Quantitative susceptibility mapping identifies hippocampal and other subcortical grey matter tissue composition changes in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is associated with widespread brain alterations. Using quantitative susceptibility mapping (QSM) alongside transverse relaxation rate ( R 2 * ), we investigated regional brain susceptibility changes in 36 patients with left-sided (LTLE) or right-sided TLE (RTLE) secondary to hippocampal sclerosis, and 27 healthy controls (HC). We compared three susceptibility calculation methods to ensure image quality. Correlations of susceptibility and R 2 * with age of epilepsy onset, frequency of focal-to-bilateral tonic-clonic seizures (FBTCS), and neuropsychological test scores were examined. Weak-harmonic QSM (WH-QSM) successfully reduced noise and removed residual background field artefacts. Significant susceptibility increases were identified in the left putamen in the RTLE group compared to the LTLE group, the right putamen and right thalamus in the RTLE group compared to HC, and a significant susceptibility decrease in the left hippocampus in LTLE versus HC. LTLE patients who underwent epilepsy surgery showed significantly lower left-versus-right hippocampal susceptibility. Significant R 2 * changes were found between TLE and HC groups in the amygdala, putamen, thalamus, and in the hippocampus. Specifically, decreased R2 * was found in the left and right hippocampus in LTLE and RTLE, respectively, compared to HC. Susceptibility and R 2 * were significantly correlated with cognitive test scores in the hippocampus, globus pallidus, and thalamus. FBTCS frequency correlated positively with ipsilateral thalamic and contralateral putamen susceptibility and with R 2 * in bilateral globi pallidi. Age of onset was correlated with susceptibility in the hippocampus and putamen, and with R 2 * in the caudate. Susceptibility and R 2 * changes observed in TLE groups suggest selective loss of low-myelinated neurons alongside iron redistribution in the hippocampi, predominantly ipsilaterally, indicating QSM's sensitivity to local pathology. Increased susceptibility and R 2 * in the thalamus and putamen suggest increased iron content and reflect disease severity.

Copy rats: Learning by observation during a foraging task by rats.

In two experiments, rats observed expert foragers in a laboratory foraging task. In both experiments, 12 towers with a food cup on top of each tower were placed in a circle. Six towers, marked with black and white stripes, had cups baited with cheese, and were located in randomly selected positions on successive trials. The other six towers were white with food cups that were sham baited with inaccessible food. In both experiments, during Phase 1, demonstrator rats eventually learned to find the baited towers, making approximately 90% correct choices in their first six choices. In Phase 2, observer rats each had an opportunity to observe, from a cage located inside the circle of towers, a now-expert demonstrator forage. Half of the observers were able to observe a cage mate, whereas the other half of the observers were able to observe a non-cage mate. After a delay of about 2 min (Experiment 1) or about 24 h (Experiment 2), the observers were allowed to forage among the rebaited towers. In both experiments, the observers performed better during their 20 Phase 2 trials than the demonstrators had performed during their first 20 Phase 1 trials. But, in both experiments, there was no clearly significant difference between the performance of observers able to watch cage mates as opposed to non-cage mates. Because the observational effect seen in both experiments survived a 24-h delay between observation and performance, it was deemed to have been based on learning.

