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BackgroundClinical high-risk (CHR) for psychosis is indicated by ultra-high risk (UHR) and basic symptom (BS) criteria; however, conversion rates are highest when both UHR and BS criteria are fulfilled (UHR&BS). While BSs are considered the most immediate expression of neurobiological aberrations underlying the development of psychosis, research on neurobiological correlates of BS is scarce.MethodsWe investigated gray matter volumes (GMV) of 20 regions of interest (ROI) previously associated with UHR criteria in 90 patients from the Bern early detection service: clinical controls (CC), first-episode psychosis (FEP), UHR, BS and UHR&BS. We expected lowest GMV in FEP and UHR&BS, and highest volume in CC with UHR and BS in-between.ResultsSignificantly, lower GMV was detected in FEP and UHR&BS patients relative to CC with no other significant between-group differences. When ROIs were analyzed separately, seven showed a significant group effect (FDR corrected), with five (inferior parietal, medial orbitofrontal, lateral occipital, middle temporal, precuneus) showing significantly lower GM volume in the FEP and/or UHR&BS groups than in the CC group (Bonferroni corrected). In the CHR group, only COGDIS scores correlated negatively with cortical volumes.ConclusionsThis is the first study to demonstrate that patients who fulfill both UHR and BS criteria – a population that has been associated with higher conversion rates – exhibit more severe GMV reductions relative to those who satisfy BS or UHR criteria alone. This result was mediated by the BS in the UHR&BS group, as only the severity of BS was linked to GMV reductions.

Increased striatal dopaminergic activity and decreased prefrontal functioning have been reported in individuals at clinical high risk (CHR) for psychosis. Abnormal metabolic rate might affect resting-state cerebral blood flow (rCBF) in the respective regions. Here, we examined if striatal and prefrontal rCBF differ between patients with CHR, first-episode psychosis (FEP), chronic schizophrenia-spectrum disorder (SZ) and controls. Two cohorts with a total of 122 participants were included and analyzed separately: 32 patients with SZ and 31 healthy controls (HC) from the University Hospital of Psychiatry, and 59 patients from the Bern Early Recognition and Intervention Center (29 with CHR, 12 with FEP, and 18 clinical controls [CC]). Ultra-high risk criteria were assessed with the Structured Interview for Psychosis-Risk Syndromes, basic symptom criteria with the Schizophrenia Proneness Instrument. rCBF was measured with pseudo-continuous arterial spin labeling 3T-Magnetic Resonance Imaging. Striatal rCBF was significantly increased and prefrontal rCBF significantly decreased in the SZ group compared to HC group and in the CHR and FEP groups compared to CC group. Striatal rCBF correlated significantly with positive symptom scores in SZ and CHR. An inverse correlation between striatal and frontal rCBF was found in controls (HC, CC), but not in patient groups (SZ, FEP, CHR). This is the first study to demonstrate increased neuronal activity within the striatum, but reduced prefrontal activity in patients with CHR, FEP, and SZ compared to the respective controls. Our results indicate that alterations in striatal and prefrontal rCBF are reflecting metabolic abnormalities preceding the onset of frank psychosis.

While analysis and interpretation of structural epileptogenic lesion is an essential task for the neuroradiologist in clinical practice, a substantial body of epilepsy research has shown that focal lesions influence brain areas beyond the epileptogenic lesion, across ensembles of functionally and anatomically connected brain areas. In this review article, we aim to provide an overview about altered network compositions in epilepsy, as measured with current advanced neuroimaging techniques to characterize the initiation and spread of epileptic activity in the brain with multimodal noninvasive imaging techniques. We focus on resting-state functional magnetic resonance imaging (MRI) and simultaneous electroencephalography/fMRI, and oppose the findings in idiopathic generalized versus focal epilepsies. These data indicate that circumscribed epileptogenic lesions can have extended effects on many brain systems. Although epileptic seizures may involve various brain areas, seizure activity does not spread diffusely throughout the brain but propagates along specific anatomic pathways that characterize the underlying epilepsy syndrome. Such a functionally oriented approach may help to better understand a range of clinical phenomena such as the type of cognitive impairment, the development of pharmacoresistance, the propagation pathways of seizures, or the success of epilepsy surgery.

Volumetric and morphometric studies have demonstrated structural abnormalities related to chronic epilepsies on a cohort- and population-based level. On a single-patient level, specific patterns of atrophy or cortical reorganization may be widespread and heterogeneous but represent potential targets for further personalized image analysis and surgical therapy. The goal of this study was to compare morphometric data analysis in 37 patients with temporal lobe epilepsies with expert-based image analysis, pre-informed by seizure semiology and ictal scalp EEG. Automated image analysis identified abnormalities exceeding expert-determined structural epileptogenic lesions in 86% of datasets. If EEG lateralization and expert MRI readings were congruent, automated analysis detected abnormalities consistent on a lobar and hemispheric level in 82% of datasets. However, in 25% of patients EEG lateralization and expert readings were inconsistent. Automated analysis localized to the site of resection in 60% of datasets in patients who underwent successful epilepsy surgery. Morphometric abnormalities beyond the mesiotemporal structures contributed to subtype characterisation. We conclude that subject-specific morphometric information is in agreement with expert image analysis and scalp EEG in the majority of cases. However, automated image analysis may provide non-invasive additional information in cases with equivocal radiological and neurophysiological findings.

