Neurophysiology of Human Perceptual Decision-Making.

The discovery of neural signals that reflect the dynamics of perceptual decision formation has had a considerable impact. Not only do such signals enable detailed investigations of the neural implementation of the decision-making process but they also can expose key elements of the brain's decision algorithms. For a long time, such signals were only accessible through direct animal brain recordings, and progress in human neuroscience was hampered by the limitations of noninvasive recording techniques. However, recent methodological advances are increasingly enabling the study of human brain signals that finely trace the dynamics of the unfolding decision process. In this review, we highlight how human neurophysiological data are now being leveraged to furnish new insights into the multiple processing levels involved in forming decisions, to inform the construction and evaluation of mathematical models that can explain intra- and interindividual differences, and to examine how key ancillary processes interact with core decision circuits.

Neurophysiological correlates of dual tasking in people with Parkinson's disease and freezing of gait.

Freezing of gait in people with Parkinson's disease (PwP) is associated with executive dysfunction and motor preparation deficits. We have recently shown that electrophysiological markers of motor preparation, rather than decision-making, differentiate PwP with freezing of gait (FOG +) and without (FOG -) while sitting. To examine the effect of locomotion on these results, we measured behavioural and electrophysiological responses in PwP with and without FOG during a target response time task while sitting (single-task) and stepping-in-place (dual-task). Behavioural and electroencephalographic data were acquired from 18 PwP (eight FOG +) and seven young controls performing the task while sitting and stepping-in-place. FOG + had slower response times while stepping compared with sitting. However, response times were significantly faster while stepping compared with sitting for controls. Electrophysiological responses showed no difference in decision-making potentials (centroparietal positivity) between groups or conditions but there were differences in neurophysiological markers of response inhibition (N2) and motor preparation (lateralized readiness potential, LRP) in FOG + while performing a dual-task. This suggests that the addition of a second complex motor task (stepping-in-place) impacts automatic allocation of resources in FOG +, resulting in delayed response times. The impact of locomotion on the generation of the N2 and LRP potentials, particularly in freezers, indirectly implies that these functions compete with locomotion for resources. In the setting of multiple complex tasks or cognitive impairment, severe motor dysfunction may result, leading to freezing of gait.

Parietal neurons encode expected gains in instrumental information.

In natural behavior, animals have access to multiple sources of information, but only a few of these sources are relevant for learning and actions. Beyond choosing an appropriate action, making good decisions entails the ability to choose the relevant information, but fundamental questions remain about the brain's information sampling policies. Recent studies described the neural correlates of seeking information about a reward, but it remains unknown whether, and how, neurons encode choices of instrumental information, in contexts in which the information guides subsequent actions. Here we show that parietal cortical neurons involved in oculomotor decisions encode, before an information sampling saccade, the reduction in uncertainty that the saccade is expected to bring for a subsequent action. These responses were distinct from the neurons' visual and saccadic modulations and from signals of expected reward or reward prediction errors. Therefore, even in an instrumental context when information and reward gains are closely correlated, individual cells encode decision variables that are based on informational factors and can guide the active sampling of action-relevant cues.

Antagonistic Interactions Between Microsaccades and Evidence Accumulation Processes During Decision Formation.

