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Contributed Talks I: Detecting and characterising microsaccades from AOSLO images of the photoreceptor mosaic using computer vision.
Fixational eye movements (FEMs), especially microsaccades (MS), are promising biomarkers of neurodegenerative disease. In vivo images of the photoreceptor mosaic acquired using an Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO) are systematically distorted by eye motion. Most methods to extract FEMs from AOSLO data rely on comparison to a motion-free reference, giving eye-position as a function of time. MS are subsequently identified using adaptive velocity thresholds (Engbert & Kliegl, 2003). We use computer vision and machine learning (ML) for detection and characterisation of MS directly from raw AOSLO images. For training and validation, we use Emulated Retinal Image CApture (ERICA), an open-source tool to generate synthetic AOSLO datasets of retinal images and ground-truth velocity profiles (Young & Smithson, 2021). To classify regions of AOSLO images that contain a MS, images were divided into a grid of 32-by-32-pixel sub-images. Predictions from rows of sub-images aligned with the fast-scan of the AOSLO were combined, giving 1ms resolution. Model performance was high (F1 scores >0.92) across plausible MS displacement magnitudes and angles, with most errors close to the velocity threshold for classification. Direct velocity predictions were also derived from regression ML models. We show that ML models can be systematically adapted for generalisation to real in vivo images, allowing characterisation of MS at much finer spatial scales than video-based eye-trackers.
A Systematic Review of Guided, Parent-Led Digital Interventions for Preadolescent Children with Emotional and Behavioural Problems
Abstract Emotional and behavioural problems (EBP) are prevalent amongst children, and guided, parent-led digital interventions offer one method of improving access to effective treatments. This systematic review (PROSPERO: CRD42023484098) aimed to examine the evidence base for, and characteristics of, these types of interventions through a narrative synthesis. Systematic searches were conducted using Medline, EMBASE, PsycINFO, Scopus and Web of Science in January 2024 and February 2025, supplemented with hand searching in March/April 2024 and February 2025. Studies were eligible if they reported outcomes related to preadolescent EBP from a guided, fully parent-led, fully digital intervention. Thirteen studies were eligible, including 2643 children and covering eight interventions (addressing anxiety problems, comorbid anxiety and depression, attention deficit hyperactivity disorder, conduct disorder and disruptive behaviour). Studies included randomised controlled trials and pre-post studies. The QualSyst checklist was used to assess study quality; all studies were rated as good quality. All studies showed statistically significant improvements in the child’s symptoms or interference levels, with small to very large effect sizes immediately post-treatment, and at least medium effect sizes by follow-up, suggesting a promising evidence base. A wide range of intervention characteristics were identified, forming a basis for future intervention development for childhood EBP. However, there was a lack of consistency in how information was reported across studies (such as completion rates) and studies lacked information on parent demographics and key intervention details. Further high quality randomised controlled trials for a wider range of EBP are needed to continue building the evidence base.
Short, Animated Storytelling Video to Reduce Addiction Stigma in 13,500 Participants Across Multiple Countries Through an Online Approach: Protocol for a Randomized Controlled Trial
Background Stigma toward people with addiction is a well-documented phenomenon that dramatically impacts help-seeking, treatment, and recovery. Interventions aimed at reducing stigma toward those with addiction must overcome the frequent mischaracterization of addiction as a failure of judgment rather than a chronic, treatable illness. Previous research has demonstrated that social contact with people recovering from addiction can promote empathy and reduce stigma, but social contact is difficult to scale. Short, animated storytelling (SAS) is a novel health communication approach that scales easily because it can leapfrog barriers associated with language, culture, literacy, and education levels. Objective This study will investigate the effect of a cross-culturally accessible SAS video intervention aimed at reducing stigma and increasing empathy toward people with addiction. We also seek to gain insight into the mechanisms of action of this SAS intervention by measuring the contribution of sound design to their effect. Methods We will conduct a randomized controlled trial with 13,500 adult participants from the United States, the United Kingdom, and South Africa, recruited online via Prolific Academic and randomized into 3 arms, per country. The 2 intervention arms will receive a wordless, social contact–based SAS video, one arm with a soundtrack and one without. The third arm will receive an educational video about addiction. Validated questionnaires will be used to assess our primary outcome, addiction stigma, and secondary outcomes, optimism, warmth toward the subject, and hopefulness, at baseline, immediately post exposure, and 2 weeks later. Ethics clearance was obtained on August 15, 2024, from the Stanford University institutional review board (protocol 76457). Results This trial was funded in January 2025 by the Heidelberg Institute of Global Health, the Faculty of Medicine at Heidelberg University, in Germany. As of March 2025, no data have been collected. The estimated start date for this trial is May 15, 2025. We expect to complete data collection by July 1, 2025, and expect results to be published in the spring of 2026. Conclusions Here, we present the protocol for an online, multicountry, randomized controlled trial. This trial is designed to measure the effect of an innovative approach to global health communication (wordless, short, and animated storytelling) on addiction stigma in 3 global regions. These findings will inform the design of future scalable, digital health storytelling interventions for global audiences while exploring the capacity of SAS to shift public health attitudes and perceptions. Furthermore, if effective, the intervention described here could be disseminated broadly via social media and other online platforms. Trial Registration ClinicalTrials.gov NCT06705205; https://clinicaltrials.gov/study/NCT06705205 International Registered Report Identifier (IRRID) PRR1-10.2196/73382
Dorsomedial and ventromedial prefrontal cortex lesions differentially impact social influence and temporal discounting.
