Visualization of the Spatiotemporal Propagation of Interictal Spikes in Temporal Lobe Epilepsy: A MEG Pilot Study.

Magnetoencephalography (MEG) is clinically used to localize interictal spikes in discrete brain areas of epilepsy patients through the equivalent current dipole (ECD) method, but does not account for the temporal dynamics of spike activity. Recent studies found that interictal spike propagation beyond the temporal lobe may be associated with worse postsurgical outcomes, but studies using whole-brain data such as in MEG remain limited. In this pilot study, we developed a tool that visualizes the spatiotemporal dynamics of interictal MEG spikes normalized to spike-free sleep activity to assess their onset and propagation patterns in patients with temporal lobe epilepsy (TLE). We extracted interictal source data containing focal epileptiform activity in awake and asleep states from seven patients whose MEG ECD clusters localized to the temporal lobe and normalized the data against spike-free sleep recordings. We calculated the normalized activity over time per cortical label, confirmed maximal activity at onset, and mapped the activity over a 10 ms interval onto each patient's brain using a custom-built Multi-Modal Visualization Tool. The onset of activity in all patients appeared near the clinically determined epileptogenic zone. By 10 ms, four of the patients had propagated source activity restricted to within the temporal lobe, and three had propagated source activity spread to extratemporal regions. Using this tool, we show that noninvasively identifying the onset and propagation of interictal spike activity in MEG can be achieved, which may help provide further insight into epileptic networks and guide surgical planning and interventions in patients with TLE.

Deficiency in Re-Orienting of Attention in Adults with Attention-Deficit Hyperactivity Disorder.

Objective: To characterize potential brain indexes of attention deficit hyperactivity disorder (ADHD) in adults. Methods: In an effort to develop objective, laboratory-based tests that can help to establish ADHD diagnosis, the brain indexes of distractibility was investigated in a group of adults. We used event-related brain potentials (ERPs) and performance measures in a forced-choice visual task. Results: Behaviorally aberrant distractibility in the ADHD group was significantly higher. Across three ERP components of distraction: N1 enhancement, P300 (P3a), and Reorienting Negativity (RON) the significant difference between ADHD and matched controls was found in the amplitude of the RON. We used non-parametric randomization tests, enabling us to statistically validated this difference between-group. Conclusions: Our main results of this feasibility study suggest that among other ERP components associated with auditory distraction, the RON response is promising index for a potential biomarker of deficient re-orienting of attention in adults s with ADHD.

Child Neurology: Functional Evaluation of the Dominant Hemisphere Using Magnetoencephalography Prior to Hemispherectomy.

Rasmussen encephalitis is a devastating progressive inflammatory disorder that leads to debilitating neurologic deficits and intractable epilepsy. Surgical treatment of the dominant hemisphere has been attempted with hesitation, given the lack of effective diagnostic tools to determine the potential functional deficits from disconnection procedures.

Delayed brain development of Rolandic epilepsy profiled by deep learning-based neuroanatomic imaging.

OBJECTIVES: Although Rolandic epilepsy (RE) has been regarded as a brain developmental disorder, neuroimaging studies have not yet ascertained whether RE has brain developmental delay. This study employed deep learning-based neuroanatomic biomarker to measure the changed feature of "brain age" in RE. METHODS: The study constructed a 3D-CNN brain age prediction model through 1155 cases of typically developing children's morphometric brain MRI from open-source datasets and further applied to a local dataset of 167 RE patients and 107 typically developing children. The brain-predicted age difference was measured to quantitatively estimate brain age changes in RE and further investigated the relevancies with cognitive and clinical variables. RESULTS: The brain age estimation network model presented a good performance for brain age prediction in typically developing children. The children with RE showed a 0.45-year delay of brain age by contrast with typically developing children. Delayed brain age was associated with neuroanatomic changes in the Rolandic regions and also associated with cognitive dysfunction of attention. CONCLUSION: This study provided neuroimaging evidence to support the notion that RE has delayed brain development. KEY POINTS: • The children with Rolandic epilepsy showed imaging phenotypes of delayed brain development with increased GM volume and decreased WM volume in the Rolandic regions. • The children with Rolandic epilepsy had a 0.45-year delay of brain-predicted age by comparing with typically developing children, using 3D-CNN-based brain age prediction model. • The delayed brain age was associated with morphometric changes in the Rolandic regions and attentional deficit in Rolandic epilepsy.

