EEG and ERP biomarkers of Alzheimer's disease: a critical review

Here we critically review studies that used electroencephalography (EEG) or event-related potential (ERP) indices as a biomarker of Alzheimer's disease. In the first part we overview studies that relied on visual inspection of EEG traces and spectral characteristics of EEG. Second, we survey analysis methods motivated by dynamical systems theory (DST) as well as more recent network connectivity approaches. In the third part we review studies of sleep. Next, we compare the utility of early and late ERP components in dementia research. In the section on mismatch negativity (MMN) studies we summarize their results and limitations and outline the emerging field of computational neurology. In the following we overview the use of EEG in the differential diagnosis of the most common neurocognitive disorders. Finally, we provide a summary of the state of the field and conclude that several promising EEG/ERP indices of synaptic neurotransmission are worth considering as potential biomarkers. Furthermore, we highlight some practical issues and discuss future challenges as well

Regional Grey Matter Structure Differences between Transsexuals and Healthy Controls-A Voxel Based Morphometry Study.

Gender identity disorder (GID) refers to transsexual individuals who feel that their assigned biological gender is incongruent with their gender identity and this cannot be explained by any physical intersex condition. There is growing scientific interest in the last decades in studying the neuroanatomy and brain functions of transsexual individuals to better understand both the neuroanatomical features of transsexualism and the background of gender identity. So far, results are inconclusive but in general, transsexualism has been associated with a distinct neuroanatomical pattern. Studies mainly focused on male to female (MTF) transsexuals and there is scarcity of data acquired on female to male (FTM) transsexuals. Thus, our aim was to analyze structural MRI data with voxel based morphometry (VBM) obtained from both FTM and MTF transsexuals (n = 17) and compare them to the data of 18 age matched healthy control subjects (both males and females). We found differences in the regional grey matter (GM) structure of transsexual compared with control subjects, independent from their biological gender, in the cerebellum, the left angular gyrus and in the left inferior parietal lobule. Additionally, our findings showed that in several brain areas, regarding their GM volume, transsexual subjects did not differ significantly from controls sharing their gender identity but were different from those sharing their biological gender (areas in the left and right precentral gyri, the left postcentral gyrus, the left posterior cingulate, precuneus and calcarinus, the right cuneus, the right fusiform, lingual, middle and inferior occipital, and inferior temporal gyri). These results support the notion that structural brain differences exist between transsexual and healthy control subjects and that majority of these structural differences are dependent on the biological gender

Emotion-Related Visual Mismatch Responses in Schizophrenia: Impairments and Correlations with Emotion Recognition.

BACKGROUND AND OBJECTIVES:Mismatch negativity (MMN) is an event-related potential (ERP) measure of preattentional sensory processing. While deficits in the auditory MMN are robust electrophysiological findings in schizophrenia, little is known about visual mismatch response and its association with social cognitive functions such as emotion recognition in schizophrenia. Our aim was to study the potential deficit in the visual mismatch response to unexpected facial emotions in schizophrenia and its association with emotion recognition impairments, and to localize the sources of the mismatch signals. EXPERIMENTAL DESIGN:The sample comprised 24 patients with schizophrenia and 24 healthy control subjects. Controls were matched individually to patients by gender, age, and education. ERPs were recorded using a high-density 128-channel BioSemi amplifier. Mismatch responses to happy and fearful faces were determined in 2 time windows over six regions of interest (ROIs). Emotion recognition performance and its association with the mismatch response were also investigated. PRINCIPAL OBSERVATIONS:Mismatch signals to both emotional conditions were significantly attenuated in patients compared to controls in central and temporal ROIs. Controls recognized emotions significantly better than patients. The association between overall emotion recognition performance and mismatch response to the happy condition was significant in the 250-360 ms time window in the central ROI. The estimated sources of the mismatch responses for both emotional conditions were localized in frontal regions, where patients showed significantly lower activity. CONCLUSIONS:Impaired generation of mismatch signals indicate insufficient automatic processing of emotions in patients with schizophrenia, which correlates strongly with decreased emotion recognition

Cross-national variations in reported discrimination among people treated for major depression worldwide: The ASPEN/INDIGO international study

Background: No study has so far explored differences in discrimination reported by people with major depressive disorder (MDD) across countries and cultures. Aims: To (a) compare reported discrimination across different countries, and (b) explore the relative weight of individual and contextual factors in explaining levels of reported discrimination in people with MDD. Method: Cross-sectional multisite international survey (34 countries worldwide) of 1082 people with MDD. Experienced and anticipated discrimination were assessed by the Discrimination and Stigma Scale (DISC). Countries were classified according to their rating on the Human Development Index (HDI). Multilevel negative binomial and Poisson models were used. Results: People living in 'very high HDI' countries reported higher discrimination than those in 'medium/low HDI' countries. Variation in reported discrimination across countries was only partially explained by individual-level variables. The contribution of country-level variables was significant for anticipated discrimination only. Conclusions: Contextual factors play an important role in anticipated discrimination. Country-specific interventions should be implemented to prevent discrimination towards people with MDD

Elementary sensory deficits in schizophrenia indexed by impaired visual mismatch negativity.

