Is Working Memory Training Effective? A Study in a School Setting

We tested the effectiveness of an intensive, on average 17-session, adaptive and computerized working-memory training program for improving performance on untrained, paper and pencil working memory tasks, standardized school achievement tasks, and teacher ratings of classroom behavior. Third-grade children received either a computerized working memory training for about 30 minutes per session (n = 156) or participated in regular classroom activities (n = 126). Results indicated strong gains in the training task. Further, pretest and posttest transfer measures of working memory and school achievement, as well as teacher ratings, showed substantial correlations with training task performance, suggesting that the training task captured abilities that were relevant for the transfer tasks. However, effect sizes of training-specific transfer gains were very small and not consistent across tasks. These results raise questions about the benefits of intensive working-memory training programs within a regular school context.     

Evaluation of a Well-Established Task-Shifting Initiative: The Lay Counselor Cadre in Botswana

Background

Evidence supports the implementation of task shifting to address health worker shortages that are common in resource-limited settings. However, there is need to learn from established programs to identify ways to achieve the strongest, most sustainable impact. This study examined the Botswana lay counselor cadre, a task shifting initiative, to explore effectiveness and contribution to the health workforce.

Methods

This evaluation used multiple methods, including a desk review, a national lay counselor survey (n = 385; response = 94%), in-depth interviews (n = 79), lay counselors focus group discussions (n = 7), lay counselors observations (n = 25), and client exit interviews (n = 47).

Results

Interview and focus group data indicate that lay counselors contribute to essentially all HIV-related programs in Botswana and they conduct the majority of HIV tests and related counseling at public health facilities throughout the country. Interviews showed that the lay counselor cadre is making the workload of more skilled health workers more manageable and increasing HIV acceptance in communities. The average score on a work-related knowledge test was 74.5%. However for 3 questions, less than half answered correctly. During observations, lay counselors demonstrated average competence for most skills assessed and clients (97.9%) were satisfied with services received. From the survey, lay counselors generally reported being comfortable with their duties; however, some reported clinical duties that extended beyond their training and mandate. Multiple factors affecting the performance of the lay counselors were identified, including insufficient resources, such as private counseling space and HIV test kits; and technical, administrative, and supervisory support.

Conclusion

Lay counselors are fulfilling an important role in Botswana''s healthcare system, serving as the entry point into HIV care, support, and treatment services.

Recommendation

For this and other similar task shifting initiatives, it is important that lay counselors'' responsibilities are clear and that training and support are adequate to optimize their effectiveness.     

Cognitive Training Improves Sleep Quality and Cognitive Function among Older Adults with Insomnia

Study Objectives

To investigate the effect of an eight-week, home-based, personalized, computerized cognitive training program on sleep quality and cognitive performance among older adults with insomnia.

Design

Participants (n = 51) were randomly allocated to a cognitive training group (n = 34) or to an active control group (n = 17). The participants in the cognitive training group completed an eight-week, home-based, personalized, computerized cognitive training program, while the participants in the active control group completed an eight-week, home-based program involving computerized tasks that do not engage high-level cognitive functioning. Before and after training, all participants'' sleep was monitored for one week by an actigraph and their cognitive performance was evaluated.

Setting

Community setting: residential sleep/performance testing facility.

Participants

Fifty-one older adults with insomnia (aged 65–85).

Interventions

Eight weeks of computerized cognitive training for older adults with insomnia.

Results

Mixed models for repeated measures analysis showed between-group improvements for the cognitive training group on both sleep quality (sleep onset latency and sleep efficiency) and cognitive performance (avoiding distractions, working memory, visual memory, general memory and naming). Hierarchical linear regressions analysis in the cognitive training group indicated that improved visual scanning is associated with earlier advent of sleep, while improved naming is associated with the reduction in wake after sleep onset and with the reduction in number of awakenings. Likewise the results indicate that improved “avoiding distractions” is associated with an increase in the duration of sleep. Moreover, the results indicate that in the active control group cognitive decline observed in working memory is associated with an increase in the time required to fall asleep.