Cortico-striato-thalamo-cerebellar networks of structural covariance underlying different epilepsy syndromes associated with generalized tonic-clonic seizures.

Generalized tonic-clonic seizures (GTCS) are the severest and most remarkable clinical expressions of human epilepsy. Cortical, subcortical, and cerebellar structures, organized with different network patterns, underlying the pathophysiological substrates of genetic associated epilepsy with GTCS (GE-GTCS) and focal epilepsy associated with focal to bilateral tonic-clonic seizure (FE-FBTS). Structural covariance analysis can delineate the features of epilepsy network related with long-term effects from seizure. Morphometric MRI data of 111 patients with GE-GTCS, 111 patients with FE-FBTS and 111 healthy controls were studied. Cortico-striato-thalao-cerebellar networks of structural covariance within the gray matter were constructed using a Winner-take-all strategy with five cortical parcellations. Comparisons of structural covariance networks were conducted using permutation tests, and module effects of disease duration on networks were conducted using GLM model. Both patient groups showed increased connectivity of structural covariance relative to controls, mainly within the striatum and thalamus, and mostly correlated with the frontal, motor, and somatosensory cortices. Connectivity changes increased as a function of epilepsy durations. FE-FBTS showed more intensive and extensive gray matter changes with volumetric loss and connectivity increment than GE-GTCS. Our findings implicated cortico-striato-thalamo-cerebellar network changes at a large temporal scale in GTCS, with FE-FBTS showing more severe network disruption. The study contributed novel imaging evidence for understanding the different epilepsy syndromes associated with generalized seizures.

Auditory-vocal control system is object for predictive processing within seconds time range.

Predictive processing across hierarchically organized time scales is one of the fundamental principles of neural computations in the cerebral cortex. We hypothesize that relatively complex aggregation of auditory and vocal brain systems that use auditory feedback for reflexive control of vocalizations can be an object for predictive processing. We used repetitive patterns of perturbations in auditory feedback during vocalizations to elicit implicit expectations that were violated by surprising direction of perturbations in one of the experimental conditions. Our results provide empirical support for the idea that formation of expectancy for integrated auditory-vocal brain systems, within the time range of seconds, resulted in two sequential neuronal processes. The first process reflects monitoring and error detection in prediction about perturbations in auditory feedback during vocalizations within the time range of seconds. The second neuronal process can be attributed to the optimization of brain predictions for sensory contingencies during vocalizations at separable and distinct timescales.

Insomnia in shift work disorder relates to occupational and neurophysiological impairment.

STUDY OBJECTIVES: To determine whether occupational and neurophysiological decrements within shift work disorder (SWD) are differentially related to its two diagnostic symptoms, insomnia and excessive sleepiness. METHODS: Thirty-four permanent night workers participated in an overnight lab protocol including a multiple sleep latency test (MSLT) and an event-related brain potential (ERP) task testing auditory target detection (P3a and P3b). At 16:00, each subject completed an Endicott Work Productivity Scale (EWPS), two Insomnia Severity Indices (ISI-Day, ISI-Night), and an Epworth Sleepiness Scale (ESS). Subjects were grouped by ISI and ESS scores into clinical phenotypes. This study compared EWPS and ERP results between alert insomniacs ("AI," reporting insomnia without sleepiness), sleepy insomniacs ("SI," reporting both insomnia and sleepiness), and controls. RESULTS: The AI group was most impaired on the EWPS, significantly more impaired than controls (25.8 ± 14.8 vs. 12.3 ± 9.4, p < 0.05). SI were not statistically different from controls (19.5 ± 8.7 vs. 12.3 ± 9.4, p > 0.05). Compared to controls, AI showed significantly attenuated P3a response (Fcz, Czp, Cpz, mean difference [MD] 1.62-1.77, p < 0.05) and target-detection P3b response (Fcz, Czp, Cpz, MD 1.28-1.64, p < 0.05). P3b in SI was not different from controls (p > 0.10), and P3a was only different at one electrode site (Cpz, MD 1.43, p < 0.01). Neither the MSLT nor the ESS correlated with EWPS scores or ERP (P3a/P3b) amplitudes (p > 0.10). However, the mean of the ISI measurements correlated with the EWPS (r = 0.409, p < 0.01) and the attention-to-novelty P3a (r = -0.410, p < 0.01). CONCLUSIONS: Among shift work disorder patients, insomnia is linked to functional and cognitive impairments. Insomniacs with normal sleepiness showed more severe impairments than insomniacs who also reported excessive sleepiness.