Volumetric and morphometric studies have demonstrated structural abnormalities related to chronic epilepsies on a cohort- and population-based level. On a single-patient level, specific patterns of atrophy or cortical reorganization may be widespread and heterogeneous but represent potential targets for further personalized image analysis and surgical therapy. The goal of this study was to compare morphometric data analysis in 37 patients with temporal lobe epilepsies with expert-based image analysis, pre-informed by seizure semiology and ictal scalp EEG. Automated image analysis identified abnormalities exceeding expert-determined structural epileptogenic lesions in 86% of datasets. If EEG lateralization and expert MRI readings were congruent, automated analysis detected abnormalities consistent on a lobar and hemispheric level in 82% of datasets. However, in 25% of patients EEG lateralization and expert readings were inconsistent. Automated analysis localized to the site of resection in 60% of datasets in patients who underwent successful epilepsy surgery. Morphometric abnormalities beyond the mesiotemporal structures contributed to subtype characterisation. We conclude that subject-specific morphometric information is in agreement with expert image analysis and scalp EEG in the majority of cases. However, automated image analysis may provide non-invasive additional information in cases with equivocal radiological and neurophysiological findings.

Background: The cerebral network that is active during rest and is deactivated during goal-oriented activity is called the default mode network (DMN). It appears to be involved in self-referential mental activity. Atypical functional connectivity in the DMN has been observed in schizophrenia. One hypothesis suggests that pathologically increased DMN connectivity in schizophrenia is linked with a main symptom of psychosis, namely, misattribution of thoughts. Methods: A resting-state pseudocontinuous arterial spin labeling (ASL) study was conducted to measure absolute cerebral blood flow (CBF) in 34 schizophrenia patients and 27 healthy controls. Using independent component analysis (ICA), the DMN was extracted from ASL data. Mean CBF and DMN connectivity were compared between groups using a 2-sample t test. Results: Schizophrenia patients showed decreased mean CBF in the frontal and temporal regions (P < .001). ICA demonstrated significantly increased DMN connectivity in the precuneus (x/y/z = -16/-64/38) in patients than in controls (P < .001). CBF was not elevated in the respective regions. DMN connectivity in the precuneus was significantly correlated with the Positive and Negative Syndrome Scale scores (P < .01). Conclusions: In schizophrenia patients, the posterior hub-which is considered the strongest part of the DMN-showed increased DMN connectivity. We hypothesize that this increase hinders the deactivation of the DMN and, thus, the translation of cognitive processes from an internal to an external focus. This might explain symptoms related to defective self-monitoring, such as auditory verbal hallucinations or ego disturbances.

PURPOSE Arterial spin labeling (ASL) magnetic resonance imaging to assess cerebral blood flow (CBF) is of increasing interest in basic research and in diagnostic applications, since ASL provides similar information to positron emission tomography about perfusion in vascular territories. However, in patients with steno-occlusive arterial disease (SOAD), CBF as measured by ASL might be underestimated due to delayed bolus arrival, and thus increased spin relaxation. We aimed to estimate the extent to which bolus arrival time (BAT) was delayed in patients with SOAD and whether this resulted in underestimation of CBF. METHODS BAT was measured using digital subtraction angiography (DSA) in ten patients with high-grade stenosis of the middle carotid artery (MCA). Regional CBF was assessed with pseudocontinuous ASL. RESULTS BATs were nonsignificantly prolonged in the stenotic hemisphere 4.1±2.0 s compared with the healthy hemisphere 3.3±0.9 s; however, there were substantial individual differences on the stenotic side. CBF in the anterior and posterior MCA territories were significantly reduced on the stenotic hemisphere. Severe stenosis was correlated with longer BAT and lower quantified CBF. CONCLUSION ASL-based perfusion measurement involves a race between the decay of the spins and the delivery of labeled blood to the region of interest. Special caution is needed when interpreting CBF values quantified in individuals with altered blood flow and delayed circulation times. However, from a clinician's point of view, an accentuation of hypoperfusion (even if caused by underestimation of CBF due to prolonged BATs) might be desirable since it indexes potentially harmful physiologic deficits.

BACKGROUND AND PURPOSE: Early stratification of degenerative processes is a prerequisite to warrant therapeutic options in prodromal Alzheimer disease. Our aim was to investigate differences in cerebral macromolecular tissue composition between patients with AD, mild cognitive impairment, and age- and sex-matched healthy controls by using model-based magnetization transfer with a binary spin-bath magnetization transfer model and magnetization transfer ratio at 1.5T. MATERIALS AND METHODS: We investigated patients with de novo AD (n = 18), MCI (n = 18), and CTRLs (n = 18). A region-of-interest analysis of the entorhinal cortex, hippocampal head and body, insula, and temporal neocortex was performed with fuzzy clustering to associate every subregion to a cluster representative for each group. RESULTS: Cluster analysis achieved a concordance of 0.92 (50 of 54 subjects) between a combination of the calculated mMT parameters (kf,kr,T2r,F,T2f) in the entorhinal cortex and the neuropsychological diagnosis. The sensitivity and specificity for the discrimination of AD from MCI reached 1 and 0.94, with a positive predictive value of 0.95 and a negative predictive value of 1. Compared with mMT, the concordance for MTR was 0.83 (45 of 54 subjects) with a lower specificity of 0.5 and positive predictive value of 0.67 to discriminate patients with AD and MCI. CONCLUSIONS: mMT imaging detects macromolecule-related alterations and allows an improved classification of patients with early AD and MCI compared with MTR.

