Evoked Potential Amplitude Change Related to Intelligence and Arousal

Using a sample of 94 adult subjects, relationships between measures of intelligence and the rate of decrease in amplitude of the average evoked potential (AEP) were examined in some detail. It was found that the rate of AEP amplitude decrease from a condition of high extrinsic inducement to activation to a condition of low extrinsic inducement to activation was significantly correlated with fluid intelligence (r= .24) and its subprocesses, but not with crystallized intelligence. This finding was interpreted as indicating that the AEP shift measure and the fluid intelligence measures indicate a kind of adaptive flexibility (or plasticity) of intellectual functioning. The results suggested that this is not a flexibility capacity that decreases significantly with aging in adulthood.     

Amplitude suppression and chaos control in epileptic EEG signals

In this paper we have proposed a novel amplitude suppression algorithm for EEG signals collected during epileptic seizure. Then we have proposed a measure of chaoticity for a chaotic signal, which is somewhat similar to measuring sensitive dependence on initial conditions by measuring Lyapunov exponent in a chaotic dynamical system. We have shown that with respect to this measure the amplitude suppression algorithm reduces chaoticity in a chaotic signal (EEG signal is chaotic). We have compared our measure with the estimated largest Lyapunov exponent measure by the largelyap function, which is similar to Wolf's algorithm. They fit closely for all but one of the cases. How the algorithm can help to improve patient specific dosage titration during vagus nerve stimulation therapy has been outlined.     

Two Measures of Auditory Evoked Response Amplitude and Their Relationship to Background EEG

All-night sleep EEG and auditory evoked responses (AERs) were recorded in 8 children whose ages ranged from 27 to 60 months. EEG intensity was measured by means of a Drohocki-type integrator. Two measures of evoked response amplitude were calculated: the peak-to-peak amplitude of the P₂N₂ component, and a multiple-component amplitude measure of the first 500 msec of the response. Both amplitude measurements were found to correlate well with each other. Changes in EEG intensity between subjects were not correlated with changes in AER amplitude, but a number of correlations between AER amplitude and EEG intensity were found within individual subjects. Further analysis suggested the latter finding might be a result of the presence of “unaveraged’EEG in individual AER plots. It is concluded that little correlation exists between AER amplitude and EEG intensity in children during sleep.     

A Zero-Setter and Voltage Reference Unit for EEG Amplifier Systems

This article describes a combined zero-setter and voltage reference unit employed by the authors in the measurement of EEG Averaged Evoked Responses. The sequential pulse generator that synchronously programs the required number of these units is outlined. The method could be of general use whenever an arbitarary zero voltage reference point or baseline is required on a signal waveform.     

Amplitude and Latency Changes in the Visual Evoked Potential to Different Stimulus Intensities

Visual evoked potentials (VEPs) were recorded from five sites (T₃, T₄, C_z, O₁, O₂) to six intensities of light flashes. Peak-to-trough amplitudes were measured for the P100-N120 and N120-P200 waveforms as well as baseline (prestimulus)-to-peak amplitudes for each component (i.e. P100, N120, and P200). Different methods of defining augmenting/reducing were compared. These included subtracting the VEP epoch mean level from mean levels within a timeband corresponding to P100 and calculating slopes both for these values and for the P100-N120 amplitudes across intensities. The technique of using slopes to describe amplitude-intensity functions was found to be unjustified and misleading. The Augmenting/Reducing groups defined by the slopes of peak-to-trough amplitudes or slopes of the timeband “amplitudes” proved to be almost mutually exclusive. Results also showed that the frequency with which actual VEP peaks occur within the appropriate timeband is very low and differs topographically. Augmenting/Reducing was then defined by monotonic increases in the P100-N120 peak-to-trough amplitudes. Augmenters and Reducers differed from each other not only for amplitude-intensity patterns but on a number of latency measures. Hemisphere differences were also found between groups. An inverse relationship was found between occipital and vertex amplitude-intensity patterns such that vertex augmenting was accompanied by occipital reducing and vice versa. Temporal and vertex amplitude-intensity patterns were similar.     

Quantitative EEG with brain mapping in strokes: Is it useful for prognosis?

Summary Thirty-two patients suffering from a stroke due to a hemispheric infarct and treated in a rehabilitation department were studied for a period of three months. They were regularly assessed by quantified EEG and mapping (three measurements) and by quantitative measurements of their performances in motor ability, activities of daily living and speech (four measurements). No correlation was found between their clinical improvement and the modifications of their EEG. Similarly no correlation was found between the initial EEG data and the clinical outcome.     

