The use of simultaneous stereo-electroencephalography and magnetoencephalography in localizing the epileptogenic focus in refractory focal epilepsy

Both magnetoencephalography and stereo-electroencephalography are used in presurgical epilepsy assessment, with contrasting advantages and limitations. It is not known whether simultaneous stereo-electroencephalography–magnetoencephalography recording confers an advantage over both individual modalities, in particular whether magnetoencephalography can provide spatial context to epileptiform activity seen on stereo-electroencephalography. Twenty-four adult and paediatric patients who underwent stereo-electroencephalography study for pre-surgical evaluation of drug-resistant focal epilepsy, were recorded using simultaneous stereo-electroencephalography–magnetoencephalography, of which 14 had abnormal interictal activity during recording. The 14 patients were divided into two groups; those with detected superficial (n = 7) and deep (n = 7) brain interictal activity. Interictal spikes were independently identified in stereo-electroencephalography and magnetoencephalography. Magnetoencephalography dipoles were derived using a distributed inverse method. There was no significant difference between stereo-electroencephalography and magnetoencephalography in detecting superficial spikes (P = 0.135) and stereo-electroencephalography was significantly better at detecting deep spikes (P = 0.002). Mean distance across patients between stereo-electroencephalography channel with highest average spike amplitude and magnetoencephalography dipole was 20.7 ± 4.4 mm. for superficial sources, and 17.8 ± 3.7 mm. for deep sources, even though for some of the latter (n = 4) no magnetoencephalography spikes were detected and magnetoencephalography dipole was fitted to a stereo-electroencephalography interictal activity triggered average. Removal of magnetoencephalography dipole was associated with 1 year seizure freedom in 6/7 patients with superficial source, and 5/6 patients with deep source. Although stereo-electroencephalography has greater sensitivity in identifying interictal activity from deeper sources, a magnetoencephalography source can be localized using stereo-electroencephalography information, thereby providing useful whole brain context to stereo-electroencephalography and potential role in epilepsy surgery planning

Age-related Differences in Prestimulus Subsequent Memory Effects Assessed with Event-related Potentials

Prestimulus subsequent memory effects (preSMEs)—differences in neural activity elicited by a task cue at encoding that are predictive of later memory performance—are thought to reflect differential engagement of preparatory processes that benefit episodic memory encoding. We investigated age differences in preSMEs indexed by differences in ERP amplitude just before the onset of a study item. Young and older adults incidentally encoded words for a subsequent memory test. Each study word was preceded by a task cue that signaled a judgment to perform on the word. Words were presented for either a short (300 msec) or long (1000 msec) duration with the aim of placing differential benefits on engaging preparatory processes initiated by the task cue. ERPs associated with subsequent successful and unsuccessful recollection, operationalized here by source memory accuracy, were estimated time-locked to the onset of the task cue. In a late time window (1000–2000 msec after onset of the cue), young adults demonstrated frontally distributed preSMEs for both the short and long study durations, albeit with opposite polarities in the two conditions. This finding suggests that preSMEs in young adults are sensitive to perceived task demands. Although older adults showed no evidence of preSMEs in the same late time window, significant preSMEs were observed in an earlier time window (500–1000 msec) that was invariant with study duration. These results are broadly consistent with the proposal that older adults differ from their younger counterparts in how they engage preparatory processes during memory encoding

Genome-Scale Oscillations in DNA Methylation during Exit from Pluripotency

Pluripotency is accompanied by the erasure of parental epigenetic memory, with naive pluripotent cells exhibiting global DNA hypomethylation both in vitro and in vivo. Exit from pluripotency and priming for differentiation into somatic lineages is associated with genome-wide de novo DNA methylation. We show that during this phase, co-expression of enzymes required for DNA methylation turnover, DNMT3s and TETs, promotes cell-to-cell variability in this epigenetic mark. Using a combination of single- cell sequencing and quantitative biophysical modeling, we show that this variability is associated with coherent, genome-scale oscillations in DNA methylation with an amplitude dependent on CpG density. Analysis of parallel single-cell transcriptional and epigenetic profiling provides evidence for oscillatory dynamics both in vitro and in vivo. These observations provide insights into the emergence of epigenetic heterogeneity during early embryo development, indicating that dynamic changes in DNA methylation might influence early cell fate decisions

