Multimodal nocturnal seizure detection in children with epilepsy: A prospective, multicenter, long-term, in-home trial.

OBJECTIVE: There is a pressing need for reliable automated seizure detection in epilepsy care. Performance evidence on ambulatory non-electroencephalography-based seizure detection devices is low, and evidence on their effect on caregiver's stress, sleep, and quality of life (QoL) is still lacking. We aimed to determine the performance of NightWatch, a wearable nocturnal seizure detection device, in children with epilepsy in the family home setting and to assess its impact on caregiver burden. METHODS: We conducted a phase 4, multicenter, prospective, video-controlled, in-home NightWatch implementation study (NCT03909984). We included children aged 4-16 years, with ≥1 weekly nocturnal major motor seizure, living at home. We compared a 2-month baseline period with a 2-month NightWatch intervention. The primary outcome was the detection performance of NightWatch for major motor seizures (focal to bilateral or generalized tonic-clonic [TC] seizures, focal to bilateral or generalized tonic seizures lasting >30 s, hyperkinetic seizures, and a remainder category of focal to bilateral or generalized clonic seizures and "TC-like" seizures). Secondary outcomes included caregivers' stress (Caregiver Strain Index [CSI]), sleep (Pittsburgh Quality of Sleep Index), and QoL (EuroQol five-dimension five-level scale). RESULTS: We included 53 children (55% male, mean age = 9.7 ± 3.6 years, 68% learning disability) and analyzed 2310 nights (28 173 h), including 552 major motor seizures. Nineteen participants did not experience any episode of interest during the trial. The median detection sensitivity per participant was 100% (range = 46%-100%), and the median individual false alarm rate was .04 per hour (range = 0-.53). Caregiver's stress decreased significantly (mean total CSI score = 8.0 vs. 7.1, p = .032), whereas caregiver's sleep and QoL did not change significantly during the trial. SIGNIFICANCE: The NightWatch system demonstrated high sensitivity for detecting nocturnal major motor seizures in children in a family home setting and reduced caregiver stress.

Parental experiences and perspectives on the value of seizure detection while caring for a child with epilepsy: A qualitative study.

INTRODUCTION: Caring for a child with epilepsy has a significant impact on parental quality of life. Seizure unpredictability and complications, including sudden unexpected death in epilepsy (SUDEP), may cause high parental stress and increased anxiety. Nocturnal supervision with seizure detection devices may lower SUDEP risk and decrease parental burden of seizure monitoring, but little is known about their added value in family homes. METHODS: We conducted semi-structured in-depth interviews with parents of children with refractory epilepsy participating in the PROMISE trial (NCT03909984) to explore the value of seizure detection in the daily care of their child. Children were aged 4-16 years, treated at a tertiary epilepsy center, had at least one nocturnal major motor seizure per week, and used a wearable seizure detection device (NightWatch) for two months at home. Data were analyzed using inductive thematic analysis. RESULTS: Twenty three parents of nineteen children with refractory epilepsy were interviewed. All parents expressed their fear of missing a large seizure and the possible consequences of not intervening in time. Some parents felt the threat of child loss during every seizure, while others thought about it from time to time. The fear could fluctuate over time, mainly associated with fluctuations of seizure frequency. Most parents described how they developed a protective behavior, driven by this fear. The way parents handled the care of their child and experienced the burden of care influenced their perceptions on the added value of NightWatch. The experienced value of NightWatch depended on the amount of assurance it could offer to reduce their fear and the associated protective behavior as well as their resilience to handle the potential extra burden of care, due to false alarms or technical problems. CONCLUSION: Healthcare professionals and device companies should be aware of parental protective behavior and the high parental burden of care and develop tailored strategies to optimize seizure detection device care.

Automated video-based detection of nocturnal motor seizures in children.