Length polymorphism in the Period 3 gene is associated with sleepiness and maladaptive circadian phase in night-shift workers.

The objective of the current study was to determine if night-shift workers carrying the five-repeat variant of the Period 3 gene show elevated levels of nocturnal sleepiness and earlier circadian phase compared with homozygotes for the four-repeat allele. Twenty-four permanent night-shift workers were randomly selected from a larger study. Participants took part in an observational laboratory protocol including an overnight multiple sleep latency test and half-hourly saliva collection for calculation of dim-light melatonin onset. Period 3(-/5) shift workers had significantly lower multiple sleep latency test during overnight work hours compared with Period 3(4/4) workers (3.52 ± 23.44 min versus 10.39 ± 6.41 min, P = 0.003). We observed no significant difference in sleepiness during early morning hours following acute sleep deprivation. Long-allele carriers indicated significantly higher sleepiness on the Epworth Sleepiness Scale administered at 17:00 hours (12.08 ± 2.55 versus 8.00 ± 1.94, P < 0.001). We observed a significantly earlier melatonin onset in Period 3(-/5) individuals compared with Period 3(4/4) shift workers (20:44 ± 6:37 versus 02:46 ± 4:58, P = 0.021). Regression analysis suggests that Period 3 genotype independently predicts sleepiness even after controlling for variations in circadian phase, but we were unable to link Period 3 to circadian phase when controlling for sleepiness. Period 3(-/5) shift workers showed both subjective and objective sleepiness in the pathological range, while their Period 3(4/4) counterparts showed sleepiness within normal limits. Period 3(-/5) night workers also show a mean circadian phase 6 h earlier (i.e. less adapted) than Period 3(4/4) workers. Because Period 3(-/5) workers have maladaptive circadian phase as well as pathological levels of sleepiness, they may be at greater risk for occupational and automotive accidents. We interpret these findings as a call for future research on the role of Period 3 in sleepiness and circadian phase, especially as they relate to night work.

Differential sleep, sleepiness, and neurophysiology in the insomnia phenotypes of shift work disorder.

STUDY OBJECTIVES: To characterize and compare insomnia symptoms within two common phenotypes of Shift Work Disorder. DESIGN: Observational laboratory and field study. SETTING: Hospital sleep center. PARTICIPANTS: 34 permanent night workers. Subjects were classified by Epworth Sleepiness Scale and Insomnia Severity Index into 3 subgroups: asymptomatic controls, alert insomniacs (AI), and sleepy insomniacs (SI). MEASUREMENTS: Sleep parameters were assessed by sleep diary. Circadian phase was evaluated by dim-light salivary melatonin onset (DLMO). Objective sleepiness was measured using the multiple sleep latency test (MSLT). Brain activity was measured using the N1 event-related potential (ERP). A tandem repeat in PER3 was genotyped from saliva DNA. RESULTS: (1) AI group showed normal MSLT scores but elevated N1 amplitudes indicating cortical hyperarousal. (2) SI group showed pathologically low MSLT scores but normal N1 amplitudes. (3) AI and SI groups were not significantly different from one another in circadian phase, while controls were significantly phase-delayed relative to both SWD groups. (4) AI showed significantly longer sleep latencies and lower sleep efficiency than controls during both nocturnal and diurnal sleep. SI significantly differed from controls in nocturnal sleep parameters, but differences during diurnal sleep periods were smaller and not statistically significant. (5) Genotype × phenotype χ² analysis showed significant differences in the PER3 VNTR: 9 of 10 shift workers reporting sleepiness in a post hoc genetic substudy were found to carry the long tandem repeat on PER3, while 4 of 14 shift workers without excessive sleepiness carried the long allele. CONCLUSIONS: Our results suggest that the sleepy insomnia phenotype is comprehensively explained by circadian misalignment, while the alert insomnia phenotype resembles an insomnia disorder precipitated by shift work.

Effects of armodafinil on simulated driving and alertness in shift work disorder.

