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In daily activities, humans must attend and respond to a range of important items and inhibit and not respond to unimportant distractions. Our current understanding of these processes is largely based on perceptually simple stimuli. This study investigates the interaction of conceptual-semantic categorization and inhibitory processing using Event Related Potentials (ERPs). Participants completed three Go-NoGo tasks that increased systematically in the degree of conceptual-semantic information necessary to respond correctly (from single items to categories of objects and animals). Findings indicate that the N2 response reflects inhibitory processing but does not change significantly with task difficulty. The P3 NoGo amplitude, on the other hand, is attenuated by task difficulty. Further, the latency of the peak of the P3 NoGo response elicited by the most difficult task is significantly later than are the peaks detected during performance of the other two tasks. Thus, the level of complexity of conceptual-semantic representations influences inhibitory processing in a systematic way. This inhibition paradigm may be a key for investigating inhibitory dysfunction in patient populations. [ABSTRACT FROM AUTHOR]

Importance: There are reported benefits from vitrectomy for diabetic macular edema (DME); however, data precede anti-vascular endothelial growth therapy (VEGF) therapy, supporting a need to assess the current role of vitrectomy., Objective: To determine rates of recruitment and efficacy outcomes of vitrectomy plus internal limiting membrane (ILM) peeling adjunctive to treat-and-extend (T&E) anti-VEGF injections for diabetic macular edema (DME)., Design, Setting, and Participants: This was a single-masked, multicenter randomized clinical trial at 21 sites in the United Kingdom from June 2018 to January 2021, evaluating single eyes of treatment-naive patients with symptomatic vision loss from DME for less than 1 year. Inclusion criteria were best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter score greater than 35 (approximate Snellen equivalent, 20/200 or better) and central subfield thickness (CST) greater than 350 μm after 3 monthly intravitreal injections of ranibizumab or aflibercept. Data analysis was performed in July 2023., Interventions: Patients were randomized 1:1 into vitrectomy plus standard care or standard care alone and further stratified into groups with vs without vitreomacular interface abnormality. Both groups received a T&E anti-VEGF injection regimen with aflibercept, 2 mg, or ranibizumab, 0.5 mg. The vitrectomy group additionally underwent pars plana vitrectomy with epiretinal membrane or ILM peel within 1 month of randomization., Main Outcomes and Measures: Rate of recruitment and distance BCVA. Secondary outcome measures were CST, change in BCVA and CST, number of injections, rate of completed follow-up, and withdrawal rate., Results: Over 32 months, 47 of a planned 100 patients were enrolled; 42 (89%; mean [SD] age, 63 [11] years; 26 [62%] male) completed 12-month follow-up visits. Baseline characteristics appeared comparable between the control (n = 23; mean [SD] age, 66 [10] years) and vitrectomy (n = 24; mean [SD] age, 62 [12] years) groups. No difference in 12-month BCVA was noted between groups, with a 12-month median (IQR) BCVA letter score of 73 (65-77) letters (Snellen equivalent, 20/40) in the control group vs 77 (67-81) letters (Snellen equivalent, 20/32) in the vitrectomy group (difference, 4 letters; 95% CI, -8 to 2; P = .24). There was no difference in BCVA change from baseline (median [IQR], -1 [-3 to 2] letters for the control group vs -2 [-8 to 2] letters for the vitrectomy group; difference, 1 letter; 95% CI, -5 to 7; P = .85). No difference was found in CST changes (median [IQR], -94 [-122 to 9] μm for the control group vs -32 [-48 to 25] μm for the vitrectomy group; difference, 62 μm; 95% CI, -110 to 11; P = .11)., Conclusions and Relevance: Enrollment goals could not be attained. However, with 47 participants, evidence did not support a clinical benefit of vitrectomy plus ILM peeling as an adjunct to a T&E regimen of anti-VEGF therapy for DME., Trial Registration: isrctn.org Identifier: ISRCTN59902040.

The neural correlates of predictive processing in language, critical for efficient sentence comprehension, is well documented in adults. Specifically, adults exhibit alpha power (9-12 Hz) suppression when processing high versus low predictability sentences. This study explores whether young children exhibit similar neural mechanisms. We analyzed EEG data from 29 children aged 3-5 years listening to sentences of varying predictability. Our results revealed significant neural oscillation differences in the 5-12 Hz range between high and low predictability sentences, similar to adult patterns. Crucially, the degree of these differences correlated with children's language abilities. These findings are the first to demonstrate the neural basis of predictive processing in young children and its association with language development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Decades of research has revealed a relationship between childhood socioeconomic status (SES) and brain development at the structural and functional levels. Of particular note is the distinction between income and maternal education, two highly correlated factors which seem to influence brain development through distinct pathways. Specifically, while a families' income-to-needs ratio is linked with physiological stress and household chaos, caregiver education influences the day-to-day language environment a child is exposed to. Variability in either one of these environmental experiences is related to subsequent brain development. While this work has the potential to inform public policies in a way that benefits children, it can also oversimplify complex factors, unjustly blame low-SES parents, and perpetuate a harmful deficit perspective. To counteract these shortcomings, researchers must consider sociodemographic differences in the broader cultural context that underlie SES-based differences in brain development. This review aims to address these issues by (a) identifying how sociodemographic mechanisms associated with SES influence the day-to-day experiences of children, in turn, impacting brain development, while (b) considering the broader cultural contexts that may differentially impact this relationship.

The number of U.S. children living in households with extended families has greatly increased in the last 4 decades. This demographic shift calls for a reevaluation of the impact of household size on children's development. Household density (HHD), measured as the ratio of people to bedrooms in a home, has been shown to negatively relate to children's language. Here, we propose that while greater HHD may result in poorer language abilities, more adults in relation to the number of children in the home may have a positive impact on children's language. To test this hypothesis, we studied relations between HHD and adult-to-child ratio with children's vocabulary scores, as well as whether maternal education and household chaos accounted for these associations. Participants included families from a range of socioeconomic and ethnic backgrounds ( N = 275; M age = 10.85; 51% female; 51% Hispanic; annual income range less than $10,000-over $100,000). In general, higher HHD was related to lower child vocabulary scores. Conversely, higher adult-to-child ratio was related to higher child vocabulary and lower household chaos. These patterns were primarily driven by effects in Hispanic families. Our results suggest that a reevaluation of household size is needed, as more adults in the home can be protective for children's language development in larger families, an effect that may vary by culture. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Previous research indicates that word learning from auditory contexts may be more effective than written context at least through fourth grade. However, no study has examined contextual differences in word learning in older school-aged children when reading abilities are more developed. Here we examined developmental differences in children's ability to deduce the meanings of unknown words from the surrounding linguistic context in the auditory and written modalities and sought to identify the most important predictors of success in each modality. A total of 89 children aged 8-15 years were randomly assigned to either read or listen to a narrative that included eight novel words, with five exposures to each novel word. They then completed three posttests to assess word meaning inferencing. Children across all ages performed better in the written modality. Vocabulary was the only significant predictor of success on the word inferencing task. Results indicate support for written stimuli as the most effective modality for novel word meaning deduction. Our findings suggest that the presence of orthographic information facilitates novel word learning even for early, less proficient readers., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Children's ability to retrieve word meanings and incorporate them into sentences, along with the neural structures that support these skills, continues to evolve throughout adolescence. Theta (4-8 Hz) activity that corresponds to word retrieval in children decreases in power and becomes more localized with age. This bottom-up word retrieval is often paired with changes in gamma (31-70 Hz), which are thought to reflect semantic unification in adults. Here, we studied gamma engagement during sentence processing using EEG time-frequency in children (ages 8-15) to unravel the developmental trajectory of the gamma network during sentence processing. Children heavily rely on semantic integration for sentence comprehension, but as they mature, semantic and syntactic processing units become distinct and localized. We observed a similar developmental shift in gamma oscillation around age 11, with younger groups (8-9 and 10-11) exhibiting broadly distributed gamma activity with higher amplitudes, while older groups (12-13 and 14-15) exhibited smaller and more localized gamma activity, especially over the left central and posterior regions. We interpret these findings as support for the argument that younger children rely more heavily on semantic processes for sentence comprehension than older children. And like adults, semantic processing in children is associated with gamma activity.

A vital and often overlooked aspect of word learning is the ability to establish deep semantic knowledge by adjusting and fine-tuning new word meanings as information becomes available. Here we studied differences in children's ability to update incorrect or incomplete word meanings by studying error types in a word inferencing task. The participants, 45 8- and 9-year-olds, read three sentences that all ended with the same nonsense word and were asked to identify the meaning of the last word. Importantly, the third sentence always provided the most useful information about the word's meaning. When children made errors, two types of responses were of interest. The first was when children gave a response that ignored the third sentence but fit one or two of the earlier ones. This suggests that the children had failed to update the meaning accurately. The second was when children were given enough information in the three sentences yet said that they were still unable to identify a word meaning. This suggests that the children would not attempt to infer a word when they were unsure of the answer. When controlling for number of correct responses, we found that children with smaller vocabularies were significantly more likely to fail to incorporate the third sentence, whereas children with large vocabularies were more likely to say that they were still unable to identify a meaning. These findings indicate that children with smaller vocabularies may be at risk of incorrectly inferring a new word's meaning rather than seeking further information to ensure accuracy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Using electroencephalography (EEG) to study the neural oscillations supporting language development is increasingly common; however, a clear understanding of the relationship between neural oscillations and traditional Event Related Potentials (ERPs) is needed to disentangle how maturation of language-related neural networks supports semantic processing throughout grade school. Theta and the N400 are both thought to index semantic retrieval but, in adults, are only weakly correlated with one another indicating they may measure somewhat unique aspects of retrieval. Here, we studied the relationship between the N400 amplitude and theta power during semantic retrieval with key indicators of language abilities including age, vocabulary, reading comprehension and phonological memory in 226 children ages 8-15 years. The N400 and theta responses were positively correlated over posterior areas, but negatively correlated over frontal areas. When controlling for the N400 amplitude, the amplitude of the theta response was predicted by age, but not by language measures. On the other hand, when controlling theta amplitude, the amplitude of the N400 was predicted by both vocabulary knowledge and age. These findings indicate that while there is a clear relationship between the N400 and theta responses, they may each index unique aspects of development related to semantic retrieval., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Socioeconomic status (SES)-related language gaps are known to widen throughout the course of the school years; however, not all children from lower SES homes perform worse than their higher SES peers on measures of language. The current study uses mediation and moderated mediation to examine how cognitive and language abilities (vocabulary, reading, phonological processing, working memory) account for individual differences in a children's ability to infer a novel word's meaning, a key component in word learning, in school-aged children from varying SES backgrounds. Vocabulary and reading comprehension mediated the relationship between SES and accuracy when inferring word meanings. The relationship between SES, vocabulary, and inferring word meaning was moderated by age, such that the influence of vocabulary on task performance was strongest in young children. The reading pathway did not interact with age effects, indicating reading is an important contributor to SES-related differences in how children infer a word's meaning throughout grade school. These findings highlight different paths by which children's trajectories for inferring word meanings may be impacted.

