Brain and neuroscience advances最新文献

It remains unclear whether the negative reinforcement pathway to problematic drinking exists, and if so, for whom. One idea that has received some support recently is that people who tend to act impulsively in response to negative emotions (i.e. people high in negative urgency) may specifically respond to negative affect with increased alcohol consumption. We tested this idea in a preregistered secondary data analysis of two ecological momentary assessment studies using college samples. Participants (N = 226) reported on their current affective state multiple times per day and also the following morning reported alcohol use of the previous night. We assessed urgency both at baseline and during the momentary affect assessments. Results from our Bayesian model comparison procedure, which penalises increasing model complexity, indicate that no combination of the variables of interest (negative affect, urgency, and the respective interactions) outperformed a baseline model that included two known demographic predictors of alcohol use. A non-preregistered exploratory analysis provided some evidence for the effect of daily positive affect, positive urgency, as well as their interaction on subsequent alcohol use. Taken together, our results suggest that college students' drinking may be better described by a positive rather than negative reinforcement cycle.

Impulsive urgency describes the tendency to act rashly when experiencing extreme emotions. This Australian study aimed to investigate the predictive utility of impulsivity, including impulsive urgency (positive and negative), across a range of problem behaviours. Data from two community samples, one retrospective (n = 281) and one current (n = 604), were analysed using hierarchical regression to determine which facets of impulsivity, as assessed with a comprehensive scale (i.e. negative urgency, positive urgency, lack or premeditation, lack of perseverance, and sensation seeking), best predicted a series of problem behaviours (i.e. problem gambling, disorderly alcohol use, online gambling disorder, obsessive-compulsive disorder behaviours, and social media addiction). The impulsive urgency facets were shown to be significant predictors across the behaviours examined. More specifically, negative urgency was the strongest predictor of disorderly alcohol use, obsessive-compulsive disorder behaviours, and social media addiction. Positive urgency was associated with problem gambling and online gambling disorder behaviours. These findings suggest that impulsive urgency is a key contributing factor in many behavioural problems and that the valence of the urgency is an important consideration when addressing a broad range of psychopathologies.

Attention involves both an ability to selectively focus on relevant information and simultaneously ignore irrelevant information (i.e. inhibitory control). Many factors impact inhibitory control such as individual differences, relative timing of stimuli presentation, distractor characteristics, and participant age. Previous research with young adults responding to an attention-demanding rapid serial visual presentations of pictures superimposed with task-irrelevant words evaluated the extent to which unattended information may be subject to inhibitory control. Surprise recognition tests following the rapid serial visual presentation task showed that recognition for unattended words presented with non-targets (i.e. non-aligned or 'NA' words) during the rapid serial visual presentation task were recognised at chance levels. However, when the unattended words were infrequently paired with the attended picture targets (i.e. target-aligned or 'TA' words), recognition rates were significantly below chance and significantly lower compared to NA words, suggesting selective inhibitory control for the previously unattended TA words. The current study adapted this paradigm to compare healthy younger and older adults' ability to engage in inhibitory control. In line with previous research, younger adults demonstrated selective inhibition with recognition rates for TA words significantly lower than NA words and chance, while NA words were recognised at chance levels. However, older adults showed no difference in recognition rates between word types (TA versus NA). Rather all items were recognised at rates significantly below chance suggesting inhibited recognition for all unattended words, regardless of when they were presented during the primary task. Finally, older adults recognised significantly fewer NA words compared to young adults. These findings suggest that older adults may experience a decline in their ability to selectively inhibit the processing of irrelevant information, while maintaining the capacity to exercise global inhibition over unattended lexical information.

