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IntroductionRisankizumab is a monoclonal antibody against subunit p19 of IL-23. It is used in the treatment of moderate/severe Crohn’s disease in patients who are at least 16 years of age and have failed previous treatment with biologics or when TNF-alpha inhibitors are unsuitable.Ustekinumab is a monoclonal antibody against subunit p40 of IL-23 and IL-12. It is also used in the treatment of moderate to severe Crohn’s disease.Little real-world data exists on the effectiveness of risankizumab in patients who have had inadequate response to ustekinumab.MethodsWe reviewed all patients with Crohn’s disease in the Newcastle Upon Tyne Hospital NHS Foundation Trust, who received first dose of risankizumab between 24/09/2019-07/11/2023 and of those we selected the cohort who had received ustekinumab previously. We reviewed electronic records to find demographic information, Crohn’s disease activity and treatment.ResultsWe identified 36 patients with Crohn’s disease who received risankizumab following an inadequate response to treatment with ustekinumab. Half of the patients had an age of onset of ≤16 years old. Most patients had ileo-colonic disease (30, 83.3%). 17 (47.2%) had stricturing disease, 3 (5.6%) had fistulating disease and 8 patients (22.2%) had perianal disease. Most patients (23, 63.8%) had prior surgical resection(s). Before starting ustekinumab, the majority of patients (30, 83.3%) tried 1 or 2 other biologics, five (13.9%) tried 3 other biologics and one was biologic naive.14 previously received ustekinumab at a standard dose interval (8 or 12 weekly), whilst 22 received ustekinumab at an escalated dose interval (4 or 6 weekly). For most patients (25, 69.3%), the decision to switch to risankizumab was based on objective evidence of active inflammation (e.g. raised fecal calprotectin, imaging or endoscopic findings).Of the 22 patients who received escalated dose ustekinumab, on treatment with risankizumab 12 (54%) had a treatment response (clinical, radiological or endoscopic), 2 (9%) went into disease remission, whilst 3 (14%) failed to improve. Of the 14 patients in the prior standard ustekinumab dosing group, 4 (28%) improved, 5 (36%) failed to improve and 1 (7%) had risankizumab stopped due to side effects. For the reminder of patients, it was too early to determine if they had responded to risankizumab. The duration of treatment with risankizumab was comparable between the two groups (average of 255 days for prior escalated ustekinumab dosing and 221 days for those on standard dosing).Abstract P270 Figure 1ConclusionIn this single centre cohort of medically refractory patients with Crohn’s disease, there was a benefit in switching from both standard and dose escalated ustekinumab to standard dose risankizumab, with over half of patients achieving clinical, radiological or endoscopic response or remission.

Therapists have discussed for a long time whether attempts to voluntarily suppress the intrusion of trauma memories are helpful to combat the distressing impacts of trauma. Mary et al. studied survivors of the 2015 Paris terrorist attacks who developed posttraumatic stress disorder and those who did not (see the Perspective by Ersche). Using functional magnetic resonance imaging, they investigated the neural networks underlying the control and suppression of memory retrieval. The results suggest that the characteristic symptoms of the disorder are not related to the memory itself but to its maladaptive control. These results offer new insights into the development of post-traumatic stress disorder and potential avenues for treatment. Science , this issue p. eaay8477 ; see also p. 734 A brain imaging study of survivors of the 2015 Paris terror attacks suggests that memory suppression shields against posttraumatic stress disorder. In the aftermath of trauma, little is known about why the unwanted and unbidden recollection of traumatic memories persists in some individuals but not others. We implemented neutral and inoffensive intrusive memories in the laboratory in a group of 102 individuals exposed to the 2015 Paris terrorist attacks and 73 nonexposed individuals, who were not in Paris during the attacks. While reexperiencing these intrusive memories, nonexposed individuals and exposed individuals without posttraumatic stress disorder (PTSD) could adaptively suppress memory activity, but exposed individuals with PTSD could not. These findings suggest that the capacity to suppress memory is central to positive posttraumatic adaptation. A generalized disruption of the memory control system could explain the maladaptive and unsuccessful suppression attempts often seen in PTSD, and this disruption should be targeted by specific treatments.

