Relation between task-related activity modulation and cortical inhibitory function in schizophrenia and healthy controls: a TMS-EEG study.

Schizophrenia has been associated with a reduced task-related modulation of cortical activity assessed through electroencephalography (EEG). However, to the best of our knowledge, no study so far has assessed the underpinnings of this decreased EEG modulation in schizophrenia. A possible substrate of these findings could be a decreased inhibitory function, a replicated finding in the field. In this pilot study, our aim was to explore the association between EEG modulation during a cognitive task and the inhibitory system function in vivo in a sample including healthy controls and patients with schizophrenia. We hypothesized that the replicated decreased task-related activity modulation during a cognitive task in schizophrenia would be related to a hypofunction of the inhibitory system. For this purpose, 27 healthy controls and 22 patients with schizophrenia (including 13 first episodes) performed a 3-condition auditory oddball task from which the spectral entropy modulation was calculated. In addition, cortical reactivity-as an index of the inhibitory function-was assessed by the administration of 75 monophasic transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex. Our results replicated the task-related cortical activity modulation deficit in schizophrenia patients. Moreover, schizophrenia patients showed higher cortical reactivity following transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex compared to healthy controls. Cortical reactivity was inversely associated with EEG modulation, supporting the idea that a hypofunction of the inhibitory system could hamper the task-related modulation of EEG activity.

Corollary Discharge Dysfunction as a Possible Substrate of Anomalous Self-experiences in Schizophrenia.

BACKGROUND AND HYPOTHESIS: Corollary discharge mechanism suppresses the conscious auditory sensory perception of self-generated speech and attenuates electrophysiological markers such as the auditory N1 Event-Related Potential (ERP) during Electroencephalographic (EEG) recordings. This phenomenon contributes to self-identification and seems to be altered in people with schizophrenia. Therefore, its alteration could be related to the anomalous self-experiences (ASEs) frequently found in these patients. STUDY DESIGN: To analyze corollary discharge dysfunction as a possible substrate of ASEs, we recorded EEG ERP from 43 participants with schizophrenia and 43 healthy controls and scored ASEs with the 'Inventory of Psychotic-Like Anomalous Self-Experiences' (IPASE). Positive and negative symptoms were also scored with the 'Positive and Negative Syndrome Scale for Schizophrenia' (PANSS) and with the 'Brief Negative Symptom Scale' (BNSS) respectively. The N1 components were elicited by two task conditions: (1) concurrent listening to self-pronounced vowels (talk condition) and (2) subsequent non-concurrent listening to the same previously self-uttered vowels (listen condition). STUDY RESULTS: The amplitude of the N1 component elicited by the talk condition was lower compared to the listen condition in people with schizophrenia and healthy controls. However, the difference in N1 amplitude between both conditions was significantly higher in controls than in schizophrenia patients. The values of these differences in patients correlated significantly and negatively with the IPASE, PANSS, and BNSS scores. CONCLUSIONS: These results corroborate previous data relating auditory N1 ERP amplitude with altered corollary discharge mechanisms in schizophrenia and support corollary discharge dysfunction as a possible underpinning of ASEs in this illness.

Corollary discharge function in healthy controls: Evidence about self-speech and external speech processing.

As we speak, corollary discharge mechanisms suppress the auditory conscious perception of the self-generated voice in healthy subjects. This suppression has been associated with the attenuation of the auditory N1 component. To analyse this corollary discharge phenomenon (agency and ownership), we registered the event-related potentials of 42 healthy subjects. The N1 and P2 components were elicited by spoken vowels (talk condition; agency), by played-back vowels recorded with their own voice (listen-self condition; ownership) and by played-back vowels recorded with an external voice (listen-other condition). The N1 amplitude elicited by the talk condition was smaller compared with the listen-self and listen-other conditions. There were no amplitude differences in N1 between listen-self and listen-other conditions. The P2 component did not show differences between conditions. Additionally, a peak latency analysis of N1 and P2 components between the three conditions showed no differences. These findings corroborate previous results showing that the corollary discharge mechanisms dampen sensory responses to self-generated speech (agency experience) and provide new neurophysiological evidence about the similarities in the processing of played-back vowels with our own voice (ownership experience) and with an external voice.

Event-related potentials associated to N-back test performance in schizophrenia.

Mapping of Event-Related Potentials (ERP) associated with auditory and visual odd-ball paradigms has shown consistent differences between healthy controls and schizophrenia patients. It may be hypothesized that higher task attentional/cognitive demand will result in larger differences in these paradigms, which may help understanding the substrates of cognitive deficits in this syndrome. To this aim, we performed an EEG study comparing the effects of increasing the attentional/cognitive load of an auditory N-back task on the Event-Related Potential in 50 subjects with schizophrenia (11 first episodes) and 35 healthy controls. We considered a post-target window of 1000 ms to explore possible between groups differences in N100, P300, and Late Slow Wave (LSW), and compared these components between 0-back ('lower attentional/cognitive load) and 1-back ('higher attentional/cognitive load') conditions. Our results showed that N100 and LSW amplitude increase from 0- to 1-back condition was significantly larger in healthy controls compared to schizophrenia patients. Furthermore, LSW amplitude difference between 0- and 1-back conditions positively correlated with performance in the behavioral cognitive assessment. Taken together, these results support that higher task attentional/cognitive load (0-back vs. 1-back condition) increase N100 amplitude differences and reveal new findings related to the LSW component in schizophrenia.

Neurophysiological differences between ADHD and control children and adolescents during the recognition phase of a working memory task.