BACKGROUND AND PURPOSE: Simultaneous EEG/fMRI is an effective noninvasive tool for identifying and localizing the SOZ in patients with focal epilepsy. In this study, we evaluated different thresholding strategies in EEG/fMRI for the assessment of hemodynamic responses to IEDs in the SOZ of drug-resistant epilepsy. MATERIALS AND METHODS: Sixteen patients with focal epilepsy were examined by using simultaneous 92-channel EEG and BOLD fMRI. The temporal fluctuation of epileptiform signals on the EEG was extracted by independent component analysis to predict the hemodynamic responses to the IEDs. We applied 3 different threshold criteria to detect hemodynamic responses within the SOZ: 1) PA, 2) a fixed threshold at P < .05 corrected for multiple comparison (FWE), and 3) FAV (4000 ± 200 activated voxels within the brain). RESULTS: PA identified the SOZ in 9 of 16 patients; FWE resulted in concordant BOLD signal correlates in 11 of 16, and FAV in 13 of 16 patients. Hemodynamic responses were detected within the resected areas in 5 (PA), 6 (FWE), and 8 (FAV) of 10 patients who remained seizure-free after surgery. CONCLUSIONS: EEG/fMRI is a noninvasive tool for the presurgical work-up of patients with epilepsy, which can be performed during seizure-free periods and is complementary to the ictal electroclinical assessment. Our findings suggest that the effectiveness of EEG/fMRI in delineating the SOZ may be further improved by the additional use of alternative analysis strategies such as FAV. BOLD : blood oxygen level–dependent EEG : electroencephalography FAV : fixed numbers of activated voxels FWE : family-wise error FWHM : full width at half maximum IC : independent component IED : interictal epileptic discharge LTLE : lateral temporal lobe epilepsy MTLE : mesial temporal lobe epilepsy PA : peak activation SOZ : seizure-onset zone

Rationale and Objectives: A particular arterial spin (ASL) labeling technique, called 3D-single-shot GRASE ASL is discussed with respect to the ability and limits of quantifying perfusion parameters. Materials and Methods: The technique enables the acquisition of perfusion weighted signal at multiple delay times (TI) in one scan. The readout part is a gradient and spin-echo combination (GRASE) that uses switched gradient rephrasing of signals to produce several times as many signals as turbo-spin-echo, which translates into faster imaging time and higher signal-to-noise ratio (SNR) per imaging time. The technique provides the possibility for model based quantification of cerebral blood flow and the determination of the bolus arrival information without use of contrast agent and thus the characterization and determination of regions that are supported by collaterals. Results: Whereas for a quantification of the permeability using ASL the SNR is not high enough, at least qualitative permeability maps can be determined, if an optimal homogenous SNR was guaranteed. This was accomplished in brain regions with a high blood supply, typically given in tumors, and by using a correction for coil sensitivity at the highest possible additional scaling. Conclusion: The single-shot 3D GRASE ASL can provide information about the principal blood supply, the transit delay of the blood flow due to a stenosis or collaterals and a qualitative measure of the permeability.

Epileptic seizures typically reveal a high degree of stereotypy, that is, for an individual patient they are characterized by an ordered and predictable sequence of symptoms and signs with typically little variability. Stereotypy implies that ictal neuronal dynamics might have deterministic characteristics, presumably most pronounced in the ictogenic parts of the brain, which may provide diagnostically and therapeutically important information. Therefore the goal of our study was to search for indications of determinism in periictal intracranial electroencephalography (EEG) studies recorded from patients with pharmacoresistent epilepsy.

BACKGROUND AND PURPOSE: Nonconvulsive status epilepticus (NCSE) is associated with a mortality rate of up to 18%, therefore requiring prompt diagnosis and treatment. Our aim was to evaluate the diagnostic value of perfusion CT (PCT) in the differential diagnosis of NCSE versus postictal states in patients presenting with persistent altered mental states after a preceding epileptic seizure. We hypothesized that regional cortical hyperperfusion can be measured by PCT in patients with NCSE, whereas it is not present in postictal states. MATERIALS AND METHODS: Nineteen patients with persistent altered mental status after a preceding epileptic seizure underwent PCT and electroencephalography (EEG). Patients were stratified as presenting with NCSE (n = 9) or a postictal state (n = 10) on the basis of clinical history and EEG data. Quantitative and visual analysis of the perfusion maps was performed. RESULTS: Patients during NCSE had significantly increased regional cerebral blood flow (P > .0001), increased regional cerebral blood volume (P > .001), and decreased (P > .001) mean transit time compared with the postictal state. Regional cortical hyperperfusion was depicted in 7/9 of patients with NCSE by ad hoc analysis of parametric perfusion maps during emergency conditions but was not a feature of postictal states. The areas of hyperperfusion were concordant with transient clinical symptoms and EEG topography in all cases. CONCLUSIONS: Visual analysis of perfusion maps detected regional hyperperfusion in NCSE with a sensitivity of 78%. The broad availability and short processing time of PCT in an emergency situation is a benefit compared with EEG. Consequently, the use of PCT in epilepsy may accelerate the diagnosis of NCSE. PCT may qualify as a complementary diagnostic tool to EEG in patients with persistent altered mental state after a preceding seizure.

