Biology subjects

Foster, B. L.

Publications and source records attributed to Foster, B. L..

14 recordsLinked to original sources

bioRxiv2026

Electrophysiological dissociation of human posterior cingulate cortex contributions to value- and memory-based decision-making

The human posterior cingulate cortex (PCC) is routinely implicated in cognition and disease, yet its specific functional contributions remain unclear. Historically, human neuroimaging has linked the region to episodic memory and the default mode network, while a distinct non-human primate electrophysiology literature has focused on economic decision-making. Integrating anatomical evidence with these literatures, it has recently been proposed that this divergence reflects subregional organization, with dorsal PCC as a potential convergence site for value-based and memory-based decisions. Here, we recorded local field potentials (LFPs) and single units from human PCC while the same participants performed matched value- and memory-based decision tasks. LFPs in dorsal but not ventral PCC showed sustained engagement across both tasks, with risk sensitivity emerging only after the decision. In contrast, single-unit activity was more temporally circumscribed and could be grouped into response profiles active before or after the decision. Dorsal but not ventral PCC engagement further extended to memory encoding, recognition, and confidence judgments. Together, these findings reveal a consistent functional dissociation, identifying dorsal PCC as a domain-general interface between evaluative and mnemonic systems. In doing so, they align human and non-human primate accounts of PCC function and help orient future targeted studies of its role in cognition and disease.

neuroscience↗

bioRxiv2026

Arousal state modulates human hippocampal ripples

Hippocampal ripples are transient, high-frequency oscillations linked to memory replay and consolidation. Ripples are well-characterized in rodents to occur during periods of behavioral inactivity (i.e., sleep, rest), viewed as "offline" states where replay can emerge with limited sensory interference. However, human studies have increasingly observed ripples during active tasks, raising the questions of whether ripple genesis and function have been misunderstood or whether there are fundamental species differences. We propose that low arousal states--predominant during offline sleep and transient during wake--may constitute a common mechanism of ripple genesis that reconciles these observations. We recorded directly from human hippocampus during sleep and wake, measuring arousal via sleep staging, pupillometry, and heart rate. Ripple occurrence consistently tracked low arousal: rates were maximal in NREM sleep, small-pupil wake states, and slow heart rate periods across sleep and wake. This modulation was stronger in anterior than posterior hippocampus and was hippocampus specific: ripple-like activity outside the hippocampus showed an opposite modulation, increasing with high arousal. These results resolve apparent species differences and provide a unifying view of offline periods as arousal dips that can emerge across behavioral states, including transiently during active wake, suggesting hippocampal ripples, and memory consolidation, occur continuously intermixed with cognition.

neuroscience↗

bioRxiv2026

TNAP and PHOSPHO1 function synergistically to afford critical control over the mineralisation of the postnatal murine skeleton

Biomineralisation is essential for skeletal integrity, yet the synergistic roles of tissue non-specific alkaline phosphatase (TNAP) and PHOSPHO1 in postnatal bone mineralisation remain poorly defined. To decipher this, we generated a novel murine model in which Alpl was deleted in Prx1- expressing cells (AlplPrx1/Prx1) in mice with a global Phospho1-/- deficiency to overcome the perinatal lethality that arises upon dual global deletion. Using a multi-modal approach to spatially phenotype the limbs of these animals, we reveal mice lacking both TNAP and PHOSPHO1 exhibit a distinct lack of mineralisation and altered anatomical structure at postnatal day 1 (PN1) and 3-weeks of age. Although viable, these mice did not thrive due to their reduced size, thus further investigations were conducted on mice with a heterozygous deletion of TNAP (Alplwt/Prx1;Phospho1-/-). Although smaller than wild-types at PN1 and 3 weeks old, these mice did not display the gross limb deformations observed in the homozygous animals and the single, functioning Alpl allele rescued the loss of biomineralisation observed following dual phosphatase deletion. At 6-weeks of age, compromised epiphyses and metaphyses were only seen in AlplPrx1/Prx1 animals. Further, we found that tibial geometry and porosity was significantly altered by Phospho1 deletion (Phospho1-/-), which was compounded in the Alplwt/Prx1;Phospho1-/- mice and linked to alterations in collagen configuration, matrix mineralisation and growth plate deformities. Together, our findings establish the mechanistic framework for TNAP and PHOSPHO1 in permissive biomineralisation, providing critical insights into this fundamental process. Significance StatementBiomineralisation is essential for skeletal development and is critically dependent on phosphatases that release inorganic phosphate for hydroxyapatite formation. Our study investigates the dual role of PHOSPHO1 and TNAP in this process, using a novel murine knockout model. Deletion of both enzymes results in complete loss of bone mineralisation, demonstrating their critical synergistic function. Further, we show that PHOSPHO1 and TNAP exhibit distinct, spatially-restricted functions in the tibia and thus enhances our understanding of the fundamentals processes underpinning biomineralisation. These findings also have clinical relevance as they have the potential to inform on treatment strategies for hypo- and hyper-mineralised pathologies.

