Brain monitoring in hospitals needs to be strengthened. / Hjerneovervåking i sykehusene må styrkes.

Careful brain monitoring saves lives and is beneficial to patients' health. Nevertheless, Norway lacks guidelines for brain monitoring in hospitals.

No effect of electrical transcranial direct current stimulation adjunct treatment for epilepsia partialis continua in POLG disease.

We report a 15-year-old female with POLG-related mitochondrial disease who developed severe multifocal epilepsia partialis continua, unresponsive to standard anti seizure drug treatment and general anesthesia. Based on an earlier case report, we treated her focal seizures that affected her right upper limb with 20-min sessions of transcranial direct current stimulation (tDCS) at an intensity of 2 mA on each of five consecutive days. The cathode was placed over the left primary motor cortex, the anode over the contralateral orbitofrontal cortex. Surface electromyography (EMG) were recorded 20 min before, 20 min during, and 20 min after four of five tDCS sessions to measure its effect on the muscle jerks. The electroencephalography (EEG) was recorded before and after tDCS to measure the frequency of spikes. Our results showed no statistically or clinically significant reduction of seizures or epileptiform activity using EEG and EMG, with this treatment protocol. To our knowledge, this is only the second time that adjunct tDCS treatment of epileptic seizures has been tried in POLG-related mitochondrial disease. Taken together with the positive findings from the earlier case report, the present study highlights that more data are needed to determine if, and under which parameters, the treatment is effective.

Visual EEG reviewing times with SCORE EEG.

OBJECTIVE: Visual EEG analysis is the gold standard for clinical EEG interpretation and analysis, but there is no published data on how long it takes to review and report an EEG in clinical routine. Estimates of reporting times may inform workforce planning and automation initiatives for EEG. The SCORE standard has recently been adopted to standardize clinical EEG reporting, but concern has been expressed about the time spent reporting. METHODS: Elapsed times were extracted from 5889 standard and sleep-deprived EEGs reported between 2015 and 2017 reported using the SCORE EEG software. RESULTS: The median review time for standard EEG was 12.5 min, and for sleep deprived EEG 20.9 min. A normal standard EEG had a median review time of 8.3 min. Abnormal EEGs took longer than normal EEGs to review, and had more variable review times. 99% of EEGs were reported within 24 h of end of recording. Review times declined by 25% during the study period. CONCLUSION: Standard and sleep-deprived EEG review and reporting times with SCORE EEG are reasonable, increasing with increasing EEG complexity and decreasing with experience. EEG reports can be provided within 24 h. SIGNIFICANCE: Clinical standard and sleep-deprived EEG reporting with SCORE EEG has acceptable reporting times.

Event-Related-Potential (ERP) Correlates of Performance Monitoring in Adults With Attention-Deficit Hyperactivity Disorder (ADHD).

Introduction: Attention-deficit hyperactivity disorder (ADHD) is one of the most frequent neurodevelopmental disorders in children and tends to persist into adulthood. Evidence from neuropsychological, neuroimaging, and electrophysiological studies indicates that alterations of error processing are core symptoms in children and adolescents with ADHD. To test whether adults with ADHD show persisting deficits and compensatory processes, we investigated performance monitoring during stimulus-evaluation and response-selection, with a focus on errors, as well as within-group correlations with symptom scores. Methods: Fifty-five participants (27 ADHD and 28 controls) aged 19-55 years performed a modified flanker task during EEG recording with 64 electrodes, and the ADHD and control groups were compared on measures of behavioral task performance, event-related potentials of performance monitoring (N2, P3), and error processing (ERN, Pe). Adult ADHD Self-Report Scale (ASRS) was used to assess ADHD symptom load. Results: Adults with ADHD showed higher error rates in incompatible trials, and these error rates correlated positively with the ASRS scores. Also, we observed lower P3 amplitudes in incompatible trials, which were inversely correlated with symptom load in the ADHD group. Adults with ADHD also displayed reduced error-related ERN and Pe amplitudes. There were no significant differences in reaction time (RT) and RT variability between the two groups. Conclusion: Our findings show deviations of electrophysiological measures, suggesting reduced effortful engagement of attentional and error-monitoring processes in adults with ADHD. Associations between ADHD symptom scores, event-related potential amplitudes, and poorer task performance in the ADHD group further support this notion.

Understanding the Epilepsy in POLG Related Disease.