STUDY OBJECTIVES: Forty-one percent of shift workers report dozing while driving. This study tested whether armodafinil improves driving simulator performance in subjects with shift work disorder (SWD). A primary outcome was performance late in the shift when workers are typically driving home. DESIGN: Randomized, double-blind, crossover. During each 12-h test session (21:30-09:30), subjects were kept awake except for multiple sleep latency testing (MSLT: 01:30, 03:30, 05:30, and 07:30). Subjective sleepiness (Karolinska Sleepiness Scale, KSS), driving performance, and cognitive performance (digit symbol substitution test and creativity on the Remote Associates Test, RAT) were evaluated during the night shift and commute home times. SETTING: Hospital-based sleep research laboratory. PARTICIPANTS: Twenty night workers (age: 42.7 ± 8.7 y, 17 F) with excessive sleepiness (≥ 10 on the Epworth Sleepiness Scale), meeting International Classification of Sleep Disorders, Second Edition (ICSD-2) criteria for SWD, and having no other medical conditions. INTERVENTIONS: Armodafinil (150 mg) or placebo at (23:45 h) on counterbalanced nights separated by 7-14 days. MEASUREMENT AND RESULTS: Primary endpoints were driving simulator performance (standard deviation of lateral position (SDLP) and off-road deviations) with four sessions starting 3.25 h after drug administration, objective sleepiness (MSLT; 1.75 to 7.75 h post-drug), and creativity (5 h post-drug). Significant effects of drug were observed for each driving measure (P < 0.05). Armodafinil significantly improved SDLP for simulator sessions at 05:30, 07:30, and 09:30, and off-road deviations at 7 h, 15 min and 9 h, 15 min post-drug (P < 0.05). Armodafinil also improved objective sleepiness from 3.7 ± 0.6 min to 9.7 ± 5.2 min (P < 0.001) and RAT score from 8.75 ± 4.9 to 11.25 ± 6.0 (P < 0.005). CONCLUSIONS: Armodafinil 150 mg early in the night shift improves driving simulator performance in SWD. Effects on sleepiness, cognition, and driving were found up to 9.5 h post-ingestion, during the critical time when many night workers are driving home.

Physiological correlates of insomnia.

Insomnia is a prevalent sleep disorder that is typically comorbid with medical, psychiatric, and other sleep disorders. Yet, it is a disorder with its own course and morbidity that can persist if untreated. This chapter describes the physiological correlates of insomnia expressed during sleep and during the daytime. Together, the data from nighttime and daytime electrophysiology, event-related brain potential recording, neuroimaging studies, sympathetic nervous system, and HPA axis monitoring all suggest that insomnia is a 24 h disorder of hyperarousal.

Sleep loss, circadian mismatch, and abnormalities in reorienting of attention in night workers with shift work disorder.

STUDY OBJECTIVES: Permanent night-shift workers may develop shift-work disorder (SWD). In the current study, we evaluated neurophysiological and behavioral indices of distractibility across times prior to the night shift (T1), during night hours (T2), and after acute sleep deprivation (T3) in permanent hospital night workers with and without SWD. METHODS: Ten asymptomatic night workers (NW) and 18 NW with SWD participated in a 25-h sleep deprivation study. Circadian phase was evaluated by dim-light salivary melatonin onset (DLMO). Objective sleepiness was evaluated using the Multiple Sleep Latency Test (MSLT). Electrophysiological distractibility was evaluated by brain event-related potentials (ERP), whereas behavioral distractibility was evaluated by performance on a visual task in an auditory-visual distraction paradigm. STATISTICAL ANALYSES: Comparisons of ERP results were performed by repeated-measures analysis of variance, and t-tests were used where appropriate. A Mann-Whitney U test was used for comparison of variables (MLST, Stanford Sleepiness Scale, and DLMO) that deviated from normal. RESULTS: First, in the SWD group, the reorienting negativity ERP amplitude was significantly attenuated compared to that in the NW group. Second, the SWD group had shorter MSLT during night shift hours (4.8 ± 4.9 min) compared to that in NW (7.8 ± 3.7 min; U = 47; z = -2.1; P < 0.03). Third, NW with SWD had a DLMO at 20:27 ± 5.0 h, whereas healthy NW had a DLMO at 05:00 ± 3.4 h (U = 43.5; z = -2.22, P < 0.03). Finally, acute sleep deprivation impaired behavioral performance and the P3a ERP in both groups. CONCLUSIONS: Our results demonstrate specific deficits in neurophysiological activity in the attentional domain among the shift-work disorder group relative to night workers.

Sleep extension normalizes ERP of waking auditory sensory gating in healthy habitually short sleeping individuals.

