EEG alpha reactivity on eyes opening discriminates patients with schizophrenia and schizoaffective disorder.

OBJECTIVE: Alpha activity in the electroencephalogram (EEG) is typically dominant during rest with closed eyes but suppressed by visual stimulation. Previous research has shown that alpha-blockade is less pronounced in schizophrenia patients compared to healthy individuals, but no studies have examined it in schizoaffective disorder. METHODS: A resting state EEG was used for the analysis of the alpha-reactivity between the eyes closed and the eyes opened conditions in overall (8 - 13 Hz), low (8 - 10 Hz) and high (10 - 13 Hz) alpha bands in three groups: schizophrenia patients (SC, n = 30), schizoaffective disorder (SA, n = 30), and healthy controls (HC, n = 36). All patients had their first psychotic episode and were receiving antipsychotic therapy. RESULTS: A significant decrease in alpha power was noted across all subjects from the eyes-closed to eyes-open condition, spanning all regions. Alpha reactivity over the posterior regions was lower in SC compared to HC within overall and high alpha. SA showed a trend towards reduced alpha reactivity compared to HC, especially evident over the left posterior region within the overall alpha. Alpha reactivity was more pronounced over the middle and right posterior regions of SA as compared to SC, particularly in the high alpha. Alpha reactivity in SC and SA patients was associated with various negative symptoms. CONCLUSIONS: Our findings imply distinct alterations in arousal mechanisms in SC and SA and their relation to negative symptomatology. Arousal is more preserved in SA. SIGNIFICANCE: This study is the first to compare the EEG features of arousal in SC and SA.

The effect of low-frequency rTMS on auditory hallucinations, EEG source localization and functional connectivity in schizophrenia.

BACKGROUND: Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) diminishes auditory hallucinations (AHs). The aims of our study were a) to assess the efficacy of LF-rTMS in a randomized, sham-controlled double-blind alignment, b) to identify the electrophysiological changes accompanying the LF-rTMS, and c) to identify the influence of LF-rTMS on brain functional connectivity (FC). METHODS: Nineteen schizophrenia patients with antipsychotic-resistant AHs were randomized to either active (n = 10) or sham (n = 9) LF-rTMS administered over the left temporo-parietal region for ten days. The clinical effect was assessed by the Auditory Hallucination Rating Scale (AHRS). The localization of the differences in electrical activity was identified by standardized low resolution brain electromagnetic tomography (sLORETA) and FC was measured by lagged phase synchronization. RESULTS: AHRS scores were significantly improved for patients receiving active rTMS compared to the sham (median reduction: 40 % vs 12 %; p = 0.01). sLORETA revealed a decrease of alpha-2, beta-1,-2 bands in the left hemisphere in the active group. Active rTMS led to a decrease of the lagged phase connectivity in beta bands originating in areas close to the site of stimulation, and to a prevailing increase of alpha-2 FC. No significant differences in current density or FC were observed in the sham group. LIMITATIONS: Limitations to our study included the small group sizes, and the disability of LORETA to assess subcortical neuronal activity. CONCLUSIONS: LF-rTMS attenuated AHs and induced a decrease of higher frequency bands on the left hemisphere. The FC changes support the assumption that LF-rTMS is linked to the modulation of cortico-cortical coupling.

Symmetric in the striate but asymmetric in the extrastriate cortex when processing three-quarter faces: Neural underpinnings for aesthetic appreciations.

Faces and their aesthetic appreciation are a core element of social interaction. Although studies have been made on facial processing when looking at faces with different perspectives, a direct comparison of faces in the left to the right perspective is missing. Portraits in classical Western art indicate a preference of the left compared to the right perspective, but the neural underpinnings of such an asymmetry still have to be clarified. Using functional magnetic resonance imaging, the current study focuses on the processing of three-quarter faces seen with different perspectives. Seventeen participants were asked to passively look at photographs of six male and six female faces with a neutral expression; the photographs were taken from the left, right, and frontal perspectives while keeping their focus on the eyes. The results showed that specific brain areas were involved in processing the three-quarter faces in either symmetric or asymmetric ways. Viewing left and right three-quarter faces resulted in two mirror-like activations in the striate cortex corresponding to the symmetric layout of the left and right perspectives. Viewing the left face resulted additionally in an enhanced activation also in the left extrastriate cortex. The right perspective of male faces elicited a lower activation compared to other perspectives in face-selective areas of the brain. Our findings suggest that the preference of the left three-quarter face emerges already in the early visual pathway presumably prior to facial identification, emotional processing, and aesthetic appreciation. Our observations may have general importance in disentangling different neural components and processing stages in the spatiotemporal characteristics of artistic expressions.

