Biology subjects

Lisi, M.

Publications and source records attributed to Lisi, M..

14 recordsLinked to original sources

bioRxiv2026

Eye movement markers of relational encoding predict scene memory precision

Recalling scenes and events depends on how information is relationally organised in memory, but it is unclear whether the organisation of eye movements during encoding, rather than simply how much is explored, shapes what is remembered. Using a scene-viewing paradigm and drawing-based free recall task to capture the content and structure of remembered scenes, we examined whether scene memory was better explained by 'lower-order' measures reflecting the magnitude and spatial extent of sampling, or 'higher-order' measures capturing gaze organisation and temporal dynamics. Relative to lower-order measures (number of fixations and scanpath length), memory precision was better predicted by repeated sampling of viewed regions (refixations) and gaze distributions (stationary gaze entropy) during encoding. Thus, the organisation of visual attention, rather than sampling quantity, contributed to scene representations that preserved relationships between elements. These findings highlight a role for spatial gaze dynamics in optimally encoding organised, relational scene representations for episodic memory.

animal behavior and cognition↗

bioRxiv2025

Protective effect of prior knowledge in ageing

Visual perception depends on both sensory input and prior knowledge, and the quality of these information sources changes across the lifespan. As people age, accumulated knowledge, and its influence on perception, tend to increase, while declines in low-level visual functions reduce input quality and bias perception toward prior information. Yet, the combined effects of these changes on higher-level visual perception remain unclear, partly because concurrent cognitive decline may complicate the use of stored knowledge. In this study, we examined how prior knowledge shapes visual perception in younger (<40 years) and older (>60 years) adults using ambiguous two-tone images, whose recognition depends on prior knowledge. Providing participants with the original photographs used to generate the two-tones triggered perceptual reorganisation, improving recognition in both groups. Although older adults recognised fewer two-tones overall - a pattern linked to reduced visual acuity - they showed a comparable benefit from prior knowledge when cued. These findings suggest that, despite age-related sensory decline, the ability to draw on prior knowledge remains robust in older adulthood and may help preserve perceptual function.

neuroscience↗

bioRxiv2025

Reduced susceptibility to experimentally-induced complex visual hallucinations with age

Visual hallucinations occur across many clinical conditions, but can also be induced experimentally in healthy individuals, using high-frequency flicker (Ganzflicker) and sensory deprivation (Ganzfeld). It is unclear how hallucinatory proneness changes across the lifespan, with prior questionnaire-based studies showing mixed results. As factors such as multi-sensory acuity loss and relatively increased reliance on prior knowledge may increase as we age, and these are considered risk factors for hallucination proneness, we hypothesised that reported decreases in hallucinations might reflect stigma-related underreporting. We therefore sought to measure hallucination proneness in 44 healthy adults spanning the adult lifespan (younger age group; n=22; age 19-39 years, mean 27.2 {+/-} 5.5; older age group n=22; age 59-79 years, mean 68.0 {+/-} 5.8), quantifying the tendency to experience complex and simple hallucinations in an experimental environment designed to elicit hallucinations. We find that reports of complex hallucinations (those representing objects, scenes, etc) are lower in older adults than in younger adults, both in real time and retrospectively. None of our measured cognitive or sensory measures (visual acuity, contrast sensitivity, perceptual reorganisation, imagery vividness, memory inhibition, and suggestibility) mediate this relationship. We conclude that reduced complex hallucination proneness appears normative in ageing, and that experiencing hallucinations in older individuals may signal underlying pathology.

neuroscience↗

bioRxiv2024

An fMRI-based Approach for Measuring Contrast Sensitivity Across the Visual Field in Visual Cortex

