critically, it is unknown if there are mechanisms for behavioral control that are distinct from those supporting the formation of goal-relevant knowledge. We performed deep phenotyping of individual dopamine system function by combining multiple PET scans, fMRI, and dopaminergic drug administration in a within-subject, double-blind, placebo-controlled design. Subjects performed a rule-based response time task, with goal-directed and automatic decision-making operationalized as model-based and model-free influences on behavior. We found a double dissociation between two aspects of ventral striatal dopamine physiology: D2/3 receptor availability and dopamine synthesis capacity. Convergent and causal evidence indicated that D2/3 receptors regulate behavioral control by enhancing model-based and blunting model-free influences on behavior but do not affect model-based knowledge formation. In contrast, dopamine synthesis capacity was linked to the formation of model-based knowledge but not behavioral control. D2/3 receptors also modulated frontostriatal functional connectivity, suggesting they regulate behavioral control by gating prefrontal inputs to the striatum. These results identify central mechanisms underlying individual and state differences in behavioral control and point to striatal D2/3 receptors as targets for interventions for improving goal-directed behavior.

neuroscience↗

bioRxiv2021

Gut microbiota features associated with Clostridioides difficile colonization in dairy calves

Diarrheal disease, a major cause of morbidity and mortality in dairy calves, is strongly associated with the health and composition of the gut microbiome. Clostridioides difficile is an opportunistic pathogen that proliferates and can produce enterotoxins when the host experiences gut dysbiosis. However, even asymptomatic colonization with C. difficile can be associated with differing degrees of microbiome disruption in a range of species, including people, swine, and dogs. Little is known about the interaction between C. difficile and the gut microbiome in dairy calves. In this study, we sought to define microbial features associated with C. difficile colonization in pre-weaned dairy calves less than 2 weeks of age. We characterized the fecal microbiota of 80 calves from 23 different farms using 16S rRNA sequencing and compared the microbiota of C. difficile-positive (n=24) and C. difficile-negative calves (n=56). Farm appeared to be the greatest source of variability in the gut microbiota. When controlling for calf age, diet, and farm location, there was no significant difference in Shannon alpha diversity (P= 0.50) or in weighted UniFrac beta diversity (P=0.19) between C. difficile-positive and -negative calves. However, there was a significant difference in beta diversity as assessed using Bray-Curtiss diversity (P=0.0077), and C. difficile-positive calves had significantly increased levels of Ruminococcus (gnavus group) (Adj. P=0.052), Lachnoclostridium (Adj. P=0.060), Butyricicoccus (Adj. P=0.060), and Clostridium sensu stricto 2 compared to C. difficile-negative calves. Additionally, C. difficile-positive calves had fewer microbial co-occurrences than C. difficile-negative calves, indicating reduced bacterial synergies. Thus, while C. difficile colonization alone is not associated with dysbiosis and is therefore unlikely to result in an increased likelihood of diarrhea in dairy calves, it may be associated with a more disrupted microbiota.

microbiology↗

bioRxiv2021

Osmolarity-regulated swelling initiates egg activation in Drosophila

Egg activation is a series of highly coordinated processes that prepare the mature oocyte for embryogenesis. Typically associated with fertilisation, egg activation results in many downstream outcomes, including the resumption of the meiotic cell cycle, translation of maternal mRNAs and cross-linking of the vitelline membrane. While some aspects of egg activation, such as initiation factors in mammals and environmental cues in sea animals, have been well-documented, the mechanics of egg activation in insects are less well understood. For many insects, egg activation can be triggered independently of fertilisation. In Drosophila melanogaster, egg activation occurs in the oviduct resulting in a single calcium wave propagating from the posterior pole of the oocyte. Here we use physical manipulations, genetics and live imaging to demonstrate the requirement of a volume increase for calcium entry at egg activation in mature Drosophila oocytes. The addition of water, modified with sucrose to a specific osmolarity, is sufficient to trigger the calcium wave in the mature oocyte and the downstream events associated with egg activation. We show that the swelling process is regulated by the conserved osmoregulatory channels, aquaporins (AQPs) and DEGenerin/Epithelial Na+ (DEG/ENaC) channels. Furthermore, through pharmacological and genetic disruption, we reveal a concentration-dependent requirement of Trpm channels to transport calcium, most likely from the perivitelline space, across the plasma membrane into the mature oocyte. Our data establishes osmotic pressure as the mechanism that initiates egg activation in Drosophila and is consistent with previous work from evolutionarily distant insects, including dragonflies and mosquitos, and shows remarkable similarities to the mechanism of egg activation in some plants.

developmental biology↗

bioRxiv2017

Spontaneous eye blink rate and dopamine synthesis capacity: Preliminary evidence for an absence of positive correlation

Dopamine is central to a number of cognitive functions and brain disorders. Given the cost of neurochemical imaging in humans, behavioral proxy measures of dopamine have gained in popularity in the past decade, such as spontaneous eye blink rate (sEBR). Increased sEBR is commonly associated with increased dopamine function based on pharmacological evidence and patient studies. Yet, this hypothesis has not been validated using in vivo measures of dopamine function in humans. In order to fill this gap, we measured sEBR and striatal dopamine synthesis capacity using [18F]DOPA PET in 20 participants (9 healthy individuals and 11 pathological gamblers). Our results, based on frequentist and Bayesian statistics, as well as region-of-interest and voxel-wise analyses, argue against a positive relationship between sEBR and striatal dopamine synthesis capacity. They show that, if anything, the evidence is in favor of a negative relationship. These results, which complement findings from a recent study that failed to observe a relationship between sEBR and dopamine D2 receptor availability, suggest that caution and nuance are warranted when interpreting sEBR in terms of a proxy measure of striatal dopamine.

neuroscience↗