Integrating high-density ERP and fMRI measures of face-elicited brain activity in 9-12-year-old children: An ERP source localization study.

Social information processing is a critical mechanism underlying children's socio-emotional development. Central to this process are patterns of activation associated with one of our most salient socioemotional cues, the face. In this study, we obtained fMRI activation and high-density ERP source data evoked by parallel face dot-probe tasks from 9-to-12-year-old children. We then integrated the two modalities of data to explore the neural spatial-temporal dynamics of children's face processing. Our results showed that the tomography of the ERP sources broadly corresponded with the fMRI activation evoked by the same facial stimuli. Further, we combined complementary information from fMRI and ERP by defining fMRI activation as functional ROIs and applying them to the ERP source data. Indices of ERP source activity were extracted from these ROIs at three a priori ERP peak latencies critical for face processing. We found distinct temporal patterns among the three time points across ROIs. The observed spatial-temporal profiles converge with a dual-system neural network model for face processing: a core system (including the occipito-temporal and parietal ROIs) supports the early visual analysis of facial features, and an extended system (including the paracentral, limbic, and prefrontal ROIs) processes the socio-emotional meaning gleaned and relayed by the core system. Our results for the first time illustrate the spatial validity of high-density source localization of ERP dot-probe data in children. By directly combining the two modalities of data, our findings provide a novel approach to understanding the spatial-temporal dynamics of face processing. This approach can be applied in future research to investigate different research questions in various study populations.

Comorbidity of concussion and depression alters brain functional connectivity in collegiate student-athletes.

Depression and concussion are highly prevalent neuropsychological disorders that often occur simultaneously. However, due to the high degree of symptom overlap between the two events, including but not limited to headache, sleep disturbances, appetite changes, fatigue, and difficulty concentrating, they may be treated in isolation. Thus, clinical awareness of additive symptom load may be missed. This study measures neuropsychological and electroencephalography (EEG) alpha band coherence differences in collegiate student-athletes with history of comorbid depression and concussion, in comparison to those with a single morbidity and healthy controls (HC). 35 collegiate athletes completed neuropsychological screenings and EEG measures. Participants were grouped by concussion and depression history. Differences in alpha band coherence were calculated using two-way ANOVA with post hoc correction for multiple comparisons. Comorbid participants scored significantly worse on neuropsychological screening, BDI-FS, and PCSS than those with a single morbidity and HC. Two-way ANOVA by group revealed significant main effects of alpha band coherence for concussion, depression, and their interaction term. Post-hoc analysis showed that comorbid participants had more abnormal alpha band coherence than single morbidity, when compared to HC. Comorbidity of concussion and depression increased symptom reporting and revealed more altered alpha band coherence than single morbidity, compared to HC. The abnormalities of the comorbid group exclusively showed decreased alpha band coherence in comparison to healthy controls. The comorbidity of depression and SRC has a compounding effect on depression symptoms, post-concussion symptoms, and brain functional connectivity. This research demonstrates a promising objective measure in comorbid individuals, previously only measured via subjective symptom reporting.

Increased resting functional connectivity in spike-wave epilepsy in WAG/Rij rats.

