Biology subjects

Brandt, A.

Publications and source records attributed to Brandt, A..

At least 19 recordsLinked to original sources

bioRxiv2026

The human hippocampus retroactively binds experiences across time

Creating memories requires linking events across seconds and minutes, but canonical mechanisms of associative plasticity operate over much shorter timescales. This poses a fundamental problem: how can the brain bind information that arrives at different times? Computational model and animal studies implicate the hippocampus in associating events across time, but when the hippocampus becomes engaged and how it interacts with representations of preceding events are unknown. Here we show, using intracranial recordings in humans forming image-word associations across a ~2-s temporal gap, that hippocampal high-frequency activity predicts later memory when the second event arrives, but not during the initial image or intervening delay. At this moment, neurons tuned to the preceding image reinstate stimulus-specific firing despite its sensory absence. Across trials, hippocampal high-frequency activity was selectively coupled to this reinstatement during successful encoding and increased before spiking of image-tuned neurons. These findings reveal a retroactive mode of hippocampal binding, whereby representations of preceding events are recruited when new information arrives. This mechanism provides a neural solution for binding experiences across the temporal discontinuities that characterize everyday life.

neuroscience↗

bioRxiv2025

Hybridogenesis as an intermediate step between sexual reproduction and parthenogenesis

Many organisms reproduce through non-canonical modes such as parthenogenesis or hybridogenesis (clonal transmission of one parents chromosomes), but whether these arise abruptly or stepwise from each other remains unclear. We address this in the stick-insect genus Bacillus, which harbors several hybrid lineages with diverse reproductive modes. From haplotype-resolved phylogenies of >500 wild-caught individuals, we infer a single, recent ([~]8,000 years) origin of all hybrids. The ancestral hybrid reproduced via hybridogenesis, which subsequently diversified into parthenogenesis and, twice independently, into triploid lineages. Laboratory crosses recapitulate this trajectory, where each step facilitated the next. These findings reveal how a single genomic perturbation can act as a catalyst for evolutionary innovation, turning the loss of sex into a driver of diversification rather than a dead end.

evolutionary biology↗

bioRxiv2025

Single-neuron encoding of rapidly learned visual information reshapes human perception

Humans can swiftly learn to recognize visual objects after minimal exposure. Integrating new information with existing knowledge requires forming enduring neuronal representations to enable future recognition. Yet, the neuronal mechanisms in the human brain underlying such rapid perceptual changes remain unclear. We recorded single-neuron activity in occipital (OC) and medial temporal lobe (MTL) regions as participants rapidly learned to recognize degraded images. OC and MTL neurons modulated their activity to encode newly learned visual information and reshape perception. Population decoding revealed that OC neurons required additional processing time to resolve the identity of learned images, delaying neuronal responses in the MTL. Our findings indicate that OC supports recognition after rapid learning via extensive recurrent processing, potentially involving higher-order neocortical areas, without relying on feedback from MTL. These results provide mechanistic constraints for biologically plausible models of visual recognition and few-shot visual learning.

neuroscience↗

bioRxiv2024

A preserved neural code for temporal order between memory formation and recall in the human medial temporal lobe

Temporal memory enables us to remember the temporal order of events happening in our life. The human medial temporal lobe (MTL) appears to contain neural representations supporting temporal memory formation, but the cellular mechanisms that preserve temporal order information for recall are largely unknown. Here, we examined whether human MTL neuronal activity represents the temporal position of events during memory formation and recall, using invasive single and multi-unit recordings in human epilepsy patients (n = 19). Participants freely navigated a virtual environment in order to explore and remember locations and temporal positions of objects. During each exploration period, they sequentially encountered two or three different objects, placed in different locations. This allowed us to examine single- and multi-unit neuronal firing rates (FR) as a function of the temporal position the objects were presented in. We found that a significant number of multi-units and single-units in various MTL regions including the hippocampus showed selectivity to the temporal position of objects during the exploration period. During recall, patients were asked to indicate which one of two objects from the same trial was found latter. Neural firing rates during recall showed a selectivity supporting recall of temporal positions. Interestingly, most of the selective single-units that stayed selective during encoding and recall preserved their temporal position preference. Our results thus suggest that neuronal activity in the human MTL contains a preserved neural code for temporal order in memory formation and recall.