Combined EEG/fMRI recordings offer a promising opportunity to detect brain areas with altered BOLD signal during interictal epileptic discharges (IEDs). These areas are likely to represent the irritative zone, which is itself a reflection of the epileptogenic zone. This paper reports on the imaging findings using independent component analysis (ICA) to continuously quantify epileptiform activity in simultaneously acquired EEG and fMRI. Using ICA derived factors coding for the epileptic activity takes into account that epileptic activity is continuously fluctuating with each spike differing in amplitude, duration and maybe topography, including subthreshold epileptic activity besides clear IEDs and may thus increase the sensitivity and statistical power of combined EEG/fMRI in epilepsy. Twenty patients with different types of focal and generalized epilepsy syndromes were investigated. ICA separated epileptiform activity from normal physiological brain activity and artifacts. In 16/20 patients, BOLD correlates of epileptic activity matched the EEG sources, the clinical semiology, and, if present, the structural lesions. In clinically equivocal cases, the BOLD correlates aided to attribute proper diagnosis of the underlying epilepsy syndrome. Furthermore, in one patient with temporal lobe epilepsy, BOLD correlates of rhythmic delta activity could be employed to delineate the affected hippocampus. Compared to BOLD correlates of manually identified IEDs, the sensitivity was improved from 50% (10/20) to 80%. The ICA EEG/fMRI approach is a safe, non-invasive and easily applicable technique, which can be used to identify regions with altered hemodynamic effects related to IEDs as well as intermittent rhythmic discharges in different types of epilepsy.

BACKGROUND Findings of cerebral cortical atrophy, white matter lesions and microhemorrhages have been reported in high-altitude climbers. The aim of this study was to evaluate structural cerebral changes in a large cohort of climbers after an ascent to extreme altitudes and to correlate these findings with the severity of hypoxia and neurological signs during the climb. METHODS Magnetic resonance imaging (MRI) studies were performed in 38 mountaineers before and after participating in a high altitude (7126m) climbing expedition. The imaging studies were assessed for occurrence of new WM hyperintensities and microhemorrhages. Changes of partial volume estimates of cerebrospinal fluid, grey matter, and white matter were evaluated by voxel-based morphometry. Arterial oxygen saturation and acute mountain sickness scores were recorded daily during the climb. RESULTS On post-expedition imaging no new white matter hyperintensities were observed. Compared to baseline testing, we observed a significant cerebrospinal fluid fraction increase (0.34% [95% CI 0.10-0.58], p = 0.006) and a white matter fraction reduction (-0.18% [95% CI -0.32--0.04], p = 0.012), whereas the grey matter fraction remained stable (0.16% [95% CI -0.46-0.13], p = 0.278). Post-expedition imaging revealed new microhemorrhages in 3 of 15 climbers reaching an altitude of over 7000m. Affected climbers had significantly lower oxygen saturation values but not higher acute mountain sickness scores than climbers without microhemorrhages. CONCLUSIONS A single sojourn to extreme altitudes is not associated with development of focal white matter hyperintensities and grey matter atrophy but leads to a decrease in brain white matter fraction. Microhemorrhages indicative of substantial blood-brain barrier disruption occur in a significant number of climbers attaining extreme altitudes.

Recent evidence suggests that humans can form and later retrieve new semantic relations unconsciously by way of hippocampus—the key structure also recruited for conscious relational (episodic) memory. If the hippocampus subserves both conscious and unconscious relational encoding/retrieval, one would expect the hippocampus to be place of unconscious-conscious interactions during memory retrieval. We tested this hypothesis in an fMRI experiment probing the interaction between the unconscious and conscious retrieval of face-associated information. For the establishment of unconscious relational memories, we presented subliminal (masked) combinations of unfamiliar faces and written occupations (“actor” or “politician”). At test, we presented the former subliminal faces, but now supraliminally, as cues for the reactivation of the unconsciously associated occupations. We hypothesized that unconscious reactivation of the associated occupation—actor or politician—would facilitate or inhibit the subsequent conscious retrieval of a celebrity’s occupation, which was also actor or politician. Depending on whether the reactivated unconscious occupation was congruent or incongruent to the celebrity’s occupation, we expected either quicker or delayed conscious retrieval process. Conscious retrieval was quicker in the congruent relative to a neutral baseline condition but not delayed in the incongruent condition. fMRI data collected during subliminal face-occupation encoding confirmed previous evidence that the hippocampus was interacting with neocortical storage sites of semantic knowledge to support relational encoding. fMRI data collected at test revealed that the facilitated conscious retrieval was paralleled by deactivations in the hippocampus and neocortical storage sites of semantic knowledge. We assume that the unconscious reactivation has pre-activated overlapping relational representations in the hippocampus reducing the neural effort for conscious retrieval. This finding supports the notion of synergistic interactions between conscious and unconscious relational memories in a common, cohesive hippocampal-neocortical memory space.