This study explored under what conditions young children would set reminders to aid their memory for delayed intentions. A computerized task requiring participants to carry out delayed intentions under varying levels of cognitive load was presented to 63 children (aged between 6.9 and 13.0 years old). Children of all ages demonstrated metacognitive predictions of their performance that were congruent with task difficulty. Only older children, however, set more reminders when they expected their future memory performance to be poorer. These results suggest that most primary school-aged children possess metacognitive knowledge about their prospective memory limits, but that only older children may be able to exercise the metacognitive control required to translate this knowledge into strategic reminder setting.

Sleep constitutes a privileged state for new memories to reactivate and consolidate. Previous work has demonstrated that consolidation can be bolstered experimentally either via delivery of reminder cues (targeted memory reactivation [TMR]) or via noninvasive brain stimulation geared toward enhancing endogenous sleep rhythms. Here, we combined both approaches, controlling the timing of TMR cues with respect to ongoing slow-oscillation (SO) phases. Prior to sleep, participants learned associations between unique words and a set of repeating images (e.g., car) while hearing a prototypical image sound (e.g., engine starting). Memory performance on an immediate test vs. a test the next morning quantified overnight memory consolidation. Importantly, two image sounds were designated as TMR cues, with one cue delivered at SO UP states and the other delivered at SO DOWN states. A novel sound was used as a TMR control condition. Behavioral results revealed a significant reduction of overnight forgetting for words associated with UP-state TMR compared with words associated with DOWN-state TMR. Electrophysiological results showed that UP-state cueing led to enhancement of the ongoing UP state and was followed by greater spindle power than DOWN-state cueing. Moreover, UP-state (and not DOWN-state) cueing led to reinstatement of target image representations. Together, these results unveil the behavioral and mechanistic effects of delivering reminder cues at specific phases of endogenous sleep rhythms and mark an important step for the endeavor to experimentally modulate memories during sleep.

Individuals often choose between remembering information using their own memory ability versus using external resources to reduce cognitive demand (i.e. 'cognitive offloading'). For example, to remember a future appointment an individual could choose to set a smartphone reminder or depend on their unaided memory ability. Previous studies investigating strategic reminder setting found that participants set more reminders than would be optimal, and this bias towards reminder-setting was predicted by metacognitive underconfidence in unaided memory ability. Due to the link between underconfidence in memory ability and excessive reminder setting, the aim of the current study was to investigate whether metacognitive training is an effective intervention to a) improve metacognitive judgment accuracy, and b) reduce bias in strategic offloading behaviour. Participants either received metacognitive training which involved making performance predictions and receiving feedback on judgment accuracy, or were part of a control group. As predicted, metacognitive training increased judgment accuracy: participants in the control group were significantly underconfident in their memory ability, whereas the experimental group showed no significant metacognitive bias. However, contrary to predictions, both experimental and control groups were significantly biased toward reminder-setting, and did not differ significantly. Therefore, reducing metacognitive bias was not sufficient to eliminate the bias towards reminders. We suggest that the reminder bias likely results in part from erroneous metacognitive evaluations, but that other factors such as a preference to avoid cognitive effort may also be relevant. Finding interventions to mitigate these factors could improve the adaptive use of external resources.

The ability to recall a detailed event from a simple reminder is supported by pattern completion, a cognitive operation performed by the hippocampus wherein existing mnemonic representations are retrieved from incomplete input. In behavioral studies, pattern completion is often inferred through the false endorsement of lure (i.e., similar) items as old. However, evidence that such a response is due to the specific retrieval of a similar, previously encoded item is severely lacking. We used eye movement (EM) monitoring during a partial-cue recognition memory task to index reinstatement of lure images behaviorally via the recapitulation of encoding-related EMs or gaze reinstatement. Participants reinstated encoding-related EMs following degraded retrieval cues and this reinstatement was negatively correlated with accuracy for lure images, suggesting that retrieval of existing representations (i.e., pattern completion) underlies lure false alarms. Our findings provide evidence linking gaze reinstatement and pattern completion and advance a functional role for EMs in memory retrieval.