Despite their small size, microsaccades can impede stimulus detections if executed at inopportune times. Although it has been shown that microsaccades evoke both inhibitory and excitatory responses across different visual regions, their impact on the higher-level neural decision processes that bridge sensory responses to action selection has yet to be examined. Here, we show that when human observers monitor stimuli for subtle feature changes, the occurrence of microsaccades long after (up to 800 ms) change onset predicts slower reaction times and this is accounted for by momentary suppression of neural signals at each key stage of decision formation: visual evidence encoding, evidence accumulation, and motor preparation. Our data further reveal that, independent of the timing of the change events, the onset of neural decision formation coincides with a systematic inhibition of microsaccade production, persisting until the perceptual report is executed. Our combined behavioral and neural measures highlight antagonistic interactions between microsaccade occurrence and evidence accumulation during visual decision-making tasks.SIGNIFICANCE STATEMENT When fixating on a location in space, we frequently make tiny eye movements called microsaccades. In the present study, we show that these microsaccades impede our ability to make perceptual decisions about visual stimuli and this impediment specifically occurs via the disruption of several processing levels of the sensorimotor network: the encoding of visual evidence itself, the accumulation of visual evidence toward a response, and effector-selective motor preparation. Furthermore, we show that the production of microsaccades is inhibited during the perceptual decision, possibly as a counteractive measure to mitigate their negative effect on behavior in this context. The combined behavioral and neural measures used in this study provide strong and novel evidence for the interaction of fixational eye movements and the perceptual decision-making process.

Neural Signature of Value-Based Sensorimotor Prioritization in Humans.

In situations in which impending sensory events demand fast action choices, we must be ready to prioritize higher-value courses of action to avoid missed opportunities. When such a situation first presents itself, stimulus-action contingencies and their relative value must be encoded to establish a value-biased state of preparation for an impending sensorimotor decision. Here, we sought to identify neurophysiological signatures of such processes in the human brain (both female and male). We devised a task requiring fast action choices based on the discrimination of a simple visual cue in which the differently valued sensory alternatives were presented 750-800 ms before as peripheral "targets" that specified the stimulus-action mapping for the upcoming decision. In response to the targets, we identified a discrete, transient, spatially selective signal in the event-related potential (ERP), which scaled with relative value and strongly predicted the degree of behavioral bias in the upcoming decision both across and within subjects. This signal is not compatible with any hitherto known ERP signature of spatial selection and also bears novel distinctions with respect to characterizations of value-sensitive, spatially selective activity found in sensorimotor areas of nonhuman primates. Specifically, a series of follow-up experiments revealed that the signal was reliably invoked regardless of response laterality, response modality, sensory feature, and reward valence. It was absent, however, when the response deadline was relaxed and the strategic need for biasing removed. Therefore, more than passively representing value or salience, the signal appears to play a versatile and active role in adaptive sensorimotor prioritization.SIGNIFICANCE STATEMENT In many situations such as fast-moving sports, we must be ready to act fast in response to sensory events and, in our preparation, prioritize courses of action that lead to greater rewards. Although behavioral effects of value biases in sensorimotor decision making have been widely studied, little is known about the neural processes that set these biases in place beforehand. Here, we report the discovery of a transient, spatially selective neural signal in humans that encodes the relative value of competing decision alternatives and strongly predicts behavioral value biases in decisions made ∼500 ms later. Follow-up manipulations of value differential, reward valence, response modality, sensory features, and time constraints establish that the signal reflects an active, feature- and effector-general preparatory mechanism for value-based prioritization.

Visuospatial Asymmetries Arise from Differences in the Onset Time of Perceptual Evidence Accumulation.

