Search

Electroencephalographic (EEG) analysis has emerged as a powerful tool for brain state interpretation and diagnosis, but not for the diagnosis of mental disorders; this may be explained by its low spatial resolution or depth sensitivity. This paper concerns the diagnosis of schizophrenia using EEG, which currently suffers from several cardinal problems: it heavily depends on assumptions, conditions and prior knowledge regarding the patient. Additionally, the diagnostic experiments take hours, and the accuracy of the analysis is low or unreliable. This article presents the "TFFO" (Time-Frequency transformation followed by Feature-Optimization), a novel approach for schizophrenia detection showing great success in classification accuracy with no false positives. The methodology is designed for single electrode recording, and it attempts to make the data acquisition process feasible and quick for most patients.

This paper tests the hypothesis that patients with schizophrenia have a deficit in selectively attending to predictable events. We used dynamic causal modeling (DCM) of electrophysiological responses - to predictable and unpredictable visual targets - to quantify the effective connectivity within and between cortical sources in the visual hierarchy in 25 schizophrenia patients and 25 age-matched controls. We found evidence for marked differences between normal subjects and schizophrenia patients in the strength of extrinsic backward connections from higher hierarchical levels to lower levels within the visual system. In addition, we show that not only do schizophrenia subjects have abnormal connectivity but also that they fail to adjust or optimize this connectivity when events can be predicted. Thus, the differential intrinsic recurrent connectivity observed during processing of predictable versus unpredictable targets was markedly attenuated in schizophrenia patients compared with controls, suggesting a failure to modulate the sensitivity of neurons responsible for passing sensory information of prediction errors up the visual cortical hierarchy. The findings support the proposed role of abnormal connectivity in the neuropathology and pathophysiology of schizophrenia., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Functional connectivity was evaluated in patients with schizophrenia (SC) and in patients with Parkinson's disease (PD) during the performance of a local contextual processing paradigm, to investigate the proposition that functional disconnection is involved with contextual processing deficits in these populations. To this end, we utilized event-related EEG signals, synchronization likelihood and graph theoretical analysis. Local context was defined as the occurrence of a predictive sequence of stimuli before the presentation of a target event. In the SC patients, we observed a decrease in path length (L) in the beta band, for the predictive sequence and for predicted and random targets, compared with controls. These abnormalities were associated with weaker frontal-temporal-parietal connections. In the PD patients we found longer L (theta band) for predicted targets, and higher cluster coefficients for both the predictive sequence (theta band) and predicted targets (alpha and theta bands), compared with controls. Detection of predicted targets was associated with weaker frontal-parietal connections in PD. No group differences were found for randomized standard stimuli in both SC and PD patients. These findings provide evidence of task-specific functional connectivity abnormalities within frontal networks during local contextual processing., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Deficits in processing contextual information are one of the main features of cognitive dysfunction in schizophrenia, but the neurophysiologic substrate underlying this dysfunction is poorly understood. We used ERPs to investigate local contextual processing in schizophrenic patients. Local context was defined as the occurrence of a short predictive series of stimuli occurring before delivery of a target event. Response times of predicted targets were faster in controls compared to patients. Schizophrenia patients failed to generate the P3b latency shift between predicted and random targets that was observed in controls and demonstrated a prominent reduction of the peak of an early latency context dependent positivity. The current study provides evidence of contextual processing deficits in schizophrenia patients by demonstrating alteration in the behavioral and neural correlates of local contextual processing., (Copyright © 2011 Society for Psychophysiological Research.)