Chronic sleep loss has been associated with increased daytime sleepiness, as well as impairments in memory and attentional processes. In the present study, we evaluated the neuronal changes of a pre-attentive process of wake auditory sensory gating, measured by brain event-related potential (ERP)--P50 in eight normal sleepers (NS) (habitual total sleep time (TST) 7 h 32 m) vs. eight chronic short sleeping individuals (SS) (habitual TST ≤6 h). To evaluate the effect of sleep extension on sensory gating, the extended sleep condition was performed in chronic short sleeping individuals. Thus, one week of time in bed (6 h 11 m) corresponding to habitual short sleep (hSS), and one week of extended time (∼ 8 h 25 m) in bed corresponding to extended sleep (eSS), were counterbalanced in the SS group. The gating ERP assessment was performed on the last day after each sleep condition week (normal sleep and habitual short and extended sleep), and was separated by one week with habitual total sleep time and monitored by a sleep diary. We found that amplitude of gating was lower in SS group compared to that in NS group (0.3 µV vs. 1.2 µV, at Cz electrode respectively). The results of the group × laterality interaction showed that the reduction of gating amplitude in the SS group was due to lower amplitude over the left hemisphere and central-midline sites relative to that in the NS group. After sleep extension the amplitude of gating increased in chronic short sleeping individuals relative to their habitual short sleep condition. The sleep condition × frontality interaction analysis confirmed that sleep extension significantly increased the amplitude of gating over frontal and central brain areas compared to parietal brain areas.

Connectivity analysis of novelty process in habitual short sleepers.

Neurophysiological processes underlying auditory memory and attention are impaired in habitually short sleepers. The aim of this study was to use dynamic causal modeling (DCM) to study the mechanisms of these impairments in short sleepers. Eight normal sleepers (total sleep time (TST)=7-8h) and nine habitual short sleepers (TST ≤ 6 h) participated. The time in bed was increased from habitual (≤ 6 h) to extended (~8.5h) for one week in the short sleep group. Event related potentials (ERPs) were collected using an auditory novelty task in "IGNORE" and "ATTEND" conditions. Fourteen DCM models were considered using different configurations of connections among the following six areas: left and right primary auditory cortices, superior temporal gyri (STG), and inferior temporal gyri (IFG). After fitting the ERPs to the 14 models (separately for the IGNORE and ATTEND conditions), the best model (across subjects) was chosen using the Bayesian model comparison. For both conditions, the connection from right-STG to right-IFG for normal sleepers was significantly greater than habitual short sleepers. This connection did not differ in habitual short sleepers before and after one week of extended sleep time. This connection for normal sleepers was not significantly greater than the habitual short sleepers after one week of extended sleep. These results show that the deficiency of novelty processing, seen in short sleepers, can be explained by the differences in connectivity of the pathway between frontal and temporal brain areas as compared to the normal sleepers. In addition, one week of extended time in bed was not enough to fully normalize this neuronal pathway between STG and IFG in short sleepers.

Circadian phase, sleepiness, and light exposure assessment in night workers with and without shift work disorder.

Most night workers are unable to adjust their circadian rhythms to the atypical hours of sleep and wake. Between 10% and 30% of shiftworkers report symptoms of excessive sleepiness and/or insomnia consistent with a diagnosis of shift work disorder (SWD). Difficulties in attaining appropriate shifts in circadian phase, in response to night work, may explain why some individuals develop SWD. In the present study, it was hypothesized that disturbances of sleep and wakefulness in shiftworkers are related to the degree of mismatch between their endogenous circadian rhythms and the night-work schedule of sleep during the day and wake activities at night. Five asymptomatic night workers (ANWs) (3 females; [mean ± SD] age: 39.2 ± 12.5 yrs; mean yrs on shift = 9.3) and five night workers meeting diagnostic criteria (International Classification of Sleep Disorders [ICSD]-2) for SWD (3 females; age: 35.6 ± 8.6 yrs; mean years on shift = 8.4) participated. All participants were admitted to the sleep center at 16:00 h, where they stayed in a dim light (<10 lux) private room for the study period of 25 consecutive hours. Saliva samples for melatonin assessment were collected at 30-min intervals. Circadian phase was determined from circadian rhythms of salivary melatonin onset (dim light melatonin onset, DLMO) calculated for each individual melatonin profile. Objective sleepiness was assessed using the multiple sleep latency test (MSLT; 13 trials, 2-h intervals starting at 17:00 h). A Mann-Whitney U test was used for evaluation of differences between groups. The DLMO in ANW group was 04:42 ± 3.25 h, whereas in the SWD group it was 20:42 ± 2.21 h (z = 2.4; p < .05). Sleep did not differ between groups, except the SWD group showed an earlier bedtime on off days from work relative to that in ANW group. The MSLT corresponding to night work time (01:00-09:00 h) was significantly shorter (3.6 ± .90 min: [M ± SEM]) in the SWD group compared with that in ANW group (6.8 ± .93 min). DLMO was significantly correlated with insomnia severity (r = -.68; p < .03), indicating that the workers with more severe insomnia symptoms had an earlier timing of DLMO. Finally, SWD subjects were exposed to more morning light (between 05:00 and 11:00 h) as than ANW ones (798 vs. 180 lux [M ± SD], respectively z = -1.7; p < .05). These data provide evidence of an internal physiological delay of the circadian pacemaker in asymptomatic night-shift workers. In contrast, individuals with SWD maintain a circadian phase position similar to day workers, leading to a mismatch/conflict between their endogenous rhythms and their sleep-wake schedule.