Conclusions

New learning is instrumental in promoting initiation and maintenance of sleep in older adults with insomnia. Lasting and personalized cognitive training is particularly indicated to generate the type of learning necessary for combined cognitive and sleep enhancements in this population.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00901641","term_id":"NCT00901641"}}NCT00901641http://clinicaltrials.gov/ct2/show/NCT00901641     

Supplementation with α-Lipoic Acid,CoQ10, and Vitamin E Augments Running Performance and Mitochondrial Function in Female Mice

Antioxidant supplements are widely consumed by the general public; however, their effects of on exercise performance are controversial. The aim of this study was to examine the effects of an antioxidant cocktail (α-lipoic acid, vitamin E and coenzyme Q10) on exercise performance, muscle function and training adaptations in mice. C57Bl/J6 mice were placed on antioxidant supplement or placebo-control diets (n = 36/group) and divided into trained (8 wks treadmill running) (n = 12/group) and untrained groups (n = 24/group). Antioxidant supplementation had no effect on the running performance of trained mice nor did it affect training adaptations; however, untrained female mice that received antioxidants performed significantly better than placebo-control mice (p ≤ 0.05). Furthermore, antioxidant-supplemented females (untrained) showed elevated respiratory capacity in freshly excised muscle fibers (quadriceps femoris) (p ≤ 0.05), reduced oxidative damage to muscle proteins (p ≤ 0.05), and increased expression of mitochondrial proteins (p ≤ 0.05) compared to placebo-controls. These changes were attributed to increased expression of proliferator-activated receptor gamma coactivator 1α (PGC-1α) (p ≤ 0.05) via activation of AMP-activated protein kinase (AMPK) (p ≤ 0.05) by antioxidant supplementation. Overall, these results indicate that this antioxidant supplement exerts gender specific effects; augmenting performance and mitochondrial function in untrained females, but does not attenuate training adaptations.     

Preliminary Evidence That Anodal Transcranial Direct Current Stimulation Enhances Time to Task Failure of a Sustained Submaximal Contraction

The purpose of this study was to determine whether anodal transcranial direct current stimulation (tDCS) delivered while performing a sustained submaximal contraction would increase time to task failure (TTF) compared to sham stimulation. Healthy volunteers (n = 18) performed two fatiguing contractions at 20% of maximum strength with the elbow flexors on separate occasions. During fatigue task performance, either anodal or sham stimulation was delivered to the motor cortex for up to 20 minutes. Transcranial magnetic stimulation (TMS) was used to assess changes in cortical excitability during stimulation. There was no systematic effect of the anodal tDCS stimulation on TTF for the entire subject set (n = 18; p = 0.64). Accordingly, a posteriori subjects were divided into two tDCS-time groups: Full-Time (n = 8), where TTF occurred prior to the termination of tDCS, and Part-Time (n = 10), where TTF extended after tDCS terminated. The TTF for the Full-Time group was 31% longer with anodal tDCS compared to sham (p = 0.04), whereas TTF for the Part-Time group did not differ (p = 0.81). Therefore, the remainder of our analysis addressed the Full-Time group. With anodal tDCS, the amount of muscle fatigue was 6% greater at task failure (p = 0.05) and the amount of time the Full-Time group performed the task at an RPE between 8–10 (“very hard”) increased by 38% (p = 0.04) compared to sham. There was no difference in measures of cortical excitability between stimulation conditions (p = 0.90). That the targeted delivery of anodal tDCS during task performance both increased TTF and the amount of muscle fatigue in a subset of subjects suggests that augmenting cortical excitability with tDCS enhanced descending drive to the spinal motorpool to recruit more motor units. The results also suggest that the application of tDCS during performance of fatiguing activity has the potential to bolster the capacity to exercise under conditions required to derive benefits due to overload.     

