Biology subjects

Kelly, S. P.

Publications and source records attributed to Kelly, S. P..

At least 19 recordsLinked to original sources

bioRxiv2026

Neural latent representation of implicit perceptual decision confidence signatures from brain-wide intracranial EEG

Human perceptual decision confidence has been associated with brain-wide signalling, albeit with inconsistencies across studies. It remains unclear whether more robust neural latent representations exist, particularly for implicit confidence. We address this by applying complementary machine learning approaches to comprehensive, brain-wide intracranial electroencephalography (iEEG) data acquired without explicit confidence reports. Using explainable feature selection methods, we elucidated key spatiotemporal iEEG components, especially in the frontal cortex, that readily distinguished confidence characteristics related to decision correctness, difficulty, and speed, and that were transferable across motor modalities. Despite inconsistencies in the features identified across methods and conditions, dimensionality reductions revealed robust low-dimensional neural latent representations. Furthermore, their neural trajectories within a shared subspace enhanced the distinguishability of confidence characteristics. Overall, our results uncover low-dimensional spatial and temporal neural latent representations underlying human implicit perceptual decision confidence that are robust to analytical methods and decision conditions.

neuroscience↗

bioRxiv2025

Neurally-Informed Models of Protracted Sequential Sampling of Long, Noise-free Stimuli

Perceptual decision behaviour is known to be well-captured by models based on sequential sampling and temporal integration, but doubts have been raised about the generality and identifiability of these operations. Here we used neurally-constrained modelling to probe their role and temporal extent in the uncertain case of perceptual judgments about long-duration stimuli with no physical noise but weak evidence. We found that accuracy steadily improved across four covertly-manipulated evidence durations, indicating protracted sampling, but these delayed behavioural reports alone were insufficient to establish the operation of integration or of a decision-terminating bound. We then elaborated the models to prescribe how they would generate decision variable signals as well as choices, and fit them additionally to the average dynamics of a centroparietal electroencephalographic signal ( CPP) that traces decision formation. This established the setting of a bound and ruled out some non-integration mechanisms. However, one extrema detection model, which evokes a stereotyped signal flagging the first bound-exceeding sample, rivalled the integration model in reproducing the evidence-dependent buildup dynamics of the CPP, alongside behavioural data. Moreover, the two models captured different features of neural motor preparation signals but neither captured all of them. We discuss the implications for the generality of integration and the technical challenges of neurally-informed modelling given limited behavioural data.

neuroscience↗

bioRxiv2025

Readout and delayed transmission of initial afferent V1 activity in decisions about stimulus contrast

Initial afferent activation of V1, indexed by the C1 component of the human VEP, is often considered to be a rudimentary stage of visual processing, operating mostly as a conduit for later stages with limited cognitive penetrability. The full suite of visual analysis entails activity across several visual areas and feedback from later areas to earlier ones. This raises the question of whether the early sensory representation indexed by the C1 is read out for perceptual decisions or whether it is passed over in favour of more advanced representations. To address this question, we asked whether the C1 would predict time-pressured stimulus contrast comparisons independently of physical stimulus conditions, a phenomenon known as choice probability. We found that the C1 did this for a narrow range of response times, indicative of decision readout since the C1 is a transient signal. This effect could not be accounted for by stimulus differences, choice history, or any other choice-predictive signal that we could identify in either the time or frequency domain, either before or after target onset. It also preceded the onset of evidence-dependent decision formation estimated from the centroparietal positivity by tens of milliseconds, together providing an approximate timeline of early evidence readout and its delayed impact on the decision.

neuroscience↗

bioRxiv2025

A Movement-Independent Signature of Urgency During Human Perceptual Decision Making

