Early clinical detection in psychotic disorders has become a major objective of mental health services, while research on the early phases of the disorder may provide important clues to the pathophysiology underlying psychotic symptoms. Thus, the identification of a clinical syndrome that reflects a predisposition to schizophrenia is fundamental from a clinical and a research perspective. The onset of schizophrenia is usually preceded by a prodromal phase characterized by functional decline and subtle negative symptoms. Structural and functional neuroimaging techniques including brain connectivity analyses have rapidly developed into a powerful tool in psychiatry. In this presentation it will be aimed to show that neuroimaging studies of the prodromal phases of psychosis have the potentials to identify core markers of vulnerability to psychosis and to clarify the onset of psychosis.

Organizer: Matti Stenroos, Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Finland

To understand and treat the human brain, we need to understand its dynamical activity. Brain oscillations, for example, have been associated with perceptive and cognitive functions, but the mechanism of coupling between the oscillations and brain function is not well understood yet. To study this coupling or the interaction between nodes in a functional brain network, we need to be able to modulate the brain in a controlled way and measure the effects of this modulation online. Non-invasive electric or magnetic brain stimulation (NIBS) offers a way for modulating the brain activity directly at electrophysiological level, and the effects of stimulation can be measured using electro- or magnetoencephalography (EEG, MEG).

To reliably measure the effects of electric stimulation during the stimulation and to ensure the repeatability of the experiment, we need dedicated hardware. To plan a stimulation study, to accurately navigate the stimulation coil, and to interpret the measured data, we greatly benefit from modeling of the stimulation and measurement. To optimally manipulate brain dynamics, we need to time the stimulation accurately with brain oscillations that need to be extracted from EEG data in near real time. In this symposium, we discuss these key methodological issues of NIBS and combined NIBS+MEG/EEG and present our latest results. The symposium brings together renowned experts in the field of methodological developments for NIBS & EEG/MEG.

The symposium is complementary to Gregor Thut's keynote lecture, taking a more methodological perspective.

We introduce a bifunctional flexible textile cap for simultaneous TES-EEG applications with novel electrode materials, textile stimulation electrodes and dry EEG electrodes. We verified the functionality of this cap in a study on ten volunteers, analyzing the stimulation effect of TES on visual evoked potentials (VEPs). In accordance to previously reported stimulation effects, the amplitude of the N75 component was modulated post stimulation. Further, we report for the first time a significant reduction of the P100 component in VEPs measured simultaneously during TES. The novel bifunctional cap overcomes limitations of conventional equipment for simultaneous TES-EEG studies.

I will provide evidence that field modeling informed by individual structural MRI combined with electromyographical recordings of peripheral muscle responses to TMS can help to pinpoint the stimulated brain region and reveal the stimulation depth of TMS. I will further show that realistic field modeling can help to determine the origin of interindividual differences in the physiological TMS effects. Finally, I will report on recent advances in Magnetic Resonance Current Density Imaging (MRCDI) to measure the current flow pattern caused by the weak currents injected by electric brain stimulation in the human brain.

To understand and treat the human brain, we need to understand its dynamical activity. Brain oscillations, for example, have been associated with perceptive and cognitive functions, but the mechanism of coupling between the oscillations and brain function is not well understood yet. To study this coupling or the interaction between nodes in a functional brain network, we need to be able to modulate the brain in a controlled way and measure the effects of this modulation online. Non-invasive electric or magnetic brain stimulation (NIBS) offers a way for modulating the brain activity directly at electrophysiological level, and the effects of stimulation can be measured using electro- or magnetoencephalography (EEG, MEG).

To reliably measure the effects of electric stimulation during the stimulation and to ensure the repeatability of the experiment, we need dedicated hardware. To plan a stimulation study, to accurately navigate the stimulation coil, and to interpret the measured data, we greatly benefit from modeling of the stimulation and measurement. To optimally manipulate brain dynamics, we need to time the stimulation accurately with brain oscillations that need to be extracted from EEG data in near real time. In this symposium, we discuss these key methodological issues of NIBS and combined NIBS+MEG/EEG and present our latest results. The symposium brings together renowned experts in the field of methodological developments for NIBS & EEG/MEG.

The symposium is complementary to Gregor Thut's keynote lecture, taking a more methodological perspective.

Using custom-built state-dependent millisecond-accurate electroencephalography-triggered transcranial magnetic stimulation (EEG-TMS) of human motor cortex, we demonstrate that phases of EEG peak negativity versus EEG peak positivity of the endogenous sensorimotor µ-alpha rhythm reflect high- vs. low-excitability states of corticospinal neurons. Moreover, otherwise identical repetitive TMS, triggered consistently at these high-excitability vs. low-excitability states, leads to LTP- vs. LTD-like change in corticospinal excitability. This raises the intriguing possibility that real-time information of instantaneous brain state can be utilized to control direction of plasticity in humans, a prospective with clear potential for therapeutic modulation of brain networks in psychiatric and neurological disease.

Several Authors proposed a dimensional approach to the reduction of schizophrenia heterogeneity. Initially, delusions, hallucination and disorganization were included in the positive dimension of psychosis. However, factor-analytic studies supported the existence of two separate clusters for the positive dimension: reality distortion, including hallucinations and delusions, and disorganization, including disorganized language and behavior, inappropriate affect and some features of cognitive impairment. These clusters emerged as separate domains of psychopathology, with distinct impacts on the outcome of schizophrenia and separate neuropsychological and brain imaging correlates.

This symposium will present recent electrophysiological and brain imaging findings supporting the neurobiological heterogeneity of reality distortion and disorganization in psychosis. Associations of these dimensions (and their constituent features) with indices of functional brain alterations in subjects at high risk for psychosis, as well as in those with first-episode or chronic schizophrenia will be reviewed.

A reduced amplitude of the auditory mismatch negativity (MMN), an ERP component thought to reflect updating of the stimulus context, is associated with positive symptoms (including auditory hallucinations) in chronic schizophrenia patients. It is unclear, however, whether the association between positive symptoms and MMN reductions can be observed in the early phase of the illness. We report that positive symptoms are associated with reductions of mismatch negativity elicited by both stimulus-change and pattern paradigms in early phase psychosis patients. This suggests that a link between positive symptom severity and brain functional alterations is present already in the earliest stages of the illness.

In subjects with schizophrenia (SCZ), the disorganization factor was found to be a strong predictor of real-life functioning. “Conceptual disorganization” (P2), “Difficulty in abstract thinking” (N5) and “Poor attention” (G11) are considered core aspects of the disorganization factor, as assessed by PANSS. The overlap of these items with neurocognitive functions is debated, and should be further investigated.

Within the Italian Network for Research on Psychoses study, electrophysiological and neurocognitive correlates of the disorganization factor and its component items were investigated.

In 145 chronic SCZ and 69 healthy controls, spectral amplitude (SAmp) differences and correlations with psychopathology and MATRICS Consensus Cognitive Battery (MCCB) scores were explored by RAGU.

A negative correlation between Alpha1 and the disorganization factor was observed in SCZ. At the item level, only ‘Difficulty in abstract thinking’ showed this correlation. MCCB neurocognitive composite score was associated with ‘Conceptual disorganization’ and ‘Difficulty in abstract thinking’ but not with Alpha1 SAmp.

Our findings suggest an heterogeneity of the disorganization dimension and a partial overlap with neurocognitive domains. The N5, “difficulties in abstract thinking”, had a unique association with alpha1 SAmp, which is thought to be involved in the formation of conceptual maps.

Formal thought disorders (FTD) are a core symptom in schizophrenia. We focus on distinguishable state cerebral blood flow (rCBF) patterns and white matter (WM) microstructure associated with FTD dimensions. We assessed FTD dimensions and imaging on a 3T MRI scanner. Positive FTD were associated with perfusion within brain regions relevant for language production, while negative FTD were associated with perfusion of semantic processing regions and fractional anisotropy in left hemispheric language system. Perfusion within the left supramarginal gyrus was associated with social functioning after 6 months. Distinguishable associations with FTD dimensions point to distinct underlying pathophysiology.

Abnormal salience processing has been found in people at ultra-high risk (UHR) for psychosis. In our study, using fMRI, we assessed the relationship between changes in the clinical features of 23 UHR and longitudinal changes in Ventral Striatum (VS) activation elicited during the Salience Attribution task. In UHR, we observed that the amelioration of abnormal beliefs over the follow-up period is linked to a longitudinal increase in VS activation during adaptive reward prediction.

Our results indicate a relationship between clinical outcome and longitudinal changes in ventral striatum during salience processing in UHR.

The neurological or psychiatric diseases distort the communication in the brain’s connected networks. In a sense, a person with a brain disorder can become unreachable due to dysfunctional integration within and across brain networks as well as impaired processing and integration of incoming sensory signals. The brain’s ability to adapt depends on feedback signaled through the five sensory channels, which produce neuronal synchrony which drives neuronal plasticity. Hence, deficiencies in communication via the senses requires alternative ways to engage adaptation in a diseased brain— one potent way is via transcranial neuromodulation, bypassing the afferents sensory channels, another one is to use the brain activity translated into signals sent as feedback via multimodal sensory channels (brain based neurofeedback).

Even in our personal experience, sometimes the ‘magic’ understanding with a dear person can get sick, we do not understand each other anymore. And, which is the wisest advice in this case? TO LISTEN!

Aiming at developing proper neuromodulation interventions, we propose listening to the brain affected by a disease via proper neuroimaging techniques.

Symposium speakers will present methods and proper strategies to define targets for neuroenhancing brain stimulation. Risto Ilmoniemi will describe the concept of feedback-controlled multi-coil TMS showing initial results. Frank Scharnowski will describe how to define targets for connectivity-based neurofeedback training aiming at normalizing dysfunctional brain networks; Toni Valero-Cabré, how to interact by invasive and non-invasive recordings and stimulations with rhythmic brain activity, with an example against neglect in stroke patients; Hartwig Siebner will describe how modeling can enhance noninvasive transcranial brain stimulation at the biophysical, network, and cognitive level; Franca Tecchio, how to personalize non-invasive neuromodulation anatomically or exploiting the neuronal dynamics of the target area, with a successful example against multiple sclerosis fatigue.

Changing the locus of transcranial magnetic stimulation (TMS) with present mechanically moved TMS coils is too slow for real-time feedback-controlled targeting. To overcome this limitation and to allow algorithmically guided closed-loop stimulation, we have introduced the concept of multi-coil TMS (mTMS) and developed technology to realize it with multiple overlapping coils. We have demonstrated that the new technology allows electronic control of stimulation location with arbitrarily small delays. In addition, with the new electronics, we have shown that TMS pulse shaping can yield information about neuronal ion-channel kinetics. I will discuss possible applications.

