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The adiabatic ionization potential of methylene has been determined to be 83772 ± 3 cm[sup -1] from a rotationally resolved photoelectron spectroscopic study of the CH[sup +][sub 2] &Xtilde;²A[sub 1] (0,0,0) ← CH[sub 2] &Xtilde; ³B[sub 1] (0,0,0) transition. This value was used to determine thermochemical quantities such as the 0 K dissociation energy of the ketene cation in CO and CH[sup +][sub 2] D[sub 0](CH[sub 2] = CO[sup +]) = 33202 ± 7 cm[sup -1], the 0 K dissociation energy of the methyl radical D[sub 0](CH[sub 2] - H) = 38179 ± 49 cm[sup -1], the 0 K dissociation threshold of methane in CH[sub 2] and H[sub 2] D[sub 0](CH[sub 2]-H[sub 2]) = 38232 ± 50 cm[sup -1] and the 0 K enthalpy of formation of CH[sub 2] Λ[sub &fnof]H... (CH[sub 2],T= 0 K)=390.73 ± 0.66 kJ mol[sup -1]. [ABSTRACT FROM AUTHOR]

In drug-resistant focal epilepsy, planning surgical resection may involve presurgical intracranial EEG recordings (iEEG) to detect seizures and other iEEG patterns to improve postsurgical seizure outcome. We hypothesized that resection of tissue generating interictal high frequency oscillations (HFOs, 80-500 Hz) in the iEEG predicts surgical outcome. Eight international epilepsy centres recorded iEEG during the patients' pre-surgical evaluation. The patients were of all ages, had epilepsy of all types, and underwent surgical resection of a single focus aiming at seizure freedom. In a prospective analysis we applied a fully automated definition of HFO which was independent of the dataset. Using an observational cohort design that was blinded to postsurgical seizure outcome, we analysed HFO rates during non-rapid-eye-movement sleep. If channels had consistently high rates over multiple epochs, they were labelled the "HFO area". After HFO analysis, centres provided the electrode contacts located in the resected volume and the seizure outcome at follow-up ≥24 months after surgery. The study was registered at www.clinicaltrials.gov (NCT05332990). We received 160 iEEG datasets. In 146 datasets (91%), the HFO area could be defined. The patients with completely resected HFO area were more likely to achieve seizure freedom compared to those without (OR 2.61 CI [1.15-5.91], P = 0.02). Among seizure free patients, the HFO area was completely resected in 31 and was not completely resected in 43. Among patients with recurrent seizures, the HFO area was completely resected in 14 and was not completely resected in 58. When predicting seizure freedom, the negative predictive value of the HFO area (68% CI [52-81]) was higher than that for the resected volume as predictor by itself (51% CI [42-59], P = 4e-5). The sensitivity and specificity for complete HFO area resection were 0.88 CI [0.72-0.98] and 0.39 CI [0.25-0.54] and the area under the curve was 0.83 CI [0.58-0.97], indicating good predictive performance. In a blinded cohort study from independent epilepsy centres, applying a previously validated algorithm for HFO marking without the need of adjusting to new datasets allowed us to validate the clinical relevance of HFOs to plan the surgical resection., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: We present a case of a 46-year-old man with Lennox-Gastaut syndrome and drug-resistant epilepsy. An adjunctive neurostimulation therapy strategy was implemented involving bilateral deep brain stimulation (DBS) of the centromedian thalamic nucleus (CMT)., Methods: Robotically assisted implantation of bilateral DBS directional lead system with 8 contacts in the CMT was performed. The clinical course was assessed in repeated in-patient follow-ups., Results: Initial DBS stimulation resulted in progressive ataxia and dysarthria significantly beyond the level seen before surgery. Deactivation of DBS coincided with improvement of dysarthria. A DBS stimulation paradigm with reduction of lateral and superior stimulation resulted in improvement and eventually complete resolution of the stimulation side effect., Discussion: This case suggests that stimulation-induced dysarthria in DBS can be improved by targeted reduction of lateral and/or superior thalamic stimulation. When dysarthria and ataxia occur during DBS, directed stimulation to medial thalamic structures and more inferior electrode contacts offers a promising strategy to reduce side effects while maintaining positive effects., (© 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.)