Epilepsy is common in polymerase gamma (POLG) related disease and is associated with high morbidity and mortality. Epileptiform discharges typically affect the occipital regions initially and focal seizures, commonly evolving to bilateral convulsive seizures which are the most common seizure types in both adults and children. Our work has shown that mtDNA depletion-i.e., the quantitative loss of mtDNA-in neurones is the earliest and most important factor of the subsequent development of cellular dysfunction. Loss of mtDNA leads to loss of mitochondrial respiratory chain (MRC) components that, in turn, progressively disables energy metabolism. This critically balanced neuronal energy metabolism leads to both a chronic and continuous attrition (i.e., neurodegeneration) and it leaves the neurone unable to cope with increased demand that can trigger a potentially catastrophic cycle that results in acute focal necrosis. We believe that it is the onset of epilepsy that triggers the cascade of damage. These events can be identified in the stepwise evolution that characterizes the clinical, Electroencephalography (EEG), neuro-imaging, and neuropathology findings. Early recognition with prompt and aggressive seizure management is vital and may play a role in modifying the epileptogenic process and improving survival.

Standardized computer-based organized reporting of EEG: SCORE - Second version.

Standardized terminology for computer-based assessment and reporting of EEG has been previously developed in Europe. The International Federation of Clinical Neurophysiology established a taskforce in 2013 to develop this further, and to reach international consensus. This work resulted in the second, revised version of SCORE (Standardized Computer-based Organized Reporting of EEG), which is presented in this paper. The revised terminology was implemented in a software package (SCORE EEG), which was tested in clinical practice on 12,160 EEG recordings. Standardized terms implemented in SCORE are used to report the features of clinical relevance, extracted while assessing the EEGs. Selection of the terms is context sensitive: initial choices determine the subsequently presented sets of additional choices. This process automatically generates a report and feeds these features into a database. In the end, the diagnostic significance is scored, using a standardized list of terms. SCORE has specific modules for scoring seizures (including seizure semiology and ictal EEG patterns), neonatal recordings (including features specific for this age group), and for Critical Care EEG Terminology. SCORE is a useful clinical tool, with potential impact on clinical care, quality assurance, data-sharing, research and education.

Development of Performance and ERPs in a Flanker Task in Children and Adolescents with Tourette Syndrome-A Follow-Up Study.

Background: Tourette Syndrome (TS) is a neurodevelopmental disorder with childhood-onset, with a typical decline in tic severity, as well as an increasing ability to suppress tics in late childhood and adolescence. These processes develop in parallel with general improvement of self-regulatory abilities, and performance monitoring during this age-span. Hence, changes in performance monitoring over time might provide insight into the regulation of tics in children and adolescents with TS. Method: We measured reaction time, reaction time variability, accuracy, and event-related potentials (ERP) in 17 children with TS, including 10 children with comorbid Attention-Deficit/Hyperactivity Disorder (ADHD), 24 children with ADHD, and 29 typically developing children, using a modified Eriksen Flanker task in two testing sessions administered on average 4.5 years apart. We then compared task performance, as well as ERP components across groups, and over time using regression models. Results: Task performance improved in all groups with age, and behavioral differences between children with TS and controls diminished at second assessment, while differences between controls and children with ADHD largely persisted. In terms of ERP, the early P3 developed earlier in children with TS compared with controls at the first assessment, but trajectories converged with maturation. ERP component amplitudes correlated with worst-ever tic scores. Conclusions: Merging trajectories between children with TS and controls are consistent with the development of compensatory self-regulation mechanisms during early adolescence, probably facilitating tic suppression, in contrast to children with ADHD. Correlations between ERP amplitudes and tic scores also support this notion.

Regularized Linear Discriminant Analysis of EEG Features in Dementia Patients.

The present study explores if EEG spectral parameters can discriminate between healthy elderly controls (HC), Alzheimer's disease (AD) and vascular dementia (VaD) using. We considered EEG data recorded during normal clinical routine with 114 healthy controls (HC), 114 AD, and 114 VaD patients. The spectral features extracted from the EEG were the absolute delta power, decay from lower to higher frequencies, amplitude, center and dispersion of the alpha power and baseline power of the entire frequency spectrum. For discrimination, we submitted these EEG features to regularized linear discriminant analysis algorithm with a 10-fold cross-validation. To check the consistency of the results obtained by our classifiers, we applied bootstrap statistics. Four binary classifiers were used to discriminate HC from AD, HC from VaD, AD from VaD, and HC from dementia patients (AD or VaD). For each model, we measured the discrimination performance using the area under curve (AUC) and the accuracy of the cross-validation (cv-ACC). We applied this procedure using two different sets of predictors. The first set considered all the features extracted from the 22 channels. For the second set of features, we automatically rejected features poorly correlated with their labels. Fairly good results were obtained when discriminating HC from dementia patients with AD or VaD (AUC = 0.84). We also obtained AUC = 0.74 for discrimination of AD from HC, AUC = 0.77 for discrimination of VaD from HC, and finally AUC = 0.61 for discrimination of AD from VaD. Our models were able to separate HC from dementia patients, and also and to discriminate AD from VaD above chance. Our results suggest that these features may be relevant for the clinical assessment of patients with dementia.