Seizure detection devices can improve epilepsy care, but wearables are not always tolerated. We previously demonstrated good performance of a real-time video-based algorithm for detection of nocturnal convulsive seizures in adults with learning disabilities. The algorithm calculates the relative frequency content based on the group velocity reconstruction from video-sequence optical flow. We aim to validate the video algorithm on nocturnal motor seizures in a pediatric population. We retrospectively analyzed the algorithm performance on a database including 1661 full recorded nights of 22 children (age = 3-17 years) with refractory epilepsy at home or in a residential care setting. The algorithm detected 118 of 125 convulsions (median sensitivity per participant = 100%, overall sensitivity = 94%, 95% confidence interval = 61%-100%) and identified all 135 hyperkinetic seizures. Most children had no false alarms; 81 false alarms occurred in six children (median false alarm rate [FAR] per participant per night = 0 [range = 0-0.47], overall FAR = 0.05 per night). Most false alarms (62%) were behavior-related (eg, awake and playing in bed). Our noncontact detection algorithm reliably detects nocturnal epileptic events with only a limited number of false alarms and is suitable for real-time use.

Ictal autonomic changes as a tool for seizure detection: a systematic review.

PURPOSE: Adequate epileptic seizure detection may have the potential to minimize seizure-related complications and improve treatment evaluation. Autonomic changes often precede ictal electroencephalographic discharges and therefore provide a promising tool for timely seizure detection. We reviewed the literature for seizure detection algorithms using autonomic nervous system parameters. METHODS: The PubMed and Embase databases were systematically searched for original human studies that validate an algorithm for automatic seizure detection based on autonomic function alterations. Studies on neonates only and pilot studies without performance data were excluded. Algorithm performance was compared for studies with a similar design (retrospective vs. prospective) reporting both sensitivity and false alarm rate (FAR). Quality assessment was performed using QUADAS-2 and recently reported quality standards on reporting seizure detection algorithms. RESULTS: Twenty-one out of 638 studies were included in the analysis. Fifteen studies presented a single-modality algorithm based on heart rate variability (n = 10), heart rate (n = 4), or QRS morphology (n = 1), while six studies assessed multimodal algorithms using various combinations of HR, corrected QT interval, oxygen saturation, electrodermal activity, and accelerometry. Most studies had small sample sizes and a short follow-up period. Only two studies performed a prospective validation. A tendency for a lower FAR was found for retrospectively validated algorithms using multimodal autonomic parameters compared to those using single modalities (mean sensitivity per participant 71-100% vs. 64-96%, and mean FAR per participant 0.0-2.4/h vs. 0.7-5.4/h). CONCLUSIONS: The overall quality of studies on seizure detection using autonomic parameters is low. Unimodal autonomic algorithms cannot reach acceptable performance as false alarm rates are still too high. Larger prospective studies are needed to validate multimodal automatic seizure detection.

Glutamate concentrations vary with antiepileptic drug use and mental slowing.

OBJECTIVE: Although antiepileptic drugs (AEDs) are effective in suppressing epileptic seizures, they also induce (cognitive) side effects, with mental slowing as a general effect. This study aimed to assess whether concentrations of MR detectable neurotransmitters, glutamate and GABA, are associated with mental slowing in patients with epilepsy taking AEDs. METHODS: Cross-sectional data were collected from patients with localization-related epilepsy using a variety of AEDs from three risk categories, i.e., AEDs with low, intermediate, and high risks of developing cognitive problems. Patients underwent 3T MR spectroscopy, including a PRESS (n=55) and MEGA-PRESS (n=43) sequence, to estimate occipital glutamate and GABA concentrations, respectively. The association was calculated between neurotransmitter concentrations and central information processing speed, which was measured using the Computerized Visual Searching Task (CVST) and compared between the different risk categories. RESULTS: Combining all groups, patients with lower processing speeds had lower glutamate concentrations. Patients in the high-risk category had a lower glutamate concentration and lower processing speed compared with patients taking low-risk AEDs. Patients taking intermediate-risk AEDs also had a lower glutamate concentration compared with patients taking low-risk AEDs, but processing speed did not differ significantly between those groups. No associations were found between the GABA concentration and risk category or processing speed. CONCLUSIONS: For the first time, a relation is shown between glutamate concentration and both mental slowing and AED use. It is suggested that the reduced excitatory action, reflected by lowered glutamate concentrations, may have contributed to the slowing of information processing in patients using AEDs with higher risks of cognitive side effects.

Autonomic nervous system functioning associated with psychogenic nonepileptic seizures: Analysis of heart rate variability.