Introduction: Current evidence indicates a modulating role of respiratory processes in cardiac interoception, yet whether altered breathing patterns influence heartbeat-evoked potentials (HEP) remains inconclusive., Methods: Here, we examined the effects of voluntary hyperventilation (VH) as part of a clinical routine examination on scalp-recorded HEPs in epilepsy patients ( N = 80)., Results: Using cluster-based permutation analyses, HEP amplitudes were compared across pre-VH and post-VH conditions within young and elderly subgroups, as well as for the total sample. No differences in the HEP were detected for younger participants or across the full sample, while an increased late HEP during pre-VH compared to post-VH was fond in the senior group, denoting decreased cardiac interoceptive processing after hyperventilation., Discussion: The present study, thus, provides initial evidence of breathing-related HEP modulations in elderly epilepsy patients, emphasizing the potential of HEP as an interoceptive neural marker that could partially extend to the representation of pulmonary signaling. We speculate that aberrant CO 2 -chemosensing, coupled with disturbances in autonomic regulation, might constitute the underlying pathophysiological mechanism behind the obtained effect. Available databases involving patient records of routine VH assessment may constitute a valuable asset in disentangling the interplay of cardiac and ventilatory interoceptive information in various patient groups, providing thorough clinical data to parse, as well as increased statistical power and estimates of effects with higher precision through large-scale studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Stoupi, Weijs, Imbach and Lenggenhager.)

Background: Enhancing slow waves, the electrophysiological (EEG) manifestation of non-rapid eye movement (NREM) sleep, could potentially benefit patients with Parkinson's disease (PD) by improving sleep quality and slowing disease progression. Phase-targeted auditory stimulation (PTAS) is an approach to enhance slow waves, which are detected in real-time in the surface EEG signal., Objective: We aimed to test whether the local-field potential of the subthalamic nucleus (STN-LFP) can be used to detect frontal slow waves and assess the electrophysiological changes related to PTAS., Methods: We recruited patients diagnosed with PD and undergoing Percept™ PC neurostimulator (Medtronic) implantation for deep brain stimulation of STN (STN-DBS) in a two-step surgery. Patients underwent three full-night recordings, including one between-surgeries recording and two during rehabilitation, one with DBS+ (on) and one with DBS- (off). Surface EEG and STN-LFP signals from Percept PC were recorded simultaneously, and PTAS was applied during sleep in all three recording sessions., Results: Our results show that during NREM sleep, slow waves of the cortex and STN are time-locked. PTAS application resulted in power and coherence changes, which can be detected in STN-LFP., Conclusion: Our findings suggest the feasibility of implementing PTAS using solely STN-LFP signal for slow wave detection, thus without a need for an external EEG device alongside the implanted neurostimulator. Moreover, we propose options for more efficient STN-LFP signal preprocessing, including different referencing and filtering to enhance the reliability of cortical slow wave detection in STN-LFP recordings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: 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. The study is an Investigator-Initiated Study. Part of the funding for this study is provided by Medtronic. Medtronic has no role in the study design, data analysis, and interpretation, and in writing the manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Accurately assessing the severity and frequency of fluctuating motor symptoms is important at all stages of Parkinson's disease management. Contrarily to time-consuming clinical testing or patient self-reporting with uncertain reliability, recordings with wearable sensors show promise as a tool for continuously and objectively assessing PD symptoms. While wearables-based clinical assessments during standardised and scripted tasks have been successfully implemented, assessments during unconstrained activity remain a challenge., Methods: We developed and implemented a supervised machine learning algorithm, trained and tested on tremor scores. We evaluated the algorithm on a 67-hour database comprising sensor data and clinical tremor scores for 24 Parkinson patients at four extremities for periods of about 3 hours. A random 25% subset of the labelled samples was used as test data, the remainder as training data. Based on features extracted from the sensor data, a Support Vector Machine was trained to predict tremor severity. Due to the inherent imbalance in tremor scores, we applied dataset rebalancing techniques., Results: Our classifier demonstrated robust performance in detecting tremor events with a sensitivity of 0.90 on the test-portion of the resampled dataset. The overall classification accuracy was high at 0.88., Conclusion: We implemented an accurate classifier for tremor monitoring in free-living environments that can be trained even with modestly sized and imbalanced datasets. This advancement offers significant clinical value in continuously monitoring Parkinson's disease symptoms beyond the hospital setting, paving the way for personalized management of PD, timely therapeutic adjustments, and improved patient quality of life., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Fernando Rodriguez et al.)

Understanding how emotional processing modulates learning and memory is crucial for the treatment of neuropsychiatric disorders characterized by emotional memory dysfunction. We investigate how human medial temporal lobe (MTL) neurons support emotional memory by recording spiking activity from the hippocampus, amygdala, and entorhinal cortex during encoding and recognition sessions of an emotional memory task in patients with pharmaco-resistant epilepsy. Our findings reveal distinct representations for both remembered compared to forgotten and emotional compared to neutral scenes in single units and MTL population spiking activity. Additionally, we demonstrate that a distributed network of human MTL neurons exhibiting mixed selectivity on a single-unit level collectively processes emotion and memory as a network, with a small percentage of neurons responding conjointly to emotion and memory. Analyzing spiking activity enables a detailed understanding of the neurophysiological mechanisms underlying emotional memory and could provide insights into how emotion alters memory during healthy and maladaptive learning., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Non-spatial attention is a fundamental cognitive mechanism that allows organisms to orient the focus of conscious awareness towards sensory information that is relevant to a behavioural goal while shifting it away from irrelevant stimuli. It has been suggested that attention is regulated by the ongoing phase of slow excitability fluctuations of neural activity in the prefrontal cortex, a hypothesis that has been challenged with no consensus. Here we developed a behavioural and non-invasive stimulation paradigm aiming at modulating slow excitability fluctuations of the inferior frontal junction. Using this approach, we show that non-spatial attention can be selectively modulated as a function of the ongoing phase of exogenously modulated excitability states of this brain structure. These results demonstrate that non-spatial attention relies on ongoing prefrontal excitability states, which are probably regulated by slow oscillatory dynamics, that orchestrate goal-oriented behaviour., (© 2024. The Author(s).)

