Norepinephrine ignites local hot spots of neuronal excitation: how arousal amplifies selectivity in perception and memory

Arousal sometimes enhances and sometimes impairs perception and memory. In our Glutamate Amplifies Noradrenergic Effects (GANE) model, glutamate at active synapses interacts with norepinephrine released by the locus coeruleus to create local ‘hot spots’ of activity that enable the selective effects of arousal. This hot spot mechanism allows local cortical regions to self-regulate norepinephrine release based on current activation levels. In turn, hot spots bias global energetic delivery and functional network connectivity to enhance processing of high priority representations and impair processing of lower priority representations.

Carotenoids but not flavonoids are associated with improvements in spatial working memory in younger adults in a flavonoid-rich v. -poor fruit and vegetable intervention study

Findings from animal studies suggest that components of fruit and vegetables (F&V) may protect against, and even reverse, age-related decline(1,2) in aspects of cognitive functioning such as spatial working memory (SWM). Human subjects in vivo and in vitro studies indicate that anti-inflammatory, anti-oxidant and cell-signalling properties of flavonoids and carotenoids, non-nutrient components of F&V, may underpin this protective effect(3–5). The Flavonoid University of Reading Study (FLAVURS), designed to explore the dose-response relationship between dietary F&V flavonoids and CVD, enabled the investigation of such an association with SWM. FLAVURS is an 18-week parallel three-arm randomised controlled dietary intervention trial with four time points, measured at 6-weekly intervals from baseline. Low F&V consumers at risk of CVD aged 26–70 years were randomly assigned to high flavonoid (HF), low flavonoid (LF) or control group. F&V intake increased by two daily 80 g portions every 6 weeks, with either HF or LF F&V, in addition to each participant's habitual diet, while controls maintained their habitual diet. At each visit, participants completed a cognitive test battery with SWM as the primary outcome. The HF group showed significantly higher levels of urinary flavonoids than LF or controls at 12 weeks (P<0.001) as expected, but surprisingly only higher levels than LF at 18 weeks (P<0.01). The LF group showed higher levels of plasma carotenoids than the other groups at 18 weeks (P<0.001). No group differences were found for SWM overall, however, age-group sub-analyses (26–50 and 51–70 years of age) showed differences from 0 to 18 weeks for younger adults, with LF improving significantly more than the other two groups on SWM (P<0.05). As nutritional absorption is known to decrease with age, separate stepwise regressions were performed on the two age groups irrespective of dietary group, with urinary flavonoids and plasma carotenoids as predictors. For younger adults, improved SWM performance from 0 to 18 weeks was associated with higher carotenoid levels, β=0.28, t(55)=2.10, P<0.05, accounting for 7.5% of the variance, R2=0.075, F(1,54)=4.41, P=0.040. For older adults, no between-group SWM differences were found. Findings suggest that F&V-based flavonoids and carotenoids may provide benefits for cognitive function, and that carotenoids in particular may improve cognitive performance in SWM. Given that these benefits were restricted to younger adults, future work is needed to test the reliability of this finding, as well as determine the mechanisms by which age-dependent differences in F&V responsiveness occur.

Enhancing prospective memory in mild cognitive impairment: the role of enactment

Prospective memory (PM) is a fundamental requirement for independent living which might be prematurely compromised in the neurodegenerative process, namely in mild cognitive impairment (MCI), a typical prodromal Alzheimer's disease (AD) phase. Most encoding manipulations that typically enhance learning in healthy adults are of minimal benefit to AD patients. However, there is some indication that these can display a recall advantage when encoding is accompanied by the physical enactment of the material. The aim of this study was to explore the potential benefits of enactment at encoding and cue-action relatedness on memory for intentions in MCI patients and healthy controls using a behavioral PM experimental paradigm. Method: We report findings examining the influence of enactment at encoding for PM performance in MCI patients and education-matched controls using a laboratory-based PM task with a factorial independent design. Results: PM performance was consistently superior when physical enactment was used at encoding and when target-action pairs were strongly associated. Importantly, these beneficial effects were cumulative and observable across both a healthy and a cognitively impaired lifespan as well as evident in the perceived subjective difficulty in performing the task. Conclusions: The identified beneficial effects of enacted encoding and semantic relatedness have unveiled the potential contribution of this encoding technique to optimize attentional demands through an adaptive allocation of resources strategies. We discuss our findings with respect to their potential impact on developing strategies to improve PM in AD sufferers.