How does the brain adjust its decision processes to ensure timely decision completion? Computational modelling and electrophysiological investigations have pointed to dynamic urgency processes that serve to progressively reduce the quantity of evidence required to reach choice commitment as time elapses. To date, such urgency dynamics have been observed exclusively in neural signals that accumulate evidence for a specific motor plan. Across three complementary experiments, we show that a classic ERP component, the Contingent Negative Variation (CNV), also traces dynamic urgency but exhibits unique properties not observed in effector-selective signals. Firstly, it provides a representation of urgency alone, growing only as a function of time and not evidence strength. Secondly, when choice reports must be withheld until a response cue, the CNV peaks and decays long before response execution, mirroring the early termination dynamics of a motor-independent evidence accumulation signal. These properties suggest that the brain may use urgency signals not only to expedite motor planning but also to hasten cognitive deliberation. These data demonstrate that urgency processes operate in a variety of perceptual choice scenarios and that they can be monitored in a model-independent manner via non-invasive brain signals. Significance StatementComputational models suggest that, when decisions are time-constrained the brain progressively lowers the amount of evidence it requires to reach choice commitment, thus increasingly sacrificing accuracy for timely decision completion. To date, neurophysiological investigations have identified signatures of these urgency effects exclusively in areas of the brain that plan the decision-reporting actions. Here, we characterise a human electroencephalogram signature of urgency that exhibits several novel properties: it traces the urgency component of the decision and terminates upon choice commitment even when the decision-reporting action is deferred until later. These observations suggest that urgency can serve to hasten the deliberation process and not just the movements that a decision entails.

neuroscience↗

bioRxiv2025

Centroparietal signals track multiple rounds of evidence accumulation in an intermittent evidence task

Making decisions often requires the integration of multiple pieces of information. An extensive body of research has investigated the neural architecture underpinning evidence accumulation in perceptual tasks where information is continuously present, but less is known about how this neural architecture operates in situations affording only intermittent glimpses of an evidence source. In two electroencephalography (EEG) experiments, participants judged the direction of up to two pulses of motion evidence separated by gaps of varying duration. Our behavioural analysis found that participants used both pulses but underutilised the second, and showed no systematic decrease in accuracy as a function of gap duration. At the neural level, motor beta lateralisation tracked cumulative evidence across pulses, maintaining a sustained representation of the decision variable through the gap and until response. In contrast, the centroparietal positivity (CPP), a previously-characterised signature of evidence accumulation, built up transiently to a peak that scaled with each pulses contribution to the decision variable (i.e. the absolute belief update it produced), falling back to baseline in between pulses. These patterns were recapitulated in a model where pulse-information transiently integrated at the CPP level is fed to and maintained at a bounded motor level. In this model, the evidence in the second pulse is only integrated to the extent that the evidence in the first pulse falls short of the bound, or not integrated at all if a bound has already been hit.

neuroscience↗

bioRxiv2024

Engineering a Biosynthetic Pathway for the Production of (+)-Brevianamides A and B in Escherichia coli

The privileged fused-ring system comprising the bicyclo[2.2.2]diazaoctane (BDO) core is prevalent in diketopiperazine (DKP) natural products with potent and diverse biological activities, with some being explored as drug candidates. Typically, only low yields of these compounds can be extracted from native fungal producing strains and the available synthetic routes remain challenging due to their structural complexity. BDO-containing DKPs including (+)-brevianamides A and B are assembled via multi-component biosynthetic pathways incorporating non-ribosomal peptide synthetases, prenyltransferases, flavin monooxygenases, cytochrome P450s and semi-pinacolases. To simplify access to this class of alkaloids, we designed an engineered biosynthetic pathway in Escherichia coli, composed of six enzymes sourced from different kingdoms of life. The pathway includes a cyclodipeptide synthase (NascA), a cyclodipeptide oxidase (DmtD2/DmtE2), a prenyltransferase (NotF), a flavin-dependent monooxygenase (BvnB), and kinases (PhoN and IPK). Cultivated in glycerol supplemented with prenol, the engineered E. coli strain produces 5.3 mg/L of (-)-dehydrobrevianamide E (4), which undergoes a terminal, ex vivo lithium hydroxide catalyzed rearrangement reaction to yield (+)-brevianamides A and B with a 46% yield and a 92:8 diastereomeric ratio. Additionally, titers of 4 were increased eight-fold by enhancing NADPH pools in the engineered E. coli strain. Our study combines synthetic biology, biocatalysis and synthetic chemistry approaches to provide a five-step engineered biosynthetic pathway for producing complex indole alkaloids in E. coli. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=94 SRC="FIGDIR/small/627567v2_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@399e92org.highwire.dtl.DTLVardef@d98faaorg.highwire.dtl.DTLVardef@1671ac1org.highwire.dtl.DTLVardef@d7bc6_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2024