Schizophrenia is a serious mental disorder characterized by a heterogeneous spectrum of clinical manifestations. Schizophrenia is basically incurable. The discovery of antipsychotic medications in the late 1940s has helped control some of the symptoms but has not reversed the course of the disorder and has had limited effect on the debilitating symptoms of the illness. In recent years brain stimulation technologies have emerged in the bio-scientific scenery. Deep brain stimulation now plays an important role in the treatment of many neurological disorders, and seems promising in treating depression. Optogenetics is a new technology that offers control over neuronal activity by turning on and off distinct neuronal populations. It has a great advantage over previous brain stimulation technologies in that it is accurate and specific to the neurons intended for activation and control. There is no evidence that brain stimulation has been investigated in schizophrenia patients. This possibility was discussed in a single commentary that proposed the hippocampus and nucleus accumbence as targets for DBS in schizophrenia, however it was emphasized that the neurophysiology and neuroanatomy of schizophrenia have not been elucidated to the extent that brain stimulation can be planned. In light of new optogenetic technology time is ripe to seriously consider optional targets of intervention in the brain of schizophrenia patients. Any such target should involve neuronal circuits (1) known to be relevant for schizophrenia, (2) involved in cognitive and brain functions that are disturbed in schizophrenia, and (3) relevant to alleged neuronal network mechanisms that are presumably damaged or malfunctioning in schizophrenia. This paper reviews the relevant literature and proposes that optogenetic interventions in schizophrenia should begin in the prefrontal cortex and the Globus-Pallidus Subthalamic nuclei systems. In the protocol for the prefrontal cortex, wide-arbore and chandelier inhibitory interneurons should be targets for optogenetic intervention and in the Globus-Pallidus Subthalamic nuclei the fast spiking neurons should be targets for optogenetic intervention. These subsystems are critical modulators of neural complexity which is directly relevant to connectivity organization in the brain. Schizophrenia is described as a disturbance of connectivity organization in the brain treatable by the relevant optogenetic interventions promoted in this paper., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been hampered by the large artifact that the TMS generates in the EEG. Using TMS with EEG necessitates a sophisticated artifact-resistant EEG system that can acquire reliable signals in the crucial several tens of milliseconds immediately following the TMS pulse. Here, we demonstrate the use of a novel artifact removal algorithm together with a 24-bit EEG system to achieve similar recordings as those obtained with the dedicated TMS-compatible EEG system., Methods: This setup was used to compare TMS-evoked responses between a group of healthy controls and a group of patients with schizophrenia, a condition in which effective neural connectivity is thought to be compromised., Results: We observe differences in TMS-evoked responses between the two groups, similar to those recently reported in a study that used a dedicated TMS-compatible EEG system., Conclusions: The standard 24-bit EEG system combined with an artifact removal algorithm produces results similar to the dedicated TMS-compatible system., Significance: This paves the way for more researchers and clinicians to use TMS-evoked responses for research and diagnosis of a wide spectrum of disorders.

Transcranial Magnetic Stimulation (TMS) is rapidly gaining acceptance as a non-invasive probe into brain functionality. We utilize TMS to study the connectivity of a simple motor network in patients of schizophrenia (N=19), and in healthy control subjects (N=9). TMS was used in an externally paced finger tapping task, perturbing the internal network oscillations invoked by the finger motion as it keeps pace with a metronome. TMS perturbations were synchronized to the metronome and applied to the network at the level of the primary motor cortex (M1). Contrary to initial expectations, TMS did not affect the sensorimotor synchronization of subjects with schizophrenia or their tapping accuracy. TMS did cause extreme deviations in the finger's trajectory, and altered the timing perceptions of subjects with schizophrenia. Additionally, it invoked high-level deficiencies related to attention and volition in the form of lapses, implying that the connectivity between modules in the brain that underlie motor control, sensorimotor synchronization, timing perception and awareness of action, can be disrupted by TMS in subjects with schizophrenia, but not in healthy subjects. The ability to disrupt high level network functions with perturbations to the lower level of M1 supports models describing deficits in connectivity of distributed networks in the brains of schizophrenia patients. It also demonstrates the use of TMS to probe connectivity between components of such networks.