Episodic memory network connectivity in temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) affects brain networks and is associated with impairment of episodic memory. Temporal and extratemporal reorganization of memory functions is described in functional magnetic resonance imaging (fMRI) studies. Functional reorganizations have been shown at the local activation level, but network-level alterations have been underinvestigated. We aim to investigate the functional anatomy of memory networks using memory fMRI and determine how this relates to memory function in TLE. METHODS: Ninety patients with unilateral TLE (43 left) and 29 controls performed a memory-encoding fMRI paradigm of faces and words with subsequent out-of-scanner recognition test. Subsequent memory event-related contrasts of words and faces remembered were generated. Psychophysiological interaction analysis investigated task-associated changes in functional connectivity seeding from the mesial temporal lobes (MTLs). Correlations between changes in functional connectivity and clinical memory scores, epilepsy duration, age at epilepsy onset, and seizure frequency were investigated, and between connectivity supportive of better memory and disease burden. Connectivity differences between controls and TLE, and between TLE with and without hippocampal sclerosis, were explored using these confounds as regressors of no interest. RESULTS: Compared to controls, TLE patients showed widespread decreased connectivity between bilateral MTLs and frontal lobes, and increased local connectivity between the anterior MTLs bilaterally. Increased intrinsic connectivity within the bilateral MTLs correlated with better out-of-scanner memory performance in both left and right TLE. Longer epilepsy duration and higher seizure frequency were associated with decreased connectivity between bilateral MTLs and left/right orbitofrontal cortex (OFC) and insula, connections supportive of memory functions. TLE due to hippocampal sclerosis was associated with greater connectivity disruption within the MTL and extratemporally. SIGNIFICANCE: Connectivity analyses showed that TLE is associated with temporal and extratemporal memory network reorganization. Increased bilateral functional connectivity within the MTL and connectivity to OFC and insula are efficient, and are disrupted by greater disease burden.

Resective, Ablative and Radiosurgical Interventions for Drug Resistant Mesial Temporal Lobe Epilepsy: A Systematic Review and Meta-Analysis of Outcomes.

Objectives: One-third of individuals with focal epilepsy do not achieve seizure freedom despite best medical therapy. Mesial temporal lobe epilepsy (MTLE) is the most common form of drug resistant focal epilepsy. Surgery may lead to long-term seizure remission if the epileptogenic zone can be defined and safely removed or disconnected. We compare published outcomes following open surgical techniques, radiosurgery (SRS), laser interstitial thermal therapy (LITT) and radiofrequency ablation (RF-TC). Methods: PRISMA systematic review was performed through structured searches of PubMed, Embase and Cochrane databases. Inclusion criteria encompassed studies of MTLE reporting seizure-free outcomes in ≥10 patients with ≥12 months follow-up. Due to variability in open surgical approaches, only comparative studies were included to minimize the risk of bias. Random effects meta-analysis was performed to calculate effects sizes and a pooled estimate of the probability of seizure freedom per person-year. A mixed effects linear regression model was performed to compare effect sizes between interventions. Results: From 1,801 screened articles, 41 articles were included in the quantitative analysis. Open surgery included anterior temporal lobe resection as well as transcortical and trans-sylvian selective amygdalohippocampectomy. The pooled seizure-free rate per person-year was 0.72 (95% CI 0.66-0.79) with trans-sylvian selective amygdalohippocampectomy, 0.59 (95% CI 0.53-0.65) with LITT, 0.70 (95% CI 0.64-0.77) with anterior temporal lobe resection, 0.60 (95% CI 0.49-0.73) with transcortical selective amygdalohippocampectomy, 0.38 (95% CI 0.14-1.00) with RF-TC and 0.50 (95% CI 0.34-0.73) with SRS. Follow up duration and study sizes were limited with LITT and RF-TC. A mixed-effects linear regression model suggests significant differences between interventions, with LITT, ATLR and SAH demonstrating the largest effects estimates and RF-TC the lowest. Conclusions: Overall, novel "minimally invasive" approaches are still comparatively less efficacious than open surgery. LITT shows promising seizure effectiveness, however follow-up durations are shorter for minimally invasive approaches so the durability of the outcomes cannot yet be assessed. Secondary outcome measures such as Neurological complications, neuropsychological outcome and interventional morbidity are poorly reported but are important considerations when deciding on first-line treatments.

The Pair Test: A computerised measure of learning and memory.