A New Method for Quantification and Assessment of Epileptiform Activity in EEG with Special Reference to Focal Nocturnal Epileptiform Activity

Quantification of epileptiform activity in EEG has been applied for decades. This has mainly been done by visual inspection of the recorded EEG. There have been many attempts using computers to quantify the activity, usually with moderate success. In a row of contexts, including Landau-Kleffner syndrome and the syndrome of epilepsy with continuous spike wave during slow sleep, the spike index (SI) has been applied to quantify ‹interictal nocturnal focal epileptiform activity’, which is suggested as a general term for the epileptiform activity enhanced by sleep. However, the SI has been implemented differently by different authors and has usually not been well described and never properly defined. This study suggests a definition of SI that gives a semiautomatic and relatively robust algorithm for assessment. The method employs spike detection by means of template matching of the current source density estimate. The percentage of time within an epoch with interspike interval (ISI) below a given limit, usually 3 s, is returned as the SI. This is calculated during daytime and in non-REM sleep. The standard epoch length is 10 min. The parameter selection is discussed in the context of the influence of spikes and bursts on cognition. The described method gives reproducible results in routine use, gives clinical valuable information, and is easily implemented in a clinical setting. There is only a minor added workload for the electroencephalographer.     

Amplitude spectrum EEG signal evidence for the dissociation of motor and perceptual spatial working memory in the human brain

This study investigated the question whether spatial working memory related to movement plans (motor working memory) and spatial working memory related to spatial attention and perceptual processes (perceptual spatial working memory) share the same neurophysiological substrate or there is evidence for separate motor and perceptual working memory streams of processing. Towards this aim, ten healthy human subjects performed delayed responses to visual targets presented at different spatial locations. Two tasks were attained, one in which the spatial location of the target was the goal for a pointing movement and one in which the spatial location of the target was used for a perceptual (yes or no) change detection. Each task involved two conditions: a memory condition in which the target remained visible only for the first 250 ms of the delay period and a delay condition in which the target location remained visible throughout the delay period. The amplitude spectrum analysis of the EEG revealed that the alpha (8–12 Hz) band signal was smaller, while the beta (13–30 Hz) and gamma (30–45 Hz) band signals were larger in the memory compared to the non-memory condition. The alpha band signal difference was confined to the frontal midline area; the beta band signal difference extended over the right hemisphere and midline central area, and the gamma band signal difference was confined to the right occipitoparietal area. Importantly, both in beta and gamma bands, we observed a significant increase in the movement-related compared to the perceptual-related memory-specific amplitude spectrum signal in the central midline area. This result provides clear evidence for the dissociation of motor and perceptual spatial working memory.     

Working Memory in Schizophrenia: An EEG Study Using Power Spectrum and Coherence Analysis to Estimate Cortical Activation and Network Behavior

This study examined regional cortical activations and cortico-cortical connectivity in a group of 20 high-functioning patients with schizophrenia and 20 healthy controls matched for age and sex during a 0- and a 2-back working memory (WM) task. An earlier study comparing schizophrenia patients with education level-matched healthy controls revealed less “optimally” organized network during the 2-back task, whereas a second study with healthy volunteers had suggested that the degree of cortical organization may be inversely proportional to educational level (less optimal functional connectivity in better educated individuals interpreted as the result of higher efficiency). In the present study, both groups succeeded in the 2-back WM task although healthy individuals had generally attained a higher level of education. First absolute power spectrum of the different frequency bands corresponding to the electrodes of each lobe was calculated. Then the mean values of coherence were calculated as an index of the average synchronization to construct graphs in order to characterize local and large scale topological patterns of cortico-cortical connectivity. The power spectra analyses showed signs of hypofrontality in schizophrenics with an asymmetry. Additionally, differences between the groups with greater changes during WM in healthy individuals were visible in all lobes more on the left side. The graph parameter results indicated decreased small-world architecture i.e. less optimal cortico-cortical functional organization in patients as compared to controls. These findings are consistent with the notion of aberrant neural organization in schizophrenics which is nevertheless sufficient in supporting adequate task performance. Ellie Pachou and Sifis Micheloyannis have equally contributed.     

Chronic Sleep Reduction: Daytime Vigilance Performance and EEG Measures of Sleepiness, With Particular Reference to "Practice" Effects

Six pairs of young adult 8-hr sleepers were divided equally into two groups, Reduction (R) and Control (C). They adhered to strict bed and arising times for six weeks. Additionally, R subjects reduced their sleep systematically to an average of 6 hrs per night. Following a baseline week, and on a weekly basis, “yoked” pairs of subjects, one from each group, were assessed for daytime sleepiness during prolonged vigilance performance, and by EEG measurement. All-night sleep EEGs were taken on R subjects before and at the end of the reduction. There were no significant differences between the groups for any of the daytime sleepiness measures, but both groups displayed significant “practice” effects over the weeks. R subjects experienced no major difficulties, except for some tiredness around awakening and lunchtime. Overall daytime sleepiness was not increased. Reduction was at the expense of REM and stage 2 sleep, and led to significant declines in sleep onset latency and in stages W + 1 at nighttime. SWS was not affected. This level of reduction in young adults seems to be achieved relatively easily.     

