Ryan Yan Yan

All Publications

• Effect of lithium on circadian activity level and flexibility in patients with bipolar disorder: results from the Oxford Lithium Trial. EBioMedicine Xu, N., Yan, Y., Saunders, K. E., Geddes, J. R., Browning, M. 2025; 115: 105676

  Abstract

  Disruption of circadian rest-activity is prevalent in patients with bipolar disorder (BD). Lithium's impact on circadian rhythms has been documented in cell lines, animal models, and pharmacogenomics studies in patients with BD. However, the causal relationship between such disruption and BD remains unclear.We investigated the early effects of lithium on circadian rest-activity in an exploratory analysis of a randomised, placebo-controlled, double-blind six-week study on patients with BD. Participants were assigned to receive either lithium or a placebo in a 1:1 ratio. Circadian activity was monitored using actigraphy, and daily affect was assessed through ecological momentary assessment. A computational model was used to quantify different types of activity variability, and the impact of lithium on activity level, activity onset time and their variability were analysed using linear mixed models.Of the thirty-five participants who began treatment, 19 received lithium and 16 received a placebo. Lithium significantly altered circadian rest-activity patterns, including reducing daytime activity levels (after 4 weeks, below as well: Cohen's d = -0.19, p = 0.002, linear mixed model, ibid.), advancing the onset of daytime activity (Cohen's d = -0.14, p = 0.018), and increasing the volatility of both daytime activity level (Cohen's d = 0.10, p = 0.002) and its onset time (Cohen's d = 0.13, p < 0.001), independent of affective symptoms changes.This study establishes a causal link between lithium treatment and reduced circadian activity with advanced circadian phase, potentially via temporarily increasing their volatility (flexibility). Significant circadian changes were detected within one week of starting lithium, highlighting their potential as an early biomarker for treatment response.This research was supported by the Wellcome Trust Strategic Award (CONBRIO: Collaborative Oxford Network for Bipolar Research to Improve Outcomes, reference No. 102,616/Z), NIHR Oxford Health Biomedical Research Centre and the NIHR Oxford cognitive health Clinical Research Facility.

  View details for DOI 10.1016/j.ebiom.2025.105676

  View details for PubMedID 40179662

• Reward positivity affects temporal interval production in a continuous timing task. Psychophysiology Yan, Y., Hunt, L. T., Hassall, C. D. 2024: e14589

  Abstract

  The neural circuits of reward processing and interval timing (including the perception and production of temporal intervals) are functionally intertwined, suggesting that it might be possible for momentary reward processing to influence subsequent timing behavior. Previous animal and human studies have mainly focused on the effect of reward on interval perception, whereas its impact on interval production is less clear. In this study, we examined whether feedback, as an example of performance-contingent reward, biases interval production. We recorded EEG from 20 participants while they engaged in a continuous drumming task with different realistic tempos (1728 trials per participant). Participants received color-coded feedback after each beat about whether they were correct (on time) or incorrect (early or late). Regression-based EEG analysis was used to unmix the rapid occurrence of a feedback response called the reward positivity (RewP), which is traditionally observed in more slow-paced tasks. Using linear mixed modeling, we found that RewP amplitude predicted timing behavior for the upcoming beat. This performance-biasing effect of the RewP was interpreted as reflecting the impact of fluctuations in reward-related anterior cingulate cortex activity on timing, and the necessity of continuous paradigms to make such observations was highlighted.

  View details for DOI 10.1111/psyp.14589

  View details for PubMedID 38615339

• The neural correlates of continuous feedback processing. Psychophysiology Hassall, C. D., Yan, Y., Hunt, L. T. 2023: e14399