Regressing Away Common Neural Choice Signals does not make them Artifacts. Comment on Frömer et al (2024, Nature Human Behaviour)

Fromer et al (2024, Nature Human Behaviour) apply a deconvolution method to correct for component overlap in the event-related potential. They report that this method eliminates signatures of sensory evidence accumulation from response-aligned measurements of the centro-parietal positivity (CPP), suggesting that these signatures arise artifactually.. Here, we argue that the analysis and interpretation of their perceptual choice data are critically flawed. We demonstrate with simulations that the deconvolution analyses used by the authors are not designed to reliably test for the presence or absence of bounded accumulation signals.

neuroscience↗

bioRxiv2024

Dissociable encoding of evolving beliefs and momentary belief updates in distinct neural decision signals

Making accurate decisions in noisy or otherwise uncertain environments requires integrating evidence over time. Using simple tasks requiring rapid evaluation of a stationary sensory feature, two human neurophysiological signals have been found to evolve with similar integration dynamics, with one (centroparietal positivity; CPP) appearing to compute the running integral and continuously feed it to the other (motor beta lateralisation; MBL). However, it remains unknown whether and how these signals serve more distinct functional roles in more complex scenarios where information arrives discontinuously and requires more computational steps to form appropriate belief updates. We employed a volatile expanded judgement task that permits dissociation of the encoding of raw sensory information in each of a series of discrete stimuli ( objective evidence), the appropriately transformed belief updates from that information ( effective evidence), and the evolving belief itself (accumulated evidence). Whereas MBL traced the evolving belief across stimuli, the CPP was found only to locally encode the effective evidence associated with each individual stimulus. Furthermore, fluctuations in CPP amplitude after each single stimulus could account for variability in the encoding of accumulated evidence in MBL. These results suggest a flexible computational hierarchy in which effective evidence can be computed sample-by-sample at an intermediate processing level to drive downstream belief updates for protracted decisions about discrete stimuli.

neuroscience↗

bioRxiv2023

Visual cortical area contributions to the transient, multifocal and steady-state VEP: A forward model-informed analysis

Central to our understanding of how visual evoked potentials (VEPs) contribute to visual processing is the question of where their anatomical sources are. Three well-established measures of low-level visual cortical activity are widely used: the first component ("C1") of the transient and multifocal VEP, and the steady-state VEP (SSVEP). Although primary visual cortex (V1) activity has often been implicated in the generation of all three signals, their dominant sources remain uncertain due to the limited resolution and methodological heterogeneity of source modelling. Here, we provide the first characterisation of all three signals in one analytic framework centred on the cruciform model, which describes how scalp topographies of V1 activity vary with stimulus location due to the retinotopy and unique folding pattern of V1. We measured the transient C1, multifocal C1, and SSVEPs driven by an 18.75Hz and 7.5Hz flicker, and regressed them against forward-models of areas V1, V2 and V3 generated from the Benson-2014 retinotopy atlas. The topographic variations of all four VEP signals across the visual field were better captured by V1 models, explaining between 2-6 times more variance than V2/V3. Models with all three visual areas improved fit further, but complementary analyses of temporal dynamics across all three signals indicated that the bulk of extrastriate contributions occur considerably later than V1. Overall, our data support the use of peak C1 amplitude and SSVEPs to probe V1 activity, although the SSVEP contains stronger extrastriate contributions. Moreover, we provide elaborated heuristics to distinguish visual areas in VEP data based on signal lateralization as well as polarity inversion.

