Oscillatory brain dynamics supporting impaired Stroop task performance in schizophrenia-spectrum disorder.

The Stroop color-word interference task, prompting slower response to color-incongruent than to congruent items, is often used to study neural mechanisms of inhibitory control and dysfunction in schizophrenia-spectrum disorders. Inconsistent findings of an augmented Stroop effect limit identification of relevant dysfunctional mechanism(s) in schizophrenia. The present study sought to advance understanding of normal and impaired neural oscillatory dynamics by distinguishing interference detection and response preparation during the Stroop task in schizophrenia-spectrum disorders via analysis of behavioral performance and 4-7 Hz (theta) and 10-30 Hz (alpha/beta) EEG oscillations in 40 patients (SZ) and 27 healthy comparison participants (HC). SZ responded more slowly and showed less dorsal anterior cingulate (dACC) theta enhancement during INC trials, less enhancement of dACC-sensorimotor cortex connectivity (theta phase synchrony) during INC trials, more alpha/beta suppression though less enhancement of that suppression during INC trials, and slower post-response alpha/beta rebound than did HC. Reaction time distributions showed larger group and Stroop effects during the 25% of trials with the slowest responses. Poorer theta phase coherence in patients indicates impaired communication between regions associated with interference processing (dACC) and response preparation (sensorimotor cortex). Results suggest a failure cascade in which compromised behavioral Stroop effects are driven at least in part by dysfunctional interference processing (less theta power increase) prompting dysfunctional motor response preparation (less alpha/beta power suppression). Inconsistent Stroop effects in past studies of schizophrenia may result from differing task parameters sampling different degrees of Stroop task difficulty.

Cross-frequency interactions between frontal theta and posterior alpha control mechanisms foster working memory.

Neural oscillatory activity in the theta (4-8 Hz) and alpha (8-14 Hz) bands has been associated with the implementation of executive function, with theta in midline frontal cortex and alpha in posterior parietal cortex related to working memory (WM) load. To identify how these spatially and spectrally distinct neural phenomena interact within a large-scale fronto-parietal network organized in service of WM, EEG was recorded while subjects performed an N-back WM task. Frontal theta power increase, paralleled by posterior alpha decrease, tracked participants' successful WM performance. These power fluctuations were inversely related both across and within trials and predicted reaction time, suggesting a functionally important communication channel within the fronto-parietal network. Granger causality analysis revealed directed parietal to frontal communication via alpha and frontal to parietal communication via theta. Results encourage consideration of these bidirectional, power-to-power, cross-frequency control mechanisms as an important feature of cerebral network organization supporting executive function.

The impact of cognitive training on spontaneous gamma oscillations in schizophrenia.

Schizophrenia patients exhibit less gamma-frequency EEG/MEG activity (>30 Hz), a finding interpreted as evidence of poor temporal neural organization and functional network communication. Research has shown that neuroplasticity-oriented training can improve task-related oscillatory dynamics, indicating some reorganization capacity in schizophrenia. Demonstrating a generalization of such task training effects to spontaneous oscillations at rest would not only enrich understanding of this neuroplastic potential but inform the interpretation of spontaneous gamma oscillations in the service of normal cognitive function. In the present study, neuromagnetic resting-state oscillatory brain activity and cognitive performance were assessed before and after training in 61 schizophrenia patients, who were randomly assigned to 4 weeks of neuroplasticity-oriented targeted cognitive training or treatment as usual (TAU). Gamma power of 40-90 Hz increased after training, but not after TAU, in a frontoparietal network. Across two types of training, this increase was related to improved cognitive test performance. These results indicate that abnormal oscillatory dynamics in schizophrenia patients manifested in spontaneous gamma activity can be changed with neuroplasticity-oriented training parallel to cognitive performance.

Same clock, different time read-out: Spontaneous brain oscillations and their relationship to deficient coding of cognitive content.

Neuronal oscillations provide an efficient means of communication, fostering functional neural states supporting action and reaction. High in the action hierarchy, cognitive abilities are severely compromised in neuropsychiatric disease such as schizophrenia. Current thinking highlights a clocking mechanism provided by the phase of an ongoing slow oscillation that offers a temporal frame for coding of perceptual and computational elements. Yet unclear is whether and how a dysregulated clocking mechanism accounts for diminished cognitive performance. Neuromagnetic oscillatory activity was related to cognitive performance assessed by the MATRICS Consensus Cognitive Battery in 58 healthy individuals (HC) and 46 schizophrenia patients (SZ). HC showed a correlation between gamma-band oscillations (>40 Hz) and working memory performance. This relationship was disrupted in several ways in SZ. First, patients evidenced lower gamma power, poorer working memory performance, and no relationship between these measures. Second, the power spectra were dominated by ~10 Hz alpha oscillations with no group differences in amplitude. However, analysis of phase-to-amplitude coupling (PAC) revealed exaggerated clocking of gamma activity by alpha phase in SZ, associated with poor working memory performance. Third, despite entrainment by the same 10 Hz clock, gamma amplitude was abnormally distributed across the duty cycle in SZ, a potential consequence of compromised interneuron inhibition. Fourth, SZ showed over-engagement of a fronto-parietal network measured by gamma phase coherence, suggesting a brain state hindering cognitive output. Such an endogenous temporal organization may be a core dysfunction in SZ: a segregation/integration input imbalance fostering reduced cognitive performance and compromised behavioral output.

