Miralena I. Tomescu

Deviant dynamics of EEG resting state pattern in 22q11.2 deletion syndrome adolescents: A vulnerability marker of schizophrenia?

Previous studies have repeatedly found altered temporal characteristics of EEG microstates in schizophrenia. The aim of the present study was to investigate whether adolescents affected by the 22q11.2 deletion syndrome (22q11DS), known to have a 30 fold increased risk to develop schizophrenia, already show deviant EEG microstates. If this is the case, temporal alterations of EEG microstates in 22q11DS individuals could be considered as potential biomarkers for schizophrenia. We used high-density (204 channel) EEG to explore between-group microstate differences in 30 adolescents with 22q11DS and 28 age-matched controls. We found an increased presence of one microstate class (class C) in the 22q11DS adolescents with respect to controls that was associated with positive prodromal symptoms (hallucinations). A previous across-age study showed that the class C microstate was more present during adolescence and a combined EEG-fMRI study associated the class C microstate with the salience resting state network, a network known to be dysfunctional in schizophrenia. Therefore, the increased class C microstates could be indexing the increased risk of 22q11DS individuals to develop schizophrenia if confirmed by our ongoing longitudinal study comparing both the adult 22q11DS individuals with and without schizophrenia, as well as schizophrenic individuals with and without 22q11DS.

Altered auditory processing in frontal and left temporal cortex in 22q11.2 deletion syndrome: a group at high genetic risk for schizophrenia.

In order to investigate electroencephalographic (EEG) biomarkers of auditory processing for schizophrenia, we studied a group with a well known high-risk profile: patients with 22q11.2 deletion syndrome (22q11 DS) have a 30% risk of developing schizophrenia during adulthood. We performed high-density EEG source imaging to measure auditory gating of the P50 component of the evoked potential and middle to late latency auditory processing in 21 participants with the 22q11.2 deletion and 17 age-matched healthy controls. While we found no indication of altered P50 suppression in 22q11 DS, we observed marked differences for the first N1 component with increased amplitudes on central electrodes, corresponding to increased activations in dorsal anterior cingulate and medial frontal cortex. We also found a left lateralized reduction of activation of primary and secondary auditory cortex during the second N1 (120ms) and the P2 component in 22q11 DS. Our results show that sensory gating and activations until 50ms were preserved in 22q11 DS, while impairments appear at latencies that correspond to higher order auditory processing. While the increased activation of cingulate and medial frontal cortex could reflect developmental changes in 22q11 DS, the reduced activity seen in left auditory cortex might serve as a biomarker for the development of schizophrenia, if confirmed by longitudinal research protocols.

Schizophrenia patients and 22q11.2 deletion syndrome adolescents at risk express the same deviant patterns of resting state EEG microstates: A candidate endophenotype of schizophrenia

Schizophrenia is a complex psychiatric disorder and many of the factors contributing to its pathogenesis are poorly understood. In addition, identifying reliable neurophysiological markers would improve diagnosis and early identification of this disease. The 22q11.2 deletion syndrome (22q11DS) is one major risk factor for schizophrenia. Here, we show further evidence that deviant temporal dynamics of EEG microstates are a potential neurophysiological marker by showing that the resting state patterns of 22q11DS are similar to those found in schizophrenia patients. The EEG microstates are recurrent topographic distributions of the ongoing scalp potential fields with temporal stability of around 80 ms that are mapping the fast reconfiguration of resting state networks. Five minutes of high-density EEG recordings was analysed from 27 adult chronic schizophrenia patients, 27 adult controls, 30 adolescents with 22q11DS, and 28 adolescent controls. In both patient groups we found increased class C, but decreased class D presence and high transition probabilities towards the class C microstates. Moreover, these aberrant temporal dynamics in the two patient groups were also expressed by perturbations of the long-range dependency of the EEG microstates. These findings point to a deficient function of the salience and attention resting state networks in schizophrenia and 22q11DS as class C and class D microstates were previously associated with these networks, respectively. These findings elucidate similarities between individuals at risk and schizophrenia patients and support the notion that abnormal temporal patterns of EEG microstates might constitute a marker for developing schizophrenia.