BACKGROUND/nEpilepsy surgery is a potentially curative treatment option for pharmacoresistent patients. If non-invasive methods alone do not allow to delineate the epileptogenic brain areas the surgical candidates undergo long-term monitoring with intracranial EEG. Visual EEG analysis is then used to identify the seizure onset zone for targeted resection as a standard procedure./n/nMETHODS/nDespite of its great potential to assess the epileptogenicty of brain tissue, quantitative EEG analysis has not yet found its way into routine clinical practice. To demonstrate that quantitative EEG may yield clinically highly relevant information we retrospectively investigated how post-operative seizure control is associated with four selected EEG measures evaluated in the resected brain tissue and the seizure onset zone. Importantly, the exact spatial location of the intracranial electrodes was determined by coregistration of pre-operative MRI and post-implantation CT and coregistration with post-resection MRI was used to delineate the extent of tissue resection. Using data-driven thresholding, quantitative EEG results were separated into normally contributing and salient channels./n/nRESULTS/nIn patients with favorable post-surgical seizure control a significantly larger fraction of salient channels in three of the four quantitative EEG measures was resected than in patients with unfavorable outcome in terms of seizure control (median over the whole peri-ictal recordings). The same statistics revealed no association with post-operative seizure control when EEG channels contributing to the seizure onset zone were studied./n/nCONCLUSIONS/nWe conclude that quantitative EEG measures provide clinically relevant and objective markers of target tissue, which may be used to optimize epilepsy surgery. The finding that differentiation between favorable and unfavorable outcome was better for the fraction of salient values in the resected brain tissue than in the seizure onset zone is consistent with growing evidence that spatially extended networks might be more relevant for seizure generation, evolution and termination than a single highly localized brain region (i.e. a “focus”) where seizures start. This study was supported by the Swiss National Science Foundation (SNF) via the projects 122010, 124089, 140332 and 155950. R.G. Andrzejak was supported by grant No. FIS-2010-18204 of the Spanish Ministry of Education and Science and funding from the Volkswagen Foundation. M. Müller acknowledges the Consejo Nacionál de Ciencia y Technología, Mexico, project 156667. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Auditory hallucinations (AH) occur in various neurological and psychiatric disorders. In psychosis, increased neuronal activity in the primary auditory cortex (PAC) contributes to AH. We investigated functional neuroanatomy of epileptic hallucinations by measuring cerebral perfusion in three patients with AH during simple partial status epilepticus. Hyperperfusion in the temporal lobe covering the PAC occurred in all patients. Our perfusion data support the hypothesis of PAC being a constituting element in the genesis of AH independent of their aetiology.

INTRODUCTION A marker predictive of hematoma expansion in the central nervous system could aid the selection of patients for hemostatic or surgical treatment. CASE REPORT Here, we present a 83-year-old patient with acute spinal subdural hematoma with paraparesis progressing to paraplegia. A contrast extravasation within the intraspinal hematoma was visualized on spinal MR indicating active bleeding (spinal spot sign). A second acquisition of contrast-enhanced MR images showed progression of contrast extravasation helping to different active bleeding from spinal arteriovenous malformations/fistula. CONCLUSIONS A "spinal spot sign" may be important for treatment decisions, notably in patients with incomplete neurological deficits at the time of imaging.

Quantitative EEG (qEEG) has modified our understanding of epileptic seizures, shifting our view from the traditionally accepted hyper-synchrony paradigm toward more complex models based on re-organization of functional networks. However, qEEG measurements are so far rarely considered during the clinical decision-making process. To better understand the dynamics of intracranial EEG signals, we examine a functional network derived from the quantification of information flow between intracranial EEG signals. Using transfer entropy, we analyzed 198 seizures from 27 patients undergoing pre-surgical evaluation for pharmaco-resistant epilepsy. During each seizure we considered for each network the in-, out- and total “hubs”, defined respectively as the time and the EEG channels with the maximal incoming, outgoing or total (bidirectional) information flow. In the majority of cases we found that the hubs occur around the middle of seizures, and interestingly not at the beginning or end, where the most dramatic EEG signal changes are found by visual inspection. For the patients who then underwent surgery, good postoperative clinical outcome was on average associated with a higher percentage of out- or total-hubs located in the resected area (for out-hubs p = 0.01, for total-hubs p = 0.04). The location of in-hubs showed no clear predictive value. We conclude that the study of functional networks based on qEEG measurements may help to identify brain areas that are critical for seizure generation and are thus potential targets for focused therapeutic interventions.