The medial prefrontal cortex (mPFC) has long been associated with economic and social decision-making in neuroimaging studies. Several debates question whether different ventral mPFC (vmPFC) and dorsal mPFC (dmPFC) regions have specific functions or whether there is a gradient supporting social and nonsocial cognition. Here, we tested an unusually large sample of rare participants with focal damage to the mPFC (N = 33), individuals with lesions elsewhere (N = 17), and healthy controls (N = 71) (total N = 121). Participants completed a temporal discounting task to estimate their baseline discounting preferences before learning the preferences of two other people, one who was more temporally impulsive and one more patient. We used Bayesian computational models to estimate baseline discounting and susceptibility to social influence after learning others' economic preferences. mPFC damage increased susceptibility to impulsive social influence compared to healthy controls and increased overall susceptibility to social influence compared to those with lesions elsewhere. Importantly, voxel-based lesion-symptom mapping (VLSM) of computational parameters showed that this heightened susceptibility to social influence was attributed specifically to damage to the dmPFC (area 9; permutation-based threshold-free cluster enhancement (TFCE) p < 0.025). In contrast, lesions in the vmPFC (areas 13 and 25) and ventral striatum were associated with a preference for seeking more immediate rewards (permutation-based TFCE p < 0.05). We show that the dmPFC is causally implicated in susceptibility to social influence, with distinct ventral portions of mPFC involved in temporal discounting. These findings provide causal evidence for sub-regions of the mPFC underpinning fundamental social and cognitive processes.
Neural dynamics of reselecting visual and motor contents in working memory after external interference.
In everyday tasks, we must often shift our focus away from internal representations held in working memory to engage with perceptual events in the external world. Here, we investigated how our internal focus is reestablished following an interrupting task by tracking the reselection of visual representations and their associated action plans in working memory. Specifically, we ask whether reselection occurs for both visual and motor memory attributes and when this reselection occurs. We developed a visual-motor working-memory task in which participants were retrospectively cued to select one of two memory items before being interrupted by a perceptual discrimination task. To determine what information was reselected, the memory items had distinct visual and motor attributes. To determine when internal representations were reselected, the interrupting task was presented at one of three distinct time points following the retro-cue. We employed electroencephalography time-frequency analyses to track the initial selection and later reselection of visual and motor representations, as operationalized through modulations of posterior alpha (8-12 Hz) activity relative to the memorized item location (visual) and of central beta (13-30 Hz) activity relative to the required response hand (motor). Our results showed that internal visual and motor contents were concurrently reselected immediately after completing the interrupting task, rather than only when internal information was required for memory-guided behavior. Thus, following interruption, we swiftly resume our internal focus in working memory through the simultaneous reselection of memorized visual representations and their associated action plans, thereby restoring internal contents to a ready-to-use state.Significance statement A key challenge for working memory is to maintain past visual representations and their associated actions while engaging with the external environment. Our cognitive system must, therefore, often juggle multiple tasks within a common time frame. Despite the ubiquity of multi-task situations in everyday life, working memory has predominantly been studied devoid of additional perceptual, attentional, and response demands during the retention interval. Here, we investigate the neural dynamics of returning to internal contents following task-relevant interruptions. Particularly, we identify which attributes of internal representations are reselected and when this reselection occurs. Our findings demonstrate that both visual and motor contents are reselected immediately and in tandem after completion of an external, interrupting task.
Evaluation of an adaptation to the Oxford Cognitive Screen for reduced visual acuity: a cohort study.