Peripheral vision is crucial for daily activities and quality of life, yet traditional measures of visual function like visual acuity primarily assess central vision. Visual field tests can evaluate peripheral vision but require extended focus combined with precise fixation, often very challenging for patients with severe sight loss. Functional MRI (fMRI) with population receptive field (pRF) mapping offers a non-invasive way to map scotomas but is limited by its reliance on single contrast levels and the necessity of accurate fixation. We developed an fMRI-based approach to measure contrast sensitivity across the visual field without the need for precise fixation. By combining large-field stimulation with varying spatial frequencies and contrast levels with either pRF mapping or a retinotopic atlas based on anatomical landmarks, we modeled contrast sensitivity in the primary visual cortex (V1) over a large (40 deg) expanse of the visual field. In seven normal-sighted participants, we characterized differences in V1 cortical sensitivity across eccentricities and visual quadrants, finding reliable and reproducible patterns of sensitivity differences at individual and session levels. To assess the methods tolerance to fixation variability, we further investigated how different levels of eye movement affect cortical sensitivity patterns in two participants. We found that cortical sensitivity patterns were largely preserved across eye movement, particularly at low spatial frequencies. This suggests that our approach can accommodate several degrees of fixation instability, making it suitable for populations with unstable or biased fixation for whom visual field maps are harder to acquire behaviorally (e.g., patients with dense central scotoma or strabismus). Additionally, our method effectively visualized cases of simulated and disease-linked sensitivity loss at the cortical level. Crucially, we demonstrated that these results could be largely recovered using a structure-based retinotopic atlas, eliminating the need for pRF mapping and precise fixation - although such an approach reduced sensitivity. This approach, integrating large-field stimulation with a retinotopic atlas, offers a promising tool for monitoring vision loss and recovery in patients with various visual impairments, addressing a significant challenge in current clinical assessments.

neuroscience↗

bioRxiv2024

Human BNST volume is not simply sexually dimorphic

The bed nucleus of the stria terminalis (BNST) is a sexually dimorphic basal forebrain region is a claim prevalent across rodent and human neuroscience research, arising from the observation that it is substantially larger in male versus female brains. Despite the pervasiveness of this claim, which may have implications for understanding sex differences in anxiety and substance use disorders, inspection of prior literature reveals a complex and nuanced picture. Research on volumetric human BNST sex differences comes from a handful of mostly small-scale post-mortem studies and two MRI studies, between them reporting no, moderate, or very large differences. This indicates the need for a more detailed systematic investigation. Addressing this, we developed a novel 3T T1-weighted (T1w) manual segmentation protocol for the BNST, which was applied to sub-millimetre resolution T1w structural MRI data in 170 young human adults. Using a Bayesian modelling approach, taking into account existing data and accounting for total brain volume, age, and sibship, we find substantial evidence favouring no sex difference in total BNST volume. We recommend that researchers exercise caution when reporting evidence of BNST sexual dimorphism, particularly when translating findings from rodent models in which the BNST may play a different, olfaction-focused, role.

neuroscience↗

bioRxiv2023

M6A reduction relieves FUS-associated ALS granules

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease due to gradual motorneurons (MN) degeneration1. Among the processes associated to ALS pathogenesis, there is the formation of cytoplasmic inclusions produced by mutant protein aggregation, among which the RNA binding protein FUS2. In this work we show that such inclusions are significantly reduced in number and dissolve faster when the RNA m6A content is diminished as a consequence of the m6A writer METTL3 knock-down. These effects were observed both in neuronal cell lines and in iPSC-derived human motor neurons expressing mutant FUS. Importantly, stress granules formed in ALS condition showed a distinctive transcriptome with respect to control cells; interestingly, after METTL3 downregulation, it reverted to similar to control. Finally, we show that FUS inclusions are reduced also in patient-derived fibroblasts treated with STM-2457, a well characterized inhibitor of METTL3 activity, paving the way for its possible use for counteracting aggregate formation in ALS.

molecular biology↗

bioRxiv2023

Flicker and Ganzfeld induced visual hallucinations differ in frequency and content