We report on oxygenation changes noninvasively recorded by multichannel continuous-wave near infrared spectroscopy (CW-NIRS) during endovascular neuroradiologic interventions requiring temporary balloon occlusion of arteries supplying the cerebral circulation. Digital subtraction angiography (DSA) provides reference data on the site, timing, and effectiveness of the flow stagnation as well as on the amount and direction of collateral circulation. This setting allows us to relate CW-NIRS findings to brain specific perfusion changes. We focused our analysis on the transition from normal perfusion to vessel occlusion, i.e., before hypoxia becomes clinically apparent. The localization of the maximal response correlated either with the core (occlusion of the middle cerebral artery) or with the watershed areas (occlusion of the internal carotid artery) of the respective vascular territories. In one patient with clinically and angiographically confirmed insufficient collateral flow during carotid artery occlusion, the total hemoglobin concentration became significantly asymmetric, with decreased values in the ipsilateral watershed area and contralaterally increased values. Multichannel CW-NIRS monitoring might serve as an objective and early predictive marker of critical perfusion changes during interventions—to prevent hypoxic damage of the brain. It also might provide valuable human reference data on oxygenation changes as they typically occur during acute stroke.

INTRODUCTION: The cerebral resting state in schizophrenia is altered, as has been demonstrated separately by electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) resting state networks (RSNs). Previous simultaneous EEG/fMRI findings in healthy controls suggest that a consistent spatiotemporal coupling between neural oscillations (EEG frequency correlates) and RSN activity is necessary to organize cognitive processes optimally. We hypothesized that this coupling is disorganized in schizophrenia and related psychotic disorders, in particular regarding higher cognitive RSNs such as the default-mode (DMN) and left-working-memory network (LWMN). METHODS: Resting state was investigated in eleven patients with a schizophrenia spectrum disorder (n = 11) and matched healthy controls (n = 11) using simultaneous EEG/fMRI. The temporal association of each RSN to topographic spectral changes in the EEG was assessed by creating Covariance Maps. Group differences within, and group similarities across frequencies were estimated for the Covariance Maps. RESULTS: The coupling of EEG frequency bands to the DMN and the LWMN respectively, displayed significant similarities that were shifted towards lower EEG frequencies in patients compared to healthy controls. CONCLUSIONS: By combining EEG and fMRI, each measuring different properties of the same pathophysiology, an aberrant relationship between EEG frequencies and altered RSNs was observed in patients. RSNs of patients were related to lower EEG frequencies, indicating functional alterations of the spatiotemporal coupling. SIGNIFICANCE: The finding of a deviant and shifted coupling between RSNs and related EEG frequencies in patients with a schizophrenia spectrum disorder is significant, as it might indicate how failures in the processing of internal and external stimuli, as commonly seen during this symptomatology (i.e. thought disorders, hallucinations), arise.

Developmental venous anomalies (DVAs) are associated with epileptic seizures; however, the role of DVA in the epileptogenesis is still not established. Simultaneous interictal electroencephalogram/functional magnetic resonance imaging (EEG/fMRI) recordings provide supplementary information to electroclinical data about the epileptic generators, and thus aid in the differentiation of clinically equivocal epilepsy syndromes. The main objective of our study was to characterize the epileptic network in a patient with DVA and epilepsy by simultaneous EEG/fMRI recordings. A 17-year-old woman with recently emerging generalized tonic–clonic seizures, and atypical generalized discharges, was investigated using simultaneous EEG/fMRI at the university hospital. Previous high-resolution MRI showed no structural abnormalities, except a DVA in the right frontal operculum. Interictal EEG recordings showed atypical generalized discharges, corresponding to positive focal blood oxygen level dependent (BOLD) correlates in the right frontal operculum, a region drained by the DVA. Additionally, widespread cortical bilateral negative BOLD correlates in the frontal and parietal lobes were delineated, resembling a generalized epileptic network. The EEG/fMRI recordings support a right frontal lobe epilepsy, originating in the vicinity of the DVA, propagating rapidly to both frontal and parietal lobes, as expressed on the scalp EEG by secondary bilateral synchrony. The DVA may be causative of focal epilepsies in cases where no concomitant epileptogenic lesions can be detected. Advanced imaging techniques, such as simultaneous EEG/fMRI, may thus aid in the differentiation of clinically equivocal epilepsy syndromes.

Focal onset epilepsies most often occur in the temporal lobes. To improve diagnosis and therapy of patients suffering from pharmacoresistant temporal lobe epilepsy it is highly important to better understand the underlying functional and structural networks. In mesial temporal lobe epilepsy (MTLE) widespread functional networks are involved in seizure generation and propagation. In this study we have analyzed the spatial distribution of hemodynamic correlates (HC) to interictal epileptiform discharges on simultaneous EEG/fMRI recordings and relative grey matter volume (rGMV) reductions in 10 patients with MTLE. HC occurred beyond the seizure onset zone in the hippocampus, in the ipsilateral insular/operculum, temporo-polar and lateral neocortex, cerebellum, along the central sulcus and bilaterally in the cingulate gyrus. rGMV reductions were detected in the middle temporal gyrus, inferior temporal gyrus and uncus to the hippocampus, the insula, the posterior cingulate and the anterior lobe of the cerebellum. Overlaps between HC and decreased rGMV were detected along the mesolimbic network ipsilateral to the seizure onset zone. We conclude that interictal epileptic activity in MTLE induces widespread metabolic changes in functional networks involved in MTLE seizure activity. These functional networks are spatially overlapping with areas that show a reduction in relative grey matter volumes.