A large body of literature indicates that disturbances of central serotonin (5-HT) function play an important role in aggressive behavior. Results from open-label and placebo-controlled trials as well as the reported inverse relationship between 5-HT function and aggression in human subjects, suggest that reduced 5-HT activity is associated with aggressive behavior. The activity of the 5-HT transporter (5-HTT), as determined by [(3)H]5-HT uptake to blood lymphocytes, was measured in 20 currently aggressive and 20 non-aggressive male schizophrenia patients. In addition, the pharmacodynamic characteristics of platelet 5-HTT were assessed by [(3)H]citalopram binding. There were no significant differences in the density (B(max)) of platelet [(3)H]citalopram binding sites between the two groups. Similarly, the dissociation constant (K(d)) values were indistinguishable. The maximum uptake velocity (V(max)) of [(3)H]5-HT to fresh lymphocytes and the K(m) values of the 5-HT to the transporter were significantly higher in currently aggressive compared to the non-aggressive schizophrenia patients. The association of high V(max) values with current aggressive behavior provides further support to the involvement of the 5-HTT in aggressive behavior as well as to the efficacy of 5-HTT blockers in the control of aggression. The role of the various components of the serotonergic system in the pathophysiology and treatment of aggressive behavior in schizophrenia needs to be further evaluated.

A rapidly growing body of data suggests that abnormalities in serotonergic function might be involved in the pathophysiology of schizophrenia and that serotonergic mechanisms play a role in the therapeutic effects of antipsychotics. The activity of the serotonin transporter (5-HTT), as determined by [(3)H]5-HT uptake to blood lymphocytes, was measured in 38 medicated schizophrenia patients (15 of them treated with typical antipsychotics and 23 treated with atypical antipsychotics) and 15 healthy control subjects. In addition, the pharmacodynamic characteristics of platelet 5-HTT were assessed by [(3)H]citalopram binding. There were no significant differences in the density (B(max)) of platelet [(3)H]citalopram binding sites between the three groups. Similarly, the dissociation constant (K(d)) values were indistinguishable. There were no significant differences in the maximal uptake velocity (V(max)) of [(3)H]5-HT to fresh lymphocytes between the three groups. The affinity (K(m)) values of 5-HT to the 5-HTT were significantly higher in schizophrenia patients treated with typical antipsychotics compared with control subjects. The K(m) values in schizophrenia patients treated with atypical antipsychotics were significantly lower compared with those observed in the group of schizophrenia patients treated with typical antipsychotics; however, they were comparable to values in the control group. The high values of K(m) associated with typical antipsychotic treatment may be relevant to the high risk of developing extrapyramidal side effects (EPS). The role of the various components of the serotonergic system in the etiopathology of schizophrenia and the mechanisms by which antipsychotics achieve their therapeutic effects need to be further evaluated.

Objective: The authors' goal was to improve the diagnosis of schizophrenia by using virtual reality technology to build a complex, multimodal environment in which cognitive functions can be studied (and measured) in parallel., Method: The authors studied sensory integration within working memory by means of computer navigation through a virtual maze. The simulated journey consisted of a series of rooms, each of which included three doors. Each door was characterized by three features (color, shape, and sound), and a single combination of features--the door-opening rule--was correct. Subjects had to learn the rule and use it. The participants were 39 schizophrenic patients and 21 healthy comparison subjects., Results: Upon completion, each subject was assigned a performance profile, including various error scores, response time, navigation ability, and strategy. A classification procedure based on the subjects' performance profile correctly predicted 85% of the schizophrenic patients (and all of the comparison subjects). Several performance variables showed significant correlations with scores on a standard diagnostic measure (Positive and Negative Syndrome Scale), suggesting potential use of these measurements for the diagnosis of schizophrenia. On the other hand, the patients did not show unusual repetition of response despite stimulus cessation (called "perseveration" in classical studies of schizophrenia), which is a common symptom of the disease. This deficit appeared only when the subjects did not receive proper explanation of the task., Conclusions: The ability to study multimodal performance simultaneously by using virtual reality technology opens new possibilities for the diagnosis of schizophrenia with objective procedures.

