Biology subjects

Kable, J. W.

Publications and source records attributed to Kable, J. W..

29 records · Page 2Linked to original sources

bioRxiv2020

The dorsal and ventral default mode networks are dissociably modulated by the valence and vividness of imagined events

Recent work has shown that the brains default mode network (DMN) is active when people imagine the future. Here we test whether future imagination can be decomposed into two dissociable psychological processes linked to different subcomponents of the DMN. While measuring brain activity with fMRI as subjects imagine future events, we manipulate the vividness of these events to modulate the demands for scene construction, and we manipulate the valence of these events to modulate the demands for evaluation. We found that one subcomponent of the DMN, the ventral DMN or medial temporal lobe subsystem, responds to the vividness but not the valence of imagined events. In contrast, another subcomponent, the dorsal or core DMN, responds to the valence but not the vividness of imagined events. This separate modifiability of different subcomponents of the DMN by vividness and valence provides strong evidence for a neurocognitive dissociation between (1) the construction of novel, imagined scenes from individual components from memory and (2) the evaluation of these constructed events as desirable or undesirable. Significance StatementPrevious work has suggested that imagination may depend on separate neural networks involved in the construction and evaluation of imagined future events. This study provides strong neural evidence for this dissociation by demonstrating that two components of the brains default mode network (DMN) uniquely and specifically respond to different aspects of imagination. The vividness of imagined events modulates the ventral DMN, but not the dorsal DMN, while the valence of imagined events modulates the dorsal DMN, but not the ventral DMN. This supports the dissociable engagement of these sub-networks in constructing and evaluating imagined future events.

neuroscience↗

bioRxiv2020

Distinct neural encoding of context-dependent error signals and context-dependent changes in behavior during adaptive learning

Effective learning requires using errors in a task-dependent manner, for example adjusting to errors that result from unpredicted environmental changes but ignoring errors that result from environmental stochasticity. Where and how the brain represents errors in a task-dependent manner and uses them to guide behavior are not well understood. We imaged the brains of human participants performing a predictive-inference task with two conditions that had different sources of errors. Their performance was sensitive to this difference, including more choice switches after fundamental changes versus stochastic fluctuations in reward contingencies. Using multi-voxel pattern classification, we identified task-dependent representations of error magnitude and past errors in posterior parietal cortex. These representations were distinct from representations of the resulting behavioral adjustments in dorsomedial frontal, anterior cingulate, and orbitofrontal cortex. The results provide new insights into how the human brain represents errors in a task-dependent manner and guides subsequent adaptive behavior.

neuroscience↗

bioRxiv2020

The complexity of model-free and model-based learning strategies

Different learning strategies are thought to fall along a continuum that ranges from simple, inflexible, and fast "model-free" strategies, to more complex, flexible, and deliberative "model-based strategies". Here we show that, contrary to this proposal, strategies at both ends of this continuum can be equally flexible, effective, and time-intensive. We analyzed behavior of adult human subjects performing a canonical learning task used to distinguish between model-free and model-based strategies. Subjects using either strategy showed similarly high information complexity, a measure of strategic flexibility, and comparable accuracy and response times. This similarity was apparent despite the generally higher computational complexity of model-based algorithms and fundamental differences in how each strategy learned: model-free learning was driven primarily by observed past responses, whereas model-based learning was driven primarily by inferences about latent task features. Thus, model-free and model-based learning differ in the information they use to learn but can support comparably flexible behavior. Statement of RelevanceThe distinction between model-free and model-based learning is an influential framework that has been used extensively to understand individual- and task-dependent differences in learning by both healthy and clinical populations. A common interpretation of this distinction that model-based strategies are more complex and therefore more flexible than model-free strategies. However, this interpretation conflates computational complexity, which relates to processing resources and generally higher for model-based algorithms, with information complexity, which reflects flexibility but has rarely been measured. Here we use a metric of information complexity to demonstrate that, contrary to this interpretation, model-free and model-based strategies can be equally flexible, effective, and time-intensive and are better distinguished by the nature of the information from which they learn. Our results counter common interpretations of model-free versus model-based learning and demonstrate the general usefulness of information complexity for assessing different forms of strategic flexibility.

