Biology subjects

Wolpe, N.

Publications and source records attributed to Wolpe, N..

7 recordsLinked to original sources

bioRxiv2026

Menstrual cycle selectively elevates anticipatory effort cost without altering reward sensitivity in human motivation

Motivation fluctuates across the menstrual cycle, yet the computational mechanisms underlying these changes remain unclear. We tested whether hormonally defined cycle phases selectively alter distinct components of effort-based motivation in naturally cycling women (n=51), who completed an effort-reward decision-making task and an effort psychophysics task in both the late-follicular and mid-luteal phases, alongside electrocardiography and ecological momentary assessment. Hierarchical Bayesian modelling revealed that the anticipated cost of physical effort (effort sensitivity) was selectively elevated in the mid-luteal phase, with no corresponding change in reward sensitivity. The luteal increase in effort sensitivity was attenuated in women who entered that phase after days of higher affective valence and arousal, indicating that positive affective state buffers cyclical motivational vulnerability. Complementing these findings, phase-related individual differences in effort the mapping between objective and perceived effort (effort differentiation) were not different by phase, but were moderated by heart rate variability and momentary affective states, revealing stable person-level variation in how the cycle shapes effortful experience. Together, these results identify effort sensitivity as a specific computational mechanism of cyclical motivational change, with implications for understanding the elevated burden of cycle-related psychiatric conditions across the female reproductive lifespan.

neuroscience↗

bioRxiv2026

Delusions Emerge from Generative Model Reorganisation rather than Faulty Inference: Insights from Hybrid Predictive Coding

Predictive coding has influenced many conceptual accounts of delusions, the bizarre and distressing beliefs that accompany a range of neuropsychiatric conditions. However, these explanations remain incomplete and have rarely been tested directly using formal modelling. Here, we present a formal account of delusional beliefs based on hybrid predictive coding, which sheds light on the computational mechanisms underpinning the core features of delusions: thematic recurrence and imperviousness to contradictory evidence. In simulation experiments, we demonstrate that a combination of contextually inadequate initialisation of beliefs and excessive certainty (a hallmark of psychosis), triggers a reorganisation of the generative model relating observed events to hidden causes. This reorganisation enables the maintenance of delusional beliefs that are thematically stable, internally consistent with external inputs, and impervious to contradictory evidence, all without an increase in prediction error. Overall, our results suggest that delusions may arise not from faulty inference, as previously argued, but as an adaptive consequence of generative models learned under atypical conditions. These findings provide mechanistic insights into the computations underpinning delusions and have important implications for a novel therapeutic strategy in terms of re-training generative models.

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bioRxiv2023

Behavioral and neuroimaging correlates of attentional biases to angry faces in individuals in remission from depression: a population-derived study

BackgroundDepressed individuals show attentional biases in the processing of emotional stimuli, such as negative face expressions. Some of these biases persist in previously depressed individuals, but their mechanisms remain largely unknown. MethodsA population-derived cohort (n = 134, 68 females; 21 - 92 years) was recruited by Cam-CAN. Functional MRI was acquired during a gender discrimination task, which used angry and neutral faces. Drift diffusion modelling (DDM) was used to investigate the latent components of the decision process, focusing on the effect of emotional valence. DDM parameters were correlated with activity in brain regions. Results14% of participants reported a history of depression in remission. The best fitting DDM specified a different drift rate for angry and neutral faces. A slower drift rate for angry faces predicted depression in remission (OR 0.092, p = 0.048). This effect persisted after accounting for current depression symptoms and drift rate for neutral faces. Participants with a slower drift rate for angry faces demonstrated increased activations in the bilateral insula, bilateral inferior frontal gyrus and bilateral parietal cortex when viewing angry relative to neutral faces. ConclusionsOur results suggest a persistent attentional bias in the processing of angry faces in individuals with depression in remission, over and above their current depressive symptoms. The imaging findings suggest that the slowing is associated with changes in areas involved in emotional regulation and evidence accumulation. Attentional biases in the processing of emotional information may reflect a trait, rather than state, in individuals with depression.

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bioRxiv2021

Prefrontal cortical connectivity mediates locus coeruleus noradrenergic regulation of inhibitory control in older adults