Sound waves are all around us resonating at audible and inaudible frequencies. Our ability to hear is crucial in providing information and enabling interaction with our environment. The human brain generates neural oscillations or brainwaves through synchronised electrical impulses. In epilepsy these brainwaves can change and form rhythmic bursts of abnormal activity outwardly appearing as seizures. When two waveforms meet, they can superimpose onto one another forming constructive, destructive or mixed interference. The effects of audible soundwaves on epileptic brainwaves has been largely explored with music. The Mozart Sonata for Two Pianos in D major, K. 448 has been examined in a number of studies where significant clinical and methodological heterogeneity exists. These studies report variable reductions in seizures and interictal epileptiform discharges. Treatment effects of Mozart Piano Sonata in C Major, K.545 and other composer interventions have been examined with some musical exposures, for example Hayden's Symphony No. 94 appearing pro-epileptic. The underlying anti-epileptic mechanism of Mozart music is currently unknown, but interesting research is moving away from dopamine reward system theories to computational analysis of specific auditory parameters. In the last decade several studies have examined inaudible low intensity focused ultrasound as a neuro-modulatory intervention in focal epilepsy. Whilst acute and chronic epilepsy rodent model studies have consistently demonstrated an anti-epileptic treatment effect this is yet to be reported within large scale human trials. Inaudible infrasound is of concern since at present there are no reported studies on the effects of exposure to infrasound on epilepsy. Understanding the impact of infrasound on epilepsy is critical in an era where sustainable energies are likely to increase exposure., Competing Interests: Declaration of Competing Interest I have no conflict of interest to disclose. I confirm that I have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (Copyright © 2022. Published by Elsevier Ltd.)

In the management of patients with critical limb ischemia endovascular revascularization plays a crucial role improving amputation-free survival, ischemic rest pain, and wound healing. Endovascular standard of care of peripheral arterial occlusive disease involves angioplasty and/or stent placement. The following discussion is intended to familiarize interventional physicians with the rationale, physiological concepts, and technical approach to developing endovascular procedures-percutaneous femoropopliteal bypass and percutaneous deep vein arterialization. Percutaneous arterial bypass procedure is designed to treat long complex Trans-Atlantic Inter-Society Consensus C and D hemodynamically significant superficial femoral artery lesions by redirecting the flow of blood from the diseased arterial segment through a femoral vein conduit. Percutaneous deep vein arterialization is used for selected "no-option" critical limb ischemia patients who cannot undergo or have failed conventional endovascular and/or surgical revascularization due to extensive occlusion of the outflow arteries. It involves creation of an arteriovenous fistula between a tibial artery and a tibial vein, disruption of venous valves, and elimination of venous collaterals. The consequent arterialization of the distal venous bed enables delivery of oxygenated pressurized arterial blood to the ischemic tissues, stimulating angiogenesis and increasing flow in the existent collateral vessels, which in turn will improve limb salvage and amputation free survival., Competing Interests: Disclosure None of the authors has identified a conflict of interest relevant to this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Alpha-methylacyl-CoA racemase (AMACR) deficiency is a rare peroxisomal disorder causing pristanic acid accumulation. Only 16 cases have been described so far. A female in her seventh decade presented with episodes of dysphasia, headache and sensory disturbance inconsistent with migraine, epilepsy or transient ischaemic attack. An MRI demonstrated unusual changes in the pons, red nuclei, thalami and white matter. Mitochondrial disease was suspected but detailed testing was negative. After eight years of symptoms, she developed a febrile encephalopathy with hemispheric dysfunction, focal convulsive seizures and coma. Her condition stabilised after one month. Lacosamide was continued for seizure prevention. The diagnosis remained elusive until whole genome sequencing revealed AMACR deficiency. Pristanic acid levels were highly elevated and dietary modification was recommended. Genetic peroxisomal disorders can present in older age; our patient is the oldest in the AMACR deficiency literature. Novel features in our case include central apnoea, dystonia and rapid eye movement behaviour disorder., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Deficits in procedural memory have been proposed to account for the language deficits in specific language impairment (SLI). A key aspect of the procedural deficit hypothesis (PDH) account of SLI is that declarative memory is intact and functions as a compensatory mechanism in the acquisition of language in individuals with SLI. The current study examined the neural correlates of lexical-phonological and lexical-semantic processing with respect to these predictions in a group of adolescents with SLI with procedural memory impairment and a group of chronologically age-matched (CA) normal controls., Methods: Participants completed tasks designed to measure procedural and declarative memory and two ERP tasks designed to assess lexical-semantic and lexical-phonological processing in the auditory modality. Procedural memory was assessed using a statistical learning task. Lexical-semantic processing was assessed using a sentence judgment task modulating semantic congruency and lexical-phonological processing was assessed using a word/nonword decision task modulating word frequency. Behavioral performance on the tasks, mean amplitude of the cortical response, and animated topographs were examined., Results: Performance on the statistical word-learning task was at chance for the adolescents with SLI, whereas declarative memory was no different from the CA controls. Behavioral accuracy on the lexical-semantic task was the same for the adolescents with SLI and CA controls but accuracy on the lexical-phonological task was significantly poorer for the adolescents with SLI as compared to the CA controls. An N400 component was elicited in response to semantic congruency on the lexical-semantic task for both groups but differences were noted in both the location and time course of the cortical response for the SLI and CA groups. An N400 component was elicited by word frequency on the lexical-phonological task for the CA controls not for the adolescents with SLI. In contrast, post hoc analysis revealed a cortical response based on imageability for the adolescents with SLI, but not CA controls. Statistical word learning was significantly correlated with speed of processing on the lexical decision task for the CA controls but not for the adolescents with SLI. In contrast, statistical word learning ability was not correlated with the modulation of the N400 on either task for either group., Conclusion: The behavioral data suggests intact semantic conceptual knowledge, but impaired lexical phonological processing for the adolescents with SLI, consistent with the PDH. The pattern of cortical activation in response to semantic congruency and word frequency suggests, however, that the processing of lexical-semantic and lexical-phonological information by adolescents with a history of SLI may be supported by both overlapping and nonoverlapping neural generators to those of CA controls, and a greater reliance on declarative memory strategies. Taken together, the findings from this study suggest that the underlying representations of words in the lexicons of adolescents with a history of SLI may differ qualitatively from those of their typical peers, but these differences may only be evident when behavioral data and neural cortical patterns of activation are examined together., (© 2022. The Author(s).)

