Temporally Dynamic Interaction between Drug Cue Reactivity and Response Inhibition: An fMRI Study among People with Methamphetamine Use Disorder

Cue-induced drug craving and disinhibition are two essential components of continued drug use and relapse in substance use disorders. While these two phenomena develop and interact across time, the temporal dynamics of their underlying neural activity and their interaction remain under-investigated. To explore these dynamics, an analysis of time-varying activation was applied to fMRI data from 62 men with methamphetamine use disorder in their first weeks of recovery in abstinence-based treatment program. Using a mixed block-event, factorial cue-reactivity/Go-NoGo task, and a sliding window across the task duration, dynamically-activated regions were identified in linear mixed effects models (LMEs). Habituation to drug cues across time was observed in the superior temporal gyri, amygdalae, left hippocampus, and right precuneus, while response-inhibition was associated with the sensitization of temporally-dynamic activations across many regions of the inhibitory frontoparietal network. Cue-reactivity and response-inhibition dynamically interact in the parahippocampal gyri and right precuneus (corrected p-value < 0.001) regions, which show a declining cue-reactivity contrast and an increasing response-inhibition contrast. Overall, the declining craving-related activations (habituation) and increasing inhibition-associated activations (sensitization) along the task duration suggest the gradual recruitment of response-inhibition process and the concurrent habituation to drug cues in areas with significant dynamic interaction. This exploratory study demonstrates the time-variance of the neural activations undergirding cue-reactivity, response-inhibition, and their interaction, and suggests potentials to assess this dynamic interaction. This preliminary evidence provides justifications for new avenues in biomarker development and interventions using cue exposure paradigms, which could promote habituation to drug cues and sensitization in inhibitory control regions.

A selective benefit of transient, but not sustained, reward to memory formation

Reward benefits to memory formation have been robustly linked to dopaminergic activity. Despite established characterization of dopaminergic mechanisms as operating at multiple timescales, potentially supporting distinct functional outcomes, the temporal dynamics by which reward might modulate memory encoding are just beginning to be investigated. In the present study, we leveraged a mixed block/event experimental design to disentangle transient and sustained reward influences on task engagement and subsequent recognition memory in an adapted monetary-incentive encoding (MIE) paradigm. Across three behavioral experiments, transient and sustained reward modulation of item and context memory was probed, at both 24-hour and ~10-minute retention intervals, to investigate the importance of overnight consolidation. In general, we observed that transient reward was associated with enhanced item memory encoding, while sustained reward modulated task engagement at encoding (specifically, increasing response speed) but did not confer a benefit to subsequent memory performance. Notably, reward benefits to item memory performance were somewhat inconsistent across the three experiments, and in contrast to predictions, we did not observe reward modulation of context memory performance or amplification of reward effects by overnight consolidation. Taken together, the observed pattern of behavior suggests potentially distinct roles for transient and sustained reward in memory encoding and cognitive performance and suggests that further investigation of the temporal dynamics of dopaminergic contributions to memory formation will advance understanding of motivated memory.

Temporal context effects are associated with cognitive status in advanced age

The perception of temporal intervals changes during the life-span, and especially older adults demonstrate specific impairments of timing abilities. Recently, we demonstrated that timing performance and cognitive status are correlated in older adults, suggesting that timing tasks can serve as a behavioral marker for the development of dementia. Easy-to-administer and retest-capable timing tasks therefore have potential as diagnostic tools for tracking cognitive decline. However, before being tested in a clinical cohort study, a further validation and specification of the original findings is warranted. Here we introduce several modifications of the original task and investigated the effects of temporal context on time perception in older adults (> 65 years) with low versus high scores in the Montreal Cognitive Assessment survey (MoCA) and a test of memory functioning. In line with our previous work, we found that temporal context effects were more pronounced with increasing memory deficits, but also that these effects are stronger for realistic compared to abstract visual stimuli. Furthermore, we show that two distinct temporal contexts influence timing behavior in separate experimental blocks, as well as in a mixed block in which both contexts are presented together. These results replicate and extend our previous findings. They demonstrate the stability of the effect for different stimulus material and show that timing tasks can reveal valuable information about the cognitive status of older adults. In the future, these findings could serve as a basis for the development of a diagnostic tool for pathological cognitive decline at an early, pre-clinical stage.