  Abstract

  Feedback processing is commonly studied by analyzing the brain's response to discrete rather than continuous events. Such studies have led to the hypothesis that rapid phasic midbrain dopaminergic activity tracks reward prediction errors (RPEs), the effects of which are measurable at the scalp via electroencephalography (EEG). Although studies using continuous feedback are sparse, recent animal work suggests that moment-to-moment changes in reward are tracked by slowly ramping midbrain dopaminergic activity. Some have argued that these ramping signals index state values rather than RPEs. Our goal here was to develop an EEG measure of continuous feedback processing in humans, then test whether its behavior could be accounted for by the RPE hypothesis. Participants completed a stimulus-response learning task in which a continuous reward cue gradually increased or decreased over time. A regression-based unmixing approach revealed EEG activity with a topography and time course consistent with the stimulus-preceding negativity (SPN), a scalp potential previously linked to reward anticipation and tonic dopamine release. Importantly, this reward-related activity depended on outcome expectancy: as predicted by the RPE hypothesis, activity for expected reward cues was reduced compared to unexpected reward cues. These results demonstrate the possibility of using human scalp-recorded potentials to track continuous feedback processing, and test candidate hypotheses of this activity.

  View details for DOI 10.1111/psyp.14399

  View details for PubMedID 37485986

• Daytime affect and sleep EEG activity: A data-driven exploration. Journal of sleep research Zhang, J. X., Ten Brink, M., Yan, Y., Goldstein-Piekarski, A., Krause, A. J., Manber, R., Kreibig, S., Gross, J. J. 2023: e13916

  Abstract

  It has long been thought that links between affect and sleep are bidirectional. However, few studies have directly assessed the relationships between: (1) pre-sleep affect and sleep electroencephalogram (EEG) activity; and (2) sleep EEG activity and post-sleep affect. This study aims to systematically explore the correlations between pre-/post-sleep affect and EEG activity during sleep. In a community sample of adults (n = 51), we measured participants' positive and negative affect in the evening before sleep and in the next morning after sleep. Participants slept at their residence for 1 night of EEG recording. Using Fourier transforms, the EEG power at each channel was estimated during rapid eye movement sleep and non-rapid eye movement sleep for the full range of sleep EEG frequencies. We first present heatmaps of the raw correlations between pre-/post-sleep affect and EEG power during rapid eye movement and non-rapid eye movement sleep. We then thresholded the raw correlations with a medium effect size |r| ≥ 0.3. Using a cluster-based permutation test, we identified a significant cluster indicating a negative correlation between pre-sleep positive affect and EEG power in the alpha frequency range during rapid eye movement sleep. This result suggests that more positive affect during the daytime may be associated with less fragmented rapid eye movement sleep that night. Overall, our exploratory results lay the foundation for confirmatory research on the relationship between daytime affect and sleep EEG activity.

  View details for DOI 10.1111/jsr.13916

  View details for PubMedID 37156757

• Pre-sleep affect predicts subsequent REM frontal theta in nonlinear fashion. Cognitive, affective & behavioral neuroscience Ten Brink, M., Yan, Y., Zhang, J., Goldstein-Piekarski, A., Krause, A., Kreibig, S., Manber, R., Gross, J. 2023

  Abstract

  Pre-sleep affect is thought to influence sleep, but associations with both sleep architecture and the electroencephalographic (EEG) power spectrum are mixed. In this pre-registered study, we assessed negative valence and arousal 1h pre-sleep in 52 adults drawn from the community, then recorded one night of polysomnography (PSG) in participants' own homes. Pre-sleep affect was not associated with nonrapid eye movement (NREM) or rapid eye movement (REM) sleep architecture parameters, but we did observe inverted U-shaped relationships between both negative valence and arousal and REM frontal theta power, such that theta power was highest at moderate negative valence and arousal, and lowest at either affective extreme. When entered into a model together, both valence and arousal accounted for independent variance. Secondary analyses revealed a similar quadratic association with pre-sleep positive valence, suggesting a nonspecific effect of pre-sleep valence on REM frontal theta. Robustness checks confirmed that effects were not explained by homeostatic sleep pressure or sleep timing. Our results suggest that mixed findings in the literaturemay reflect different ends of a quadratic function, underscoring the importance of assessing how different components of pre-sleep affect relate to sleep.

  View details for DOI 10.3758/s13415-022-01051-7

  View details for PubMedID 36702991