Item-specific overlap between hallucinatory experiences and cognition in the general population: A three-step multivariate analysis of international multi-site data.

Hallucinatory experiences (HEs) can be pronounced in psychosis, but similar experiences also occur in nonclinical populations. Cognitive mechanisms hypothesized to underpin HEs include dysfunctional source monitoring, heightened signal detection, and impaired attentional processes. Using data from an international multisite study on non-clinical participants (N = 419), we described the overlap between two sets of variables - one measuring cognition and the other HEs - at the level of individual items. We used a three-step method to extract and examine item-specific signal, which is typically obscured when summary scores are analyzed using traditional methodologies. The three-step method involved: (1) constraining variance in cognition variables to that which is predictable from HE variables, followed by dimension reduction, (2) determining reliable HE items using split-halves and permutation tests, and (3) selecting cognition items for interpretation using a leave-one-out procedure followed by repetition of Steps 1 and 2. The results showed that the overlap between HEs and cognition variables can be conceptualized as bi-dimensional, with two distinct mechanisms emerging as candidates for separate pathways to the development of HEs: HEs involving perceptual distortions on one hand (including voices), underpinned by a low threshold for signal detection in cognition, and HEs involving sensory overload on the other hand, underpinned by reduced laterality in cognition. We propose that these two dimensions of HEs involving distortions/liberal signal detection, and sensation overload/reduced laterality may map onto psychosis-spectrum and dissociation-spectrum anomalous experiences, respectively.

Correlates of Hallucinatory Experiences in the General Population: An International Multisite Replication Study.

Hallucinatory experiences can occur in both clinical and nonclinical groups. However, in previous studies of the general population, investigations of the cognitive mechanisms underlying hallucinatory experiences have yielded inconsistent results. We ran a large-scale preregistered multisite study, in which general-population participants (N = 1,394 across 11 data-collection sites and online) completed assessments of hallucinatory experiences, a measure of adverse childhood experiences, and four tasks: source memory, dichotic listening, backward digit span, and auditory signal detection. We found that hallucinatory experiences were associated with a higher false-alarm rate on the signal detection task and a greater number of reported adverse childhood experiences but not with any of the other cognitive measures employed. These findings are an important step in improving reproducibility in hallucinations research and suggest that the replicability of some findings regarding cognition in clinical samples needs to be investigated.

Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison.

The recent renaissance of psychedelic science has reignited interest in the similarity of drug-induced experiences to those more commonly observed in psychiatric contexts such as the schizophrenia-spectrum. This report from a multidisciplinary working group of the International Consortium on Hallucinations Research (ICHR) addresses this issue, putting special emphasis on hallucinatory experiences. We review evidence collected at different scales of understanding, from pharmacology to brain-imaging, phenomenology and anthropology, highlighting similarities and differences between hallucinations under psychedelics and in the schizophrenia-spectrum disorders. Finally, we attempt to integrate these findings using computational approaches and conclude with recommendations for future research.

EEG activity for semantic task in paranoid schizophrenia.

We identified a potential neurophysiological marker for processing of verbal cues in paranoid schizophrenia: high desynchronization in the beta-2 band in the right parietal area for meaningless cues, and no synchronization differences in the beta-2 and gamma bands in the left prefrontal area pointing to deficient categorization of the stimuli.

Mu rhythm separation from the mix with alpha rhythm: Principal component analyses and factor topography.