Combined variants in reading epilepsy; coexisting anterior and posterior variants camouflaged as heat cramps where the patient finds his own diagnosis searching the internet.

Reading epilepsy is a form of reflex-induced seizures. Two entities are postulated as part of a clinical spectrum; one anterior variant with jaw jerks and orofacial myoclonia and another posterior variant with visual symptoms and alexia or dyslexia. We present a case with suggestible evidence of both conditions coexisting within the same patient, a finding that, to our knowledge, has not been previously reported. The diagnosis in this specific case was contributed to by the patient searching the internet.

Performance Monitoring in Medication-Naïve Children with Tourette Syndrome.

BACKGROUND: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder and its impact on cognitive development needs further study. Evidence from neuropsychological, neuroimaging and electrophysiological studies suggests that the decline in tic severity and the ability to suppress tics relate to the development of self-regulatory functions in late childhood and adolescence. Hence, tasks measuring performance monitoring might provide insight into the regulation of tics in children with TS. METHOD: Twenty-five children with TS, including 14 with comorbid Attention-deficit/ hyperactivity disorder (ADHD), 39 children with ADHD and 35 typically developing children aged 8-12 years were tested with a modified Eriksen-Flanker task during a 34-channel electroencephalography (EEG) recording. Task performance, as well as stimulus-locked and response-locked event-related potentials (ERP) were analyzed and compared across groups. RESULTS: Participants did not differ in their behavioral performance. Children with TS showed higher amplitudes of an early P3 component of the stimulus-locked ERPs in ensemble averages and in separate trial outcomes, suggesting heightened orienting and/or attention during stimulus evaluation. In response-locked averages, children with TS had a slightly higher positive complex before the motor response, likely also reflecting a late P3. Groups did not differ in post-response components, particularly in the error-related negativity (ERN) and error-related positivity (Pe). CONCLUSIONS: These findings suggest that children with TS may employ additional attentional resources as a compensatory mechanism to maintain equal behavioral performance.

Presupplementary Motor Area Contributes to Altered Error Monitoring in Obsessive-Compulsive Disorder.

BACKGROUND: Hyperactive performance monitoring, as measured by the error-related negativity (ERN) in the event-related potential, is a reliable finding in obsessive-compulsive disorder (OCD) research and may be an endophenotype of the disorder. Imaging studies revealed inconsistent results as to which brain regions are involved in altered performance monitoring in OCD. We investigated performance monitoring in OCD with simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) signals to determine the neural source of the enhanced ERN. METHODS: Concurrent EEG and fMRI data were collected from 20 patients with OCD and 22 healthy control subjects during a flanker task. Independent component analysis was used separately on EEG and fMRI to segment the data functionally and focus on processes of interest. The ERN, hemodynamic responses following errors, and intraindividual correlation of the ERN and blood oxygen level-dependent activity were compared between groups. RESULTS: Patients with OCD showed significantly increased ERN amplitudes. Blood oxygen level-dependent activity in midcingulate cortex was not significantly different between groups. Increased activation of the right amygdala and the subgenual anterior cingulate cortex following errors was observed in patients with OCD. Increased intraindividual correlation of the ERN and activity of the presupplementary motor area was found in patients with OCD compared with healthy controls. CONCLUSIONS: Higher error-related activity was found in the amygdala and subgenual anterior cingulate cortex, suggesting a stronger affective response toward errors in patients with OCD. Additionally, increased correlation of the ERN and presupplementary motor area may indicate stronger recruitment of proactive control in OCD.

Reduced error signalling in medication-naive children with ADHD: associations with behavioural variability and post-error adaptations.