Working memory (WM) maintenance relies on multiple brain regions and inter-regional communications. The hippocampus and entorhinal cortex (EC) are thought to support this operation. Besides, EC is the main gateway for information between the hippocampus and neocortex. However, the circuit-level mechanism of this interaction during WM maintenance remains unclear in humans. To address these questions, we recorded the intracranial electroencephalography from the hippocampus and EC while patients ( N  = 13, six females) performed WM tasks. We found that WM maintenance was accompanied by enhanced theta/alpha band (2-12 Hz) phase synchronization between the hippocampus to the EC. The Granger causality and phase slope index analyses consistently showed that WM maintenance was associated with theta/alpha band-coordinated unidirectional influence from the hippocampus to the EC. Besides, this unidirectional inter-regional communication increased with WM load and predicted WM load during memory maintenance. These findings demonstrate that WM maintenance in humans engages the hippocampal-entorhinal circuit, with the hippocampus influencing the EC in a load-dependent manner., (Copyright © 2024 Li, Cao et al.)

Background: Glioblastoma is the most common and most aggressive malignant primary brain tumor in adults. Glioblastoma cells synthesize and secrete large quantities of the excitatory neurotransmitter glutamate, driving epilepsy, neuronal death, tumor growth and invasion. Moreover, neuronal networks interconnect with glioblastoma cell networks through glutamatergic neuroglial synapses, activation of which induces oncogenic calcium oscillations that are propagated via gap junctions between tumor cells. The primary objective of this study is to explore the efficacy of brain-penetrating anti-glutamatergic drugs to standard chemoradiotherapy in patients with glioblastoma., Methods/design: GLUGLIO is a 1:1 randomized phase Ib/II, parallel-group, open-label, multicenter trial of gabapentin, sulfasalazine, memantine and chemoradiotherapy (Arm A) versus chemoradiotherapy alone (Arm B) in patients with newly diagnosed glioblastoma. Planned accrual is 120 patients. The primary endpoint is progression-free survival at 6 months. Secondary endpoints include overall and seizure-free survival, quality of life of patients and caregivers, symptom burden and cognitive functioning. Glutamate levels will be assessed longitudinally by magnetic resonance spectroscopy. Other outcomes of interest include imaging response rate, neuronal hyperexcitability determined by longitudinal electroencephalography, Karnofsky performance status as a global measure of overall performance, anticonvulsant drug use and steroid use. Tumor tissue and blood will be collected for translational research. Subgroup survival analyses by baseline parameters include segregation by age, extent of resection, Karnofsky performance status, O 6 -methylguanine DNA methyltransferase (MGMT) promotor methylation status, steroid intake, presence or absence of seizures, tumor volume and glutamate levels determined by MR spectroscopy. The trial is currently recruiting in seven centers in Switzerland., Trial Registration: NCT05664464. Registered 23 December 2022., (© 2024. The Author(s).)

The sense of agency is a fundamental aspect of human self-consciousness, whose neural correlates encompass widespread brain networks. Research has explored the neuromodulatory properties of the sense of agency with noninvasive brain stimulation, which induces exogenous manipulations of brain activity; however, it is unknown whether endogenous modulation of the sense of agency is also achievable. We investigated whether the sense of agency can be self-regulated with electroencephalography-based neurofeedback. We conducted 2 experiments in which healthy humans performed a motor task while their motor control was artificially disrupted, and gave agency statements on their perceived control. We first identified the electrophysiological response to agency processing, and then applied neurofeedback in a parallel, sham-controlled design, where participants learnt to self-modulate their sense of agency. We found that behavioral measures of agency and performance on the task decreased with the increasing disruption of control. This was negatively correlated with power spectral density in the theta band, and positively correlated in the alpha and beta bands, at central and parietal electrodes. After neurofeedback training of central theta rhythms, participants improved their actual control over the task, and this was associated with a significant decrease in the frequency band trained via neurofeedback. Thus, self-regulation of theta rhythms can improve sensory-guided behavior., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We evaluate whether interictal spikes, epileptiform HFOs and their co-occurrence (Spike + HFO) were included in the resection area with respect to seizure outcome. We also characterise the relationship between high frequency oscillations (HFOs) and propagating spikes. We analysed intracranial EEG of 20 patients that underwent resective epilepsy surgery. The co-occurrence of ripples and fast ripples was considered an HFO event; the co-occurrence of an interictal spike and HFO was considered a Spike + HFO event. HFO distribution and spike onset were compared in cases of spike propagation. Accuracy in predicting seizure outcome was 85% for HFO, 60% for Spikes, and 79% for Spike + HFO. Sensitivity was 57% for HFO, 71% for Spikes and 67% for Spikes + HFO. Specificity was 100% for HFO, 54% for Spikes and 85% for Spikes + HFO. In 2/2 patients with spike propagation, the spike onset included the HFO area. Combining interictal spikes with HFO had comparable accuracy to HFO. In patients with propagating spikes, HFO rate was maximal at the onset of spike propagation., (© 2023. The Author(s).)