Hallucinatory experiences, defined as perception in the absence of external stimuli, can occur in both pathological and non-pathological states and can be broadly phenomenologically divided into those of a simple and a complex nature. Non-pathological visual hallucinations can be induced experimentally using a variety of stimulation conditions. To assess whether these techniques drive a shared underlying hallucinatory mechanism, despite these differences, we compared two methods: flicker and perceptual deprivation (Ganzfeld). Specifically, we measured the frequency and complexity of the hallucinations produced by these techniques. We utilised button press, retrospective drawing, interviews, and questionnaires to quantify hallucinatory experience in 20 participants. With both experimental techniques, we found that simple hallucinations were more common than complex hallucinations. We also found that on average, flicker was more effective than Ganzfeld at eliciting a higher number of hallucinations, though Ganzfeld hallucinations were longer than flicker hallucinations. There was no interaction between experimental condition and hallucination complexity, suggesting that the increased bottom-up visual input in flicker increased both simple and complex hallucinations similarly. A correlation was observed between the total proportional time spent hallucinating in flicker and Ganzfeld, which was replicated in a retrospective questionnaire measure of experienced intensity, suggesting a shared hallucinatory mechanism between the two methodologies. We attribute these findings to a shared low-level core hallucinatory mechanism, such as excitability of visual cortex, which is amplified in flicker compared to Ganzfeld due to heightened bottom-up input.

neuroscience↗

bioRxiv2023

Immortalization and transformation of primary cells mediated by engineered ecDNAs

Focal gene amplifications are among the most common cancer-associated mutations, but their evolution and contribution to tumorigenesis have proven challenging to recapitulate in primary cells and model organisms. Here we describe a general approach to engineer large (>1 Mbp) focal amplifications mediated by extrachromosomal circular DNAs (ecDNAs, also known as "double minutes") in a spatiotemporally controlled manner in cancer cell lines and in primary cells derived from genetically engineered mice. With this strategy, ecDNA formation can be coupled with expression of fluorescent reporters or other selectable markers to enable the identification and tracking of ecDNA-containing cells. We demonstrate the feasibility of this approach by engineering MDM2-containing ecDNAs in near-diploid human cells, showing that GFP expression can be used to track ecDNA dynamics under physiological conditions or in the presence of specific selective pressures. We also apply this approach to generate mice harboring inducible Myc- and Mdm2-containing ecDNAs analogous to those spontaneously occurring in human cancers. We show that the engineered ecDNAs rapidly accumulate in primary cells derived from these animals, promoting proliferation, immortalization, and transformation.

cancer biology↗

bioRxiv2022

Emergence of perceptual reorganisation from prior knowledge in human development and Convolutional Neural Networks

Perception in the mature human visual system relies heavily on prior knowledge. Here we show for the first time that prior-knowledge-induced reshaping of visual perception emerges gradually, and late in childhood. To isolate the effects of prior knowledge on vision, we presented 4-to-12-year-olds and adults with two-tone images, which are degraded photos that are hard to recognise on first viewing. In adults, seeing the original photo causes a perceptual reorganisation leading to sudden, mandatory recognition of the two-tone version - a well-documented process relying on top-down signalling from higher-order brain areas to early visual cortex. We find that children younger than 7 to 9 years, however, do not experience this knowledge-guided shift, despite viewing the original photo immediately before each two-tone. To assess potential computations underlying this development we compared human performance to three state-of-the-art neural networks with varying architectures. We found that the best-performing architecture behaved much like 4- to 5-year-old humans, who display a feature-based rather than holistic processing strategy akin to neural networks. Our results reveal a striking age-related shift in the reconciliation of prior knowledge with sensory input, which may underpin the development of many perceptual abilities.

neuroscience↗

bioRxiv2022

Different integration of conflicting motion signals in perception and eye movements during object tracking

The ability to accurately perceive and track moving objects is crucial for many everyday activities. In this study, we use a "double-drift stimulus" Lisi and Cavanagh (2015); Shapiro et al. (2010); Tse and Hsieh (2006) to explore the processing of visual motion signals that underlie perception, pursuit, and saccade responses to a moving object. Participants were presented with peripheral moving apertures filled with noise that either drifted orthogonally to the apertures direction or had no net motion. Participants were asked to saccade to and track these targets with their gaze as soon as they appeared, and then to report their direction. In the trials with internal motion, the target disappeared at saccade onset so that the first 100 ms of the post-saccadic pursuit response was driven uniquely by peripheral information gathered before saccade onset. This provided independent measures of perceptual, pursuit, and saccadic responses to the double-drift stimulus on a trial-by-trial basis. Our analysis revealed systematic differences between saccadic responses on one hand and perceptual and pursuit responses on the other. These differences are unlikely to be caused by differences in the processing of motion signals because saccade and pursuit appear to use a common motion processing mechanism (e.g., Erkelens, 2006; Fleuriet and Goffart, 2012). We conclude that our results are instead due to a difference in how the processing mechanisms underlying perception, pursuit, and saccades combine motor signals with target position. These findings advance our understanding of the mechanisms underlying dissociation in visual processing between perception and eye movements.