Epileptic seizures are associated with high behavioral stereotypy of the patients. In the EEG of epilepsy patients characteristic signal patterns can be found during and between seizures. Here we use ordinal patterns to analyze EEGs of epilepsy patients and quantify the degree of signal determinism. Besides relative signal redundancy and the fraction of forbidden patterns we introduce the fraction of under-represented patterns as a new measure. Using the logistic map, parameter scans are performed to explore the sensitivity of the measures to signal determinism. Thereafter, application is made to two types of EEGs recorded in two epilepsy patients. Intracranial EEG shows pronounced determinism peaks during seizures. Finally, we demonstrate that ordinal patterns may be useful for improving analysis of non-invasive simultaneous EEG-fMRI.

Foreknowledge about upcoming events may be exploited to optimize behavioural responses. In a previous work, using an eye movement paradigm, we showed that different types of partial foreknowledge have different effects on saccadic efficiency. In the current study, we investigated the neural circuitry involved in processing of partial foreknowledge using functional magnetic resonance imaging. Fourteen subjects performed a mixed antisaccade, prosaccade paradigm with blocks of no foreknowledge, complete foreknowledge or partial foreknowledge about stimulus location, response direction or task. We found that saccadic foreknowledge is processed primarily within the well-known oculomotor network for saccades and antisaccades. Moreover, we found a consistent decrease in BOLD activity in the primary and secondary visual cortex in all foreknowledge conditions compared to the no-foreknowledge conditions. Furthermore we found that the different types of partial foreknowledge are processed in distinct brain areas: response foreknowledge is processed in the frontal eye field, while stimulus foreknowledge is processed in the frontal and parietal eye field. Task foreknowledge, however, revealed no positive BOLD correlate. Our results show different patterns of engagement in the saccade-related neural network depending upon precisely what type of information is known ahead.

Epileptic seizures are due to the pathological collective activity of large cellular assemblies. A better understanding of this collective activity is integral to the development of novel diagnostic and therapeutic procedures. In contrast to reductionist analyses, which focus solely on small-scale characteristics of ictogenesis, here we follow a systems-level approach, which combines both small-scale and larger-scale analyses. Peri-ictal dynamics of epileptic networks are assessed by studying correlation within and between different spatial scales of intracranial electroencephalographic recordings (iEEG) of a heterogeneous group of patients suffering from pharmaco-resistant epilepsy. Epileptiform activity as recorded by a single iEEG electrode is determined objectively by the signal derivative and then subjected to a multivariate analysis of correlation between all iEEG channels. We find that during seizure, synchrony increases on the smallest and largest spatial scales probed by iEEG. In addition, a dynamic reorganization of spatial correlation is observed on intermediate scales, which persists after seizure termination. It is proposed that this reorganization may indicate a balancing mechanism that decreases high local correlation. Our findings are consistent with the hypothesis that during epileptic seizures hypercorrelated and therefore functionally segregated brain areas are re-integrated into more collective brain dynamics. In addition, except for a special sub-group, a highly significant association is found between the location of ictal iEEG activity and the location of areas of relative decrease of localised EEG correlation. The latter could serve as a clinically important quantitative marker of the seizure onset zone (SOZ).

This study aimed to develop a new linguistic based functional magnetic resonance imaging (fMRI)-sentence decision task that reliably detects hemispheric language dominance.FMRI was performed in 13 healthy right-handed controls and 20 patients at 1.5 T prior to neurosurgery. The main components of language were assessed with different paradigms (rhyme, synonym, and sentence). In controls, activations were quantified by a volume of interest analysis. Four neuroimagers tested a visual rating score in the patients group. Interrater agreement and concordance between fMRI and Wada test were calculated.In healthy controls, the frontal language area was activated by the sentence and synonym task in 100% and in 73% by the rhyme task. The temporal language area was activated in 100% by the sentence-, in 64% by the synonym, and in 55% by the rhyme task. In the patients group, interrater agreement was .90 for activations in the inferior frontal and .97 in the superior temporal gyrus. Correlation between the WADA test and fMRI was .86 for the sentence, and .89 for the synonym task.The sentence task provides robust activations in putative essential language areas and can be used for visual analysis of predefined areas to facilitate interpretation of clinical fMRI.

Multimodal imaging was performed in Rasmussen Encephalitis (RE) during episodes of complex-partial and focal motor status epilepticus including independent component analysis of BOLD-fMRI, arterial spin labeling perfusion imaging and diffusion tensor imaging. The active epileptic network and topographically independent brain areas showed regional hyperperfusion and progressive atrophy. The results suggest that hyperperfusion outside of the epileptic network represent active inflammation in RE and the imaging protocol presented here, allows assessing thereby the disease activity non-invasively.