Most cases with new onset refractory status epilepticus (NORSE) remain cryptogenic despite extensive diagnostic workup. The aim of this study was to analyze the etiology and clinical features of NORSE and investigate known or potentially novel autoantibodies in cryptogenic NORSE (cNORSE). We retrospectively assessed the medical records of adults with status epilepticus at a Swiss tertiary referral center between 2010 and 2021. Demographic, diagnostic, therapeutic, and outcome parameters were characterized. We performed post hoc screening for known or potentially novel autoantibodies including immunohistochemistry (IHC) on rat brain with cerebrospinal fluid (CSF) and serum samples of cNORSE. Twenty patients with NORSE were identified. Etiologies included infections (n = 4), Creutzfeldt-Jakob disease (n = 1), CASPR2 autoimmune encephalitis (n = 1), and carotid artery stenosis with recurrent perfusion deficit (n = 1). Thirteen cases (65%) were cryptogenic despite detailed evaluation. A posteriori IHC for neuronal autoantibodies yielded negative results in all available serum (n = 11) and CSF (n = 9) samples of cNORSE. Our results suggest that neuronal antibodies are unlikely to play a major role in the pathogenesis of cNORSE. Future studies should rather focus on other-especially T-cell- and cytokine-mediated-mechanisms of autoinflammation in this devastating disease, which is far too poorly understood so far., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Owing to its unique connectivity profile with cortical brain regions, and its suggested role in the subcortical propagation of seizures, the anterior nucleus of the thalamus (ANT) has been proposed as a key deep brain stimulation (DBS) target in drug-resistant epilepsy. However, the spatio-temporal interaction dynamics of this brain structure, and the functional mechanisms underlying ANT DBS in epilepsy remain unknown. Here, we study how the ANT interacts with the neocortex in vivo in humans and provide a detailed neurofunctional characterization of mechanisms underlying the effectiveness of ANT DBS, aiming at defining intraoperative neural biomarkers of responsiveness to therapy, assessed at 6 months post-implantation as the reduction in seizure frequency. A cohort of 15 patients with drug-resistant epilepsy (n = 6 males, age = 41.6 ± 13.79 years) underwent bilateral ANT DBS implantation. Using intraoperative cortical and ANT simultaneous electrophysiological recordings, we found that the ANT is characterized by high amplitude θ (4-8 Hz) oscillations, mostly in its superior part. The strongest functional connectivity between the ANT and the scalp EEG was also found in the θ band in ipsilateral centro-frontal regions. Upon intraoperative stimulation in the ANT, we found a decrease in higher EEG frequencies (20-70 Hz) and a generalized increase in scalp-to-scalp connectivity. Crucially, we observed that responders to ANT DBS treatment were characterized by higher EEG θ oscillations, higher θ power in the ANT, and stronger ANT-to-scalp θ connectivity, highlighting the crucial role of θ oscillations in the dynamical network characterization of these structures. Our study provides a comprehensive characterization of the interaction dynamic between the ANT and the cortex, delivering crucial information to optimize and predict clinical DBS response in patients with drug-resistant epilepsy., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Both the hippocampus and amygdala are involved in working memory (WM) processing. However, their specific role in WM is still an open question. Here, we simultaneously recorded intracranial EEG from the amygdala and hippocampus of epilepsy patients while performing a WM task, and compared their representation patterns during the encoding and maintenance periods. By combining multivariate representational analysis and connectivity analyses with machine learning methods, our results revealed a functional specialization of the amygdala-hippocampal circuit: The mnemonic representations in the amygdala were highly distinct and decreased from encoding to maintenance. The hippocampal representations, however, were more similar across different items but remained stable in the absence of the stimulus. WM encoding and maintenance were associated with bidirectional information flow between the amygdala and the hippocampus in low-frequency bands (1-40 Hz). Furthermore, the decoding accuracy on WM load was higher by using representational features in the amygdala during encoding and in the hippocampus during maintenance, and by using information flow from the amygdala during encoding and that from the hippocampus during maintenance, respectively. Taken together, our study reveals that WM processing is associated with functional specialization and interaction within the amygdala-hippocampus circuit., (© 2023. The Author(s).)