Targeted training modifies oscillatory brain activity in schizophrenia patients.

Effects of both domain-specific and broader cognitive remediation protocols have been reported for neural activity and overt performance in schizophrenia (SZ). Progress is limited by insufficient knowledge of relevant neural mechanisms. Addressing neuronal signal resolution in the auditory system as a mechanism contributing to cognitive function and dysfunction in schizophrenia, the present study compared effects of two neuroplasticity-based training protocols targeting auditory-verbal or facial affect discrimination accuracy and a standard rehabilitation protocol on magnetoencephalographic (MEG) oscillatory brain activity in an auditory paired-click task. SZ were randomly assigned to either 20 daily 1-hour sessions over 4 weeks of auditory-verbal training (N = 19), similarly intense facial affect discrimination training (N = 19), or 4 weeks of treatment as usual (TAU, N = 19). Pre-training, the 57 SZ showed smaller click-induced posterior alpha power modulation than did 28 healthy comparison participants, replicating Popov et al. (2011b). Abnormally small alpha decrease 300-800 ms around S2 improved more after targeted auditory-verbal training than after facial affect training or TAU. The improvement in oscillatory brain dynamics with training correlated with improvement on a measure of verbal learning. Results replicate previously reported effects of neuroplasticity-based psychological training on oscillatory correlates of auditory stimulus differentiation, encoding, and updating and indicate specificity of cortical training effects.

Changing facial affect recognition in schizophrenia: effects of training on brain dynamics.

Deficits in social cognition including facial affect recognition and their detrimental effects on functional outcome are well established in schizophrenia. Structured training can have substantial effects on social cognitive measures including facial affect recognition. Elucidating training effects on cortical mechanisms involved in facial affect recognition may identify causes of dysfunctional facial affect recognition in schizophrenia and foster remediation strategies. In the present study, 57 schizophrenia patients were randomly assigned to (a) computer-based facial affect training that focused on affect discrimination and working memory in 20 daily 1-hour sessions, (b) similarly intense, targeted cognitive training on auditory-verbal discrimination and working memory, or (c) treatment as usual. Neuromagnetic activity was measured before and after training during a dynamic facial affect recognition task (5 s videos showing human faces gradually changing from neutral to fear or to happy expressions). Effects on 10-13 Hz (alpha) power during the transition from neutral to emotional expressions were assessed via MEG based on previous findings that alpha power increase is related to facial affect recognition and is smaller in schizophrenia than in healthy subjects. Targeted affect training improved overt performance on the training tasks. Moreover, alpha power increase during the dynamic facial affect recognition task was larger after affect training than after treatment-as-usual, though similar to that after targeted perceptual-cognitive training, indicating somewhat nonspecific benefits. Alpha power modulation was unrelated to general neuropsychological test performance, which improved in all groups. Results suggest that specific neural processes supporting facial affect recognition, evident in oscillatory phenomena, are modifiable. This should be considered when developing remediation strategies targeting social cognition in schizophrenia.

Functional cognitive and cortical abnormalities in chronic and first-admission schizophrenia.

Evoked and induced event-related neural oscillations have recently been proposed as a key mechanism supporting higher-order cognition. Cognitive decay and abnormal electromagnetic sensory gating reliably distinguish schizophrenia (SZ) patients and healthy individuals, demonstrated in chronic (CHR) and first-admission (FA) patients. Not yet determined is whether altered event-related modulation of oscillatory activity is manifested at early stages of SZ, thus reflects and perhaps embodies the development of psychopathology, and provides a mechanism for the gating deficit. The present study compared behavioral and functional brain measures in CHR and FA samples. Cognitive test performance (MATRICS Consortium Cognitive Battery, MCCB), neuromagnetic event-related fields (M50 gating ratio), and oscillatory dynamics (evoked and induced modulation of 8-12Hz alpha) during a paired-click task were assessed in 35 CHR and 31 FA patients meeting the criteria for ICD-10 diagnoses of schizophrenia as well as 28 healthy comparison subjects (HC). Both patient groups displayed poorer cognitive performance, higher M50 ratio (poorer sensory gating), and less induced modulation of alpha activity than did HC. Induced alpha power decrease in bilateral posterior regions varied with M50 ratio in HC but not SZ, whereas orbitofrontal alpha power decrease was related to M50 ratio in SZ but not HC. Results suggest disruption of oscillatory dynamics at early stages of illness, which may contribute to deficient information sampling, memory updating, and higher cognitive functioning.