Time frequency analysis of the EEG is increasingly used to study the neural oscillations supporting language comprehension. Although this method holds promise for developmental research, most existing work focuses on adults. Theta power (4-8 Hz) in particular often corresponds to semantic processing of words in isolation and in ongoing text. Here we investigated how the timing and topography of theta engagement to individual words during written sentence processing changes between childhood and adolescence (8-15 years). Results show that topographically, the theta response is broadly distributed in children, occurring over left and right central-posterior and midline frontal areas, and localizes to left central-posterior areas by adolescence. There were two notable developmental shifts. First, in response to each word, early (150-300 msec) theta engagement over frontal areas significantly decreases between 8 and 9 years and 10-11 years. Second, throughout the sentence, theta engagement over the right parietal areas significantly decreases between 10 and 11 years and 12-13 years with younger children's theta response remaining significantly elevated between words compared to adolescents'. We found no significant differences between 12 and 13 years and 14-15 years. These findings indicate that children's engagement of the language network during sentence processing continues to change through middle childhood but stabilizes into adolescence., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This is an updated version of a Cochrane Review previously published in 2019. Catamenial epilepsy describes worsening seizures in relation to the menstrual cycle and may affect around 40% of women with epilepsy. Vulnerable days of the menstrual cycle for seizures are perimenstrually (C1 pattern), at ovulation (C2 pattern), and during the luteal phase (C3 pattern). A reduction in progesterone levels premenstrually and reduced secretion during the luteal phase is implicated in catamenial C1 and C3 patterns. A reduction in progesterone has been demonstrated to reduce sensitivity to the inhibitory neurotransmitter in preclinical studies, hence increasing risk of seizures. A pre-ovulatory surge in oestrogen has been implicated in the C2 pattern of seizure exacerbation, although the exact mechanism by which this surge increases risk is uncertain. Current treatment practices include the use of pulsed hormonal (e.g. progesterone) and non-hormonal treatments (e.g. clobazam or acetazolamide) in women with regular menses, and complete cessation of menstruation using synthetic hormones (e.g. medroxyprogesterone (Depo-Provera) or gonadotropin-releasing hormone (GnRH) analogues (triptorelin and goserelin)) in women with irregular menses. Catamenial epilepsy and seizure exacerbation is common in women with epilepsy. Women may not receive appropriate treatment for their seizures because of uncertainty regarding which treatment works best and when in the menstrual cycle treatment should be taken, as well as the possible impact on fertility, the menstrual cycle, bone health, and cardiovascular health. This review aims to address these issues to inform clinical practice and future research., Objectives: To evaluate the efficacy and tolerability of hormonal and non-hormonal treatments for seizures exacerbated by the menstrual cycle in women with regular or irregular menses. We synthesised the evidence from randomised and quasi-randomised controlled trials of hormonal and non-hormonal treatments in women with catamenial epilepsy of any pattern., Search Methods: We searched the following databases on 20 July 2021 for the latest update: Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (1946 to 19 July 2021). CRS Web includes randomised controlled trials (RCTs) or quasi-RCTs from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. We used no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies., Selection Criteria: We included RCTs and quasi-RCTs of blinded or open-label design that randomised participants individually (i.e. cluster-randomised trials were excluded). We included cross-over trials if each treatment period was at least 12 weeks in length and the trial had a suitable wash-out period. We included the following types of interventions: women with any pattern of catamenial epilepsy who received a hormonal or non-hormonal drug intervention in addition to an existing antiepileptic drug regimen for a minimum treatment duration of 12 weeks., Data Collection and Analysis: We extracted data on study design factors and participant demographics for the included studies. The primary outcomes of interest were: proportion seizure-free, proportion of responders (at least 50% decrease in seizure frequency from baseline), and change in seizure frequency. Secondary outcomes included: number of withdrawals, number of women experiencing adverse events of interest (seizure exacerbation, cardiac events, thromboembolic events, osteoporosis and bone health, mood disorders, sedation, menstrual cycle disorders, and fertility issues), and quality of life outcomes., Main Results: Following title, abstract, and full-text screening, we included eight full-text articles reporting on four double-blind, placebo-controlled RCTs. We included two cross-over RCTs of pulsed norethisterone, and two parallel RCTs of pulsed progesterone recruiting a total of 192 women aged between 13 and 45 years with catamenial epilepsy. We found no RCTs for non-hormonal treatments of catamenial epilepsy or for women with irregular menses. Meta-analysis was not possible for the primary outcomes, therefore we undertook a narrative synthesis. For the two RCTs evaluating norethisterone versus placebo (24 participants), there were no reported treatment differences for change in seizure frequency. Outcomes for the proportion seizure-free and 50% responders were not reported. For the two RCTs evaluating progesterone versus placebo (168 participants), the studies reported conflicting results for the primary outcomes. One progesterone RCT reported no significant difference between progesterone 600 mg/day taken on day 14 to 28 and placebo with respect to 50% responders, seizure freedom rates, and change in seizure frequency for any seizure type. The other progesterone RCT reported a decrease in seizure frequency from baseline in the progesterone group that was significantly higher than the decrease in seizure frequency from baseline in the placebo group. The results of secondary efficacy outcomes showed no significant difference between groups in the pooled progesterone RCTs in terms of treatment withdrawal for any reason (pooled risk ratio (RR) 1.56, 95% confidence interval (CI) 0.81 to 3.00, P = 0.18, I 2 = 0%) or treatment withdrawals due to adverse events (pooled RR 2.91, 95% CI 0.53 to 16.17, P = 0.22, I 2 = 0%). No treatment withdrawals were reported from the norethisterone RCTs. The RCTs reported limited information on adverse events, although one progesterone RCT reported no significant difference in the number of women experiencing adverse events (diarrhoea, dyspepsia, nausea, vomiting, fatigue, nasopharyngitis, dizziness, headache, and depression). No studies reported on quality of life. We judged the evidence for outcomes related to the included progesterone RCTs to be of low to moderate certainty due to risk of bias, and for outcomes related to the included norethisterone RCTs to be of very low certainty due to serious imprecision and risk of bias., Authors' Conclusions: This review provides very low-certainty evidence of no treatment difference between norethisterone and placebo, and moderate- to low-certainty evidence of no treatment difference between progesterone and placebo for catamenial epilepsy. However, as all the included studies were underpowered, important clinical effects cannot be ruled out. Our review highlights an overall deficiency in the literature base on the effectiveness of a wide range of other hormonal and non-hormonal interventions currently being used in practice, particularly for those women who do not have regular menses. Further clinical trials are needed in this area., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Purpose: To analyze the outcomes of revision surgery for idiopathic full-thickness macular holes that have failed to close after primary surgery, and also to assess factors predicting success and to review the relative effect of adjunctive surgical techniques., Methods: A multicenter retrospective study. Anatomical closure rates and visual acuity change between pre and postrevision surgery were assessed. Hole size, age, symptom duration, surgical interval, and reduced hole size were analyzed as predictive factors for success. Effectiveness of adjunctive surgical techniques was reviewed., Results: Seventy-seven eyes were included in the study. Anatomical closure was achieved in 71% (55/77) cases. There was a median gain of 11 Early Treatment of Diabetic Retinopathy Score letters in all holes and 14 letters in closed holes. Full-thickness macular holes that increased in size by more than 10% following primary surgery had a closure rate of 50% compared with 80% in holes that reduced by 10% or stayed the same (P = 0.015). Increasing hole size is associated with a modest reduction in odds of closure (odds ratio = 0.99; P = 0.04). Surgical interval <2 months is not associated with better outcomes compared with >2 months (P = 0.14)., Conclusion: Revision surgery for full-thickness macular holes that have failed to close after primary surgery is associated with high closure rates and significant visual gains.

Aims: Determinants of the changing incidence of childhood-onset type 1 diabetes remain uncertain. We determined the recent time-trend of type 1 diabetes incidence in Wales and explored the role of vitamin D by evaluating the influence of season both at diagnosis and at birth., Methods: Data from all Welsh paediatric units 1990-2019, and from primary care to determine ascertainment., Results: Log-linear modelling indicated a non-linear secular trend in incidence with peak and subsequent decline. The peak occurred around June 2010: 31∙3 cases/year/100,000 children aged < 15y. It occurred earlier in children younger at diagnosis and earlier in boys. There were more cases in males aged <2y and >12y but more in females aged 9-10 y. More were diagnosed in winter. Also, children born in winter had less risk of future diabetes., Conclusions: The risk of developing type 1 diabetes before age 15y in Wales is no longer increasing. The data on season are consistent with a preventative role for vitamin D both during pregnancy and later childhood. Metereological Office data shows increasing hours of sunlight since 1980 likely to increase vitamin D levels with less diabetes. Additional dietary supplementation with vitamin D might further reduce the incidence of type 1 diabetes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Depressive disorders are the most common psychiatric comorbidity in people with epilepsy, affecting around one-third, with a significant negative impact on quality of life. There is concern that people may not be receiving appropriate treatment for their depression because of uncertainty regarding which antidepressant or class works best, and the perceived risk of exacerbating seizures. This review aimed to address these issues, and inform clinical practice and future research. This is an updated version of the original Cochrane Review published in Issue 12, 2014., Objectives: To evaluate the efficacy and safety of antidepressants in treating depressive symptoms and the effect on seizure recurrence, in people with epilepsy and depression., Search Methods: For this update, we searched CRS Web, MEDLINE, SCOPUS, PsycINFO, and ClinicalTrials.gov (February 2021). We searched the World Health Organization Clinical Trials Registry in October 2019, but were unable to update it because it was inaccessible. There were no language restrictions., Selection Criteria: We included randomised controlled trials (RCTs) and prospective non-randomised studies of interventions (NRSIs), investigating children or adults with epilepsy, who were treated with an antidepressant and compared to placebo, comparative antidepressant, psychotherapy, or no treatment for depressive symptoms.  DATA COLLECTION AND ANALYSIS: The primary outcomes were changes in depression scores (proportion with a greater than 50% improvement, mean difference, and proportion who achieved complete remission) and change in seizure frequency (mean difference, proportion with a seizure recurrence, or episode of status epilepticus). Secondary outcomes included the number of participants who withdrew from the study and reasons for withdrawal, quality of life, cognitive functioning, and adverse events. Two review authors independently extracted data for each included study. We then cross-checked the data extraction. We assessed risk of bias using the Cochrane tool for RCTs, and the ROBINS-I for NRSIs. We presented binary outcomes as risk ratios (RRs) with 95% confidence intervals (CIs) or 99% CIs for specific adverse events. We presented continuous outcomes as standardised mean differences (SMDs) with 95% CIs, and mean differences (MDs) with 95% CIs.  MAIN RESULTS: We included 10 studies in the review (four RCTs and six NRSIs), with 626 participants with epilepsy and depression, examining the effects of antidepressants. One RCT was a multi-centre study comparing an antidepressant with cognitive behavioural therapy (CBT). The other three RCTs were single-centre studies comparing an antidepressant with an active control, placebo, or no treatment. The NRSIs reported on outcomes mainly in participants with focal epilepsy before and after treatment for depression with a selective serotonin reuptake inhibitor (SSRI); one NRSI compared SSRIs to CBT.  We rated one RCT at low risk of bias, three RCTs at unclear risk of bias, and all six NRSIs at serious risk of bias. We were unable to conduct any meta-analysis of RCT data due to heterogeneity of treatment comparisons. We judged the certainty of evidence to be moderate to very low across comparisons, because single studies contributed limited outcome data, and because of risk of bias, particularly for NRSIs, which did not adjust for confounding variables. More than 50% improvement in depressive symptoms ranged from 43% to 82% in RCTs, and from 24% to 97% in NRSIs, depending on the antidepressant given. Venlafaxine improved depressive symptoms by more than 50% compared to no treatment (mean difference (MD) -7.59 (95% confidence interval (CI) -11.52 to -3.66; 1 study, 64 participants; low-certainty evidence); the results between other comparisons were inconclusive. Two studies comparing SSRIs to CBT reported inconclusive results for the proportion of participants who achieved complete remission of depressive symptoms.  Seizure frequency data did not suggest an increased risk of seizures with antidepressants compared to control treatments or baseline. Two studies measured quality of life; antidepressants did not appear to improve quality of life over control. No studies reported on cognitive functioning. Two RCTs and one NRSI reported comparative data on adverse events; antidepressants did not appear to increase the severity or number of adverse events compared to controls. The NSRIs reported higher rates of withdrawals due to adverse events than lack of efficacy. Reported adverse events for antidepressants included nausea, dizziness, sedation, headache, gastrointestinal disturbance, insomnia, and sexual dysfunction.  AUTHORS' CONCLUSIONS: Existing evidence on the effectiveness of antidepressants in treating depressive symptoms associated with epilepsy is still very limited. Rates of response to antidepressants were highly variable. There is low certainty evidence from one small RCT (64 participants) that venlafaxine may improve depressive symptoms more than no treatment; this evidence is limited to treatment between 8 and 16 weeks, and does not inform longer-term effects. Moderate to low evidence suggests neither an increase nor exacerbation of seizures with SSRIs.  There are no available comparative data to inform the choice of antidepressant drug or classes of drug for efficacy or safety for treating people with epilepsy and depression. RCTs of antidepressants utilising interventions from other treatment classes besides SSRIs, in large samples of patients with epilepsy and depression, are needed to better inform treatment policy. Future studies should assess interventions across a longer treatment duration to account for delayed onset of action, sustainability of treatment responses, and to provide a better understanding of the impact on seizure control., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Mental rotation has emerged as an important predictor of success in Science, Technology, Engineering, and Math (STEM). By the age of 4.5 years, boys outperform girls in these abilities. Because parents use less spatial language with girls at this age (Pruden and Levine, 2017), the amount of spatial language that children are exposed to at home is believed to be one potential contributor to this disparity in preschool age children. To date, it is unclear if this gender difference continues when children enter school. To address this question in this study, children not yet in kindergarten (PreK) and kindergarten and first grade children (K+) were recorded playing with their mothers using magnetic tile toys followed by children's completion of a mental rotation task. As expected, mothers used more spatial language with PreK boys than girls; however, this relationship reversed in K+, with mothers using significantly more spatial language with girls than boys. Surprisingly, despite this, boys outperformed girls on the mental rotation task. These findings suggest that although girls' exposure to spatial language is higher after entry into school, this language difference is not reflected in increases in mental rotation abilities. Thus, earlier exposure to spatial language may be vital for the development of mental rotation abilities., (© 2020 John Wiley & Sons Ltd.)