Healthy subjects tend to exhibit a bias of visual attention whereby left hemifield stimuli are processed more quickly and accurately than stimuli appearing in the right hemifield. It has long been held that this phenomenon arises from the dominant role of the right cerebral hemisphere in regulating attention. However, methods that would enable more precise understanding of the mechanisms underpinning visuospatial bias have remained elusive. We sought to finely trace the temporal evolution of spatial biases by leveraging a novel bilateral dot motion detection paradigm. In combination with electroencephalography, this paradigm enables researchers to isolate discrete neural signals reflecting the key neural processes needed for making these detection decisions. These include signals for spatial attention, early target selection, evidence accumulation, and motor preparation. Using this method, we established that three key neural markers accounted for unique between-subject variation in visuospatial bias: hemispheric asymmetry in posterior α power measured before target onset, which is related to the distribution of preparatory attention across the visual field; asymmetry in the peak latency of the early N2c target-selection signal; and, finally, asymmetry in the onset time of the subsequent neural evidence-accumulation process with earlier onsets for left hemifield targets. Our development of a single paradigm to dissociate distinct processing components that track the temporal evolution of spatial biases not only advances our understanding of the neural mechanisms underpinning normal visuospatial attention bias, but may also in the future aid differential diagnoses in disorders of spatial attention.SIGNIFICANCE STATEMENT The significance of this research is twofold. First, it shows that individual differences in how humans direct their attention between left and right space reflects physiological differences in how early the brain starts to accumulate evidence for the existence of a visual target. Second, the novel methods developed here may have particular relevance to disorders of attention, such as unilateral spatial neglect. In the case of spatial neglect, pathological inattention to left space could have multiple underlying causes, including biased attention, impaired decision formation, or a motor deficit related to one side of space. Our development of a single paradigm to dissociate each of these components may aid in supporting more precise differential diagnosis in such heterogeneous disorders.

Abstract and Effector-Selective Decision Signals Exhibit Qualitatively Distinct Dynamics before Delayed Perceptual Reports.

UNLABELLED: Electrophysiological research has isolated neural signatures of decision formation in a variety of brain regions. Studies in rodents and monkeys have focused primarily on effector-selective signals that translate the emerging decision into a specific motor plan, but, more recently, research on the human brain has identified an abstract signature of evidence accumulation that does not appear to play any direct role in action preparation. The functional dissociations between these distinct signal types have only begun to be characterized, and their dynamics during decisions with deferred actions with or without foreknowledge of stimulus-effector mapping, a commonly studied task scenario in single-unit and functional imaging investigations, have not been established. Here we traced the dynamics of distinct abstract and effector-selective decision signals in the form of the broad-band centro-parietal positivity (CPP) and limb-selective ß-band (8-16 and 18-30 Hz) EEG activity, respectively, during delayed-reported motion direction decisions with and without foreknowledge of direction-response mapping. With foreknowledge, the CPP and ß-band signals exhibited a similar gradual build-up following evidence onset, but whereas choice-predictive ß-band activity persisted up until the delayed response, the CPP dropped toward baseline after peaking. Without foreknowledge, the CPP exhibited identical dynamics, whereas choice-selective ß-band activity was eliminated. These findings highlight qualitative functional distinctions between effector-selective and abstract decision signals and are of relevance to the assumptions founding functional neuroimaging investigations of decision-making. SIGNIFICANCE STATEMENT: Neural signatures of evidence accumulation have been isolated in numerous brain regions. Although animal neurophysiology has largely concentrated on effector-selective decision signals that translate the emerging decision into a specific motor plan, recent research on the human brain has isolated abstract neural signatures of decision formation that are independent of specific sensory and motor requirements. Here, we examine the functional distinctions between the two distinct classes of decision variable signal during decisions with deferred actions with and without foreknowledge of stimulus-effector mapping. We find salient distinctions in the dynamics of abstract versus effector-selective decision signals in the human brain, in terms of sustainment through response delays and contingency on foreknowledge of stimulus-response mapping.

Attention Strongly Modulates Reliability of Neural Responses to Naturalistic Narrative Stimuli.

Attentional engagement is a major determinant of how effectively we gather information through our senses. Alongside the sheer growth in the amount and variety of information content that we are presented with through modern media, there is increased variability in the degree to which we "absorb" that information. Traditional research on attention has illuminated the basic principles of sensory selection to isolated features or locations, but it provides little insight into the neural underpinnings of our attentional engagement with modern naturalistic content. Here, we show in human subjects that the reliability of an individual's neural responses with respect to a larger group provides a highly robust index of the level of attentional engagement with a naturalistic narrative stimulus. Specifically, fast electroencephalographic evoked responses were more strongly correlated across subjects when naturally attending to auditory or audiovisual narratives than when attention was directed inward to a mental arithmetic task during stimulus presentation. This effect was strongest for audiovisual stimuli with a cohesive narrative and greatly reduced for speech stimuli lacking meaning. For compelling audiovisual narratives, the effect is remarkably strong, allowing perfect discrimination between attentional state across individuals. Control experiments rule out possible confounds related to altered eye movement trajectories or order of presentation. We conclude that reliability of evoked activity reproduced across subjects viewing the same movie is highly sensitive to the attentional state of the viewer and listener, which is aided by a cohesive narrative.