Effects of 12 Weeks High-Intensity & Reduced-Volume Training in Elite Athletes

It was investigated if high-intensity interval training (HIT) at the expense of total training volume improves performance, maximal oxygen uptake and swimming economy. 41 elite swimmers were randomly allocated to a control (CON) or HIT group. For 12 weeks both groups trained ∼12 h per week. HIT comprised ∼5 h vs. 1 h and total distance was ∼17 km vs. 35 km per week for HIT and CON, respectively. HIT was performed as 6-10×10-30 s maximal effort interspersed by 2–4 minutes of rest. Performance of 100 m all-out freestyle and 200 m freestyle was similar before and after the intervention in both HIT (60.4±4.0 vs. 60.3±4.0 s; n = 13 and 133.2±6.4 vs. 132.6±7.7 s; n = 14) and CON (60.2±3.7 vs. 60.6±3.8 s; n = 15 and 133.5±7.0 vs. 133.3±7.6 s; n = 15). Maximal oxygen uptake during swimming was similar before and after the intervention in both the HIT (4.0±0.9 vs. 3.8±1.0 l O₂×min⁻¹; n = 14) and CON (3.8±0.7 vs. 3.8±0.7 l O₂×min⁻¹; n = 11) group. Oxygen uptake determined at fixed submaximal speed was not significantly affected in either group by the intervention. Body fat % tended to increase (P = 0.09) in the HIT group (15.4±1.6% vs. 16.3±1.6%; P = 0.09; n = 16) and increased (P<0.05) in the CON group (13.9±1.5% vs. 14.9±1.5%; n = 17). A distance reduction of 50% and a more than doubled HIT amount for 12 weeks did neither improve nor compromise performance or physiological capacity in elite swimmers.     

After Being Challenged by a Video Game Problem,Sleep Increases the Chance to Solve It

In the past years many studies have demonstrated the role of sleep on memory consolidation. It is known that sleeping after learning a declarative or non-declarative task, is better than remaining awake. Furthermore, there are reports of a possible role for dreams in consolidation of declarative memories. Other studies have reported the effect of naps on memory consolidation. With similar protocols, another set of studies indicated that sleep has a role in creativity and problem-solving. Here we hypothesised that sleep can increase the likelihood of solving problems. After struggling to solve a video game problem, subjects who took a nap (n = 14) were almost twice as likely to solve it when compared to the wake control group (n = 15). It is interesting to note that, in the nap group 9 out 14 subjects engaged in slow-wave sleep (SWS) and all solved the problem. Surprisingly, we did not find a significant involvement of Rapid Eye Movement (REM) sleep in this task. Slow-wave sleep is believed to be crucial for the transfer of memory-related information to the neocortex and implement intentions. Sleep can benefit problem-solving through the generalisation of newly encoded information and abstraction of the gist. In conclusion, our results indicate that sleep, even a nap, can potentiate the solution of problems that involve logical reasoning. Thus, sleep''s function seems to go beyond memory consolidation to include managing of everyday-life events.     

Cholesteryl Ester Transfer Protein Inhibitors in the Treatment of Dyslipidemia: A Systematic Review and Meta-Analysis

Cholesteryl ester transfer protein (CETP) inhibitors are gaining substantial research interest for raising high density lipoprotein cholesterol levels. The aim of the research was to estimate the efficacy and safety of cholesteryl ester transfer protein inhibitors as novel lipid modifying drugs. Systematic searches of English literature for randomized controlled trials (RCT) were collected from MEDLINE, EBASE, CENTRAL and references listed in eligible studies. Two independent authors assessed the search results and only included the double-blind RCTs by using cholesteryl ester transfer protein inhibitors as exclusively or co-administrated with statin therapy irrespective of gender in enrolled adult subjects. Two independent authors extracted the data by using predefined data fields. Of 503 studies identified, 14 studies met the inclusion criteria, and 12 studies were included into the final meta-analysis. Our meta-analysis revealed that CETP inhibitors increased the HDL-c levels (n = 2826, p<0.00001, mean difference (MD)  = 20.47, 95% CI [19.80 to 21.15]) and total cholesterol (n = 3423, p = 0.0002, MD = 3.57, 95%CI [1.69 to 5.44] to some extent combined with a reduction in triglyceride (n = 3739, p<0.00001, MD = −10.47, 95% CI [−11.91 to −9.03]) and LDL-c (n = 3159, p<0.00001, MD = −17.12, 95% CI [−18.87 to −15.36]) irrespective of mono-therapy or co-administration with statins. Subgroup analysis suggested that the lipid modifying effects varied according to the four currently available CETP inhibitors. CETP inhibitor therapy did not increase the adverse events when compared with control. However, we observed a slight increase in blood pressure (SBP, n = 2384, p<0.00001, MD = 2.73, 95% CI [2.14 to 3.31], DBP, n = 2384, p<0.00001, MD = 1.16, 95% CI [0.73 to 1.60]) after CETP inhibitor treatment, which were mainly ascribed to the torcetrapib treatment subgroup. CETP inhibitors therapy is associated with significant increase in HDL-c and decrease in triglyceride and LDL-c with satisfactory safety and tolerability in patients with dyslipidemia. However, the side-effect on blood pressure deserves more consideration in future studies.     