<p>Brain training via real-time fMRI-based neurofeedback can improve performance and clinical symptoms in neurological and psychiatric patients. Here, we inform the training by the connectivity between brain areas rather than the activity of a single node. Using this novel connectivity-based neurofeedback, we improved emotion regulation by training participants to voluntarily increase top-down connectivity from cognitive prefrontal areas onto limbic structures. Moreover, neurofeedback can help substance use disorder patients to learn voluntary control over neurotransmitter centers such as the dopaminergic midbrain, thus indirectly modifying their dopaminergic reward system. These novel methodological innovations allow to more specifically target disease-related brain malfunctions.</p>

<p>We are manipulating the brain activity by means of non-invasive and invasive bursts, in dependence on surface and intracerebral EEG recordings. In healthy humans, the rhythmic bursts TMS manipulation of the right Frontal Eye Fields increases the fronto-parietal synchrony and the conscious visual detection in a frequency specific manner. In treatment-resistant epilepsy patients implanted with depth electrodes, stimulated for clinical purposes with electrical bursts, the local neuronal power increases in a manner dependent on stimulation intensity, frequency, phase and position. We will discuss how manipulating brain networks’ synchrony may open new avenues to treat stroke visuo‑spatial neglect.</p>

The human brain can be stimulated with a wide range of non-invasive transcranial brain stimulation (NTBS) techniques. These methods have great potential as neuroscientific and therapeutic tools, but the application is hampered by substantial intra- and inter-subject variability of the acute and outlasting NTBS effects on brain function. In this talk, I will provide an overview over our recent attempts to obtain a mechanistic understanding of NTBS applying a triple-M approach, consisting of brain mapping, modeling and modulation. I will show how anatomically and physiologically informed NTBS can be used to shape human brain function. I will then show how multi-level modelling at the biophysical, local and network level can reveal how NTBS shapes neural activity in the human brain. Finally, I will touch on novel realizations of NTBS such as targeting brain oscillations with TMS or ultra-high frequency repetitive TMS.

I will present a successful example of adapting to fatigue-related brain dysfunction in people with multiple sclerosis a transcranial direct current stimulation (tDCS), which had increased endurance against fatigue in healthy subjects. The adaptation required a personalized electrode designed and positioned based on the patient’s 3D-brain MRI. While this compensation required an anatomical personalization, we are also personalizing a current-modulated transcranial electric stimulation (tES), by mimicking the local dynamics of the ongoing neuronal activity of the target region. We derived the target neurodynamics by Functional Source Separation (FSS)-equipped electroencephalography (EEG) and we obtained an enhancement of the neuromodulation effects, in particular at individual level.

It has been long suggested that the different symptom domains of schizophrenia are best explained in terms of aberrant connectivity within distributed brain networks.

Electrophysiological and brain imaging studies might contribute to disentangle the neurobiological basis of different psychopathological dimensions which might be related to disconnection within different networks.

The aim of our symposium will be to summarize recent electrophysiological and brain imaging findings of altered connectivity in psychotic disorders and their association with psychopathological domains.

We will report brain electrical microstate correlates of positive symptoms and discuss the involved pathophysiological mechanisms. This report will in particular be based on a recent meta-analysis conducted across the available literature, novel data we have obtained from at-risk patients, and existing literature on the fMRI BOLD correlates of particular microstate classes. The overall picture from this analysis points at a dysbalance between processes that integrate and evaluate representations of information from the external world with representations of internal states.

Negative symptoms represent a key aspect of schizophrenia, with a worse outcome and a poor response to pharmacological treatment. They cluster into two domains: “avolition”, which includes apathy, anhedonia and asociality, and “expressive deficit”, which includes blunted affect and alogia.

The aim of this study was to investigate the different neurobiological correlates of negative symptoms domains using brain electrical microstates (MS), which reflect global, subsecond patterns of functional connectivity.

Resting EEGs were recorded in 142 schizophrenia patients (SCZ) and in 64 healthy controls (HC), recruited within the add-on EEG study of the Italian Network for Research on Psychoses. Four microstates classes (MS-A to MS-D) were quantified in terms of relative time contribution, duration and occurrence. We tested group differences on MS parameters and the relationships with negative symptom domains, assessed using the Brief Negative Symptoms Scale (BNSS).

SCZ, in comparison to HC, showed increased contribution (p=0.009) and duration (p=0.016) of MS-C.

As regard to negative symptoms, the total score of the BNSS was positively correlated with the contribution of MS-A (r= 0.19, p<0.03). Only avolition (r=0.22, p<0.01) and not expressive deficit (r=0.12, p=0.15) was correlated with contribution of MS-A. Within the avolition domain, anticipatory anhedonia (r=0.20, p=0.02), apathy (r=0.20, p=0.02) and asociality (r=0.25, p=0.003), but not consummatory anhedonia (r=0.13, p=0.13), were positively correlated with MS-A.

Our results support different neurobiological underpinnings of negative symptom domains and suggest the idea that only anticipatory anhedonia and not consummatory anhedonia shares common pathophysiological mechanisms with avolition.

<p>We investigated relations between resting-state EEG Source Functional Connectivity (EEG-SFC) and Expressive Deficit (ED) and Avolition (AV) measured with BNSS, in subjects with Schizophrenia (SCZ).</p>

<p>Out of 97 chronic, stabilized SCZ recorded, we selected 25 in upper (HIGH-ED) and 24 in the lower (LOW-ED) quartile of BNSS-ED and 27 in upper (HIGH-AV) and 24 in the lower (LOW-AV) quartile of BNSS-AV.</p>

<p>Respect to LOW-ED, HIGH-ED showed significant increased alpha connectivity in fronto-cingulate, para-hippocampal and insular inter-hemispheric regions. No significant difference emerged between HIGH-AV and LOW-AV in the source connectivity.</p>

<p>Subgrouping SCZ according to negative symptom severity reveals heterogeneous patterns of resting-state EEG-SFC.</p>

Auditory cortices show pathological activation during auditory verbal hallucinations (AVH) in schizophrenia, and reduced cortical gray matter volumes at first hospitalization that worsen with disease course. Here we explored the role of interhemispheric transcallosal connectivity in AVH in 31 first episode schizophrenia-spectrum psychosis (FESz). Spearman’s rank-order correlation revealed a relationship between reduced generalized functional anisotropy and increased AVH (rho = -.43, p =.016). This finding suggests that impaired structural connectivity between left and right hemisphere auditory cortices may play a role in AVH and the emergence of psychosis.

[Introduction] We investigated the changes in directional cross frequency interactions between theta and alpha oscillations, across six cortical regions, induced by a symptom provocation procedure, in patients with obsessive compulsive disorder (OCD), and in a normal control group.

[Methods] Nine OCD outpatients and nine healthy controls participated in this study. Awake, eyes closed EEG was recorded under conditions (C1) initial rest, (C2) while gently holding a clean paper towel, and (C3) under the instruction to imagine that the towel is repulsively contaminated (symptom provocation, SP). For each condition, signals of cortical electric neuronal activity (i.e. current density) were calculated with sLORETA at medial-prefrontal, precuneus, inferior-parietal, and dorsolateral-prefrontal cortices. Instantaneous amplitudes for the theta (4-8Hz) and alpha (9-14Hz) bands were obtained and used for computing Granger causal directional cross-frequency, cross-cortical interactions.

[Results] The effect of SP was assessed by comparing conditions C2 minus C3. In controls, SP is characterized by a significant increase in mPFC theta due to right fronto-parietal alpha. In contrast, SP in the OCD group mainly displayed alpha-alpha RIPL alpha decrease due to RDLPFC. A direct comparison of OCD and normal controls in the SP condition (C2) showed significant frontal decreases of theta-alpha interactions.

[Discussion] The symptom provocation procedure induced functional changes of cross-frequency connections both in OCD and control mainly involving core right hemisphere network nodes. Functional cross-frequency interactions involving all frontal nodes were decreased in OCD compared to controls during SP. These results support the use of cross-frequency interactions a possible trait marker of OCD.

Background: Neurexan® is a medicinal product containing four ingredients; passionflower, oats, coffee and zinc valerianate. It has been shown to reduce nervousness, restlessness, acute stress, and insomnia by modulating biological auto-regulating processes. Induced stress sensitizes the amygdala, which increases vigilance and in turn drives the stress response. This is mediated by an amygdala-prefrontal cortex circuit, in which stress impairs the top-down cognitive functions of prefrontal regions, while strengthening the emotional bottom-up responses of the amygdala. We therefore hypothesized that Neurexan® may induce changes in amygdala activation during emotion processing elicited by an emotional expectancy task.

Method: The drug effect was investigated in a randomized, placebo-controlled, double-blind, two-period-crossover clinical trial. The brain response of 37 male subjects to the emotional expectancy paradigm was measured after intake of a single dose of Neurexan® or placebo by 3T functional magnetic resonance imaging. During the task, negative, positive, and neutral IAPS pictures were presented, half of them preceded by visual cues. The visual cues before picture presentation were arrows pointing up (positive picture), down (negative picture) and to the right (neutral picture). The drug effect was assessed with paired t-test comparing drug and placebo condition in the contrast expectancy positive > expectancy negative.

Results: We found amygdala activation in response to expected pictures. Furthermore, we observed significant differences in activation of the left amygdala during the expectancy task under drug compared to placebo condition. The differences in activation are explained by reduced changes in amygdala reactivity modulated by Neurexan® during expectancy of emotional pictures.

Objectives: Neurexan® is a medicinal product containing four ingredients, passionflower, oats, coffee, and zinc valerianate. Neurexan® has been shown to reduce nervousness, restlessness, acute stress, and insomnia. Recent research suggested that it attenuates the neuroendocrine stress response in healthy volunteers. It is known that acute stress initiates changes in functional connectivity (FC) between amygdala and cortical regions. Additionally, changes in amygdala centered resting state functional connectivity (rs-FC) are also associated with trait and pathological anxiety. In the present study, we explored if Neurexan® moderates the effect of acute stress on the amygdala-centered rs-FC and if this is further influenced by trait anxiety or behaviors related to anxiety symptoms.

Methods: Thirty-nine healthy male subjects (age=43.7±9.8) participated in a double-blind, randomized, placebo-controlled, crossover clinical trial employing fMRI imaging. In each scanning session, an 11-min resting state (RS) measurement was performed at two time points: after the intake of a single dose of Neurexan® or placebo (RS1), and after the participants completed the stress task (RS2). Bilateral centromedial (CeA) and basolateral (BLA) subregions of the amygdala were used as seeds to calculate resting state FC maps. The treatment effects were analyzed with whole–brain within–subject ANOVA.

