Biology subjects

Spitzer, B.

Publications and source records attributed to Spitzer, B..

15 recordsLinked to original sources

bioRxiv2026

Abstract and Concrete Working Memory Information in Human Visual Cortex

Neural correlates of visuospatial working memory (WM) information have been found in frontal, parietal, and early visual areas, but the principles by which distributed WM storage is topographically organised remain subject to debate. Here, we used functional magnetic resonance imaging, representational geometry analysis, and vision models to examine the extent to which WM representations across the cortical hierarchy may differ in terms of visuospatial abstraction. During retro-cued WM maintenance of rotated real-world objects, we found robust encoding of the objects orientation in both parietal and occipital visual areas. The representational format of this encoding was independent of the objects physical appearance and was surprisingly invariant across areas, indicating a high level of visuospatial abstraction even in the early visual cortex. Interestingly, we also found evidence for an orthogonal, object-specific orientation representation within the same areas, likely reflecting the sample stimulis concrete visual appearance. The latter--but not the former--type of distributed representation emerged also in a contemporary vision model. Together, the findings indicate the widespread co-existence of abstract (generalised) and concrete-visual representations multiplexed within the same brain areas. In contrast, prototypical orientation biases emerged only in the parietal cortex, suggesting a distinction between generalisation and categorisation in WM abstraction.

neuroscience↗

bioRxiv2024

Long-Term Effects of Working Memory Retrieval From Prioritized and Deprioritized States

Which factors determine whether information temporarily held in working memory (WM) can later be remembered from long-term memory (LTM)? Previous work has shown that retrieving ("testing") memories from LTM can benefit their future LTM recall. Here, we examined the extent to which a benefit for subsequent LTM may also occur after retrieval from WM, depending on whether the WM contents were retrieved from a prioritized or deprioritized state. In three experiments, we combined variants of a novel visual WM paradigm with a subsequent surprise LTM recall test. We found a LTM benefit of WM testing both for prioritized and deprioritized WM contents, which, interestingly, was stronger for the deprioritized information. This pattern showed similarly across experiments with different priority manipulations. Subsequent LTM benefits generally occurred after WM testing with a recall-like test format (continuous report), but not after simple WM comparisons against a probe. The surprisingly larger LTM benefit for deprioritized WM contents may reflect enhanced encoding of the participants own subjective WM report - as opposed to the originally presented sample information - into LTM.

neuroscience↗

bioRxiv2024

Asymmetric learning and adaptability to changes in relational structure during transitive inference

Humans and other animals can generalise from local to global relationships in a transitive manner. Recent research has shown that asymmetrically biased learning, where beliefs about only the winners (or losers) of local comparisons are updated, is well-suited for inferring relational structures from sparse feedback. However, less is known about how belief-updating biases intersect with humans capacity to adapt to changes in relational structure, where re-valuing an item may have downstream implications for inferential knowledge pertaining to unchanged items. We designed a transitive inference paradigm involving one of two possible changepoints for which an asymmetric (winner-or loser-biased) learning policy was more or less optimal. Participants (N=83) exhibited differential sensitivity to changes in relational structure: whereas participants readily learned that a hitherto low-ranking item increased its rank, moving a high-ranking item down the hierarchy impaired downstream inferential knowledge. Behaviour best captured by an adaptive reinforcement learning model which exhibited a predominantly winner-biased learning policy but also modulated its degree of asymmetry as a function of its choice preference strength. Our results indicate that asymmetric learning not only accounts for efficient inference of latent relational structures, but also for differences in the ease with which learners accommodate structural changes. Author SummaryWhen reasoning about relationships between objects, events, or people, humans can readily use previous experiences to infer relations that they have never encountered before. For example, if Anna beats Bruce at tennis, and Bruce beats Clara, then one can predict that Anna will likely also beat Clara. Human learning in such transitive inference problems tends to be winner-biased - that is, upon observing Annas victory over Bruce, a spectator would be more likely to attribute this outcome to Annas skill than to Bruces lack thereof. However, in a constantly changing world whose comparative relations are rarely static, humans must also be able to infer how changes in the outcomes of certain comparisons bear on other relationships within a transitive hierarchy. Combining behavioural testing and computational modelling, we show that a learning strategy that preferentially focuses on the winners of comparisons induces greater flexibility for certain types of hierarchy changes than for others. In addition, we provide evidence that humans may dynamically adjust their degree of learning asymmetry according to the current strength of their beliefs about the relations under comparison.