Seizures in patients with brain metastases have an impact on morbidity and quality of life. The influence of tumor growth on the risk of seizures in these patients is not well defined. In this cohort study, we evaluated adult patients from the University Hospital of Zurich following resection of brain metastases from solid tumors, with or without preoperative seizures, at 3, 6, 9, and 12 months postoperatively. Brain magnetic resonance imaging was assessed for tumor progression using the Response Assessment in Neuro-Oncology criteria. The quarterly risk of unprovoked seizures was modeled with mixed effects logistic regression. We analyzed 444 time frames in 220 patients. Progression of brain metastases was independently associated with seizures during the respective quarterly follow-up period (odds ratio = 3.9, 95% confidence interval = 1.3-11.3, p = .014). Complete resection of brain metastases was associated with a lower risk of seizures (odds ratio = .2, 95% confidence interval = .04-.7, p = .015). Postoperative progression of brain metastases quadrupled the risk of seizures; therefore, vigorous follow-up may be useful to identify tumor progression and gauge the risk of seizures. The identification of patients at high seizure risk may have implications for treatment decisions and influence aspects of daily life. Breakthrough seizures may indicate brain metastases progression., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Deep brain stimulation (DBS) electrodes provide an unparalleled window to record and investigate neuronal activity right at the core of pathological brain circuits. In Parkinson's disease (PD), basal ganglia beta-oscillatory activity (13-35 Hz) seems to play an outstanding role. Conventional DBS, which globally suppresses beta-activity, does not meet the requirements of a targeted treatment approach given the intricate interplay of physiological and pathological effects of beta-frequencies. Here, we wanted to characterise the local field potential (LFP) in the subthalamic nucleus (STN) in terms of beta-burst prevalence, amplitude and length between movement and rest as well as during self-paced as compared to goal-directed motor control. Our electrophysiological recordings from externalised DBS-electrodes in nine patients with PD showed a marked decrease in beta-burst durations and prevalence during movement as compared to rest as well as shorter and less frequent beta-bursts during cued as compared to self-paced movements. These results underline the importance of beta-burst modulation in movement generation and are in line with the clinical observation that cued motor control is better preserved than self-paced movements. Furthermore, our findings motivate the use of adaptive DBS based on beta-bursts, which selectively trim longer beta-bursts, as it is more suitable and efficient over a range of motor behaviours than conventional DBS., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The maintenance of items in working memory (WM) relies on a widespread network of cortical areas and hippocampus where synchronization between electrophysiological recordings reflects functional coupling. We investigated the direction of information flow between auditory cortex and hippocampus while participants heard and then mentally replayed strings of letters in WM by activating their phonological loop. We recorded local field potentials from the hippocampus, reconstructed beamforming sources of scalp EEG , and - additionally in four participants - recorded from subdural cortical electrodes. When analyzing Granger causality, the information flow was from auditory cortex to hippocampus with a peak in the [4 8] Hz range while participants heard the letters. This flow was subsequently reversed during maintenance while participants maintained the letters in memory. The functional interaction between hippocampus and the cortex and the reversal of information flow provide a physiological basis for the encoding of memory items and their active replay during maintenance., Competing Interests: VD, PM, LS, LI, JS No competing interests declared, (© 2022, Dimakopoulos et al.)