There is increasing interest in the assessment of learning and memory in typically developing children as well as in children with neurodevelopmental disorders. However, neuropsychological assessments have been hampered by the dearth of standardised tests that enable direct comparison between distinct memory processes or between types of stimulus materials. We developed a tablet-based paired-associate learning paradigm, the Pair Test, based on neurocognitive models of learning and memory. The aims are to (i) establish the utility of this novel memory tool for use with children across a wide age range, and (ii) examine test validity, reliability and reproducibility of the construct. The convergent validity of the test was found to be adequate, and higher test reliability was shown for the Pair Test compared to standardised measures. Moderate test-retest reproducibility was shown, despite a long time interval between sessions (14 months). Moreover, the Pair Test is able to capture developmental changes in memory, and can therefore chart the developmental trajectory of memory and learning functions across childhood and adolescence. Finally, we used this novel instrument to acquire normative data from 130 typically developing children, aged 8-18 years. Age-stratified normative data are provided for learning, delayed recall and delayed recognition, for measures of verbal and non-verbal memory. The Pair Test thus provides measures of learning and memory accounting for encoding, consolidation and retrieval processes. As such, the standardised test results can be used to determine the status of learning and memory in healthy children, and also to identify deficits in paediatric patients at risk of damage to the neural network underlying mnemonic functions.

Agua4All: Providing Safe Drinking Water in Rural California Communities.

INTRODUCTION: Drinking water instead of sugar-sweetened beverages may reduce obesity and dental caries. Tap water is more affordable and sustainable than bottled water and more likely to contain fluoride, which prevents caries. To address inequities in access to safe tap water, cross-sector partners established the Agua4All safe drinking-water program in 2 rural San Joaquin Valley, California, communities. The program's objective was to examine Agua4All's feasibility, acceptability, and effect on water intake. METHODS: We provided bottle-filling stations dispensing safe water at 12 sites in 2 communities and provided limited promotional support. To compare the effect of different levels of promotion, sites in 1 community also received a promotions toolkit, a stipend, and assistance in developing and conducting their own promotional activities (site-led promotion). Beverage intake at sites was observed at baseline (pre-installation), at time 1 (post-installation), and at times 2 and 3 (post-promotion). Flowmeters tracked water dispensings. Staff interviews examined implementation barriers and facilitators. RESULTS: From baseline to time 3, a nonsignificant increase (21.16%) occurred in the proportion of people drinking water at sites with water stations and site-led promotion compared with sites with water stations and limited promotion (5.13%) (P = .14). Mean daily gallons of water taken from stations per site was 3.61 (standard deviation, 3.84). Most staff members (77%) at the sites preferred water stations to traditional drinking fountains. CONCLUSION: Bottle-filling stations with safe water and site-led promotion are a promising strategy for increasing water intake in communities without safe tap water. Larger studies should examine the effects of such stations on intake of sugar-sweetened beverages and on overall health.

A Guide to Designing a Memory fMRI Paradigm for Pre-surgical Evaluation in Temporal Lobe Epilepsy.

There has been increasing interest in the clinical and experimental use of memory functional Magnetic Resonance Imaging (fMRI). The 2017 American Academy of Neurology practice guidelines on the use of pre-surgical cognitive fMRI suggests that verbal memory fMRI could be used to lateralize memory functions in people with Temporal Lobe Epilepsy (TLE) and should be used to predict post-operative verbal memory outcome. There are however technical and methodological considerations, to optimize both the sensitivity and specificity of this imaging modality. Below we discuss these constraints and suggest recommendations to consider when designing a memory fMRI paradigm.

A Functional MRI Paradigm Suitable for Language and Memory Mapping in Pediatric Temporal Lobe Epilepsy.

Functional Magnetic Resonance Imaging (fMRI) is a technique frequently used to determine the territories of eloquent tissue that serve critical functions, such as language. This can be particularly useful as part of the pre-surgical assessment for temporal lobe epilepsy (TLE) in order to predict cognitive outcome and guide surgical decision-making. Whereas language fMRI is widely used, memory fMRI is less frequently employed in adult TLE, and lacking in childhood TLE. We have developed a combined language/memory fMRI paradigm that is suitable for children, to provide clinically useful information for surgical planning in pediatric TLE. We evaluated this paradigm in 28 healthy children, aged 8 to 18 years. The advantages of this paradigm are: (a) it examines the functional mapping of language and memory networks within one scanning session, (b) provides assessment of both memory encoding- and retrieval-related neural networks, (c) examines recall-based retrieval to engage hippocampal involvement compared to recognition-based retrieval, and (d) provides overt verbal responses to monitor in-scanner memory performance. This novel fMRI paradigm was designed for language and memory mapping in pediatric TLE and could provide clinically useful information for surgical planning. Finally, parallel versions of the paradigm allow the comparison of brain activations pre- and post-surgical intervention.