What is traditional acupuncture - exploring goals and processes of treatment in the context of women with early breast cancer

Background: Despite the increasing popularity of acupuncture, there remains uncertainty as to its effectiveness and how it brings about change. Particular questions are posed over whether acupuncture research has sufficient model validity and reflects acupuncture as practised. Exploring traditional acupuncture (TA) in practice should help to expose processes essential to the theory of TA. The aim of this study was to examine what TA practitioners aim to achieve, their rationale and how they follow this through in their practice. Methods: A longitudinal study of TA for women with early breast cancer (EBC) was performed. Study participants comprised 14 women with EBC and two experienced TA practitioners, all taking part in in-depth interviews, conducted before and after receipt of up to 10 treatment sessions, and analysed using grounded theory methods. Additional data came from practitioner treatment logs and diaries. Results: Practitioners sought long-term goals of increasing strength and enabling coping as well as immediate relief of symptoms. They achieved this through a continuous process of treatment, following through the recursive and individualized nature of TA and adjusted, via differential diagnosis, to the rapidly fluctuating circumstances of individual women. Establishing trust and good rapport with the women aided disclosure which was seen as essential in order to clarify goals during chemotherapy. This process was carefully managed by the practitioners and the resultant therapeutic relationship was highly valued by the women. Conclusion: This study provided insight into the interdependent components of TA helping to demonstrate the multiple causal pathways to change through the continuous process of new information, insights and treatment changes. A good therapeutic relationship was not simply something valued by patients but explicitly used by practitioners to aid disclosure which in turn affected details of the treatment. The therapeutic relationship was therefore a vital and integral part of the treatment process

Distinct neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex

Functional magnetic resonance imaging (fMRI) is among the foremost methods for mapping human brain function but provides only an indirect measure of underlying neural activity. Recent findings suggest that the neurophysiological correlates of the fMRI blood oxygenation level-dependent (BOLD) signal might be regionally specific. We examined the neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex, where differences in neural architecture might result in a different relationship between the respective signals. Fifteen human neurosurgical patients (10 female, 5 male) implanted with depth electrodes performed a verbal free recall task while electrophysiological activity was recorded simultaneously from hippocampal and neocortical sites. The same patients subsequently performed a similar version of the task during a later fMRI session. Subsequent memory effects (SMEs) were computed for both imaging modalities as patterns of encoding-related brain activity predictive of later free recall. Linear mixed-effects modeling revealed that the relationship between BOLD and gamma-band SMEs was moderated by the lobar location of the recording site. BOLD and high gamma (70–150 Hz) SMEs positively covaried across much of the neocortex. This relationship was reversed in the hippocampus, where a negative correlation between BOLD and high gamma SMEs was evident. We also observed a negative relationship between BOLD and low gamma (30–70 Hz) SMEs in the medial temporal lobe more broadly. These results suggest that the neurophysiological correlates of the BOLD signal in the hippocampus differ from those observed in the neocortex

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

BACKGROUND: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. METHODS: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. FINDINGS: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. INTERPRETATION: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. FUNDING: National Institute for Health Research, Health Technology Assessment programme

Web 2.0 systems supporting childhood chronic disease management: A pattern language representation of a general architecture

