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Highlights: [•] Reaction times and P3b latencies of predicted targets were prolonged in depression. [•] P3b amplitudes were attenuated in major depressive disorder during processing of predictive contextual information, as well as target N1 amplitudes. [•] Processing of local contextual processing is altered in major depressive disorder. [ABSTRACT FROM AUTHOR]

Abstract: 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 [3H]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 [3H]citalopram binding. There were no significant differences in the density (B max) of platelet [3H]citalopram binding sites between the two groups. Similarly, the dissociation constant (K d) values were indistinguishable. The maximum uptake velocity (V max) of [3H]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. [Copyright &y& Elsevier]

Abstract: 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 [3H]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 [3H]citalopram binding. There were no significant differences in the density (B max) of platelet [3H]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 [3H]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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

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.

The combination of Transcranial Magnetic Stimulation (TMS) with Electroencephalography (EEG) exposes the brain’s global response to localized and abrupt stimulations. However, large electric artifacts are induced in the EEG by the TMS, obscuring crucial stages of the brain’s response. Artifact removal is commonly performed by data processing techniques. However, an experimentally verified physical model for the origin and structure of the TMS-induced discharge artifacts, by which these methods can be justified or evaluated, is still lacking. We re-examine the known contribution of the skin in creating the artifacts, and outline a detailed model for the relaxation of the charge accumulated at the electrode-gel-skin interface due to the TMS pulse. We then experimentally validate implications set forth by the model. We find that the artifacts decay like a power law in time rather than the commonly assumed exponential. In fact, the skin creates a power-law decay of order 1 at each electrode, which is turned into a power law of order 2 by the reference electrode. We suggest an artifact removal method based on the model which can be applied from times after the pulse as short as 2 milliseconds onwards to expose the full EEG from the brain. The method can separate the capacitive discharge artifacts from those resulting from cranial muscle activation, demonstrating that the capacitive effect dominates at short times. Overall, our insight into the physical process allows us to accurately access TMS-evoked EEG responses that directly follow the TMS pulse, possibly opening new opportunities in TMS-EEG research. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We study the interplay between motor programs and their timing in the brain by using precise pulses of transcranial magnetic stimulation (TMS) applied to the primary motor cortex. The movement of the finger performing a tapping task is periodically perturbed in synchronization with a metronome. TMS perturbation can profoundly affect both the finger trajectory and its kinematics, hut the tapping accuracy itself is surprisingly not affected. The motion of the finger during the TMS perturbation can he categorized into two abnormal behaviors that subjects were unaware of: a doubling of the frequency of the tap and a stalling of the finger for half the period. More stalls occurred as the tapping frequency increased. In addition, an enhancement of the velocity of the finger on its way up was observed. We conclude that the timing process involved in controlling the tapping movement is separate from the motor processes in charge of execution of the motor commands. We speculate that the TMS is causing a release of the motor plan ahead of time into activation mode. The observed doubles and stalls are then the result of an indirect interaction in the brain, making use of an existing motor plan to correct the preactivation and obtain the temporal goal of keeping the beat. [ABSTRACT FROM AUTHOR]

Highlights: [•] Evaluation of functional connectivity using EEG and graph theory. [•] Schizophrenia and PD patients perform contextual processing task. [•] Stimulus-specific decrease of path length in schizophrenia patients. [•] Context-dependent increase of path length and clustering coefficient in PD patients. [•] Abnormalities associated with weaker connections within frontal networks. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

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. [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]

• Increased functional connectivity during processing of predictive stimuli in MDD. • Functional connectivity changes in beta band and within frontal networks in MDD. • Findings may indicate compensatory mechanisms for neural insufficiency in MDD. The study investigated the underlying mechanisms associated with the ability of patients with major depressive disorder (MDD) to utilize predictive contextual information in order to facilitate detection of predictable versus random targets. To this end we evaluated EEG event-related functional connectivity during the processing of predictive stimuli in MDD and control subjects. A target detection task was used where targets were either preceded by randomized sequences of standards, or by sequences that included a predictive sequence. Functional connectivity was evaluated using synchronization likelihood and graph theory. The cluster coefficient and local efficiency values were greater in MDD compared to controls, during the processing of the three stimuli consisting of the predictive sequence, in the beta frequency band, suggesting an increased structured network organization. These changes were associated with increased functional connectivity within frontal networks in MDD patients compared to controls. However, no significant functional connectivity group-changes were observed for target conditions or randomized standards. These findings suggest that MDD is associated with context-specific functional connectivity abnormalities during the processing of predictive stimuli. [ABSTRACT FROM AUTHOR]