neuroscience↗

bioRxiv2022

Exploring the frame effect

Probes flashed within a moving frame are dramatically displaced (Ozkan et al, 2021; Wong &Mack, 1981). The effect is much larger than that seen on static or moving probes (induced motion, Duncker, 1929; Wallach et al, 1978). These flashed probes are often perceived with the separation they have in frame coordinates -- a 100% effect. Here we explore this frame effect on flashed tests with several versions of the standard stimulus. We find that the frame effect holds for smoothly or abruptly displacing frames, even when the frame changed shape or orientation between the endpoints of its travel. The path could be non-linear, even circular. The effect was driven by perceived not physical motion. When there were competing overlapping frames, the effect was determined by which frame was attended. There were a number of constraints that limited the effect. A static anchor near the flashes suppressed the effect but an extended static texture did not. If the probes were continuous rather than flashed, the effect was abolished. The observational reports of 30 online participants suggest that the frame effect is robust to many variations in its shape and path and leads to a perception of flashed tests in their locations relative to the frame as if the frame were stationary. Our results highlight the role of frame continuity and of the grouping of the flashes with the frame in generating the frame effect.

neuroscience↗

bioRxiv2021

Consciously detecting and recognizing a stimulus without knowing what it looks like

What is the role of sensory processing in conscious perception? Current theories of consciousness are divided on this question. Some propose that conscious perception arises during the buildup of sensory representations. Other argue for a secondary process that broadcasts these representations to higher-level areas. This second view makes a counter-intuitive prediction: one could consciously perceive abstract representations untied to any low-level sensory feature. We tested this prediction by combining visual masking with retrospective cueing. We found that when visually masked words were followed by a semantically related auditory word, participants were better at detecting this past word and reporting its identity, but were strikingly unable to report its visual features (letter casing or position on screen). This suggests that retro-cueing can help a semantic representation reach awareness even after the associated sensory information has been masked. The mechanisms of conscious access might thus be largely independent from early sensory build-up.

neuroscience↗

bioRxiv2020

Serial integration of sensory evidence for perceptual decisions and oculomotor responses

Perceptual decisions often require the integration of noisy sensory evidence over time. This process is formalized with sequential sampling models, where evidence is accumulated up to a decision threshold before a choice is made. Although intuition suggests that decision formation must precede the preparation of a motor response (i.e., the action used to communicate the choice), neurophysiological findings have suggested that these two processes might be one and the same. To test this idea, we developed a reverse-correlation protocol in which the visual stimuli that influence decisions can be distinguished from those guiding motor responses. In three experiments, we found that the temporal weighting function of oculomotor responses did not overlap with the relatively early weighting function of stimulus properties having an impact on decision formation. These results support a timeline in which perceptual decisions are formed, at least in part, prior to the preparation of a motor response.

neuroscience↗

bioRxiv2017

Discrete confidence levels revealed by sequential decisions

Whether humans are optimal decision makers is still a debated issue in the realm of perceptual decisions. Taking advantage of the direct link between an optimal decision-making and the confidence in that decision, we offer a new dual-decisions method of inferring such confidence without asking for its explicit valuation. Our method circumvents the well-known miscalibration issue with explicit confidence reports as well as the specification of the cost-function required by opt-out or post-decision wagering methods. We show that observers inferred confidence in their first decision and its use in a subsequent decision (conditioned upon the correctness of the first) fall short of both the ideal Bayesian strategy, as well as of an under-sampling approximation or a modified Bayesian strategy augmented with an additional bias term to accommodate global miscalibration of confidence. The observed data are instead significantly better fitted by a model positing that observers use only few confidence levels or states, at odds with the continuous confidence function of stimulus level prescribed by a normative behavior. These findings question the validity of normative-Bayesian accounts of subjective confidence and metaperceptual judgments.

neuroscience↗