Biology subjects

Feldman, R.

Publications and source records attributed to Feldman, R..

7 recordsLinked to original sources

bioRxiv2026

Divergent Behavioral and Circuit-Level Adaptations to Acute and Chronic Gastric Electrical Stimulation

Anxiety disorders are highly prevalent and often refractory to existing treatments, motivating the development of alternative neuromodulatory strategies. Peripheral bioelectronic approaches targeting the gut-brain axis such as vagus nerve stimulation (VNS) demonstrate that modulation of visceral afferent pathways can influence central emotional circuits. Gastric electrical stimulation (GES) is a clinically established therapy for gastrointestinal motility disorders. While the stomach is densely innervated by vagal afferents, the effect of GES on anxiety-related behavior has not been systematically examined. We sought to identify neural pathways engaged by GES and effects of continuous chronic GES on behavior. To do this, we developed a gastric stimulation platform for rodents, a fully implantable, untethered system enabling chronic neuromodulation in freely moving rats. We combined this with cross-species whole-brain activity mapping in mice to interrogate circuit-level mechanisms. Using open field and elevated plus mazes, together with machine-learning-based behavioral tracking and multivariate modeling, we show that acute GES induces a robust, context-dependent anxiogenic phenotype characterized by reduced exploration and increased freezing, particularly in novel open-field environments. In contrast, chronic GES produces a divergent post-stimulation behavioral profile marked by enhanced exploratory behavior relative to acutely stimulated animals, indicating temporally dynamic reorganization of anxiety-related behavior. Principal component analysis and hierarchical clustering further revealed that stimulation reshapes the multivariate structure of behavioral features rather than shifting animals along a single anxiety continuum. Whole-brain c-Fos mapping revealed anatomically distributed modulation of limbic-cortical networks following gastric stimulation, including suppression of ventral medial entorhinal cortex, excitation of nucleus tractus solitarii and heterogeneous recruitment of amygdalar and hippocampal subregions. These circuit-level patterns align with the behavioral dissociation between contextual exploration and explicit threat avoidance, providing convergent cross-species evidence that gastric stimulation engages distributed anxiety-related networks. Together, these findings establish the first freely moving behavioral model of chronic gastric neuromodulation, demonstrate temporally dynamic and context-sensitive effects on anxiety-like behavior, and provide systems-level validation that the stomach can serve as a viable peripheral access point for modulating central emotional circuits.

bioengineering↗

bioRxiv2023

A transmission chain linking Mycobacterium ulcerans with Aedes notoscriptus mosquitoes, possums and human Buruli ulcer cases in southeastern Australia

In temperate southeastern Australia over the past two decades there has been a marked progressive increase in human cases of Buruli ulcer, an infection of subcutaneous tissue caused by Mycobacterium ulcerans. Native possums are the major local environmental reservoir of M. ulcerans as they not only develop Buruli lesions but they also shed M. ulcerans in their excreta. However the way humans acquire M. ulcerans from possums has not been determined. Previous case-control studies, insect field surveys and vector competence studies have suggested a role for mosquitoes in M. ulcerans transmission between possums and humans. To explore these links we conducted an extensive, 4-month structured mosquito field survey and four ad hoc field surveys across an area of 350km2 on the Mornington Peninsula, an area endemic for Buruli ulcer to the south of the major metropolitan city of Melbourne. We then compared spatial and temporal patterns of M. ulcerans-positive mosquito occurrence with M. ulcerans-positive possums (established by previous possum excreta surveys) and human Buruli ulcer cases across the region. We used metabarcoding to assess mosquito blood-feeding host preference and to reconstruct M. ulcerans genomes from positive mosquitoes to test epidemiological inferences. We collected 66,325 mosquitoes spanning 26 different species from 180 repeatedly sampled traps over a 4-month period. Culex molestus and Aedes notoscriptus were the dominant species (42% and 35% of trapped mosquitoes, respectively). PCR screening 25% of trapped mosquitoes revealed a significant association between M. ulcerans and Ae. notoscriptus (p<0.0001) with a maximum likelihood estimate (MLE) of 5.88 M. ulcerans positive mosquitoes per 1,000 tested. Using spatial scanning statistics, we also observed significant overlap between clusters of M. ulcerans-positive Ae. notoscriptus, M. ulcerans-positive possum excreta and human Buruli ulcer cases. Metabarcoding analyses of blood-fed Ae. notoscriptus showed individual mosquitoes had fed both on humans and native possums. Enrichment genome sequencing from PCR-positive mosquitoes confirmed shared M. ulcerans genome single-nucleotide polymorphism (SNP) profiles between mosquitoes, possum excreta and clinical human isolates within the same regions. These findings indicate that Ae. notoscriptus likely transmit M. ulcerans in southeastern Australia and highlight mosquito control as a plausible means to control the Buruli ulcer epidemic in our region.