Results: A significant effect of Neurexan® was found on rs-FC between left centromedial amygdala and cortical regions including the left PFC and IFG as well as right centromedial amygdala and precuneus, right IFG and IPL. Furthermore, anxiety measures predicted the Neurexan® effect on stress-induced rs-FC changes from right BLA to vmPFC, left Amygdala, and right IFG.

Objectives: Cardiovascular function is critical to adaptive behavior and can be measured by heart rate variability (HRV) which is controlled by the Autonomic Nervous System (ANS). Previous studies have shown that the ongoing variability in ANS tone measured by HRV is associated with stress-induced changes in dACC and amygdala functional connectivity. Neurexan®, a medicinal product sold over the counter, contains passionflower, oats, coffee and zinc valerianate. It has been investigated in patients with symptoms related to acute stress, nervousness/restlessness, and insomnia. The previous research suggested attenuated neuroendocrine stress response in healthy volunteers, altered stress reactivity, and lowered amygdala activation after Neurexan® intake. This study explores the effects of Neurexan® on the sympathetic and parasympathetic nervous systems and the stress responsivity in ANS measured by HRV.

Methods: Thirty-nine healthy male subjects participated in a double-blind, randomized, placebo-controlled, two-period crossover study assessing HRV during the scanning sessions. On the first treatment day, half of the participants took Neurexan® (N=20) or placebo (N=19) and vice versa on the second day. The participants performed the ScanSTRESS, which uses arithmetic and mental rotation tasks to induce stress, after intake of Neurexan® or placebo, respectively. Heart rate was continuously measured by photoplethysmography.

Results: To measure the drug effect, we performed paired t-test between drug and placebo conditions during the stress task. We found a significant drug effect in low frequency and high frequency ratio (LF/HF ratio) (p = 0.01; T=-2.5). Under drug LF/HF was significantly reduced compared to placebo, suggesting a dampened stress response.

The P300 is one of the most investigated event-related potentials (ERPs) in the study of psychiatric disorders. Nevertheless it suffers from a lack of specificity and sensitivity. In previous studies (Campanella et al., 2010; 2012), the application of a more ecological bimodal oddball design has shown an increased sensitivity of the P300 component .

In the present ongoing study we compare the results of a classic oddball design procedure with those of a more ecological bimodal design in three groups of patients presenting schizophrenia (SZ), schizoaffective (SA) and bipolar (BD) disorder matched to a group of healthy controls (HC). Patients were examined at three times: T0: admission at the hospital; T1: before leaving the hospital; and T2: six months after leaving the hospital. Patients were assessed through a structured clinical interview (SCID, ref), and a completion of different clinical evaluation scales (PANSS, Young Mania Scale, Beck, Stai,…). All groups were then confronted to an EEG recording (20 channels, A.N.T. software) during successive oddball tasks.

The objectives of this study are twofold: (1) investigate whether the use of a specific oddball task (visual vs. auditory vs. cross-modal) allowed to enhance the discriminative power of the P300 between psychotic patients and healthy controls; and (2) investigate the correlations between the evolution from To to T2 of the P300 and the evolution of the clinical evaluation of the patient.

Here we would like to present further results of this clinical study, especially those of the group of patients presenting schizophrenia.

Background: Neurexan®, a medicinal product sold over the counter, contains four ingredients; passionflower, oats, coffee and zinc valerianate. Neurexan® has been investigated in patients with symptoms related to acute stress, nervousness/restlessness, and insomnia. The previous research suggested an attenuated neuroendocrine stress response in healthy volunteers induced by Neurexan®. This study further explores the effects of Neurexan® on cognitive performance and attention that can be assessed by the oddball paradigm. It is generally recognized that stress is associated with cognitive impairments. Expecting that Neurexan® reduces the stress level, we hypothesized that subjects in the placebo group would be more susceptible to distraction compared to treatment group.

Methods: In a randomized, placebo-controlled, double-blind, two-period crossover trial, brain responses of 39 healthy, moderately stressed males were measured during an unattended auditory oddball paradigm via 64-channel electroencephalogram (EEG) after intake of a single dose of Neurexan® or placebo. The paradigm consisted of 80% standard tones and two types of deviant tones (10% frequency deviant; 10% duration deviant), presented in a pseudo-randomized order.

Results: Significant effect of Neurexan® on the latency of mismatch negativity decreased latency under treatment) was observed with repeated-measures ANOVA. The main effect of treatment (F(1,37)=4.297, p=.045, η2=.104) and significant treatment x deviant-type interaction (F(1,37)=8.828, p=.005, η2=.193) were found. Further Wilcoxon-test for paired samples showed that reduction of latency was present for the frequency deviant stimuli (z(37)=-2.85, p=.004).

Conclusion: Significant reduction of MMN latency under drug suggests that Neurexan® leads to subtle primary processing changes in term of reaction time.

Since the discovery of LSD, serotonergic hallucinogens have been used to experimentally model psychosis, even in animals. Its translational validity can be verified by the degree of similarity between various measurable values in both species. Consensus in behavior (disorganization, increased anxiety, occurrence of stereotypical movements) and information processing was already observed. Similarity in the EEG signal between psychotic patients and intoxicated rats has not yet been verified.

The aim of this study was to describe changes in cortical EEG after administration of various serotonergic hallucinogens – psilocin, LSD, mescaline and DOB and compare these results with human data of psychotic patients.

12 rats for each group were implanted with 14 cortical electrodes. EEG was recorded seven days later. After the first ten minutes of recording (baseline), the treatment was applied and recording continued for another 90 minutes. Only signal of selected time segments of behavioral inactivity was evaluated. Quantitative (spectral and coherence) analysis in the Neuroguide program was performed.

EEG power spectral analysis revealed a general decrease in absolute EEG power in all frequency bands in all drug conditions. A common reduction in coherences, especially fronto-temporal in higher frequencies has also been shown.

Serotonergic hallucinogens cause profound electrophysiological changes in the rat brain. The results also revealed some characteristic patterns in the EEG of individual substances. The observed decrease in functional connectivity in rats was also observed in human subjects under the influence of psychedelics and is, in some cases, a common finding in psychotic patients.

Introduction: The presented method deals with changes in human and rats brain functional EEG connectivity conditioned by administration of psilocin (in rats) and psilocybin (in human). The searched similarities between rats and human models are difficult to be found when preserving low-level information e.g. all combinations of connections within all frequency bands in all epochs. Here, we show that unique functional brain clusters coherently modulated by a particular substance are embedded in multi-dimensional space of coherences and can be extracted by appropriate dimensional reduction technique.

Methods: EEG recordings were acquired with respect to pharmacokinetics of psilocin (in rats) and psilocybin (in human). Weighted phase lag indices (WPLI) were calculated at four time epochs after administration. WPLI time differences between epochs were calculated and t-Distributed Stochastic Neighbor embedding (t-SNE) reduced data dimension. A number of clusters was determined by silhouette clustering index and similarities were labeled by k-means algorithm. Surrogate series preserving power spectrum of instantaneous angular frequency in EEG data were generated to statistically address the clustering properties.

Results: Preliminary results of psilocin in rats clearly showed four clusters of connections. Three clusters were localized intra-hemispherically and only one connected both hemispheres together. In human, the psilocybin resulted in two symmetric clusters distributed mostly intra-hemispherically.

Conclusion: Developed method is capable to extract individual (rats or human) and common (rats and human) long term connectivity dynamics induced by drug administration.

This work was supported by the grants GACR 17-23718S, AZV 15-29370A, Progres Q35, and project LO1611 under the NPU I program.

[Introduction] Transcranial Direct Current Stimulation (tDCS) is getting interests in treatment of psychiatric disorders. As the electrode montage of tDCS defines flow of stimulation current, optimization of an electrode montage is crucial for treatment applications.

The aim of this study is to investigate tDCS effects with different montages in patients with major depression.

[Methods] Eighteen patients and 20 healthy controls (HC) participated. 1 mA tDCS was administered for 20 min either on the DLPFC (F5 EEGelectrode) or medial prefrontal cortex (AFz). Patients and HC received tDCS on one of the site in a randomized order. The Positive and negative affect schedule (PANAS) and State-Trait Anxiety Inventory (STAI) tests were measured before and after tDCS for each session.

[Results] We found that PANAS negative affect scores in the patient group decreased after tDCS only in the F5 stimulation, while no effect in the AFz stimulation condition. No significant tDCS effects were observed in the STAI scores of patients. In controls, there was no significant changes neither in PANAS scores nor STAI scores.

[Conclusion] A previous tDCS study on location of F3 EEG electrode showed no significant changes in PANAS scores in patients with major depression (Wolkenstein and Plewnia, 2013). We consider this discrepancy can be explained by the difference in electrode montages. In conclusion, we argue that the anterior part of the DLPFC could have stronger potency for the treatment of major depression, consistent with subregional difference in treatment efficacy of rTMS on major depression.

Background

Disorganized speech has been shown to be related to functional and grey matter abnormalities in schizophrenia. However, the relationship between white matter and disorganized speech is poorly understood. We investigated the association between formal thought disorders (FTDs) and white matter microstructure in 61 patients with schizophrenia spectrum disorders. We hypothesized that FTDs are related to important fibers of the language system such as the uncinate fascicle and superior and inferior longitudinal fascicle.

Methods

The Bern Psychopathology Scale (BPS) organizes schizophrenia symptoms in three neurobiological dimensions, i.e. language, limbic and motor. The BPS was used to rate the dimension of language abnormalities ranging from negative FTDs to positive FTDs. Tract-based spatial statistics (TBSS) was used to study whole brain white matter abnormalities. Fractional anisotropy (FA) values were correlated with the BPS language dimension including age, gender, antipsychotic medication and the motor and affective dimensions of the BPS as covariates.

Results

The TBSS analysis indicated increased FA in left-hemispheric pathways of the language system in patients with negative FTDs; and lower FA values for patients with positive FTDs at p<0.05 (FWE corrected). The fiber tracts associated with FTDs included the left uncinate fascicle, superior and inferior longitudinal fascicle and the inferior fronto-occipital fascicle.

Discussion

We found an association of FTDs in schizophrenia and disturbed WM in language related pathways. Our findings are in line with the literature, linking FTDs in schizophrenia to structural and functional abnormalities in the language system. Thus, altered white matter properties in relevant fiber tracts may represent distinct pathobiology of specific formal thought disorders.

Objective : The aim of the study was to identify electrophysiological biomarkers of major depressive disorder (MDD) through high-density EEG technique.

Methods: Seven patients suffering from MDD and eight healthy controls underwent EEG recording using 128 or 256 scalp electrodes during eyes closed resting-state conditions. Microstate analysis was performed at individual and group levels. Microstate variants were identified and their parameters such as mean correlation, mean duration, time coverage, and segment count density were evaluated.