OBJECTIVE: Psychogenic nonepileptic seizures (PNESs) resemble epileptic seizures but originate from psychogenic rather than organic causes. Patients with PNESs are often unable or unwilling to reflect on underlying emotions. To gain more insight into the internal states of patients during PNES episodes, this study explored the time course of heart rate variability (HRV) measures, which provide information about autonomic nervous system functioning and arousal. METHODS: Heart rate variability measures were extracted from double-lead electrocardiography data collected during 1-7days of video-electroencephalography monitoring of 20 patients with PNESs, in whom a total number of 118 PNESs was recorded. Heart rate (HR) and HRV measures in time and frequency domains (standard deviation of average beat-to-beat intervals (SDANN), root mean square of successive differences (RMSSD), high-frequency (HF) power, low-frequency (LF) power, and very low-frequency (VLF) power) were averaged over consecutive five-minute intervals. Additionally, quantitative analyses of Poincaré plot parameters (SD1, SD2, and SD1/SD2 ratio) were performed. RESULTS: In the five-minute interval before PNES, HR significantly (p<0.05) increased (d=2.5), whereas SDANN (d=-0.03) and VLF power (d=-0.05) significantly decreased. During PNES, significant increases in HF power (d=0.0006), SD1 (d=0.031), and SD2 (d=0.016) were observed. In the five-minute interval immediately following PNES, SDANN (d=0.046) and VLF power (d=0.073) significantly increased, and HR (d=-5.1) and SD1/SD2 ratio (d=-0.14) decreased, compared to the interval preceding PNES. CONCLUSION: The results suggest that PNES episodes are preceded by increased sympathetic functioning, which is followed by an increase in parasympathetic functioning during and after PNES. Future research needs to identify the exact nature of the increased arousal that precedes PNES.

Neurophysiological correlates of dissociative symptoms.

OBJECTIVE: Dissociation is a mental process with psychological and somatoform manifestations, which is closely related to hypnotic suggestibility and essentially shows the ability to obtain distance from reality. An increased tendency to dissociate is a frequently reported characteristic of patients with functional neurological symptoms and syndromes (FNSS), which account for a substantial part of all neurological admissions. This review aims to investigate what heart rate variability (HRV), EEG and neuroimaging data (MRI) reveal about the nature of dissociation and related conditions. METHODS: Studies reporting HRV, EEG and neuroimaging data related to hypnosis, dissociation and FNSS were identified by searching the electronic databases Pubmed and ScienceDirect. RESULTS: The majority of the identified studies concerned the physiological characteristics of hypnosis; relatively few investigations on dissociation related FNSS were identified. General findings were increased parasympathetic functioning during hypnosis (as measured by HRV), and lower HRV in patients with FNSS. The large variety of EEG and functional MRI investigations with diverse results challenges definite conclusions, but evidence suggests that subcortical as well as (pre)frontal regions serve emotion regulation in dissociative conditions. Functional connectivity analyses suggest the presence of altered brain networks in patients with FNSS, in which limbic areas have an increased influence on motor preparatory regions. CONCLUSIONS: HRV, EEG and (functional) MRI are sensitive methods to detect physiological changes related to dissociation and dissociative disorders such as FNSS, and can possibly provide more information about their aetiology. The use of such measures could eventually provide biomarkers for earlier identification of patients at risk and appropriate treatment of dissociative conditions.

Pitfalls in EEG Analysis in Patients With Nonconvulsive Status Epilepticus: A Preliminary Study.

Objective: Electroencephalography (EEG) interpretations through visual (by human raters) and automated (by computer technology) analysis were still not reliable for the diagnosis of nonconvulsive status epilepticus (NCSE). This study aimed to identify typical pitfalls in the EEG analysis and make suggestions as to how those pitfalls might be avoided. Methods: We analyzed the EEG recordings of individuals who had clinically confirmed or suspected NCSE. Epileptiform EEG activity during seizures (ictal discharges) was visually analyzed by 2 independent raters. We investigated whether unreliable EEG visual interpretations quantified by low interrater agreement can be predicted by the characteristics of ictal discharges and individuals' clinical data. In addition, the EEG recordings were automatically analyzed by in-house algorithms. To further explore the causes of unreliable EEG interpretations, 2 epileptologists analyzed EEG patterns most likely misinterpreted as ictal discharges based on the differences between the EEG interpretations through the visual and automated analysis. Results: Short ictal discharges with a gradual onset (developing over 3 s in length) were liable to be misinterpreted. An extra 2 min of ictal discharges contributed to an increase in the kappa statistics of >0.1. Other problems were the misinterpretation of abnormal background activity (slow-wave activities, other abnormal brain activity, and the ictal-like movement artifacts), continuous interictal discharges, and continuous short ictal discharges. Conclusion: A longer duration criterion for NCSE-EEGs than 10 s that is commonly used in NCSE working criteria is recommended. Using knowledge of historical EEGs, individualized algorithms, and context-dependent alarm thresholds may also avoid the pitfalls.

