Minimum spanning tree analysis of EEG resting-state functional networks in schizophrenia.

Schizophrenia is a serious and complex mental disease, known to be associated with various subtle structural and functional deviations in the brain. Recently, increased attention is given to the analysis of brain-wide, global mechanisms, strongly altering the communication of long-distance brain areas in schizophrenia. Data of 32 patients with schizophrenia and 28 matched healthy control subjects were analyzed. Two minutes long 64-channel EEG recordings were registered during resting, eyes closed condition. Average connectivity strength was estimated with Weighted Phase Lag Index (wPLI) in lower frequencies: delta and theta, and Amplitude Envelope Correlation with leakage correction (AEC-c) in higher frequencies: alpha, beta, lower gamma and higher gamma. To analyze functional network topology Minimum Spanning Tree (MST) algorithms were applied. Results show that patients have weaker functional connectivity in delta and alpha frequency bands. Concerning network differences, the result of lower diameter, higher leaf number, and also higher maximum degree and maximum betweenness centrality in patients suggest a star-like, and more random network topology in patients with schizophrenia. Our findings are in accordance with some previous findings based on resting-state EEG (and fMRI) data, suggesting that MST network structure in schizophrenia is biased towards a less optimal, more centralized organization.

A comparison of visual and acoustic mismatch negativity as potential biomarkers in schizophrenia.

Mismatch negativity (MMN) is an event-related potential (ERP) component generated when an unexpected deviant stimulus occurs in a pattern of standard stimuli. Several studies showed that the MMN response to both auditory and visual stimuli is attenuated in schizophrenia. While previous studies investigated auditory and visual MMN in different cohorts, here we examined the potential clinical utility of MMN responses to auditory and visual stimuli within the same group of patients. Altogether 39 patients with schizophrenia and 39 healthy controls matched in age, gender, and education were enrolled. We recorded EEG using 64 channels in eight experimental blocks where we presented auditory and visual stimulus sequences. Mismatch responses were obtained by subtracting responses to standard from the physically identical deviant stimuli. We found a significant MMN response to the acoustic stimuli in the control group, whereas no significant mismatch response was observed in the patient group. The group difference was significant for the acoustic stimuli. The 12 vane windmill pattern evoked a significant MMN response in the early time window in the control group but not in the patient group. The 6 vane windmill pattern evoked MMN only in the patient group. However, we found no significant difference between the groups. Furthermore, we found no correlation between the clinical variables and the MMN amplitudes. Our results suggest that predictive processes underlying mismatch generation in patients with schizophrenia may be more affected in the acoustic compared to the visual domain. Acoustic MMN tends to be a more promising biomarker in schizophrenia.

Distractor filtering and its electrophysiological correlates in schizophrenia.

OBJECTIVE: Patients with schizophrenia are characterized by compromised working memory (WM) performance and increased distractibility. Theta synchronization (especially over the frontal midline areas) is related to cognitive control and executive processes during WM encoding and retention. Alpha event-related desynchronization (ERD) is associated with information processing and attention. METHODS: Participants (35 patients and 39 matched controls) performed a modified Sternberg WM task, containing salient and non-salient distractor items in the retention period. A high-density 128 channel EEG was recorded during the task. Theta (4-7 Hz) and fast alpha (10-13 Hz) event-related spectral perturbation (ERSP) were analyzed during the retention and encoding period. RESULTS: Patients with schizophrenia showed worse WM performance and increased attentional distractibility in terms of lower hit rates and increased distractor-related commission errors compared to healthy controls. Theta synchronization was modulated by condition (learning vs. distractor) in both groups but it was modulated by salience only in controls. Furthermore, salience of distractors modulated less the fast alpha ERD in patients. CONCLUSIONS: Our results suggest that patients with schizophrenia process salient and non-salient distracting information less efficiently and show weaker cognitive control compared to controls. SIGNIFICANCE: These differences may partly account for diminished WM performance and increased distractibility in schizophrenia.

Salient distractors open the door of perception: alpha desynchronization marks sensory gating in a working memory task.