BACKGROUND: The Oxford Cognitive Screen (OCS) was specifically designed for acute stroke survivors and to be inclusive of aphasia, neglect, motor impairments. However, reduced visual acuity (VA), including lack of access to required reading glasses, can impact completion rates and performance. The aim of the study was to evaluate contrast enhanced OCS-tasks for completion rates and equivalence to the original version. METHODS: Adult stroke survivors were asked to complete two versions (standard and adapted) of two tasks (broken hearts cancellation and trails) in a randomized order, to determine relative completion rates and equivalency. A bedside vision assessment, completed by an orthoptist was collected, including near and distance VA with required refractive correction if available. Two groups were created based on near VA; normal near VA (≥0.2LogMAR) and reduced near VA (<0.2LogMAR). RESULTS: Five hundred participants were recruited, 56.8% male, mean age 70.62 years. Mean near VA was 0.278 (SD0.277) LogMAR. The broken hearts and trails tasks were completed by 2.2% (p=0.041) and 0.4% (p=0.791) more participants respectively with the adapted version. Participants completing both versions with good near VA were used to analyze equivalence. All the lower and upper bounds of the two one-sided test of equivalence fell within the range of 0.5SD for all scores, indicating that the means are equivalent. Analysis of impairment detection revealed fair to good agreement. CONCLUSION: The adapted version is suitable for stroke survivors with reduced near VA to complete the assessment. In the presence of good VA, the tasks were deemed to be equivalent.
A view-based decision mechanism for rewards in the primate amygdala.
Primates make decisions visually by shifting their view from one object to the next, comparing values between objects, and choosing the best reward, even before acting. Here, we show that when monkeys make value-guided choices, amygdala neurons encode their decisions in an abstract, purely internal representation defined by the monkey's current view but not by specific object or reward properties. Across amygdala subdivisions, recorded activity patterns evolved gradually from an object-specific value code to a transient, object-independent code in which currently viewed and last-viewed objects competed to reflect the emerging view-based choice. Using neural-network modeling, we identified a sequence of computations by which amygdala neurons implemented view-based decision making and eventually recovered the chosen object's identity when the monkeys acted on their choice. These findings reveal a neural mechanism in the amygdala that derives object choices from abstract, view-based computations, suggesting an efficient solution for decision problems with many objects.
Mechanisms of adjustments to different types of uncertainty in the reward environment across mice and monkeys.
Despite being unpredictable and uncertain, reward environments often exhibit certain regularities, and animals navigating these environments try to detect and utilize such regularities to adapt their behavior. However, successful learning requires that animals also adjust to uncertainty associated with those regularities. Here, we analyzed choice data from two comparable dynamic foraging tasks in mice and monkeys to investigate mechanisms underlying adjustments to different types of uncertainty. In these tasks, animals selected between two choice options that delivered reward probabilistically, while baseline reward probabilities changed after a variable number (block) of trials without any cues to the animals. To measure adjustments in behavior, we applied multiple metrics based on information theory that quantify consistency in behavior, and fit choice data using reinforcement learning models. We found that in both species, learning and choice were affected by uncertainty about reward outcomes (in terms of determining the better option) and by expectation about when the environment may change. However, these effects were mediated through different mechanisms. First, more uncertainty about the better option resulted in slower learning and forgetting in mice, whereas it had no significant effect in monkeys. Second, expectation of block switches accompanied slower learning, faster forgetting, and increased stochasticity in choice in mice, whereas it only reduced learning rates in monkeys. Overall, while demonstrating the usefulness of metrics based on information theory in examining adaptive behavior, our study provides evidence for multiple types of adjustments in learning and choice behavior according to uncertainty in the reward environment.
Role of the amygdala in decisions under ambiguity and decisions under risk: evidence from patients with Urbach-Wiethe disease.
Various neuropsychological studies have shown that decision-making deficits can occur in a wide range of patients with brain damage or dysfunctions. Decisions under ambiguity, as measured with the Iowa Gambling Task, primarily depend on the integrity of the ventromedial prefrontal cortex and the amygdala, as well as on further brain regions such as the somatosensory cortex. However, little is known about the specific role of these structures in decisions under risk measured with tasks that offer explicit rules for gains and losses and winning probabilities, for example, the Game of Dice Task. We aimed to investigate the potential role of the amygdala for decisions under risk. For this purpose, we examined three patients with Urbach-Wiethe disease--a rare syndrome associated with selective bilateral mineralisation of the amygdalae. Neuropsychological performance was assessed with the Iowa Gambling Task (decisions under ambiguity), the Game of Dice Task (decisions under risk), and an extensive neuropsychological test battery focussing on executive functions. Furthermore, previous studies found relationships between generating skin conductance responses and deciding advantageously in the Iowa Gambling Task. Accordingly, we recorded skin conductance responses during both decision tasks as a measure of emotional reactivity. Results indicate that patients with selective amygdala damage have lower scores in both decisions under ambiguity and decisions under risk. Decisions under risk are especially compromised in patients who also demonstrate deficits in executive functioning. In both gambling tasks, patients showed reduced skin conductance responses compared to healthy comparison subjects. The results suggest that deciding advantageously under risk conditions involves both the use of feedback from previous trials, as required by decisions under ambiguity, and in addition, executive functions.