Background: Collins and Quillian ( Acta Psychol 1970;33:304-314) proposed that semantic representations in the human brain could have a "networklike" theoretical construct. Thought disorders in schizophrenia have been described as disturbances in the spread of activation within semantic networks. Semantic networks are typically evaluated indirectly via reaction times of priming tasks. Medications may interfere with the reaction time of patients, thus, we sought to investigate semantic networks, independent of time, by having patients and controls rate textual associations in sentences organized to various degrees., Methods: Twenty-eight schizophrenic patients (17 non-thought-disordered and 11 thought-disordered) and 27 healthy controls performed a rating of textual associations task in which they were asked to rate the associative relationship between concepts in sentences on a scale from 1 (totally dissociated) to 10 (completely associated). The task contained 3 sets of sentences; organized meaningful sentences, vague sentences (intermediately disorganized), and completely disorganized sentences. To avoid order effects, sentences were randomly mixed at presentation., Results: Analysis of variance calculations indicated significant differences among the 3 groups (controls, thought-disordered, and non-thought-disordered). The differences were greater for the vague sentences. Compared with controls, schizophrenic patients demonstrated increased SDs in rating associative values between concepts in the sentences, which is higher in disorganized sentences. Inadequate ability to identify and rate associations in disorganized sentences is discussed in the context of disordered semantic networks of schizophrenic patients.

Our goal is to develop a new family of automatic tools for the diagnosis of schizophrenia, using Virtual Reality Technology (VRT). VRT is specifically suitable for this purpose, because it allows for multi-modal stimulation in a complex setup, and the simultaneous measurement of multiple parameters. In this work we studied sensory integration within working memory, in a navigation task through a VR maze. Along the way subjects pass through multiple rooms that include three doors each, only one of which can be used to legally exit the room. Specifically, each door is characterized by three features (color, shape and sound), and only one combination of features -- as determined by a transient opening rule -- is legal. The opening rule changes over time. Subjects must learn the rule and use it for successful navigation throughout the maze. 39 schizophrenic patients and 21 healthy controls participated in this study. Upon completion, each subject was assigned a performance profile, including various error scores, response time, navigation ability and strategy. We developed a classification procedure based on the subjects' performance profile, which correctly predicted 85% of the schizophrenic patients (and all the controls). We observed that a number of parameters showed significant correlation with standard diagnosis scores (PANSS), suggesting the potential use of our measurements for future diagnosis of schizophrenia. On the other hand, our patients did not show unusual repetition of response despite stimulus cessation (called perseveration in classical studies of schizophrenia), which is usually considered a robust marker of the disease. Interestingly, this deficit only appeared in our study when subjects did not receive proper explanation of the task.

The rubber-hand illusion (RHI), an illusion in which tactile sensations are referred to a synthetic alien limb, is enhanced in schizophrenia patients. Somatosensory evoked responses of the illusion were compared between schizophrenia patients and normal control subjects. Schizophrenia patients had significant alterations in long latency evoked responses during the illusion. These findings support the hypothesis of alterations in associative higher-level neuronal activity in schizophrenia. The findings support previous results pointing to alterations in associative brain regions in schizophrenia.

Patients with schizophrenia have thinking disorders such as delusions or hallucinations because they have a deficit in the ability to systematize and integrate information. Therefore, they cannot integrate or systematize visual, auditory, and tactile stimuli. The multimodal integration model of the brain can provide a theoretical background from which one can approach multimodal stimulus integration. In this study, we suggest a virtual reality system for the multi-modal assessment of cognitive ability of schizophrenia patients. The virtual reality system can provide multimodal stimuli, such as visual and auditory stimuli, to the patient and can evaluate the patient's multimodal integration and working memory integration abilities by making the patient interpret and react to multimodal stimuli, which must be remembered for a given period of time. The clinical study showed that the virtual reality program developed is comparable to those of the Wisconsin Card Sorting Test (WCST) and the Standard Progressive Matrices (SPM), and it provides some information related to the schizophrenic patients' behavior in 3D virtual environment.