Cognitive neuroscience using wearable magnetometer arrays: Non-invasive assessment of language function.

Recent work has demonstrated that Optically Pumped Magnetometers (OPMs) can be utilised to create a wearable Magnetoencephalography (MEG) system that is motion robust. In this study, we use this system to map eloquent cortex using a clinically validated language lateralisation paradigm (covert verb generation: 120 trials, ∼10 min total duration) in healthy adults (n = 3). We show that it is possible to lateralise and localise language function on a case by case basis using this system. Specifically, we show that at a sensor and source level we can reliably detect a lateralising beta band (15-30 Hz) desynchronization in all subjects. This is the first study of human cognition using OPMs and not only highlights this technology's utility as tool for (developmental) cognitive neuroscience but also its potential to contribute to surgical planning via mapping of eloquent cortex, especially in young children.

The perfect match: Do criminal stereotypes bias forensic evidence analysis?

This research provided the first empirical test of the hypothesis that stereotypes bias evaluations of forensic evidence. A pilot study (N = 107) assessed the content and consensus of 20 criminal stereotypes by identifying perpetrator characteristics (e.g., sex, race, age, religion) that are stereotypically associated with specific crimes. In the main experiment (N = 225), participants read a mock police incident report involving either a stereotyped crime (child molestation) or a nonstereotyped crime (identity theft) and judged whether a suspect's fingerprint matched a fingerprint recovered at the crime scene. Accompanying the suspect's fingerprint was personal information about the suspect of the type that is routinely available to fingerprint analysts (e.g., race, sex) and which could activate a stereotype. Participants most often perceived the fingerprints to match when the suspect fit the criminal stereotype, even though the prints did not actually match. Moreover, participants appeared to be unaware of the extent to which a criminal stereotype had biased their evaluations. These findings demonstrate that criminal stereotypes are a potential source of bias in forensic evidence analysis and suggest that suspects who fit criminal stereotypes may be disadvantaged over the course of the criminal justice process. (PsycINFO Database Record

Aerobic fitness and executive control of relational memory in preadolescent children.

PURPOSE: the neurocognitive benefits of an active lifestyle in childhood have public health and educational implications, especially as children in today's technological society are becoming increasingly overweight, unhealthy, and unfit. Human and animal studies show that aerobic exercise affects both prefrontal executive control and hippocampal function. This investigation attempts to bridge these research threads by using a cognitive task to examine the relationship between aerobic fitness and executive control of relational memory in preadolescent 9- and 10-yr-old children. METHOD: higher-fit and lower-fit children studied faces and houses under individual item (i.e., nonrelational) and relational encoding conditions, and the children were subsequently tested with recognition memory trials consisting of previously studied pairs and pairs of completely new items. With each subject participating in both item and relational encoding conditions, and with recognition test trials amenable to the use of both item and relational memory cues, this task afforded a challenge to the flexible use of memory, specifically in the use of appropriate encoding and retrieval strategies. Hence, the task provided a test of both executive control and memory processes. RESULTS: lower-fit children showed poorer recognition memory performance than higher-fit children, selectively in the relational encoding condition. No association between aerobic fitness and recognition performance was found for faces and houses studied as individual items (i.e., nonrelationally). CONCLUSIONS: the findings implicate childhood aerobic fitness as a factor in the ability to use effective encoding and retrieval executive control processes for relational memory material and, possibly, in the strategic engagement of prefrontal- and hippocampal-dependent systems.

The cyclin-dependent kinase inhibitors, cki-1 and cki-2, act in overlapping but distinct pathways to control cell cycle quiescence during C. elegans development.