Building a robust vocabulary in grade school is essential for academic success. Children from lower socioeconomic status (SES) households on average perform below their higher SES peers on word learning tasks, negatively impacting their vocabulary; however, significant variability exists within this group. Many children from low SES homes perform as well as, or better than, their higher SES peers on measures of word learning. The current study addresses what processes underlie this variability, by comparing the neural oscillations of 44 better versus worse word learners (ages 8-15 years) from lower SES households as they infer the meaning of unknown words. Better word learners demonstrated increases in theta and beta power as a word was learned, whereas worse word learners exhibited decreases in alpha power. These group differences in neural oscillatory engagement during word learning indicate there may be different strategies employed based on differences in children's skills. Notably, children with greater vocabulary knowledge are more likely to exhibit larger beta increases; a strategy which is associated with better word learning. This sheds new light on the mechanisms that support word learning in children from low SES households., Competing Interests: Conflict of Interest Statement: The authors have no known conflicts of interest to disclose.

Background: This is an updated version of the original Cochrane Review published in 2008 and updated in 2013. Epilepsy is a common neurological condition which affects up to 1% of the population. Approximately 30% of people with epilepsy do not respond to treatment with currently available drugs. The majority of these people have focal epilepsy. Vigabatrin is an antiepileptic drug licensed for use in drug-resistant epilepsy., Objectives: To assess the efficacy and tolerability of vigabatrin as an add-on therapy for people with drug-resistant focal epilepsy., Search Methods: For the latest update of this review, we searched the following databases on 1 November 2018: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid 1946 to 31 October 2018), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. The Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL) are both included in the Cochrane Register of Studies (CRS Web). We checked reference lists of retrieved studies for additional reports of relevant studies and contacted Hoechst Marion Roussel (manufacturers of vigabatrin) in 2000., Selection Criteria: We included randomised, double-blind, placebo-controlled, fully published trials of vigabatrin in people of any age with drug-resistant focal epilepsy., Data Collection and Analysis: Two review authors assessed trials for inclusion and extracted data using the standard methodological procedures expected by Cochrane. Primary analysis was by intention-to-treat (ITT). We evaluated: 50% or greater reduction in seizure frequency, treatment withdrawal, adverse effects, dose-response analysis, cognitive outcomes and quality of life. We presented results as risk ratios (RR) with 95% or 99% confidence intervals (CI)., Main Results: We identified 11 trials that included 756 participants (age range: 10 to 64 years). The trials tested vigabatrin doses between 1 g/day and 6 g/day. All 11 trials displayed a risk of bias across at least three risk of bias domains. Predominantly, the risk of bias was associated with: allocation concealment (selection bias), blinding of outcome assessment (detection bias) and incomplete outcome data (attrition bias). Participants treated with vigabatrin may be two to three times more likely to obtain a 50% or greater reduction in seizure frequency compared with those treated with placebo (RR 2.60, 95% CI 1.87 to 3.63; 4 studies; low-certainty evidence). Those treated with vigabatrin may also be three times more likely to have treatment withdrawn although we are uncertain (RR 2.86, 95% CI 1.25 to 6.55; 4 studies; very low-certainty evidence). Compared to placebo, participants given vigabatrin were more likely to experience adverse effects: dizziness/light-headedness (RR 1.74, 95% CI 1.05 to 2.87; 9 studies; low-certainty evidence), fatigue (RR 1.65, 95% CI 1.08 to 2.51; 9 studies; low-certainty evidence), drowsiness (RR 1.70, 95% CI 1.18 to 2.44; 8 studies) and depression (RR 3.28, 95% CI 1.30 to 8.27; 6 studies). Although the incidence rates were higher among participants receiving vigabatrin compared to those receiving placebo, the effect was not significant for the following adverse effects: ataxia (RR 2.76, 95% CI 0.96 to 7.94; 7 studies; very low-certainty evidence), nausea (RR 3.57, 95% CI 0.63 to 20.30; 4 studies), abnormal vision (RR 1.64, 95% CI 0.67 to 4.02; 5 studies; very low-certainty evidence), headache (RR 1.23, 95% CI 0.79 to 1.92; 9 studies), diplopia (RR 1.76, 99% CI 0.94 to 3.30) and nystagmus (RR 1.53, 99% CI 0.62 to 3.76; 2 studies; low-certainty evidence). Vigabatrin had little to no effect on cognitive outcomes or quality of life., Authors' Conclusions: Vigabatrin may significantly reduce seizure frequency in people with drug-resistant focal epilepsy. The results largely apply to adults and should not be extrapolated to children under 10 years old. Short-term follow-up of participants showed that some adverse effects were associated with its use. Analysis of longer-term observational studies elsewhere, however, has demonstrated that vigabatrin use can lead to the development of visual field defects., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

To test the hypothesis that semantic processes are represented in multiple subsystems, we recorded electroencephalogram (EEG) as we elicited object memories using the modified Semantic Object Retrieval Test, during which an object feature, presented as a visual word [VW], an auditory word [AW], or a picture [Pic], was followed by a second feature always presented as a visual word. We performed both hypothesis-driven and data-driven analyses using event-related potentials (ERPs) time locked to the second stimulus. We replicated a previously reported left fronto-temporal ERP effect (750-1000 ms post-stimulus) in the VW task, and also found that this ERP component was only present during object memory retrieval in verbal (VW, AW) as opposed to non-verbal (Pic) stimulus types. We also found a right temporal ERP effect (850-1000 ms post-stimulus) that was present in auditory (AW) but not in visual (VW, Pic) stimulus types. In addition, we found an earlier left temporo-parietal ERP effect between 350 and 700 ms post-stimulus and a later midline parietal ERP effect between 700 and 1100 ms post-stimulus, present in all stimulus types, suggesting common neural mechanisms for object retrieval processes and object activation, respectively. These findings support multiple semantic subsystems that respond to varying stimulus modalities, and argue against an ultimate unitary amodal semantic analysis., (Published by Elsevier B.V.)