In drug-resistant focal epilepsy, interictal high-frequency oscillations (HFOs) recorded from intracranial EEG (iEEG) may provide clinical information for delineating epileptogenic brain tissue. The iEEG electrode contacts that contain HFO are hypothesized to delineate the epileptogenic zone; their resection should then lead to postsurgical seizure freedom. We test whether our prospective definition of clinically relevant HFO is in agreement with postsurgical seizure outcome. The algorithm is fully automated and is equally applied to all data sets. The aim is to assess the reliability of the proposed detector and analysis approach. We use an automated data-independent prospective definition of clinically relevant HFO that has been validated in data from two independent epilepsy centres. In this study, we combine retrospectively collected data sets from nine independent epilepsy centres. The analysis is blinded to clinical outcome. We use iEEG recordings during NREM sleep with a minimum of 12 epochs of 5 min of NREM sleep. We automatically detect HFO in the ripple (80-250 Hz) and in the fast ripple (250-500 Hz) band. There is no manual rejection of events in this fully automated algorithm. The type of HFO that we consider clinically relevant is defined as the simultaneous occurrence of a fast ripple and a ripple. We calculate the temporal consistency of each patient's HFO rates over several data epochs within and between nights. Patients with temporal consistency <50% are excluded from further analysis. We determine whether all electrode contacts with high HFO rate are included in the resection volume and whether seizure freedom (ILAE 1) was achieved at ≥2 years follow-up. Applying a previously validated algorithm to a large cohort from several independent epilepsy centres may advance the clinical relevance and the generalizability of HFO analysis as essential next step for use of HFO in clinical practice., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: The present study firstly aimed to identify context patterns in sport and exercise among adolescents at lower and upper secondary education. The organisational, social and competitive contexts of leisure-time sport and exercise were included as pattern indicators. The second aim was to examine the stability of these patterns across educational transition. The last aim was to investigate whether a subjective evaluation of the transition influences whether people stay in the same pattern across time., Methods: One-year longitudinal data of 392 adolescents were analysed., Results: Both before and after the educational transition, four context patterns were identified: the traditional competitive club athletes with friends, the self-organised individualists, the non-club-organised sportspersons and the mostly inactives. More than half of the individuals stayed in the same pattern across time. When individuals changed pattern, their change was most often from the self-organised individualists and the non-club-organised to the mostly inactives. A subjective evaluation of the transition influenced the stability of only the traditional competitive club athletes with friends. The chance of these people staying in the same pattern decreased with increased transitional stress., Conclusions: Knowledge about the stability and change of context patterns can be used to make recommendations for policy strategies and to develop more individually-tailored promotion programs., (© 2021. The Author(s).)

The hippocampus is a locus of working memory (WM) with anterior and posterior subregions that differ in their transcriptional and external connectivity patterns. However, the involvement and functional connections between these subregions in WM processing are poorly understood. To address these issues, we recorded intracranial EEG from the anterior and the posterior hippocampi in humans (seven females and seven males) who maintained a set of letters in their WM. We found that WM maintenance was accompanied by elevated low-frequency activity in both the anterior and posterior hippocampus and by increased theta/alpha band (3-12 Hz) phase synchronization between anterior and posterior subregions. Cross-frequency and Granger prediction analyses consistently showed that the correct WM trials were associated with theta/alpha band-coordinated unidirectional influence from the posterior to the anterior hippocampus. In contrast, WM errors were associated with bidirectional interactions between the anterior and posterior hippocampus. These findings imply that theta/alpha band synchrony within the hippocampus may support successful WM via a posterior to anterior influence. A combination of intracranial recording and a fine-grained atlas may be of value in understanding the neural mechanisms of WM processing. SIGNIFICANCE STATEMENT Working memory (WM) is crucial to everyday functioning. The hippocampus has been proposed to be a subcortical node involved in WM processes. Previous studies have suggested that the anterior and posterior hippocampi differ in their external connectivity patterns and gene expression. However, it remains unknown whether and how human hippocampal subregions are recruited and coordinated during WM tasks. Here, by recording intracranial electroencephalography simultaneously from both hippocampal subregions, we found enhanced power in both areas and increased phase synchronization between them. Furthermore, correct WM trials were associated with a unidirectional influence from the posterior to the anterior hippocampus, whereas error trials were correlated with bidirectional interactions. These findings indicate a long-axis specialization in the human hippocampus during WM processing., (Copyright © 2022 the authors.)