Functional connectivity of dissociation in patients with psychogenic non-epileptic seizures.

INTRODUCTION: Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures, but lack epileptiform brain activity. Instead, the cause is assumed to be psychogenic. An abnormal coping strategy may be exhibited by PNES patients, as indicated by their increased tendency to dissociate. Investigation of resting-state networks may reveal altered routes of information and emotion processing in PNES patients. The authors therefore investigated whether PNES patients differ from healthy controls in their resting-state functional connectivity characteristics and whether these connections are associated with the tendency to dissociate. METHODS: 11 PNES patients without psychiatric comorbidity and 12 healthy controls underwent task-related paradigms (picture-encoding and Stroop paradigms) and resting-state functional MRI (rsfMRI). Global cognitive performance was tested using the Raven's Matrices test and participants completed questionnaires for evaluating dissociation. Functional connectivity analysis on rsfMRI was based on seed regions extracted from task-related fMRI activation maps. RESULTS: The patients displayed a significantly lower cognitive performance and significantly higher dissociation scores. No significant differences were found between the picture-encoding and Stroop colour-naming activation maps between controls and patients with PNES. However, functional connectivity maps from the rsfMRI were statistically different. For PNES patients, stronger connectivity values between areas involved in emotion (insula), executive control (inferior frontal gyrus and parietal cortex) and movement (precentral sulcus) were observed, which were significantly associated with dissociation scores. CONCLUSION: The abnormal, strong functional connectivity in PNES patients provides a neurophysiological correlate for the underlying psychoform and somatoform dissociation mechanism where emotion can influence executive control, resulting in altered motor function (eg, seizure-like episodes).

Multimodal nocturnal seizure detection: Do we need to adapt algorithms for children?

OBJECTIVE: To assess the performance of a multimodal seizure detection device, first tested in adults (sensitivity 86%, PPV 49%), in a pediatric cohort living at home or residential care. METHODS: In this multicenter, prospective, video-controlled cohort-study, nocturnal seizures were detected by heartrate and movement changes in children with epilepsy and intellectual disability. Participants with a history of >1 monthly major motor seizure wore Nightwatch bracelet at night for 3 months. Major seizures were defined as tonic-clonic, generalized tonic >30 s, hyperkinetic, or clusters (>30 min) of short myoclonic or tonic seizures. The video of all events (alarms and nurse diaries) and about 10% of whole nights were reviewed to classify major seizures, and minor or no seizures. RESULTS: Twenty-three participants with focal or generalized epilepsy and nightly motor seizures were evaluated during 1511 nights, with 1710 major seizures. First 1014 nights, 4189 alarms occurred with average of 1.44/h, showing average sensitivity of 79.9% (median 75.4%) with mean PPV of 26.7% (median 11.1%) and false alarm rate of 0.2/hour. Over 90% of false alarms in children was due to heart rate (HR) part of the detection algorithm. To improve this rate, an adaptation was made such that the alarm was only triggered when the wearer was in horizontal position. For the remaining 497 nights, this was tested prospectively, 384 major seizures occurred. This resulted in mean PPV of 55.5% (median 58.1%) and a false alarm rate 0.08/h while maintaining a comparable mean sensitivity of 79.4% (median 93.2%). SIGNIFICANCE: Seizure detection devices that are used in bed which depend on heartrate and movement show similar sensitivity in children and adults. However, children do show general higher false alarm rate, mostly triggered while awake. By correcting for body position, the false alarms can be limited to a level that comes close to that in adults.

MMPI-II personality profiles of patients with psychogenic nonepileptic seizures.

