Pre-stroke disability and stroke severity as predictors of discharge destination from an acute stroke ward.

BACKGROUND AND RATIONALE: Reliable prediction of discharge destination in acute stroke informs discharge planning and can determine the expectations of patients and carers. There is no existing model that does this using routinely collected indices of pre-morbid disability and stroke severity. METHODS: Age, gender, pre-morbid modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) were gathered prospectively on an acute stroke unit from 1,142 consecutive patients. A multiclass random forest classifier was used to train and validate a model to predict discharge destination. RESULTS: Used alone, the mRS is the strongest predictor of discharge destination. The NIHSS is only predictive when combined with our other variables. The accuracy of the final model was 70.4% overall with a positive predictive value (PPV) and sensitivity of 0.88 and 0.78 for home as the destination, 0.68 and 0.88 for continued inpatient care, 0.7 and 0.53 for community hospital, and 0.5 and 0.18 for death, respectively. CONCLUSION: Pre-stroke disability rather than stroke severity is the strongest predictor of discharge destination, but in combination with other routinely collected data, both can be used as an adjunct by the multidisciplinary team to predict discharge destination in patients with acute stroke.

A deep learning framework for neuroscience.

Systems neuroscience seeks explanations for how the brain implements a wide variety of perceptual, cognitive and motor tasks. Conversely, artificial intelligence attempts to design computational systems based on the tasks they will have to solve. In artificial neural networks, the three components specified by design are the objective functions, the learning rules and the architectures. With the growing success of deep learning, which utilizes brain-inspired architectures, these three designed components have increasingly become central to how we model, engineer and optimize complex artificial learning systems. Here we argue that a greater focus on these components would also benefit systems neuroscience. We give examples of how this optimization-based framework can drive theoretical and experimental progress in neuroscience. We contend that this principled perspective on systems neuroscience will help to generate more rapid progress.

Action boosts episodic memory encoding in humans via engagement of a noradrenergic system.

We are constantly interacting with our environment whilst we encode memories. However, how actions influence memory formation remains poorly understood. Goal-directed movement engages the locus coeruleus (LC), the main source of noradrenaline in the brain. Noradrenaline is also known to enhance episodic encoding, suggesting that action could improve memory via LC engagement. Here we demonstrate, across seven experiments, that action (Go-response) enhances episodic encoding for stimuli unrelated to the action itself, compared to action inhibition (NoGo). Functional magnetic resonance imaging, and pupil diameter as a proxy measure for LC-noradrenaline transmission, indicate increased encoding-related LC activity during action. A final experiment, replicated in two independent samples, confirmed a novel prediction derived from these data that emotionally aversive stimuli, which recruit the noradrenergic system, modulate the mnemonic advantage conferred by Go-responses relative to neutral stimuli. We therefore provide converging evidence that action boosts episodic memory encoding via a noradrenergic mechanism.

Cortical beta oscillations are associated with motor performance following visuomotor learning.

People vary in their capacity to learn and retain new motor skills. Although the relationship between neuronal oscillations in the beta frequency range (15-30 Hz) and motor behaviour is well established, the electrophysiological mechanisms underlying individual differences in motor learning are incompletely understood. Here, we investigated the degree to which measures of resting and movement-related beta power from sensorimotor cortex account for inter-individual differences in motor learning behaviour in the young and elderly. Twenty young (18-30 years) and twenty elderly (62-77 years) healthy adults were trained on a novel wrist flexion/extension tracking task and subsequently retested at two different time points (45-60 min and 24 h after initial training). Scalp EEG was recorded during a separate simple motor task before each training and retest session. Although short-term motor learning was comparable between young and elderly individuals, there was considerable variability within groups with subsequent analysis aiming to find the predictors of this variability. As expected, performance during the training phase was the best predictor of performance at later time points. However, regression analysis revealed that movement-related beta activity significantly explained additional variance in individual performance levels 45-60 min, but not 24 h after initial training. In the context of disease, these findings suggest that measurements of beta-band activity may offer novel targets for therapeutic interventions designed to promote rehabilitative outcomes.

Computing Value from Quality and Quantity in Human Decision-Making.

How organisms learn the value of single stimuli through experience is well described. In many decisions, however, value estimates are computed "on the fly" by combining multiple stimulus attributes. The neural basis of this computation is poorly understood. Here we explore a common scenario in which decision-makers must combine information about quality and quantity to determine the best option. Using fMRI, we examined the neural representation of quality, quantity, and their integration into an integrated subjective value signal in humans of both genders. We found that activity within inferior frontal gyrus (IFG) correlated with offer quality, while activity in the intraparietal sulcus (IPS) specifically correlated with offer quantity. Several brain regions, including the anterior cingulate cortex (ACC), were sensitive to an interaction of quality and quantity. However, the ACC was uniquely activated by quality, quantity, and their interaction, suggesting that this region provides a substrate for flexible computation of value from both quality and quantity. Furthermore, ACC signals across subjects correlated with the strength of quality and quantity signals in IFG and IPS, respectively. ACC tracking of subjective value also correlated with choice predictability. Finally, activity in the ACC was elevated for choice trials, suggesting that ACC provides a nexus for the computation of subjective value in multiattribute decision-making.SIGNIFICANCE STATEMENT Would you prefer three apples or two oranges? Many choices we make each day require us to weigh up the quality and quantity of different outcomes. Using fMRI, we show that option quality is selectively represented in the inferior frontal gyrus, while option quantity correlates with areas of the intraparietal sulcus that have previously been associated with numerical processing. We show that information about the two is integrated into a value signal in the anterior cingulate cortex, and the fidelity of this integration predicts choice predictability. Our results demonstrate how on-the-fly value estimates are computed from multiple attributes in human value-based decision-making.