HIV and SIV Induce Alterations in CNS CaMKII Expression and Activation : A Potential Mechanism for Cognitive Impairment

The molecular mechanisms underlying learning and memory impairment in patients with HIV-associated neurological disease have remained unclear. Calcium/calmodulin-dependent kinase II (CaMKII) has key roles in synaptic potentiation and memory storage in neurons and also may have immunomodulatory functions. To determine whether HIV and simian immunodeficiency virus (SIV) induce alterations in CaMKII expression and/or activation (autophosphorylation) in the brain, we measured CaMKII alterations by quantitative immunoblotting in both an in vitro HIV/neuronal culture model and in vivo in an SIV-infected macaque model of HIV-associated neurological damage. Using primary rat hippocampal neuronal cultures treated with culture supernatants harvested from HIV-1–infected human monocyte-derived macrophages (HIV/MDM), we found that CaMKII activation declined after exposure of neurons to HIV/MDM. Consistent with our in vitro measurements, a significant decrease in CaMKII activation was present in both the hippocampus and frontal cortex of SIV-infected macaques compared with uninfected animals. In SIV-infected animals, total CaMKII expression in the hippocampus correlated well with levels of synaptophysin. Furthermore, CaMKII expression in both the hippocampus and frontal cortex was inversely correlated with viral load in the brain. These findings suggest that alterations in CaMKII may compromise synaptic function in the early phases of chronic neurodegenerative processes induced by HIV.More than 30 million people worldwide are infected with the human immunodeficiency virus (HIV; World Health Organization UNAIDS 2008). Although highly active antiretroviral therapies have dramatically improved survival rates and health-related quality of life for patients, HIV-associated neurocognitive disorders remain a significant public health problem.¹ In the highly active antiretroviral therapies era, the prevalence of less severe forms of HIV-associated neurocognitive disorders has increased in individuals who are not immunosuppressed.^2,3 Learning and memory impairment is common in HIV-infected individuals with estimates ranging from 40 to 60% of patients.^4,5 Synaptodendritic injury has emerged as a possible cause of these deficits in HIV, as well as other neurodegenerative diseases including Alzheimer disease, Parkinson disease, and schizophrenia.^6,7,8,9In particular, studies have implicated altered neuronal synaptic transmission and plasticity changes in the hippocampus as the mechanism underlying the cognitive impairment observed in HIV patients. In a murine model of HIV encephalitis (HIVE), for example, neuronal damage in the hippocampus was associated with impaired spatial learning.¹⁰ Neuropsychological tests in rhesus monkeys infected with simian immunodeficiency virus (SIV) have demonstrated similar functional impairment attributable to the hippocampus, consistent with psychomotor and memory impairment observed in HIV-infected humans.¹¹ However, the mechanisms underlying HIV-induced alterations in synaptic plasticity and long-term potentiation (LTP), the synaptic mechanism of memory storage, in the hippocampus have not been defined.Calcium/calmodulin-dependent kinase II (CaMKII) is necessary for the induction of LTP in the hippocampus. Once activated by calcium flux through the N-methyl-D-aspartic acid (NMDA) channel, CaMKII initiates the biochemical cascade that potentiates synaptic transmission. The kinase functions as a molecular switch with stable “on” (phosphorylated) and “off” (unphosphorylated) states, a mechanism that may underlie synaptic potentiation and memory storage in neurons.¹² In addition to serving as a transducer in LTP induction, CaMKII is also responsible for the persistence of LTP, a crucial aspect of memory.¹³ Autophosphorylation of threonine 286 of CaMKII is critical for persistent activation of CaMKII as mutation of this site eliminates phosphorylation and also blocks LTP.¹⁴ This mutation also interferes with experience-dependent plasticity in vivo and with memory, demonstrating an important consolidating role for CaMKII in cognitive function.^15,16,17Given the diverse roles that CaMKII plays in neuronal development, maturation, and plasticity, changes in CaMKII expression and activity may have significant implications for the pathophysiology of HIV CNS disease. In particular, HIV-induced alterations in neuronal CaMKII expression and activation may impair synaptodendritic function in key brain regions. To determine whether HIV induces alterations in neuronal CaMKII expression and activation in the hippocampus, we examined CNS CaMKII alterations both in vitro and in vivo. Cultured rat hippocampal neurons were treated with supernatants harvested from HIV-infected human monocyte-derived macrophages, an established in vitro model of HIV-induced neuronal damage, to measure HIV-induced alterations in CaMKII protein in neurons.^18,19 We also studied CaMKII alterations in the CNS using an SIV/macaque model of HIV-associated neurological damage. CaMKII expression and activation were measured in the hippocampus and frontal cortex of 12 rhesus macaques inoculated with the neurovirulent clone SIV/17E-Fr and the immunosuppressive strain SIV/DeltaB670. Synaptophysin expression, an established marker of synaptic integrity, was measured in SIV-infected macaques to determine whether CaMKII alterations are a molecular correlate of synaptic pathology in HIV CNS disease. CNS viral replication and host inflammatory responses were also evaluated to identify factors that potentially mediate alterations in CNS CaMKII expression and activation.     