The Impact of Financial Reward Contingencies on Cognitive Function Profiles in Adult ADHD

Objectives

Although it is well established that cognitive performance in children with attention-deficit/hyperactivity disorder (ADHD) is affected by reward and that key deficits associated with the disorder may thereby be attenuated or even compensated, this phenomenon in adults with ADHD has thus far not been addressed. Therefore, the aim of the present study was to examine the motivating effect of financial reward on task performance in adults with ADHD by focusing on the domains of executive functioning, attention, time perception, and delay aversion.

Methods

We examined male and female adults aged 18–40 years with ADHD (n = 38) along with a matched control group (n = 40) using six well-established experimental paradigms.

Results

Impaired performance in the ADHD group was observed for stop-signal omission errors, n-back accuracy, reaction time variability in the continuous performance task, and time reproduction accuracy, and reward normalized time reproduction accuracy. Furthermore, when rewarded, subjects with ADHD exhibited longer reaction times and fewer false positives in the continuous performance task, which suggests the use of strategies to prevent impulsivity errors.

Conclusions

Taken together, our results support the existence of both cognitive and motivational mechanisms for the disorder, which is in line with current models of ADHD. Furthermore, our data suggest cognitive strategies of “stopping and thinking” as a possible underlying mechanism for task improvement that seems to be mediated by reward, which highlights the importance of the interaction between motivation and cognition in adult ADHD.     

Modafinil Increases the Latency of Response in the Hayling Sentence Completion Test in Healthy Volunteers: A Randomised Controlled Trial

Background

Modafinil is a medication licensed for the treatment of narcolepsy. However, it has been reported that healthy individuals without wakefulness disorders are using modafinil off-label to enhance cognitive functioning. Although some studies have reported that modafinil improves cognitive task performance in healthy volunteers, numerous other studies have failed to detect cognitive enhancing effects of modafinil on several well-established neuropsychological tasks. Interestingly, several clinical and preclinical studies have found that improved cognitive task performance by modafinil is accompanied by slower response times. This observation raises the question as to whether this slowing of response time in healthy volunteers is a necessary and sufficient condition for cognitive enhancement with modafinil. The aim of the current experiment was to explore this question by investigating the effects of modafinil on the Hayling Sentence Completion Test (HSCT).

Methodology

Sixty-four healthy volunteers received either a single dose (200 mg) of modafinil (n = 32) or placebo (n = 32) in a randomized, double-blind, placebo-controlled, parallel group study in which the principal outcome measures were response latencies on the response initiation and response inhibition sections of the HSCT.

Principal Findings

Participants dosed with modafinil had significantly longer mean response latencies on the HSCT for both the response initiation and response inhibition compared to participants dosed with placebo. However, participants in both groups made a similar number of errors on each of these measures, indicating that modafinil did not enhance the accuracy of performance of the task relative to placebo.