BACKGROUND: We examined the blood-oxygen level-dependent (BOLD) activation in brain regions that signal errors and their association with intraindividual behavioural variability and adaptation to errors in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: We acquired functional MRI data during a Flanker task in medication-naive children with ADHD and healthy controls aged 8-12 years and analyzed the data using independent component analysis. For components corresponding to performance monitoring networks, we compared activations across groups and conditions and correlated them with reaction times (RT). Additionally, we analyzed post-error adaptations in behaviour and motor component activations. RESULTS: We included 25 children with ADHD and 29 controls in our analysis. Children with ADHD displayed reduced activation to errors in cingulo-opercular regions and higher RT variability, but no differences of interference control. Larger BOLD amplitude to error trials significantly predicted reduced RT variability across all participants. Neither group showed evidence of post-error response slowing; however, post-error adaptation in motor networks was significantly reduced in children with ADHD. This adaptation was inversely related to activation of the right-lateralized ventral attention network (VAN) on error trials and to task-driven connectivity between the cingulo-opercular system and the VAN. LIMITATIONS: Our study was limited by the modest sample size and imperfect matching across groups. CONCLUSION: Our findings show a deficit in cingulo-opercular activation in children with ADHD that could relate to reduced signalling for errors. Moreover, the reduced orienting of the VAN signal may mediate deficient post-error motor adaptions. Pinpointing general performance monitoring problems to specific brain regions and operations in error processing may help to guide the targets of future treatments for ADHD.

Acetylcholine mediates behavioral and neural post-error control.

Humans often commit errors when they are distracted by irrelevant information and no longer focus on what is relevant to the task at hand. Adjustments following errors are essential for optimizing goal achievement. The posterior medial frontal cortex (pMFC), a key area for monitoring errors, has been shown to trigger such post-error adjustments by modulating activity in visual cortical areas. However, the mechanisms by which pMFC controls sensory cortices are unknown. We provide evidence for a mechanism based on pMFC-induced recruitment of cholinergic projections to task-relevant sensory areas. Using fMRI in healthy volunteers, we found that error-related pMFC activity predicted subsequent adjustments in task-relevant visual brain areas. In particular, following an error, activity increased in those visual cortical areas involved in processing task-relevant stimulus features, whereas activity decreased in areas representing irrelevant, distracting features. Following treatment with the muscarinic acetylcholine receptor antagonist biperiden, activity in visual areas was no longer under control of error-related pMFC activity. This was paralleled by abolished post-error behavioral adjustments under biperiden. Our results reveal a prominent role of acetylcholine in cognitive control that has not been recognized thus far. Regaining optimal performance after errors critically depends on top-down control of perception driven by the pMFC and mediated by acetylcholine. This may explain the lack of adaptivity in conditions with reduced availability of cortical acetylcholine, such as Alzheimer's disease.

EEG Spectral Features Discriminate between Alzheimer's and Vascular Dementia.

Alzheimer's disease (AD) and vascular dementia (VaD) present with similar clinical symptoms of cognitive decline, but the underlying pathophysiological mechanisms differ. To determine whether clinical electroencephalography (EEG) can provide information relevant to discriminate between these diagnoses, we used quantitative EEG analysis to compare the spectra between non-medicated patients with AD (n = 77) and VaD (n = 77) and healthy elderly normal controls (NC) (n = 77). We use curve-fitting with a combination of a power loss and Gaussian function to model the averaged resting-state spectra of each EEG channel extracting six parameters. We assessed the performance of our model and tested the extracted parameters for group differentiation. We performed regression analysis in a multivariate analysis of covariance with group, age, gender, and number of epochs as predictors and further explored the topographical group differences with pair-wise contrasts. Significant topographical differences between the groups were found in several of the extracted features. Both AD and VaD groups showed increased delta power when compared to NC, whereas the AD patients showed a decrease in alpha power for occipital and temporal regions when compared with NC. The VaD patients had higher alpha power than NC and AD. The AD and VaD groups showed slowing of the alpha rhythm. Variability of the alpha frequency was wider for both AD and VaD groups. There was a general decrease in beta power for both AD and VaD. The proposed model is useful to parameterize spectra, which allowed extracting relevant clinical EEG key features that move toward simple and interpretable diagnostic criteria.

Equity theory and fair inequality: a neuroeconomic study.