developmental biology↗

bioRxiv2026

Neural representations of visual memory in inferotemporal cortex reveal a generalizable framework for translating between spikes and field potentials

Translating neurophysiological findings requires understanding the relationship between common measures of brain activity in animals (spiking activity) and humans (local field potentials, LFP). Prior work suggests alignment between population spiking and high-gamma activity (HGA, 50-150 Hz) of the LFP; however, this is not always observed and is consequently debated. Here, we show that this alignment and prior failures depend on the underlying coding scheme. First, we examined neural representations of variables related to visual memory in macaque inferotemporal cortex. We found that spikes and HGA were strikingly aligned for variables encoded as population response magnitude (novelty, recency, and memorability). However, a variable encoded as a distributed pattern of activity (category) was misaligned. Next, we showed that these insights generalize across many published studies, accounting for prior alignment successes and failures. These results provide a framework for translating between spikes and LFPs, highlighting the scenarios likely to be fruitful for translation.

neuroscience↗

bioRxiv2025

Comparative Evaluation of Three Calcium Silicate-Based Materials for Direct Pulp Capping: An In Vivo Study in Mice.

IntroductionVital pulp treatments (VPT) aim to conservatively manage deep caries and/or damage to preserve the vitality and function of the pulp. This minimally invasive approach is still debated when performing direct pulp capping (DPC), a treatment in which a protective biocompatible material is directly placed over the dental pulp, due to microbial risks inherent with pulp exposure and difficulties in sealing the exposure to protect the pulp from subsequent bacterial ingress. Several limitations associated with Mineral Trioxide Aggregate (MTA) such as long setting time and discoloration have promoted the development of next-generation MTA derivatives with enhanced physical, chemical, and biological properties. As these materials are relatively new, existing studies are limited in scope, lacking a comprehensive assessment of both reparative dentin formation and the sealing ability, which are critical parameters for determining long-term clinical success. These assessments require preclinical models, and while the mouse model offers the opportunity to explore the molecular mechanisms guiding reparative dentinogenesis, the materials and techniques optimized for human dentition present technical challenges in mice due to their small size. AimWe aimed to optimize a DPC technique to use in mice by comparing the tissue responses and the sealing ability of three calcium silicate capping agents: Bioceramic putty (BC), Biodentine (BD), and Theracal-LC (TLC) to a control material known to seal well but cause desiccation that would lead to tissue damage; Cavit-G (CG). Material and methodsDPC was performed on the maxillary first molar of C57BL/6 female mice. Reparative dentin was assessed with micro-computed tomography (micro-CT) and histological assessment of dentin bridge formation at 21 days. The sealing ability of the capping materials was evaluated using micro-CT. ResultsAll three calcium silicate materials showed good biocompatibility and the ability to form a dentin bridge. Micro-CT quantifications of material voids demonstrated superior seals with bioceramic putty and Theracal-LC groups as compared to Biodentine. ConclusionsReady-to-use, premixed capping agents exhibit better sealing ability in mice, while promoting dentin bridge formation to protect the dental pulp.