Conclusions

This study demonstrated that administration of single 200 mg doses of modafinil to healthy individuals increased the latency of responses in the performance of the HSCT, a task that is highly sensitive to prefrontal executive function, without enhancing accuracy of performance. This finding may provide important clues to defining the limitations of modafinil as a putative cognitive enhancer.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02051153","term_id":"NCT02051153"}}NCT02051153     

Evoked Potentials and Neuropsychological Tests Validate Positron Emission Topography (PET) Brain Metabolism in Cognitively Impaired Patients

Fluorodeoxyglucose (FDG) Positron Emission Topography (PET) brain hypometabolism (HM) correlates with diminished cognitive capacity and risk of developing dementia. However, because clinical utility of PET is limited by cost, we sought to determine whether a less costly electrophysiological measure, the P300 evoked potential, in combination with neuropsychological test performance, would validate PET HM in neuropsychiatric patients. We found that patients with amnestic and non-amnestic cognitive impairment and HM (n = 43) evidenced significantly reduced P300 amplitudes, delayed latencies, and neuropsychological deficits, compared to patients with normal brain metabolism (NM; n = 187). Data from patients with missing cognitive test scores (n = 57) were removed from the final sample, and logistic regression modeling was performed on the modified sample (n = 173, p = .000004). The logistic regression modeling, based on P300 and neuropsychological measures, was used to validate membership in the HM vs. NM groups. It showed classification validation in 13/25 HM subjects (52.0%) and in 125/148 NM subjects (84.5%), correlating with total classification accuracy of 79.8%. In this paper, abnormal P300 evoked potentials coupled with cognitive test impairment validates brain metabolism and mild/moderate cognitive impairment (MCI). To this end, we cautiously propose incorporating electrophysiological and neuropsychological assessments as cost-effective brain metabolism and MCI indicators in primary care. Final interpretation of these results must await required additional studies confirming these interesting results.     

Computerized Cognitive Training in Cognitively Healthy Older Adults: A Systematic Review and Meta-Analysis of Effect Modifiers

Background

New effective interventions to attenuate age-related cognitive decline are a global priority. Computerized cognitive training (CCT) is believed to be safe and can be inexpensive, but neither its efficacy in enhancing cognitive performance in healthy older adults nor the impact of design factors on such efficacy has been systematically analyzed. Our aim therefore was to quantitatively assess whether CCT programs can enhance cognition in healthy older adults, discriminate responsive from nonresponsive cognitive domains, and identify the most salient design factors.

Methods and Findings

We systematically searched Medline, Embase, and PsycINFO for relevant studies from the databases'' inception to 9 July 2014. Eligible studies were randomized controlled trials investigating the effects of ≥4 h of CCT on performance in neuropsychological tests in older adults without dementia or other cognitive impairment. Fifty-two studies encompassing 4,885 participants were eligible. Intervention designs varied considerably, but after removal of one outlier, heterogeneity across studies was small (I ² = 29.92%). There was no systematic evidence of publication bias. The overall effect size (Hedges'' g, random effects model) for CCT versus control was small and statistically significant, g = 0.22 (95% CI 0.15 to 0.29). Small to moderate effect sizes were found for nonverbal memory, g = 0.24 (95% CI 0.09 to 0.38); verbal memory, g = 0.08 (95% CI 0.01 to 0.15); working memory (WM), g = 0.22 (95% CI 0.09 to 0.35); processing speed, g = 0.31 (95% CI 0.11 to 0.50); and visuospatial skills, g = 0.30 (95% CI 0.07 to 0.54). No significant effects were found for executive functions and attention. Moderator analyses revealed that home-based administration was ineffective compared to group-based training, and that more than three training sessions per week was ineffective versus three or fewer. There was no evidence for the effectiveness of WM training, and only weak evidence for sessions less than 30 min. These results are limited to healthy older adults, and do not address the durability of training effects.