PURPOSE: Functional magnetic resonance imaging (fMRI)-based resting functional connectivity is well suited for measuring slow correlated activity throughout brain networks. Epilepsy involves chronic changes in normal brain networks, and recent work demonstrated enhanced resting fMRI connectivity between the hemispheres in childhood absence epilepsy. An animal model of this phenomenon would be valuable for investigating fundamental mechanisms and testing therapeutic interventions. METHODS: We used fMRI-based resting functional connectivity for studying brain networks involved in absence epilepsy. Wistar Albino Glaxo rats from Rijswijk (WAG/Rij) exhibit spontaneous episodes of staring and unresponsiveness accompanied by spike-wave discharges (SWDs) resembling human absence seizures in behavior and electroencephalography (EEG). Simultaneous EEG-fMRI data in epileptic WAG/Rij rats in comparison to nonepileptic Wistar controls were acquired at 9.4 T. Regions showing cortical fMRI increases during SWDs were used to define reference regions for connectivity analysis to investigate whether chronic seizure activity is associated with changes in network resting functional connectivity. KEY FINDINGS: We observed high degrees of cortical-cortical correlations in all WAG/Rij rats at rest (when no SWDs were present), but not in nonepileptic controls. Strongest connectivity was seen between regions most intensely involved in seizures, mainly in the bilateral somatosensory and adjacent cortices. Group statistics revealed that resting interhemispheric cortical-cortical correlations were significantly higher in WAG/Rij rats compared to nonepileptic controls. SIGNIFICANCE: These findings suggest that activity-dependent plasticity may lead to long-term changes in epileptic networks even at rest. The results show a marked difference between the epileptic and nonepileptic animals in cortical-cortical connectivity, indicating that this may be a useful interictal biomarker associated with the epileptic state.

Selective head cooling in the acute phase of concussive injury: a neuroimaging study.

Introduction: Neurovascular decoupling is a common consequence after brain injuries like sports-related concussion. Failure to appropriately match cerebral blood flow (CBF) with increases in metabolic demands of the brain can lead to alterations in neurological function and symptom presentation. Therapeutic hypothermia has been used in medicine for neuroprotection and has been shown to improve outcome. This study aimed to examine the real time effect of selective head cooling on healthy controls and concussed athletes via magnetic resonance spectroscopy (MRS) and arterial spin labeling (ASL) measures. Methods: 24 participants (12 controls; 12 concussed) underwent study procedures including the Post-Concussion Symptom Severity (PCSS) Rating Form and an MRI cooling protocol (pre-cooling (T1 MPRAGE, ASL, single volume spectroscopy (SVS)); during cooling (ASL, SVS)). Results: Results showed general decreases in brain temperature as a function of time for both groups. Repeated measures ANOVA showed a significant main effect of time (F = 7.94, p < 0.001) and group (F = 22.21, p < 0.001) on temperature, but no significant interaction of group and time (F = 1.36, p = 0.237). CBF assessed via ASL was non-significantly lower in concussed individuals at pre-cooling and generalized linear mixed model analyses demonstrated a significant main effect of time for the occipital left ROI (F = 11.29, p = 0.002) and occipital right ROI (F = 13.39, p = 0.001). There was no relationship between any MRI metric and PCSS symptom burden. Discussion: These findings suggest the feasibility of MRS thermometry to monitor alterations of brain temperature in concussed athletes and that metabolic responses in response to cooling after concussion may differ from controls.

Dynamic time course of typical childhood absence seizures: EEG, behavior, and functional magnetic resonance imaging.

Absence seizures are 5-10 s episodes of impaired consciousness accompanied by 3-4 Hz generalized spike-and-wave discharge on electroencephalography (EEG). The time course of functional magnetic resonance imaging (fMRI) changes in absence seizures in relation to EEG and behavior is not known. We acquired simultaneous EEG-fMRI in 88 typical childhood absence seizures from nine pediatric patients. We investigated behavior concurrently using a continuous performance task or simpler repetitive tapping task. EEG time-frequency analysis revealed abrupt onset and end of 3-4 Hz spike-wave discharges with a mean duration of 6.6 s. Behavioral analysis also showed rapid onset and end of deficits associated with electrographic seizure start and end. In contrast, we observed small early fMRI increases in the orbital/medial frontal and medial/lateral parietal cortex >5 s before seizure onset, followed by profound fMRI decreases continuing >20 s after seizure end. This time course differed markedly from the hemodynamic response function (HRF) model used in conventional fMRI analysis, consisting of large increases beginning after electrical event onset, followed by small fMRI decreases. Other regions, such as the lateral frontal cortex, showed more balanced fMRI increases followed by approximately equal decreases. The thalamus showed delayed increases after seizure onset followed by small decreases, most closely resembling the HRF model. These findings reveal a complex and long-lasting sequence of fMRI changes in absence seizures, which are not detectable by conventional HRF modeling in many regions. These results may be important mechanistically for seizure initiation and termination and may also contribute to changes in EEG and behavior.