Response inhibition is a core executive function enabling adaptive behaviour in dynamic environments. Human and animal models indicate that inhibitory control and control networks are modulated by noradrenaline, arising from the locus coeruleus. The integrity (i.e., cellular density) of the locus coeruleus noradrenergic system can be estimated from magnetization transfer sensitive magnetic resonance imaging, in view of neuromelanin present in noradrenergic neurons of older adults. Noradrenergic psychopharmacological studies indicate noradrenergic modulation of prefrontal and frontostriatal stopping-circuits in association with behavioural change. Here we test the noradrenergic hypothesis of inhibitory control, in healthy adults. We predicted that locus coeruleus integrity is associated with age-adjusted variance in response inhibition, mediated by changes in connectivity between frontal inhibitory control regions. In a preregistered analysis, we used magnetization transfer MRI images from N=63 healthy adults aged above 50 years who performed a stop-signal task, with atlas-based measurement of locus coeruleus contrast. We confirm that better response inhibition is correlated with locus coeruleus integrity and stronger connectivity between pre-supplementary motor area and right inferior frontal gyrus, but not volumes of the cortical regions. We confirmed a significant role of prefrontal connectivity in mediating the effect of individual differences in the locus coeruleus on behaviour, whereby this effect was moderated by age, over and above adjustment for the mean effects of age. Our results support the hypothesis that in normal populations, as in clinical settings, the locus coeruleus noradrenergic system regulates inhibitory control.

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bioRxiv2019

Apathy is associated with reduced precision of prior beliefs about action outcomes

Apathy is a debilitating syndrome that is associated with reduced goal-directed behaviour. Although apathy is common and detrimental to prognosis in many neuropsychiatric diseases, its underlying mechanisms remain controversial. We propose a new model of apathy, in the context of Bayesian theories of brain function, whereby actions require predictions of their outcomes to be held with sufficient precision for explaining away differences in sensory inputs. In this active inference model, apathy would result from reduced precision of prior beliefs about action outcomes. Healthy adults (N=47) performed a visuomotor task that independently manipulated physical effort and reward, and served to estimate the precision of priors. Participants perception of their performance was biased towards the target, which was accounted for by precise prior beliefs about action outcomes. Crucially, prior precision was negatively associated with apathy. The results support a Bayesian account of apathy, that could inform future studies of clinical populations.

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bioRxiv2018

Motor learning decline with age is related to differences in the explicit memory system

The ability to adapt ones movements to changes in the environment is fundamental in everyday life, but this ability changes across the lifespan. Although often regarded as an implicit process, recent research has also linked motor adaptation with explicit learning processes. To understand how these processes contribute to differences in motor adaptation with age, we combined a visuomotor learning paradigm with cognitive tasks that measure implicit and explicit processes, and structural brain imaging. In a large population-based cohort from the Cambridge Centre for Ageing and Neuroscience (n=322, aged 18-89 years) we first confirmed that the degree of adaptation to an angular perturbation of visual feedback declined with age. There were no associations between adaptation and sensory attenuation, which has been previously hypothesised to contribute to implicit motor learning. However, interactions between age and scores on two independent memory tasks showed that explicit memory performance was a progressively stronger determinant of motor learning with age. Similarly, interactions between age and grey matter volume in the medial temporal lobe, amygdala and hippocampus showed that grey matter volume in these regions became a stronger determinant of adaptation in older adults. The convergent behavioural and structural imaging results suggest that age-related differences in the explicit memory system is a contributor to the decline in motor adaptation in older age. These results may reflect the more general compensatory reliance on cognitive strategies to maintain motor performance with age.\n\nSIGNIFICANCE STATEMENTThe central nervous system has a remarkable capacity to learn new motor skills and adapt to new environmental dynamics. This capacity is impaired with age, and in many brain disorders. We find that explicit memory performance and its associated medial temporal brain regions deteriorate with age, but the association between this brain system and individual differences in motor learning becomes stronger in older adults. We propose that these results reflect an increased reliance on cognition in order to maintain adaptive motor skill performance. This difference in learning strategy has implications for interventions to improve motor skills in older adults.

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bioRxiv2017

Sensory attenuation is related to dopamine dose in Parkinson’s disease

Abnormal initiation and control of voluntary movements are among the principal manifestations of Parkinsons disease (PD). However, the processes underlying these abnormalities and their potential remediation by dopamine treatment remain poorly understood. Normally, movements depend on the integration of sensory information with the predicted consequences of action. This integration leads to a suppression in the intensity of predicted sensations, and increases the relative salience of unexpected stimuli to facilitate the control of movements. We examined this integration process and its relation to dopamine in PD, by measuring sensorimotor attenuation - the reduction in the perceived intensity of predicted sensations from self-generated versus external actions. Patients with idiopathic PD (n=18) and population-derived controls (n=175) matched a set of target forces applied to their left index finger by a torque motor. To match the force, participants either pressed with their right index finger ( Direct condition) or used a linear potentiometer that controlled a motor ( Slider condition). We found that despite changes in sensitivity to different forces, overall sensory attenuation did not differ between medicated PD patients and controls. Importantly, the degree of attenuation was negatively related to PD motor severity but positively related to individual patient dopamine dose, as measured by levodopa dose equivalency. The results suggest that dopamine could regulate the integration of sensorimotor prediction with sensory information to facilitate the control of voluntary movements.

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