Results: Cross-validation criterion used to determine the most dominant topographies revealed six (A-F) microstates. The six microstates across subjects in each group explained more than 80% of global variance. Results of two-way repeated measures ANOVA revealed significant group x microstate interaction for segment count density. Post-hoc test revealed significant group difference for class A microstate, which showed decreased value in MDD patients.

Conclusion: Parameters revealed by microstate analysis are suggested to be possible electrophysiological biomarkers of functional brain abnormities in MDD patients.

The study has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 739939

Functional magnetic resonance imaging (fMRI) is useful to explore the brain’s functional organization and to examine whether functional organization is altered in patients with mental disorders. Functional connectivity can be defined as the synchrony of neural activity among regions. Areas of the brain which exhibit signal fluctuations correlated in time are assumed to be functionally connected. Independent component analysis allows us to decompose fMRI data into independent and non-Gaussian spatiotemporal components without any use of a reference function or predefined seed voxel. Independent component analysis is extensively applied as an exploratory analysis for the investigation of resting state functional connectivity. To examine the resting-state functional connectivity of mental disorders we evaluated resting-state networks in 20 patients with schizophrenia and 20 healthy participants using 3T MRI scanner. This study was approved by the local ethics committee, and written informed consent was obtained from all participants recruited. Independent component analysis was performed for all data using MELODIC of FSL (FMRIB, Oxford University, UK). Preliminary analysis showed that under each diagnostic grope similar pattern of functional connectivity was observed, however, there was anatomically aberrant activity in patients compared to control. We are planning to conduct deeper analysis of dual regression with increase the number of subject.

Background: Preterm birth has been associated with an increased risk for ADHD-like behavioural symptoms and cognitive impairments. However, direct comparisons across ADHD and preterm-born samples on neurophysiological measures are limited. The aim of this analysis was to test whether quantitative EEG (QEEG) measures identify differences or similarities in preterm-born adolescents, compared to term-born adolescents with and without ADHD, during resting-state and cognitive task conditions. Methods: We directly compared QEEG activity between 186 preterm-born adolescents, 69 term-born adolescents with ADHD and 135 term-born control adolescents during an eyes-open resting-state condition (EO), which previously discriminated between the adolescents with ADHD and controls, and during a cued continuous performance task (CPT-OX). Results: Absolute delta power was the only frequency range to demonstrate a significant group-by-condition interaction. The preterm group, like the ADHD group, displayed significantly higher delta power during EO, compared to the control group. In line with these findings, parent-rated ADHD symptoms in the preterm group were significantly correlated with delta power during rest. While the preterm and control groups did not differ with regard to absolute delta power during CPT-OX, the ADHD group showed significantly higher absolute delta power compared to both groups. Conclusion: Our results provide evidence for overlapping excess in the absolute delta range in preterm-born adolescents and term-born adolescents with ADHD during rest. During CPT-OX, preterm-born adolescents resembled controls. Increased delta power during rest may be a potential general marker of brain trauma, pathology or neurotransmitter disturbances.

Auditory Sensory Gating in Schizophrenia: relation with cognitive functioning, social cognition, socio-relational functioning

The neurophysiological effect of EMDR and TF-CBT in PTSD: an EEG study

Psychoses are aetiologically complex disorders that affect about 1 − 2% of the population during their lifetime. Psychotic symptoms are thought to represent disturbances in higher-order brain functions that can be grouped according to their dysfunction in one or more of the following three neural brain circuitries: language, affect, motor function. Dysfunction of the neural language brain circuitry has already been linked to disturbances in expressive speech and formal thought disorders. However, it remains currently unknown if the language brain circuitry is only disturbed in psychosis, or if already individuals at familial or clinical high-risk show some extend of aberrancy.

To examine the whole spectrum form health to psychosis, four different subject groups are being examined: healthy controls (HC), first-degree relatives of psychosis patients (REL), a clinical high-risk group (CHR) and psychosis patients (PAT). In total, 120 subjects (30 per group) will complete a lexical priming task during electroencephalography and functional magnetic resonance imaging.

On a behavioural level, we expect to find subtle language dysfunction in the REL and CHR group. Furthermore, we hypothesize that aberrant neural activation patterns are present during the language task in PAT, CHR and REL groups in comparison to HC individuals. Finally, we aim to depict that aberrant neural activation in language - related brain areas is most pronounced in the PAT group and to a lesser extend present in the REL group. With this study, we hope to improve diagnostic strategies, treatments and outcome predictions.

Visual backward masking (VBM) is a very sensitive endophenotype of schizophrenia. Masking deficits are highly correlated with reduced EEG amplitudes. In VBM, a target stimulus is followed by a mask, which decreases performance on the target. Here, we investigated the neural correlates of VBM in unaffected siblings of schizophrenia patients. We had three conditions: target only and two VBM conditions, with long and short inter-stimulus intervals (ISI). Patients’ performance was impaired, while the siblings performed at the same level as the controls. Interestingly, EEG peak amplitudes were higher in siblings compared to controls, while they were lower in patients relative to controls as previously reported. For siblings, EEG amplitudes were at the same level in all conditions. For controls and patients, EEG peak amplitudes increased with task difficult, e.g., amplitudes in the long ISI condition were lower than in short ISI condition. Our results suggest that unaffected siblings of schizophrenia patients use a compensation mechanism tuning the brain to maximum performance in all conditions. Since siblings are already at the peak of their activations, increasing the task difficulty does not change brain processing.

Despite identical diagnosis, patients with psychosis show a variety of clinical symptoms. Various psychosis symptoms relate to a disturbed perception, experience, regulation or expression of emotions. Previous research indicates that emotional dysregulation may form a distinct psychosis symptom dimension that is linked to aberrant function and structure of the limbic system and its cortico-basal ganglia and cortico-cortical connections. However, the nature of emotional dysregulation in psychosis has not been studied extensively yet. We expect that disturbed affect in psychosis may be best conceptualized as a dimension, that varies with psychosis vulnerability.

Neural activation patterns are investigated using functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) from four different subject groups: patients with psychosis, subjects at clinical high-risk for psychosis, first-degree relatives of patients with psychosis and healthy controls. During fMRI and EEG examination, a specifically developed face perception task is being used. The presented stimuli are short animations of faces that vary in certain characteristics: gender (male, female), aesthetic (high, low), head movement (up, down) and gaze direction (direct, averted). Subsequently, all face stimuli are rated with regard to gender, dominance, trustworthiness, aggressiveness, health and attractiveness.

We hypothesize that the four study groups differ in terms of event-related potentials and brain activation patterns in affect-related brain regions. Furthermore, we expect that these differences are being linked to measures of emotionality and emotional processes such as emotion regulation and perception. The expected results will give further insights in the psychopathology of psychosis and might improve future diagnostic and treatment options.

We have previously shown that EEG microstates during resting-state have a deviant pattern of temporal presence in a group of adolescents with 22q11.2 deletion syndrome (Tomescu et al., 2014), as well as in a different group of adults diagnosed with schizophrenia (Tomescu et al., 2015). To further explore the relationship between this deviant pattern and the development of schizophrenia, we computed partial least squares correlation (PLSC) between the temporal presence (characterized by the global explained variance (GEV) and duration) of the microstates and the symptoms assessed using the 19 item symptom scale from the structured interview for prodromal syndromes (SIPS, Miller et al., 2003) . The PLSC analysis allowed us to identify patterns of GEV and duration that covary with prodromal symptoms by computing latent variables (LVs), which represent the optimal link between these two modalities (Krishnan et al., 2010). Using permutation testing, we obtained a significant latent variable (5000 iterations, p= 0.03) explaining 62% of the covariance. This LV is characterized by significantly positive loadings of the GEV of microstates A and B and significantly negative loadings of the duration of microstates C and D. These temporal patterns (weighted by the loadings of the latent variable) were negatively correlated with several mostly negative prodromal symptoms, including social anhedonia (r=-0.441, p=0.014), expression of emotion (r=-0.45, p=0.01), experience of emotions and self (r=-0.37 (p=0.04), and disorganized communication (r=-0.36, p=0.050). Thus, temporal patterns of EEG microstates might be related to the severity of prodromal, negative symptoms in the 22q11DS.

Flexible adaptation to conflicting task demands plays an important role in everyday life and is impaired in many psychiatric disorders. As a prerequisite, cognitive control comes into play when task demands conflict, which may be reflected in brainelectrical activity as enhanced N2 amplitude under conflict (monitoring) in various tasks. Cognitive control may also play a role in Attention Deficit/Hyperactivity Disorder (ADHD), but studies on N2-Enhancement revealed mixed results.

The current study contrasts three task demands tapping conflict monitoring and cognitive control and their relation to ADHD. This was done in a sample of 94 children with ADHD in comparison to 43 Controls, aged 8 to 15 years using a Flanker-Task paradigm by contrasting processing of congruent and incongruent stimuli, and in Continuous Performance Tests by contrasting Go-Nogo demands and processing of additionally presented incongruent stimuli.

All three demands for cognitive control revealed significant N2-Enhancement, but differential ADHD effects thereon: N2-Enhancements in the CPT regarding Go-Nogo and processing of additional incongruent Flankers was similar in ADHD and Controls, while Flanker-Task Congruency revealed medium-sized ADHD effects.

The current results indicate that children with ADHD have medium-sized difficulties with cognitive control during some particular demand (e.g. with Flanker-Task Congruency that requires frequent responding) but not on others (e.g. during response-control in CPTs that require responding in only 10% of all trials). This highlights the importance of clinical studies for understanding cognitive control in different demands, and it may also indicate that moderators like arousal may play an important role for ADHD deficits.

To generate new treatments for ASD it is critical to understand the deviations in brain function from typically developing controls (TD) and to derive robust biomarkers to quantify those. Resting state EEG is a unique tool to explore non-invasively – and across a broad age range – the dynamics of spontaneous neuronal activity. Here we explored the developmental changes in ASD from childhood to adulthood in resting state EEG powerspectrum in the LEAP dataset of EU-AIMS (www.eu-aims.eu), using n=294 high functioning ASD and TD individuals from 6 to 30 years. More specifically, we investigated the alpha rhythm – the hallmark of resting state EEG, linked to sensory-motor and cognitive processes – and the powerspectrum over frequencies from 1 to 32 Hz at the sensor level and in source space. We quantified developmental trajectories with linear mixed effect models, accounting for confounding factors such as gender, IQ and site. Known typical developmental trajectories were recovered: with increasing age the alpha peak frequency increased, its amplitude decreased, relative power in 2-6Hz decreased and relative power 10-32Hz increased. The developmental changes in the ASD group followed closely that of the TD subjects, and accordingly no significant group effects were found. Additionally, no evidence for increased heterogeneity in ASD was found, since the modeled variances in both groups did not differ significantly. Overall, this indicates that the baseline 1 to 32 Hz power matures in high functioning ASD following a typical developmental trajectory.