neuroscience↗

bioRxiv2024

Theta-phase locking of single neurons during human spatial memory

The precise timing of single-neuron activity in relation to local field potentials may support various cognitive functions. Extensive research in rodents, along with some evidence in humans, suggests that single-neuron activity at specific phases of theta oscillations plays a crucial role in memory processes. Our fundamental understanding of such theta-phase locking in humans and its dependency on basic electrophysiological properties of the local field potential is still limited, however. Here, using single-neuron recordings in epilepsy patients performing a spatial memory task, we thus aimed at improving our understanding of factors modulating theta-phase locking in the human brain. Combining a generalized-phase approach for frequency-adaptive theta-phase estimation with time-resolved spectral parameterization, our results show that theta-phase locking is a strong and prevalent phenomenon across human medial temporal lobe regions, both during spatial memory encoding and retrieval. Neuronal theta-phase locking increased during periods of elevated theta power, when clear theta oscillations were present, and when aperiodic activity exhibited steeper slopes. Theta-phase locking was similarly strong during successful and unsuccessful memory, and most neurons activated at similar theta phases between encoding and retrieval. Some neurons changed their preferred theta phases between encoding and retrieval, in line with the idea that different memory processes are separated within the theta cycle. Together, these results help disentangle how different properties of local field potentials and memory states influence theta-phase locking of human single neurons. This contributes to a better understanding of how interactions between single neurons and local field potentials may support human spatial memory.

neuroscience↗

bioRxiv2023

Fibroblast-derived IL-11 is a driver and therapeutic target in Peutz-Jeghers syndrome polyposis

Peutz-Jeghers syndrome (PJS) is associated with early-onset and recurring gastrointestinal hamartomatous polyposis caused by hereditary inactivating mutations in the tumor suppressor gene LKB1 (STK11). Due to lack of efficient prophylactic therapies PJS patients require regular surgical interventions and have an increased risk of cancer. LKB1-deficient fibroblasts have been identified as drivers of polyposis, but a safely druggable target remains to be identified. Here we investigate tumorigenic mechanisms in PJS polyps using single-cell RNA sequencing of predisposed and tumor tissue and identified a ST2-expressing crypt top fibroblast (CTF) cluster enriched in polyps. The relevance of CTFs was supported by the fast polyposis following deletion of Lkb1 in CTFs. The transcriptional signature characterizing the ST2+ fibroblasts (ST2-CTFs) was enriched in inflammation-associated fibroblasts, and PJS polyposis was exacerbated by inflammation. Cell-cell communication analysis identified the ST2-CTF signature gene interleukin 11 (IL-11) as an upstream regulator of the ST2-CTFs, and consistently, reprogramming toward ST2 fibroblasts in vitro was dependent on IL-11. Importantly, a neutralizing IL-11 antibody efficiently reduced the tumor burden in a PJS mouse model. In summary, our results reveal ST2+ tumorigenic fibroblasts as drivers of PJS polyposis and identify IL-11 as the key mediator and a potential therapeutic target in PJS.

cancer biology↗

bioRxiv2023

Haplotype independence contributes to evolvability in the long-term absence of sex in a mite

Some unique asexual species persist over time and contradict the consensus that sex is a prerequisite for long-term evolutionary survival. How they escape the dead-end fate remains enigmatic. Here, we generated a haplotype-resolved genome assembly based on a single individual and collected genomic data from worldwide populations of the parthenogenetic diploid oribatid mite Platynothrus peltifer to identify signatures of persistence without sex. We found that haplotypes diverge independently since the transition to asexuality at least 20 my ago. Multiple lines of evidence indicate disparate evolutionary trajectories between haplotypic blocks. Our findings imply that such haplotypic independence can lead to non-canonical routes of evolvability, helping some species to adapt, diversify and persist for millions of years in the absence of sex. One-Sentence SummaryFunctionally different chromosome sets in an asexual mite species showcase a survival strategy spanning millions of years.