Effects of Stimulus Size and Contrast on the Initial Primary Visual Cortical Response in Humans.

Decades of intracranial electrophysiological investigation into the primary visual cortex (V1) have produced many fundamental insights into the computations carried out in low-level visual circuits of the brain. Some of the most important work has been simply concerned with the precise measurement of neural response variations as a function of elementary stimulus attributes such as contrast and size. Surprisingly, such simple but fundamental characterization of V1 responses has not been carried out in human electrophysiology. Here we report such a detailed characterization for the initial "C1" component of the scalp-recorded visual evoked potential (VEP). The C1 is known to be dominantly generated by initial afferent activation in V1, but is difficult to record reliably due to interindividual anatomical variability. We used pattern-pulse multifocal VEP mapping to identify a stimulus position that activates the left lower calcarine bank in each individual, and afterwards measured robust negative C1s over posterior midline scalp to gratings presented sequentially at that location. We found clear and systematic increases in C1 peak amplitude and decreases in peak latency with increasing size as well as with increasing contrast. With a sample of 15 subjects and ~180 trials per condition, reliable C1 amplitudes of -0.46 µV were evoked at as low a contrast as 3.13% and as large as -4.82 µV at 100% contrast, using stimuli of 3.33° diameter. A practical implication is that by placing sufficiently-sized stimuli to target favorable calcarine cortical loci, robust V1 responses can be measured at contrasts close to perceptual thresholds, which could greatly facilitate principled studies of early visual perception and attention.

Mapping standard ophthalmic outcome sets to metrics currently reported in eight eye hospitals.

BACKGROUND: To determine alignment of proposed international standard outcomes sets for ophthalmic conditions to metrics currently reported by eye hospitals. METHODS: Mixed methods comparative benchmark study, including eight eye hospitals in Australia, India, Singapore, Sweden, U.K., and U.S. All are major international tertiary care and training centers in ophthalmology. Main outcome measure is consistency of ophthalmic outcomes measures reported. RESULTS: International agreed standard outcomes (ICHOM) sets are available for cataract surgery (10 metrics) and macular degeneration (7 metrics). The eight hospitals reported 22 different metrics for cataract surgery and 2 for macular degeneration, which showed only limited overlap with the proposed ICHOM metrics. None of the hospitals reported patient reported visual functioning or vision-related quality of life outcomes measures (PROMs). Three hospitals (38%) reported rates for uncomplicated cataract surgeries only. There was marked variation in how and at what point postoperatively visual outcomes following cataract, cornea, glaucoma, strabismus and oculoplastics procedures were reported. Seven (87.5%) measured post-operative infections and four (50%) measured 30 day unplanned reoperation rates. CONCLUSIONS: Outcomes reporting for ophthalmic conditions currently widely varies across hospitals internationally and does not include patient-reported outcomes. Reaching consensus on measures and consistency in data collection will allow meaningful comparisons and provide an evidence base enabling improved sharing of "best practices" to improve eye care globally. Implementation of international standards is still a major challenge and practice-based knowledge on measures should be one of the inputs of the international standardization process.

Evidence of substantial development of inhibitory control and sustained attention between 6 and 8years of age on an unpredictable Go/No-Go task.