neuroscience↗

bioRxiv2019

Genetic Underpinnings of Risky Behavior Relate to Altered Neuroanatomy

Previous research points to the heritability of risk-taking behaviour. However, evidence on how genetic dispositions are translated into risky behaviour is scarce. Here, we report a genetically-informed neuroimaging study of real-world risky behaviour across the domains of drinking, smoking, driving, and sexual behaviour, in a European sample from the UK Biobank (N= 12,675). We find negative associations between risky behaviour and grey matter volume (GMV) in distinct brain regions, including amygdala, ventral striatum, hypothalamus, and dorsolateral prefrontal cortex (dlPFC). These effects replicate in an independent sample recruited from the same population (N=13,004). Polygenic risk scores for risky behaviour, derived from a genome-wide association study in an independent sample (N=297,025), are inversely associated with GMV in dlPFC, putamen, and hypothalamus. This relation mediates ~2.2% of the association between genes and behaviour. Our results highlight distinct heritable neuroanatomical features as manifestations of the genetic propensity for risk taking. One Sentence SummaryRisky behaviour and its genetic associations are linked to less grey matter volume in distinct brain regions.

neuroscience↗

bioRxiv2019

Disruption of Nrxn1α within excitatory forebrain circuits drives value-based dysfunction

Goal-directed behaviors, complex action sequences that maximize reward, are essential for normal function and are significantly impaired across neuropsychiatric disorders. Despite extensive associations between genetic mutations and these brain disorders, the mechanisms by which candidate genes contribute to goal-directed dysfunction remains unclear, owing to challenges in (1) describing aspects of reward processing that drive goal-directed dysfunction, (2) localizing these deficits to specific brain circuits and (3) relating changes in physiology to behavioral alterations. Here we examined mice with mutations in Neurexin1, a presynaptically-localized adhesion molecule with widespread neuropsychiatric dis ease association, in value-based decision-making paradigms. We found that Neurexin1 knockout animals exhibited blunted choice bias towards outcomes associated with greater benefits. Mutant mice were similarly impaired in avoiding costlier, benefit-neutral actions. Analysis of trial-by-trial choice data via reinforcement learning models suggested these behavioral patterns were driven largely by deficits in the updating and representation of choice values. Employing conditional gene ablation and region-specific Cre-recombinase strains, we revealed that Neurexin1 disruption within forebrain excitatory projection neurons, but not thalamic population s, recapitulated most aspects of the whole-brain knockout phenotype. Finally, utilizing in vivo recordings of direct pathway spiny neuron population calcium activity, we demonstrated that selective knockout of Neurexin1 within forebrain excitatory neurons disrupts reward-associated neural signals within striatum, a major site of feedback-based learning. By relating deficits in value-based decision-making to region-specific Nrxn1 disruption and changes in reward-associated neural activity, we reveal potential neural substrates for the pathophysiology of neuropsychiatric disease-associated cognitive dysfunction.

neuroscience↗

bioRxiv2019

Functional brain network reconfiguration during learning in a dynamic environment

When learning about dynamic and uncertain environments, people should update their beliefs most strongly when new evidence is most informative, such as when the environment undergoes a surprising change or existing beliefs are highly uncertain. Here we show that modulations of surprise and uncertainty are encoded in a particular, temporally dynamic pattern of whole-brain functional connectivity, and this encoding is enhanced in individuals that adapt their learning dynamics more appropriately in response to these factors. The key feature of this whole-brain pattern of functional connectivity is stronger connectivity, or functional integration, between the fronto-parietal and other functional systems. Our results provide new insights regarding the association between dynamic adjustments in learning and dynamic, large-scale changes in functional connectivity across the brain.

neuroscience↗

bioRxiv2019

Links between autobiographical memory richness and temporal discounting in older adults

When making choices between smaller, sooner rewards and larger, later ones, people tend to discount or devalue future outcomes. This propensity can be maladaptive, especially as individuals age and their decisions about health, investments, and relationships become increasingly consequential. Individual differences in temporal discounting in older adults have been associated with episodic memory abilities, as well as with cortical thickness in the entorhinal cortex. The mechanism by which better memory might lead to more future-oriented choice remains unclear, however. Here we used a fine-grained measure of autobiographical memory richness (Autobiographical Interview scoring protocol) to examine which categories of episodic details are associated with temporal discounting in cognitively normal older adults. We also examined whether recalling autobiographical memories prior to choice can alter temporal discounting in this group. Time, place, and perceptual details, but not event or emotion/thought details, were associated with temporal discounting. Furthermore, time, place, and perceptual details and temporal discount rates were associated with entorhinal cortical thickness. Retrieving autobiographical memories prior to choice did not affect temporal discounting overall, but the extent to which the memories were rich in event and time details predicted whether they would reduce discounting after they were recalled. Thus, more future-oriented decision-makers may have more contextual (i.e., time, place, and perceptual) details in their recollections overall, and retrieving central event details at the time of choice may shift decisions toward being more patient. These findings will help with the development of interventions to nudge intertemporal choices, especially in older adults with memory decline.