Habitual short sleep impacts frontal switch mechanism in attention to novelty.

STUDY OBJECTIVES: Reduced time in bed relative to biological sleep need is common. The impact of habitual short sleep on auditory attention has not been studied to date. In the current study, we utilized novelty oddball tasks to evaluate the effect of habitual short sleep on brain function underlying attention control processes measured by the mismatch negativity (MMN, index of pre-attentive stage), P3a (attention-dependent), and P3b (memory-dependent) event related brain potentials (ERPs). An extended time in bed in a separate study was used to evaluate the possible reversal of the impairments of these processes in habitual short sleepers. METHODS: Ten self-defined short sleepers (total sleep time [TST] ≤ 6 h) and 9 normal-sleeping subjects with TST 7-8 h, participated. ERPs were recorded via a 64-channel EEG system. Two test conditions: "ignore" and "attend" were implemented. The ERPs were analyzed and compared between groups on the 2 task conditions and frontal/central/parietal electrodes by 3-factor ANOVA. Sleep diary data were compared between groups by t-test. Sleep was recorded by the Zeo sleep monitoring system for a week in both habitual and extended sleep conditions at home. RESULTS: The main findings of the present study show that short sleeping individuals had deficiency in activity of the MMN and P3a brain responses over frontal areas compared to normal-sleeping subjects. The P3b amplitude was increased over frontal areas and decreased over parietal with respect to the control group. Extension of time in bed for one week increased TST (from 5.7 h to 7.4 h), and concomitantly MMN amplitude increased from -0.1 µV up to -1.25 µV over frontal areas. CONCLUSIONS: Reduced time in bed is associated with deficiency of the neuronal process associated with change detection, which may recover after one week of sleep extension, whereas attention-dependent neural processes do not normalize after this period of time in habitually short sleeping individuals and may require longer recovery periods.

An assessment of MEG coherence imaging in the study of temporal lobe epilepsy.

PURPOSE: This study examines whether magnetoencephalographic (MEG) coherence imaging is more sensitive than the standard single equivalent dipole (ECD) model in lateralizing the site of epileptogenicity in patients with drug-resistant temporal lobe epilepsy (TLE). METHODS: An archival review of ECD MEG analyses of 30 presurgical patients with TLE was undertaken with data extracted subsequently for coherence analysis by a blinded reviewer for comparison of accuracy of lateralization. Postoperative outcome was assessed by Engel classification. MEG coherence images were generated from 10 min of spontaneous brain activity and compared to surgically resected brain areas outlined on each subject's magnetic resonance image (MRI). Coherence values were averaged independently for each hemisphere to ascertain the laterality of the epileptic network. Reliability between runs was established by calculating the correlation between epochs. Match rates compared the results of each of the two MEG analyses with optimal postoperative outcome. KEY FINDINGS: The ECD method provided an overall match rate of 50% (13/16 cases) for Engel class I outcomes, with 37% (11/30 cases) found to be indeterminate (i.e., no spikes identified on MEG). Coherence analysis provided an overall match rate of 77% (20/26 cases). Of 19 cases without evidence of mesial temporal sclerosis, coherence analysis correctly lateralized the side of TLE in 11 cases (58%). Sensitivity of the ECD method was 41% (indeterminate cases included) and that of the coherence method 73%, with a positive predictive value of 70% for an Engel class Ia outcome. Intrasubject coherence imaging reliability was consistent from run-to-run (correlation > 0.90) using three 10-min epochs. SIGNIFICANCE: MEG coherence analysis has greater sensitivity than the ECD method for lateralizing TLE and demonstrates reliable stability from run-to-run. It, therefore, improves upon the capability of MEG in providing further information of use in clinical decision-making where the laterality of TLE is questioned.