Conclusions

CCT is modestly effective at improving cognitive performance in healthy older adults, but efficacy varies across cognitive domains and is largely determined by design choices. Unsupervised at-home training and training more than three times per week are specifically ineffective. Further research is required to enhance efficacy of the intervention. Please see later in the article for the Editors'' Summary     

Improved Working Memory but No Effect on Striatal Vesicular Monoamine Transporter Type 2 after Omega-3 Polyunsaturated Fatty Acid Supplementation

Studies in rodents indicate that diets deficient in omega-3 polyunsaturated fatty acids (n–3 PUFA) lower dopamine neurotransmission as measured by striatal vesicular monoamine transporter type 2 (VMAT2) density and amphetamine-induced dopamine release. This suggests that dietary supplementation with fish oil might increase VMAT2 availability, enhance dopamine storage and release, and improve dopamine-dependent cognitive functions such as working memory. To investigate this mechanism in humans, positron emission tomography (PET) was used to measure VMAT2 availability pre- and post-supplementation of n–3 PUFA in healthy individuals. Healthy young adult subjects were scanned with PET using [¹¹C]-(+)-α-dihydrotetrabenzine (DTBZ) before and after six months of n–3 PUFA supplementation (Lovaza, 2 g/day containing docosahexaenonic acid, DHA 750 mg/d and eicosapentaenoic acid, EPA 930 mg/d). In addition, subjects underwent a working memory task (n-back) and red blood cell membrane (RBC) fatty acid composition analysis pre- and post-supplementation. RBC analysis showed a significant increase in both DHA and EPA post-supplementation. In contrast, no significant change in [¹¹C]DTBZ binding potential (BP_ND) in striatum and its subdivisions were observed after supplementation with n–3 PUFA. No correlation was evident between n–3 PUFA induced change in RBC DHA or EPA levels and change in [¹¹C]DTBZ BP_ND in striatal subdivisions. However, pre-supplementation RBC DHA levels was predictive of baseline performance (i.e., adjusted hit rate, AHR on 3-back) on the n-back task (y = 0.19+0.07, r² = 0.55, p = 0.009). In addition, subjects AHR performance improved on 3-back post-supplementation (pre 0.65±0.27, post 0.80±0.15, p = 0.04). The correlation between n-back performance, and DHA levels are consistent with reports in which higher DHA levels is related to improved cognitive performance. However, the lack of change in [¹¹C]DBTZ BP_ND indicates that striatal VMAT2 regulation is not the mechanism of action by which n–3 PUFA improves cognitive performance.     

The Relation between Resting State Connectivity and Creativity in Adolescents before and after Training

An important component of creativity is divergent thinking, which involves the ability to generate novel and useful problem solutions. In this study, we tested the relation between resting-state functional connectivity of brain areas activated during a divergent thinking task (i.e., supramarginal gyrus, middle temporal gyrus, medial frontal gyrus) and the effect of practice in 32 adolescents aged 15–16. Over a period of two weeks, an experimental group (n = 16) conducted an 8-session Alternative Uses Task (AUT) training and an active control group (n = 16) conducted an 8-session rule switching training. Resting-state functional connectivity was measured before (pre-test) and after (post-test) training. Across groups at pre-test, stronger connectivity between the middle temporal gyrus and bilateral postcentral gyrus was associated with better divergent thinking performance. The AUT-training, however, did not significantly change functional connectivity. Post hoc analyses showed that change in divergent thinking performance over time was predicted by connectivity between left supramarginal gyrus and right occipital cortex. These results provide evidence for a relation between divergent thinking and resting-state functional connectivity in a task-positive network, taking an important step towards understanding creative cognition and functional brain connectivity.     

Should Prior FIT Results Be Incorporated as an Additional Variable to Estimate Risk of Colorectal Neoplasia? A Prospective Study of 5,813 Screening Colonoscopies

Background

Recent studies showed that previous negative results from faecal immunochemical tests (FITs) for colorectal cancer (CRC) screening was associated with lower risk of advanced neoplasia (AN). We evaluated whether prior FIT results should be included to estimate the risk of AN in 2008–2012.

Methods

A community-based screening practice recruited 5,813 asymptomatic residents aged 50 to 70 years in Hong Kong for CRC screening. We included study participants who had (1). positive FIT with subsequent colonoscopy workup (FIT+ group; n = 356); (2). negative FIT in three consecutive years and received a colonoscopy (FIT- group; n = 857); (3). received colonoscopy without FIT (colonoscopy group; n = 473); and (4). received both colonoscopy and FIT at the same time (combined group; n = 4,127). One binary logistic regression model evaluated whether prior FIT results were associated with colonoscopy findings of AN.