Dynamics of alpha oscillations elucidate facial affect recognition in schizophrenia.

Impaired facial affect recognition is characteristic of schizophrenia and has been related to impaired social function, but the relevant neural mechanisms have not been fully identified. The present study sought to identify the role of oscillatory alpha activity in that deficit during the process of facial emotion recognition. Neuromagnetic brain activity was monitored while 44 schizophrenia patients and 44 healthy controls viewed 5-s videos showing human faces gradually changing from neutral to fearful or happy expressions or from the neutral face of one poser to the neutral face of another. Recognition performance was determined separately by self-report. Relative to prestimulus baseline, controls exhibited a 10- to 15-Hz power increase prior to full recognition and a 10- to 15-Hz power decrease during the postrecognition phase. These results support recent proposals about the function of alpha-band oscillations in normal stimulus evaluation. The patients failed to show this sequence of alpha power increase and decrease and also showed low 10- to 15-Hz power and high 10- to 15-Hz connectivity during the prestimulus baseline. In light of the proposal that a combination of alpha power increase and functional disconnection facilitates information intake and processing, the finding of an abnormal association of low baseline alpha power and high connectivity in schizophrenia suggests a state of impaired readiness that fosters abnormal dynamics during facial affect recognition.

Protective effect of Aronia melanocarpa fruit juice pretreatment in a model of carbon tetrachloride-induced hepatotoxicity in rats.

UNLABELLED: The main active ingredients of Aronia melanocarpa fruit juice (AMFJ) are phenolic substances, mainly flavonoids from the anthocyanin subclass. AIM: The aim of the present study was to investigate the effect of AMFJ applied as pretreatment in a model of carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. MATERIAL AND METHODS: AMFJ was given orally to rats for 2 days at doses of 5, 10 and 20 ml/kg either alone or as pretreatment before the oral application of CCl4 (0.2 ml/kg, 2 days). The plasma activities of aspartate transaminase (AST) and alanine transaminase (ALT) were measured as markers of the liver cell damage. The levels of malondialdehyde (MDA), a lipid peroxidation marker, were determined in rat liver and plasma. RESULTS: Administration of CCl4 caused an elevation of plasma AST and ALT activities. It also induced an elevation of MDA levels in rat liver and plasma. AMFJ applied alone in the tested doses did not cause any significant changes in the measured enzyme activities and in MDA levels. AMFJ applied as pretreatment prevented the CCl4-induced increase of AST and ALT activities, and also prevented the elevation of plasma and liver MDA levels. CONCLUSIONS: AMFJ showed a protective effect in a model of CCl4-induced hepatotoxicity in rats. This effect might be due to the antioxidant activity of its active ingredients.

Protective effect of BP 2-94, a histamine H3-receptor agonist prodrug, in a model of carbon tetrachloride-induced hepatotoxicity in rats.

UNLABELLED: BP 2-94 is a prodrug of the H3-receptor agonist (R)-alpha-methylhistamine [(R)-alpha-MeHA]. BP 2-94 displayed anti-inflammatory, antinociceptive and ulcero-protective properties in experimental animals. AIM: The aim of the present study was to investigate the effect of BP 2-94 in a model of carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. MATERIALS AND METHODS: In order to investigate the effect of BP 2-94 it was applied to rats either alone (20, 40 and 60 micromol kg(-1), 4 days) or as a pretreatment (20, 40 and 60 micromol kg(-1), 4 days) before the application of CCl4 (0,2 ml kg(-1), 2 days). RESULTS: BP 2-94 in the tested doses did not cause significant changes in the plasma aspartate transaminase (AST) and alanine transaminase (ALT) activities and the liver microscopic appearance was normal. Hepatocyte damage, as evident by local areas of liver necrosis and elevated levels of plasma AST and ALT, occurred in rats following acute exposure to CCl4 (0,2 ml kg(-1), 2 days). BP 2-94 applied as a pretreatment dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of plasma AST and ALT activities in response to CCl4. CONCLUSIONS: BP 2-94 had a hepatoprotective effect in a model of CCl4-induced toxicity in rats. This effect might be due the H3-agonistic activity of its active metabolite (R)-alpha-MeHA.