Andrea Daverio

Altered resting-state EEG source functional connectivity in schizophrenia: the effect of illness duration

Despite the increasing body of evidence supporting the hypothesis of schizophrenia as a disconnection syndrome, studies of resting-state EEG Source Functional Connectivity (EEG-SFC) in people affected by schizophrenia are sparse. The aim of the present study was to investigate resting-state EEG-SFC in 77 stable, medicated patients with schizophrenia (SCZ) compared to 78 healthy volunteers (HV). In order to study the effect of illness duration, SCZ were divided in those with a short duration of disease (SDD; n = 25) and those with a long duration of disease (LDD; n = 52). Resting-state EEG recordings in eyes closed condition were analyzed and lagged phase synchronization (LPS) indices were calculated for each ROI pair in the source-space EEG data. In delta and theta bands, SCZ had greater EEG-SFC than HV; a higher theta band connectivity in frontal regions was observed in LDD compared with SDD. In the alpha band, SCZ showed lower frontal EEG-SFC compared with HV whereas no differences were found between LDD and SDD. In the beta1 band, SCZ had greater EEG-SFC compared with HVs and in the beta2 band, LDD presented lower frontal and parieto-temporal EEG-SFC compared with HV. In the gamma band, SDD had greater connectivity values compared with LDD and HV. This study suggests that resting state brain network connectivity is abnormally organized in schizophrenia, with different patterns for the different EEG frequency components and that EEG can be a powerful tool to further elucidate the complexity of such disordered connectivity.

The Val66Met polymorphism of the BDNF gene influences trigeminal Pain-Related evoked responses

UNLABELLED Cortical pain processing is associated with large-scale changes in neuronal connectivity, resulting from neural plasticity phenomena of which brain-derived neurotrophic factor (BDNF) is a central driver. The common single nucleotide polymorphism Val66Met is associated with reduced BDNF activity. Using the trigeminal pain-related evoked potential (tPREP) to repeated electrical painful stimuli, we investigated whether the methionine substitution at codon 66 of the BDNF gene was associated with changes in cortical processing of noxious stimuli. Fifty healthy volunteers were genotyped: 30 were Val/Val and 20 were Met-carriers. tPREPs to 30 stimuli of the right supraorbital nerve using a concentric electrode were recorded. The N2 and P2 component latencies and the N2-P2 amplitude were measured over the 30 stimuli and separately, by dividing the measurements in 3 consecutive blocks of 10 stimuli. The average response to the 30 stimuli did not differ in latency or amplitude between the 2 genotypes. There was a decrease in the N2-P2 amplitude between first and third block in the Val/Val group but not in Met-carriers. BDNF Val66Met is associated with reduced decremental response to repeated electrical stimuli, possibly as a result of ineffective mechanisms of synaptic memory and brain plasticity associated with the polymorphism. PERSPECTIVE BDNF Val66Met polymorphism affects the tPREP N2-P2 amplitude decrement and influences cortical pain processing through neurotrophin-induced neural plasticity, or through a direct BDNF neurotransmitter-like effect. Our findings suggest that upcoming BDNF central agonists might in the future play a role in pain management.

Neurobiological response to EMDR therapy in clients with different psychological traumas.

We assessed cortical activation differences in real-time upon exposure to traumatic memory between two distinct groups of psychologically traumatized clients also in comparison with healthy controls. We used electroencephalography (EEG) to compare neuronal activation throughout the bilateral stimulation phase of Eye Movement Desensitization and Reprocessing (EMDR) sessions. We compared activation between the first (T0) and the last (T1) session, the latter performed after processing the index trauma. The group including all clients showed significantly higher cortical activity in orbito-frontal cortex at T0 shifting at T1 toward posterior associative regions. However, the subgroup of clients with chronic exposure to the traumatic event showed a cortical firing at both stages which was closer to that of controls. For the first time EEG monitoring enabled to disclose neurobiological differences between groups of clients with different trauma histories during the reliving of the traumatic event. Cortical activations in clients chronically exposed to traumatic memories were moderate, suggesting an association between social and environmental contexts with the neurobiological response to trauma exposure and psychotherapy.