BACKGROUND: EEG mu rhythm suppression is assessed in experiments on the execution, observation and imagination of movements. It is utilised for studying of actions, language, empathy in healthy individuals and preservation of sensorimotor system functions in patients with schizophrenia and autism spectrum disorders. While EEG alpha and mu rhythms are recorded in the same frequency range (8-13 Hz), their specification becomes a serious issue. THE NEW METHOD: is based on the spatial and functional characteristics of the mu wave, which are: (1) the mu rhythm is located over the sensorimotor cortex; (2) it desynchronises during movement processing and does not respond on the eyes opening. In EEG recordings, we analysed the mu rhythm under conditions with eyes opened and eyes closed (baseline), and during a motor imagery task with eyes closed. EEG recordings were processed by principal component analysis (PCA). RESULTS: The analysis of EEG data with the proposed approach revealed the maximum spectral power of mu rhythm localised in the sensorimotor areas. During motor imagery, mu rhythm was suppressed more in frontal and central sites than in occipital sites, whereas alpha rhythm was suppressed more in parietal and occipital sites. Mu rhythm desynchronization in sensorimotor sites during motor imagery was greater than alpha rhythm desynchronization. The proposed method enabled EEG mu rhythm separation from its mix with alpha rhythm. CONCLUSIONS: EEG mu rhythm separation with the proposed method satisfies its classical definition.

Morality in advertising: An fMRI study on persuasion in communication.

Advertising slogans serve the function of persuasive communication by presenting catchy phrases. To decide whether a slogan is convincing or not, cognitive reasoning is assumed to be complemented by a more implicit and intuitive route of information processing, presumably similar to evaluating normative judgments in moral statements. We employed functional magnetic resonance imaging (fMRI) while Western male subjects judged advertising slogans and moral statements as another decision task with subjective nature. Compared to a neutral control condition that targeted declarative memory and to an aesthetic-related condition, the evaluation processes in both domains engaged the anterior medial prefrontal cortex (mPFC), which is associated with decision-making incorporating personal value. Conjoint activations were also observed in the left temporoparietal junction (TPJ) when compared to the aesthetics condition. Results are discussed with reference to domain-independence, a suspected difference to aesthetic-like appreciations, and functional organization in the mPFC and the TPJ.

Disrupted Sense of Agency as a State Marker of First-Episode Schizophrenia: A Large-Scale Follow-Up Study.

Background: Schizophrenia is often characterized by a general disruption of self-processing and self-demarcation. Previous studies have shown that self-monitoring and sense of agency (SoA, i.e., the ability to recognize one's own actions correctly) are altered in schizophrenia patients. However, research findings are inconclusive in regards to how SoA alterations are linked to clinical symptoms and their severity, or cognitive factors. Methods: In a longitudinal study, we examined 161 first-episode schizophrenia patients and 154 controls with a continuous-report SoA task and a control task testing general cognitive/sensorimotor processes. Clinical symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Results: In comparison to controls, patients performed worse in terms of recognition of self-produced movements even when controlling for confounding factors. Patients' SoA score correlated with the severity of PANSS-derived "Disorganized" symptoms and with a priori defined symptoms related to self-disturbances. In the follow-up, the changes in the two subscales were significantly associated with the change in SoA performance. Conclusion: We corroborated previous findings of altered SoA already in the early stage of schizophrenia. Decreased ability to recognize self-produced actions was associated with the severity of symptoms in two complementary domains: self-disturbances and disorganization. While the involvement of the former might indicate impairment in self-monitoring, the latter suggests the role of higher cognitive processes such as information updating or cognitive flexibility. The SoA alterations in schizophrenia are associated, at least partially, with the intensity of respective symptoms in a state-dependent manner.

Cannabis-induced altered states of consciousness are associated with specific dynamic brain connectivity states.