Background: This is an updated version of the original Cochrane Review, published in 2016, Issue 7. Sudden Unexpected Death in Epilepsy (SUDEP) is defined as sudden, unexpected, witnessed or unwitnessed, non-traumatic or non-drowning death of people with epilepsy, with or without evidence of a seizure, excluding documented status epilepticus and in whom postmortem examination does not reveal a structural or toxicological cause for death. SUDEP has a reported incidence of 1 to 2 per 1000 patient-years and represents the most common epilepsy-related cause of death. The presence and frequency of generalised tonic-clonic seizures (GTCS), male sex, early age of seizure onset, duration of epilepsy, and polytherapy are all predictors of risk of SUDEP. The exact pathophysiology of SUDEP is currently unknown, although GTCS-induced cardiac, respiratory, and brainstem dysfunction appears likely. Appropriately chosen antiepileptic drug treatment can render around 70% of patients free of all seizures. However, around one-third will remain drug-resistant despite polytherapy. Continuing seizures place patients at risk of SUDEP, depression, and reduced quality of life. Preventative strategies for SUDEP include reducing the occurrence of GTCS by timely referral for presurgical evaluation in people with lesional epilepsy and advice on lifestyle measures; detecting cardiorespiratory distress through clinical observation and seizure, respiratory, and heart rate monitoring devices; preventing airway obstruction through nocturnal supervision and safety pillows; reducing central hypoventilation through physical stimulation and enhancing serotonergic mechanisms of respiratory regulation using selective serotonin reuptake inhibitors (SSRIs); and reducing adenosine and endogenous opioid-induced brain and brainstem depression., Objectives: To assess the effectiveness of interventions in preventing SUDEP in people with epilepsy by synthesising evidence from randomised controlled trials of interventions and cohort and case-control non-randomised studies., Search Methods: For the latest update we searched the following databases without language restrictions: Cochrane Register of Studies (CRS Web, 4 February 2019); MEDLINE (Ovid, 1946 to 1 February 2019); SCOPUS (1823 to 4 February 2019); PsycINFO (EBSCOhost, 1887 to 4 January 2019); CINAHL Plus (EBSCOhost, 1937 to 4 February 2019); ClinicalTrials.gov (5 February 2019); and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP, 5 February 2019). We checked the reference lists of retrieved studies for additional reports of relevant studies and contacted lead study authors for any relevant unpublished material. We identified any grey literature studies published in the last five years by searching: Zetoc database; ISI Proceedings; International Bureau for Epilepsy (IBE) congress proceedings database; International League Against Epilepsy (ILAE) congress proceedings database; abstract books of symposia and congresses, meeting abstracts, and research reports., Selection Criteria: We aimed to include randomised controlled trials (RCTs), quasi-RCTs, and cluster-RCTs; prospective non-randomised cohort controlled and uncontrolled studies; and case-control studies of adults and children with epilepsy receiving an intervention for the prevention of SUDEP. Types of interventions included: early versus delayed pre-surgical evaluation for lesional epilepsy; educational programmes; seizure-monitoring devices; safety pillows; nocturnal supervision; selective serotonin reuptake inhibitors (SSRIs); opiate antagonists; and adenosine antagonists., Data Collection and Analysis: We aimed to collect data on study design factors and participant demographics for included studies. The primary outcome of interest was the number of deaths from SUDEP. Secondary outcomes included: number of other deaths (unrelated to SUDEP); change in mean depression and anxiety scores (as defined within the study); clinically important change in quality of life, that is any change in quality of life score (average and endpoint) according to validated quality of life scales; and number of hospital attendances for seizures., Main Results: We identified 1277 records from the databases and search strategies. We found 10 further records by searching other resources (handsearching). We removed 469 duplicate records and screened 818 records (title and abstract) for inclusion in the review. We excluded 785 records based on the title and abstract and assessed 33 full-text articles. We excluded 29 studies: eight studies did not assess interventions to prevent SUDEP; eight studies were review articles, not clinical studies; five studies measured sensitivity of devices to detect GTCS but did not directly measure SUDEP; six studies assessed risk factors for SUDEP but not interventions for preventing SUDEP; and two studies did not have a control group. We included one cohort study and three case-control studies of serious to critical risk of bias. The 6-month prospective cohort study observed no significant effect of providing patients with SUDEP information on drug compliance and quality of life, anxiety and depression levels. The study was too short and with no deaths observed in either group to determine a protective effect. Two case control studies reported a protective effect for nocturnal supervision against SUDEP. However due to significant heterogeneity, the results could not be combined in meta-analysis. One study of 154 SUDEP cases and 616 controls reported an unadjusted odds ratio (OR) of 0.34 (95% CI 0.22 to 0.53; P < 0.0001). The same study demonstrated the protective effect was independent of seizure control, suggesting that nocturnal supervision is not just a surrogate marker of seizure control. The second case-control study of 48 SUDEP cases and 220 controls reported an unadjusted OR of 0.08 (95% CI 0.02 to 0.27; P < 0.0001). The third case-control study of residential care centre patients who were already receiving physical checks more than 15 minutes apart throughout the night did not report any protective effect for additional nocturnal supervision (physical checks < 15 minutes apart; use of listening devices; dormitory setting; and use of bed sensors). However the same study did ascertain a difference between centres: the residential centre with the lowest level of supervision had the highest incidence of SUDEP. The case-control studies did not report on quality of life or depression and anxiety scores., Authors' Conclusions: We found limited, very low-certainty evidence that supervision at night reduces the incidence of SUDEP. Further research is required to identify the effectiveness of other current interventions - for example seizure detection devices, safety pillows, SSRIs, early surgical evaluation, educational programmes, and opiate and adenosine antagonists - in preventing SUDEP in people with epilepsy., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Children from low-socioeconomic status (SES) homes have significantly smaller vocabularies than their higher-SES peers, a gap that increases over the course of the school years. One reason for the increase in this vocabulary gap during the school years is that children from low-SES homes learn fewer words from context than their higher-SES peers. To better understand how the process of word learning from context might differ in children related to SES, we investigated changes in the N400 event-related potential (ERP) as children from low- and higher-SES homes learned new words using only the surrounding linguistic context. There were no differences in the N400 response to known words related to SES. In response to the target word being learned, children from higher-SES homes, like adults in previous studies, exhibited an attenuation of the N400 across exposures as they attached meaning to it. Children from low-SES homes did not show this same attenuation. These findings support previous work showing that children from low-SES homes may have differences or more variability in the neural components supporting language processing, and they extend previous work to illustrate how this variability may relate to word learning and, ultimately, vocabulary growth., (Copyright © 2019 Elsevier Inc. All rights reserved.)

There is increasing evidence that children from low income homes exhibit differences in brain, language and cognitive development. To better understand these differences and how they relate to one another, we compared the resting state EEG of forty-five 8-15-year-olds from low-income homes and 45 age and sex matched children from higher income homes who completed a battery of language and cognitive assessments. Children from low income homes performed worse on language tasks and exhibited differences in resting state EEG including more theta and less alpha power. To investigate the relationship between language, cognition and resting state EEG we performed multiple regression analyses. Better working memory was related to lower resting state theta power. There was an interaction between alpha and vocabulary, such that only for children from low income homes, greater resting state alpha was related to higher vocabulary scores. Both relationships held when controlling for resting state changes in the other frequency band, indicating they are somewhat independent effects. These findings shed new light on SES, neural development and cognitive and language outcomes in school-aged children., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Catamenial epilepsy describes a worsening of seizures in relation to the menstrual cycle and may affect around 40% of women with epilepsy. Vulnerable days of the menstrual cycle for seizures are perimenstrually (C1 pattern), at ovulation (C2 pattern), and during the luteal phase (C3 pattern). A reduction in progesterone levels premenstrually and reduced secretion during the luteal phase is implicated in catamenial C1 and C3 patterns. A reduction in progesterone has been demonstrated to reduce sensitivity to the inhibitory neurotransmitter in preclinical studies, hence increasing risk of seizures. A pre-ovulatory surge in oestrogen has been implicated in the C2 pattern of seizure exacerbation, although the exact mechanism by which this surge increases risk is uncertain. Current treatment practices include the use of pulsed hormonal (e.g. progesterone) and non-hormonal treatments (e.g. clobazam or acetazolamide) in women with regular menses, and complete cessation of menstruation using synthetic hormones (e.g. medroxyprogesterone (Depo-Provera) or gonadotropin-releasing hormone (GnRH) analogues (triptorelin and goserelin)) in women with irregular menses.Catamenial epilepsy and seizure exacerbation is common in women with epilepsy, and may have a significant negative impact on quality of life. Women may not be receiving appropriate treatment for their seizures because of uncertainty regarding which treatment works best and when in the menstrual cycle treatment should be taken, as well as the possible impact on fertility, the menstrual cycle, bone health, and cardiovascular health. This review aimed to address these issues in order to inform clinical practice and future research., Objectives: To evaluate the efficacy and tolerability of hormonal and non-hormonal treatments for seizures exacerbated by the menstrual cycle in women with regular or irregular menses. We synthesised the evidence from randomised controlled trials of hormonal and non-hormonal treatments in women with catamenial epilepsy of any pattern., Search Methods: We searched the following databases to 10 January 2019: Cochrane Register of Studies (CRS Web; includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL)), MEDLINE (Ovid: 1946 to 9 January 2019), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We used no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies., Selection Criteria: We included randomised and quasi-randomised controlled trials (RCTs) of blinded or opeṉlabel design that randomised participants individually (i.e. cluster-randomised trials were excluded). We included cross-over trials if each treatment period was at least 12 weeks in length and the trial had a suitable wash-out period. Types of interventions included: women with any pattern of catamenial epilepsy who received a hormonal or non-hormonal drug intervention in addition to an existing antiepileptic drug regimen for a minimum treatment duration of 12 weeks., Data Collection and Analysis: We extracted data on study design factors and participant demographics for the included studies. The primary outcomes of interest were: proportion seizure-free, proportion of responders (at least 50% decrease in seizure frequency from baseline), and mean change in seizure frequency. Secondary outcomes included: number of withdrawals, number of women experiencing adverse events of interest (seizure exacerbation, cardiac events, thromboembolic events, osteoporosis and bone health, mood disorders, sedation, menstrual cycle disorders, and fertility issues), and quality of life outcomes., Main Results: We identified 62 records from the databases and search strategies. Following title, abstract, and full-text screening, we included eight full-text articles reporting on four double-blind, placebo-controlled RCTs. We included two cross-over RCTs of pulsed norethisterone and two parallel RCTs of pulsed progesterone recruiting a total of 192 women aged between 13 and 45 years with catamenial epilepsy. We found no RCTs for non-hormonal treatments of catamenial epilepsy or for women with irregular menses.Meta-analysis was not possible for the primary outcomes, therefore we undertook a narrative synthesis. For the two RCTs evaluating norethisterone versus placebo (24 participants), there were no reported treatment differences for mean change in seizure frequency. Outcomes for the proportion seizure-free and 50% responders were not reported. For the RCTs evaluating progesterone versus placebo (168 participants), the studies reported conflicting results on the primary outcomes. One progesterone RCT reported no significant difference between progesterone 600 mg/day taken on day 14 to 28 and placebo with respect to 50% responders, seizure freedom rates, and change in seizure frequency for any seizure type. The other progesterone RCT reported that the decrease in seizure frequency from baseline in the progesterone group was significantly higher than the decrease in seizure frequency from baseline in the placebo group.Results of secondary efficacy outcomes showed no significant difference in terms of treatment withdrawal for any reason in the pooled progesterone RCTs when compared to placebo (pooled risk ratio (RR) 1.56, 95% confidence interval (CI) 0.81 to 3.00, P = 0.18, I 2 = 0%) or for treatment withdrawals due to adverse events (pooled RR 2.91, 95% CI 0.53 to 16.17, P = 0.22, I 2 = 0%). No treatment withdrawals from the norethisterone RCTs were reported. The RCTs reported limited information on adverse events, although one progesterone RCT reported no significant difference in the number of women experiencing adverse events (diarrhoea, dyspepsia, nausea, vomiting, fatigue, nasopharyngitis, dizziness, headache, and depression). No studies reported on quality of life.We judged the evidence from the included progesterone RCTs to be of low to moderate certainty due to risk of bias and from the included norethisterone RCTs to be of very low certainty due to serious imprecision and risk of bias., Authors' Conclusions: This review provides very low-certainty evidence of no treatment difference between norethisterone and placebo, and moderate- to low-certainty evidence of no treatment difference between progesterone and placebo for catamenial epilepsy. However, as all the included studies were underpowered, important clinical effects cannot be ruled out.Our review highlighted an overall deficiency in the literature base on the effectiveness of a wide range of other hormonal and non-hormonal interventions currently being used in practice, particularly for those patients who do not have regular menses. Further clinical trials are needed in this area.

