2018-04-06, Popova, Petia, Rockstroh, Brigitte, Miller, Gregory A, Wienbruch, Christian, Carolus, Almut, Popov, Tzvetan G.

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.

2015, Popov, Tzvetan G., Carolus, Almut, Schubring, David, Popova, Petia, Miller, Gregory A., Rockstroh, Brigitte

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.

2014, Carolus, Almut, Schubring, David, Popov, Tzvetan G., Popova, Petia, Miller, Gregory A., Rockstroh, Brigitte

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 8–12 Hz 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.

2018-02, Schalinski, Inga, Teicher, Martin H., Carolus, Almut, Rockstroh, Brigitte

Background
Exposure to adverse childhood experiences (ACE) and cognitive deficits are both prevalent in psychosis. While it has been repeatedly demonstrated that ACE contribute to cognitive dysfunctions, the specific nature of this contribution remains elusive. Recent evidence suggests that types of adversities during critical periods have deleterious effects on brain structures that are important for cognitive functioning. The present study sought to clarify which types of adversities experienced at which time during development aggravate cognitive deficits in psychosis.

Methods
Exposure to abuse and neglect during childhood and adolescence were retrospectively assessed in N = 168 adult individuals with psychotic disorder. Conditioned random forest regression was used to define the importance of type and timing of ACE for predicting domains of the MATRICS Consensus Cognitive Battery (MCCB).

Results
Significant importance of ACE was determined for 5 out of 7 MCCB domains. Particularly abuse at age 3 contributed to dysfunctional cognitive domains attention, learning, and working memory. Social cognition was related to neglect experienced at 11–12 years, and to cumulative ACE.

Conclusion
Abuse and neglect at periods when children spend substantial time in their families affect cognitive functioning, and hence aggravate dysfunction in psychosis. Results support the neurodevelopmental perspective on psychosis and the diagnostic value of type and timing of ACE.

2015, Carolus, Almut, Popova, Petia, Rockstroh, Brigitte

Theoretischer Hintergrund:
Kognitive Funktionseinschränkungen sind zentrales Merkmal schizophrener Erkrankungen und werden entsprechend im Behandlungskonzept berücksichtigt. Kognitive Remediationsprogramme gelten als wirksam, Effektstärken als moderat. Trainingsvarianten werden zur Effektoptimierung erprobt.

Fragestellung:
Ist gezieltes Funktionstraining in neuroplastizitäts-orientiertem Lernkontext effektiver als breitgefächertes Behandlungsprogramm und werden Effekte durch das Erkrankungsstadium moduliert?

Methode:
Bei 59 chronisch und 31 ersthospitalisierten schizophren Erkrankten wurden kognitive Defizite über Testleistungen der MATRICS Consensus Cognitive Test Battery gegenüber 25 gesunder Kontrollpersonen erfasst. Testleistungen vor, nach 4-wöchiger Interventionsphase mit zwei spezifischen Trainings oder Standardbehandlung und 3-monatiger Katamnese prüften den Einfluss von Interventionstypus und Erkrankungsstadium auf Leistungsverbesserung.

Ergebnisse:
Sowohl chronische wie erstmals behandelte Patienten aller Behandlungsgruppen verbesserten sich signifikant über die Messzeitpunkte, obwohl Defizite relativ zu Kontrollen fortbestanden.

Schlussfolgerungen:
Spezifisches Training verbessert kognitive Funktionen nicht über Zeit/Remissionseffekte hinaus.

2014, Popova, Petia, Popov, Tzvetan G., Wienbruch, Christian, Carolus, Almut, Miller, Gregory A., Rockstroh, Brigitte

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 patientswere 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 expressionswere assessed viaMEG 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 modulationwas 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.

2015, Carolus, Almut

2014-03, Popov, Tzvetan G., Rockstroh, Brigitte, Popova, Petia, Carolus, Almut, Miller, Gregory A.

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.