Impaired attention and network connectivity in childhood absence epilepsy.

Patients with childhood absence epilepsy (CAE) often demonstrate impaired interictal attention, even with control of their seizures. No previous study has investigated the brain networks involved in this impairment. We used the continuous performance task (CPT) of attentional vigilance and the repetitive tapping task (RTT), a control motor task, to examine interictal attention in 26 children with CAE and 22 matched healthy controls. Each subject underwent simultaneous 3T functional magnetic resonance imaging-electroencephalography (fMRI-EEG) and CPT/RTT testing. Areas of activation on fMRI during the CPT task were correlated with behavioral performance and used as seed regions for resting functional connectivity analysis. All behavioral measures reflecting inattention were significantly higher in patients. Correlation analysis revealed that impairment on all measures of inattention on the CPT task was associated with decreased medial frontal cortex (MFC) activation during CPT. In addition, analysis of resting functional connectivity revealed an overall decrease within an 'attention network' in patients relative to controls. Patients demonstrated significantly impaired connectivity between the right anterior insula/frontal operculum (In/FO) and MFC relative to controls. Our results suggest that there is impaired function in an attention network comprising anterior In/FO and MFC in patients with CAE. These findings provide an anatomical and functional basis for impaired interictal attention in CAE, which may allow the development of improved treatments targeted at these networks.

Impaired consciousness in temporal lobe seizures: role of cortical slow activity.

Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness. Early work suggested that altered consciousness may occur with bilateral or dominant temporal lobe seizure involvement. However, other bilateral temporal lobe disorders do not impair consciousness. More recent work supports a 'network inhibition hypothesis' in which temporal lobe seizures disrupt brainstem-diencephalic arousal systems, leading indirectly to depressed cortical function and impaired consciousness. Indeed, prior studies show subcortical involvement in temporal lobe seizures and bilateral frontoparietal slow wave activity on intracranial electroencephalography. However, the relationships between frontoparietal slow waves and impaired consciousness and between cortical slowing and fast seizure activity have not been directly investigated. We analysed intracranial electroencephalography recordings during 63 partial seizures in 26 patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural responsiveness was determined based on blinded review of video during seizures and classified as impaired (complex-partial seizures) or unimpaired (simple-partial seizures). We observed significantly increased delta-range 1-2 Hz slow wave activity in the bilateral frontal and parietal neocortices during complex-partial compared with simple-partial seizures. In addition, we confirmed prior work suggesting that propagation of unilateral mesial temporal fast seizure activity to the bilateral temporal lobes was significantly greater in complex-partial than in simple-partial seizures. Interestingly, we found that the signal power of frontoparietal slow wave activity was significantly correlated with the temporal lobe fast seizure activity in each hemisphere. Finally, we observed that complex-partial seizures were somewhat more common with onset in the language-dominant temporal lobe. These findings provide direct evidence for cortical dysfunction in the form of bilateral frontoparietal slow waves associated with impaired consciousness in temporal lobe seizures. We hypothesize that bilateral temporal lobe seizures may exert a powerful inhibitory effect on subcortical arousal systems. Further investigations will be needed to fully determine the role of cortical-subcortical networks in ictal neocortical dysfunction and may reveal treatments to prevent this important negative consequence of temporal lobe epilepsy.

Cortical potential imaging of somatosensory evoked potentials by means of the boundary element method in pediatric epilepsy patients.