The upstream Variable Number Tandem Repeat polymorphism of the monoamine oxidase type A gene influences trigeminal pain‐related evoked responses

Monoamines have an important role in neural plasticity, a key factor in cortical pain processing that promotes changes in neuronal network connectivity. Monoamine oxidase type A (MAOA) is an enzyme that, due to its modulating role in monoaminergic activity, could play a role in cortical pain processing. The X‐linked MAOA gene is characterized by an allelic variant of length, the MAOA upstream Variable Number Tandem Repeat (MAOA‐uVNTR) region polymorphism. Two allelic variants of this gene are known, the high‐activity MAOA (HAM) and low‐activity MAOA (LAM). We investigated the role of MAOA‐uVNTR in cortical pain processing in a group of healthy individuals measured by the trigeminal electric pain‐related evoked potential (tPREP) elicited by repeated painful stimulation. A group of healthy volunteers was genotyped to detect MAOA‐uVNTR polymorphism. Electrical tPREPs were recorded by stimulating the right supraorbital nerve with a concentric electrode. The N2 and P2 component amplitude and latency as well as the N2–P2 inter‐peak amplitude were measured. The recording was divided into three blocks, each containing 10 consecutive stimuli and the N2–P2 amplitude was compared between blocks. Of the 67 volunteers, 37 were HAM and 30 were LAM. HAM subjects differed from LAM subjects in terms of amplitude of the grand‐averaged and first‐block N2–P2 responses (HAM>LAM). The N2–P2 amplitude decreased between the first and third block in HAM subjects but not LAM subjects. The MAOA‐uVNTR polymorphism seemed to influence the brain response in a repeated tPREP paradigm and suggested a role of the MAOA as a modulator of neural plasticity related to cortical pain processing.

P300 Correlates of Cognitive Dysfunctions in Schizophrenia

Introduction P300 is an event-related potential (ERP) thought to reflect attention, working memory and context integration and has been shown to be consistently reduced in patients with Schizophrenia. Despite a possible relation between P300 components and cognitive deficits in Schizophrenia has been hypothesized, few studies addressed this hypothesis. Objectives In the context of a multicenter study of the Italian Network for Research on Psychoses, our study focused on the investigation of auditory P300 component in relation to clinical and cognitive domains in patients with Schizophrenia. Methods ERPs were recorded in 64 chronic, stabilized patients with Schizophrenia during a standard oddball task. N1 and P3b latency and amplitude were assessed at Fz and Pz, respectively. State of art instruments was used for clinical assessment. Cognitive indices (from the seven cognitive domains of the Measurement and Treatment of Cognition in Schizophrenia, MATRICS) were expressed as Z-scores from an Italian normative sample. Results Correlation analysis revealed associations of P3b latency with age, education, PANSS-DIS, processing speed, working memory, St. Hans parkinsonism subscale. In a multiple linear regression model, processing speed was an independent significant predictor of P3b latency. Conclusion For the first time, a strong relation between P3b latency and processing speed impairment was shown in Schizophrenia. Processing speed is considered a central factor in the relation between cognitive deficits and functional outcome in chronic schizophrenia. The association with P3b latency might shed lights in the neural basis of this complex construct.

Metabolic and Electrophysiological Changes Associated to Clinical Improvement in Two Severely Traumatized Subjects Treated With EMDR—A Pilot Study

Neuroimaging represents a powerful tool to investigate the neurobiological correlates of Eye Movements Desensitization and Reprocessing (EMDR). The impact of EMDR on cortical and sub-cortical brain regions has been proven by several investigations demonstrating a clear association between symptoms disappearance and changes in cortical structure and functionality. The aim of this study was to assess by electroencephalography (EEG) and for the first time by positron emission tomography (PET) the changes occurring after EMDR therapy in two cases of psychological trauma following brain concussion and comatose state due to traffic accident. A 28 and a 29 years old men underwent extensive neuropsychological examination, which investigated: (i) categorical and phonological verbal fluency; (ii) episodic verbal memory; (iii) executive functions; (iv) visuospatial abilities; (v) attention and working memory as well as clinical assessment by means of psychopathological tests (CAPS, IES, BDI, SCL90R, and DES). They were then treated by eight sessions of EMDR. During the first session EEG monitoring was continuously performed and 18F-FDG PET scans, depicting brain metabolism, were acquired at rest within a week (T0). After the last session, in which the two clients were considered to be symptoms-free, neuropsychological, clinical, and PET assessment were repeated (T1). PET data were semi-quantitatively compared to a group of 18 normal controls, as for EEG the preferential cortical activations were disclosed by thresholding the individual z-score to a p < 0.05. There was a significant improvement in clinical condition for both clients associated with a significant decrease in CAPS scores. IES and BDI were found to be pathological at T0 and improved at T1 in only one subject. Visuo-constructive abilities and abstract reasoning improved after EMDR in both subjects. As for EEG, the most striking changes occurred in fronto-temporal-parietal cortex in subject 1 while subject 2 showed only minor changes. PET showed more pronounced metabolism in orbito-frontal and prefrontal cortex at T1 as compared to T0 in both subjects. In conclusion both clients had a clear clinical improvement in PTSD symptoms associated with metabolic and electrophysiological changes in limbic and associative cortex, respectively, highlighting the value of EMDR also in such extreme pathological conditions.