Focusing attention on relevant information while ignoring distracting stimuli is essential to the efficacy of working memory. Alpha- and theta-band oscillations have been linked to the inhibition of anticipated and attentionally avoidable distractors. However, the neurophysiological background of the rejection of task-irrelevant stimuli appearing in the focus of attention is not fully understood. We aimed to examine whether theta and alpha-band oscillations serve as an indicator of successful distractor rejection. Twenty-four students were enrolled in the study. 64-channel EEG was recorded during a modified Sternberg working memory task where weak and strong (salient) distractors were presented during the retention period. Event-related spectral perturbation in the alpha frequency band was significantly modulated by the saliency of the distracting stimuli, while theta oscillation was modulated by the need for cognitive control. Moreover, stronger alpha desynchronization to strong relative to weak distracting stimuli significantly increased the probability of mistakenly identifying the presented distractor as a member of the memory sequence. Therefore, our results suggest that alpha activity reflects the vulnerability of attention to distracting salient stimuli.

From basic perception deficits to facial affect recognition impairments in schizophrenia.

While impaired facial emotion recognition and magnocellular deficits in visual perception are core features of schizophrenia, their relationship is still unclear. Our aim was to analyze the oscillatory background of these processes and to investigate the connection between the magnocellular pathway deficit and the abnormal facial affect processing. Thirty-nine subjects with schizophrenia and forty socially matched healthy controls subjects were enrolled. A 128 channel EEG was recorded in three experimental tasks: first, participants viewed magnocellular biased low-spatial frequency (LSF) and parvocellular biased high-spatial frequency (HSF) Gabor-patches, then faces and houses were presented and in the third task a facial affect recognition task was presented with happy, sad and neutral faces. Event-related theta (4-7 Hz) synchronization (ERS) (i.e. an increase in theta power) by magnocellular biased stimuli was decreased in patients relative to controls, while no similar differences were found between groups in the parvocellular biased condition. ERS was significantly lower in patients compared to healthy controls both in the face and in the emotion recognition task. Theta ERS to magnocellular biased stimuli, but not to parvocellular biased stimuli, were correlated with emotion recognition performance. These findings indicate a bottom up disruption of face perception and emotion recognition in schizophrenia.

Impaired mixed emotion processing in the right ventrolateral prefrontal cortex in schizophrenia: an fMRI study.

BACKGROUND: Schizophrenia has a negative effect on the activity of the temporal and prefrontal cortices in the processing of emotional facial expressions. However no previous research focused on the evaluation of mixed emotions in schizophrenia, albeit they are frequently expressed in everyday situations and negative emotions are frequently expressed by mixed facial expressions. METHODS: Altogether 37 subjects, 19 patients with schizophrenia and 18 healthy control subjects were enrolled in the study. The two study groups did not differ in age and education. The stimulus set consisted of 10 fearful (100%), 10 happy (100%), 10 mixed fear (70% fear and 30% happy) and 10 mixed happy facial expressions. During the fMRI acquisition pictures were presented in a randomized order and subjects had to categorize expressions by button press. RESULTS: A decreased activation was found in the patient group during fear, mixed fear and mixed happy processing in the right ventrolateral prefrontal cortex (VLPFC) and the right anterior insula (RAI) at voxel and cluster level after familywise error correction. No difference was found between study groups in activations to happy facial condition. Patients with schizophrenia did not show a differential activation between mixed happy and happy facial expression similar to controls in the right dorsolateral prefrontal cortex (DLPFC). CONCLUSIONS: Patients with schizophrenia showed decreased functioning in right prefrontal regions responsible for salience signaling and valence evaluation during emotion recognition. Our results indicate that fear and mixed happy/fear processing are impaired in schizophrenia, while happy facial expression processing is relatively intact.

Deficits in low beta desynchronization reflect impaired emotional processing in schizophrenia.