Inhibitory control and sustained attention are important cognitive abilities; however, their developmental trajectories remain unclear. In total, 35 6-year-olds, 32 8-year-olds, and 37 10-year-olds performed a Go/No-Go task; this required frequent responding to stimuli with infrequent inhibition to a target that appeared unpredictably. Children performed this task three times over 12months. Response time variability and accuracy measures, linked to inhibition and sustained attention, were assessed. Specifically, fast Fourier transform and ex-Gaussian analyses of response time data provided several measures of response time variability; these measures are thought to represent different components of sustained attention. The 6-year-olds performed less well than the older groups on most measures. The 8-year-olds exhibited greater momentary fluctuations in response time and made more long responses than the 10-year-olds; otherwise, there were few differences between the two older groups. Response inhibition and sustained attention developed significantly between 6 and 8years of age, with subtle changes in attentional control between 8 and 11years of age.

Tracking neural correlates of successful learning over repeated sequence observations.

The neural correlates of memory formation in humans have long been investigated by exposing subjects to diverse material and comparing responses to items later remembered to those forgotten. Tasks requiring memorization of sensory sequences afford unique possibilities for linking neural memorization processes to behavior, because, rather than comparing across different items of varying content, each individual item can be examined across the successive learning states of being initially unknown, newly learned, and eventually, fully known. Sequence learning paradigms have not yet been exploited in this way, however. Here, we analyze the event-related potentials of subjects attempting to memorize sequences of visual locations over several blocks of repeated observation, with respect to pre- and post-block recall tests. Over centro-parietal regions, we observed a rapid P300 component superimposed on a broader positivity, which exhibited distinct modulations across learning states that were replicated in two separate experiments. Consistent with its well-known encoding of surprise, the P300 deflection monotonically decreased over blocks as locations became better learned and hence more expected. In contrast, the broader positivity was especially elevated at the point when a given item was newly learned, i.e., started being successfully recalled. These results implicate the Broad Positivity in endogenously-driven, intentional memory formation, whereas the P300, in processing the current stimulus to the degree that it was previously uncertain, indexes the cumulative knowledge thereby gained. The decreasing surprise/P300 effect significantly predicted learning success both across blocks and across subjects. This presents a new, neural-based means to evaluate learning capabilities independent of verbal reports, which could have considerable value in distinguishing genuine learning disabilities from difficulties to communicate the outcomes of learning, or perceptual impairments, in a range of clinical brain disorders.

Response time variability under slow and fast-incentive conditions in children with ASD, ADHD and ASD+ADHD.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) show significant behavioural and genetic overlap. Both ADHD and ASD are characterised by poor performance on a range of cognitive tasks. In particular, increased response time variability (RTV) is a promising indicator of risk for both ADHD and ASD. However, it is not clear whether different indices of RTV and changes to RTV according to task conditions are able to discriminate between the two disorders. METHODS: Children with ASD (n = 19), ADHD (n = 18), ASD + ADHD (n = 29) and typically developing controls (TDC; n = 26) performed a four-choice RT task with slow-baseline and fast-incentive conditions. Performance was characterised by mean RT (MRT), standard deviation of RT (SD-RT), coefficient of variation (CV) and ex-Gaussian distribution measures of Mu, Sigma and Tau. RESULTS: In the slow-baseline condition, categorical diagnoses and trait measures converged to indicate that children with ADHD-only and ASD + ADHD demonstrated increased MRT, SD-RT, CV and Tau compared to TDC and ASD-only. Importantly, greater improvement in MRT, SD-RT and Tau was demonstrated in ADHD and ASD + ADHD from slow-baseline to fast-incentive conditions compared to TDC and ASD-only. CONCLUSIONS: Slower and more variable RTs are markers of ADHD compared to ASD and typically developing controls during slow and less rewarding conditions. Energetic factors and rewards improve task performance to a greater extent in children with ADHD compared to children with ASD. These findings suggest that RTV can be distinguished in ASD, ADHD and ASD + ADHD based on the indices of variability used and the conditions in which they are elicited. Further work identifying neural processes underlying increased RTV is warranted, in order to elucidate disorder-specific and disorder-convergent aetiological pathways.