INTRODUCTION: Mismatch negativity (MMN) is an automatic brain response to unexpected events. It represents a prediction error (PE) response, reflecting the difference between the sensory input and predictions. While deficits in auditory MMN are well known in schizophrenia, only few studies investigated impairments in predictive visual processing in schizophrenia. These studies used complex stimuli such as motion direction and emotional facial expressions. Here we studied whether automatic predictive processing of elementary features such as orientation is also impaired in schizophrenia. METHODS: Altogether 28 patients with schizophrenia and 27 healthy controls matched in age, gender, and education participated in the study. EEG was recorded using 128 channels in the two experimental blocks. Using an oddball paradigm, horizontal stripes of Gabor patches were presented as frequent standards and vertical stripes as rare deviants in one block. Stimulus probabilities were swapped in the other block. Mismatch responses were obtained by subtracting responses to standard from those to deviant stimuli. RESULTS: We found significant mismatch responses in healthy controls but not in patients in the prefrontal and occipital-parietal regions in the 90-200ms interval. Furthermore patients showed significantly decreased deviant minus standard difference waveforms relative to controls in the same regions with moderate to large effect sizes. CONCLUSIONS: Our findings demonstrate that predictive processing of unattended low-level visual features such as orientation is impaired in schizophrenia. Our results complement reports of sensory deficits found in tasks requiring attentive processing and suggest that deficits are present in automatic visual sensory processes putatively mediated by glutamatergic functioning

EEG Alpha and Beta Band Functional Connectivity and Network Structure Mark Hub Overload in Mild Cognitive Impairment During Memory Maintenance

Background: While decreased alpha and beta-band functional connectivity (FC) and changes in network topology have been reported in Alzheimer’s disease, it is not yet entirely known whether these differences can mark cognitive decline in the early stages of the disease. Our study aimed to analyze electroencephalography (EEG) FC and network differences in the alpha and beta frequency band during visuospatial memory maintenance between Mild Cognitive Impairment (MCI) patients and healthy elderly with subjective memory complaints. Methods: Functional connectivity and network structure of 17 MCI patients and 20 control participants were studied with 128-channel EEG during a visuospatial memory task with varying memory load. FC between EEG channels was measured by amplitude envelope correlation with leakage correction (AEC-c), while network analysis was performed by applying the Minimum Spanning Tree (MST) approach, which reconstructs the critical backbone of the original network. Results: Memory load (increasing number of to-be-learned items) enhanced the mean AEC-c in the control group in both frequency bands. In contrast to that, after an initial increase, the MCI group showed significantly (p < 0.05) diminished FC in the alpha band in the highest memory load condition, while in the beta band this modulation was absent. Moreover, mean alpha and beta AEC-c correlated significantly with the size of medial temporal lobe structures in the entire sample. The network analysis revealed increased maximum degree, betweenness centrality, and degree divergence, and decreased diameter and eccentricity in the MCI group compared to the control group in both frequency bands independently of the memory load. This suggests a rerouted network in the MCI group with a more centralized topology and a more unequal traffic load distribution. Conclusion: Alpha- and beta-band FC measured by AEC-c correlates with cognitive load-related modulation, with subtle medial temporal lobe atrophy, and with the disruption of hippocampal fiber integrity in the earliest stages of cognitive decline. The more integrated network topology of the MCI group is in line with the “hub overload and failure” framework and might be part of a compensatory mechanism or a consequence of neural disinhibition

Stigma and discrimination against people with schizophrenia related to medical services.

OBJECTIVE: To investigate whether people with schizophrenia experience discrimination when using health care services. METHODS: A cross-sectional survey in 27 countries in centres affiliated to the INDIGO Research Network, using face-to-face interviews with 777 participants with schizophrenia (62% male and 38% female). We analysed the data related to health issues, including health care, disrespect of mental health staff, and also personal privacy, safety and security, starting a family, pregnancy and childbirth. Discrimination was measured by the Discrimination and Stigma Scale (DISC), which consists of 36 items comprising three sub-scales: positive experienced discrimination; negative experienced discrimination; and anticipated discrimination. RESULTS: More than 17% of patients experienced discrimination when treated for physical health care problems. More than 38% of participants felt disrespected by mental health staff, with higher ratings in the post-communist countries. CONCLUSIONS: Mental health service providers have a key role in decreasing stigma in their provision of health care, and by doing more against stigmatizing and discriminating practices on the therapeutic and organizational level. This will require a change of attitudes and practices among mental and physical health care staff