School-aged and adolescent children continue to demonstrate improvements in how they integrate and comprehend real-time, auditory language over this developmental time period, which can have important implications for academic and social success. To better understand developmental changes in the neural processes engaged during language comprehension in this age group, we use electroencephalography to investigate how 8-9 year old, 12-13 year olds, and adults process semantics and syntax in naturally paced, auditory sentences. Participants listened to semantically and syntactically correct and incorrect sentences and were asked to complete an acceptability judgment task. When processing a semantic error, developmental differences were observed in theta, but not the N400, suggesting that the N400 may be too gross a measure to identify more subtle aspects of semantic development that occur in the school years. For the syntactic task, errors resulted in a larger P600 and greater beta decrease than correct sentences, but the amplitude and location of the P600 and amplitude of beta decreases differed as a function of age, suggesting specialization of syntactic skills is ongoing through adolescence. The current findings shed new light on the development of the neural oscillations supporting language comprehension and suggest that the neural substrates underlying semantic processing reach adult-like levels at a younger age than those underlying syntactic processing., (© 2018 John Wiley & Sons Ltd.)

Event related potentials (ERPs) and time frequency analysis of the EEG can identify the temporally distinct coordination of groups of neurons across brain regions during sentence processing. Although there are strong arguments that ERP components and neural oscillations are driven by the same changes in the neural signal, others argue that the lack of clear associations between the two suggests oscillatory dynamics are more than just time frequency representations of ERP components, making it unclear how the two are related. The current study seeks to examine the neural activity underlying auditory sentence processing of both semantic and syntactic errors to clarify if ERP and time frequency analyses identify the same or unique neural responses. Thirty-nine adults completed an auditory semantic judgment task and a grammaticality judgment task. As expected, the semantic judgment task elicited a larger N400 and greater increase in theta power for semantic errors compared to correct sentences and the syntactic judgment task elicited a greater P600 and beta power decrease for both grammatical error types compared to syntactically correct sentences. Importantly, we identified a significant relationship between the N400 and P600 ERPs and theta and beta oscillatory dynamics during semantic and syntactic processing. These findings suggest that ERPs and neural oscillations measure similar neural processes; however, unaccounted for variance may indicate that neural oscillations provide additional information regarding fluctuations in power within a given frequency band. Future studies that vary semantic and syntactic complexity are necessary to understand the cognitive processes that are indexed by these oscillations., (Published by Elsevier B.V.)

To investigate differences in inhibitory control and processing speed over the life span, participants in 7- to 8-, 10- to 11-, 12- to 15-, 18- to 25-, and 54- to 80-year-old age cohorts completed a Go/No-Go task requiring varying levels of semantic categorization. Discriminant function analysis of correct rejection rates (CRRs), hit rates (HRs), and reaction times (RTs) revealed a function on which CRR loaded positively and RT loaded negatively, across categorization levels. Scores increased from youngest to the younger adult cohort and decreased for the older adult cohort. On a second function, CRR and RT loaded positively and HR loaded negatively across categorization levels. Scores were highest for the older adult cohort and higher for the youngest cohort than for the younger adult cohort. The results suggest change along 2 dimensions might underlie cognitive development: (a) combined increased inhibitory control and processing speed and (b) combined increased speed and decreased biased responding for better inhibitory control. In addition, 2 dimensions might underlie senescence: (a) combined decreased inhibitory control and processing speed and (b) combined decreased speed and increased biased responding for better inhibitory control. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Although very young children seem to process ongoing language quickly and effortlessly, neuroimaging and behavioral studies reveal that children continue to mature in their language skills through adolescence. During this prolonged development, children likely engage the same basic cognitive processes and neural mechanisms to perform language tasks as adults, but in somewhat different ways. In this study we used time frequency analysis of EEG to identify developmental differences in the engagement of neural oscillations between children (ages 10-12) and adults while listening to naturally-paced sentences. Adults displayed consistent beta changes throughout the sentence compared to children, thought to be related to efficient syntactic integration, and children displayed more broadly distributed theta changes than adults, thought to be related to more effortful semantic integration. Few differences in alpha, related to verbal working memory, existed between groups. These findings shed new light on developmental changes in the neuronal processes underlying language comprehension., (Published by Elsevier Inc.)

Background: Presurgical evaluation for temporal lobe epilepsy routinely assesses speech and memory lateralization and anatomic localization of the motor and visual areas but not baseline musical processing. This is paramount in a musician. Although validated tools exist to assess musical ability, there are no reported functional magnetic resonance imaging (fMRI) paradigms to assess musical processing. We examined the utility of a novel fMRI paradigm in an 18-year-old left-handed pianist who underwent surgery for a left temporal low-grade ganglioglioma., Methods: Preoperative evaluation consisted of neuropsychological evaluation, T1-weighted and T2-weighted magnetic resonance imaging, and fMRI. Auditory blood oxygen level-dependent fMRI was performed using a dedicated auditory scanning sequence. Three separate auditory investigations were conducted: listening to, humming, and thinking about a musical piece., Results: All auditory fMRI paradigms activated the primary auditory cortex with varying degrees of auditory lateralization. Thinking about the piece additionally activated the primary visual cortices (bilaterally) and right dorsolateral prefrontal cortex. Humming demonstrated left-sided predominance of auditory cortex activation with activity observed in close proximity to the tumor., Conclusions: This study demonstrated an fMRI paradigm for evaluating musical processing that could form part of preoperative assessment for patients undergoing temporal lobe surgery for epilepsy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The relationship between children's slow vocabulary growth and the family's low socioeconomic status (SES) has been well documented. However, previous studies have often focused on infants or preschoolers and primarily used static measures of vocabulary at multiple time points. To date, there is no research investigating whether SES predicts a child's word learning abilities in grade school and, if so, what mediates this relationship. In this study, 68 children aged 8-15 years performed a written word learning from context task that required using the surrounding text to identify the meaning of an unknown word. Results revealed that vocabulary knowledge significantly mediated the relationship between SES (as measured by maternal education) and word learning. This was true despite the fact that the words in the linguistic context surrounding the target word are typically acquired well before 8 years of age. When controlling for vocabulary, word learning from written context was not predicted by differences in reading comprehension, decoding, or working memory. These findings reveal that differences in vocabulary growth between grade school children from low and higher SES homes are likely related to differences in the process of word learning more than knowledge of surrounding words or reading skills. Specifically, children from lower SES homes are not as effective at using known vocabulary to build a robust semantic representation of incoming text to identify the meaning of an unknown word., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Growing evidence suggests that cognitive control processes are impaired in amnestic mild cognitive impairment (aMCI); however the nature of these alterations needs further examination. The current study examined differences in electroencephalographic theta and alpha power related to cognitive control processes involving response execution and response inhibition in 22 individuals with aMCI and 22 age-, sex-, and education-matched cognitively normal controls. Two Go/NoGo tasks involving semantic categorization were used. In the basic categorization task, Go/NoGo responses were made based on exemplars of a single car (Go) and a single dog (NoGo). In the superordinate categorization task, responses were made based on multiple exemplars of objects (Go) and animals (NoGo). Behavioral data showed that the aMCI group had more false alarms during the NoGo trials compared to controls. The EEG data revealed between group differences related to response type in theta (4-7 Hz) and low-frequency alpha (8-10 Hz) power. In particular, the aMCI group differed from controls in theta power during the NoGo trials at frontal and parietal electrodes, and in low-frequency alpha power during Go trials at parietal electrodes. These results suggest that alterations in theta power converge with behavioral deterioration in response inhibition, whereas alterations in low-frequency alpha power appear to precede behavioral changes in response execution. Both behavioral and electrophysiological correlates combined provide a more comprehensive characterization of cognitive control deficits in aMCI.