bioengineering↗

bioRxiv2023

Dissociable contributions of the medial parietal cortex to recognition memory

Human neuroimaging studies of episodic memory retrieval routinely observe the engagement of specific cortical regions beyond the medial temporal lobe. Of these, medial parietal cortex (MPC) is of particular interest given its ubiquitous, and yet distinct, functional characteristics during different types of retrieval tasks. Specifically, while recognition memory and autobiographical recall tasks are both used to probe episodic retrieval, these paradigms consistently drive distinct patterns of response within MPC. This dissociation adds to growing evidence suggesting a common principle of functional organization across memory related brain structures, specifically regarding the control or content demands of memory-based decisions. To carefully examine this putative organization, we used a high-resolution fMRI dataset collected at ultra-high field (7T) while subjects performed thousands of recognition-memory trials to identify MPC regions responsive to recognition-decisions or semantic content of stimuli within and across individuals. We observed interleaving, though distinct, functional subregions of MPC where responses were sensitive to either recognition decisions or the semantic representation of stimuli, but rarely both. In addition, this functional dissociation within MPC was further accentuated by distinct profiles of connectivity bias with the hippocampus during task and rest. Finally, we show that recent observations of person and place selectivity within MPC reflect category specific responses from within identified semantic regions that are sensitive to mnemonic demands. Together, these data better account for how distinct patterns of MPC responses can occur as a result of task demands during episodic retrieval and may reflect a common principle of organization throughout hippocampal-neocortical memory systems. Significance statementMedial parietal cortex (MPC) plays a growing role in contemporary theories of episodic memory, as it is reliably observed in human neuroimaging to be engaged during tasks of recognition and retrieval. However, the spatial pattern of MPC engagement consistently differs across these putatively similar episodic memory tasks. Despite a large literature indicating that the MPC is important for episodic memory, there is little consensus about its specific role. Here, we employed precision-neuroimaging to identify dissociable interleaving MPC subregions, where activity reflected either memory-based decision-making or stimulus content. This dissociation within MPC provides a better understanding for how retrieval demands shape response patterns and speaks to growing evidence for a common principle of organization across memory structures of the human brain.

neuroscience↗

bioRxiv2023

Individual-specific memory reinstatement patterns within human face-selective cortex

Humans have the remarkable ability to vividly retrieve sensory details of past events. According to the theory of sensory reinstatement, during remembering, brain regions involved in the sensory processing of prior events are reactivated to support this perception of the past. Recently, several studies have emphasized potential transformations in the spatial organization of reinstated activity patterns. In particular, studies of scene stimuli suggest a clear anterior shift in the location of retrieval activations compared with those during perception. However, it is not clear that such transformations occur universally, with evidence lacking for other important stimulus categories, particularly faces. Critical to addressing these questions, and to studies of reinstatement more broadly, is the growing importance of considering meaningful variations in the organization of sensory systems across individuals. Therefore, we conducted a multi-session neuroimaging study to first carefully map individual participants face-selective regions within ventral temporal cortex (VTC), followed by a second session to examine the correspondence of activity patterns during face memory encoding and retrieval. Our results showed distinct configurations of face-selective regions within the VTC across individuals. While a significant degree of overlap was observed between face perception and memory encoding, memory retrieval engagement exhibited a more selective and constricted reinstatement pattern within these regions. Importantly, these activity patterns were consistently tied to individual-specific neural substrates, but did not show any consistent direction of spatial transformation (e.g., anteriorization). To provide further insight to these findings, we also report on unique human intracranial recordings from VTC under the same experimental conditions. Our findings highlight the importance of considering individual variations in functional neuroanatomy in the context of assessing the nature of cortical reinstatement. Consideration of such factors will be important for establishing general principles shaping the neural transformations that occur from perception to memory.

neuroscience↗

bioRxiv2023

Mouse Homolog of Human IRF8G388S Mutation Provides Novel Insight into Osteoclastogenesis and Tooth Root Resorption