Cannabis has been shown to cause structural and functional neurocognitive changes in heavy users. Cannabis use initiation aligns with brain development trajectories; therefore, it is imperative that the potential neurological implications of cannabis use are understood. Males and females reach neurodevelopmental milestones at different rates making it necessary to consider biological sex in all cannabis and brain-based research. Through use of a systamatic review in accordance with PRISMA guidelines, we aimed to understand the interaction between biological sex and cannabis use on brain-based markers. In total, 18 articles containing a sex-based analysis of cannabis users were identified. While the majority of studies (n = 11) reported no sex by cannabis use interactions on brain-based markers, those that reported findings (n = 8) suggest females may be more susceptible to cannabis' neurotoxic effects. Unfortunately, a large portion of the literature was excluded due to no sex-based analysis. In addition, studies that reported no sex differences often contained a reduced number of females which may result in some studies being underpowered for sex-based analyses, making it difficult to draw firm conclusions. Suggestions to improve cannabis and sex-based reseach are proposed.

Synapse loss is associated with cognitive decline in Alzheimer's disease, and owing to their plastic nature, synapses are an ideal target for therapeutic intervention. Oligomeric amyloid beta around amyloid plaques is known to contribute to synapse loss in mouse models and is associated with synapse loss in human Alzheimer's disease brain tissue, but the mechanisms leading from Aβ to synapse loss remain unclear. Recent data suggest that the fast-activating and -inactivating voltage-gated potassium channel subtype 3.4 (Kv3.4) may play a role in Aβ-mediated neurotoxicity. Here, we tested whether this channel could also be involved in Aβ synaptotoxicity. Using adeno-associated virus and clustered regularly interspaced short palindromic repeats technology, we reduced Kv3.4 expression in neurons of the somatosensory cortex of APP/PS1 mice. These mice express human familial Alzheimer's disease-associated mutations in amyloid precursor protein and presenilin-1 and develop amyloid plaques and plaque-associated synapse loss similar to that observed in Alzheimer's disease brain. We observe that reducing Kv3.4 levels ameliorates dendritic spine loss and changes spine morphology compared to control virus. In support of translational relevance, Kv3.4 protein was observed in human Alzheimer's disease and control brain and is associated with synapses in human induced pluripotent stem cell-derived cortical neurons. We also noted morphological changes in induced pluripotent stem cell neurones challenged with human Alzheimer's disease-derived brain homogenate containing Aβ but, in this in vitro model, total mRNA levels of Kv3.4 were found to be reduced, perhaps as an early compensatory mechanism for Aβ-induced damage. Overall, our results suggest that approaches to reduce Kv3.4 expression and/or function in the Alzheimer's disease brain could be protective against Aβ-induced synaptic alterations.

Performance on an emotional stop-signal task designed to assess emotional response inhibition has been associated with Negative Urgency and psychopathology, particularly self-injurious behaviors. Indeed, difficulty inhibiting prepotent negative responses to aversive stimuli on the emotional stop-signal task (i.e. poor negative emotional response inhibition) partially explains the association between Negative Urgency and non-suicidal self-injury. Here, we combine existing data sets from clinical (hospitalised psychiatric inpatients) and non-clinical (community/student participants) samples aged 18-65 years (N = 450) to examine the psychometric properties of this behavioural task and evaluate hypotheses that emotional stop-signal task metrics relate to distinct impulsive traits among participants who also completed the UPPS-P (n = 223). We specifically predicted associations between worse negative emotional response inhibition (i.e. commission errors during stop-signal trials representing negative reactions to unpleasant images) and Negative Urgency, whereas commission errors to positive stimuli - reflecting worse positive emotional response inhibition - would relate to Positive Urgency. Results support the emotional stop-signal task's convergent and discriminant validity: as hypothesised, poor negative emotional response inhibition was specifically associated with Negative Urgency and no other impulsive traits on the UPPS-P. However, we did not find the hypothesised association between positive emotional response inhibition and Positive Urgency. Correlations between emotional stop-signal task performance and self-report measures were the modest, similar to other behavioural tasks. Participants who completed the emotional stop-signal task twice (n = 61) additionally provide preliminary evidence for test-retest reliability. Together, findings suggest adequate reliability and validity of the emotional stop-signal task to derive candidate behavioural markers of neurocognitive functioning associated with Negative Urgency and psychopathology.