evolutionary biology↗

bioRxiv2023

Neurons in the human entorhinal cortex map abstract emotion space

When animals move through space, neurons in their entorhinal cortex activate periodically at multiple locations to form a map of the spatial environment. These grid cells may also map non-physical, conceptual spaces to support various other complex behaviors. Here, using intracranial recordings in neurosurgical patients performing an emotional memory task, we find that neurons in the human medial temporal lobe activate in a grid-like pattern across a two-dimensional feature space characterized by emotional valence and arousal. These neurons were different from cells tuned solely to valence or arousal, were preferentially located in the entorhinal cortex, and exhibited theta-phase locking. Our observation of grid-like neuronal activity during emotional processing in humans supports the idea that the neural structure of cognitive maps generalizes beyond spatial navigation.

neuroscience↗

bioRxiv2023

Evolution of alternative reproductive systems in Bacillus stick insects

Reproduction is a key feature of all organisms, yet the way in which it is achieved varies greatly across the tree of life. One striking example of this variation is the stick insect genus Bacillus, in which five different reproductive modes have been described: sex, facultative and obligate parthenogenesis, and two highly unusual reproductive modes: hybridogenesis and androgenesis. Under hybridogenesis, the entire genome from the paternal species is eliminated, and replaced each generation by mating with the corresponding species. Under androgenesis, an egg is fertilized but the developing diploid offspring bear two paternal genomes, and no maternal genome, as a consequence of unknown mechanisms. Here, we re-evaluate previous descriptions of Bacillus lineages and the proposed F1 hybrid ancestries of the hybridogenetic and obligately parthenogenetic lineages (based on allozymes and karyotypes) from Sicily, where all these reproductive modes are found. We generate a chromosome-level genome assembly for a facultative parthenogenetic species (B. rossius) and combine extensive field sampling with RADseq and mtDNA data. We identify and genetically corroborate all previously described species and confirm the ancestry of hybrid lineages. All hybrid lineages have fully retained their F1 hybrid constitution throughout the genome, indicating that the elimination of the paternal genome in hybridogens is always complete and that obligate parthenogenesis in Bacillus hybrid species is not associated with an erosion of heterozygosity as known in other hybrid asexuals. Our results provide a stepping stone towards understanding the transitions between reproductive modes and the proximate mechanisms of genome elimination.

evolutionary biology↗

bioRxiv2023

Maintenance and transformation of representational formats during working memory prioritization

Visual working memory depends on both material-specific brain areas in the ventral visual stream (VVS) that support the maintenance of stimulus representations and on regions in prefrontal cortex (PFC) that control these representations. Recent studies identified stimulus-specific working memory contents via representational similarity analysis (RSA) and analyzed their representational format using deep neural networks (DNNs) as models of the multi-layered hierarchy of information processing. How executive control prioritizes relevant working memory contents and whether this affects their representational formats remains an open question, however. Here, we addressed this issue using a multi-item working memory task involving a retro-cue that prompted participants to maintain one particular item. We exploited the excellent spatiotemporal resolution of intracranial EEG (iEEG) recordings in epilepsy patients and analyzed activity at electrodes in VVS (n=28 patients) and PFC (n=16 patients). During encoding, we identified category-specific information in both VVS and PFC. During maintenance, this information re-occurred in VVS but not in the PFC - suggesting a transformation of PFC representations from encoding to maintenance which putatively reflects the prioritization process. We thus applied RSA in combination with different DNN architectures to investigate the representational format of prioritized working memory contents. Representations during the maintenance period matched representations in deep layers of recurrent but not feedforward DNNs, in both VVS and PFC. While recurrent DNN representations matched PFC representations in the beta band following the retro-cue, they corresponded to VVS representations in a lower theta-alpha frequency range (3-14Hz) towards the end of the maintenance period. Findings could be replicated in recurrent DNNs with two different architectures and using two different training sets. Together, these results demonstrate that VWM relies on representational transformations in VVS and PFC that give rise to distinct coding schemes of prioritized contents.