BACKGROUND: Cannabis, and specifically one of its active compounds delta-9-tetrahydrocannabinol in recreational doses, has a variety of effects on cognitive processes. Most studies employ resting state functional magnetic resonance imaging techniques to assess the stationary effects of cannabis and to-date one report addressed the impact of delta-9-tetrahydrocannabinol on the dynamics of whole-brain functional connectivity. METHODS: Using a repeated-measures, within-subjects design, 19 healthy occasional cannabis users (smoking cannabis ⩽2 per week) underwent resting state functional magnetic resonance imaging scans. Each subject underwent two scans: in the intoxicated condition, shortly after smoking a cannabis cigarette, and in the non-intoxicated condition, with the subject being free from cannabinoids for at least one week before. All sessions were randomized and performed in a four-week interval. Data were analysed employing a standard independent component analysis approach with subsequent tracking of the functional connectivity dynamics, which allowed six connectivity clusters (states) to be individuated. RESULTS: Using standard independent component analysis in resting state functional connectivity, a group effect was found in the precuneus connectivity. With a dynamic independent component analysis approach, we identified one transient connectivity state, characterized by high connectivity within and between auditory and somato-motor cortices and anti-correlation with subcortical structures and the cerebellum that was only found during the intoxicated condition. Behavioural measures of the subjective experiences of changed perceptions and tetrahydrocannabinol plasma levels during intoxication were associated with this state. CONCLUSIONS: With the help of the dynamic connectivity approach we could elucidate neural correlates of the transitory perceptual changes induced by delta-9-tetrahydrocannabinol in cannabis users, and possibly identify a biomarker of cannabis intoxication.

Cognitive Profiles and Functional Connectivity in First-Episode Schizophrenia Spectrum Disorders - Linking Behavioral and Neuronal Data.

The character of cognitive deficit in schizophrenia is not clear due to the heterogeneity in research results. In heterogeneous conditions, the cluster solution allows the classification of individuals based on profiles. Our aim was to examine the cognitive profiles of first-episode schizophrenia spectrum disorder (FES) subjects based on cluster analysis, and to correlate these profiles with clinical variables and resting state brain connectivity, as measured with magnetic resonance imaging. A total of 67 FES subjects were assessed with a neuropsychological test battery and on clinical variables. The results of the cognitive domains were cluster analyzed. In addition, functional connectivity was calculated using ROI-to-ROI analysis with four groups: Three groups were defined based on the cluster analysis of cognitive performance and a control group with a normal cognitive performance. The connectivity was compared between the patient clusters and controls. We found different cognitive profiles based on three clusters: Cluster 1: decline in the attention, working memory/flexibility, and verbal memory domains. Cluster 2: decline in the verbal memory domain and above average performance in the attention domain. Cluster 3: generalized and severe deficit in all of the cognitive domains. FES diagnoses were distributed among all of the clusters. Cluster comparisons in neural connectivity also showed differences between the groups. Cluster 1 showed both hyperconnectivity between the cerebellum and precentral gyrus, the salience network (SN) (insula cortex), and fronto-parietal network (FPN) as well as between the PreCG and SN (insula cortex) and hypoconnectivity between the default mode network (DMN) and seeds of SN [insula and supramarginal gyrus (SMG)]; Cluster 2 showed hyperconnectivity between the DMN and cerebellum, SN (insula) and precentral gyrus, and FPN and IFG; Cluster 3 showed hypoconnectivity between the DMN and SN (insula) and SN (SMG) and pallidum. The cluster solution confirms the prevalence of a cognitive decline with different patterns of cognitive performance, and different levels of severity in FES. Moreover, separate behavioral cognitive subsets can be linked to patterns of brain functional connectivity.

EEG coherence in a mental arithmetic task performance in first episode schizophrenia and schizoaffective disorder.