The aim of the present study was to assess the feasibility of identifying the primary hand sensory area and central sulcus in pediatric patients using the cortical potential imaging (CPI) method from the scalp recorded somatosensory evoked potentials (SEPs). The CPI method was used to reconstruct the cortical potential distribution from the scalp potentials with the boundary element (3-layer: scalp, skull and brain) head model based on MR images of individual subjects. The cortical potentials estimated from the pre-operative scalp SEPs of four pediatric patients, were compared with the post-op subdural SEP recordings made in the same subjects. Estimated and directly recorded cortical SEP maps showed comparable spatial patterns on the cortical surface in four patients (spatial correlation coefficient >0.7 in the SEP spikes). For two of four patients, the estimated waveforms correlated significantly to the waveforms obtained by direct cortical recordings. The present results demonstrated the feasibility of the cortical potential imaging approach in noninvasive imaging spatial distribution and temporal waveforms of cortical potentials for pediatric patients. These also suggest that the CPI method may provide a promising means of estimating the cortical potential and noninvasive localizing the central sulcus to aid surgical planning for pediatric patients.

The intensity and connectivity of spontaneous brain activity in a language network relate to aging and language.

Neuroimaging studies often either look at functional activation in response to an explicit task, or functional connectivity (i.e., interregional correlations) during resting-state. Few studies have looked at the intensity of brain activity or its relationship with age, behavior, and language. The current study investigated both intensity (i.e., the Amplitude of Low-Frequency Fluctuations, ALFF) and the functional connectivity of spontaneous brain activity during rest and their relationship with age and language. A life-span sample of individuals (N = 152) completed a battery of neuropsychological tests to assess basic cognitive functions and resting-state functional MRI data to assess spontaneous brain activity. Focusing on an extend language network, the mean ALFF and total degree were calculated for this network. We found that increased age was associated with more intense activity (i.e., higher ALFF) but lower within-network connectivity. Additionally, these increases in activity within the language network during resting-state were related to worse language ability, particularly in younger adults, supporting a dedifferentiation account of cognition. Our results support the utility of using resting-state data as an indicator of cognition and support the role of ALFF as a potential biomarker in characterizing the relationships between resting-state brain activity, age, and cognition.

Focal BOLD fMRI changes in bicuculline-induced tonic-clonic seizures in the rat.

Generalized tonic-clonic seizures cause widespread physiological changes throughout the cerebral cortex and subcortical structures in the brain. Using combined blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at 9.4 T and electroencephalography (EEG), these changes can be characterized with high spatiotemporal resolution. We studied BOLD changes in anesthetized Wistar rats during bicuculline-induced tonic-clonic seizures. Bicuculline, a GABA(A) receptor antagonist, was injected systemically and seizure activity was observed on EEG as high-amplitude, high-frequency polyspike discharges followed by clonic paroxysmal activity of lower frequency, with mean electrographic seizure duration of 349 s. Our aim was to characterize the spatial localization, direction, and timing of BOLD signal changes during the pre-ictal, ictal and post-ictal periods. Group analysis was performed across seizures using paired t-maps of BOLD signal superimposed on high-resolution anatomical images. Regional analysis was then performed using volumes of interest to quantify BOLD timecourses. In the pre-ictal period we found focal BOLD increases in specific areas of somatosensory cortex (S1, S2) and thalamus several seconds before seizure onset. During seizures we observed BOLD increases in cortex, brainstem and thalamus and BOLD decreases in the hippocampus. The largest ictal BOLD increases remained in the focal regions of somatosensory cortex showing pre-ictal increases. During the post-ictal period we observed widespread BOLD decreases. These findings support a model in which "generalized" tonic-clonic seizures begin with focal changes before electrographic seizure onset, which progress to non-uniform changes during seizures, possibly shedding light on the etiology and pathophysiology of similar seizures in humans.

Simultaneous EEG, fMRI, and behavior in typical childhood absence seizures.