neuroscience↗

bioRxiv2019

Subjective value, not a grid-like code, describes neural activity in ventromedial prefrontal cortex during value-based decision-making

Across many studies, ventromedial prefrontal cortex (vmPFC) activity has been found to correlate with subjective value during value-based decision-making. Recently, however, vmPFC has also been shown to reflect a hexagonal gridlike code during navigation through physical and conceptual space. This raises the possibility that the subjective value correlates previously observed in vmPFC may have actually been a misconstrued gridlike signal. Here, we first show that, in theory, a hexagonal gridlike code of two-dimensional attribute space could mimic vmPFC activity previously attributed to subjective value. However, using fMRI data from a large number of subjects performing an intertemporal choice task, we show clear and unambiguous evidence that subjective value is a better description of vmPFC activity than a hexagonal gridlike code. In fact, we find no significant evidence at all for a hexagonal gridlike code in vmPFC activity during intertemporal choice. This result limits the generality of gridlike modulation as description of vmPFC activity. We suggest that vmPFC may flexibly switch representational schemes so as to encode the most relevant information for the current task.

neuroscience↗

bioRxiv2019

Pupil diameter encodes the idiosyncratic, cognitive complexity of belief updating

Pupils tend to dilate in response to surprising events, but it is not known whether these responses are primarily stimulus driven or instead reflect a more nuanced relationship between pupil-linked arousal systems and cognitive expectations. Using an auditory adaptive decision-making task, we show that evoked pupil diameter is more parsimoniously described as signaling violations of learned, top-down expectations than changes in low-level stimulus properties. We further show that both baseline and evoked pupil diameter is modulated by the degree to which individual subjects use these violations to update their subsequent expectations, as reflected in the complexity of their updating strategy. Together these results demonstrate a central role for idiosyncratic cognitive processing in how arousal systems respond to new inputs and, via our complexity-based analyses, provide a unified framework for understanding these effects in terms of both inference processes aimed to reduce belief uncertainty and more traditional notions of mental effort.

neuroscience↗

bioRxiv2019

Neural and behavioral correlates of declarative memory are associated with temporal discounting in older adults

When facing decisions involving trade-offs between smaller, sooner and larger, delayed rewards, people tend to discount the value of future rewards. There are substantial individual differences in this tendency toward temporal discounting, however. One neurocognitive system that may underlie these individual differences is episodic memory, given the overlap in the neural circuitry involved in imagining the future and remembering the past. Here we tested this hypothesis in older adults, including both those that were cognitively normal and those with amnestic mild cognitive impairment (MCI). We found that performance on neuropsychological measures of episodic memory retrieval was associated with temporal discounting, such that people with better memory discounted delayed rewards less. This relationship was specific to episodic memory and temporal discounting, since executive function (another cognitive ability) was unrelated to temporal discounting, and episodic memory was unrelated to risk tolerance (another decision-making preference). We also examined cortical thickness and volume in medial temporal lobe regions critical for episodic memory. Entorhinal cortical thickness was associated with reduced temporal discounting, with episodic memory performance partially mediating this association. The inclusion of MCI participants was critical to revealing these associations between episodic memory and entorhinal cortical thickness and temporal discounting. These effects were larger in the MCI group, reduced after controlling for MCI status, and statistically significant only when including MCI participants in analyses. Overall, these findings suggest that individual differences in temporal discounting are driven by episodic memory function, and that a decline in medial temporal lobe structural integrity may impact temporal discounting.

neuroscience↗

bioRxiv2018

Individuals with ventromedial frontal damage have more unstable but still fundamentally transitive preferences

The ventromedial frontal lobes (VMF) are important for decision-making, but the precise causal role of the VMF in the decision process has not yet fully been established. Previous studies have suggested that individuals with VMF damage violate transitivity, a hallmark axiom of rational decisions. However, these prior studies cannot properly distinguish whether individuals with VMF damage are truly prone to choosing irrationally from whether their preferences are simply more variable. We had individuals with focal VMF damage, individuals with other frontal damage, and healthy controls make repeated choices across three categories - artwork, chocolate bar brands, and gambles. Using sophisticated tests of transitivity, we find that, without exception, individuals with VMF damage make rational decisions consistent with transitive preferences, even though they exhibit greater variability in their preferences. That is, the VMF is necessary for having strong and reliable preferences, but not for being a rational decision maker. VMF damage affects the noisiness with which value is assessed, but not the consistency with which value is sought.

neuroscience↗