Cyclin-dependent kinase inhibitors (CKIs) are major contributors to the decision to enter or exit the cell cycle. The Caenorhabditis elegans genome encodes two CKIs belonging to the Cip/Kip family, cki-1 and cki-2. cki-1 has been shown to act as a canonical negative regulator of cell cycle entry, while the role of cki-2 remains unclear. We identified cki-2 in a genome-wide RNAi screen to reveal genes essential for developmental cell cycle quiescence. Examination of cki-2 knockout animals revealed extra rounds of cell divisions, verifying a role in establishing or maintaining the temporary cell cycle arrest. Despite the overlapping defects, the pathways mediated by cki-1 and cki-2 are discrete since the extra cell phenotype conferred by a putative cki-2(null) mutation is enhanced upon additional loss of cki-1 activity. Moreover, the extra cell division defect of cki-2 is not increased with the additional loss of lin-35 Rb, as is seen with cki-1. Thus, both cki-1 and cki-2 mediate cell cycle quiescence, but our genetic and phenotypic analyses demonstrate that they act within distinct pathways to exert control over the cell cycle machinery.

Aerobic fitness and cognitive development: Event-related brain potential and task performance indices of executive control in preadolescent children.

The relationship between aerobic fitness and executive control was assessed in 38 higher- and lower-fit children (M-sub(age) = 9.4 years), grouped according to their performance on a field test of aerobic capacity. Participants performed a flanker task requiring variable amounts of executive control while event-related brain potential responses and task performance were assessed. Results indicated that higher-fit children performed more accurately across conditions of the flanker task and following commission errors when compared to lower-fit children, whereas no group differences were observed for reaction time. Neuroelectric data indicated that P3 amplitude was larger for higher- compared to lower-fit children across conditions of the flanker task, and higher-fit children exhibited reduced error-related negativity amplitude and increased error positivity amplitude compared to lower-fit children. The data suggest that fitness is associated with better cognitive performance on an executive control task through increased cognitive control, resulting in greater allocation of attentional resources during stimulus encoding and a subsequent reduction in conflict during response selection. The findings differ from those observed in adult populations by indicating a general rather than a selective relationship between aerobic fitness and cognition.

Wheeze detection in the pediatric intensive care unit: comparison among physician, nurses, respiratory therapists, and a computerized respiratory sound monitor.

OBJECTIVE: To correlate wheeze detection in the pediatric intensive care unit among staff members (a physician, nurses, and respiratory therapists [RTs]) and digital recordings from a computerized respiratory sound monitor (PulmoTrack). METHODS: We prospectively studied 11 patients in the pediatric intensive care unit. A physician, nurses, and RTs auscultated the patients and recorded their opinions about the presence of wheeze at baseline and then every hour for 6 hours. The clinician auscultated while the PulmoTrack recorded the lung sounds. The data were analyzed by a technician trained in interpretation of acoustic data and by a panel of experts blinded to the source of the recorded data, who scored all tracks for the presence or absence of wheeze. The degree of correlation among the expert panel, the staff, and the PulmoTrack was evaluated with the Kappa coefficient and McNemar's test. The determinations of the expert panel were taken as the true state (accepted standard). RESULTS: The PulmoTrack and expert panel were in agreement on detection of wheeze during inspiration, expiration, and the whole breath cycle; in all cases the Kappa coefficients were 0.54, 0.42, and 0.50 respectively. The PulmoTrack was significantly more sensitive than the physician (P = .002), nurses (P < .001), or RTs (P = .001). However, the specificity of the PulmoTrack was not significantly different from that of the physician, nurses, or RTs. CONCLUSIONS: Between the physician, RTs, and nurses there was agreement about the presence of wheeze in critically ill patients in the pediatric intensive care unit. Compared to the objective acoustic measurements from the PulmoTrack, the intensive care unit staff was similar in their ability to detect the absence of wheeze. The PulmoTrack was better than the staff in detecting wheeze.

A 5' distal palindrome within the mouse mammary tumor virus-long terminal repeat recruits a mammary gland-specific complex and is required for a synergistic response to progesterone plus prolactin.