PURPOSE: Absence seizures cause transient impairment of consciousness. Typical absence seizures occur in children, and are accompanied by 3-4-Hz spike-wave discharges (SWDs) on electroencephalography (EEG). Prior EEG-functional magnetic resonance imaging (fMRI) studies of SWDs have shown a network of cortical and subcortical changes during these electrical events. However, fMRI during typical childhood absence seizures with confirmed impaired consciousness has not been previously investigated. METHODS: We performed EEG-fMRI with simultaneous behavioral testing in 37 children with typical childhood absence epilepsy (CAE). Attentional vigilance was evaluated by a continuous performance task (CPT), and simpler motor performance was evaluated by a repetitive tapping task (RTT). RESULTS: SWD episodes were obtained during fMRI scanning from 9 patients among the 37 studied. fMRI signal increases during SWDs were observed in the thalamus, frontal cortex, primary visual, auditory, somatosensory, and motor cortex, and fMRI decreases were seen in the lateral and medial parietal cortex, cingulate gyrus, and basal ganglia. Omission error rate (missed targets) with SWDs during fMRI was 81% on CPT and 39% on RTT. For those seizure epochs during which CPT performance was impaired, fMRI changes were seen in cortical and subcortical structures typically involved in SWDs, whereas minimal changes were observed for the few epochs during which performance was spared. DISCUSSION: These findings suggest that typical absence seizures involve a network of cortical-subcortical areas necessary for normal attention and primary information processing. Identification of this network may improve understanding of cognitive impairments in CAE, and may help guide development of new therapies for this disorder.

Tunable Hollow Pt@Ru Dodecahedra via Galvanic Replacement for Efficient Methanol Oxidation.

Pt-Ru nanocrystals are promising electrocatalysts for methanol oxidation in fuel cells. However, owing to the lattice mismatch and high reduction potential of Ru, the shape-controlled synthesis of Pt-Ru nanocrystals faces great challenges. Herein, we employ a galvanic replacement method to synthesize tunable hollow Pt@Ru dodecahedra via controlling the precursor concentration. Two typical structures, hollow Pt@Ru dodecahedra (h-Pt@Ru) and deformed hollow Pt@Ru dodecahedra (d-Pt@Ru), are obtained to exhibit superior electrocatalytic activities for methanol oxidation. The optimal d-Pt@Ru dodecahedra present a mass activity of 0.80 A mgPt-1 and a specific activity of 1.61 mA cmPt-2, which are 5.25 and 7.78 times higher than those of the commercial Pt/C, respectively. Remarkably, both h-Pt@Ru and d-Pt@Ru show lower oxidation potentials and higher CO-poisoning resistance for methanol oxidation than PtRu nanoparticles (NPs) and commercial Pt/C. This is attributed to the hollow dodecahedron structures with optimal spatial elemental distributions, leading to high utilization of Pt at edges and corners and the exposure of abundant Pt-Ru interfaces. Our strategy offers a facile method to engineer bimetallic metal catalysts regardless of lattice mismatch.

Neurobiological effect of selective brain cooling after concussive injury.

The search for effective treatment facilitating recovery from concussive injury, as well as reducing risk for recurrent concussion is an ongoing challenge. This study aimed to determine: a) feasibility of selective brain cooling to facilitate clinical symptoms resolution, and b) biological functions of the brain within athletes in acute phase of sports-related concussion. Selective brain cooling for 30 minutes using WElkins sideline cooling system was administered to student-athletes suffering concussive injury (n=12; tested within 5±3 days) and those without history of concussion (n=12). fMRI and ASL sequences were obtained before and immediately after cooling to better understanding the mechanism by which cooling affects neurovascular coupling. Concussed subjects self-reported temporary relief from physical symptoms after cooling. There were no differences in the number or strength of functional connections within Default Mode Network (DMN) between groups prior to cooling. However, we observed a reduction in the strength and number of connections of the DMN with other ROIs in both groups after cooling. Unexpectedly, we observed a significant increase in cerebral blood flow (CBF) assessed by ASL after selective cooling in the concussed subjects compared to the normal controls. We suggest that compromised neurovascular coupling in acute phase of injury may be temporarily restored by cooling to match CBF with surges in the metabolic demands of the brain. Upon further validation, selective brain cooling could be a potential clinical tool in the minimization of symptoms and pathological changes after concussion.