neuroscience↗

bioRxiv2022

Ripple-locked coactivity of stimulus-specific neurons supports human associative memory

Associative memory is the ability to encode and retrieve relations between different stimuli. To better understand its neural basis, we investigated whether associative memory involves precisely timed spiking of neurons in the medial temporal lobes that exhibit stimulus-specific tuning. Using single-neuron recordings from epilepsy patients performing an associative object-location memory task, we identified the object- and place-specific neurons that encoded the separate elements of each memory. When patients encoded and retrieved particular memories, the relevant object- and place-specific neurons activated synchronously during hippocampal ripples. This ripple-locked coactivity of stimulus-specific neurons emerged over time as the patients associative learning progressed. Our results suggest a cellular account of associative memory, in which hippocampal ripples coordinate the activity of specialized cellular populations to facilitate links between stimuli.

neuroscience↗

bioRxiv2022

Convection and extracellular matrix binding control interstitial transport of extracellular vesicles

Extracellular vesicles (EVs) influence a host of normal and pathophysiological processes in vivo. Compared to soluble mediators, EVs are relatively large (~30-150 nm) and can traffic a wide range of proteins on their surface including extracellular matrix (ECM) binding proteins. We isolated EVs from the MCF10 series - a model human cell line of breast cancer progression - and demonstrated increasing presence of laminin-binding integrins 3{beta}1 and 6{beta}1 on the EVs as the malignant potential of the MCF10 cells increased. Transport of the EVs within a microfluidic device under controlled physiological interstitial flow (0.15-0.75 m/s) demonstrated that convection was the dominant mechanism of transport. Binding of the EVs to the ECM enhanced the spatial concentration and gradient, which was partially mitigated by blocking integrins 3{beta}1 and 6{beta}1. Our studies demonstrate that convection and ECM binding are the dominant mechanisms controlling EV interstitial transport and should be leveraged in the design of nanotherapeutics.

bioengineering↗

bioRxiv2021

Rapid diversification of the Australian Amitermes group during late Cenozoic climate change

Late Cenozoic climate change led to the progressive aridification of Australia over the past 15 million years. This gradual biome turnover fundamentally changed Australias ecosystems, opening new niches and prompting diversification of plants and animals. One example is the Australian Amitermes Group (AAG), consisting of the Australian Amitermes and affiliated genera. Although it represents the most speciose and diverse higher termite group in Australia, little is known about its evolutionary history. We used ancestral range reconstruction and diversification analyses to illuminate 1) the origin and phylogenetic relationships of the AAG, 2) biogeographical processes leading to the current continent-wide distribution, and 3) timing and pattern of diversification in the context of late Cenozoic climate change. By estimating the first time-calibrated phylogeny, we show that the AAG is a monophyletic group, whose ancestor arrived ~11-10 million years ago from Southeast Asia. Ancestral range reconstruction indicates that Australias monsoon region was the launching point for a continental radiation that has been shaped by range expansions and within-area speciation rather than vicariance. We found that multiple arid species diversified from mesic and tropical ancestors in the Plio-Pleistocene, but also observed diversification in the opposite direction. Finally, we show that two pulses of rapid diversification coincided with past climate change during the late Miocene and early Pliocene. Consistent with rapid diversification, species accumulation slowed, likely caused by progressive niche saturation. This study provides a stepping stone for predicting the future response of Australias termite fauna in the face of human-mediated climate change.