Previously, we reported a novel mutation in the Interferon Regulatory Factor 8 (IRF8) gene associated with multiple idiopathic cervical root resorption (MICRR), an aggressive form of tooth root resorption mediated by increased osteoclast activity. The IRF8 G388S variant in the highly conserved C-terminal motif is predicted to alter the protein structure, likely impairing IRF8 function. To investigate the molecular basis of MICRR and IRF8 function, we generated Irf8 knock-in (KI) mice using CRISPR/Cas9 modeling the human IRF8G388S mutation. The heterozygous (Het) and homozygous (Homo) Irf8 KI mice showed no gross morphological defects, and the development of hematopoietic cells was unaffected and similar to that in wild-type (WT) mice. The Irf8 KI Het and Homo mice showed no difference in macrophage gene signatures important for antimicrobial defenses and inflammatory cytokine production. Consistent with the phenotype observed in MICRR patients, Irf8 KI Het and Homo mice demonstrated significantly increased osteoclast formation and resorption activity in vivo and in vitro when compared to WT mice. The oral ligature inserted Irf8 KI Het and Homo mice displayed increased osteoclast-mediated alveolar bone loss and tooth root resorption compared to WT mice. The increased osteoclastogenesis noted in KI mice is due to the inability of mutant Irf8 G388S isoform to negatively inhibit NFATc1-dependent transcriptional activation and downstream osteoclast specific transcripts. This translational study delineates the IRF8 domain important for osteoclast function and provides novel insights into the IRF8 mutation associated with MICRR. Irf8G388S mutation mainly affects osteoclastogenesis while sparing immune cell development and function. The Irf8 KI mice serve as a novel translational model for studying the etiopathology of MICRR and developing targeted therapies for MICRR and other skeletal disorders mediated by increased osteoclast activity.

genetics↗

bioRxiv2023

Sulcal morphology of posteromedial cortex substantially differs between humans and chimpanzees

Recent studies identify a surprising coupling between evolutionarily new sulci and the functional organization of human posteromedial cortex (PMC). Yet, no study has compared this modern PMC sulcal patterning between humans and non-human hominoids. To fill this gap in knowledge, we first manually defined 918 sulci in 120 chimpanzee (Pan Troglodytes) hemispheres and 1619 sulci in 144 human hemispheres. We uncovered four new PMC sulci, and quantitatively identified species differences in incidence, depth, and surface area. Interestingly, some PMC sulci are more common in humans and others, in chimpanzees. Further, we found that the prominent marginal ramus of the cingulate sulcus differs significantly between species. Contrary to classic observations, the present results reveal that the surface anatomy of PMC substantially differs between humans and chimpanzees -- findings which lay a foundation for better understanding the evolution of neuroanatomical-functional and neuroanatomical-behavioral relationships in this highly expanded region of the human cerebral cortex.

neuroscience↗

bioRxiv2022

Distinct population and single-neuron selectivity for executive and episodic processing in human dorsal posterior cingulate

Posterior cingulate cortex (PCC) is an enigmatic region implicated in psychiatric and neurological disease, yet its role in cognition remains unclear. Human studies link PCC to episodic memory and default mode network (DMN), while findings from the non-human primate emphasize executive processes more associated with the cognitive control network (CCN) in humans. We hypothesized this difference reflects an important functional division between dorsal (executive) and ventral (episodic) PCC. To test this, we utilized human intracranial recordings of population and single unit activity targeting dorsal PCC during an alternated executive/episodic processing task. Dorsal PCC population responses were significantly enhanced for executive, compared to episodic, task conditions, consistent with the CCN. Single unit recordings, however, revealed four distinct functional types with unique executive (CCN) or episodic (DMN) response profiles. Our findings provide critical electrophysiological data from human PCC, bridging incongruent views within and across species, furthering our understanding of PCC function.

neuroscience↗

bioRxiv2021

A new tripartite landmark in posterior cingulate cortex

Understanding brain structure-function relationships, and their development and evolution, is central to neuroscience research. Here, we show that morphological differences in posterior cingulate cortex (PCC), a hub of functional brain networks, predict individual differences in macroanatomical, microstructural, and functional features of PCC. Manually labeling 4,319 sulci in 552 hemispheres, we discovered a consistently localized shallow cortical indentation (termed the inframarginal sulcus; ifrms) within PCC that is absent from neuroanatomical atlases, yet co-localized with a region within the cognitive control, but not default mode, network. Morphological analyses in humans and chimpanzees showed that unique properties of the ifrms differ across the lifespan and between hominoid species. Intriguingly, the consistency of the ifrms also debunks the uniqueness of the morphology of Einsteins PCC. These findings support a classic theory that shallow, tertiary sulci serve as landmarks in association cortices. They also beg the question: how many other cortical indentations have we missed?