Results

The proportion of participants having AN/CRC was 18.0% (FIT+), 5.5% (FIT-), 8.0% (colonoscopy group), and 4.3% (combined group), respectively. When compared with the colonoscopy group, those in the FIT- group were not significantly more or less likely to have AN/CRC (AOR  = 0.77, 95% C.I. = 0.51 to 1.18, p  = 0.230). Having one (AOR = 0.73, 95% C.I. 0.48–1.12, p = 0.151) or three consecutive negative FIT result (AOR = 0.98, 95% C.I. 0.60–1.62, p = 0.944) were not associated with lower risks of AN/CRC. Subjects in the FIT+ group was 3.32-fold (95% C.I. 2.07 to 5.32, p<0.001) more likely to have AN/CRC.

Conclusions

These findings indicated that subjects with negative FIT findings could be risk stratified similarly as those who had not previously received FIT.     

Sleep Deprivation Impairs Consolidation of Cued Fear Memory in Rats

Post-learning sleep facilitates negative memory consolidation and also helps preserve it over several years. It is believed, therefore, that sleep deprivation may help prevent consolidation of fearful memory. Its effect, however, on consolidation of negative/frightening memories is not known. Cued fear-conditioning (CuFC) is a widely used model to understand the neural basis of negative memory associated with anxiety disorders. In this study, we first determined the suitable circadian timing for consolidation of CuFC memory and changes in sleep architecture after CuFC. Thereafter, we studied the effect of sleep deprivation on CuFC memory consolidation. Three sets of experiments were performed in male Wistar rat (n = 51). In experiment-I, animals were conditioned to cued-fear by presenting ten tone-shock paired stimuli during lights-on (7 AM) (n = 9) and lights-off (7 PM) (n = 9) periods. In experiment-II, animals were prepared for polysomnographic recording (n = 8) and changes in sleep architecture after CuFC was determined. Further in experiment-III, animals were cued fear-conditioned during the lights-off period and were randomly divided into four groups: Sleep-Deprived (SD) (n = 9), Non-Sleep Deprived (NSD) (n = 9), Stress Control (SC) (n = 9) and Tone Control (n = 7). Percent freezing amount, a hallmark of fear, was compared statistically in these groups. Rats trained during the lights-off period exhibited significantly more freezing compared to lights-on period. In CuFC trained animals, total sleep amount did not change, however, REM sleep decreased significantly. Further, out of total sleep time, animals spent proportionately more time in NREM sleep. Nevertheless, SD animals exhibited significantly less freezing compared to NSD and SC groups. These data suggest that sleep plays an important role in the consolidation of cued fear-conditioned memory.     

Functional Neuroanatomy of Executive Function after Neonatal Brain Injury in Adults Who Were Born Very Preterm

Individuals who were born very preterm (VPT; <33 gestational weeks) are at risk of experiencing deficits in tasks involving executive function in childhood and beyond. In addition, the type and severity of neonatal brain injury associated with very preterm birth may exert differential effects on executive functioning by altering its neuroanatomical substrates. Here we addressed this question by investigating with functional magnetic resonance imaging (fMRI) the haemodynamic response during executive-type processing using a phonological verbal fluency and a working memory task in VPT-born young adults who had experienced differing degrees of neonatal brain injury. 12 VPT individuals with a history of periventricular haemorrhage and ventricular dilatation (PVH+VD), 17 VPT individuals with a history of uncomplicated periventricular haemorrhage (UPVH), 13 VPT individuals with no history of neonatal brain injury and 17 controls received an MRI scan whilst completing a verbal fluency task with two cognitive loads (‘easy’ and ‘hard’ letters). Two groups of VPT individuals (PVH+VD; n = 10, UPVH; n = 8) performed an n-back task with three cognitive loads (1-, 2-, 3-back). Results demonstrated that VPT individuals displayed hyperactivation in frontal, temporal, and parietal cortices and in caudate nucleus, insula and thalamus compared to controls, as demands of the verbal fluency task increased, regardless of type of neonatal brain injury. On the other hand, during the n-back task and as working memory load increased, the PVH+VD group showed less engagement of the frontal cortex than the UPVH group. In conclusion, this study suggests that the functional neuroanatomy of different executive-type processes is altered following VPT birth and that neural activation associated with specific aspects of executive function (i.e., working memory) may be particularly sensitive to the extent of neonatal brain injury.     

