Persistence of Neuronal Alterations in Alcohol-Dependent Patients at Conclusion of the Gold Standard Withdrawal Treatment: Evidence From ERPs.

Background: One of the main challenges for clinicians is to ensure that alcohol withdrawal treatment is the most effective possible after discharge. To address this issue, we designed a pilot study to investigate the efficacy of the rehabilitation treatment on the main stages of information processing, using an electroencephalographic method. This topic is of main importance as relapse rates after alcohol withdrawal treatment remain very high, indicating that established treatment methods are not fully effective in all patients in the long run. Method: We examined in alcohol-dependent patients (ADP) the effects of the benzodiazepine-based standard detoxification program on event-related potential components at incoming (D0) and completion (D15) of the treatment, using tasks of increasing difficulty (with and without workload) during an auditory oddball target paradigm. Untreated non-alcohol-dependent-volunteers were used as matching controls. Results: At D0, ADP displayed significantly lower amplitude for all ERP components in both tasks, as compared to controls. At D15, this difference disappeared for the amplitude of the N1 component during the workload-free task, as well as the amplitude of the P3b for both tasks. Meanwhile, the amplitude of the N2 remained lower in both tasks for ADP. At D0, latencies of N2 and P3b in both task conditions were longer in ADP, as compared to controls, whilst the latency of N1 was unchanged. At D15, the N2 latency remained longer for the workload condition only, whereas the P3b latency remained longer for the workload-free task only. Conclusion: The present pilot results provide evidence for a persistence of impaired parameters of ERP components, especially the N2 component. This suggests that neural networks related to attention processing remain dysfunctional. Longitudinal long-term follow-up of these patients is mandatory for further assessment of a link between ERP alterations and a later risk of relapse.

False memory production in schizophrenia: A neurophysiological investigation.

BACKGROUND: The topic of false memory in schizophrenia has been well documented in earlier research contributions. To date, there is no study exploring the implications of specific neural networks during this phenomenon in patients suffering from schizophrenia. METHODS: We compared 17 patients suffering from psychosis (SCZ) to 33 healthy controls (HC) performing a verbal memory task designed to produce false memories, i.e. the Deese-Roediger-McDermott paradigm (DRM). Electroencephalography was used to specifically analyze the P2 and N400 event-related potentials components. RESULTS: The SCZ patients showed a reduced ability to distinguish between true and false memories as assessed by the A' index which was calculated based on the false and true memory rates. The morphology of the P2 differed in frontal electrode region with a lower amplitude in SCZ. In addition, the amplitude of N400 was more pronounced (more negative) in HC than in SCZ in centro-parietal electrode site. CONCLUSIONS: We suggest that the differences found in P2 amplitude are associated with difficulties of SCZ patients to efficiently compare item-specific features of a mnesic elements to incoming stimuli which impair the subsequent verbal memory information processing reflected by the N400 component amplitude decrease. These results are consistent with the idea that SCZ use a different strategy while they perform the DRM paradigm.

Impaired social cognition in schizophrenia during the Ultimatum Game: An EEG study.

BACKGROUND: Schizophrenia has a core feature of cognitive dysfunctions. Since these deficits are predictive for patients' functional outcome, understanding their origin is of great importance to improve their daily lives. A specific component of the deficit involves social decision-making, which can be studied using the Ultimatum Game (UG). In this task, a "proposer" proposes a share of money to a "responder", who can either accept or reject this offer. If the responder accepts the proposal, both win money. If the responder refuses, both players end up with nothing. Therefore, the UG evaluates decision-making strategies and social interaction. METHODS: We compared the neuronal bases of schizophrenic patients with healthy controls, while performing the UG. Electroencephalography (EEG) was used to find differences in the event-related potential (ERP) components typical for the UG, namely the P2 and feedback-related negativity (FRN). Source reconstruction was further used to define the origin of these differences. RESULTS: In the proposer condition, no differences were found in amplitude of the P2 and FRN components. In contrast, in the responder condition, significant differences were found for the amplitude of the FRN (p=0.009). Using source reconstruction, a different activation in a border zone of the dorsolateral and the medial prefrontal cortex was revealed in schizophrenic patients to underlie this component. CONCLUSIONS: We suggest that the difference found in the FRN amplitude is associated with difficulties of patients in interpreting another's behavior. Although schizophrenic patients correctly activate neuronal bases in the proposer condition, they were not able to activate the same networks in the responder condition, thereby exposing their difficulties in social interaction.

Differences in Social Decision-Making between Proposers and Responders during the Ultimatum Game: An EEG Study.