This comparative study explored whether psychogenic nonepileptic seizures (PNES) are a unique disorder with distinctive personality characteristics or (seen from the personality profile) PNES are allied with the domain of a general functional somatic symptom and syndrome (FSSS). We compared the Minnesota Multiphasic Personality Inventory 2 (MMPI-2) results for 41 patients with newly diagnosed PNES and 43 patients with newly diagnosed insomnia. There were no statistically significant quantitative scoring differences on the main clinical scales, indicating that there is no substantial difference in "personality makeup" between the two groups with a FSSS. Additional subscale analysis indicated that patients with PNES reported significantly more somatic complaints (Hysteria 4) and bizarre sensory experiences (Schizophrenia 6). Further profile analysis revealed that the personality pattern of patients with PNES was characterized by a strong tendency toward "conversion V, a lack of control pattern and less excessive worries" as compared with patients with insomnia. Patients with PNES are characterized by a stronger tendency toward somatization and externalization, which has treatment implications.

Evaluation of two anti-seizure medication strategies in refractory epilepsy patients from a tertiary center with complementary insights from data visualization.

OBJECTIVE: To evaluate the healthcare resources in a tertiary center related to exclusive use of non-enzyme inducing anti-seizure medications relative to concomitant use of enzyme-inducing anti-seizure medications in patients with refractory epilepsy. METHODS: In this retrospective case-time-control study, we compared the effects of two anti-seizure medication strategies: exclusively non-inducing anti-seizure medications (NIND) or a combination of NIND and inducing anti-seizure medications (IND+). The primary outcome parameter was the number of consultations with relevant healthcare professionals in our tertiary center, assessed with a negative binomial regression model, adjusting for several covariates like blood drug level and time interval (TI). Results from statistical models were visualized to explore the contribution of all covariates on the outcome in the total population and in subgroups. RESULTS: From the 21538 patients with refractory epilepsy referred to our center 1648 patients met the inclusion criteria. The regression model showed that the IND + strategy was significantly associated with fewer consultations compared to the NIND strategy (p < 0.001), reflected in an incidence risk ratio (IRR) of 0.844 (0.799-0.890). Visualization of subgroups, defined by anti-seizure medications strategy, revealed patterns in contribution of blood drug level measurements on the outcome. Although sex was not included as a covariate in the regression model, as it was eliminated by the backward-elimination approach, visualization of this subgroup showed differences in effects of blood drug level and TI. CONCLUSION: For patients with refractory epilepsy in our tertiary center, treatment following the IND + strategy is associated with fewer consultations with healthcare professionals compared to the NIND strategy. Comprehensive visualization of the results facilitated the exploration of effects of covariates across subgroups.

Psychogenic nonepileptic seizures in adults with epilepsy and intellectual disability: A neglected area.

PURPOSE: To describe the main characteristics of psychogenic nonepileptic seizures (PNES) in adults with epilepsy and intellectual disability (ID), and to analyse the differences regarding psychosocial functioning, epilepsy severity and ID between patients with PNES and a control group without PNES. METHODS: Medical records of adults with ID and epilepsy living at an epilepsy care facility (N = 240) were screened for PNES and evaluated by a neurologist. A control group consisting of patients with epilepsy and ID, without PNES, was matched according to age, sex and level of ID. Characteristics of PNES and epilepsy were provided by the subject's nursing staff or retrieved from patient charts, psychosocial data were collected by standardised questionnaires and level of ID was individually assessed using psychometric instruments. RESULTS: The point prevalence of PNES was 7.1%. The patients with PNES (n = 15) were most often female and had a mild or moderate level of ID. Compared to controls, they showed more depressive symptoms, experienced more negative life events and had more often an ID discrepancy (ID profile with one domain particularly more impaired than another). Stress-related triggers were recognised in a large majority by the nursing staff. CONCLUSION: PNES appears to be a relatively rare diagnostic entity among inpatients with both epilepsy and ID. However, the complexity of diagnosing PNES in this population, and the similarities in stress-related triggers for PNES in patients with and without ID, suggest that PNES may be underdiagnosed in the ID population. Diagnostic challenges of PNES and, as subcategory, reinforced behavioural patterns are discussed.

Chronic antiepileptic drug use and functional network efficiency: A functional magnetic resonance imaging study.