Attitude and perception of urology by fifth-year (GEMPIII) students at the end of their mixed block rotation at Wits Medical School

Background This University Medical School offers a 6-year MBBCh programme, of which the fifth year consists of seven blocks of 6 weeks each of which 2 weeks are mixed rotations in specialities such as ophthalmology, ear–nose–throat and urology. The purpose of the study was to assess the current urology knowledge and skills confidence amongst undergraduate medical students regarding urological diagnostic and therapeutic procedures, in order to evaluate the current curriculum for possible need of improvement. Methods This was a qualitative survey of 250 fifth-year medical students from September 2019 to February 2020. The survey was conducted by means of a questionnaire consisting of two parts: The first component covered the students perceptions of the urology rotation, and the second component contained the students self-evaluations. The aim of the study was to evaluate students perceptions of the current urology curriculum and to assess the possible need for improvement in urological knowledge and skill. Results Of 250 (100%) voluntary participants, 159 (63.6%) were female and 91(36.4%) were male. The majority of students considered their urology knowledge on lithiasis/stone disease and erectile dysfunction sufficient and were comfortable with male catheterisation. Voiding dysfunction, paediatric urology and uro-oncology were the subjects students commonly expressed a deficit in. There was a statistical significant difference in females having a more positive attitude to urology, than males (p = 0.02). No statistical significant difference in attitude to urology was found between students who rotated in one center opposed to students who rotated in another center. Indeed, the majority of students had a negative attitude to urology at the end of the mixed block rotations regardless of the training location. Unattractivity and lack of knowledge were the most common reasons for not choosing urology as a career. Conclusion The study reveals a need for improvement in basic urological knowledge and skills during the mixed block rotation. A more practical curriculum, taking into account: bedside teachings, attendance of urological clinics and more exposure to urological patients, are some suggestions to be considered in improving the urological educational curriculum.

Mixed slip-trip perturbation training for improving reactive responses in people with chronic stroke

Block perturbation training led to development of favorable reactive responses to counteract treadmill-based, slip-like and trip-like stance perturbations among people with chronic stroke. During mixed block, previously acquired adaptive changes in reactive responses from slip-block training were not maintained, probably due to interference offered by trip block. Instead, on trip-like perturbations, trip block-induced adaptation was maintained and continued to show further improvement. Our findings might provide future direction for designing effective mixed perturbation training paradigms to counteract both opposing perturbation types.

Rewards Enhance Proactive and Reactive Control in Adolescence and Adulthood

Cognitive control allows the coordination of cognitive processes to achieve goals. Control may be sustained in anticipation of goal-relevant cues (proactive control) or transient in response to the cues themselves (reactive control). Adolescents typically exhibit a more reactive pattern than adults in the absence of incentives. We investigated how reward modulates cognitive control engagement in a letter-array working memory (WM) task in 30 adolescents (12–17 years) and 20 adults (23–30 years) using a mixed block- and event-related functional magnetic resonance imaging design. After a Baseline run without rewards, participants performed a Reward run where 50% trials were monetarily rewarded. Accuracy and reaction time (RT) differences between Reward and Baseline runs indicated engagement of proactive control, which was associated with increased sustained activity in the bilateral anterior insula (AI), right dorsolateral prefrontal cortex (PFC) and right posterior parietal cortex (PPC). RT differences between Reward and No reward trials of the Reward run suggested additional reactive engagement of cognitive control, accompanied with transient activation in bilateral AI, lateral PFC, PPC, supplementary motor area, anterior cingulate cortex, putamen and caudate. Despite behavioural and neural differences during Baseline WM task performance, adolescents and adults showed similar modulations of proactive and reactive control by reward.