microbiology↗

bioRxiv2023

Attachment Stimuli Trigger Widespread Synchrony across Multiple Brains

Infant stimuli elicit widespread neural and behavioral response in human adults and such massive allocation of resources attests to the evolutionary significance of the primary attachment. Here, we examined whether attachment-related cues also trigger cross-brain concordance, generating greater neural uniformity among individuals. Post-partum mothers were imaged twice in oxytocin/placebo administration design and stimuli included four ecological videos; two of infant/mother alone (Alone) and two mother-infant dyadic contexts (Social). Theory-driven analysis measured cross-brain synchrony in preregistered nodes of the parental caregiving network (PCN), which integrates subcortical structures underpinning mammalian mothering with cortical areas implicated in simulation, mentalization, and emotion regulation, and data--driven analysis assessed brain-wide concordance using whole brain parcellation. Results demonstrated widespread cross-brain synchrony in both the PCN and across the neuroaxis, from primary sensory and somatosensory areas, through insular-cingulate regions, to temporal and prefrontal cortices. The Social context yielded significantly more cross-brain concordance, with PCNs striatum, parahipporcampal gyrus, superior temporal sulcus, anterior cingulate cortex (ACC), and prefrontal cortex displaying cross-brain synchrony only to mother-infant social cues. Moment-by-moment fluctuations in mother-infant social synchrony, ranging from episodes of gaze aversion to rhythmically-coordinated positive bouts, were tracked online by cross-brain concordance in the pre-registered ACC. Findings indicate that social attachment stimuli, representing evolutionary-salient universal cues that require no verbal narrative for immediate comprehension, trigger substantial inter-brain concordance and suggest that the mother-infant bond, an icon standing at the heart of human civilization, may function to glue brains into a unified experience and bind humans into social groups. Significance StatementInfant stimuli elicit widespread neural response in human adults, attesting to their evolutionary significance, but do they also trigger cross-brain concordance and induce neural uniformity among perceivers? We measured cross-brain synchrony to ecological mother-infant videos. We employed theory-driven analysis, measuring cross-brain concordance in the parenting network, and data-driven analysis, assessing brain-wide concordance using whole-brain parcellation. Attachment cues triggered widespread cross-brain concordance in both the parenting network and across the neuroaxis. Moment-by-moment fluctuations in behavioral synchrony were tracked online by cross-brain variability in ACC. Attachment reminders bind humans brains into a unitary experience and stimuli characterized by social synchrony enhance neural similarity among participants, describing one mechanism by which attachment bonds provide the neural template for the consolidation of social groups.

neuroscience↗

bioRxiv2022

Technologically-Assisted Communication Attenuates Inter-Brain Synchrony

The transition to technologically-assisted communication has permeated all facets of human social life; yet, its impact on the social brain is still unknown and the effects may be most notable during key developmental transitions. Applying a two-brain perspective, the current pre-registered study measured mother-child brain-to-brain synchrony using hyperscanning EEG at the transition to adolescence during live face-to-face interaction versus technologically-assisted remote communication. The live interaction elicited 9 significant cross-brain links between densely inter-connected frontal and temporal areas in the beta range [14-30 Hz]. Mothers right frontal region connected with childs right and left frontal, temporal, and central regions, suggesting its regulatory role in organizing the two-brain dynamics. In contrast, the remote interaction elicited only 1 significant cross-brain-cross-hemisphere link, attenuating the robust right-to-right-brain connectivity during live social moments that communicates socio-affective signals. Furthermore, while the level of social behavior was comparable between the two interactions, brain-behavior links emerged only during the live exchange, suggesting that remote interactions yield a somewhat thinner biobehavioral experience. Mother-child right temporal-temporal synchrony linked with moments of shared gaze and the degree of child engagement and empathic behavior was associated with right frontal-frontal synchrony. Our findings indicate that human co-presence is underpinned by specific neurobiological processes, suggest potential reasons for "zoom fatigue", and open a much-needed discussion on the cost of social technology for brain maturation, particularly among youth. HighlightsO_LITechnologically-assisted communication is prevalent; yet, its impact on the social brain is unknown C_LIO_LIWe measured mother-child brain-to-brain synchrony during live and technologically-assisted remote interaction C_LIO_LIThe live interaction elicited 9 cross-brain links between densely inter-connected frontal and temporal areas in the beta range C_LIO_LIThe remote interaction yielded only 1 significant cross-brain cross-hemisphere link C_LIO_LIBrain-behavior linked emerged only during the live interaction C_LIO_LIFurther research should examine the cost of social technology to brain maturation, particularly among youth. C_LI