Finding positive meaning in past negative memories is associated with enhanced mental health. Yet it remains unclear whether it leads to updates in the memory representation itself. Since memory can be labile after retrieval, this leaves the potential for modification whenever its reactivated. Across four experiments, we show that positively reinterpreting negative memories adaptively updates them, leading to the re-emergence of positivity at future retrieval. Focusing on the positive aspects after negative recall leads to enhanced positive emotion and changes in memory content during recollection one week later, remaining even after two months. Consistent with a reactivation-induced reconsolidation account, memory updating occurs only after a reminder and twenty four hours, but not a one hour delay. Multi-session fMRI showed adaptive updates are reflected in greater hippocampal and ventral striatal pattern dissimilarity across retrievals. This research highlights the mechanisms by which updating of maladaptive memories occurs through a positive emotion-focused strategy. Finding positive meaning in past negative events is associated with enhanced mental health. Here the authors show this adaptively updates memory, leading to enhanced positive emotion and content at future retrieval, which remains two months later.

Mental contrasting with implementation intentions (MCII) is an effective self-regulation strategy for goal pursuit. Despite growing interest in MCII within behaviour change research, relatively little is known about how such self-regulation strategies operate in real-world sport training environments or whether simple digital reminders may support their enactment. This exploratory randomized intervention study examined whether adding WhatsApp reminder messages to a contextually adapted MCII intervention was associated with changes in university students’ self-efficacy in tennis training. A total of 31 university students from a university tennis club were randomly assigned to either an MCII-only condition or an MCII intervention combined with WhatsApp reminder messages delivered prior to training sessions. Self-efficacy was assessed before and after a four-week intervention period using the General Self-Efficacy Scale (GSES). Within-group analyses did not reveal statistically significant changes in self-efficacy in either intervention condition. However, between-group comparison of change scores indicated a significant difference favouring the reminder-supported MCII condition ( U  = 94.50, p = 0.015), although the estimated effect size should be interpreted cautiously given the small sample. Session attendance did not differ between groups, suggesting that differences in intervention exposure were unlikely to account for the observed outcome. These findings suggest that integrating simple digital reminder messages into MCII-based interventions may support the application of self-regulation strategies in sport training contexts. Given the exploratory design and limited statistical power, the findings should be interpreted cautiously and require confirmation in larger, prospectively registered trials.

After psychological trauma, recurrent intrusive visual memories may be distressing and disruptive. Preventive interventions post trauma are lacking. Here we test a behavioural intervention after real-life trauma derived from cognitive neuroscience. We hypothesized that intrusive memories would be significantly reduced in number by an intervention involving a computer game with high visuospatial demands (Tetris), via disrupting consolidation of sensory elements of trauma memory. The Tetris-based intervention (trauma memory reminder cue plus c. 20 min game play) vs attention-placebo control (written activity log for same duration) were both delivered in an emergency department within 6 h of a motor vehicle accident. The randomized controlled trial compared the impact on the number of intrusive trauma memories in the subsequent week (primary outcome). Results vindicated the efficacy of the Tetris-based intervention compared with the control condition: there were fewer intrusive memories overall, and time-series analyses showed that intrusion incidence declined more quickly. There were convergent findings on a measure of clinical post-trauma intrusion symptoms at 1 week, but not on other symptom clusters or at 1 month. Results of this proof-of-concept study suggest that a larger trial, powered to detect differences at 1 month, is warranted. Participants found the intervention easy, helpful and minimally distressing. By translating emerging neuroscientific insights and experimental research into the real world, we offer a promising new low-intensity psychiatric intervention that could prevent debilitating intrusive memories following trauma.