Real-time Quantitative Polymerase Chain Reaction: A Potential Tool for Genetic Analysis in Neuropathology

Since its introduction in the early- to mid-1980s, the polymerase chain reaction (PCR) has been modified and optimized for an increasing number of applications. Early on, the focus was on the amplification of a specific nucleic acid template into quantities amenable to identification and experimental manipulation. While this remains an important application, recent technology has allowed the use of PCR to accurately quantitate the amount of a specific nucleic acid template present in a complex sample. Rather than simply analyzing the final product amount following the course of sequential cycles of amplification, quantitative PCR allows one to measure the accumulation of PCR product during the course of the reaction ("real-time PCR"). Under the appropriate conditions the number of PCR cycles required for the accumulation of a specific amount of product (during the exponential phase of the reaction) is a reflection of the relative amount of nucleic acid template present in the sample under analysis. Real-time quantitative PCR allows one to analyze a relatively large number of samples in a short period of time, potentially allowing multiple markers to be applied on a sample within a time frame consistent with clinical settings. In this overview, we will highlight the uses of real-time quantitative PCR as a potential diagnostic tool in neuropathology, focusing on the analysis of CNS tumors.     

Functional Connectivity and Quantitative EEG in Women with Alcohol Use Disorders: A Resting-State Study

This study was aimed at exploring the electroencephalographic features associated with alcohol use disorders (AUD) during a resting-state condition, by using quantitative EEG and Functional Connectivity analyses. In addition, we explored whether EEG functional connectivity is associated with trait impulsivity. Absolute and relative powers and Synchronization Likelihood (SL) as a measure of functional connectivity were analyzed in 15 AUD women and fifteen controls matched in age, gender and education. Correlation analysis between self-report impulsivity as measured by the Barratt impulsiveness Scale (BIS-11) and SL values of AUD patients were performed. Our results showed increased absolute and relative beta power in AUD patients compared to matched controls, and reduced functional connectivity in AUD patients predominantly in the beta and alpha bands. Impaired connectivity was distributed at fronto-central and occipito-parietal regions in the alpha band, and over the entire scalp in the beta band. We also found that impaired functional connectivity particularly in alpha band at fronto-central areas was negative correlated with non-planning dimension of impulsivity. These findings suggest that functional brain abnormalities are present in AUD patients and a disruption of resting-state EEG functional connectivity is associated with psychopathological traits of addictive behavior.     

Quantitative Interpretation of Genetic Toxicity Dose-Response Data for Risk Assessment and Regulatory Decision-Making: Current Status and Emerging Priorities

The screen-and-bin approach for interpretation of genotoxicity data is predicated on three false assumptions: that genotoxicants are rare, that genotoxicity dose–response functions do not contain a low-dose region mechanistically characterized by zero-order kinetics, and that genotoxicity is not a bona fide toxicological endpoint. Consequently, there is a need to develop and implement quantitative methods to interpret genotoxicity dose–response data for risk assessment and regulatory decision-making. Standardized methods to analyze dose–response data, and determine point-of-departure (PoD) metrics, have been established; the most robust PoD is the benchmark dose (BMD). However, there are no standards for regulatory interpretation of mutagenicity BMDs. Although 5–10% is often used as a critical effect size (CES) for BMD determination, values for genotoxicity endpoints have not been established. The use of BMDs to determine health-based guidance values (HBGVs) requires assessment factors (AFs) to account for interspecies differences and variability in human sensitivity. Default AFs used for other endpoints may not be appropriate for interpretation of in vivo mutagenicity BMDs. Analyses of published dose–response data showing the effects of compensatory pathway deficiency indicate that AFs for sensitivity differences should be in the range of 2–20. Additional analyses indicate that the AF to compensate for short treatment durations should be in the range of 5–15. Future work should use available data to empirically determine endpoint-specific CES values; similarly, to determine AF values for BMD adjustment. Future work should also evaluate the ability to use in vitro dose–response data for risk assessment, and the utility of probabilistic methods for determination of mutagenicity HBGVs. Environ. Mol. Mutagen. 61:66–83, 2020. © 2019 Her Majesty the Queen in Right of Canada     