OBJECTIVES: To evaluate the coherence values of the cortical bands in patients with first episode schizophrenia and schizoaffective disorder during the performance of a mental arithmetic task. METHOD: We analysed EEG coherence in the resting state and subsequently while counting down from 200 in steps of 7 in 32 first episode schizophrenia patients (SZ), 32 patients with first episode schizoaffective disorder (SA) and 40 healthy controls (HC). RESULTS: Task performance in HC is characterised by decreased coherence in the alpha bands and increased coherence in the beta 2 and gamma bands in frontal sites. In SZ, coherence decreases in the alpha band, whereas in SA it substantially increases in the alpha, beta1, beta 2 and gamma bands. CONCLUSIONS: Despite no differences in performance on a behavioural level, SA patients demonstrate a paradoxical increase in both low and fast frequency bands during the performance of a mental arithmetic task, while, patients with SZ show a decreased coherence in the alpha band, presumably alluding to the excessive excitatory (in SA) and inhibitory (in SZ) mechanisms in cognitive processing. SIGNIFICANCE: The current study provides evidence for the distinction of neurophysiological mechanisms of cognitive processing between SZ and SA.

Theoretical Modeling of Cognitive Dysfunction in Schizophrenia by Means of Errors and Corresponding Brain Networks.

The current evidence of cognitive disturbances and brain alterations in schizophrenia does not provide the plausible explanation of the underlying mechanisms. Neuropsychological studies outlined the cognitive profile of patients with schizophrenia, that embodied the substantial disturbances in perceptual and motor processes, spatial functions, verbal and non-verbal memory, processing speed and executive functioning. Standardized scoring in the majority of the neurocognitive tests renders the index scores or the achievement indicating the severity of the cognitive impairment rather than the actual performance by means of errors. At the same time, the quantitative evaluation may lead to the situation when two patients with the same index score of the particular cognitive test, demonstrate qualitatively different performances. This may support the view why test paradigms that habitually incorporate different cognitive variables associate weakly, reflecting an ambiguity in the interpretation of noted cognitive constructs. With minor exceptions, cognitive functions are not attributed to the localized activity but eventuate from the coordinated activity in the generally dispersed brain networks. Functional neuroimaging has progressively explored the connectivity in the brain networks in the absence of the specific task and during the task processing. The spatio-temporal fluctuations of the activity of the brain areas detected in the resting state and being highly reproducible in numerous studies, resemble the activation and communication patterns during the task performance. Relatedly, the activation in the specific brain regions oftentimes is attributed to a number of cognitive processes. Given the complex organization of the cognitive functions, it becomes crucial to designate the roles of the brain networks in relation to the specific cognitive functions. One possible approach is to identify the commonalities of the deficits across the number of cognitive tests or, common errors in the various tests and identify their common "denominators" in the brain networks. The qualitative characterization of cognitive performance might be beneficial in addressing diffuse cognitive alterations presumably caused by the dysconnectivity of the distributed brain networks. Therefore, in the review, we use this approach in the description of standardized tests in the scope of potential errors in patients with schizophrenia with a subsequent reference to the brain networks.

Perception of direct vs. averted gaze in portrait paintings: An fMRI and eye-tracking study.

In this study, we use separate eye-tracking measurements and functional magnetic resonance imaging to investigate the neuronal and behavioral response to painted portraits with direct versus averted gaze. We further explored modulatory effects of several painting characteristics (premodern vs modern period, influence of style and pictorial context). In the fMRI experiment, we show that the direct versus averted gaze elicited increased activation in lingual and inferior occipital and the fusiform face area, as well as in several areas involved in attentional and social cognitive processes, especially the theory of mind: angular gyrus/temporo-parietal junction, inferior frontal gyrus and dorsolateral prefrontal cortex. The additional eye-tracking experiment showed that participants spent more time viewing the portrait's eyes and mouth when the portrait's gaze was directed towards the observer. These results suggest that static and, in some cases, highly stylized depictions of human beings in artistic portraits elicit brain activation commensurate with the experience of being observed by a watchful intelligent being. They thus involve observers in implicit inferences of the painted subject's mental states and emotions. We further confirm the substantial influence of representational medium on brain activity.

"Lazarus Response" to Olaparib in a Virtually Chemonaive Breast Cancer Patient Carrying Gross BRCA2 Gene Deletion.