The Ultimatum Game (UG) is a typical paradigm to investigate social decision-making. Although the behavior of humans in this task is already well established, the underlying brain processes remain poorly understood. Previous investigations using event-related potentials (ERPs) revealed three major components related to cognitive processes in participants engaged in the responder condition, the early ERP component P2, the feedback-related negativity (FRN) and a late positive wave (late positive component, LPC). However, the comparison of the ERP waveforms between the responder and proposer conditions has never been studied. Therefore, to investigate condition-related electrophysiological changes, we applied the UG paradigm and compared parameters of the P2, LPC and FRN components in twenty healthy participants. For the responder condition, we found a significantly decreased amplitude and delayed latency for the P2 component, whereas the mean amplitudes of the LPC and FRN increased compared to the proposer condition. Additionally, the proposer condition elicited an early component consisting of a negative deflection around 190 ms, in the upward slope of the P2, probably as a result of early conflict-related processing. Using independent component analysis (ICA), we extracted one functional component time-locked to this deflection, and with source reconstruction (LAURA) we found the anterior cingulate cortex (ACC) as one of the underlying sources. Overall, our findings indicate that intensity and time-course of neuronal systems engaged in the decision-making processes diverge between both UG conditions, suggesting differential cognitive processes. Understanding the electrophysiological bases of decision-making and social interactions in controls could be useful to further detect which steps are impaired in psychiatric patients in their ability to attribute mental states (such as beliefs, intents, or desires) to oneself and others. This ability is called mentalizing (also known as theory of mind).

Assessment of mental workload: A new electrophysiological method based on intra-block averaging of ERP amplitudes.

The present study contributes to the current debate about electrophysiological measurements of mental workload. Specifically, the allocation of attentional resources during different complexity levels of tasks and its changes over time are of great interest. Therefore, we investigated mental workload using tasks varying in difficulty during an auditory oddball target paradigm. For data analysis, we applied a novel method to compute event-related potentials (ERPs) by intra-block epoch averaging of P2, P3a and P3b amplitude components for the infrequent target stimuli. We obtained eight consecutive blocks of 5 epochs each, which allowed us to develop an electrophysiological parameter to measure mental workload. In both the easy and the more constraining tasks, the amplitude of P2 decreased beginning with the second block of the sequence. In contrast, the amplitudes of P3a and P3b components linearly decreased following the repetition of the target in the more constraining task, but not in the easy task. Statistical analysis revealed intra-block differences on amplitudes of ERPs of interest between the easy and the more constraining tasks, confirming this method as a measure to assess mental workload. Since a subject is his own control, the present method represents an electrophysiological parameter for individual measurement of mental workload and may therefore be applicable in clinical routine.

What animals can teach clinicians about the hippocampus.

Abnormalities in hippocampal structure and function have been reported in a number of human neuropathological and neurodevelopmental disorders, including Alzheimer's disease, autism spectrum disorders, Down syndrome, epilepsy, and schizophrenia. Given the complexity of these disorders, animal studies are invaluable and remain to date irreplaceable, providing fundamental knowledge regarding the basic mechanisms underlying normal and pathological human brain structure and function. However, there is a prominent ill-conceived view in current research that scientists should be restricted to using animal models of human diseases that can lead to results applicable to humans within a few years. Although there is no doubt that translational studies of this kind are important and necessary, limiting animal studies to applicable questions is counterproductive and will ultimately lead to a lack of knowledge and an inability to address human health problems. Here, we discuss findings regarding the normal postnatal development of the monkey hippocampal formation, which provide an essential framework to consider the etiologies of different neuropathological disorders affecting human hippocampal structure and function. We focus on studies of gene expression in distinct hippocampal regions that shed light on some basic mechanisms that might contribute to the etiology of schizophrenia. We argue that researchers, as well as clinicians, should not consider the use of animals in research only as 'animal models' of human diseases, as they will continue to need and benefit from a better understanding of the normal structure and functions of the hippocampus in 'model animals'.

miRNA regulation of gene expression: a predictive bioinformatics analysis in the postnatally developing monkey hippocampus.

Regulation of gene expression in the postnatally developing hippocampus might contribute to the emergence of selective memory function. However, the mechanisms that underlie the co-regulation of expression of hundreds of genes in different cell types at specific ages in distinct hippocampal regions have yet to be elucidated. By performing genome-wide microarray analyses of gene expression in distinct regions of the monkey hippocampal formation during early postnatal development, we identified one particular group of genes exhibiting a down-regulation of expression, between birth and six months of age in CA1 and after one year of age in CA3, to reach expression levels observed at 6-12 years of age. Bioinformatics analyses using NCBI, miRBase, TargetScan, microRNA.org and Affymetrix tools identified a number of miRNAs capable of regulating the expression of these genes simultaneously in different cell types, i.e., in neurons, astrocytes and oligodendrocytes. Interestingly, sixty-five percent of these miRNAs are conserved across species, from rodents to humans; whereas thirty-five percent are specific to primates, including humans. In addition, we found that some genes exhibiting greater down-regulation of their expression were the predicted targets of a greater number of these miRNAs. In sum, miRNAs may play a fundamental role in the co-regulation of gene expression in different cell types. This mechanism is partially conserved across species, and may thus contribute to the similarity of basic hippocampal characteristics across mammals. This mechanism also exhibits a phylogenetic diversity that may contribute to more subtle species differences in hippocampal structure and function observed at the cellular level.