Shift work sleep disorder is associated with an attenuated brain response of sensory memory and an increased brain response to novelty: an ERP study.

STUDY OBJECTIVE: To study the neurophysiological changes in attention and memory functions in shift work sleep disorder (SWSD), using event-related brain potentials (ERPs). PARTICIPANTS: 9 healthy night workers (NW) (mean age = 40 y; SD +/- 8.9 y); 8 night workers meeting diagnostic criteria for SWSD (mean age = 37 y +/- 9.4 y) and 9 healthy day workers (DW) (mean age = 35 y +/- 7.3 y). METHODS AND PROCEDURE: Using standard PSG the sleep related measures (TIB, TST, SOL, SE, and sleep stage distribution) were obtained prior to EEG/ERP study. Measures of habitual sleep were obtained from 2 week sleep logs and sleepiness was assessed with standardized measures. Using 32-EEG leads the ERPs to 3 types of sounds (novel, duration deviant, and simple tone) were obtained. The mismatch negativity (MMN) reflecting memory processing and P3a-reflecting the shift of involuntary attention were obtained. STATISTICAL ANALYSIS: The statistical comparisons of ERPs and sleep related parameters were performed using repeated measured ANOVAs and t-tests where appropriate. RESULTS: Patients with SWSD had reduced TST and increased WASO relative to healthy workers. ERP results demonstrated significant attenuation of MMN amplitude over frontal regions in SWSD patients relative to NW and DW. In the SWSD patients, the P3a was increased to novelty across frontocentral brain regions with respect to the same locations in healthy controls. CONCLUSION: The ERP evidence of sensory memory reduction and attentional hyper-reaction to novel sound in conjunction with disturbed sleep suggests the need for more neurophysiological studies in SWSD workers.

Cortical locations of maximal spindle activity: magnetoencephalography (MEG) study.

The aim of this study was to determine the main cortical regions related to maximal spindle activity of sleep stage 2 in healthy individual subjects during a brief morning nap using magnetoencephalography (MEG). Eight volunteers (mean age: 26.1 +/- 8.7, six women) all right handed, free of any medical psychiatric or sleep disorders were studied. Whole-head 148-channel MEG and a conventional polysomnography montage (EEG; C3, C4, O1 and O2 scalp electrodes and EOG, EMG and ECG electrodes) were used for data collection. Sleep MEG/EEG spindles were visually identified during 15 min of stage 2 sleep for each participant. The distribution of brain activity corresponding to each spindle was calculated using a combination of independent component analysis and a current source density technique superimposed upon individual MRIs. The absolute maximum of spindle activation was localized to frontal, temporal and parietal lobes. However, the most common cortical regions for maximal source spindle activity were precentral and/or postcentral areas across all individuals. The present study suggests that maximal spindle activity localized to these two regions may represent a single event for two types of spindle frequency: slow (at 12 Hz) and fast (at 14 Hz) within global thalamocortical coherence.

Intracranial recording and source localization of auditory brain responses elicited at the 50 ms latency in three children aged from 3 to 16 years.

Maturational studies of the auditory-evoked brain response at the 50 ms latency provide an insight into why this response is aberrant in a number of psychiatric disorders that have developmental origin. Here, using intracranial recordings we found that neuronal activity of the primary contributors to this response can be localised at the lateral part of Heschl's gyrus already at the age of 3.5 years. This study provides results to support the notion that deviations in cognitive function(s) attributed to the auditory P50 in adults might involve abnormalities in neuronal activity of the frontal lobe or in the interaction between the frontal and temporal lobes. Validation and localisation of progenitors of the adults' P50 in young children is a much-needed step in the understanding of the biological significance of different subcomponents that comprise the auditory P50 in the adult brain. In combination with other approaches investigating neuronal mechanisms of auditory P50, the present results contribute to the greater understanding of what and why neuronal activity underlying this response is aberrant in a number of brain dysfunctions. Moreover, the present source localisation results of auditory response at the 50 ms latency might be useful in paediatric neurosurgery practice.