Deficit schizophrenia (DS) is characterized by the presence of primary, enduring negative symptoms, and has different course, risk factors and clinical features with respect to non-deficit schizophrenia (ND).

Our aim was to investigate differences in white matter connectivity patterns in subjects with DS compared to ND and healthy controls (HC), using probabilistic analysis of diffusion tensor imaging (DTI) data.

Forty-six subjects with chronic schizophrenia (SCZ) and 35 HC, matched for age and gender, were examined using DTI. SCZ were classified as DS (n=9) or ND (n=37) using the Schedule for the Deficit Syndrome (SDS). Further assessments included the Positive and Negative Syndrome Scale (PANSS) and the MATRICS Consensus Cognitive Battery. Connectivity index (CI, % of the probabilistic streamlines originating from a region that reach a second one) and Fractional Anisotropy (FA) of the connections between bilateral dorso-lateral prefrontal cortex (DLPFC), nucleus accumbens (NAcc), amygdala (AMY) and insular cortex (IC) were examined.

We found a reduced CI between right AMY and DLPFC in SCZ compared to HC (p<0,0044), while there were no differences between DS and ND. DS showed an increased CI from right AMY to dorsal-anterior IC compared to ND (p<0,0036). Finally, in SCZ the FA of right NAcc-DLPFC connections directly correlated with PANSS disorganization dimension (p<0.0031).

These findings confirm previous evidences of distinct neurobiological substrates for different symptom dimensions and clinical subtypes of SCZ. Primary and persistent negative symptoms seem to be related to abnormal connectivity of brain regions involved in guiding goal-directed behavior based on experienced value.

Dysfunction of the reward system is probably related to the avolition/apathy domain of negative symptoms in schizophrenia. In particular, structural and functional abnormalities were reported in key regions within the reward system, including the ventral-tegmental area (VTA), the nucleus accumbens (NAcc), the orbito-frontal cortex (OFC) as well as the amygdala (AMY) and the insular cortex (IC).

Our aim was to investigate the white matter connectivity patterns within these regions in male subjects with schizophrenia, using probabilistic analysis of diffusion tensor imaging (DTI) data.

Thirty male subjects with schizophrenia (SCZ) and 17 male healthy controls (HC) matched for age, underwent DTI. SCZ were evaluated clinically with the Schedule for Deficit Syndrome (SDS), Positive and Negative Syndrome Scale (PANSS) and the MATRICS consensus cognitive battery (MCCB). Pathways connecting the AMY and the NAcc with the OFC and IC were evaluated.

Reduced fractional anisotropy (FA) was observed in left AMY-ventral anterior IC connection (p<0.0048), in SCZ compared to controls. This abnormality was negatively correlated with the avolition/apathy (p<0.0023) but not with the expressive deficit scores. SCZ showed also reduced connectivity indices (% of the probabilistic streamlines originating from a region that reach a second one) between right NAcc and medial OFC as compared to controls (p<0.0001). Finally the left NAcc-dorsal anterior IC connectivity index was negatively correlated with working memory (WM) scores (p<0.0013).

Our results confirm that the avolition/apathy but not the expressive deficit domain is related to reward system abnormalities. Distinct alterations seem to underlie cognitive impairment and avolition/apathy.

Introduction. Abnormalities in cognitive functions and motivation are core aspects of schizophrenia. One of the crucial aspects of cognitive impairment is the disturbance of cognitive control, or the ability to flexibly adjust behavior in accordance with one’s intentions and goals. A large literature has emerged focusing on the anterior N2 as a correlate of cognitive control based on motivational value.

Aims. Given the clinical importance of goal-directed behavior impairments in schizophrenia as a strong predictor of functional outcome, we aimed to study the impact of reward- and avoidance-based motivation on cognitive control using event-related potentials (ERPs).

Method. ERPs were recorded during the execution of the "Monetary Incentive Delay (MID)” task in 34 patients with schizophrenia (SCZ) stabilized on second generation antipsychotics and 22 healthy controls (HC). Negative symptom domains (avolition/apathy and expressive deficit), positive and disorganization dimensions were also assessed in SCZ.

Results. We did not observe any group difference in N2 amplitude or latency. In the HC group, N2 amplitude was significantly larger for anticipation of large punishment than reward and for all incentive conditions than neutral one. Unlike HC, N2 amplitude in SCZ did not discriminate motivational relevance. N2 amplitude was not correlated with psychopathological dimensions in SCZ.

Conclusion. Our results suggest that the discrimination of motivational value appears to be impaired in SCZ, independently of psychopathology. Future studies should be aimed to assess whether distinct subgroups within SCZ, in particular those with deficit features, might be characterized by this abnormality.

Long-term schizophrenia (Sz) and first episode schizophrenia spectrum (FE) patients have deficits in processing auditory and visual stimuli evidenced by reduced event-related potentials. Multisensory integration (MSI) is the process by which information from multiple modalities are integrated into a coherent percept. Findings from studies of non-linguistic MSI in Sz are equivocal. No studies have assessed MSI in FE. This study examined MSI by presenting 18 first episode matched healthy controls (FEHC), 26 chronic schizophrenia matched healthy controls (SzHC), 21 FE, and 29 Sz with auditory (A), visual (V), and simultaneous audiovisual (AV) stimuli. Auditory stimuli were presented as groups of 4 tones (1 kHz, 50ms, 5ms rise/fall, 330ms SOA, 750ms ITI). Visual stimuli (small blue circle, 50ms) were also presented in groups of 4. AV stimuli were the simultaneous presentation of the A and V stimuli. Participants were asked to sit silently and attend to the stimuli presented. MSI was calculated by subtracting the sum of the unisensory stimuli from the simultaneous audiovisual stimulus [AV – (A+V)]. MSI amplitude was calculated as the average voltage between 95-115ms and 180-190ms at PO9 and PO10, where previous studies have looked for MSI interactions. MSI at 95-115ms was more negative in SzHC (p=.011) compared to Sz, but no group differences were found in FE and FEHC (p=.968). MSI at 180-190ms was not significantly different from controls for Sz or FE. These results suggest that early MSI is impaired in Sz but not FE, and may serve as an indicator of disease progression.

Primary auditory cortex pathophysiology is linked to auditory deficits and auditory verbal hallucinations in schizophrenia. The aim of this study was to replicate associations between reductions in the magnitude of the mismatch negativity (MMN) response during a passive auditory task and reductions in gray matter volume in Heschl’s gyrus in subjects with first-episode schizophrenia (FESz). Participants included 28 FESz and 28 healthy control subjects matched for age, parental socioeconomic status, IQ, sex, and handedness. Freesurfer was used to segment white matter, gray matter, and pial surfaces from T1-weighted structural 3T MRI data (1mm x 1mm x 1mm). Gray matter was measured in left Heschl’s gyrus (containing primary auditory cortex). Pitch-deviant and duration-deviant MMN responses were measured as the averaged amplitude within a 100-ms window at Fz. In FESz, total gray matter volume in Heschl’s gyrus correlated with the magnitude of pitch MMN (rho = -.38, p <.05) and duration MMN (r = -.44, p <.05). There were no significant correlations between MMNs and Heschl’s gray matter volumes in the healthy control group, and the pathological correlations in FESz were significantly different from healthy controls (Fisher Z p <.05). Smaller Heschl’s gyrus in first episode schizophrenia patients is related to a smaller magnitude MMN for both pitch and duration deviants. This pathological relationship between MMN amplitude and Heschl’s gyrus volume in FESz suggests the presence of pre-psychosis gray matter loss in a subset of patients, and may be useful for tracking disease progression and as an outcome measure of successful interventions

The N1 auditory evoked potential is reduced in long-term schizophrenia (Sz) and in the first episode schizophrenia spectrum (FE). N1 is increased by attention, and this modulation is impaired in Sz. It is not known whether FE can modulate N1 by attention. This study examined N1 modulation by attention (Negative Difference; Nd) in FE, early in disease course. Thirteen FE and 11 matched healthy control (HC) participants heard sounds while watching a silent video. Participants heard repetitious tones in a typical AEP task (1k Hz, 50 ms duration, 5 ms rise/fall, 80 dB), spaced 1050 ms to 1550 ms apart. In one condition, participants were told to ignore tones, while in the other condition participants pressed a button to every 7th tone. Continuous EEG was recorded between DC and 104 Hz. After high pass filtering at 0.5 Hz and ICA artifact correction, data were low pass filtered at 20 Hz, epoched, and artifact rejected, and averages constructed. N1 amplitude was calculated as average voltage between 100 ms and 110 ms at Cz. Of primary importance, N1 amplitude was differentially affected by attention between groups (p =0.002). HC showed larger N1 with attention (p =0.01), but FE did not (p =0.27). This may reflect a long-range functional disconnection between cognitive control cortical areas and auditory sensory cortex early in disease course. Clinically, the lack of attention-related Nd in FE suggests it may serve as a sensitive biomarker for the detection of the schizophrenia prodrome among clinical high-risk individuals.

Auditory verbal hallucinations (AVH) are common in schizophrenia and may relate to abnormal connectivity between auditory cortices. We examined transcallosal auditory cortex tracts in 14 AVH+ first-episode schizophrenia patients (FESz), 15 AVH- FESz, and 23 healthy controls with diffusion spectrum imaging (DSI). AVH+ scored at least a 2 on auditory hallucinations, voices commenting, or voices conversing measured with the Scale for the Assessment of Positive Symptoms (SAPS). Groups were matched for age, parental socioeconomic status, education, IQ, gender, and handedness. A deterministic fiber tracking algorithm identified transcallosal auditory fibers, defined as 1000 fibers traversing the posterior third of the corpus callosum and ending bilaterally in Brodmann’s area 22, Heschl’s gyrus, or planum temporale. MANOVA revealed transcallosal auditory cortex connectivity differences between groups (F(6, 94) = 2.34, p = .038) driven by tract volume (F(2, 49) = 3.46, p =.039) and generalized functional anisotropy (gFA, F(2, 49) = 4.77, p = .013). Pairwise t-tests indicated lower gFA and greater tract volume for AVH+ vs AVH- (p’s < .05). Healthy controls trended towards greater gFA (p = .068) vs AVH+ and tract volume (p = .063) vs AVH-. All other comparisons were nonsignificant (p >.1). Reduced fiber tract directionality indicates less efficient transcallosal auditory connectivity in AVH+ FESz; smaller tract volume indicates potential reduced structural auditory cortex connectivity in AVH-. Interhemispheric auditory cortex functional connectivity abnormalities may underlie AVH in schizophrenia even early in disease course while overall structural connectivity differences may affect AVH- individuals. Interhemispheric connectivity differences may underlie symptom-level phenotypes.