The effect of repetitive subconcussive collisions on brain integrity in collegiate football players over a single football season: A multi-modal neuroimaging study.

The cumulative effect of repetitive subconcussive collisions on the structural and functional integrity of the brain remains largely unknown. Athletes in collision sports, like football, experience a large number of impacts across a single season of play. The majority of these impacts, however, are generally overlooked, and their long-term consequences remain poorly understood. This study sought to examine the effects of repetitive collisions across a single competitive season in NCAA Football Bowl Subdivision athletes using advanced neuroimaging approaches. Players were evaluated before and after the season using multiple MRI sequences, including T1-weighted imaging, diffusion tensor imaging (DTI), arterial spin labeling (ASL), resting-state functional MRI (rs-fMRI), and susceptibility weighted imaging (SWI). While no significant differences were found between pre- and post-season for DTI metrics or cortical volumes, seed-based analysis of rs-fMRI revealed significant (p < 0.05) changes in functional connections to right isthmus of the cingulate cortex (ICC), left ICC, and left hippocampus. ASL data revealed significant (p < 0.05) increases in global cerebral blood flow (CBF), with a specific regional increase in right postcentral gyrus. SWI data revealed that 44% of the players exhibited outlier rates (p < 0.05) of regional decreases in SWI signal. Of key interest, athletes in whom changes in rs-fMRI, CBF and SWI were observed were more likely to have experienced high G impacts on a daily basis. These findings are indicative of potential pathophysiological changes in brain integrity arising from only a single season of participation in the NCAA Football Bowl Subdivision, even in the absence of clinical symptoms or a diagnosis of concussion. Whether these changes reflect compensatory adaptation to cumulative head impacts or more lasting alteration of brain integrity remains to be further explored.

Estimation of number of independent brain electric sources from the scalp EEGs.

In electromagnetic source analysis, many source localization strategies require the number of sources as an input parameter (e.g., spatio-temporal dipole fitting and the multiple signal classification). In the present study, an information criterion method, in which the penalty functions are selected based on the spatio-temporal source model, has been developed to estimate the number of independent dipole sources from electromagnetic measurements such as the electroencephalogram (EEG). Computer simulations were conducted to evaluate the effects of various parameters on the estimation of the source number. A three-concentric-spheres head model was used to approximate the head volume conductor. Three kinds of typical signal sources, i.e., the damped sinusoid sources, sinusoid sources with one frequency band and sinusoid sources with two separated frequency bands, were used to simulate the oscillation characteristics of brain electric sources. The simulation results suggest that the present method can provide a good estimate of the number of independent dipole sources from the EEG measurements. In addition, the present simulation results suggest that choosing the optimal penalty function can successfully reduce the effect of noise on the estimation of number of independent sources. The present study suggests that the information criterion method may provide a useful means in estimating the number of independent brain electrical sources from EEG/MEG measurements.

Impaired consciousness in patients with absence seizures investigated by functional MRI, EEG, and behavioural measures: a cross-sectional study.