No Association of the BDNF Val66met Polymorphism with Implicit Associative Vocabulary and Motor Learning

Brain-derived neurotrophic factor (BDNF) has been suggested to play a major role in plasticity, neurogenesis and learning in the adult brain. The BDNF gene contains a common val66met polymorphism associated with decreased activity-dependent excretion of BDNF and a potential influence on behaviour, more specifically, on motor learning. The objective of this study was to determine the influence of the BDNF val66met polymorphism on short-term implicit associative learning and whether its influence is cognitive domain-specific (motor vs. language). A sample of 38 young healthy participants was genotyped, screened for background and neuropsychological differences, and tested with two associative implicit learning paradigms in two different cognitive domains, i.e., motor and vocabulary learning. Subjects performed the serial reaction time task (SRTT) to determine implicit motor learning and a recently established associative vocabulary learning task (AVL) for implicit learning of action and object words. To determine the influence of the BDNF polymorphism on domain-specific implicit learning, behavioural improvements in the two tasks were compared between val/val (n = 22) and met carriers (val/met: n = 15 and met/met: n = 1). There was no evidence for an impact of the BDNF val66met polymorphism on the behavioural outcome in implicit short-term learning paradigms in young healthy subjects. Whether this polymorphism plays a relevant role in long-term training paradigms or in subjects with impaired neuronal plasticity or reduced learning capacity, such as aged individuals, demented patients or patients with brain lesions, has to be determined in future studies.     

Peptidomic Identification of Serum Peptides Diagnosing Preeclampsia

We sought to identify serological markers capable of diagnosing preeclampsia (PE). We performed serum peptide analysis (liquid chromatography mass spectrometry) of 62 unique samples from 31 PE patients and 31 healthy pregnant controls, with two-thirds used as a training set and the other third as a testing set. Differential serum peptide profiling identified 52 significant serum peptides, and a 19-peptide panel collectively discriminating PE in training sets (n = 21 PE, n = 21 control; specificity = 85.7% and sensitivity = 100%) and testing sets (n = 10 PE, n = 10 control; specificity = 80% and sensitivity = 100%). The panel peptides were derived from 6 different protein precursors: 13 from fibrinogen alpha (FGA), 1 from alpha-1-antitrypsin (A1AT), 1 from apolipoprotein L1 (APO-L1), 1 from inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), 2 from kininogen-1 (KNG1), and 1 from thymosin beta-4 (TMSB4). We concluded that serum peptides can accurately discriminate active PE. Measurement of a 19-peptide panel could be performed quickly and in a quantitative mass spectrometric platform available in clinical laboratories. This serum peptide panel quantification could provide clinical utility in predicting PE or differential diagnosis of PE from confounding chronic hypertension.     

A Behavioral Mechanism of How Increases in Leg Strength Improve Old Adults’ Gait Speed

We examined a behavioral mechanism of how increases in leg strength improve healthy old adults’ gait speed. Leg press strength training improved maximal leg press load 40% (p = 0.001) and isometric strength in 5 group of leg muscles 32% (p = 0.001) in a randomly allocated intervention group of healthy old adults (age 74, n = 15) but not in no-exercise control group (age 74, n = 8). Gait speed increased similarly in the training (9.9%) and control (8.6%) groups (time main effect, p = 0.001). However, in the training group only, in line with the concept of biomechanical plasticity of aging gait, hip extensors and ankle plantarflexors became the only significant predictors of self-selected and maximal gait speed. The study provides the first behavioral evidence regarding a mechanism of how increases in leg strength improve healthy old adults’ gait speed.