evolutionary biology↗

bioRxiv2020

Haplotype divergence supports ancient asexuality in the oribatid mite Oppiella nova

Sex strongly impacts genome evolution via recombination and segregation. In the absence of these processes, haplotypes within lineages of diploid organisms are predicted to accumulate mutations independently of each other and diverge over time. This so-called Meselson effect is regarded as a strong indicator of the long-term evolution under obligate asexuality. Here, we present genomic and transcriptomic data of three populations of the asexual oribatid mite species Oppiella nova and its sexual relative Oppiella subpectinata. We document strikingly different patterns of haplotype divergence between the two species, strongly supporting Meselson effect like evolution and ancient asexuality in O. nova: (I) Variation within individuals exceeds variation between populations in O. nova but vice versa in O. subpectinata. (II) Two O. nova sub-lineages feature a high proportion of heterozygous genotypes and lineage-specific haplotypes, indicating that haplotypes diverged independently within the two lineages after their split. (III) The deepest split in gene trees generally separates haplotypes in O. nova, but populations in O. subpectinata. (IV) Tree topologies of the two haplotypes match each other. Our findings provide positive evidence for the absence of sex over evolutionary time in O. nova and suggest that asexual oribatid mites can escape the dead-end fate usually associated with asexual lineages.

evolutionary biology↗

bioRxiv2020

Systematic evaluation of genome sequencing as a first-tier diagnostic test for prenatal and pediatric disorders

Current clinical guidelines recommend three genetic tests for the assessment of fetal structural anomalies: karyotype to detect microscopically-visible balanced and unbalanced chromosomal rearrangements, chromosomal microarray (CMA) to detect sub-microscopic copy number variants (CNVs), and exome sequencing (ES) to identify individual nucleotide changes in coding sequence. Advances in genome sequencing (GS) analysis suggest that it is poised to displace the sequential application of all three conventional tests to become a single diagnostic approach for the assessment of fetal structural anomalies. However, systematic benchmarking is required to assure that GS can capture the full mutational spectrum associated with fetal structural anomalies and to accurately quantify the added diagnostic yield of GS. We applied a novel GS analytic framework that included the discovery, filtration, and interpretation of nine classes of genomic variation to 7,195 individuals. We assessed the sensitivity of GS to detect diagnostic variants (pathogenic or likely pathogenic) from three standard-of-care tests using 1,612 autism spectrum disorder quartet families (ASD; n=6,448) with matched GS, ES, and CMA data, and validated these findings in 46 fetuses with a clinically reportable variant originally identified by karyotype, CMA, or ES. We then assessed the added diagnostic yield of GS in 249 trios (n=747) comprising a fetus with a structural anomaly detected by ultrasound and two unaffected parents that were pre-screened with a combination of all three standard-of-care tests. Across both cohorts, our GS analytic framework identified 98.2% of all diagnostic variants detected by standard-of-care tests, including 100% of those originally detected by CMA (n=88) and ES (n=61), as well as 78.6% (n=11/14) of the chromosomal rearrangements identified by karyotype. The diagnostic yield from GS was 7.8% across all 1,612 ASD probands, almost two-fold more than CMA (4.4%) and three-fold more than ES (3.0%). We also demonstrated that the yield of ES can approach that of GS when CNVs are captured with high sensitivity from exome data (7.4% vs. 7.8%, respectively). In 249 pre-screened fetuses with structural anomalies, GS provided an additional diagnostic yield of 0.4% beyond the combination of all three tests (karyotype, CMA, and ES). Applying our benchmarking results to existing data indicates that GS can achieve an overall diagnostic yield of 46.1% in unselected fetuses with fetal structural anomalies, providing an estimated 17.2% increase in diagnostic yield over karyotype, 14.1% over CMA, and 36.1% over ES when sequence variants are assessed, and 4.1% when CNVs are also identified from exome data. In this study we demonstrate that GS is sensitive to the detection of almost all pathogenic variation captured by karyotype, CMA, and ES, provides a superior diagnostic yield than any individual test by a wide margin, and contributes a modest increase in diagnostic yield beyond the combination of all three tests. We also outline several strategies to aid the interpretation of GS variants that are cryptic to conventional technologies, which we anticipate will be increasingly encountered as comprehensive variant identification from GS is performed. Taken together, these data suggest GS warrants consideration as a first-tier diagnostic approach for fetal structural anomalies.