Connectivity-based parcellation of the human frontal polar cortex

The frontal pole corresponds to Brodmann area (BA) 10, the largest single architectonic area in the human frontal lobe. Generally, BA10 is thought to contain two or three subregions that subserve broad functions such as multitasking, social cognition, attention, and episodic memory. However, there is a substantial debate about the functional and structural heterogeneity of this large frontal region. Previous connectivity-based parcellation studies have identified two or three subregions in the human frontal pole. Here, we used diffusion tensor imaging to assess structural connectivity of BA10 in 35 healthy subjects and delineated subregions based on this connectivity. This allowed us to determine the correspondence of structurally based subregions with the scheme previously defined functionally. Three subregions could be defined in each subject. However, these three subregions were not spatially consistent between subjects. Therefore, we accepted a solution with two subregions that encompassed the lateral and medial frontal pole. We then examined resting-state functional connectivity of the two subregions and found significant differences between their connectivities. The medial cluster was connected to nodes of the default-mode network, which is implicated in internally focused, self-related thought, and social cognition. The lateral cluster was connected to nodes of the executive control network, associated with directed attention and working memory. These findings support the concept that there are two major anatomical subregions of the frontal pole related to differences in functional connectivity.

Providing extrinsic reward for test performance undermines long-term memory acquisition

Based on numerous studies showing that testing studied material can improve long-term retention more than restudying the same material, it is often suggested that the number of tests in education should be increased to enhance knowledge acquisition. However, testing in real-life educational settings often entails a high degree of extrinsic motivation of learners due to the common practice of placing important consequences on the outcome of a test. Such an effect on the motivation of learners may undermine the beneficial effects of testing on long-term memory because it has been shown that extrinsic motivation can reduce the quality of learning. To examine this issue, participants learned foreign language vocabulary words, followed by an immediate test in which one-third of the words were tested and one-third restudied. To manipulate extrinsic motivation during immediate testing, participants received either monetary reward contingent on test performance or no reward. After 1 week, memory for all words was tested. In the immediate test, reward reduced correct recall and increased commission errors, indicating that reward reduced the number of items that can benefit from successful retrieval. The results in the delayed test revealed that reward additionally reduced the gain received from successful retrieval because memory for initially successfully retrieved words was lower in the reward condition. However, testing was still more effective than restudying under reward conditions because reward undermined long-term memory for concurrently restudied material as well. These findings indicate that providing performance–contingent reward in a test can undermine long-term knowledge acquisition.

Activation of G-protein-coupled receptor 30 is sufficient to enhance spatial recognition memory in ovariectomized rats

In ovariectomized rats, administration of estradiol, or selective estrogen receptor agonists that activate either the alpha or beta isoforms, have been shown to enhance spatial cognition on a variety of learning and memory tasks, including those that capitalize on the preference of rats to seek out novelty. Although the effects of the putative estrogen G-protein-coupled receptor 30 (GPR30) on hippocampus-based tasks have been reported using food-motivated tasks, the effects of activation of GPR30 receptors on tasks that depend on the preference of rats to seek out spatial novelty remain to be determined. Therefore, the aim of the current study was to determine if short-term treatment of ovariectomized rats with G-1, an agonist for GPR30, would mimic the effects on spatial recognition memory observed following short-term estradiol treatment. In Experiment 1, ovariectomized rats treated with a low dose (1mug) of estradiol 48h and 24h prior to the information trial of a Y-maze task exhibited a preference for the arm associated with the novel environment on the retention trial conducted 48h later. In Experiment 2, treatment of ovariectomized rats with G-1 (25mug) 48h and 24h prior to the information trial of a Y-maze task resulted in a greater preference for the arm associated with the novel environment on the retention trial. Collectively, the results indicated that short-term treatment of ovariectomized rats with a GPR30 agonist was sufficient to enhance spatial recognition memory, an effect that also occurred following short-term treatment with a low dose of estradiol.