Quantitative EEG in Alzheimer's disease: Cognitive state,resting state and association with disease severity

Background

Quantitative electroencephalogram (qEEG) recorded during cognitive tasks has been shown to differentiate between patients with Alzheimer's disease (AD) and healthy individuals. However, the association between various qEEG markers recorded during mnestic paradigms and clinical measures of AD has not been studied in detail.

Objective

To evaluate if ‘cognitive’ qEEG is a useful diagnostic option, particularly if memory paradigms are used as cognitive stimulators.

Methods

This study is part of the Prospective Registry on Dementia in Austria (PRODEM), a multicenter dementia research project. A cohort of 79 probable AD patients was included in a cross-sectional analysis. qEEG recordings performed in resting states were compared with recordings during cognitively active states. Cognition was evoked with a face–name paradigm and a paired-associate word list task, respectively. Relative band powers, coherence and auto-mutual information were computed as functions of MMSE scores for the memory paradigms and during rest. Analyses were adjusted for the co-variables age, sex, duration of dementia and educational level.

Results

MMSE scores explained 36–51% of the variances of qEEG-markers. Face–name encoding with eyes open was superior to resting state with eyes closed in relative theta and beta1 power as well as coherence, whereas relative alpha power and auto-mutual information yielded more significant results during resting state with eyes closed. The face–name task yielded stronger correlations with MMSE scores than the verbal memory task.

Conclusion

qEEG alterations recorded during mnestic activity, particularly face–name encoding showed the highest association with the MMSE and may serve as a clinically valuable marker for disease severity.     

吗氯贝胺单次口服后药代动力学与脑电功率谱的关系

探讨健康人吗氯贝胺药代动力学参数与定量脑电图改变之间的关系。１２例受试单次口服吗氯贝胺３００ｍｇ，分次取血测定血浆浓度。同时测定服药前后定量脑电图改变。吗氯贝胺的消除半衰期１．８５±０．５５ｈｒ；达峰时间（Ｔｐｅａｋ）１．３５±１．１０ｈｒ；峰浓度（Ｃｍａｘ）２８４０±６８５μｇ／Ｌ；血浆清除率（ＣＬ／Ｆ）３０．７８±９．１７Ｌ／ｈｒ。服药后定量脑电图的Ａｌｐｈａｌ频段相对功率谱增加，而Ｂｅｔａ２频段，Ｄｅｌｔａ频段某些导联相对功率谱下降。药物达峰时间与峰浓度与脑电图改变有一定关联。     

CD1 Expression in Human Atherosclerosis : A Potential Mechanism for T Cell Activation by Foam Cells

Atherosclerotic plaques are chronic inflammatory lesions composed of dysfunctional endothelium, smooth muscle cells, lipid-laden macrophages, and T lymphocytes. This study analyzed atherosclerotic tissue specimens for expression of CD1 molecules, a family of cell surface proteins that present lipid antigens to T cells, and examined the possibility that CD1+ lipid-laden macrophages might present antigen to T cells. Immunohistochemical studies using a panel of specific monoclonal antibodies demonstrated expression of each of the four previously characterized human CD1 proteins (CD1a, -b, -c, and -d) in atherosclerotic plaques. Expression of CD1 was not observed in normal arterial specimens and appeared to be restricted to the CD68+ lipid-laden foam cells of atherosclerotic lesions. CD1 molecules colocalized in areas of the arterial wall that also contained abundant T lymphocytes, suggesting potential interactions between CD1+ cells and plaque-infiltrating lymphocytes in situ. Using CD1-expressing foam cells derived from macrophages in vitro, we demonstrated the ability of such cells to present lipid antigens to CD1 restricted T cells. Given the abundant T cells, CD1+ macrophages, and lipid accumulation in atherosclerotic plaques, we propose a potential role for lipid antigen presentation by CD1 proteins in the generation of the inflammatory component of these lesions.     

Mean-Field Models for EEG/MEG: From Oscillations to Waves

Brain Topography - Neural mass models have been used since the 1970s to model the coarse-grained activity of large populations of neurons. They have proven especially fruitful for understanding...