neuroscience↗

bioRxiv2023

Prior probability cues bias sensory encoding with increasing task exposure

When observers have prior knowledge about the likely outcome of their perceptual decisions, they exhibit robust behavioural biases in reaction time and choice accuracy. Computational modelling typically attributes these effects to strategic adjustments in the criterion amount of evidence required to commit to a choice alternative - usually implemented by a starting point shift - but recent work suggests that expectations may also fundamentally bias the encoding of the sensory evidence itself. Here, we recorded neural activity with EEG while participants performed a contrast discrimination task with valid, invalid, or neutral probabilistic cues across multiple testing sessions. We measured sensory evidence encoding via contrast-dependent steady-state visual-evoked potentials (SSVEP), while a read-out of criterion adjustments was provided by effector-selective mu-beta band activity over motor cortex. In keeping with prior modelling and neural recording studies, cues evoked substantial biases in motor preparation consistent with criterion adjustments, but we additionally found that the cues produced a significant modulation of the SSVEP during evidence presentation. While motor preparation adjustments were observed in the earliest trials, the sensory-level effects only emerged with extended task exposure. Our results suggest that, in addition to strategic adjustments to the decision process, probabilistic information can also induce subtle biases in the encoding of the evidence itself.

neuroscience↗

bioRxiv2023

Intracranial electroencephalography reveals effector-independent evidence accumulation dynamics in multiple human brain regions

Neural representations of perceptual decision formation that are abstracted from specific motor requirements have previously been identified in humans using non-invasive electrophysiology, however, it is currently unclear where these originate in the brain. Here, we capitalized on the high spatiotemporal precision of intracranial EEG to localize such abstract decision signals. Presurgical epilepsy patients judged the direction of random-dot stimuli and responded either with a speeded button press (N=23), or vocally, after a randomized delay (N=11). We found a widely distributed motor-independent network of regions where high-frequency activity exhibited key characteristics consistent with evidence accumulation, including a gradual build-up that was modulated by the strength of the sensory evidence, and an amplitude that predicted subjects choice accuracy and response time. Our findings offer a new view on the brain networks governing human decision making.

neuroscience↗

bioRxiv2023

Confidence is predicted by pre- and post-choice decision signal dynamics

It is well established that ones confidence in a choice can be influenced by new evidence encountered after commitment has been reached, but the processes through which post-choice evidence is sampled remain unclear. To investigate this, we traced the pre- and post-choice dynamics of electrophysiological signatures of evidence accumulation (Centro-parietal Positivity, CPP) and motor preparation (mu/beta band) to determine their sensitivity to participants confidence in their perceptual discriminations. Pre-choice CPP amplitudes scaled with confidence both when confidence was reported simultaneously with choice, or when reported 1-second after the initial direction decision. When additional evidence was presented during the post-choice delay period, the CPP continued to evolve after the initial choice, with a more prolonged build-up on trials with lower confidence in the alternative that was finally endorsed, irrespective of whether this entailed a change-of-mind. Further investigation established that this pattern was accompanied by earlier post-choice CPP peak latency, earlier lateralisation of motor preparation signals toward the ultimately chosen response, and faster confidence reports when participants indicated high certainty that they had made a correct or incorrect initial choice. These observations are consistent with confidence-dependent stopping theories according to which post-choice evidence accumulation ceases when a criterion level of confidence in a choice alternative has been reached. Our findings have implications for current models of choice confidence, and predictions they may make about EEG signatures.

neuroscience↗

bioRxiv2022

Balancing true and false detection of intermittent sensory targets by adjusting the inputs to the evidence accumulation process