Electrophysiological indices of surround suppression in humans.

Surround suppression is a well-known example of contextual interaction in visual cortical neurophysiology, whereby the neural response to a stimulus presented within a neuron's classical receptive field is suppressed by surrounding stimuli. Human psychophysical reports present an obvious analog to the effects seen at the single-neuron level: stimuli are perceived as lower-contrast when embedded in a surround. Here we report on a visual paradigm that provides relatively direct, straightforward indices of surround suppression in human electrophysiology, enabling us to reproduce several well-known neurophysiological and psychophysical effects, and to conduct new analyses of temporal trends and retinal location effects. Steady-state visual evoked potentials (SSVEP) elicited by flickering "foreground" stimuli were measured in the context of various static surround patterns. Early visual cortex geometry and retinotopic organization were exploited to enhance SSVEP amplitude. The foreground response was strongly suppressed as a monotonic function of surround contrast. Furthermore, suppression was stronger for surrounds of matching orientation than orthogonally-oriented ones, and stronger at peripheral than foveal locations. These patterns were reproduced in psychophysical reports of perceived contrast, and peripheral electrophysiological suppression effects correlated with psychophysical effects across subjects. Temporal analysis of SSVEP amplitude revealed short-term contrast adaptation effects that caused the foreground signal to either fall or grow over time, depending on the relative contrast of the surround, consistent with stronger adaptation of the suppressive drive. This electrophysiology paradigm has clinical potential in indexing not just visual deficits but possibly gain control deficits expressed more widely in the disordered brain.

The classic P300 encodes a build-to-threshold decision variable.

The P300 component of the human event-related potential has been the subject of intensive experimental investigation across a five-decade period, owing to its apparent relevance to a wide range of cognitive functions and its sensitivity to numerous brain disorders, yet its exact contribution to cognition remains unresolved. Here, we carry out key analyses of the P300 elicited by transient auditory and visual targets to examine its potential role as a 'decision variable' signal that accumulates evidence to a decision bound. Consistent with the latter, we find that the P300 reaches a stereotyped amplitude immediately prior to response execution and that its rate of rise scales with target detection difficulty and accounts for trial-to-trial variance in RT. Computational simulations of an accumulation-to-bound decision process faithfully captured P300 dynamics when its parameters were set by model fits to the RT distributions. Thus, where the dominant explanatory accounts have conceived of the P300 as a unitary neural event, our data reveal it to be a dynamically evolving neural signature of decision formation. These findings place the P300 at the heart of a mechanistically principled framework for understanding decision-making in both the typical and atypical human brain.

Rate of vision loss in neovascular age-related macular degeneration explored.

PURPOSE: To explore decline in visual acuity in patients with neovascular age-related macular degeneration (n-AMD) awaiting intravitreal bevacizumab or ranibizumab treatment following initial diagnosis and after disease reactivation. METHODS: Retrospective analysis of 74 treatment-naïve patients (84 eyes) in two centers in Córdoba, Argentina. The time between treatment indication and intravitreal injection, and the changes in BCVA produced during this delay were studied in both periods. A linear regression model to search the impact of time on progression visual impairment was conducted. RESULTS: In both periods, a significant reduction in vision occurred awaiting intravitreal injection. The longer the delay, the greater the vision loss (R2 = 0.55 p < 0.01) and the less improvement following treatment (Pearson coefficient -0.26). The result of the model shows that the change in vision as a function of initial delay were best described by a polynomic model with a mean loss of 5 letters in the first 3 weeks, a slowdown in the rate of change of VA, and a dependence of visual acuity at the moment of diagnosis . The loss of visual acuity after reactivation shows the same behavior as at the onset of the disease but independent of visual acuity prior to reactivation. CONCLUSION: Visual loss awaiting injection intravitreal anti-VEGF is clinically significant and with an asymptotic pattern, with early rapid loss of vision in both the onset of the disease and the reactivation. Initiation of anti-VEGF treatment must be undertaken urgently, as should retreatment of disease activation to reduce visual loss.

