Tzvetan Popov

Neuromagnetic indication of dysfunctional emotion regulation in affective disorders

Dysfunctional emotion regulation is often reported in affective disorders, but it is unclear whether this dysfunction concerns initial processing of emotional input or regulation of resulting emotion. The present study addressed these aspects in 27 depressive and 15 borderline personality disorder patients and 28 healthy controls who were instructed to either passively view unpleasant and neutral pictures or downregulate emotional responses by reappraisal, while neuromagnetic brain activity was measured. All three groups showed more early response to unpleasant than to neutral pictures, whereas patients failed to show subsequent activity suppression under instructions to down-regulate. This deficient emotion regulation was evident primarily in those subjects reporting high childhood adversity. Results support intact emotional input processing but impaired emotion regulation in affective disorders and indicate a moderating influence of early life stress.

Prestimulus oscillatory power and connectivity patterns predispose conscious somatosensory perception

Significance Experimental use of near-threshold stimuli is regarded as an important approach to study neural processes leading to conscious access (defined in operational terms as “reportability”). Looking to what extent prestimulus periods contribute to the variability of perceptual states has become increasingly popular, frequently pointing to an increased excitability of relevant sensory regions. Here, we aim to extend this “local” perspective by a network approach. A framework called “Windows to Consciousness” is introduced. We postulate that along with an enhanced excitability, preestablished pathways of information flow are a crucial ingredient, determining whether an upcoming near-threshold stimulus will be consciously perceived. Using magnetoencephalography combined with state-of-the-art source-imaging approaches, we are able to report supportive evidence. Which aspects of our sensory environment enter conscious awareness does not only depend on physical features of the stimulus, but also critically on the so-called current brain state. Results from magnetoencephalography/EEG studies using near-threshold stimuli have consistently pointed to reduced levels of α- (8–12 Hz) power in relevant sensory areas to predict whether a stimulus will be consciously perceived or not. These findings have been mainly interpreted in strictly “local” terms of enhanced excitability of neuronal ensembles in respective cortical regions. The present study aims to introduce a framework that complements this rather local perspective, by stating that the functional connectivity architecture before stimulation will predetermine information flow. Thus, information computed at a local level will be distributed throughout a network, thereby becoming consciously accessible. Data from a previously published experiment on conscious somatosensory near-threshold perception was reanalyzed focusing on the prestimulus period. Analysis of spectral power showed reduced α-power mainly in the contralateral S2 and middle frontal gyrus to precede hits, thus overall supporting the current literature. Furthermore, differences between hits and misses were obtained on global network (graph theoretical) features in the same interval. Most importantly, in accordance with our framework, we could show that the somatosensory cortex is “more efficiently” integrated into a distributed network in the prestimulus period. This finding means that when a relevant sensory stimulus impinges upon the system, it will encounter preestablished pathways for information flow. In this sense, prestimulus functional connectivity patterns form “windows” to conscious perception.

Specific cognitive training normalizes auditory sensory gating in schizophrenia : a randomized trial

BACKGROUND The ratio of scalp-recorded brain responses occurring 50 msec after paired clicks (S2-evoked P50/S1-evoked P50) serves as a measure of sensory gating. An abnormally large ratio is commonly found in schizophrenia and is considered as a sign of reduced sensory gating or otherwise dysfunctional organization of the auditory/verbal system as a factor contributing to psychopathology and cognitive dysfunction in schizophrenia. This initial randomized clinical trial compared the efficacy of two 4-week, computer-based cognitive training methods that emphasize either auditory discrimination and verbal memory or a broader range of cognitive functions in schizophrenia. METHODS Thirty-nine schizophrenia patients (ICD-F20.0 diagnosis) were assigned to Cognitive Exercises (CE) or Cognitive Package (Cogpack). The M50, the magnetoencephalographic analogue of electroencephalographic P50, and performance on verbal learning and memory tests were used to evaluate training effects. RESULTS As expected, patients exhibited higher pretreatment gating ratios than 28 age-matched healthy comparison participants. Gating ratios decreased after CE but not after Cogpack. Cognitive test performance improved more after CE than after Cogpack. CONCLUSIONS Appropriately specific psychological training changes the neural performance in schizophrenia, normalizing sensory and cognitive function.

Adjusting Brain Dynamics in Schizophrenia by Means of Perceptual and Cognitive Training

Background In a previous report we showed that cognitive training fostering auditory-verbal discrimination and working memory normalized magnetoencephalographic (MEG) M50 gating ratio in schizophrenia patients. The present analysis addressed whether training effects on M50 ratio and task performance are mediated by changes in brain oscillatory activity. Such evidence should improve understanding of the role of oscillatory activity in phenomena such as M50 ratio, the role of dysfunctional oscillatory activity in processing abnormalities in schizophrenia, and mechanisms of action of cognitive training. Methodology/Principal Findings Time-locked and non-time-locked oscillatory activity was measured together with M50 ratio in a paired-click design before and after a 4-week training of 36 patients randomly assigned to specific cognitive exercises (CE) or standard (comparison) cognitive training (CP). Patient data were compared to those of 15 healthy controls who participated in two MEG measurements 4 weeks apart without training. Training led to more time-locked gamma-band response and more non-time-locked alpha-band desynchronization, moreso after CE than after CP. Only after CE, increased alpha desynchronization was associated with normalized M50 ratio and with improved verbal memory performance. Thus, both types of cognitive training normalized gamma activity, associated with improved stimulus encoding. More targeted training of auditory-verbal discrimination and memory additionally normalized alpha desynchronization, associated with improved elaborative processing. The latter presumably contributes to improved auditory gating and cognitive function. Conclusions/Significance Results suggest that dysfunctional interplay of ocillatory activity that may contribute to auditory processing disruption in schizophrenia can be modified by targeted training.