neuroscience↗

bioRxiv2022

Geometry of visual working memory information in human gaze patterns

Stimulus-dependent eye movements have been recognized as a potential confound in decoding visual working memory information from neural signals. Here, we combined eye-tracking with representational geometry analyses to uncover the very information in miniature gaze patterns while participants (n = 41) were cued to maintain visual object orientations. Although participants were discouraged from breaking fixation via real-time feedback, small gaze shifts (< 1 degree) robustly encoded the to-be-maintained stimulus orientation, with evidence for encoding two sequentially presented orientations at the same time. While the orientation encoding upon stimulus presentation was object-specific, it changed to a more object-independent format during cued maintenance, particularly when attention had been temporarily withdrawn from the memorandum. Finally, categorical reporting biases increased after unattended storage, with indications of biased gaze geometries emerging already during the maintenance periods prior to behavioral reporting. These findings disclose a wealth of information in gaze patterns during visuospatial working memory, and suggest systematic changes in representational format when memory contents have been unattended.

neuroscience↗

bioRxiv2022

Clonal evolution during metastatic spread in high-risk neuroblastoma

High-risk neuroblastoma is generally metastatic and often lethal. Using genomic profiling of 470 sequential and spatially separated samples from 283 patients, we characterize subtype-specific genetic evolutionary trajectories from diagnosis, through progression and end-stage metastatic disease. Clonal tracing timed disease initiation to embryogenesis. Continuous acquisition of structural variants at disease defining loci (MYCN, TERT, MDM2-CDK4) followed by convergent evolution of mutations targeting shared pathways emerged as the predominant feature of progression. At diagnosis metastatic clones were already established at distant sites where they could stay dormant, only to cause relapses years later and spread via metastasis-to-metastasis and polyclonal seeding after therapy.

genomics↗

bioRxiv2022

Prioritization of semantic over visuo-perceptual aspects in multi-item working memory

Working Memory (WM) keeps information temporarily available for upcoming tasks. How the contents of WM are distinguished from perceptual representations on the one hand, and from long-term memories on the other, is still debated. Here, we leveraged recent evidence for a reversal of processing dynamics when retrieving episodic long-term memories as opposed to perceiving visual input. In two experiments (n=75 and n=103), we asked participants to hold one or more items in WM and to report their low-level perceptual and high-level semantic qualities. In both experiments, we found faster responses to the items semantic qualities, indicating prioritization over visuo-perceptual aspects, when two or more items were held concurrently in WM. These dynamics of accessing information in multi-item WM were akin to those in retrieving episodic long-term memories and opposite to those in processing visual inputs. Little to no semantic prioritization was evident during single-item maintenance, consistent with a strictly capacity-limited focus of attention within which WM information can be transformed into a prospective action plan.

neuroscience↗

bioRxiv2022

EEG-representational geometries and psychometric distortions in approximate numerical judgment

When judging the average value of sample stimuli (e.g., numbers) people tend to either over- or underweight extreme sample values, depending on task context. In a context of overweighting, recent work has shown that extreme sample values were overly represented also in neural signals, in terms of an anti-compressed geometry of number samples in multivariate electroencephalography (EEG) patterns. Here, we asked whether neural representational geometries may also reflect underweighting of extreme values (i.e., compression) which has been observed behaviorally in a great variety of tasks. We used a simple experimental manipulation (instructions to average a single-stream or to compare dual-streams of samples) to induce compression or anti-compression in behavior when participants judged rapid number sequences. Model-based representational similarity analysis (RSA) replicated the previous finding of neural anti-compression in the dual-stream task, but failed to provide evidence for neural compression in the single-stream task, despite the evidence for compression in behavior. Instead, the results suggested enhanced neural processing of extreme values in either task, regardless of whether extremes were over- or underweighted in subsequent behavioral choice. We further observed more general differences in the neural representation of the sample information between the two tasks. The results suggest enhanced processing of extreme values as the brains default. Such a default raises new questions about the origin of common psychometric distortions, such as diminishing sensitivity for larger values.

neuroscience↗

bioRxiv2021

Control over sampling boosts numerical evidence processing in human decisions from experience