<p>Abstract</p> <p>Background</p> <p>Chronic disease management is a global health concern. By the time they reach adolescence, 10–15% of all children live with a chronic disease. The role of educational interventions in facilitating adaptation to chronic disease is receiving growing recognition, and current care policies advocate greater involvement of patients in self-care. Web 2.0 is an umbrella term for new collaborative Internet services characterized by user participation in developing and managing content. Key elements include Really Simple Syndication (RSS) to rapidly disseminate awareness of new information; weblogs (blogs) to describe new trends, wikis to share knowledge, and podcasts to make information available on personal media players. This study addresses the potential to develop Web 2.0 services for young persons with a chronic disease. It is acknowledged that the management of childhood chronic disease is based on interplay between initiatives and resources on the part of patients, relatives, and health care professionals, and where the balance shifts over time to the patients and their families.</p> <p>Methods</p> <p>Participatory action research was used to stepwise define a design specification in the form of a pattern language. Support for children diagnosed with diabetes Type 1 was used as the example area. Each individual design pattern was determined graphically using card sorting methods, and textually in the form <it>Title, Context, Problem, Solution, Examples and References</it>. <it>Application references </it>were included at the lowest level in the graphical overview in the pattern language but not specified in detail in the textual descriptions.</p> <p>Results</p> <p>The design patterns are divided into functional and non-functional design elements, and formulated at the levels of organizational, system, and application design. The design elements specify access to materials for development of the competences needed for chronic disease management in specific community settings, endorsement of self-learning through online peer-to-peer communication, and systematic accreditation and evaluation of materials and processes.</p> <p>Conclusion</p> <p>The use of design patterns allows representing the core design elements of a Web 2.0 system upon which an 'ecological' development of content respecting these constraints can be built. Future research should include evaluations of Web 2.0 systems implemented according to the architecture in practice settings.</p

Prefrontal Cortex Lesions Impair Object-Spatial Integration

How and where object and spatial information are perceptually integrated in the brain is a central question in visual cognition. Single-unit physiology, scalp EEG, and fMRI research suggests that the prefrontal cortex (PFC) is a critical locus for object-spatial integration. To test the causal participation of the PFC in an object-spatial integration network, we studied ten patients with unilateral PFC damage performing a lateralized object-spatial integration task. Consistent with single-unit and neuroimaging studies, we found that PFC lesions result in a significant behavioral impairment in object-spatial integration. Furthermore, by manipulating inter-hemispheric transfer of object-spatial information, we found that masking of visual transfer impairs performance in the contralesional visual field in the PFC patients. Our results provide the first evidence that the PFC plays a key, causal role in an object-spatial integration network. Patient performance is also discussed within the context of compensation by the non-lesioned PFC

Intergenerational family support for ‘Generation Rent’:The family home for socially disengaged young people

This paper critically discusses the concept of intergenerational family support in housing for young people. Recognizing increased difficulties faced by the younger generation in the housing market, this paper highlights that support from older family members is increasingly important. Nonetheless, it is critiqued that the role of the family home has been largely ignored in the current ‘generation rent’ discourse. By drawing on recent youth studies debates, this paper argues living in the family home could be an important form of support in housing, especially for marginalized youth. This paper presents insights from qualitative studies in Hong Kong and Scotland and analyses interview accounts of socially disengaged young people. It reflects how remaining at the family home could be interpreted as intergenerational support, and further elicits complexities in expectations, negotiations and emotions involved. This analysis offers new evidence and a more nuanced perspective of intergenerational family support in housing research

On the Role of Attention in Binocular Rivalry: Electrophysiological Evidence

During binocular rivalry visual consciousness fluctuates between two dissimilar monocular images. We investigated the role of attention in this phenomenon by comparing event-related potentials (ERPs) when binocular-rivalry stimuli were attended with when they were unattended. Stimuli were dichoptic, orthogonal gratings that yielded binocular rivalry and dioptic, identically oriented gratings that yielded binocular fusion. Events were all possible orthogonal changes in orientation of one or both gratings. We had two attention conditions: In the attend-to-grating condition, participants had to report changes in perceived orientation, focussing their attention on the gratings. In the attend-to-fixation condition participants had to report changes in a central fixation target, taking attention away from the gratings. We found, surprisingly, that attending to rival gratings yielded a smaller ERP component (the N1, from 160–210 ms) than attending to the fixation target. To explain this paradoxical effect of attention, we propose that rivalry occurs in the attend-to-fixation condition (we found an ERP signature of rivalry in the form of a sustained negativity from 210–300 ms) but that the mechanism processing the stimulus changes is more adapted in the attend-to-grating condition than in the attend-to-fixation condition. This is consistent with the theory that adaptation gives rise to changes of visual consciousness during binocular rivalry