Early Auditory Deviance Detection and Functional Outcome in Patients with Schizophrenia

Introduction The Mismatch Negativity (MMN) is an event-related potential (ERP) sensitive to early auditory deviance detection and has been shown to be reduced in patients with schizophrenia. Moreover, MMN amplitude reduction to duration deviant tones was found to be related to functional outcomes particularly, to social cognition and real-life functioning. Objectives In the context of a multicentre study of the Italian Network for Research on Psychoses, our study focused on the investigation of early auditory discrimination components in relation to functioning in real-life in patients with schizophrenia. Methods ERPs were recorded in 64 chronic, stabilized patients with schizophrenia during the presentation of standard, duration deviants and frequency deviants tones while watching a cartoon. The Specific Level of Functioning (SLOF) scale was used to measure real-life functioning. Psychopathology, neurocognition and social cognition were measured by state of art instruments. Regression analyses were carried out using SLOF domains as dependent variables and MMN, psychopathology, neurocognition, extrapyramidal symptoms and social cognition as independent predictors. Results Latency of MMN entered the regression equation only for the SLOF domain of common activities explaining less variance than social cognition and positive symptoms. Conclusion In stabilized patients with schizophrenia pre-attentive deficits, as indexed by MMN and P3a amplitude reduction, do not show any association with psychopathology or functioning. Latency of MMN was an independent predictor of some aspects of functioning with a smaller effect than social cognition and psychopathology domains.

Emdr Therapy Changes the Resting-state Eeg

Introduction During the Eye Movement Desensitization and Reprocessing (EMDR) changes of brain electrical activity was recently demonstrated in victims of psychological traumas. Objectives Thirty-one victims of psychological traumas were investigated at the first EMDR session (t0) and at the last one performed after processing the index trauma (t1). Aims To investigate differences in EEG source activity and EEG source functional connectivity (EEG-SFC) in eyes closed condition before the beginning of t0 and t1 EMDR therapy session. Methods Electrical source activity was computed by eLORETA from a 37-channel EEG. EEG-SFC analysis was based on the lagged phase synchronization (LPS), derived by a two-step eLORETA procedure: dimensionality reduction of inverse matrix from 6239 voxels to 28 regions of interest (ROIs); LPS indices computation, for each spectrum band, in all possible ROI pairs. Results Resting-state EEG source activity resulted in a low frequency increase of posterior cingulate cortex and a high frequency (beta2 and gamma) decrease in right prefrontal and parietal cortex between t0 and t1. Significant enhancements of EEG-SFC were detected in t1 respect to t0 between ROI pairs of theta band right temporo-parahippocampal regions and alpha band fronto-parietal regions. Conclusions Significant modifications of resting-state electrical brain activity were present after EMDR therapy. These findings suggest that the elaboration of psychological traumas induced by EMDR produces, in a resting-state condition, an enhancement of activity and functional connectivity of cerebral sources involved in cognitive control and emotional processing.

EPA-1793 – Enhancement of right hemisphere eeg functional connectivity after emdr therapy

Introduction Brain connectivity changes have been recently demonstrated in victims of psychological traumas treated with the eye movement desensitization and reprocessing (EMDR). Objectives Forty victims of psychological traumas were investigated at the first EMDR session (t0) and at the last one performed after processing the index trauma (t1). Aims To investigate differences in EEG functional source connectivity during bilateral ocular stimulation (BS) during EMDR therapy at t0 and t1. Methods Brain electrical activity during whole EMDR sessions was record with a 37-channel EEG. EEG functional connectivity analysis was based on the lagged phase synchronization (LPS), derived by a two-step eLoreta procedure: dimensionality reduction of inverse matrix from 6239 voxels to 28 regions of interest (ROIs); LPS index computation, for each spectrum band, in all possible ROI pairs. Results Significant differences were detected between t0 and t1 in alpha band LPS indexes. A prevalent enhancement in right intrahemispheric functional connectivity was found in t1 respect to t0, particularly among ROI pairs of (a) frontal regions (anterior frontal, orbital frontal, lateral frontal cortices) and limbic structures (anterior cingulate cortex, ACC), (b) frontal regions and associative areas (insula cortex, parietal lobe), (c) ACC and primary visual cortex and (d) ACC and associative areas. Conclusions These findings suggest that EMDR efficacy is associated to electrical brain connectivity changes during BS. An enhancement in the right hemisphere alpha band functional connectivity of areas involved in cognitive control, emotional processing and visual associative functions may play a key role in the elaboration of psychological traumas.