BACKGROUND: The neural underpinnings of impaired consciousness and of the variable severity of behavioural deficits from one absence seizure to the next are not well understood. We aimed to measure functional MRI (fMRI) and electroencephalography (EEG) changes in absence seizures with impaired task performance compared with seizures in which performance was spared. METHODS: In this cross-sectional study done at the Yale School of Medicine, CT, USA, we recruited patients from 59 paediatric neurology practices in the USA. We did simultaneous EEG, fMRI, and behavioural testing in patients aged 6-19 years with childhood or juvenile absence epilepsy, and with an EEG with typical 3-4 Hz bilateral spike-wave discharges and normal background. The main outcomes were fMRI and EEG amplitudes in seizures with impaired versus spared behavioural responses analysed by t test. We also examined the timing of fMRI and EEG changes in seizures with impaired behavioural responses compared with seizures with spared responses. FINDINGS: 93 patients were enrolled between Jan 1, 2005, and Sept 1, 2013; we recorded 1032 seizures in 39 patients. fMRI changes during seizures occurred sequentially in three functional brain networks. In the default mode network, fMRI amplitude was 0·57% (SD 0·26) for seizures with impaired and 0·40% (0·16) for seizures with spared behavioural responses (mean difference 0·17%, 95% CI 0·11-0·23; p<0·0001). In the task-positive network, fMRI amplitude was 0·53% (SD 0·29) for seizures with impaired and 0·39% (0·15) for seizures with spared behavioral responses (mean difference 0·14%, 95% CI 0·08-0·21; p<0·0001). In the sensorimotor-thalamic network, fMRI amplitude was 0·41% (0·25) for seizures with impaired and 0·34% (0·14) for seizures with spared behavioural responses (mean difference 0·07%, 95% CI 0·01-0·13; p=0·02). Mean fractional EEG power in the frontal leads was 50·4 (SD 15·2) for seizures with impaired and 24·8 (6·5) for seizures with spared behavioural responses (mean difference 25·6, 95% CI 21·0-30·3); middle leads 35·4 (6·5) for seizures with impaired, 13·3 (3·4) for seizures with spared behavioural responses (mean difference 22·1, 95% CI 20·0-24·1); posterior leads 41·6 (5·3) for seizures with impaired, 24·6 (8·6) for seizures with spared behavioural responses (mean difference 17·0, 95% CI 14·4-19·7); p<0·0001 for all comparisons. Mean seizure duration was longer for seizures with impaired behaviour at 7·9 s (SD 6·6), compared with 3·8 s (3·0) for seizures with spared behaviour (mean difference 4·1 s, 95% CI 3·0-5·3; p<0·0001). However, larger amplitude fMRI and EEG signals occurred at the outset or even preceding seizures with behavioural impairment. INTERPRETATION: Impaired consciousness in absence seizures is related to the intensity of physiological changes in established networks affecting widespread regions of the brain. Increased EEG and fMRI amplitude occurs at the onset of seizures associated with behavioural impairment. These finding suggest that a vulnerable state might exist at the initiation of some absence seizures leading them to have more severe physiological changes and altered consciousness than other absence seizures. FUNDING: National Institutes of Health, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Science, the Loughridge Williams Foundation, and the Betsy and Jonathan Blattmachr Family.

On the estimation of the number of dipole sources in EEG source localization.

OBJECTIVE: The purpose of the present study was to determine the number of the equivalent dipole sources corresponding to the scalp EEG using the information criterion method based on the instantaneous-state modeling. METHODS: A three-concentric-spheres head model was used to represent the head volume conductor. The Powell algorithm was used to solve the inverse problem of estimating the equivalent dipoles from the scalp EEG. The information criterion with different penalty functions was used to determine the dipole number. Computer simulations were conducted to evaluate effects of various parameters on the estimation of dipole number. RESULTS: The present results suggest that the present method is able to estimate the number of equivalent current dipoles (ECDs) from instantaneous scalp EEG measurements, and that increase in the electrode number can improve the accuracy of estimation of the ECD number. For two ECDs, the best performance of estimation with 20% white noise were 85%, 92% and 94%, when 64, 128 and 256 electrodes are used, respectively. When there are 3 ECDs, the present results suggest that using 256 electrodes gave up to 82% estimation accuracy. The present simulation results also indicate that the accuracies of identification are similar when the minimum distance between dipoles is either 1 or 2 cm, which was used in the simulation. It was also found that the different penalty functions used in the information criterion method could have substantial influence on the estimation accuracy. CONCLUSIONS: The present method can estimate the number of ECDs from instantaneous scalp EEG distribution for up to three dipoles. SIGNIFICANCE: The successful estimation of the number of ECDs will play an important role in expanding the applicability of dipole source localization to multiple sources.