Individuals with long-term schizophrenia (SZ) show reductions in simple mismatch negativity (MMN) to infrequent stimulus parameter deviance, and in complex MMN to infrequent pattern deviance. First episode schizophrenia-spectrum individuals (FE) show less reduction of simple MMN. Complex pattern deviance may be more suitable for elucidating subtle deficits in auditory perception at first-episode, and may be more useful for distinguishing between those with and those without schizophrenia. We measured complex MMN to an extra fourth tone amongst standard groups of three tones (1 kHz, 50 ms duration, 5 ms rise/fall, 80 dB, 330 ms SOA, 800 ms ITI) in 23 SZ), and 20 matched healthy controls (HCSZ), and in 21 FE (within 6 months of first-episode), and 20 matched healthy controls (HCFE). Both HCSZ and HCFE produced two complex MMNs: one early ~150 ms after deviant-onset and one late ~400 ms after deviant-onset. SZ showed significant reductions in the late complex MMN (p=.03, d=0.67), as did FE (p=.01, d=0.85). Both individuals with long-term schizophrenia and individuals at their first-break showed impaired complex MMN, specifically later in deviance detection processing. In contrast with simple MMN, complex MMN may be a more sensitive biomarker of the presence of schizophrenia early in disease course. To assess whether complex MMN has greater sensitivity to detect incipient psychosis, both simple MMN and complex MMN will be measured in prodromal individuals.

Psychotic disorders are highly complex with regard to their symptomatic characteristics and aetiology. About 1-2% of the population are affected by psychosis during their lifetime. Impairments in motor function that occur in psychosis have been associated with aberrant neural activity and structure. It is still unclear whether differences in motor ability in healthy individuals are similarly related to distinct brain activation patterns in motor-related brain areas, suggesting that impairments in psychosis patients are extreme values on a trait continuum. In the present study, we examine the neural underpinnings of motor function on the spectrum from health to psychosis.

We investigate the neural correlates by conducting electroencephalography (EEG) as well as functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) in 120 subjects from four different groups: psychosis patients, subjects with a clinical high-risk for psychosis, first-degree relatives of psychosis patients and healthy controls. During MRI and EEG measurement, subjects perform an ankle movement task as well as a biological motion recognition task, using the point light walker paradigm. In addition, physiological markers such as heart rate variability and force variability are recorded.

We hypothesize functional and structural neural abnormalities in the motor areas in relation to the strength of the behavioural disturbances. Our results will provide new insights into the neural basis, as well as the aetiology of motor function in psychosis.

We used a logistic discriminant analysis (LDA) to determine a QEEG predictive model of response to four-week trial of low-frequency transcranial magnetic stimulation (LF-rTMS) on right prefrontal cortex in patients with major depression who failed to previous antidepressant treatment (N=25). Out of the set of 836 variables generated by the Neuroguide software, we selected 12 significant (p˂0.001) variables using a t-test. This number has been then reduced within LDA by means of a stepwise method on 5 predictors (p˂0.05):alpha asymmetry (ASAL) C3-Cz, ASAL C4-Cz , theta asymmetry (TAS) C4-T4, TAS T3 – T4 and theta peak (TP) C4. The LDA model containing these five variables demonstrated correct classification on 88 %. Furthermore, it shows a good overall model fit based on -2 Log Likelihood (p˂0.001). Sequential and eliminating employment of bootstrapping (N=10000) on the original 12 variables confirmed that the QEEG parameters of TAS T3-T4 (p=0.0001), ASAL2 C4-F8 (p=0.01), ASAL1 C3-Cz (p=0.03), ASAL C3-Cz (p=0.04) demonstrate robust resistancy against bias while keeping a satisfactory level of overall classification. Our findings confirm the ability of QEEG data analysis to create a suitable prediction model. An important part of our model is the T3-T4 predictor, which demonstrates both predictive sensitivity and bias resistance. From our model, it can be concluded that higher temporal theta asymmetry (T3 > T4) indicates a significantly higher chance of therapeutic response to rTMS therapy for pharmaco-resistant depression.

Supported by Czech Science Foundation, grant nr. 17-07070S and Ministry of Health of the Czech Republic, grant nr. 16-31380A.

Avolition is a key negative symptom of schizophrenia for which there is no effective treatment. It is correlated to poor functional outcome and real life motivation. Dysfunctions of different motivation processes were documented in patients with avolition. Altered connectivity within dopaminergic (DA) cortico-striatal circuits, involved in motivation processes, might underlie most of these dysfunctions. The highest number of DA neurons involved in motivation circuits are located in the ventro-tegmental area (VTA). In light of these observations, our study investigated relationships between the resting-state functional connectivity (RS-FC) of the VTA and avolition.

We used resting state functional magnetic resonance imaging to study RS-FC in 22 healthy controls (HC) and in 26 patients with schizophrenia, treated with second generation antipsychotics only, divided in high (HA=13) and low avolition (LA=13) subgroups. We also assessed the relationships of VTA RS-FC with avolition, assessed using the Schedule for the Deficit Syndrome.

HA patients, in comparison to LA patients and HC, showed significantly reduced VTA RS-FC with the right (R) ventrolateral prefrontal cortex (VLPFC), left (L) VLPFC, R insula (INS), L INS and R lateral occipital complex (LOC). A reduced RS-FC was found for LA patients, with respect to HC, only in L INS and L VLPFC. Significant negative correlations were found between avolition and RS-FC of VTA with R INS, R VLPFC and L INS.

Conclusion. Our findings demonstrate that avolition in schizophrenia is linked to dysconnection of VTA from key cortical regions involved in retrieval of outcome values of actions to motivate behavior.

Introduction: Cannabis is the most widely consumed illicit substance with an estimated annual prevalence of 182, 5 million people worldwide in 2014. While the effect of cannabis on cognition has already been investigated, these studies mostly employed intravenously delivered, high doses of Δ-9-THC where participants were unable to influence neither the amount nor the speed of intake. Present study adopted a naturalistic design (subjects using their regular dose of their own cannabis the way they would normally do) focusing on selected cognitive domains and their underlying neurophysiology.

Method: Attention, mental flexibility, psychomotor speed (PEBL battery tasks – TMT, CPT) and P300 (auditory oddball paradigm) were measured 30 minutes after cannabis intoxication in 34 occasional, 31 chronic cannabis users and 30 non-using adults. Phenomenology was objectified by Altered States of Consciousness Scale and Brief Psychiatric Rating Scale. THC and THC-COOH were determined from blood analysis 30 and 60 minutes after cannabis intake.

Results: Although cannabis users had significantly higher APZ and BPRS scores, the groups did not differ in terms of their cognitive performance. Likewise, no between-group differences were observed in terms of P300 amplitude, latency or area under curve. Further analysis only revealed smaller P200 amplitude and shorter N200 latencies in occasional users when compared to non-using controls.

Conclusion: Unimpaired profile of selected cognitive functions both at behavioral and neurophysiological level was an unexpected finding suggesting a possible tolerance to the cognitive-impairing effects of cannabis provided the subjects are able to control the rate of intoxication.

Altered resting-state EEG source functional connectivity in Autism Spectrum Disorder

Introduction: Neurexan®, a medicinal product sold over the counter (OTC), contains passionflower, oats, coffee and zinc valerianate. Neurexan® has been previously investigated in patients with symptoms related to acute stress, nervousness/restlessness, and insomnia. The underlying neuronal mechanisms that lead to the reduction of those symptoms are less clear. The anterior cingulate cortex (ACC) and the Amygdala are the two areas important in stress reaction. Previous studies showed that especially the dorsal ACC (dACC) influences the generation of autonomic arousal. Additionally, it was found that the dACC is activated under cognitive stress. Thus, the dACC seems to be an important area controlling stress reactivity. We hypothesize Neurexan® to induce changes in the activation of dACC and associated areas during a stress task.

Methods: The treatment effect of a single dose was investigated using a randomized, placebo-controlled, double-blind, two-period-crossover design on thirty-nine healthy males. The stress response was induced using the ScanSTRESS which uses arithmetic tasks as well as mental rotation tasks.

Results&Conclusion: We found higher activation during psychosocial stress (stress > control; rotation and arithmetics together) in the anterior insula, premotor area bilaterally, angular gyrus, occipital lobe, and cerebellum. Paired-t-test analysis showed a significant cluster in the region of interest right dACC for the contrast placebo > drug in rotation stress > rotation control after correcting for multiple testing in the ROI. A single dose of Neurexan® significantly reduces right dACC activation during psychosocial stress compared to placebo.

Relation between Cognition and Resting-state EEG source functional connectivity in Schizophrenia

The serotonergic hallucinogen psilocybin and its active metabolite psilocin nowadays receive a lot of attention as a research tool for modeling psychosis. The aim of the study was to assess psilocin-induced changes in quantitative EEG (QEEG) in rats in order to explore the role of different serotonergic receptors in psilocin action.

EEG was recorded in freely moving rats after implantation of 12 active electrodes onto the surface of the cortex. EEG power spectra (local synchronization) and coherence (long projections) were analyzed comparing the drugs’ effect in time to the baseline record. Only EEG traces corresponding to behavioral inactivity were included in the analysis. We used psilocin, selective 5HT receptor antagonists and antipsychotics.

Psilocin generally decreased both EEG absolute spectral power and EEG coherences. The changes in spectral power induced by psilocin were normalized partially by all substances used, mainly in the lower frequency bands. However, only 5HT1A and 5HT2A antagonists partially normalized the psilocin-induced decrease of EEG coherences. The specific QEEG pattern of each substance and the temporal dynamics of QEEG changes will be presented.

Psilocin-induced changes in QEEG in rats are very similar to our human data with psilocybin and are in accordance with the concept of psychosis as a disconnection syndrome. All the specific 5HT antagonists and both antipsychotic drugs specifically affected the EEG spectral power induced by psilocin. Surprisingly, only 5HT1A and 5HT2A antagonists were able to partially reverse psilocin-induced disconnection.

This study was supported by LO1611/NPUI, MICR VI20172020056; Progres Q35; and European Regional Development Fund.