Impairment of executive functions including attention and working memory (WM) have been proposed as an important feature of Attention Deficit and Hyperactivity Disorder (ADHD). During the recognition phase of a delayed match-to-sample test (DMTS) a reduced N2pc component, related to the attentional selection of the memorized item and a reduced distractor positivity (Pd), related to the processing suppression of distractors are expected in ADHD subjects. For the purpose of the study, twenty-nine ADHD subjects diagnosed with a structured interview and the DuPaul questionnaire, were included in the study. Thirty-four control subjects were recruited from public schools and matched by age (from 6 to 17 years old) and gender with the ADHD group. Reaction times (RTs), errors, and Event Related Potentials (ERPs) were obtained in a DMTS task during the recognition phase in correct trials. RTs and errors were higher in ADHD subjects compared to the control group. Specifically, errors were much higher in ADHD than in controls. The cluster mass permutation statistics showed a significant N2pc component in both groups during the recognition phase, but a significant Pd component was present only in controls. The present results suggest that in correct trials ADHD children use the same neural resources to select the memorized item from WM with similar efficacy than controls, although a lower Pd suggests a difficulty in suppressing distractors.

Neurobiological underpinnings of cognitive subtypes in psychoses: A cross-diagnostic cluster analysis.

Schizophrenia and bipolar disorder include patients with different characteristics, which may hamper the definition of biomarkers. One of the dimensions with greater heterogeneity among these patients is cognition. Recent studies support the identification of different patients' subgroups along the cognitive domain using cluster analysis. Our aim was to validate clusters defined on the basis of patients' cognitive status and to assess its relation with demographic, clinical and biological measurements. We hypothesized that subgroups characterized by different cognitive profiles would show differences in an array of biological data. Cognitive data from 198 patients (127 with chronic schizophrenia, 42 first episodes of schizophrenia and 29 bipolar patients) were analyzed by a K-means cluster approach and were compared on several clinical and biological variables. We also included 155 healthy controls for further comparisons. A two-cluster solution was selected, including a severely impaired group and a moderately impaired group. The severely impaired group was associated with higher illness duration and symptoms scores, lower thalamus and hippocampus volume, lower frontal connectivity and basal hypersynchrony in comparison to controls and the moderately impaired group. Moreover, both patients' groups showed lower cortical thickness and smaller functional connectivity modulation than healthy controls. This study supports the existence of different cognitive subgroups within the psychoses with different neurobiological underpinnings.

Attention-deficit/hyperactivity disorder in children and adolescents: An event-related potential study of working memory.

Working memory (WM) impairments have been frequently observed as an important feature of attention-deficit/hyperactivity disorder (ADHD). Event-related potential (ERP) differences between ADHD and healthy controls (HC) would be expected during WM task performance. Especially, the so-called slow wave (SW), which is related to the retention process, might present amplitude differences in ADHD. In this ERP study participated twenty-nine ADHD children and adolescents and thirty-four HC. WM performance was assessed using the Working Memory Test Battery for Children (WMTB-C), and ERPs were analyzed with a Delayed Match-To-Sample (DMTS) task. ADHD sample showed worse behavioral performance in both WMTB-C and DMTS task, and higher SW amplitude during the retention phase of the DMTS task. Additionally, the principal component analysis indicated that the scores on the component explaining the centro-parietal SW were significantly different between ADHD subjects and HC. The observed impaired neurophysiological activity during the encoding and retention periods in ADHD, which would be the origin of the behavioral deficits in WM task performance, might be reflecting a delayed maturation of the neural processes underlying the centro-parietal SW.

Frequency coupling of low and high frequencies in the EEG of ADHD children and adolescents in closed and open eyes conditions.

The present report examines the possible differences in absolute Power Spectral Density (PSD), the topography of brain rhythms, and low frequency (delta and theta) vs. beta PSD when attention deficit disorder (ADHD) children and controls are compared. These results would potentially be useful to test the validity of the developmental lag and differential developmental models for ADHD. The EEG resting state under the experimental conditions of open and closed eyes were recorded in samples of control subjects and children with ADHD (6-17 years old). The PSD from 0 to 46 Hz was calculated and ANOVAs were performed to compare the groups of subjects in the two experimental conditions. To observe differences in the co-maturation of the brain rhythms between the groups of subjects, correlations of the PSD of all frequency ranges were computed. These results showed an increase in delta power in children with ADHD compared to control subjects. The topographies of the different brain rhythms were similar in children with ADHD and controls. The maturational power-to-power frequency-coupling between low frequencies and beta rhythms was lower in children with ADHD. The increased delta PSD in ADHD and the similar brain rhythms topographies in children with ADHD and controls support the developmental lag model, whereas the decreased co-maturation of low frequencies vs. beta PSD in children with ADHD suggests a differential maturation rate for low and beta frequencies in children with ADHD compared to controls.

Event related potentials changes associated with the processing of auditory valid and invalid targets as a function of previous trial validity in a Posner's paradigm.

The present study tries to analyze the neural basis of the so-called "Inter-trial Validity-Invalidity Effects" by means of Event-Related Potentials. The N1, P2, P3a and P3b components were examined. The aim is to show the sequential effects on Event-Related Potentials by analyzing the effect of previous trial condition (n-1) in the processing of current trial target (n). Event-Related Potentials results indicate that the N1 and P2 components show higher negativity in valid trials preceded by invalid trials with respect to valid trials preceded by valid trials, elicited by the so-called "Processing Negativity". Next, the P3a and P3b components show increased positivity in invalid trials preceded by valid trials compared to invalid trials preceded by invalid trials. Present results suggest that there is a dynamic updating of attentional resources and working memory, due to the influence of previous trial condition (n-1) on the current trial processing (n). This dynamic updating would be higher after trial validity changes, and it would be compatible with the Bayesian Brain Model.