Decreased resting functional connectivity after traumatic brain injury in the rat.

Traumatic brain injury (TBI) contributes to about 10% of acquired epilepsy. Even though the mechanisms of post-traumatic epileptogenesis are poorly known, a disruption of neuronal networks predisposing to altered neuronal synchrony remains a viable candidate mechanism. We tested a hypothesis that resting state BOLD-fMRI functional connectivity can reveal network abnormalities in brain regions that are connected to the lesioned cortex, and that these changes associate with functional impairment, particularly epileptogenesis. TBI was induced using lateral fluid-percussion injury in seven adult male Sprague-Dawley rats followed by functional imaging at 9.4T 4 months later. As controls we used six sham-operated animals that underwent all surgical operations but were not injured. Electroencephalogram (EEG)-functional magnetic resonance imaging (fMRI) was performed to measure resting functional connectivity. A week after functional imaging, rats were implanted with bipolar skull electrodes. After recovery, rats underwent pentyleneterazol (PTZ) seizure-susceptibility test under EEG. For image analysis, four pairs of regions of interests were analyzed in each hemisphere: ipsilateral and contralateral frontal and parietal cortex, hippocampus, and thalamus. High-pass and low-pass filters were applied to functional imaging data. Group statistics comparing injured and sham-operated rats and correlations over time between each region were calculated. In the end, rats were perfused for histology. None of the rats had epileptiform discharges during functional imaging. PTZ-test, however revealed increased seizure susceptibility in injured rats as compared to controls. Group statistics revealed decreased connectivity between the ipsilateral and contralateral parietal cortex and between the parietal cortex and hippocampus on the side of injury as compared to sham-operated animals. Injured animals also had abnormal negative connectivity between the ipsilateral and contralateral parietal cortex and other regions. Our data provide the first evidence on abnormal functional connectivity after experimental TBI assessed with resting state BOLD-fMRI.

Intracranial EEG surface renderings: new insights into normal and abnormal brain function.

Intracranial electro-encephalography (icEEG) provides a unique opportunity to record directly from the human brain and is clinically important for planning epilepsy surgery. However, traditional visual analysis of icEEG is often challenging. The typical simultaneous display of multiple electrode channels can prevent an in-depth understanding of the spatial-time course of brain activity. In recent decades, advances in the field of neuroimaging have provided powerful new tools for the analysis and display of signals in the brain. These methods can now be applied to icEEG to map electrical signal information onto a three-dimensional rendering of a patient's cortex and graphically observe the changes in voltage over time. This approach provides rapid visualization of seizures and normal activity propagating over the brain surface and can also illustrate subtle changes that might be missed by traditional icEEG analysis. In addition, the direct mapping of signal information onto accurate anatomical structures can assist in the precise targeting of sites for epilepsy surgery and help correlate electrical activity with behavior. Bringing icEEG data into a standardized anatomical space will also enable neuroimaging methods of statistical analysis to be applied. As new technologies lead to a dramatic increase in the rate of data acquisition, these novel visualization and analysis techniques will play an important role in processing the valuable information obtained through icEEG.

Three-dimensional source imaging from simultaneously recorded ERP and BOLD-fMRI.

We present the 3-D EEG source images reconstructed by using the minimum norm least square (MNLS) method in combination with the functional magnetic resonance imaging (fMRI) statistical parametric mapping. For a group of five normal subjects, electroencephalogram (EEG) and fMRI signals responding to the full-view checkerboard pattern-reversal visual stimulation were recorded simultaneously and separately. The electrical activities in V1/V2 and V5 were successfully imaged in the N75-P100-N145 and P100-N145 components, respectively. The present results demonstrate the merits of high-resolution spatiotemporal functional neuroimaging by integrating the simultaneously recorded fMRI and EEG data.