Visual processing deficits in 22q11.2 Deletion Syndrome

Carriers of the rare 22q11.2 microdeletion present with a high percentage of positive and negative symptoms and a high genetic risk for schizophrenia. Visual processing impairments have been characterized in schizophrenia, but less so in 22q11.2 Deletion Syndrome (DS). Here, we focus on visual processing using high-density EEG and source imaging in 22q11.2DS participants (N = 25) and healthy controls (N = 26) with an illusory contour discrimination task. Significant differences between groups emerged at early and late stages of visual processing. In 22q11.2DS, we first observed reduced amplitudes over occipital channels and reduced source activations within dorsal and ventral visual stream areas during the P1 (100–125 ms) and within ventral visual cortex during the N1 (150–170 ms) visual evoked components. During a later window implicated in visual completion (240–285 ms), we observed an increase in global amplitudes in 22q11.2DS. The increased surface amplitudes for illusory contours at this window were inversely correlated with positive subscales of prodromal symptoms in 22q11.2DS. The reduced activity of ventral and dorsal visual areas during early stages points to an impairment in visual processing seen both in schizophrenia and 22q11.2DS. During intervals related to perceptual closure, the inverse correlation of high amplitudes with positive symptoms suggests that participants with 22q11.2DS who show an increased brain response to illusory contours during the relevant window for contour processing have less psychotic symptoms and might thus be at a reduced prodromal risk for schizophrenia.

From swing to cane: Sex differences of EEG resting-state temporal patterns during maturation and aging

While many insights on brain development and aging have been gained by studying resting-state networks with fMRI, relating these changes to cognitive functions is limited by the temporal resolution of fMRI. In order to better grasp short-lasting and dynamically changing mental activities, an increasing number of studies utilize EEG to define resting-state networks, thereby often using the concept of EEG microstates. These are brief (around 100 ms) periods of stable scalp potential fields that are influenced by cognitive states and are sensitive to neuropsychiatric diseases. Despite the rising popularity of the EEG microstate approach, information about age changes is sparse and nothing is known about sex differences. Here we investigated age and sex related changes of the temporal dynamics of EEG microstates in 179 healthy individuals (6–87 years old, 90 females, 204-channel EEG). We show strong sex-specific changes in microstate dynamics during adolescence as well as at older age. In addition, males and females differ in the duration and occurrence of specific microstates. These results are of relevance for the comparison of studies in populations of different age and sex and for the understanding of the changes in neuropsychiatric diseases.

EEG Indices of Cortical Network Formation and Their Relevance for Studying Variance in Subjective Experience and Behavior

The EEG is a highly sensitive marker for brain state, such as development, different states of consciousness and neuropsychiatric disorders. The classical spectral quantification of EEG suffers from requiring analysis epochs of 1 s or more that may contain several, and potentially quite different brain functional states. Based on the identification of subsecond time periods of stable scalp electric fields, EEG microstate analysis provides information about brain state on a time-scale that is compatible with the speed of human information processing. The present chapter reviews the conceptual underpinnings of EEG microstate analysis, introduces the methodology, and presents an overview of the available empirical findings that link EEG microstates to subjective experience and behavior under normal and abnormal conditions.

P358 EEG resting states are altered in focal epilepsy

Introduction Resting states represent the basic “atoms of thought” in the resting EEG but were found to be altered in a number of psychiatric and dementia conditions. In most studies, 4 basic maps are described (A = auditory, B = visual, C = salience, D = attention). In the present study we wanted to determine if EEG resting states are also altered in patients with chronic epilepsy Methods 25 patients with chronic unifocal epilepsy were included. All patients underwent 37 channel EEGs. Three minutes of wake EEG without any detectable spikes were selected. We fitted the 4 EEG microstates to the: (i) EEG of patient without any visible spike and (ii) resting-state EEGs of 48 healthy-controls (HC). Global Explained Variance (GEV), Mean duration (MD) and Time Coverage (TC) were used to characterize the map amount. Results We found a significant GEV increase of map-D (p  Conclusion Physiologic resting state networks are significantly altered in patients with chronic epilepsy, which affects mainly the so-called salience (map-C) and attention states (map-D). Saliency networks include the anterior insula and dorsal anterior cingulate and play a crucial role in identifying relevant events to guide and adapt behavior. The increase of the attention map (parietal cortex, anterior cingulate, thalamus) probably reflects compensation of impaired salience functions. Further studies will determine if these changes could become an EEG biomarker of epilepsy, e.g. for patients with spike-negative EEG.