This report describes an estrogen receptor-positive breast cancer patient, who relapsed at two and a half years after the completion of adjuvant chemotherapy while being on the aromatase inhibition. Based on the clinical evidence for potential sensitivity of the tumor to hormone ablation, everolimus was added to continuing exemestane treatment. Oral chemotherapy was administered at further disease progression, however, it lasted only for 10 days due to rapidly deteriorating condition of the patient. BRCA test was performed just before the failure of endocrine therapy and revealed a gross deletion within BRCA2 gene. Since the patient already developed contraindications to the standard chemotherapy, olaparib (300 mg twice a day) was given as a last hope option. The patient demonstrated a "Lazarus response": the performance status and the results of the biochemical tests went back to the norm within first two weeks of treatment. Positron emission tomography-computed tomography (PET-CT) was performed at one month after the start of olaparib therapy, and revealed complete metabolic response for all multiple metastatic lesions located in the liver, bones, small pelvis, lungs, mediastinum, retroperitoneum, etc. Cytotoxic therapy and poly ADP-ribose polymerase (PARP) inhibitors are known to have virtually identical mechanisms of tumor escape from the treatment, which are confined to the restoration of BRCA proficiency within cancer cells. The pronounced tumor response to the treatment in this patient can be attributed to the lack of recent exposure to standard cytotoxic treatment as well as to the inability of tumors with gross BRCA rearrangements to restore BRCA function via secondary mutation. This observation calls for comprehensive evaluation of PARP inhibitors in chemonaive patients with hereditary cancer.

Comparative Analysis of Theory of Mind Tests in First Episode Psychosis Patients.

The research is based on comparative analysis of 'Hinting Task', 'Faux Pas', and 'Reading the Mind in the Eyes' tests sensitivity in detection of Theory of Mind deficits. The study included 20 subjects with schizophrenia and schizophrenia spectrum disorders with the first episode of psychosis. Every subject performed the three proposed tests. It was shown that success rate of the three tests differed significantly. The non-verbal test 'Reading the Mind in the Eyes' caused the most difficulties. The success rate percentage of this test performance correlated negatively with the severity of psychopathological symptoms evaluated according to the PANSS scale. Thus, 'Reading the Mind in the Eyes' test is the most sensitive out of the three to Theory of Mind deficits detection, which may be used for diagnostic purposes.

Is there an optimal cognitive application to be used for cognitive remediation in clinical psychiatric practice?

Cognitive dysfunction is a common characteristic across a number of psychiatric conditions. With growing technological advances, application based cognitive remediation (cognitive apps) is becoming steadily popular due to its accessibility, ease of use and minimal interference with the activities of daily life. However, despite a number of benefits that application based cognitive training possesses, it is not clear, whether the utilisation of these apps is a reliable approach that can be recommended in clinical psychiatric practice in order to restore cognition. In the present review, we have analysed eleven applications which trained the cognitive domains of memory, attention, language, processing speed, executive function and perception with respect to the structure and function of the applications, duration of use and measuring and monitoring of user progress and assessed them, based on the published data, for efficacy in the general population and clinical subgroups of the population. We conclude that, given that there are differences between the apps, given that there is a difference between the general population using these apps and groups suffering pathological conditions using them, given that cognitive deficits are caused by different pathological processes in different illnesses and that different illnesses present with different ranges of deficits, it is not possible to make blanket recommendations for the use of the apps. Nor is there sufficient published evidence for any of the apps to be specifically recommended for cognitive remediation. More evidence, such as trials of specific apps in different conditions, trials of specific apps against therapist guided techniques and blind trials of different apps against each other are necessary before recommendations of particular apps for particular remedial treatments can be made. Nor can 'brain training' in normal populations be seen as preventing cognitive decline or be seen as proof that cognitive remediation can improve cognition in pathological groups. Our paper serves as a useful reference to what apps are available, how they compare, and what the published evidence is, with a view to planning further research.

Is motor imagery different in catatonic schizophrenia?

Catatonic schizophrenia, a rare subtype in this disease group, is characterized by motor disturbances. The current study investigated the reactivity of electroencephalographic mu rhythm in a motion imagery task in two single cases of first-episode catatonic schizophrenia, assuming they would show less mu rhythm reduction compared to paranoid schizophrenic patients and healthy controls.