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with the progressive dysfunction of cognitive ability. Previous research has indicated that the default mode network (DMN) is closely related to cognition and is impaired in Alzheimer’s disease. Because recent studies have shown that different frequency bands represent specific physiological functions, DMN functional connectivity studies of the different frequency bands based on resting state fMRI (RS-fMRI) data may provide new insight into AD pathophysiology. In this study, we explored the functional connectivity based on well-defined DMN regions of interest (ROIs) from the five frequency bands: slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), slow-3 (0.073-0.198 Hz), slow-2 (0.198-0.25 Hz) and low-frequency oscillations (LFO) (0.01-0.08Hz). We found that the altered functional connectivity patterns are mainly in the frequency band of slow-5 and slow-4 and that the decreased connections are long distance, but some relatively short connections are increased. In addition, the functional connectivity fingerprint of the DMN in AD is frequency dependent and differs between the slow-5 and slow-4 bands. Mini-Mental State Examination (MMSE) scores were significantly correlated with the altered functional connectivity patterns in the slow-5 and slow-4 bands. These results indicate that frequency-dependent functional connectivity changes might provide potential biomarkers for AD pathophysiology.

One character of autism spectrum disorder (ASD) is restricted and repetitive patterns of behavior, interests, or activities. The characters are related to the abilities of selection of task-relevant information and inhibition of task-irrelevant information. The abilities are proposed to be related to phase synchronization between the distant motor and sensory areas in human electroencephalography (EEG) studies. It is however, not clear about the relationship of the synchronization with ASD symptoms. To address the issue, we measured EEG data during two types of simple motor-response tasks (an auditory-motor response task (AM) and a single visual-motor response task (VM)) and two types of select-motor-response tasks (an auditory-select-motor response task (ASM) and a single visual-select-motor response task (VSM)). Behavioral results showed that the response time for ASM and VSM tasks was longer than that for the AM and VM tasks. Interestingly, the prolong times were positively correlated with the ASD symptoms. The time-frequency analyses for the EEG data showed that the alpha phases between the motor and visual areas during only the VM and VSM tasks and between the motor and auditory areas in only the AM and ASM tasks. These task-relevant alpha phase synchronizations were decreased in the participants with high scores of the ASD symptoms. These results suggested that the ASD deficits would be associated with the decrements of the alpha synchronizations between the motor areas and the task-relevant sensory areas.

Quality of the raw data crucially impacts the validity of analyses and interpretation of scientific results obtained from electroencephalography (EEG). Therefore, regular assessments of EEG data quality are essential to ensure that established standards are met, particularly for multicenter studies.

EEG data are collected from N=68 patients within an ongoing multicenter study ESCAlife (involving Bochum, Homburg, Köln, Mainz, Mannheim, Marburg, Oldenburg, Rostock, Tübingen, Würzburg) of children, adolescents and adults (6 - 45 years) with ADHD in the ESCAbrain subproject. Resting state eyes open and eyes closed (4 minutes) EEG data are collected to identify potential predictors of treatment response. The EEG is recorded using a 22-channel EEG cap (Brain Products) and a sampling rate of 256 Hz (DC-70 Hz). As ADHD patients are prone to EEG artifacts, a regular data quality assessment focused on typical artefacts was conducted.

For data processing, the software BrainVision Analyzer (Brain Products) is used. The percentage of artifact-free epochs is calculated for each dataset as an index of data quality. Furthermore, the percentage of blink-artifact-related ICA-components is determined and compared across study centers and participants. Age of the participants, ADHD symptom severity, as well as the different study sites (comprising potentially relevant variables such as the electromagnetic environment, the training, and the experience of the staff with EEG recordings) are explored as relevant factors that might influence data quality.

Finally, corrective actions are discussed that were adopted to improve data quality.

This work was supported by the research consortium on ADHD, ESCA-Life, funded by the German Federal Ministry of Education and Research (FKZ 01EE1408E).

Introduction

The neurophysiological effects of neurofeedback (NF) as a treatment for children with ADHD are still unclear. This randomized controlled trial analysed EEG power spectra before and after 25 sessions of slow-cortical potentials neurofeedback compared to electromyogram (EMG) biofeedback as a semi-active control group.

Methods

Children with ADHD (n=150, age 7-9 y) were randomly assigned to 25 training sessions of SCP- neurofeedback or EMG feedback. The neurofeedback group had to regulate slow EEG activity at Cz, while the EMG-feedback control group had to regulate relative electromyographic activity of the musculus supraspinati. Each training session consisted of three runs with visual feedback and one run without feedback which aims to transfer the learned skills into daily life. EEG power spectra topographies (21 channels) during resting with eyes closed from pre and post-intervention was analysed.

Results

Both interventions showed comparable reductions of theta and alpha activity during the eyes closed condition which was more prominent at central and posterior scalp localisations. A time by group interaction was found for beta frequencies over the central cortex. The EMG control group showed reduced beta power after the training sessions.

Conclusion:

This study provides evidence for nonspecific neurophysiological changes after neurofeedback and EMG training. The general reduction in both groups of theta and alpha power could reflect increased attention although effects of maturation of the brain cannot be excluded. The specific reduction in beta power after EMG biofeedback could be related to a better motor control and inhibition.

Resting-state 18F-fallypride positron emission tomography was performed on 25 patients (mean(±sd) age: 31.6±12.2) with schizophrenia (20 medication-naïve and 5 previously medicated for a brief period) and 19 age- and sex-matched healthy volunteers (mean(±sd) age: 29.2±9.3).

Two neuropsychological tasks known to activate frontal and temporal lobe function were chosen, specifically the Wisconsin Card Sorting Test (WCST) and the California Verbal Learning Test (CVLT). Magnetic resonance images in standard Talairach position and segmented into gray and white matter were co-registered to the fallypride images, and the AFNI stereotaxic atlas was applied. Selective AFNI regions of interest (ROIs) were calculated from each subject. We calculated product-moment correlation coefficients between each ROI and the brain areas. Patients with schizophrenia showed negative correlations between binding potential and performance on WCST perseverative errors and CVLT learning slope, while healthy volunteers showed better performance with high binding potential in the frontal cortex and right temporal lobe. The healthy volunteers show positive correlations (red/yellow) indicating that high binding potential is associated with better performance. However patients show the reverse (blue) indicating low binding potential is associated with better performance for WCST.

. The positive correlation may be interpreted as less dopamine is associated with better performance in healthy volunteers. However patients with schizophrenia showed the reverse which suggests a compensatory dopamine system response.These results suggest that partial agonist treatment may assist cognitive performance in schizophrenia.

Background: Motor abnormalities are frequent in schizophrenia. Likewise, schizophrenia is faced with structural and functional dysconnectivity. Here, we tested whether resting state connectivity in the motor system would be aberrant in schizophrenia and linked to motor behavior abnormalities.

Method: In total, 46 patients and 44 controls underwent BOLD resting state scans for 8 mins and performed a comprehensive motor battery. Regions of interest (ROI) were cortical motor areas, basal ganglia, thalamus and motor cerebellum. We computed ROI-to-ROI functional connectivity using CONN. Principal component analyses of motor behavioral data produced four factors (primary motor, catatonia and dyskinesia, coordination, and spontaneous motor activity). We tested group differences in connectivity as well as correlations betwenn motor factor scores and connectivity values.

Results: Schizophrenia was characterized by hyperconnectivity in three main areas: motor cortices to thalamus, motor cortices to cerebellum, and prefrontal cortex to the subthalamic nucleus. In patients, thalamocortical hyperconnectivity was linked to catatonia and dyskinesia, whereas aberrant connectivity between rostral anterior cingulate and caudate was linked to the primary motor factor. Likewise, connectivity between motor cortex and cerebellum correlated with spontaneous motor activity.

Discussion: Altered resting state functional connectivity suggests a specific intrinsic and tonic neural abnormality in the motor system in schizophrenia. Furthermore, altered neural activity at rest was linked to motor abnormalities on the behavioral level. Thus, aberrant resting state connectivity may indicate a system out of balance, which produces characteristic behavioral alterations

Dyscoordination of perceptual sequencing systems is central to many cognitive deficits in schizophrenia. This is well-illustrated by neurophysiological deficits in auditory perceptual grouping and segmentation based on rhythmic sequence structure. Here we examine the N2 and auditory sequence potential (ASP) as they relate to network coordination within sensorimotor sequencing systems in participants at the first psychotic episode (FESz). Twenty-three FESz and 23 matched healthy controls (HC) ignored tone groups while watching a silent cartoon. Stimuli comprised 300 groups of three identical tones (1 kHz; 80 dB; 50 ms duration; 330 ms SOA, 800 ms ITI). Beta entrainment, N2, and ASP were measured to standard groups. ASP sources were localized using minimum-norm estimation for individuals with structural MRI (FESz=14; HC=14). ASP was reduced in FESz compared to HC (p<0.05). N2 responses were not significantly reduced (p>0.1). Source analysis revealed that ASP was generated primarily in bilateral primary auditory cortex (A1) and supplementary motor area (SMA). ASP activity in SMA (p<0.001), but not A1 (p>0.1) was reduced for FESz compared to matched controls. Further, coherent beta-band oscillatory activity was entrained to stimulus onset in HC, but not FESz, and this entrainment correlated with ASP activity in A1 and SMA (r’s>0.3). These results suggest that deficits in auditory pattern processing in schizophrenia occur early in the disease course. Reductions in beta entrainment and SMA activity suggest systems-level dysfunction in sensorimotor sequencing networks in FESz. Further work will assess symptom and functioning concomitants in deficits in this fundamental complex perceptual process.

Psilocybin is a serotonergic psychedelic with an agonist activity at 5-HT2A/C and 5-HT1A receptors. It is used as a research tool to study neurobiology of psychosis as well as it is gaining attention as a possible therapeutic tool to treat depression, anxiety and addiction. It has been already shown that psychedelics including psilocybin acutely induce desynchronization of the alpha activity occipitally and disconnection during the peak of intoxication. However understanding of the dynamics of these changes has not been evaluated yet. Therefore the current study focuses on the behavioural and EEG effects of psilocybin at several time points during the 6 hours of intoxication. Twenty volunteers with a balanced gender ratio (10M/10F) have entered the study. Each participant underwent two sessions with oral psilocybin (0.26 mg/kg) or a placebo in a double blinded crossover design. In most of the subjects, psilocybin induced fully psychedelic effects as measured by psychometric scales, the effects peaked between 1-2 h after administration. Decreased current density of the alpha band in the occipital region which diminished over time was the most robust finding. The connectivity analyses showed biphasic effect on overall connectivity indicating two different connectivity states at the peak of intoxication and 6h after the ingestion. Results will be discussed in relation to the potential therapeutic effects of psilocybin. This study was supported by the projects ED2.1.00/03.0078, LO1611/NPU I, MICR VI20172020056, MH CZ - DRO (NIMH-CZ, 00023752) and PROGRES Q35.