Decisions about noisy stimuli are widely understood to be made by accumulating evidence up to a decision bound that can be adjusted according to task demands. However, relatively little is known about how such mechanisms operate in continuous monitoring contexts requiring intermittent target detection. Here, we examined neural decision processes underlying detection of 1-second coherence-targets within continuous random dot motion, and how they are adjusted across contexts with Weak, Strong, or randomly Mixed weak/strong targets. Our prediction was that decision bounds would be set lower when weak targets are more prevalent. Behavioural hit and false alarm rate patterns were consistent with this, and were well-captured by a bound-adjustable leaky accumulator model. However, beta-band EEG signatures of motor preparation contradicted this, instead indicating lower bounds in the Strong-target context. We thus tested two alternative models in which decision bound dynamics were constrained directly by Beta measurements, respectively featuring leaky accumulation with adjustable leak, and non-leaky accumulation of evidence referenced to an adjustable sensory-level criterion. We found that the latter model best explained both behaviour and neural dynamics, highlighting novel means of decision policy regulation and the importance of neurally-informed modelling.

neuroscience↗

bioRxiv2021

Multiphasic value biases in fast-paced decisions

Perceptual decisions are biased toward higher-value options when overall gains can be improved. When stimuli demand immediate reactions, the neurophysiological decision process dynamically evolves through distinct phases of growing anticipation, detection and discrimination, but how value biases are exerted through these phases remains unknown. Here, by parsing motor preparation dynamics in human electrophysiology, we uncovered a multiphasic pattern of countervailing biases operating in speeded decisions. Anticipatory preparation of higher-value actions began earlier, conferring a "starting point"-advantage at stimulus onset, but the delayed preparation of lower-value actions was steeper, conferring a value-opposed buildup rate bias. This, in turn, was countered by a transient deflection toward the higher value action evoked by stimulus detection. A neurally-constrained process model featuring anticipatory urgency, biased detection, and accumulation of growing stimulus-discriminating evidence, successfully captured both behavior and motor preparation dynamics. Thus, an intricate interplay of distinct biasing mechanisms serves to prioritise time-constrained perceptual decisions.

neuroscience↗

bioRxiv2019

Life out of water: Genomic and physiological mechanisms underlying skin phenotypic plasticity

The Devonian radiation of vertebrates from aquatic into terrestrial habitats required behavioral, physiological, and morphological adaptations. Changes to skin structure and function were likely crucial, but adaptations were needed to resolve contrasting demands of maintaining a mechanical and physiological barrier while also facilitating ion and gas transport. Little is known of the mechanisms that underlie skin plasticity and adaptation between water and air. We performed experiments using two isogenic lineages of an amphibious killifish (Kryptolebias marmoratus from brackish and freshwater habitats) and used transcriptional and morphological data to reveal mechanisms recruited to resolve the dual challenges of skin providing both a barrier and an exchange interface during terrestrial acclimation. Transcriptional regulators of skin morphogenesis were quickly activated upon emersion. Regulation of cell-cell adhesion complexes, coupled with pathways homologous with those that regulate stratum corneum formation, was consistent with barrier function and mechanical reinforcement. Cutaneous respiration was associated with regulation of angiogenesis pathways and with blood vessel architecture that facilitated extremely short diffusion distances and direct delivery to ionocyotes. Evolutionary analyses revealed directional selection operating on proteins involved in barrier and respiratory functions, reinforcing the importance of these mechanisms for enabling the amphibious lifestyle of K. marmoratus. Fish from brackish niches were more resilient to emersion and also differed from freshwater fish in ionoregulatory responses to emersion. We conclude that plasticity of barrier, respiratory, and ionoregulatory functions in skin evolved to support the amphibious lifestyle of K. marmoratus; similar processes may have facilitated the terrestrial radiation of ancient fishes.\n\nSignificance statementThe transition of vertebrate life from water to land coincided with solving multiple physiological challenges including avoiding drying out while also exchanging gases and ions with the environment. Though changes in the skin were likely important, little is known of the mechanisms that underlie skin flexibility and adaptation between water and air. We performed air exposure experiments with an amphibious killifish; gene expression profiling, microscopy, and evolutionary analysis of proteins revealed cell structures, proteins, and molecular pathways that support skin flexibility and adaptations during air exposure, and ion regulation contributed to differences in killifish abilities to adjust to air. Amphibious killifish are useful models to help us understand changes that enable water to air transitions in contemporary and ancient fishes.