Early life stress and psychiatric disorder modulate cortical responses to affective stimuli

Altered affective processing has been proposed as mediating between early life stress (ELS) and subsequent psychopathology. The present study examined whether ELS influences affective cortical processing differently in psychiatric patients and healthy subjects. The number of stressful experiences before onset of puberty was assessed in 50 inpatients with diagnoses of Major Depressive Disorder, schizophrenia, drug addiction, or Borderline Personality Disorder and in 20 healthy comparison subjects. Subjects monitored pleasant, neutral, and unpleasant pictures during magnetoencephalographic recording. Suppression of right-posterior activity 160-210 ms after stimulus onset was associated with certain diagnoses and high ELS. Results confirmed specific contributions of ELS versus adult stress, comorbid posttraumatic stress disorder, or depression.

Modulation of α power and functional connectivity during facial affect recognition

Research has linked oscillatory activity in the α frequency range, particularly in sensorimotor cortex, to processing of social actions. Results further suggest involvement of sensorimotor α in the processing of facial expressions, including affect. The sensorimotor face area may be critical for perception of emotional face expression, but the role it plays is unclear. The present study sought to clarify how oscillatory brain activity contributes to or reflects processing of facial affect during changes in facial expression. Neuromagnetic oscillatory brain activity was monitored while 30 volunteers viewed videos of human faces that changed their expression from neutral to fearful, neutral, or happy expressions. Induced changes in α power during the different morphs, source analysis, and graph-theoretic metrics served to identify the role of α power modulation and cross-regional coupling by means of phase synchrony during facial affect recognition. Changes from neutral to emotional faces were associated with a 10–15 Hz power increase localized in bilateral sensorimotor areas, together with occipital power decrease, preceding reported emotional expression recognition. Graph-theoretic analysis revealed that, in the course of a trial, the balance between sensorimotor power increase and decrease was associated with decreased and increased transregional connectedness as measured by node degree. Results suggest that modulations in α power facilitate early registration, with sensorimotor cortex including the sensorimotor face area largely functionally decoupled and thereby protected from additional, disruptive input and that subsequent α power decrease together with increased connectedness of sensorimotor areas facilitates successful facial affect recognition.

Enhanced resting-state oscillations in schizophrenia are associated with decreased synchronization during inattentional blindness

Patients suffering from schizophrenia have been characterized by an apparent lack of theta (around 6 Hz) and gamma (>40 Hz) brain oscillatory activity during task execution. The neurocognitive reasons for these abnormal synchronization patterns, however, remain elusive. Recording the electroencephalogramm (EEG) during a selective visual attention task, the current study investigates whether abnormal brain oscillatory resting‐state activity in the theta band might account for a lack of task‐related brain oscillatory activity in schizophrenia. EEGs were recorded from 26 patients with schizophrenia and 26 healthy matched controls during rest and during the execution of a selective visual attention task, in which an unexpected object (monkey) appeared on the screen. On a behavioral level, patients were less likely to report perceiving the unexpected event than controls. Controls showed a stronger increase in task‐related theta power than patients in prefrontal, parietal, and occipital brain regions. Task‐related theta power change differed between patients who perceived, and patients who did not perceive the unexpected event. Moreover, patients showed higher levels of theta power during rest than controls, whereas the absolute theta power values during the selective attention task did not differ between groups. These results suggest that the failure to increase oscillatory activity during a cognitive task can be accounted for by abnormally high oscillatory activity in a resting state. This finding has important implications for future studies examining abnormal brain oscillatory activity in schizophrenia, which usually treat resting‐state activity as a baseline for task‐related activity. Hum Brain Mapp 34:2266–2275, 2013.

Evoked and induced oscillatory activity contributes to abnormal auditory sensory gating in schizophrenia.

The ratio of magnetoencephalogram-recorded brain responses occurring 50ms after paired clicks (S2-evoked M50/S1-evoked M50) serves as a measure of sensory gating. An abnormally large ratio is commonly found in schizophrenia. Whether this abnormality indicates impaired gating is debated. Using event-related oscillations the present study sought to elucidate processes contributing to the phenomenon of altered M50 gating ratio. Schizophrenia inpatients (n=50) showed the expected large M50 gating ratio relative to 48 healthy controls, which correlated with less induced frontally generated activity in the 10-15Hz frequency band starting 200ms before the onset of S2. Patients also produced smaller alpha (8-12Hz) and gamma (60-80Hz) responses to S1. Results suggest that the deviant gating ratio in schizophrenia is a consequence of a complex alteration in the processing of incoming information that cannot be attributed to impaired gating alone.

Cross-frequency dynamics of neuromagnetic oscillatory activity : Two mechanisms of emotion regulation

Hemodynamic and electromagnetic neuroimaging suggests a sequence of intraregional and interregional activity during emotion processing. Oscillatory activity within trials may offer insight into neural mechanisms involved in this process. MEG was measured in 24 subjects during passive viewing of neutral and unpleasant pictures and emotion regulation by cognitive reappraisal. Regulation prompted more gamma increase and alpha decrease to picture onset than did passive viewing. Source analysis confirmed differential modulation of these power changes in occipitoparietal regions during passive viewing and larger power changes in prefrontal regions during regulation. Local coupling of alpha phase to gamma amplitude within a medial prefrontal region and long-range synchrony of medial prefrontal, occipital, and temporoparietal regions index mechanisms of prefrontal top-down contribution to emotion processing.

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.