When acquiring information about choice alternatives, decision makers may have varying levels of control over which and how much information they sample before making a choice. How does control over sampling affect the quality of experience-based decisions? Here, combining variants of a numerical sampling task with neural recordings, we show that control over when to stop sampling can enhance (i) behavioral choice accuracy, (ii) the build-up of parietal decision signals, and (iii) the encoding of numerical sample information in multivariate electroencephalogram (EEG) patterns. None of these effects were observed when participants could only control which alternatives to sample, but not when to stop sampling. Furthermore, levels of control had no effect on early sensory signals or on the extent to which sample information leaked from memory. The results indicate that freedom to stop sampling can amplify decisional evidence processing from the outset of information acquisition and lead to more accurate choices.

neuroscience↗

bioRxiv2021

Asymmetric learning facilitates human inference of transitive relations

Humans and other animals are capable of inferring never-experienced relations (e.g., A>C) from other relational observations (e.g., A>B and B>C). The processes behind such transitive inference are subject to intense research. Here, we demonstrate a new aspect of relational learning, building on previous evidence that transitive inference can be accomplished through simple reinforcement learning mechanisms. We show in simulations that inference of novel relations benefits from an asymmetric learning policy, where observers update only their belief about the winner (or loser) in a pair. Across 4 experiments (n=145), we find substantial empirical support for such asymmetries in inferential learning. The learning policy favoured by our simulations and experiments gives rise to a compression of values which is routinely observed in psychophysics and behavioural economics. In other words, a seemingly biased learning strategy that yields well-known cognitive distortions can be beneficial for transitive inferential judgments.

neuroscience↗

bioRxiv2020

Concurrent visual working memory bias in perception and decision making

Previous work has shown bidirectional crosstalk between Working Memory (WM) and perception such that the contents of WM can alter concurrent percepts and vice versa. Here, we examine WM-perception interactions in a new task setting. Participants judged the proportion of colored dots in a stream of visual displays while concurrently holding location- and color information in memory. Spatiotemporally resolved psychometrics disclosed a modulation of perceptual sensitivity consistent with a bias of visual spatial attention towards the memorized location. However, this effect was short-lived, suggesting that the visuospatial WM information was rapidly deprioritized during processing of new perceptual information. Independently, we observed robust bidirectional biases of categorical color judgments, in that perceptual decisions and mnemonic reports were attracted to each other. These biases occurred without reductions in overall perceptual sensitivity compared to control conditions without a concurrent WM load. The results conceptually replicate and extend previous findings in visual search and suggest that crosstalk between WM and perception can arise at multiple levels, from sensory-perceptual to decisional processing.

neuroscience↗

bioRxiv2019

Oncologic Therapy Shapes the Fitness Landscape of ClonalHematopoiesis

Clonal hematopoiesis (CH) is frequent in cancer patients and associated with increased risk of therapy related myeloid neoplasms (tMN). To define the relationship between CH, oncologic therapy, and tMN progression, we studied 24,439 cancer patients. We show that previously treated patients have increased rates of CH, with enrichment of mutations in DNA Damage Response (DDR) genes (TP53, PPM1D, CHEK2). Exposure to radiation, platinum and topoisomerase II inhibitors have the strongest association with CH with evidence of dose-dependence and gene-treatment interactions. We validate these associations in serial sampling from 525 patients and show that exposure to cytotoxic and radiation therapy imparts a selective advantage specifically in hematopoietic cells with DDR mutations. In patients who progressed to tMN, the clone at CH demarcated the dominant clone at tMN diagnosis. CH mutational features predict risk of therapy-related myeloid neoplasm in solid tumor patients with clinical implications for early detection and treatment decisions.

genetics↗

bioRxiv2019

Impaired Desynchronization of Beta Activity Underlies Memory Deficits in People with Parkinson’s Disease

There is a pressing need to better understand the mechanisms underpinning the increasingly recognised non-motor deficits in Parkinsons disease. Brain activity during Parkinsons disease is excessively synchronized within the beta range (12-30Hz). However, relatively little is known about how the abnormal beta rhythms impact on non-motor symptoms. In healthy adults, beta desynchronization is necessary for successful episodic memory formation. We investigated whether there was a direct relationship between decreased beta modulation and memory formation in Parkinsons disease. Electroencephalography recordings were made during an established memory-encoding paradigm. Parkinsons participants showed impaired memory strength (P = 0.023) and reduced beta desynchronization (P = 0.014) relative to controls. Longer disease duration was correlated with a larger reduction in beta desynchronization, and a concomitant reduction in memory performance. These novel results extend the notion that pathological beta activity is causally implicated in the motor and (lesser appreciated) non-motor deficits inherent to Parkinsons disease.