AIM: To increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug (AED) treatment. METHODS: The relation between functional magnetic resonance-acquired brain network measures, AED use, and cognitive function was investigated. Three groups of patients with epilepsy with a different risk profile for developing cognitive side effects were included: A "low risk" category (lamotrigine or levetiracetam, n = 16), an "intermediate risk" category (carbamazepine, oxcarbazepine, phenytoin, or valproate, n = 34) and a "high risk" category (topiramate, n = 5). Brain connectivity was assessed using resting state functional magnetic resonance imaging and graph theoretical network analysis. The Computerized Visual Searching Task was used to measure central information processing speed, a common cognitive side effect of AED treatment. RESULTS: Central information processing speed was lower in patients taking AEDs from the intermediate and high risk categories, compared with patients from the low risk category. The effect of risk category on global efficiency was significant (P < 0.05, ANCOVA), with a significantly higher global efficiency for patient from the low category compared with the high risk category (P < 0.05, post-hoc test). Risk category had no significant effect on the clustering coefficient (ANCOVA, P > 0.2). Also no significant associations between information processing speed and global efficiency or the clustering coefficient (linear regression analysis, P > 0.15) were observed. CONCLUSION: Only the four patients taking topiramate show aberrant network measures, suggesting that alterations in functional brain network organization may be only subtle and measureable in patients with more severe cognitive side effects.

Medial temporal lobe activity during semantic classification using a flexible fMRI design.

In this study, we evaluated the use of a self-paced fMRI design, to allow a flexible speed of responding with only four alternating stimulus blocks to minimize the influence of task switching on a group of young subjects. This was done in view of our intention to use such a design on groups of elderly and demented subjects in the near future. In addition, the hypothesis was tested that the medial temporal lobe is involved in semantic memory similar to episodic memory using a semantic retrieval task. In line with previous imaging studies that compared a semantic (living/nonliving) to a perceptual (alphabetically ascending/descending) classification condition, activity was seen in lateral temporal and inferior frontal regions, indicating the applicability of our design. Additional activity was seen in the right, and, at a slightly lower threshold, also in the left MTL, providing support for the involvement of the MTL in retrieval from semantic memory.

A paced visual serial addition test for fMRI.

BACKGROUND AND PURPOSE: The Paced Auditory Serial Attention Task (PASAT) is an attention and information processing task used in patients with diffuse brain disorders, like cerebral trauma and multiple sclerosis (MS). Based on the PASAT we used a adapted version of the test to assess several cognitive functions with fMRI. In this study we investigated the activation pattern on a group and individual level and upon parametric stimulation. METHODS: Nine young, healthy, right-handed subjects (mean age 24 years) were studied. The test contrasts an adding-and-memory stage with a control stage in a block design, at two different speeds. Group average maps (random effects analysis, p=0.05) were created to identify the brain areas subserving this task. For each area found active in the group map, the percentage of individuals showing activation in that same anatomical area was calculated. RESULTS: Group activation was localized in the superior and inferior parietal lobe bilaterally, the superior frontal gyrus bilaterally, the left medial frontal gyrus, the left inferior frontal gyrus and adjacent part of the insula, the anterior part of the cingulate gyrus and some cerebellar areas. For the main activated areas, 78-100% of the individual subjects showed activation in that same area. Contrasting the low speed with the high speed condition yielded activation with a considerable individual variation. CONCLUSION: The group mean activated areas were located mainly in the frontal and parietal lobes and those areas were also activated in the majority of the subjects, indicating limited inter-individual variation, rendering this test suitable for clinical applications in a variety of neurological disorders.

Resting-state networks and dissociation in psychogenic non-epileptic seizures.

OBJECTIVE: Psychogenic non-epileptic seizures (PNES) are epilepsy-like episodes which have an emotional rather than organic origin. Although PNES have often been related to the process of dissociation, the psychopathology is still poorly understood. To elucidate underlying mechanisms, the current study applied independent component analysis (ICA) on resting-state fMRI to investigate alterations within four relevant networks, associated with executive, fronto-parietal, sensorimotor, and default mode activation, and within a visual network to examine specificity of between-group differences. METHODS: Twenty-one patients with PNES without psychiatric or neurologic comorbidities and twenty-seven healthy controls underwent resting-state functional MR imaging at 3.0T (Philips Achieva). Additional neuropsychological testing included Raven's Matrices test and dissociation questionnaires. ICA with dual regression was used to identify resting-state networks in all participants, and spatial maps of the networks of interest were compared between patients and healthy controls. RESULTS: Patients displayed higher dissociation scores, lower cognitive performance and increased contribution of the orbitofrontal, insular and subcallosal cortex in the fronto-parietal network; the cingulate and insular cortex in the executive control network; the cingulate gyrus, superior parietal lobe, pre- and postcentral gyri and supplemental motor cortex in the sensorimotor network; and the precuneus and (para-) cingulate gyri in the default-mode network. The connectivity strengths within these regions of interest significantly correlated with dissociation scores. No between-group differences were found within the visual network, which was examined to determine specificity of between-group differences. CONCLUSIONS: PNES patients displayed abnormalities in several resting-state networks that provide neuronal correlates for an underlying dissociation mechanism.