physiology↗

bioRxiv2019

Multifaceted adaptation of the neural decision process with prior knowledge of time constraints and stimulus probability

When selecting actions in response to noisy sensory stimuli, the brain can exploit prior knowledge of time constraints, stimulus discriminability and stimulus probability to hone the decision process. Although behavioral models typically explain such effects through adjustments to decision criteria only, the full range of underlying neural process adjustments remains to be established. Here, we draw on human neurophysiological signals reflecting decision formation to construct and constrain a multi-tiered model of prior-informed motion discrimination, in which a motor-independent representation of cumulative evidence feeds build-to-threshold motor signals that receive additional dynamic urgency and bias signal components. The neurally-informed model not only provides a superior quantitative fit to prior-biased behavior across three distinct task regimes (easy, time-pressured and weak evidence), but also reveals adjustments to evidence accumulation rate, urgency rate, and the timing of accumulation onset and motor execution which go undetected or are discrepant in more standard diffusion-model analysis of behavior.

neuroscience↗

bioRxiv2019

The role of premature evidence accumulation in making difficult perceptual decisions under temporal uncertainty

The computations and neural processes underpinning decision making have primarily been investigated using highly simplified tasks in which stimulus onsets cue observers to start accumulating choice-relevant information. Yet, in daily life we are rarely afforded the luxury of knowing precisely when choice-relevant information will appear. Here, we examined neural indices of decision formation while subjects discriminated subtle stimulus feature changes whose timing relative to stimulus onset ( foreperiod) was uncertain. Joint analysis of behavioral error patterns and neural decision signal dynamics indicated that subjects systematically began the accumulation process before any informative evidence was presented, and further, that accumulation onset timing varied systematically as a function of the foreperiod of the preceding trial. These results suggest that the brain can adjust to temporal uncertainty by strategically modulating accumulation onset timing according to statistical regularities in the temporal structure of the sensory environment with particular emphasis on recent experience.

neuroscience↗

bioRxiv2019

Dynamics of visual contextual interactions is altered in Parkinson's disease

Over the last decades, psychophysical and electrophysiological studies in patients and animal models of Parkinsons disease (PD), have consistently revealed a number of visual abnormalities. In particular, specific alterations of contrast sensitivity curves, electroretinogram (ERG), and visual evoked potentials (VEP), have been attributed to dopaminergic retinal depletion. However, fundamental mechanisms of cortical visual processing, such as normalization or "gain-control" computations, have not yet been examined in PD patients. Here we measured electrophysiological indices of gain control in both space (surround suppression) and time (sensory adaptation) in PD patients based on steady-state VEP (ssVEP). Compared to controls, patients exhibited a significantly higher initial ssVEP amplitude that quickly decayed over time, and greater relative suppression of ssVEP amplitude as a function of surrounding stimulus contrast. Meanwhile, EEG frequency spectra were broadly elevated in patients relative to controls. Thus, contrary to what might be expected given the reduced contrast sensitivity often reported in PD, visual neural responses are not weaker; rather, they are initially larger but undergo an exaggerated degree of spatial and temporal gain control and are embedded within a greater background noise level. We conclude that compensatory cortical mechanisms may play a role in determining dysfunctional center-surround interactions at the retinal level.

neuroscience↗