neuroscience↗

bioRxiv2021

Neural Representation of the Relational Self from Infancy to Adulthood

Investigations into the neural underpinnings of the "self" highlight its complexity and multi-dimensionality and emphasize that various aspects of the self are sustained by different neural systems. Here, we focused on the Relational Self, a dimension denoting the self-within-attachment-relationships that taps the continuity of attachment across individual development and affiliative bonds. Mothers and children were followed across two decades and videotaped in naturalistic interactions at three ages: infancy (3-6 months), childhood (9-12 years), and young adulthood (18-24 years). During fMRI scanning, young adults were exposed to videos of their own mother-child interactions from the three ages versus matched unfamiliar interactions. Relational Self-stimuli elicited greater activations across preregistered nodes of the human caregiving network, including thalamus-to-brainstem, amygdala, hippocampus, ACC, insula, and temporal cortex. Critically, Relational Self-stimuli were age-invariant in most regions of interest despite large variability of stimuli across multiple self-related features, such as similarity, temporal distance, affect, or mentalization, and Bayesian analysis indicated strong evidence for lack of age-related differences. PPI analysis demonstrated that Relational Self-stimuli elicited tighter connectivity between the ACC and insula. Greater child social engagement during interaction with mother correlated with higher ACC and insula response to Relational Self-stimuli. Findings highlight an important novel dimension in the neural representation of the self, suggest that the Relational Self may be sustained by a paralimbic interface integrating exteroceptive and interoceptive self-related signals, and demonstrate overlap in the attachment network of parents and children, lending support to perspectives on the continuity of attachment and self across the individuals developmental history. Significance StatementDescribing the neural underpinnings of the "self" is inherently complex due to the multi-dimensionality of the construct. Following mothers and children from infancy to adulthood, we focused on the Relational Self, a dimension denoting the self-within-attachment-relationships, and exposed young adults to own versus unfamiliar mother-child interactions across their relational history. Relational Self stimuli triggered greater activations in the human caregiving network, including thalamus-to-brainstem, amygdala, hippocampus, ACC, insula, and temporal cortex, were age-invariant, and elicited tighter connectivity between ACC and insula, creating a paralimbic interface of interoception-exteroception sustaining the Relational Self. Findings highlight a novel dimension in the neural representation of the self and lend support to perspectives emphasizing the cross-generational transmission of attachment and its continuity across the individuals developmental history.

neuroscience↗

bioRxiv2020

Mother Brain is Wired for Social Moments

Reorganization of the maternal brain, primed by oxytocin surge during childbirth, triggers the species-typical maternal social behavior. These brief social moments carry profound effects on the infants social brain and likely have a distinct signature in the maternal brain. Utilizing a double-blind, oxytocin/placebo administration crossover design, we imaged mothers twice while observing three naturalistic maternal-infant contexts in the home ecology; "unavailable", "unresponsive", and "social", when mothers engaged in synchronous pick-a-boo play. We found four processes by which mothers brain registers social moments. Salience - social moments increased activations throughout the maternal brain network; Brain-behavior coupling - caregiving behavior linked with socially-driven neural response; Oxytocin sensitivity - administration impacted neural response mainly to the social context; and Temporal engrams-consistent temporal patterns in insula and TP characterized response to social play. Findings describe how mothers brain compiles and amplifies these precious social moments to generate dyad-specific brain-behavior patterns that initiate the cross-generational transmission of human sociality.

neuroscience↗

bioRxiv2020

Synchronous Caregiving from Birth to Adulthood Tunes Humans' Social Brain

Mammalian young are born with immature brains and rely on the mothers body and caregiving behavior for maturation of neurobiological systems that sustain adult sociality. However, the parent-child precursors of humans social brain are unknown. We followed human neonates, who received or were deprived of maternal bodily contact, to adulthood, repeatedly measuring mother-child interactive synchrony. We tested the neural basis of empathic accuracy in adulthood and utilized multivariate techniques to distinguish brain regions sensitive to others distinct emotions from those globally activated by the vicarious stance. A network comprising the amygdala, insula, and temporal pole underpinned empathic accuracy, which was shaped by mother-child synchrony across development. Synchronous experiences with mother or father in infancy impacted adults neural empathy, highlighting the benefits of humans bi-parental rearing. Findings demonstrate the centrality of synchronous caregiving across development for tuning humans social brain.

neuroscience↗