Basic symptoms and gray matter volumes of patients at clinical high risk for psychosis.

BACKGROUND: Clinical 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. METHODS: We 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. RESULTS: Significantly, 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. CONCLUSIONS: This 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.

The neural network of saccadic foreknowledge.

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.

Detecting functional hubs of ictogenic networks.

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.

Forbidden ordinal patterns of periictal intracranial EEG indicate deterministic dynamics in human epileptic seizures.

PURPOSE: 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. METHODS: We assessed the number of forbidden ordinal patterns of 110 periictal multichannel intracranial EEG studies of 16 patients. Ordinal patterns are derived from the rank order of short sequences of consecutive EEG values. Ordinal patterns are well suited for analyzing real-world time series, for they have low sensitivity for many forms of noise and are applicable to nonstationary data. Although Gaussian random dynamics generate all possible ordinal patterns for a given sequence length, deterministic dynamics typically manifest with less random and more regular signals that miss a certain number of all the possible ordinal patterns. These missing ordinal patterns are referred to as "forbidden ordinal patterns." In this study, the number of forbidden ordinal patterns n(fp) of an EEG signal was interpreted as an indication of determinism, when it was larger than the number of forbidden patterns occurring in amplitude adjusted Fourier transform surrogates. We computed n(fp) for each EEG signal in a time-resolved way by using a moving-window approach. Then we specifically investigated n(mean)(fp) denoting the average number of forbidden patterns across all EEG signals, and n(max)(fp), which represents the number of forbidden patterns occurring in the EEG signal with the largest n(fp) during the seizure-onset period. KEY FINDINGS: The average number of forbidden patterns of all EEG signals, n(mean)(fp), typically first increased and then decreased during the seizures. However, these changes were not statistically significant relative to the preseizure time period. In contrast, n(max)(fp)typically increased significantly during the first third of the seizure period and then gradually decreased toward and beyond seizure termination. In those patients who became seizure free following surgery, a larger percentage of the EEG signals containing the maximal number of forbidden patterns during the seizure-onset period tended to be recorded from within the visually identified seizure-onset zones. SIGNIFICANCE: Our findings demonstrate a spatiotemporally limited shift of neuronal dynamics toward a more deterministic dynamic regimen, specifically pronounced during the seizure-onset period. Assessing the number of forbidden ordinal patterns of intracranial EEG provides quantitative and observer-independent information. We propose that it is at least partially complementary to classical visual EEG reading and may be diagnostically helpful to better delineate ictogenic parts of the brain.

Trapped in a Glass Bell Jar: Neural Correlates of Depersonalization and Derealization in Subjects at Clinical High-Risk of Psychosis and Depersonalization-Derealization Disorder.

BACKGROUND: Depersonalization (DP) and derealization (DR) are symptoms of a disruption of perceptual integration leading to an altered quality of subjective experiences such as feelings of unreality and detachment from the self (DP) or the surroundings (DR). Both DP and DR often occur in concert with other symptoms, for example in subjects at clinical high-risk (CHR) for psychosis, but also appear isolated in the form of DP/DR disorder. Despite evidence that DP/DR causes immense distress, little is known about their neurobiological underpinnings. Therefore, we investigated the neural correlates of DP/DR using pseudo-continuous arterial spin labeling MRI. METHODS: We evaluated the frequency of DP/DR symptoms in a clinical sample (N = 217) of help-seeking individuals from the Early Detection and Intervention Centre for Mental Crisis (CHR, n = 97; clinical controls (CC), n = 91; and first-episode psychosis (FEP), n = 29). Further, in a subsample of those CHR subjects who underwent MRI, we investigated the resting-state regional cerebral blood flow (rCBF). Here, individuals with (n = 21) and without (n = 23) DP/DR were contrasted. Finally, rCBF was measured in a small independent second sample of patients with DP/DR disorder (n = 6) and healthy controls (HC, n = 6). RESULTS: In the complete clinical sample, significantly higher frequency of DP/DR was found in CHR compared to CC (50.5 vs. 16.5%; χ2 (2) = 24.218, p ≤ 0.001, Cramer's V = 0.359) as well as in FEP compared to CC (37.9 vs. 16.5%; χ2 (2) = 5.960, p = 0.015, Cramer's V = 0.223). In MRI, significantly lower rCBF was detected in the left orbitofrontal cortex in CHR with vs. without DP/DR (x/y/z = -16/42/-22, p < 0.05, FWE corrected). In patients with DP/DR disorder, significantly higher rCBF was detected in the left caudate nucleus (x/y/z = -18/-32/18, p < 0.05) compared to HC. CONCLUSIONS: This study shows that DP/DR symptoms are frequently found in CHR subjects. Investigating two separate DP/DR populations with an identical neuroimaging technique, our study also indicates that there may be divergent pathophysiological mechanisms-decreased neuronal activity in the orbitofrontal cortex, but increased activity within the caudate nucleus-leading to a final common pathway with similar psychopathological symptoms. This suggests that both top-down (orbitofrontal cortex) and bottom-up (caudate nucleus) mechanisms could contribute to the emergence of DP/DR.

Functional and structural correlates of abnormal involuntary movements in psychosis risk and first episode psychosis.