The present paper reports results from, to our knowledge, the first study designed to examine the neuronal responses to income inequality in situations in which individuals have made different contributions in terms of work effort. We conducted an experiment that included a prescanning phase in which the participants earned money by working, and a neuronal scanning phase in which we examined how the brain responded when the participants evaluated different distributions of their earnings. We provide causal evidence for the relative contribution of work effort being crucial for understanding the hemodynamic response in the brain to inequality. We found a significant hemodynamic response in the striatum to deviations from the distribution of income that was proportional to work effort, but found no effect of deviations from the equal distribution of income. We also observed a striking correlation between the hemodynamic response in the striatum and the self-reported evaluation of the income distributions. Our results provide, to our knowledge, the first set of neuronal evidence for equity theory and suggest that people distinguish between fair and unfair inequalities.

Working memory networks and activation patterns in schizophrenia and bipolar disorder: comparison with healthy controls.

BACKGROUND: Schizophrenia and bipolar disorder are severe mental disorders with overlapping genetic and clinical characteristics, including cognitive impairments. An important question is whether these disorders also have overlapping neuronal deficits. AIMS: To determine whether large-scale brain networks associated with working memory, as measured with functional magnetic resonance imaging (fMRI), are the same in both schizophrenia and bipolar disorder, and how they differ from those in healthy individuals. METHOD: Patients with schizophrenia (n = 100) and bipolar disorder (n = 100) and a healthy control group (n = 100) performed a 2-back working memory task while fMRI data were acquired. The imaging data were analysed using independent component analysis to extract large-scale networks of task-related activations. RESULTS: Similar working memory networks were activated in all groups. However, in three out of nine networks related to the experimental task there was a graded response difference in fMRI signal amplitudes, where patients with schizophrenia showed greater activation than those with bipolar disorder, who in turn showed more activation than healthy controls. Secondary analysis of the patient groups showed that these activation patterns were associated with history of psychosis and current elevated mood in bipolar disorder. CONCLUSIONS: The same brain networks were related to working memory in schizophrenia, bipolar disorder and controls. However, some key networks showed a graded hyperactivation in the two patient groups, in line with a continuum of neuronal abnormalities across psychotic disorders.

Tracking whole-brain connectivity dynamics in the resting state.

Spontaneous fluctuations are a hallmark of recordings of neural signals, emergent over time scales spanning milliseconds and tens of minutes. However, investigations of intrinsic brain organization based on resting-state functional magnetic resonance imaging have largely not taken into account the presence and potential of temporal variability, as most current approaches to examine functional connectivity (FC) implicitly assume that relationships are constant throughout the length of the recording. In this work, we describe an approach to assess whole-brain FC dynamics based on spatial independent component analysis, sliding time window correlation, and k-means clustering of windowed correlation matrices. The method is applied to resting-state data from a large sample (n = 405) of young adults. Our analysis of FC variability highlights particularly flexible connections between regions in lateral parietal and cingulate cortex, and argues against a labeling scheme where such regions are treated as separate and antagonistic entities. Additionally, clustering analysis reveals unanticipated FC states that in part diverge strongly from stationary connectivity patterns and challenge current descriptions of interactions between large-scale networks. Temporal trends in the occurrence of different FC states motivate theories regarding their functional roles and relationships with vigilance/arousal. Overall, we suggest that the study of time-varying aspects of FC can unveil flexibility in the functional coordination between different neural systems, and that the exploitation of these dynamics in further investigations may improve our understanding of behavioral shifts and adaptive processes.

The learning-oddball paradigm: data of 24 separate individuals illustrate its potential usefulness as a new clinical tool.

OBJECTIVE: In a previous article reporting group data, we presented event-related potentials (ERPs), which were evoked by randomly presented target stimuli in a 'learning-oddball' task. These ERPs contained a large N2-P3 complex that decreased and a Contingent Negative Variation (CNV) that increased when the targets were presented in a regular fashion. Using the learning-oddball paradigm, the aim of the present paper was to determine ERP effects of introducing regularity in individual participants. METHODS: The data from the previous study were re-analyzed at the level of the individual participant, extracting individual sigmoid curves by means of wavelet-denoising and focusing on RTs, and CNV, N2, and P3 ERP components. RESULTS: Most participants displayed significant sigmoid curves with respect to the P3 component (22 of the 24 participants - 22/24), the N2 component (20/24), and/or the CNV (19/24) component. In contrast, reaction times (RTs) appeared less sensitive to incidental learning (15/24). Modest correlations were observed between RTs and N2 component amplitudes. CONCLUSIONS: It is possible to extract significant ERP changes to introducing regularity in individual participants. SIGNIFICANCE: Tracking ERP changes within the learning-oddball paradigm might be a useful tool to assess pattern detection capacities in individual patients.