Empirical data from previous investigations showed that emotion processing is reflected in beta, and especially in low beta event related desynchronization (ERD) (i.e. a decrease in low beta power). While recognition of social information and emotion processing are impaired in schizophrenia, no previous study analyzed induced and evoked beta oscillations in patients with schizophrenia during emotion processing. Twenty-eight subjects with schizophrenia and twenty-seven healthy controls subjects were enrolled in the study. The two study groups did not differ in age, gender and education. Participants viewed positive, neutral and negative scenes selected from the International Affective Picture System (IAPS) while 128-channel EEG was recorded. A significantly weaker low beta ERD was detected in patients relative to controls for the negative stimulus condition in the right parieto-occipital and temporal regions. Patients with decreased beta ERD showed more prominent negative symptoms and more severe deficits in psychosocial functioning. Only in the control group stronger beta ERD was detected for the negative stimuli relative to positive and neutral stimuli in the same regions. Our major finding is that impaired emotion processing in schizophrenia is reflected in decreased low beta ERD and in the diminished differences between low beta ERD to negative and non-negative emotional stimuli. Furthermore, it was found that patients with decreased beta ERD show more prominent negative symptoms and more severe deficits in psychosocial functioning.

Elementary sensory deficits in schizophrenia indexed by impaired visual mismatch negativity.

INTRODUCTION: Mismatch negativity (MMN) is an automatic brain response to unexpected events. It represents a prediction error (PE) response, reflecting the difference between the sensory input and predictions. While deficits in auditory MMN are well known in schizophrenia, only few studies investigated impairments in predictive visual processing in schizophrenia. These studies used complex stimuli such as motion direction and emotional facial expressions. Here we studied whether automatic predictive processing of elementary features such as orientation is also impaired in schizophrenia. METHODS: Altogether 28 patients with schizophrenia and 27 healthy controls matched in age, gender, and education participated in the study. EEG was recorded using 128 channels in the two experimental blocks. Using an oddball paradigm, horizontal stripes of Gabor patches were presented as frequent standards and vertical stripes as rare deviants in one block. Stimulus probabilities were swapped in the other block. Mismatch responses were obtained by subtracting responses to standard from those to deviant stimuli. RESULTS: We found significant mismatch responses in healthy controls but not in patients in the prefrontal and occipital-parietal regions in the 90-200ms interval. Furthermore patients showed significantly decreased deviant minus standard difference waveforms relative to controls in the same regions with moderate to large effect sizes. CONCLUSIONS: Our findings demonstrate that predictive processing of unattended low-level visual features such as orientation is impaired in schizophrenia. Our results complement reports of sensory deficits found in tasks requiring attentive processing and suggest that deficits are present in automatic visual sensory processes putatively mediated by glutamatergic functioning.

Monitoring the early signs of cognitive decline in elderly by computer games: an MRI study.

BACKGROUND: It is anticipated that current and future preventive therapies will likely be more effective in the early stages of dementia, when everyday functioning is not affected. Accordingly the early identification of people at risk is particularly important. In most cases, when subjects visit an expert and are examined using neuropsychological tests, the disease has already been developed. Contrary to this cognitive games are played by healthy, well functioning elderly people, subjects who should be monitored for early signs. Further advantages of cognitive games are their accessibility and their cost-effectiveness. PURPOSE: The aim of the investigation was to show that computer games can help to identify those who are at risk. In order to validate games analysis was completed which measured the correlations between results of the 'Find the Pairs' memory game and the volumes of the temporal brain regions previously found to be good predictors of later cognitive decline. PARTICIPANTS AND METHODS: 34 healthy elderly subjects were enrolled in the study. The volume of the cerebral structures was measured by MRI. Cortical reconstruction and volumetric segmentation were performed by Freesurfer. RESULTS: There was a correlation between the number of attempts and the time required to complete the memory game and the volume of the entorhinal cortex, the temporal pole, and the hippocampus. There was also a correlation between the results of the Paired Associates Learning (PAL) test and the memory game. CONCLUSIONS: The results gathered support the initial hypothesis that healthy elderly subjects achieving lower scores in the memory game have increased level of atrophy in the temporal brain structures and showed a decreased performance in the PAL test. Based on these results it can be concluded that memory games may be useful in early screening for cognitive decline.