Pro-tumorigenic electrochemical synapses between neurons and brain tumour cells in preclinical studies suggest unfavourable effects of epilepsy on patient survival. We investigated associations of epilepsy and survival in three cohorts of brain tumour patients (meningioma, glioblastoma and brain metastases). Cohorts were segregated into three groups for comparative analyses: (i) no epilepsy; (ii) epilepsy without status epilepticus; and (iii) status epilepticus. Status epilepticus was considered a surrogate of extensive neuronal hyperexcitability. The main outcome was progression-free survival (meningioma) and overall survival (glioblastoma and brain metastases), adjusted for established prognostic factors and onset of epilepsy by time-dependent multivariate Cox modelling. The primary analysis population comprised 1792 patients (742 meningioma, 249 glioblastoma, 801 brain metastases). Epilepsy was associated with favourable prognostic factors. However, on multivariate analyses, status epilepticus was associated with inferior overall survival of patients with glioblastoma [status epilepticus versus no epilepsy multivariate hazard ratio (HR) 3.72, confidence interval (CI) 1.78-7.76, P < 0.001] and brain metastases (status epilepticus versus no epilepsy HR 2.30, CI 1.10-4.79, P = 0.026). Among brain metastases patients, but not among patients with meningioma or glioblastoma, epilepsy was similarly associated with inferior overall survival (epilepsy versus no epilepsy HR 2.16, CI 1.60-2.93, P < 0.001). We conclude that epilepsy may convey inferior survival of patients with malignant brain tumours., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The burst suppression pattern in clinical electroencephalographic (EEG) recordings is an important diagnostic tool because of its association with comas of various etiologies, as with hypoxia, drug related intoxication or deep anesthesia. The detection of bursts and the calculation of burst/suppression ratio are often used to monitor the level of anesthesia during treatment of status epilepticus. However, manual counting of bursts is a laborious process open to inter-rater variation and motivates a need for automatic detection., Methods: We describe a novel unsupervised learning algorithm that detects bursts in EEG and generates burst-per-minute estimates for the purpose of monitoring sedation level in an intensive care unit (ICU). We validated the algorithm on 29 hours of burst annotated EEG data from 29 patients suffering from status epilepticus and hemorrhage., Results: We report competitive results in comparison to neural networks learned via supervised learning. The mean absolute error (SD) in bursts per minute was 0.93 (1.38)., Conclusion: We present a novel burst suppression detection algorithm that adapts to each patient individually, reports bursts-per-minute quickly, and does not require manual fine-tuning unlike previous approaches to burst-suppression pattern detection., Significance: Our algorithm for automatic burst suppression quantification can greatly reduce manual oversight in depth of sedation monitoring., 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 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Introduction: Spinal cord injury (SCI) is a devastating condition with immediate impact on the individual's health and quality of life. Major functional recovery reaches a plateau 3-4 months after injury despite intensive rehabilitative training. To enhance training efficacy and improve long-term outcomes, the combination of rehabilitation with electrical modulation of the spinal cord and brain has recently aroused scientific interest with encouraging results. The mesencephalic locomotor region (MLR), an evolutionarily conserved brainstem locomotor command and control centre, is considered a promising target for deep brain stimulation (DBS) in patients with SCI. Experiments showed that MLR-DBS can induce locomotion in rats with spinal white matter destructions of >85%., Methods and Analysis: In this prospective one-armed multi-centre study, we investigate the safety, feasibility, and therapeutic efficacy of MLR-DBS to enable and enhance locomotor training in severely affected, subchronic and chronic American Spinal Injury Association Impairment Scale C patients in order to improve functional recovery. Patients undergo an intensive training programme with MLR-DBS while being regularly followed up until 6 months post-implantation. The acquired data of each timepoint are compared with baseline while the primary endpoint is performance in the 6-minute walking test. The clinical trial protocol was written in accordance with the Standard Protocol Items: Recommendations for Interventional Trials checklist., Ethics and Dissemination: This first in-man study investigates the therapeutic potential of MLR-DBS in SCI patients. One patient has already been implanted with electrodes and underwent MLR stimulation during locomotion. Based on the preliminary results which promise safety and feasibility, recruitment of further patients is currently ongoing. Ethical approval has been obtained from the Ethical Committee of the Canton of Zurich (case number BASEC 2016-01104) and Swissmedic (10000316). Results will be published in peer-reviewed journals and presented at conferences., Trial Registration Number: NCT03053791., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The purpose of this study was to investigate a potential psychological mechanism of green exercise on perceived stress. More precisely, it was analyzed whether the relationship between the natural environment of physical activity and perceived stress was mediated by recovery experiences, namely by psychological detachment and relaxation. An ecological momentary assessment approach was used, meaning that specific recovery experiences were assessed directly in real-life situations and multiple times. Materials and methods: Thirty five women and 27 men took part in the ecological momentary assessment study over seven days ( M age = 32.30 years, SD = 10.23, 53% had a degree from a university or a university of applied science). If participants were involved in PA lasting at least 10 min on a given day, they had to answer questionnaires on the smartphone both prior to the activity and immediately afterwards. Perceived naturalness, psychological detachment and relaxation were assessed after physical activity events, whereas perceived stress was measured before and after each physical activity event. A two-level mediation analysis was conducted. The direct and indirect effect of perceived naturalness on perceived stress after engagement in physical activity was analyzed on the within- and between-person levels. Results and conclusion: Results showed that the relaxation as a recovery experience served as mediator between perceived naturalness and perceived stress after engagement in physical activity, but only on a within-person level. This means that the more natural a given individual appraised the physical activity environment, the more relaxed he or she felt during physical activity (β = 0.3 22, p < 0.0005). Furthermore the more relaxed the individual was, the less stress he or she perceived after exercising (β = -0.221, p < 0.0005). The psychological detachment as a recovery experience in contrast, did not serve as mediator, neither at the within- and the between-person level. Considering the indirect effect of perceived naturalness on perceived stress and the importance of relaxation experiences, current findings suggest that research should put greater emphasis on examining the specific psychological mechanisms of green exercise to make even better use of its beneficial effects in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schmid, Imbach, Klaperski and Sudeck.)