Internal and external influences on the rate of sensory evidence accumulation in the human brain.

We frequently need to make timely decisions based on sensory evidence that is weak, ambiguous, or noisy resulting from conditions in the external environment (e.g., a cluttered visual scene) or within the brain itself (e.g., inattention, neural noise). Here we examine how externally and internally driven variations in the quality of sensory evidence affect the build-to-threshold dynamics of a supramodal "decision variable" signal and, hence, the timing and accuracy of decision reports in humans. Observers performed a continuous-monitoring version of the prototypical two-alternative dot-motion discrimination task, which is known to strongly benefit from sequential sampling and temporal accumulation of evidence. A centroparietal positive potential (CPP), which we previously established as a supramodal decision signal based on its invariance to motor or sensory parameters, exhibited two key identifying properties associated with the "decision variable" long described in sequential sampling models: (1) its buildup rate systematically scaled with sensory evidence strength across four levels of motion coherence, consistent with temporal integration; and (2) its amplitude reached a stereotyped level at the moment of perceptual report executions, consistent with a boundary-crossing stopping criterion. The buildup rate of the CPP also strongly predicted reaction time within coherence levels (i.e., independent of physical evidence strength), and this endogenous variation was linked with attentional fluctuations indexed by the level of parieto-occipital α-band activity preceding target onset. In tandem with the CPP, build-to-threshold dynamics were also observed in an effector-selective motor preparation signal; however, the buildup of this motor-specific process significantly lagged that of the supramodal process.

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.

An eye on equity: faricimab-driven health equity improvements in diabetic macular oedema using a distributional cost-effectiveness analysis from a UK societal perspective.

BACKGROUND/OBJECTIVES: Diabetic macular oedema (DMO) is a leading cause of blindness in developed countries, with significant disease burden associated with socio-economic deprivation. Distributional cost-effectiveness analysis (DCEA) allows evaluation of health equity impacts of interventions, estimation of how health outcomes and costs are distributed in the population, and assessments of potential trade-offs between health maximisation and equity. We conducted an aggregate DCEA to determine the equity impact of faricimab. METHODS: Data on health outcomes and costs were derived from a cost-effectiveness model of faricimab compared with ranibizumab, aflibercept and off-label bevacizumab using a societal perspective in the base case and a healthcare payer perspective in scenario analysis. Health gains and health opportunity costs were distributed across socio-economic subgroups. Health and equity impacts, measured using the Atkinson inequality index, were assessed visually on an equity-efficiency impact plane and combined into a measure of societal welfare. RESULTS: At an opportunity cost threshold of £20,000/quality-adjusted life year (QALY), faricimab displayed an increase in net health benefits against all comparators and was found to improve equity. The equity impact increased the greater the concerns for reducing health inequalities over maximising population health. Using a healthcare payer perspective, faricimab was equity improving in most scenarios. CONCLUSIONS: Long-acting therapies with fewer injections, such as faricimab, may reduce costs, improve health outcomes and increase health equity. Extended economic evaluation frameworks capturing additional value elements, such as DCEA, enable a more comprehensive valuation of interventions, which is of relevance to decision-makers, healthcare professionals and patients.

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. Participants undergoing invasive electrophysiological monitoring for epilepsy were asked to judge the direction of random-dot stimuli and respond either with a speeded button press (N = 24), or vocally, after a randomized delay (N = 12). We found a widely distributed motor-independent network of regions where high-frequency activity exhibited key characteristics consistent with evidence accumulation, including a gradual buildup that was modulated by the strength of the sensory evidence, and an amplitude that predicted participants' choice accuracy and response time. Our findings offer a new view on the brain networks governing human decision-making.