neuroscience↗

bioRxiv2021

Orientation and color tuning of the human visual gamma rhythm

Narrowband gamma oscillations (NBG: [~]20-60Hz) in visual cortex reflect rhythmic fluctuations in population activity generated by underlying circuits tuned for stimulus location, orientation, and color. Consequently, the amplitude and frequency of induced NBG activity is highly sensitive to these stimulus features. For example, in the non-human primate, NBG displays biases in orientation and color tuning at the population level. Such biases may relate to recent reports describing the large-scale organization of single-cell orientation and color tuning in visual cortex, thus providing a potential bridge between measurements made at different scales. Similar biases in NBG population tuning have been predicted to exist in the human visual cortex, but this has yet to be fully examined. Using intracranial recordings from human visual cortex, we investigated the tuning of NBG to orientation and color, both independently and in conjunction. NBG was shown to display a cardinal orientation bias (horizontal) and also an end- and mid-spectral color bias (red/blue and green). When jointly probed, the cardinal bias for orientation was attenuated and an end-spectral preference for red and blue predominated. These data both elaborate on the close, yet complex, link between the population dynamics driving NBG oscillations and known feature selectivity biases in visual cortex, adding to a growing set of stimulus dependencies associated with the genesis of NBG. Together, these two factors may provide a fruitful testing ground for examining multi-scale models of brain activity, and impose new constraints on the functional significance of the visual gamma rhythm. Significance StatementOscillations in electrophysiological activity occur in visual cortex in response to stimuli that strongly drive the orientation or color selectivity of visual neurons. The significance of this induced gamma rhythm to brain function remains unclear. Answering this question requires understanding how and why some stimuli can reliably generate gamma activity while others do not. We examined how different orientations and colors independently and jointly modulate gamma oscillations in the human brain. Our data show gamma oscillations are greatest for certain orientations and colors that reflect known biases in visual cortex. Such findings complicate the functional significance of gamma activity, but open new avenues for linking circuits to population dynamics in visual cortex. ClassificationNeuroscience

neuroscience↗

bioRxiv2020

Stability of ripple events during task engagement in human hippocampus

Periods of cognitive disengagement, such as rest or sleep, are thought to support the progressive consolidation of episodic memories. During these states, the hippocampus displays transient high-frequency oscillatory bursts, known as ripples, which are thought to promote interactions with the neocortex, consolidating memory traces. More recent findings have suggested ripples in the human hippocampus may also occur during task engagement, particularly for tasks requiring episodic memory processes. However, it is unclear if hippocampal ripples occur during other cognitive states or whether ripple properties are modulated by specific types of task demands. In addition, identifying genuine hippocampal ripple events in the human brain can be methodological challenging. To address these questions, we used intracranial recordings from the human hippocampus to quantify ripple events across perceptual, memory and resting task states. Using spectro-temporal identification of hippocampal ripples, we observed highly similar ripple event properties across tasks, with a modest yet significant increase in ripple properties (rate, duration & amplitude) during resting task states. These ripple event attributes did not differ between hemisphere, nor across or within the time of day examined. Supporting data further highlighted that while hippocampal ripples occurred during all task states, these rates were typically lower than that observed during sleep. Together, these findings highlight that hippocampal ripples occur consistently, but sparsely, during a broad range of cognitive task states. Such findings may be incorporated into existing models of systems consolidation, whereby hippocampal ripples help to initially establish latent memory traces.

neuroscience↗

bioRxiv2020

Monocyte Subsets with High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8

Osteoclasts (OCs) are bone resorbing cells formed by the serial fusion of monocytes. In mice and humans, three distinct subsets of monocytes exist; however, it is unclear if all of them exhibit osteoclastogenic potential. Here we show that in wild-type mice, Ly6Chi and Ly6Cint monocytes are the primary source of OC formation when compared to Ly6C- monocytes. Their osteoclastogenic potential is dictated by increased expression of signaling receptors and activation of pre-established transcripts, as well as de novo gain in enhancer activity and promoter changes. In the absence of IRF8, a transcription factor important for myelopoiesis and osteoclastogenesis, all three monocyte subsets are programmed to display higher osteoclastogenic potential. Enhanced NFATc1 nuclear translocation and amplified transcriptomic and epigenetic changes initiated at early developmental stages direct the increased osteoclastogenesis in Irf8 deficient mice. Collectively, our study provides novel insights into the transcription factors and active cis-regulatory elements that regulate OC differentiation.

immunology↗