Objective: The management of brain tumour patients who would like to resume driving is complex, and needs multidisciplinary input and a consensus among treating physicians. The Swiss Neuro-Oncology Society (SwissNOS) and the Swiss Society for Legal Medicine (SGRM) aim to provide guidance on how to assess “fitness-to-drive” of glioblastoma patients and to harmonise the relevant procedures in Switzerland., Methods: At several meetings, Swiss neuro-oncologists discussed common practices on how to advise patients with a stable, i.e., non-progressive, glioblastoma, who wish to resume driving after the initial standard tumour treatment. All participants of the SwissNOS meetings were invited twice to return a questionnaire (modified Delphi process) on specific tools/procedures they commonly use to assess “fitness-to-drive” of their patients. Answers were analysed to formulate a tentative consensus for a structured and reasonable approach., Results: Consensus on minimum requirements for a “fitness-to-drive” programme for glioblastoma patients could be reached among Swiss neuro-oncologists. The recommendations were based on existing guidelines and expert opinions regarding patients with seizures, visual disturbances, cognitive impairment or focal deficits for safe driving. At this point in time, the Swiss neuro-oncologists agreed on the following requirements for glioblastoma patients after the initial standard therapy and without a seizure for at least 12 months: (1) stable cranial magnetic resonance imaging (MRI) according to Response Assessment in Neuro-Oncology (RANO) criteria, to be repeated every 3 months; (2) thorough medical history, including current or new medication, a comprehensive neurological examination at baseline (T0) and every 3 months thereafter, optionally an electrocencephalogram (EEG) at baseline; (3) ophthalmological examination including visual acuity and intact visual fields; and (4) optional neuropsychological assessment with a focus on safe driving. Test results have to be compatible with safe driving at any time-point. Patients should be informed about test results and optionally sign a document., Conclusions: We propose regular thorough clinical neurological examination and brain MRI, optional EEG, neuropsychological and visual assessments to confirm “fitness-to-drive” for glioblastoma patients after initial tumour-directed therapy. The proposed “fitness-to-drive” assessments for glioblastoma patients serves as the basis for a prospective Swiss Pilot Project GLIODRIVE (BASEC ProjectID 2020-00365) to test feasibility, adherence and safety in a structured manner for patients who wish to resume driving. Research will focus on confirming the usefulness of the proposed tools in predicting “fitness-to-drive” and match results with events obtained from the road traffic registry (Strassenverkehrsamt).

Continuous patient monitoring is essential to achieve an effective and optimal patient treatment in the intensive care unit. In the specific case of epilepsy it is the only way to achieve a correct diagnosis and a subsequent optimal medication plan if possible. In addition to automatic vital sign monitoring, epilepsy patients need manual monitoring by trained personnel, a task that is very difficult to be performed continuously for each patient. Moreover, epileptic manifestations are highly personalized even within the same type of epilepsy. In this work we assess two machine learning methods, dictionary learning and an autoencoder based on long short-term memory (LSTM) cells, on the task of personalized epileptic event detection in videos, with a set of features that were specifically developed with an emphasis on high motion sensitivity. According to the strengths of each method we have selected different types of epilepsy, one with convulsive behaviour and one with very subtle motion. The results on five clinical patients show a highly promising ability of both methods to detect the epileptic events as anomalies deviating from the stable/normal patient status., (©2020 AMIA - All rights reserved.)

Objectives:  While the efficacy of deep brain stimulation (DBS) to treat various neurological disorders is undisputed, the surgical methods differ widely and the importance of intraoperative microelectrode recording (MER) or macrostimulation (MS) remains controversially debated. The objective of this study is to evaluate the impact of MER and MS on intraoperative lead placement., Patients and Methods:  We included 101 patients who underwent awake bilateral implantation of electrodes in the subthalamic nucleus with MER and MS for Parkinson's disease from 2009 to 2017 in a retrospective observational study. We analyzed intraoperative motor outcomes between anatomically planned stimulation point (PSP) and definite stimulation point (DSP), lead adjustments and Unified Parkinson's Disease Rating Scale Item III (UPDRS-III), levodopa equivalent daily dose (LEDD), and adverse events (AE) after 6 months., Results:  We adjusted 65/202 leads in 47/101 patients. In adjusted leads, MS results improved significantly when comparing PSP and DSP ( p  < 0.001), resulting in a number needed to treat of 9.6. After DBS, UPDRS-III and LEDD improved significantly after 6 months in adjusted and nonadjusted patients ( p  < 0.001). In 87% of leads, the active contact at 6 months still covered the optimal stimulation point during surgery. In total, 15 AE occurred., Conclusion:  MER and MS have a relevant impact on the intraoperative decision of final lead placement and prevent from a substantial rate of poor stimulation outcome. The optimal stimulation points during surgery and chronic stimulation strongly overlap. Follow-up UPDRS-III results, LEDD reductions, and DBS-related AE correspond well to previously published data., Competing Interests: None declared., (Thieme. All rights reserved.)