Progesterone (P) and prolactin (PRL) fulfill crucial roles during growth and differentiation of the mammary epithelium, and each has been implicated in the pathogenesis of mammary cancer. We previously identified that these hormones synergistically stimulate the proliferation of mouse mammary epithelial cells in vivo, although the mechanism(s) underlying their cooperative effect are unknown. We now report a novel pathway by which P and PRL synergize to activate transcription from the long terminal repeat (LTR) of the mouse mammary tumor virus-LTR (MMTV-LTR) in T47D breast cancer cells. Using serial 5' and 3' deletions of the MMTV-LTR, in addition to selective mutations, we identified that a previously uncharacterized inverted palindrome on the distal enhancer (-941/-930), in addition to a signal transducer and activator of transcription 5 site, was essential for the synergistic activation of transcription by P and PRL. Notably, hormone synergy occurred via a mechanism that was independent of the P receptor DNA-binding elements found in the proximal MMTV-LTR hormone-response element. The palindrome specifically recruited a protein complex (herein termed mammary gland-specific complex) that was almost exclusive to normal and cancerous mammary cells. The synergy between P and PRL occurred via a Janus kinase 2 and c-Src/Fyn-dependent signaling cascade downstream of P and PRL receptors. Combined, our data outline a novel pathway in T47D cells that may facilitate the action(s) of P and PRL during mammary development and breast cancer.

The relation of aerobic fitness to stroop task performance in preadolescent children.

PURPOSE: We investigated the relation between aerobic fitness and interference control--one component of executive control--in 74 children between 7 and 12 yr of age. METHOD: Participants completed a paper-and-pencil version of the Stroop color-word task and the FITNESSGRAM, a valid and reliable test measuring different components of physical fitness (i.e., aerobic, muscle, and body composition). During each condition of the Stroop task (word, color, color-word), participants were instructed to read aloud as many items as possible in 45 s. Data were also collected on IQ and personal and health demographics to account for other factors influencing the relationship between fitness and executive function. RESULTS: Older children and those with higher IQ responded to more items correctly during each of the three conditions. Greater aerobic fitness was also associated with better performance on each of the three Stroop conditions independently of the other variables. CONCLUSION: These findings suggest that increased levels of fitness may be beneficial to cognition during preadolescent development.

Self-efficacy effects on neuroelectric and behavioral indices of action monitoring in older adults.

The relationships between self-efficacy (SE), i.e., beliefs in personal capabilities, and behavioral and neuroelectric (i.e., ERN, Pe) indices of action monitoring were investigated in 40 older adults (13 male) during the completion of a flanker paradigm performed under task conditions emphasizing either accuracy or speed. SE relative to task performance during both conditions was assessed prior to each cognitive task. Results indicated that high-SE older adults exhibited larger ERN and Pe amplitudes compared to low-SE older adults under the accuracy instruction condition. Additionally, a moderating effect of SE on the relationship between ERN and post-error response accuracy was revealed in the accuracy condition, with greater ERN amplitude associated with greater post-error accuracy in the high-SE group. No significant relationships were evident between ERN and post-error accuracy in the low-SE group. Further, no significant relationships involving SE were observed in the speed condition. The findings suggest that SE may be related to neuroelectric and behavioral indices of action monitoring in older adults when task demands require greater attention to action monitoring processes.

Physical fitness and academic achievement in third- and fifth-grade students.

The relationship between physical fitness and academic achievement has received much attention owing to the increasing prevalence of children who are overweight and unfit, as well as the inescapable pressure on schools to produce students who meet academic standards. This study examined 259 public school students in third and fifth grades and found that field tests of physical fitness were positively related to academic achievement. Specifically, aerobic capacity was positively associated with achievement, whereas BMI was inversely related. Associations were demonstrated in total academic achievement, mathematics achievement, and reading achievement, thus suggesting that aspects of physical fitness may be globally related to academic performance in preadolescents. The findings are discussed with regards to maximizing school performance and the implications for educational policies.