neuroscience↗

bioRxiv2019

Selective integration during sequential sampling in posterior neural signals

Decisions are typically made after integrating information about multiple attributes of alternatives in a choice set. The computational mechanisms by which this integration occurs have been a focus of extensive research in humans and other animals. Where observers are obliged to consider attributes in turn, a framework known as \"selective integration\" can capture salient biases in human choices. The model proposes that successive attributes compete for processing resources and integration is biased towards the alternative with the locally preferred attribute. Quantitative analysis shows that this model, although it discards choice-relevant information, is optimal when the observers decisions are corrupted by noise that occurs beyond the sensory stage. Here, we used scalp electroencephalographic (EEG) recordings to test a neural prediction of the model: that locally preferred attributes should be encoded with higher gain in neural signals over posterior cortex. Over two sessions, human observers (of either sex) judged which of two simultaneous streams of bars had the higher (or lower) average height. The selective integration model fit the data better than a rival model without bias. Single-trial analysis showed that neural signals contralateral to the preferred attribute covaried more steeply with the decision information conferred by locally preferred attributes. These findings provide neural evidence in support of selective integration, complementing existing behavioural work.\n\nSignificance StatementWe often make choices about stimuli with multiple attributes, such as when deciding which car to buy on the basis of price, performance and fuel economy. A model of the choice process, known as selective integration, proposes that rather than taking all of the decision-relevant information equally into account when making choices, we discard or overlook a portion of it. Although information is discarded, this strategy can lead to better decisions when memory is limited. Here, we test and confirm predictions of the model about the brain signals that occur when different stimulus attributes of stimulus are being evaluated. Our work provides the first neural support for the selective integration model.

neuroscience↗

bioRxiv2018

Neural structure mapping in human probabilistic reward learning

Humans can learn abstract concepts that describe invariances over relational patterns in data. One such concept, known as magnitude, allows stimuli to be compactly represented by a single dimension (i.e. on a mental line), for example according to their cardinality, size or value. Here, we measured representations of magnitude in humans by recording neural signals whilst they viewed symbolic numbers. During a subsequent reward-guided learning task, the neural patterns elicited by novel complex visual images reflected their pay-out probability in a way that suggested they were encoded onto the same mental number line. Our findings suggest that in humans, learning about values is accompanied by structural alignment of value representations with neural codes for the concept of magnitude.

neuroscience↗

bioRxiv2017

MEF2C phosphorylation is required for chemotherapy resistance in acute myeloid leukemia

HIGHLIGHTSO_LIMEF2C S222 phosphorylation is a specific marker of chemotherapy resistance in diagnostic AML patient specimens.\nC_LIO_LIMEF2C S222 phosphorylation is dispensable for normal hematopoiesis in mice, as established using genome editing in vivo, but is required for MLL-AF9 induced leukemogenesis.\nC_LIO_LIMARK kinases specifically phosphorylate MEF2C S222, potentiating its transcriptional activity.\nC_LIO_LIChemical inhibition of MARK-induced MEF2C phosphorylation overcomes chemotherapy resistance of and exhibits selectivity toxicity against MEF2C-activated human AML cells.\nC_LI\n\nSUMMARYIn acute myeloid leukemia, chemotherapy resistance remains prevalent and poorly understood. Using functional proteomics of patient AML specimens, we identified MEF2C S222 phosphorylation as a specific marker of primary chemoresistance. We found that Mef2cS222A/S222A knock-in mutant mice engineered to block MEF2C phosphorylation exhibited normal hematopoiesis, but were resistant to leukemogenesis induced by MLL-AF9. MEF2C phosphorylation was required for leukemia stem cell maintenance, and induced by MARK kinases in cells. Treatment with the selective MARK inhibitor MRT199665 caused apoptosis of MEF2C-activated human AML cell lines and primary patient specimens, but not those lacking MEF2C phosphorylation. These findings identify kinase-dependent dysregulation of transcription factor control as a determinant of therapy response in AML, with immediate potential for improved diagnosis and therapy for this disease.

cancer biology↗