Olanzapine is a substrate of the cytochrome P450 enzyme (CYP) 1A2. In this study, pharmacokinetic interactions and clinical effects of adding the CYP1A2 inhibitor fluvoxamine to steady-state olanzapine was examined in patients suffering from schizophrenia. Eight patients had been treated for at least 3 months with 10 to 20 mg/day olanzapine. Fluvoxamine (100 mg/day) was added (week 0) to the olanzapine treatment and continued for 8 weeks. Concentrations of olanzapine and its metabolite N-desmethylolanzapine and of fluvoxamine were analyzed at weeks 0, 1, 4, and 8. Addition of fluvoxamine resulted in a 12% to 112% ( < 0.01) increase of olanzapine from 31 +/- SD 15 ng/mL (week 0) to 56 +/- 31 ng/mL (week 8) in all patients. N-desmethylolanzapine concentrations were not significantly changed ( > 0.05). Fluvoxamine concentrations were 48 +/- 26 ng/mL on week 1 and 83 +/- 47 ng/mL on week 8. It is concluded that fluvoxamine affects olanzapine degradation and thus increases olanzapine concentrations. Although the combination was well tolerated in this sample and the negative symptom response appeared to be favorable in at least five patients, the combination therapy of olanzapine and fluvoxamine should be used cautiously and should be controlled by therapeutic drug monitoring to avoid olanzapine-induced side effects or intoxications.

Abstract: Background: As an Ancient Chinese proverb says “The beginning of wisdom is to call things by their right names” thus we must start calling mental disorders by the names of their underlying brain disturbances. Without knowledge of the causes of mental disorders, their cures will remain elusive. Methods: Neuroanalysis is a literature-based re-conceptualization of mental disorders as disturbances of brain organization. Psychosis and schizophrenia can be re-conceptualized as disturbances to connectivity and hierarchical dynamics in the brain; mood disorders can be re-conceptualized as disturbances to optimization dynamics and free energy in the brain, and finally personality disorders can be re-conceptualized as disordered default-mode networks in the brain. Results and conclusions: Knowledge and awareness of the disease algorithms of mental disorders will become critical because powerful technologies for controlling brain activity are developing and becoming available. The time will soon come when psychiatrists will be asked to define the exact ‘algorithms’ of disturbances in their psychiatric patients. Neuroanalysis can be a starting point for the response to that challenge. [Copyright &y& Elsevier]

Background: Virtual Reality is an interactive three-dimensional computer generated environment. Providing a complex and multi-modal environment, VR can be particularly useful for the study of complex cognitive functions and brain disorders. Here we used a VR world to measure the distortion in reality perception in schizophrenia patients. Methods: 43 schizophrenia patients and 29 healthy controls navigated in a VR environment and were asked to detect incoherencies, such as a cat barking or a tree with red leaves. Results: Whereas the healthy participants reliably detected incoherencies in the virtual experience, 88% of the patients failed in this task. The patients group had specific difficulty in the detection of audio-visual incoherencies; this was significantly correlated with the hallucinations score of the PANSS. Conclusions: By measuring the distortion in reality perception in schizophrenia patients, we demonstrated that Virtual Reality can serve as a powerful experimental tool to study complex cognitive processes. [ABSTRACT FROM AUTHOR]

Patients with schizophrenia have thinking disorders such as delusions or hallucinations because they have a deficit in the ability to systematize and integrate information. Therefore, they cannot integrate or systematize visual, auditory, and tactile stimuli. The multimodal integration model of the brain can provide a theoretical background from which one can approach multimodal stimulus integration. In this study, we suggest a virtual reality system for the multi-modal assessment of cognitive ability of schizophrenia patients. The virtual reality system can provide multimodal stimuli, such as visual and auditory stimuli, to the patient and can evaluate the patient's multimodal integration and working memory integration abilities by making the patient interpret and react to multimodal stimuli, which must be remembered for a given period of time. The clinical study showed that the virtual reality program developed is comparable to those of the Wisconsin Card Sorting Test (WCST) and the Standard Progressive Matrices (SPM), and it provides some information related to the schizophrenic patients' behavior in 3D virtual environment. [ABSTRACT FROM AUTHOR]

Presents an electroencephalograph study of functional connectivity and working memory in schizophrenia. Importance of connectivity for simulation of working memory; Failure of schizophrenics to activate the neural networks of the fronto-temporal regions; Findings supporting a 'disconnection syndrome' for schizophrenia.