Aim: Mood disorders patients present difficulties to switch away from negative and self-focused automatic thoughts, which might represent the basis for incapacitating symptoms such as rumination. We aimed to investigate the activity in neural networks when patients have to switch between internally and externally focused attention and correlations with rumination scale.

Method: We compared a group of 20 euthymic bipolar patients and a group of 20 matched heathy controls during a fMRI task where they either rate how they are feeling, or how many letters are in the stimulus, using positive and negative adjectives.

Results: The “externally focused” condition elicited activity in a classical attentional network, and the “internally focused” condition in a network with central activations in medial prefrontal and cingulate regions, validating our paradigm. Bipolar patients showed significantly higher activity than controls in the vmPFC, PCC and parietal cortex, and in particular increased activity in pregenual ACC during the internal trials, which correlated with the tendency to ruminate. Switching from an internal to an external trial revealed higher activity in the entorhinal cortex for patients, especially after a negative trial. Repetition of negative internal trials also showed increased and correlated activity in medial areas.

Conclusion: Patients showed higher activity in medial cortical areas during the internally-focused condition, supporting the notion of an enhancement of self-processing in those patients. Negative valence might additionally trigger more activity in network associated with autobiographic memory and rumination.

Simultaneous MR-PET-EEG (magnetic resonance imaging - positron emission tomography – electroencephalography), a new tool for the investigation of neuronal networks in the human brain, is presented here for the first time. It enables the assessment of molecular metabolic information with high spatial and temporal resolution in a given brain simultaneously. Here, we characterize the brain’s default mode network (DMN) in healthy male subjects using multimodal fingerprinting by quantifying energy metabolism via 2- [18F]fluoro-2-desoxy-D-glucose PET (FDG-PET), the inhibition – excitation balance of neuronal activation via magnetic resonance spectroscopy (MRS), its functional connectivity via fMRI and its electrophysiological signature via EEG. The trimodal approach reveals a complementary fingerprint. Neuronal activation within the DMN as assessed with fMRI is positively correlated with the mean standard uptake value of FDG. Electrical source localization of EEG signals shows a significant difference between the dorsal DMN and sensorimotor network in the frequency range of δ, θ, α and β–1, but not with β–2 and β–3. In addition to basic neuroscience questions addressing neurovascular-metabolic coupling, this new methodology lays the foundation for individual physiological and pathological fingerprints for a wide research field addressing healthy aging, gender effects, plasticity and different psychiatric and neurological diseases.

Introduction: EEG signals recorded during simultaneous fMRI are contaminated by strong artifacts, among which the ballistocardiographic (BCG), induced by subject’s cardiac activity, is the most challenging to be removed due to its complex non-stationary nature.

The presence of BCG residuals in EEG data may hide true, or generate spurious, correlations between EEG and fMRI time-courses. In this study, we propose an adaptive optimal basis set (AOBS) method for BCG removal, which uses artifact spatio-temporal features to firmly reduce BCG residuals.

Methods: Each EEG signal was epoched based on BCG rather than ECG events, to ensure more effective artifact characterization by Principal Component Analysis (PCA). Furthermore, the artifactual components to be removed were automatically identified from the data, based on signal features.

AOBS method performance was evaluated in terms of BCG removal and brain signal preservation, with respect to Average Artifact Subtraction (AAS), Independent Component Analysis (ICA) and Optimal Basis Set (OBS), using high-density EEG data acquired during simultaneous fMRI in 6 subjects.

Results: As compared to alternative methods, the application of AOBS led to a remarkable BCG artifact attenuation. Specifically, it yielded a percentage of BCG residuals equal to 7.51%, versus 19.16%, 13.81% and 13.21%, for AAS, ICA and OBS, respectively.

Conclusions: AOBS method enables reliable and effective reduction of BCG residuals. It is easy to use and does not require parameter tuning. Thus, it may find wide application in the field of simultaneous EEG-fMRI, especially for applications in which no data epoching and averaging is possible, e.g. resting-state studies.

NeuroPycon is an open-source multi-modal brain data analysis kit which provides Python-based pipelines for advanced multi-thread processing of fMRI, MEG and EEG data, with a focus on connectivity and graph analyses [1].

NeuroPycon is based on NiPype framework [2] which facilitates data analyses by wrapping many commonly-used neuroimaging software into a common python framework. Therefore, a major strength of NeuroPycon is that it relies on (and interfaces with) several freely available Python packages developed for efficient and fast parallel processing and that it seamlessly connects with existing open-science neuroimaging and signal processing toolboxes.

The flexible design allows users to configure analysis pipelines defined by connecting different nodes, where each node may be a user-defined function or a well-established tool or python-wrapped module (e.g. MNE-python for MEG analysis [3], etc.).

The current implementation of NeuroPycon contains three different packages:

- ephypype includes pipelines for electrophysiology analysis; current implementations allow for MEG/EEG data import, data pre-processing and cleaning by an automatic removal of eyes and heart related artefacts, sensor or source-level connectivity analyses

- graphpype allows to study functional connectivity exploiting graph-theoretical metrics including also modular partitions

- clipype is a command line interface for ephypype package.

NeuroPycon will shortly be available for download via github (installation via Docker) and is currently being documented. Future developments include fusion of multi-modal data (ex. MEG and fMRI or iEEG and fMRI).

References

1. Bullmore, Sporns (2009), Nat Rev Neurosci

2. Gorgolewski et al. (2011) Front. Neuroinform

3. Gramfort et al. (2013), Front. Neurosci

Background: Epilepsy is a widespread brain networks disorder with a high risk of recurrent unprovoked epileptic seizures associated with impaired awareness or convulsions. The main feature in pathological epileptic EEG is the presence of spikes. Brain connectivity is an important tool to explore this pathological network aspects, but there are many open issues on the methods consistency. The choice of the parameters in the connectivity estimation, e.g., the selection of the p-order of the multivariate autoregressive model, is fundamental to avoid meaningless results such as spurious connections. In epileptic EEG during spikes, both Akaike Information Criterion (AIC) and Bayesian Information Criterion are often not effective in the determination of the optimal p order, i.e., AIC increased monotonically with increasing model order.

Methods: In the pre-operative EEG of 9 patients we applied the same analysis to the sources time-courses and their time-reversal versions in order to detect false-positive connections. In particular, we computed Partial Directed Coherence (PDC) in the source space varying p in the range [2-20] for both dipoles and reverse-dipoles. In the ideal case with infinitive signal-to-noise-ratio, the connectivity matrix computed from the reverse-dipoles should be the transpose of the original connectivity one. Therefore, we defined as optimal p-order the one which minimizes the absolute difference between the two connectivity matrices.

Results: The optimal p-order varied in the range [8-19] for each different type of spike-time series.

Conclusion: Future development will be to validate our methodology using concordance of connectivity with surgical resection in post-operatively seizure free patients.

After stroke, functional recovery may be promoted through rehabilitation. In such cases, a remapping of affected limbs to other regions of the cortex is often observed. High spatial resolution neuroimaging techniques, like magnetic resonance imaging (MRI), can be used to investigate the anatomical changes in the brain, but their low temporal resolution provides less insight of dynamic changes of brain function. In contrast, electroencephalography (EEG) has an excellent temporal resolution to measure such transient events, hindered in turn by its low spatial resolution. This study introduces a multimodal brain imaging technique to improve the spatial resolution of EEG to study stroke. The limitations of EEG are complemented by constraints derived from anatomical MRI and diffusion weighted imaging (DWI). EEG data was acquired from patients (N = 3) and healthy controls (N = 2) while electrical stimuli were delivered sequentially at index finger in left and right hand, respectively. A reasonably accurate estimation for active sources and inter-source connectivity was achieved in this study. Results indicate the changes of information flow in the brain after stroke, although the interpretation of these results in terms of neuroplasticity relearning is yet to be performed. This study provides evidence of this method being useful to track the information flow in the brain and may lead to a precise prognostic model of stroke.

Paralysis has a severe impact on a patient’s quality of life and entails a high emotional burden and life-long social and financial costs. Restoring movement and independence for the paralyzed remains a challenging clinical problem, currently with no viable solution. Recent demonstrations of intracortical brain-computer interfaces, neuroprosthetic devices that create a link between a person and a computer based on a person’s brain activity, have brought hope for their potential to restore movement and communication. While the intracortical brain-computer interfaces have steadily improved over the last decade, our recent success in linking brain activity with the newly developed techniques for spinal cord stimulation look to revolutionize locomotor rehabilitation. Specifically, our brain-spine interface restored weight-bearing locomotion of the paralyzed leg as early as six days post-injury in macaques1. New approaches in identifying neural features and designing decoding algorithms, which transform neural signals into computer commands, aim to deliver both stable and accurate control over clinically relevant periods of several months. To this end, we developed signal processing and decoder calibration approaches that enabled a person with long-stable tetraplegia to control a communication brain-computer interface for 138 days with an unchanged decoder2. Preliminary clinical studies suggest that these concepts and technologies are directly translatable to therapeutic strategies for people with paralysis.

1. M. Capogrosso*, T. Milekovic*, D. Borton*, et al., A brain–spine interface alleviating gait deficits after spinal cord injury in primates. Nature 539, 284-288 (2016).

2. T. Milekovic, et al., Stable asynchronous BCIs based on field potentials for communication, BCCN Conference

Introduction: Neurexan®, a medicinal product sold over the counter (OTC), contains passionflower, oat, coffee and zinc valerianate. Neurexan® has been investigated in patients with symptoms related to acute stress, nervousness and insomnia. Amygdala is involved in the development of fear and emotional behavior. Acute stress sensitizes the amygdala, thereby increasing vigilance/anxiety, which in turn promotes the stress response. Amygdala reactivity to negative stimuli is a reliable phenotype that closely associates with stress regulation and can be assessed with Hariri paradigm. Furthermore, a linkage between an increased level of stress hormones and increased emotional response to angry faces has been shown in patients with social phobia. Previous investigation suggested an attenuated neuroendocrine stress response in healthy volunteers induced by Neurexan®. Thus, our aim was to further explore the effect of Neurexan® on the emotional brain response in the amygdala.

Methods: In a randomized, placebo-controlled, double-blind, two-period crossover trial brain response to the Hariri task, an emotional paradigm, of 39 healthy, moderate stressed males was measured after intake of a single dose of Neurexan® and placebo control via 3 Tesla fMRI. Data were preprocessed and analyzed in SPM12.

Results&Conclusion: Hariri task was firstly validated for negative emotional faces response. Significant (peak level FWE corrected) bilateral activations of fusiform gyri, amygdalae and prefrontal cortex as well as unilateral activation in right thalamus were confirmed as previously reported. Paired t-test showed a significant reduction of BOLD response to negative faces in the left amygdala (p<0.05) during the Neurexan® session as compared to placebo.