To better understand how toddlers integrate multiple learning strategies to acquire verbs, we compared sensorimotor recruitment and comparison learning because both strategies are thought to boost children's access to scene-level information. For sensorimotor recruitment, we tested having toddlers use dolls as agents and compared this strategy with having toddlers observe another person enact verbs with dolls. For comparison learning, we compared providing pairs of: (a) training scenes in which animate objects with similar body-shapes maintained agent/patient roles with (b) scenes in which objects with dissimilar body-shapes switched agent/patient roles. Only comparison learning boosted verb comprehension.

How the brain combines the neural representations of features that comprise an object in order to activate a coherent object memory is poorly understood, especially when the features are presented in different modalities (visual vs. auditory) and domains (verbal vs. nonverbal). We examined this question using three versions of a modified Semantic Object Retrieval Test, where object memory was probed by a feature presented as a written word, a spoken word, or a picture, followed by a second feature always presented as a visual word. Participants indicated whether each feature pair elicited retrieval of the memory of a particular object. Sixteen subjects completed one of the three versions (N=48 in total) while their EEG were recorded simultaneously. We analyzed EEG data in four separate frequency bands (delta: 1-4Hz, theta: 4-7Hz; alpha: 8-12Hz; beta: 13-19Hz) using a multivariate data-driven approach. We found that alpha power time-locked to response was modulated by both cross-modality (visual vs. auditory) and cross-domain (verbal vs. nonverbal) probing of semantic object memory. In addition, retrieval trials showed greater changes in all frequency bands compared to non-retrieval trials across all stimulus types in both response-locked and stimulus-locked analyses, suggesting dissociable neural subcomponents involved in binding object features to retrieve a memory. We conclude that these findings support both modality/domain-dependent and modality/domain-independent mechanisms during semantic object memory retrieval., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Sudden Unexpected Death in Epilepsy (SUDEP) is defined as sudden, unexpected, witnessed or unwitnessed, non-traumatic or non-drowning death of people with epilepsy, with or without evidence of a seizure, excluding documented status epilepticus and in whom postmortem examination does not reveal a structural or toxicological cause for death. SUDEP has a reported incidence of 1 to 2 per 1000 patient years and represents the most common epilepsy-related cause of death. The presence and frequency of generalised tonic-clonic seizures (GTCS), male sex, early age of seizure onset, duration of epilepsy, and polytherapy are all predictors of risk of SUDEP. The exact pathophysiology of SUDEP is currently unknown, although GTCS-induced cardiac, respiratory, and brainstem dysfunction appears likely. Appropriately chosen antiepileptic drug treatment can render around 70% of patients free of all seizures. However, around one-third will remain drug refractory despite polytherapy. Continuing seizures place patients at risk of SUDEP, depression, and reduced quality of life. Preventative strategies for SUDEP include reducing the occurrence of GTCS by timely referral for presurgical evaluation in people with lesional epilepsy and advice on lifestyle measures; detecting cardiorespiratory distress through clinical observation and seizure, respiratory, and heart rate monitoring devices; preventing airway obstruction through nocturnal supervision and safety pillows; reducing central hypoventilation through physical stimulation and enhancing serotonergic mechanisms of respiratory regulation using selective serotonin reuptake inhibitors (SSRIs); reducing adenosine and endogenous opioid-induced brain and brainstem depression., Objectives: To assess the effectiveness of interventions in preventing SUDEP in people with epilepsy by synthesising evidence from randomised controlled trials of interventions and cohort and case-control non-randomised studies., Search Methods: We searched the following databases: Cochrane Epilepsy Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL, Issue 11, 2015) via the Cochrane Register of Studies Online (CRSO); MEDLINE (Ovid, 1946 onwards); SCOPUS (1823 onwards); PsycINFO (EBSCOhost, 1887 onwards); CINAHL Plus (EBSCOhost, 1937 onwards); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We used no language restrictions. The date of the last search was 12 November 2015. We checked the reference lists of retrieved studies for additional reports of relevant studies and contacted lead study authors for any relevant unpublished material. We identified duplicate studies by screening reports according to title, authors' names, location, and medical institute, omitting any duplicated studies. We identified any grey literature studies published in the last five years by searching: Zetoc database; ISI Proceedings; International Bureau for Epilepsy (IBE) congress proceedings database; International League Against Epilepsy (ILAE) congress proceedings database; abstract books of symposia and congresses, meeting abstracts, and research reports., Selection Criteria: We aimed to include randomised controlled trials (RCTs), quasi-RCTs, and cluster-RCTs; prospective non-randomised cohort controlled and uncontrolled studies; and case-control studies of adults and children with epilepsy receiving an intervention for the prevention of SUDEP. Types of interventions included: early versus delayed pre-surgical evaluation for lesional epilepsy; educational programmes; seizure-monitoring devices; safety pillows; nocturnal supervision; selective serotonin reuptake inhibitors (SSRIs); opiate antagonists; and adenosine antagonists., Data Collection and Analysis: We aimed to collect data on study design factors and participant demographics for included studies. The primary outcome of interest was the number of deaths from SUDEP. Secondary outcomes included: number of other deaths (unrelated to SUDEP); change in mean depression and anxiety scores (as defined within the study); clinically important change in quality of life, that is any change in quality of life score (average and endpoint) according to validated quality of life scales; and number of hospital attendances for seizures., Main Results: We identified 582 records from the databases and search strategies. We found 10 further records by searching other resources (handsearching). We removed 211 duplicate records and screened 381 records (title and abstract) for inclusion in the review. We excluded 364 records based on the title and abstract and assessed 17 full-text articles. We excluded 15 studies: eight studies did not assess interventions to prevent SUDEP; five studies measured sensitivity of devices to detect GTCS but did not directly measure SUDEP; and two studies assessed risk factors for SUDEP but not interventions for preventing SUDEP. One listed study is awaiting classification.We included one case-control study at serious risk of bias within a qualitative analysis in this review. This study of 154 cases of SUDEP and 616 controls ascertained a protective effect for the presence of nocturnal supervision (unadjusted odds ratio (OR) 0.34, 95% confidence interval (CI) 0.22 to 0.53) and when a supervising person shared the same bedroom or when special precautions, for example a listening device, were used (unadjusted OR 0.41, 95% CI 0.20 to 0.82). This effect was independent of seizure control. Non-SUDEP deaths; changes to anxiety, depression, and quality of life; and number of hospital attendances were not reported., Authors' Conclusions: We found very low-quality evidence of a preventative effect for nocturnal supervision against SUDEP. Further research is required to identify the effectiveness of other current interventions, for example seizure detection devices, safety pillows, SSRIs, early surgical evaluation, educational programmes, and opiate and adenosine antagonists in preventing SUDEP in people with epilepsy.

Although very young children process ongoing language quickly and effortlessly, research indicates that they continue to improve and mature in their language skills through adolescence. This prolonged development may be related to differing engagement of semantic and syntactic processes. This study used event related potentials and time frequency analysis of EEG to identify developmental differences in neural engagement as children (ages 10-12) and adults performed an auditory verb agreement grammaticality judgment task. Adults and children revealed very few differences in comprehending grammatically correct sentences. When identifying grammatical errors, however, adults displayed widely distributed beta and theta power decreases that were significantly less pronounced in children. Adults also demonstrated a significant P600 effect, while children exhibited an apparent N400 effect. Thus, when identifying subtle grammatical errors in real time, adults display greater neural activation that is traditionally associated with syntactic processing whereas children exhibit greater activity more commonly associated with semantic processing. These findings support previous claims that the cognitive and neural underpinnings of syntactic processing are still developing in adolescence, and add to them by more clearly identifying developmental changes in the neural oscillations underlying grammatical processing., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We examined the effects of amnestic mild cognitive impairment (aMCI) on behavioral (response times and error rates) and scalp-recorded event-related potential (ERP) measures of response execution and inhibition, using Go/NoGo tasks involving basic and superordinate semantic categorization. Twenty-five aMCI (16 F; 68.5±8 years) and 25 age- and gender-matched normal control subjects (16 F; 65.4±7.1 years) completed two visual Go/NoGo tasks. In the single car task, responses were made based on single exemplars of a car (Go) and a dog (NoGo) (basic). In the object animal task, responses were based on multiple exemplars of objects (Go) and animals (NoGo) (superordinate). The aMCI subjects had higher commission errors on the NoGo trials compared to the control subjects, whereas both groups had comparable omission errors and reaction times during the Go trials. The aMCI subjects had significantly prolonged N2 ERP latency during Go and NoGo trials across tasks compared to the controls. Both groups showed similar categorization effects and response type effects in N2/P3 ERP latencies and P3 amplitude. Our findings indicate that altered early neural processing indexed by N2 latency distinguishes subjects with aMCI from controls during the Go/NoGo task. Prolonged Go-N2 latency in aMCI appears to precede behavioral changes in response execution, whereas prolonged NoGo-N2 latency underlies behavioral deterioration in response inhibition.