BACKGROUND: Abnormal involuntary movements (AIM) may occur throughout the course of psychosis. While AIM are thought to indicate striatal abnormalities, the functional and structural correlates of increased AIM remain elusive. Here, we examined the prevalence of AIM in patients with clinical high risk for psychosis (CHR), first episode psychosis (FEP) and clinical controls (CC). Furthermore, we tested the association of AIM with regional cerebral blood flow (rCBF), grey matter volume (GMV), and premorbid IQ. METHODS: We conducted a video-based analysis of AIM in patients with CHR (n = 45), FEP (n = 10) and CC (n = 39), recruited in the Early Detection and Intervention Center, Bern. Premorbid intelligence was evaluated using the Peabody Picture Vocabulary test. Additionally, arterial spin labeling MRIs and structural MRIs were acquired in a subgroup of the sample to investigate the association of AIM with rCBF and GMV. RESULTS: Higher total AIM scores were detected in CHR (p = 0.02) and FEP (p = 0.04) as compared to CC. When separated for different muscle groups, lips and perioral movements were significantly increased in CHR patients as compared to CC (p = 0.009). AIM scores correlated positively with rCBF in the premotor cortex, Brodmann area 6 (p < 0.05, FWE corrected). Negative correlations were found between AIM and GMV of the corresponding caudal middle frontal gyrus (p = 0.04, FWE corrected) and premorbid intelligence (p = 0.02). CONCLUSIONS: AIM were more frequent in the psychosis spectrum than in clinical controls. Neuroimaging findings indicate an involvement of cortical motor areas in abnormal motor behavior, instead of pure basal ganglia pathology.

BOLD correlates of continuously fluctuating epileptic activity isolated by independent component analysis.

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.

Theta burst transcranial magnetic stimulation is associated with increased EEG synchronization in the stimulated relative to unstimulated cerebral hemisphere.

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.

Increased Striatal and Reduced Prefrontal Cerebral Blood Flow in Clinical High Risk for Psychosis.

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.

Publisher Correction: Personalized structural image analysis in patients with temporal lobe epilepsy.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Striatal cerebral blood flow, executive functioning, and fronto-striatal functional connectivity in clinical high risk for psychosis.

BACKGROUND: Patients at clinical high risk (CHR) for psychosis exhibit increased striatal cerebral blood flow (CBF) during the resting state and impaired cognitive function. However, the relation between CBF and cognitive impairment is unknown. We therefore studied the association between striatal CBF and executive functioning and evaluated the functional connectivity (FC) between dorsal striatum and the frontal cortex in CHR. METHODS: In total, 47 participants [29 with CHR, 18 matched clinical controls (CC)] were assessed for ultra-high-risk criteria and basic symptoms and were tested for executive functioning using the trail making test-B (TMT-B). Resting state mean CBF and FC were calculated from arterial spin labeling 3T MRI data. RESULTS: Striatal CBF was highest in CHR patients with TMT-B deficits and was significantly higher than that in CC with and without TMT-B impairment. Further, a significantly lower CBF FC between the dorsal striatum and the anterior cingulate cortex was revealed in CHR. CONCLUSIONS: Our study suggests that higher striatal CBF might represent focal pathology in CHR and is associated with disrupted cingulo-striatal FC and executive dysfunctions.

Personalized structural image analysis in patients with temporal lobe epilepsy.

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.

Implication of cerebral circulation time in intracranial stenosis measured by digital subtraction angiography on cerebral blood flow estimation measured by arterial spin labeling.

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.

Focal and Generalized Patterns of Cerebral Cortical Veins Due to Non-Convulsive Status Epilepticus or Prolonged Seizure Episode after Convulsive Status Epilepticus - A MRI Study Using Susceptibility Weighted Imaging.

OBJECTIVE: The aim of this study was to investigate variant patterns of cortical venous oxygenation during status epilepticus (SE) using susceptibility-weighted imaging (SWI). METHODS: We analyzed magnetic resonance imaging (MRI) scans of 26 patients with clinically witnessed prolonged seizures and/or EEG-confirmed SE. All MRI exams encompassed SWI, dynamic susceptibility contrast perfusion MRI (MRI-DSC) and diffusion-weighted imaging (DWI). We aimed to identify distinct patterns of SWI signal alterations that revealed regional or global increases of cerebral blood flow (CBF) and DWI restrictions. We hypothesized that SWI-related oxygenation patterns reflect ictal or postictal patterns that resemble SE or sequelae of seizures. RESULTS: Sixteen patients were examined during nonconvulsive status epilepticus (NCSE) as confirmed by EEG, a further ten patients suffered from witnessed and prolonged seizure episode ahead of imaging without initial EEG. MRI patterns of 15 of the 26 patients revealed generalized hyperoxygenation by SWI in keeping with either global or multifocal cortical hyperperfusion. Eight patients revealed a focal hyperoxygenation pattern related to focal CBF increase and three patients showed a focal deoxygenation pattern related to focal CBF decrease. CONCLUSIONS: SWI-related hyper- and deoxygenation patterns resemble ictal and postictal CBF changes within a range from globally increased to focally decreased perfusion. In all 26 patients the SWI patterns were in keeping with ictal hyperperfusion (hyperoxygenation patterns) or postictal hypoperfusion (deoxygenation patterns) respectively. A new finding of this study is that cortical venous patterns in SWI can be not only focally, but globally attenuated. SWI may thus be considered as an alternative contrast-free MR sequence to identify perfusion changes related to ictal or postictal conditions.

Morphological Brain Changes after Climbing to Extreme Altitudes--A Prospective Cohort Study.

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 (7126 m) 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 7000 m. 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.

Spinal Spot Sign.

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.

Static and dynamic characteristics of cerebral blood flow during the resting state in schizophrenia.

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.

Hippocampus is place of interaction between unconscious and conscious memories.

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.

Resected Brain Tissue, Seizure Onset Zone and Quantitative EEG Measures: Towards Prediction of Post-Surgical Seizure Control.

BACKGROUND: Epilepsy 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. METHODS: Despite 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. RESULTS: In 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. CONCLUSIONS: We 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.

Monitoring cerebral oxygenation during balloon occlusion with multichannel NIRS.

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.