Theta burst transcranial magnetic stimulation (TBS) may induce behavioural changes that outlast the stimulation period. The neurophysiological basis of these behavioural changes are currently under investigation. Given the evidence that cortical information processing relies on transient synchronization and desynchronization of neuronal assemblies, we set out to test whether TBS is associated with changes of neuronal synchronization as assessed by surface EEG. In four healthy subjects one TBS train of 600 pulses (200 bursts, each burst consisting of 3 pulses at 30 Hz, repeated at intervals of 100 ms) was applied over the right frontal eye field and EEG synchronization was assessed in a time-resolved manner over 60 min by using a non-overlapping moving window. For each time step the linear cross-correlation matrix for six EEG channels of the right and for the six homotopic EEG channels of the left hemisphere were computed and their largest eigenvalues used to assess changes of synchronization. Synchronization was computed for broadband EEG and for the delta, theta, alpha, beta and gamma frequency bands. In all subjects EEG synchronization of the stimulated hemisphere was significantly and persistently increased relative to EEG synchronization of the unstimulated hemisphere. This effect occurred immediately after TBS for the theta, alpha, beta and gamma frequency bands and 10-20 min after TBS for broadband and delta frequency band EEG. Our results demonstrate that TBS is associated with increased neuronal synchronization of the cerebral hemisphere ipsilateral to the stimulation site relative to the unstimulated hemisphere. We speculate that enhanced synchronization interferes with cortical information processing and thus may be a neurophysiological correlate of the impaired behavioural performance detected previously.

University Hospital of Psychiatry Bern, Bern, Switzerland (D Hubl MD, Prof W Strik MD); Institute of Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland (M Hauf MD); Department of Psychiatric Neurophysiology, University Hospital of Psychiatry Bern, Bern, Switzerland (C van Swam lic phil, Prof T Dierks MD); and Division of Neuropsychological Rehabilitation, Department of Neurology, Inselspital, University of Bern, Bern, Switzerland (Prof R Muri MD)

Auditory hallucinations comprise a critical domain of psychopathology in schizophrenia. Repetitive transcranial magnetic stimulation (TMS) has shown promise as an intervention with both positive and negative reports. The aim of this study was to test resting-brain perfusion before treatment as a possible biological marker of response to repetitive TMS. Twenty-four medicated patients underwent resting-brain perfusion magnetic resonance imaging with arterial spin labeling (ASL) before 10 days of repetitive TMS treatment. Response was defined as a reduction in the hallucination change scale of at least 50%. Responders (n=9) were robustly differentiated from nonresponders (n=15) to repetitive TMS by the higher regional cerebral blood flow (CBF) in the left superior temporal gyrus (STG) (P

Currently, a variety of linear and nonlinear measures is in use to investigate spatiotemporal interrelation patterns of multivariate time series. Whereas the former are by definition insensitive to nonlinear effects, the latter detect both nonlinear and linear interrelation. In the present contribution we employ a uniform surrogate-based approach, which is capable of disentangling interrelations that significantly exceed random effects and interrelations that significantly exceed linear correlation. The bivariate version of the proposed framework is explored using a simple model allowing for separate tuning of coupling and nonlinearity of interrelation. To demonstrate applicability of the approach to multivariate real-world time series we investigate resting state functional magnetic resonance imaging (rsfMRI) data of two healthy subjects as well as intracranial electroencephalograms (iEEG) of two epilepsy patients with focal onset seizures. The main findings are that for our rsfMRI data interrelations can be described by linear cross-correlation. Rejection of the null hypothesis of linear iEEG interrelation occurs predominantly for epileptogenic tissue as well as during epileptic seizures.

Background Transcranial magnetic stimulation (TMS) is a novel therapeutic approach, used in patients with pharmacoresistant auditory verbal hallucinations (AVH). To investigate the neurobiological effects of TMS on AVH, we measured cerebral blood flow with pseudo-continuous magnetic resonance-arterial spin labeling 20 ± 6 hours before and after TMS treatment. Methods Thirty patients with schizophrenia or schizoaffective disorder were investigated. Fifteen patients received a 10-day TMS treatment to the left temporoparietal cortex, and 15 received the standard treatment. The stimulation location was chosen according to an individually determined language region determined by a functional magnetic resonance imaging language paradigm, which identified the sensorimotor language area, area Spt (sylvian parietotemporal), as the target region. Results TMS-treated patients showed positive clinical effects, which were indicated by a reduction in AVH scores ( p ≤ .001). Cerebral blood flow was significantly decreased in the primary auditory cortex ( p ≤ .001), left Broca's area ( p ≤ .001), and cingulate gyrus ( p ≤ .001). In control subjects, neither positive clinical effects nor cerebral blood flow decreases were detected. The decrease in cerebral blood flow in the primary auditory cortex correlated with the decrease in AVH scores ( p ≤ .001). Conclusions TMS reverses hyperactivity of language regions involved in the emergence of AVH. Area Spt acts as a gateway to the hallucination-generating cerebral network. Successful therapy corresponded to decreased cerebral blood flow in the primary auditory cortex, supporting its crucial role in triggering AVH and contributing to the physical quality of the false perceptions.