genomics↗

bioRxiv2020

A learned map for places and concepts in the human MTL

Distinct lines of research in both humans and animals point to a specific role of the hippocampus in both spatial and episodic memory function. The discovery of concept cells in the hippocampus and surrounding medial-temporal lobe (MTL) regions suggests that the MTL maps physical and semantic spaces with a similar neural architecture. Here, we studied the emergence of such maps using MTL micro-wire recordings from 20 patients navigating a virtual environment featuring salient landmarks with established semantic meaning. We present several key findings: The array of local field potentials in the MTL contains sufficient information to decode subjects instantaneous location in the environment. Closer examination revealed that the field potentials represent both the subjects locations in virtual space and in high-dimensional semantic space. We further show that both spatial and semantic representations strengthen over time. This learning effect appears as subjects increase their knowledge of the environments spatial and semantic layout. Similarly, we observe a learning effect on temporal sequence coding. Over time, field potentials come to represent future locations, even after controlling for spatial proximity. This predictive coding of future states, more so than the strength of spatial representations per se, explains variability in subjects navigation performance. Our results thus support the conceptualization of the MTL as a memory space, building semantic knowledge, spatial and non-spatial, from episodic experience to plan future actions and predict their outcomes. Significance statementUsing rare micro-wire recordings, we studied the representation of spatial, semantic and temporal information in the human MTL. Our findings demonstrate that subjects acquire a cognitive map that simultaneously represents the spatial and semantic relations between landmarks. We further show that the same learned representation is used to predict future states, implicating MTL cell assemblies as the building blocks of prospective memory functions.

neuroscience↗

bioRxiv2020

A neural code of egocentric spatial information in human medial temporal lobe

Spatial navigation relies on neural systems that encode information about places, distances, and directions in relation to the external world or relative to the navigating organism. Since the proposal of cognitive maps, the neuroscience of navigation has focused on allocentric (world-referenced) neural representations including place, grid, and head-direction cells. Here, using single-neuron recordings during virtual navigation, we identify "anchor cells" in the human brain as a neural code for egocentric (self-centered) spatial maps: Anchor cells represent egocentric directions towards "anchor points" located in the environmental center or periphery. Anchor cells were abundant in parahippocampal cortex, supported full vectorial representations of egocentric space, and were integrated into a neural memory network. Neurons encoding allocentric direction complemented anchor-cell activity, potentially assisting anchor cells in transforming percepts into allocentric representations. Anchor cells may facilitate egocentric navigation strategies, may support route planning from egocentric viewpoints, and may underlie the first-person perspective in episodic memories.

neuroscience↗

bioRxiv2018

Reactivated spatial context guides episodic recall

The medial temporal lobe (MTL) is known as the locus of spatial coding and episodic memory, but the interaction between these cognitive domains, as well as the extent to which they rely on common neurophysiological mechanisms is poorly understood. Here, we use a hybrid spatial-episodic memory task to determine how spatial information is dynamically reactivated in sub-regions of the MTL and how this reactivation guides recall of episodic information. Our results implicate theta oscillations across the MTL as a common neurophysiological substrate for spatial coding in navigation and episodic recall. We further show that spatial context information is initially retrieved in the hippocampus (HC) and subsequently emerges in the parahippocampal gyrus (PHG). Finally, we demonstrate that hippocampal theta phase modulates parahippocampal gamma amplitude during retrieval of spatial context, suggesting a role for cross frequency coupling in coding and transmitting retrieved spatial information.

neuroscience↗