Decision-making, errors, and confidence in the brain.
To provide a fundamental basis for understanding decision-making and decision confidence, we analyze a neuronal spiking attractor-based model of decision-making. The model predicts probabilistic decision-making with larger neuronal responses and larger functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) responses on correct than on error trials because the spiking noise-influenced decision attractor state of the network is consistent with the external evidence. Moreover, the model predicts that the neuronal activity and the BOLD response will become larger on correct trials as the discriminability ΔI increases and confidence increases and will become smaller as confidence decreases on error trials as ΔI increases. Confidence is thus an emergent property of the model. In an fMRI study of an olfactory decision-making task, we confirm these predictions for cortical areas including medial prefrontal cortex and the cingulate cortex implicated in choice decision-making, showing a linear increase in the BOLD signal with ΔI on correct trials, and a linear decrease on error trials. These effects were not found in a control area, the orbitofrontal cortex, where reward value useful for the choice is represented on a continuous scale but that is not implicated in the choice itself. This provides a unifying approach to decision-making and decision confidence and to how spiking-related noise affects choice, confidence, synaptic and neuronal activity, and fMRI signals.
From affective value to decision-making in the prefrontal cortex.
Representing the affective value of a reward on a continuous scale may occur separately from making a binary, for example yes vs no, decision about whether to choose the reward. To investigate whether these are separable processes, we used functional magnetic resonance imaging to measure activations produced by pleasant warm, unpleasant cold, and affectively complex combinations of these stimuli applied to the hand. On some trials the affective value was rated on a continuous scale, and on different trials a yes-no decision was made about whether the stimulus should be repeated in future. Decision-making contrasted with just rating the affective stimuli revealed activations in the medial prefrontal cortex area 10, implicating this area in binary decision-making. Activations related to the pleasantness ratings and which were not influenced when a binary decision was made were found in the pregenual cingulate and parts of the orbitofrontal cortex, implicating these regions in the continuous representation of affective value. When a decision was yes vs. no, effects were found in the dorsal cingulate cortex, agranular (anterior) insula and ventral tegmental area, implicating these areas in initiating actions to obtain goals.
The orbitofrontal cortex and beyond: from affect to decision-making.
The orbitofrontal cortex represents the reward or affective value of primary reinforcers including taste, touch, texture, and face expression. It learns to associate other stimuli with these to produce representations of the expected reward value for visual, auditory, and abstract stimuli including monetary reward value. The orbitofrontal cortex thus plays a key role in emotion, by representing the goals for action. The learning process is stimulus-reinforcer association learning. Negative reward prediction error neurons are related to this affective learning. Activations in the orbitofrontal cortex correlate with the subjective emotional experience of affective stimuli, and damage to the orbitofrontal cortex impairs emotion-related learning, emotional behaviour, and subjective affective state. With an origin from beyond the orbitofrontal cortex, top-down attention to affect modulates orbitofrontal cortex representations, and attention to intensity modulates representations in earlier cortical areas of the physical properties of stimuli. Top-down word-level cognitive inputs can bias affective representations in the orbitofrontal cortex, providing a mechanism for cognition to influence emotion. Whereas the orbitofrontal cortex provides a representation of reward or affective value on a continuous scale, areas beyond the orbitofrontal cortex such as the medial prefrontal cortex area 10 are involved in binary decision-making when a choice must be made. For this decision-making, the orbitofrontal cortex provides a representation of each specific reward in a common currency.
Experimentally revealed stochastic preferences for multicomponent choice options.
Realistic, everyday rewards contain multiple components. An apple has taste and size. However, we choose in single dimensions, simply preferring some apples to others. How can such single-dimensional preference relationships refer to multicomponent choice options? Here, we measured how stochastic choices revealed preferences for 2-component milkshakes. The preferences were intuitively graphed as indifference curves that represented the orderly integration of the 2 components as trade-off: parts of 1 component were given up for obtaining 1 additional unit of the other component without a change in preference. The well-ordered, nonoverlapping curves satisfied leave-one-out tests, followed predictions by machine learning decoders and correlated with single-dimensional Becker-DeGroot-Marschak (BDM) auction-like bids for the 2-component rewards. This accuracy suggests a decision process that integrates multiple reward components into single-dimensional estimates in a systematic fashion. In interspecies comparisons, human performance matched that of highly experienced laboratory monkeys, as measured by accuracy of the critical trade-off between bundle components. These data describe the nature of choices of multicomponent choice options and attest to the validity of the rigorous economic concepts and their convenient graphic schemes for explaining choices of human and nonhuman primates. The results encourage formal behavioral and neural investigations of normal, irrational, and pathological economic choices. (PsycInfo Database Record (c) 2020 APA, all rights reserved).