This study explored noun and verb retrieval using a sentence completion task to expand upon previous findings from picture naming tasks. Participants completed sentences missing either a target noun or verb in the final position. Non-target responses were coded for substitution type, imageability and frequency. Like picture naming, nouns and verbs differed in non-target substitution type-within-category substitutions were primarily nouns and out-of-category substitutions were primarily verbs. Imageability predicted multiple substitution types for both word classes, whereas frequency predicted noun substitution types but not verbs. Findings support theories of noun and verb differences in semantic retrieval, showing the robustness of this effect across methodologies, and shed new light on the influence of imageability and frequency during semantic retrieval.

We used event-related potentials (ERPs) to study age effects of perceptual (basic-level) vs. perceptual-semantic (superordinate-level) categorization on cognitive control using the go/nogo paradigm. Twenty-two younger (11 M; 21 ± 2.2 years) and 22 older adults (9 M; 63 ± 5.8 years) completed two visual go/nogo tasks. In the single-car task (SiC) (basic), go/nogo responses were made based on single exemplars of a car (go) and a dog (nogo). In the object animal task (ObA) (superordinate), responses were based on multiple exemplars of objects (go) and animals (nogo). Each task consisted of 200 trials: 160 (80%) 'go' trials that required a response through button pressing and 40 (20%) 'nogo' trials that required inhibition/withholding of a response. ERP data revealed significantly reduced nogo-N2 and nogo-P3 amplitudes in older compared to younger adults, whereas go-N2 and go-P3 amplitudes were comparable in both groups during both categorization tasks. Although the effects of categorization levels on behavioral data and P3 measures were similar in both groups with longer response times, lower accuracy scores, longer P3 latencies, and lower P3 amplitudes in ObA compared to SiC, N2 latency revealed age group differences moderated by the task. Older adults had longer N2 latency for ObA compared to SiC, in contrast, younger adults showed no N2 latency difference between SiC and ObA. Overall, these findings suggest that age differentially affects neural processing related to cognitive control during semantic categorization. Furthermore, in older adults, unlike in younger adults, levels of categorization modulate neural processing related to cognitive control even at the early stages (N2)., (Published by Elsevier B.V.)

Background: Event Related Potentials (ERPs) elicited by visual stimuli have increased our understanding of developmental disorders and adult cognitive abilities for decades; however, these studies are very difficult with populations who cannot sustain visual attention such as infants and young children. Current methods for studying such populations include requiring a button response, which may be impossible for some participants, and experimenter monitoring, which is subject to error, highly variable, and spatially imprecise., New Method: We developed a child-centered methodology to integrate EEG data acquisition and eye-tracking technologies that uses "attention-getters" in which stimulus display is contingent upon the child's gaze. The goal was to increase the number of trials retained. Additionally, we used the eye-tracker to categorize and analyze the EEG data based on gaze to specific areas of the visual display, compared to analyzing based on stimulus presentation., Results Compared With Existing Methods: The number of trials retained was substantially improved using the child-centered methodology compared to a button-press response in 7-8 year olds. In contrast, analyzing the EEG based on eye gaze to specific points within the visual display as opposed to stimulus presentation provided too few trials for reliable interpretation., Conclusions: By using the linked EEG-eye-tracker we significantly increased data retention. With this method, studies can be completed with fewer participants and a wider range of populations. However, caution should be used when epoching based on participants' eye gaze because, in this case, this technique provided substantially fewer trials., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Depressive disorders are the most common psychiatric comorbidity in patients with epilepsy, affecting around one-third, with a significant negative impact on quality of life. There is concern that patients may not be receiving appropriate treatment for their depression because of uncertainty regarding which antidepressant or class works best and the perceived risk of exacerbating seizures. This review aims to address these issues and inform clinical practice and future research., Objectives: We aimed to review and synthesise evidence from randomised controlled trials of antidepressants and prospective non-randomised studies of antidepressants used for treating depression in patients with epilepsy. The primary objectives were to evaluate the efficacy and safety of antidepressants in treating depressive symptoms and the effect on seizure recurrence., Search Methods: We conducted a search of the following databases: the Cochrane Epilepsy Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 5), MEDLINE (Ovid), SCOPUS, PsycINFO, www.clinicaltrials.gov and conference proceedings, including studies published up to 31 May 2014. There were no language restrictions., Selection Criteria: We included randomised controlled trials (RCTs) and prospective non-randomised cohort controlled and uncontrolled studies investigating children or adults with epilepsy treated with an antidepressant for depressive symptoms. The intervention group consisted of patients receiving an antidepressant drug in addition to an existing antiepileptic drug regimen. The control group(s) consisted of patients receiving a placebo, comparative antidepressant, psychotherapy or no treatment in addition to an existing antiepileptic drug regimen., Data Collection and Analysis: We extracted data on trial design factors, patient demographics and outcomes for each study. The primary outcomes were changes in depression scores (proportion with a greater than 50% improvement or mean difference) and change in seizure frequency (mean difference or proportion with a seizure recurrence or episode of status epilepticus, or both). Secondary outcomes included the number of patients withdrawing from the study and reasons for withdrawal, as well as any adverse events. Two authors undertook data extraction separately for each included study. We then cross-checked the data extraction. We assessed risk of bias using a version of the extended Cochrane Collaboration tool for assessing risk of bias in both randomised and non-randomised studies. We presented binary outcomes as risk ratios (RRs) with 95% confidence intervals (CIs). We presented continuous outcomes as standardised mean differences (SMDs) with 95% CIs, and mean differences (MDs) with 95% CIs. If possible we intended to use meta-regression techniques to investigate possible sources of heterogeneity however this was not possible due to lack of data., Main Results: We included in the review eight studies (three RCTs and five prospective cohort studies) including 471 patients with epilepsy treated with an antidepressant. The RCTs were all single-centre studies comparing an antidepressant versus active control, placebo or no treatment. The five non-randomised prospective cohort studies reported on outcomes mainly in patients with partial epilepsy treated for depression with a selective serotonin reuptake inhibitor (SSRI). We rated all the RCTs and one prospective cohort study as having unclear risk of bias. We rated the four other prospective cohort studies as having high risk of bias. We were unable to perform any meta-analysis for the proportion with a greater than 50% improvement in depression scores because the studies reported on different treatment comparisons. The results are presented descriptively and show a varied responder rate of between 24% and 97%, depending on the antidepressant given. For the mean difference in depression score we were able to perform a limited meta-analysis of two prospective cohort studies of citalopram, including a total of 88 patients. This gave low quality evidence for the effect estimate of 1.17 (95% CI 0.96 to 1.38) in depression scores. Seizure frequency data were not reported in any RCTs and we were unable to perform any meta-analysis for prospective cohort studies due to the different treatment comparisons. The results are presented descriptively and show that treatment in three studies with a selective serotonin reuptake inhibitor did not significantly increase seizure frequency. Patients given an antidepressant were more likely to withdraw due to adverse events than inefficacy. Reported adverse events for SSRIs included nausea, dizziness, sedation, gastrointestinal disturbance and sexual dysfunction. Across three comparisons we rated the evidence as moderate quality due to the small sizes of the contributing studies and only one study each contributing to the comparisons. We rated the evidence for the final comparison as low quality as there was concern over the study methods in the two contributing studies., Authors' Conclusions: Existing evidence on the effectiveness of antidepressants in treating depressive symptoms associated with epilepsy is very limited. Only one small RCT demonstrated a statistically significant effect of venlafaxine on depressive symptoms. We have no high quality evidence to inform the choice of antidepressant drug or class of drug in treating depression in people with epilepsy. This review provides low quality evidence of safety in terms of seizure exacerbation with SSRIs, but there are no available comparative data on antidepressant classes and safety in relation to seizures. There are currently no comparative data on antidepressants and psychotherapy in treating depression in epilepsy, although psychotherapy could be considered in patients unwilling to take antidepressants or where there are unacceptable side effects. Further comparative clinical trials of antidepressants and psychotherapy in large cohorts of patients with epilepsy and depression are required to better inform treatment policy in the future.

The present study examined the transfer of higher-order cognitive strategy training to inhibitory control. Middle school students enrolled in a comprehension- and reasoning-focused cognitive strategy training program and passive controls participated. The training program taught students a set of steps for inferring essential gist or themes from materials. Both before and after training or a comparable duration in the case of the passive controls, participants completed a semantically cued Go/No-Go task that was designed to assess the effects of depth of semantic processing on response inhibition and components of event-related potentials (ERP) related to response inhibition. Depth of semantic processing was manipulated by varying the level of semantic categorization required for response selection and inhibition. The SMART-trained group showed inhibitory control gains and changes in fronto-central P3 ERP amplitudes on inhibition trials; whereas, the control group did not. The results provide evidence of the transfer of higher-order cognitive strategy training to inhibitory control and modulation of ERPs associated with semantically cued inhibitory control. The findings are discussed in terms of implications for cognitive strategy training, models of cognitive abilities, and education., (Published by Elsevier Inc.)

The present study examined functional MRI (fMRI) BOLD signal changes in response to object categorization during response selection and inhibition. Young adults (N=16) completed a Go/NoGo task with varying object categorization requirements while fMRI data were recorded. Response inhibition elicited increased signal change in various brain regions, including medial frontal areas, compared with response selection. BOLD signal in an area within the right angular gyrus was increased when higher-order categorization was mandated. In addition, signal change during response inhibition varied with categorization requirements in the left inferior temporal gyrus (lIT). lIT-mediated response inhibition when inhibiting the response only required lower-order categorization, but lIT mediated both response selection and inhibition when selecting and inhibiting the response required higher-order categorization. The findings characterized mechanisms mediating response inhibition associated with semantic object categorization in the 'what' visual object memory system.