Neurophysiological correlates of increased verbal working memory in high-dissociative participants: a functional MRI study.

BACKGROUND: Dissociation, defined as a disruption in usually integrated mental functions, is found not only in DSM-IV dissociative disorders, but also in post-traumatic stress disorder and eating disorders. Dissociative phenomena are also common in the general population, and may reflect a constitutionally determined cognitive style rather than a pathological trait acquired through experiencing adverse life events. In pathological dissociation, evidence has been presented for episodic memory dysfunction. In contrast, in high-dissociative subjects increased performance has been found for episodic memory and dual task performance. These findings have been linked to changes in working memory capacity. METHOD: In the present study, the authors sought to extend these findings by using functional magnetic resonance imaging during performance of two parametric working memory tasks. We tested 21 healthy low- and high-dissociative participants. RESULTS: High-dissociative participants performed slightly better during both tasks. Imaging data showed that both groups activated similar networks for both tasks, i.e. (bilateral) dorsolateral (DL) and ventrolateral prefrontal cortex (PFC), parietal cortex, and supplementary motor area. Group x task interactions were found in the high-dissociative group in L DLPFC and L parietal cortex; in the low-dissociative group in R fusiform gyrus. The differences in the high-dissociative group were independent from performance differences, implying that high-dissociative subjects generally recruit this network to a greater extent. CONCLUSIONS: These results confirm earlier findings using a verbal WM task in high-dissociative participants, and are compatible with the conceptualization of non-pathological dissociation as an information-processing style, characterized by distinct attentional and mnemonic abilities.

An fMRI study of planning-related brain activity in patients with moderately advanced multiple sclerosis.

INTRODUCTION: Cognitive impairment occurs in a substantial number of multiple sclerosis (MS) patients and often includes frontal lobe dysfunction. We used functional magnetic resonance imaging (fMRI) to study planning, an executive function, in moderately impaired MS patients. METHODS: An fMRI version of the Tower of London (ToL) test was used to study patterns of brain activation in 23 MS patients and 18 healthy controls. The median score on the Expanded Disability Status Scale (EDSS) for the MS patients was 4. fMRI data were analysed using whole brain random effects analysis as well as region of interest (ROI)-based methods to assess group effects. Within the MS group, associations with behavioural data and measures of disease severity (lesion load from structural MRI) were examined. RESULTS: Test performance in MS patients was significantly worse than in controls. Group analysis for the MS patients and the controls showed for both groups globally the same areas of activation, located in the frontal and parietal lobes bilaterally and the cerebellum. Although visual inspection suggested a larger extent of activation in the MS group, no statistically significant differences between groups were found. In the ROI analysis, statistically significant larger extent of activation was only found in the cerebellum. No association between disease severity and brain activity could be determined in the MS group. CONCLUSION: In MS patients with moderate disability and structural damage, the pattern and extent of brain activation during planning were maintained despite poorer performance. In contrast to other studies showing increased activity, the failure to do so in our group may reflect exhaustion of adaptive mechanisms.

Frontostriatal system in planning complexity: a parametric functional magnetic resonance version of Tower of London task.

In the present study, we sought to investigate which brain structures are recruited in planning tasks of increasing complexity. For this purpose, a parametric self-paced pseudo-randomized event-related functional MRI version of the Tower of London task was designed. We tested 22 healthy subjects, enabling assessment of imaging results at a second (random effects) level of analysis. Compared with baseline, planning activity was correlated with increased blood oxygenation level-dependent (BOLD) signal in the dorsolateral prefrontal cortex, striatum, premotor cortex, supplementary motor area, and visuospatial system (precuneus and inferior parietal cortex). Task load was associated with increased activity in these same regions. In addition, increasing task complexity was correlated with activity in the left anterior prefrontal cortex, a region supposed to be specifically involved in third-order higher cognitive functioning.