Triple dissociation of attention and decision computations across prefrontal cortex.

Naturalistic decision-making typically involves sequential deployment of attention to choice alternatives to gather information before a decision is made. Attention filters how information enters decision circuits, thus implying that attentional control may shape how decision computations unfold. We recorded neuronal activity from three subregions of the prefrontal cortex (PFC) while monkeys performed an attention-guided decision-making task. From the first saccade to decision-relevant information, a triple dissociation of decision- and attention-related computations emerged in parallel across PFC subregions. During subsequent saccades, orbitofrontal cortex activity reflected the value comparison between currently and previously attended information. In contrast, the anterior cingulate cortex carried several signals reflecting belief updating in light of newly attended information, the integration of evidence to a decision bound and an emerging plan for what action to choose. Our findings show how anatomically dissociable PFC representations evolve during attention-guided information search, supporting computations critical for value-guided choice.

Movement-related beta oscillations show high intra-individual reliability.

Oscillatory activity in the beta frequency range (15-30Hz) recorded from human sensorimotor cortex is of increasing interest as a putative biomarker of motor system function and dysfunction. Despite its increasing use in basic and clinical research, surprisingly little is known about the test-retest reliability of spectral power and peak frequency measures of beta oscillatory signals from sensorimotor cortex. Establishing that these beta measures are stable over time in healthy populations is a necessary precursor to their use in the clinic. Here, we used scalp electroencephalography (EEG) to evaluate intra-individual reliability of beta-band oscillations over six sessions, focusing on changes in beta activity during movement (Movement-Related Beta Desynchronization, MRBD) and after movement termination (Post-Movement Beta Rebound, PMBR). Subjects performed visually-cued unimanual wrist flexion and extension. We assessed Intraclass Correlation Coefficients (ICC) and between-session correlations for spectral power and peak frequency measures of movement-related and resting beta activity. Movement-related and resting beta power from both sensorimotor cortices was highly reliable across sessions. Resting beta power yielded highest reliability (average ICC=0.903), followed by MRBD (average ICC=0.886) and PMBR (average ICC=0.663). Notably, peak frequency measures yielded lower ICC values compared to the assessment of spectral power, particularly for movement-related beta activity (ICC=0.386-0.402). Our data highlight that power measures of movement-related beta oscillations are highly reliable, while corresponding peak frequency measures show greater intra-individual variability across sessions. Importantly, our finding that beta power estimates show high intra-individual reliability over time serves to validate the notion that these measures reflect meaningful individual differences that can be utilised in basic research and clinical studies.

Pharmacological Fingerprints of Contextual Uncertainty.

Successful interaction with the environment requires flexible updating of our beliefs about the world. By estimating the likelihood of future events, it is possible to prepare appropriate actions in advance and execute fast, accurate motor responses. According to theoretical proposals, agents track the variability arising from changing environments by computing various forms of uncertainty. Several neuromodulators have been linked to uncertainty signalling, but comprehensive empirical characterisation of their relative contributions to perceptual belief updating, and to the selection of motor responses, is lacking. Here we assess the roles of noradrenaline, acetylcholine, and dopamine within a single, unified computational framework of uncertainty. Using pharmacological interventions in a sample of 128 healthy human volunteers and a hierarchical Bayesian learning model, we characterise the influences of noradrenergic, cholinergic, and dopaminergic receptor antagonism on individual computations of uncertainty during a probabilistic serial reaction time task. We propose that noradrenaline influences learning of uncertain events arising from unexpected changes in the environment. In contrast, acetylcholine balances attribution of uncertainty to chance fluctuations within an environmental context, defined by a stable set of probabilistic associations, or to gross environmental violations following a contextual switch. Dopamine supports the use of uncertainty representations to engender fast, adaptive responses.

Acute stress selectively impairs learning to act.

Stress interferes with instrumental learning. However, choice is also influenced by non-instrumental factors, most strikingly by biases arising from Pavlovian associations that facilitate action in pursuit of rewards and inaction in the face of punishment. Whether stress impacts on instrumental learning via these Pavlovian associations is unknown. Here, in a task where valence (reward or punishment) and action (go or no-go) were orthogonalised, we asked whether the impact of stress on learning was action or valence specific. We exposed 60 human participants either to stress (socially-evaluated cold pressor test) or a control condition (room temperature water). We contrasted two hypotheses: that stress would lead to a non-selective increase in the expression of Pavlovian biases; or that stress, as an aversive state, might specifically impact action production due to the Pavlovian linkage between inaction and aversive states. We found support for the second of these hypotheses. Stress specifically impaired learning to produce an action, irrespective of the valence of the outcome, an effect consistent with a Pavlovian linkage between punishment and inaction. This deficit in action-learning was also reflected in pupillary responses; stressed individuals showed attenuated pupillary responses to action, hinting at a noradrenergic contribution to impaired action-learning under stress.

The social contingency of momentary subjective well-being.

Although social comparison is a known determinant of overall life satisfaction, it is not clear how it affects moment-to-moment variation in subjective emotional state. Using a novel social decision task combined with computational modelling, we show that a participant's subjective emotional state reflects not only the impact of rewards they themselves receive, but also the rewards received by a social partner. Unequal outcomes, whether advantageous or disadvantageous, reduce average momentary happiness. Furthermore, the relative impacts of advantageous and disadvantageous inequality on momentary happiness at the individual level predict a subject's generosity in a separate dictator game. These findings demonstrate a powerful social influence upon subjective emotional state, where emotional reactivity to inequality is strongly predictive of altruism in an independent task domain.

Computations of uncertainty mediate acute stress responses in humans.

The effects of stress are frequently studied, yet its proximal causes remain unclear. Here we demonstrate that subjective estimates of uncertainty predict the dynamics of subjective and physiological stress responses. Subjects learned a probabilistic mapping between visual stimuli and electric shocks. Salivary cortisol confirmed that our stressor elicited changes in endocrine activity. Using a hierarchical Bayesian learning model, we quantified the relationship between the different forms of subjective task uncertainty and acute stress responses. Subjective stress, pupil diameter and skin conductance all tracked the evolution of irreducible uncertainty. We observed a coupling between emotional and somatic state, with subjective and physiological tuning to uncertainty tightly correlated. Furthermore, the uncertainty tuning of subjective and physiological stress predicted individual task performance, consistent with an adaptive role for stress in learning under uncertain threat. Our finding that stress responses are tuned to environmental uncertainty provides new insight into their generation and likely adaptive function.

Single-unit recordings in the macaque face patch system reveal limitations of fMRI MVPA.

Multivariate pattern analysis (MVPA) of fMRI data has become an important technique for cognitive neuroscientists in recent years; however, the relationship between fMRI MVPA and the underlying neural population activity remains unexamined. Here, we performed MVPA of fMRI data and single-unit data in the same species, the macaque monkey. Facial recognition in the macaque is subserved by a well characterized system of cortical patches, which provided the test bed for our comparison. We showed that neural population information about face viewpoint was readily accessible with fMRI MVPA from all face patches, in agreement with single-unit data. Information about face identity, although it was very strongly represented in the populations of units of the anterior face patches, could not be retrieved from the same data. The discrepancy was especially striking in patch AL, where neurons encode both the identity and viewpoint of human faces. From an analysis of the characteristics of the neural representations for viewpoint and identity, we conclude that fMRI MVPA cannot decode information contained in the weakly clustered neuronal responses responsible for coding the identity of human faces in the macaque brain. Although further studies are needed to elucidate the relationship between information decodable from fMRI multivoxel patterns versus single-unit populations for other variables in other brain regions, our result has important implications for the interpretation of negative findings in fMRI multivoxel pattern analyses.

Understanding the behavioural consequences of noninvasive brain stimulation.

Transcranial electrical stimulation (tES) influences neural activity in a way that can elicit behavioural change but may also improve high-level cognition or ameliorate symptoms in neuropsychiatric disorders. However, the current fervour for tES contrasts with the paucity of mechanistically detailed models of how stimulation causes behavioural change. Here we challenge the plausibility of several common assumptions and interpretations of tES and discuss how to bridge the ravines separating our understanding of the behavioural and neural consequences of tES. We argue that rational application of tES should occur in tandem with computational neurostimulation and appropriate physiological and behavioural assays. This will aid appreciation of the limitations of tES and generate testable predictions of how tES expresses its effects on behaviour.

Predicting the behavioral impact of transcranial direct current stimulation: issues and limitations.

The transcranial application of weak currents to the human brain has enjoyed a decade of widespread use, providing a simple and powerful tool for non-invasively altering human brain function. However, our understanding of current delivery and its impact upon neural circuitry leaves much to be desired. We argue that the credibility of conclusions drawn with transcranial direct current stimulation (tDCS) is contingent upon realistic explanations of how tDCS works, and that our present understanding of tDCS limits the technique's use to localize function in the human brain. We outline two central issues where progress is required: the localization of currents, and predicting their functional consequence. We encourage experimenters to eschew simplistic explanations of mechanisms of transcranial current stimulation. We suggest the use of individualized current modeling, together with computational neurostimulation to inform mechanistic frameworks in which to interpret the physiological impact of tDCS. We hope that through mechanistically richer descriptions of current flow and action, insight into the biological processes by which transcranial currents influence behavior can be gained, leading to more effective stimulation protocols and empowering conclusions drawn with tDCS.