Imaging markers of mild cognitive impairment: multivariate analysis of CBF SPECT

This study aimed to investigate cross-sectional and longitudinal changes of regional cerebral blood flow (rCBF) in preclinical dementia using single photon emission computed tomography (SPECT). SPECT and cognitive function were investigated in 39 mild cognitive impairment (MCI) subjects and 20 age-matched controls. All subjects were followed longitudinally 19 months on average, 16 MCI subjects progressed to Alzheimer's disease (AD), who were retrospectively defined as progressive mild cognitive impairment (PMCI) at baseline and 23 MCI subjects remained stable and were defined as stable mild cognitive impairment (SMCI) at baseline. SPECT was performed both at the initial investigation and at follow-up. Image data were analyzed using multivariate analysis, SPM and volume of interest (VOI)-based analysis. Significant covariate patterns were derived, which differentiate among PMCI, SMCI and controls at baseline as well as describe the longitudinal progression of PMCI. The combined SPECT and neuropsychology increased the diagnostic accuracy of PMCI at baseline. SPECT and neuropsychological testing can be used objectively for both baseline diagnosis and to monitor changes in brain function during very early AD.     

Event-related synchronization of alpha activity in early Alzheimer's disease and mild cognitive impairment: an MEG study combining beamformer and group comparison

In patients with Alzheimer's disease (AD), it is sometimes challenging to identify typical findings in electroencephalography (EEG) or magnetoencephalography (MEG) such as a slowing of the posterior dominant activity or an increase in slow activity. In this MEG study, we evaluated the event-related synchronization (ERS) of alpha activity after eye closing in patients with early AD and mild cognitive impairment (MCI) who presented no slow MEG pattern. Thirteen patients with probable AD and thirteen patients with MCI, who met NINCDS-ADRDA and Petersen's diagnostic criteria, respectively, were enrolled. We also selected fourteen age-matched normal control subjects. MEG activity was acquired during eye-open and eye-closed states. The ERS after eye closing within 8-15Hz frequency band was calculated and its cortical source was superimposed on the individual's MRI by using the beamformer implemented in Brain Electrical Source Analysis (BESA). The Source image was converted into a standardized image, and group comparisons across patients with AD, MCI and controls were performed using BrainVoyager QX. The averaged ERS was observed dominantly in posterior regions in all three groups. Significant difference in ERS was observed only for the comparison between AD patients and controls, with AD patients showing increased ERS in frontal regions. Frontal shift of posterior alpha activity was observed clearly in AD patients using the combination of beamformer and group comparison.     

Brain oscillatory responses to an auditory-verbal working memory task in mild cognitive impairment and Alzheimer's disease.

We report preliminary findings on EEG oscillatory correlates of working memory in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Event-related desynchronization (ERD) and synchronization (ERS) of the 1-20 Hz EEG frequencies were studied using wavelet transforms in elderly controls, MCI patients and mild probable AD patients performing an auditory-verbal Sternberg memory task. Behaviourally, the AD patients made more errors than the controls and the MCI group. Statistically significant differences during the encoding of the memory set were found between the controls and the MCI group, such that the latter group showed ERD in the approximately 10-20 Hz frequencies. The findings may reflect different, compensatory encoding strategies in MCI. During retrieval, the most obvious differences were observed between the controls and the AD group: the ERD in the approximately 7-17 Hz frequencies was absent in the AD group particularly in anterior and left temporal electrode locations. This finding might indicate that AD is associated with deficient lexical-semantic processing during the retrieval phase in working memory tasks. Future studies with larger patient groups are needed to establish the diagnostic value of ERD/ERS patterns in MCI and AD.     

Effects of normal aging on event-related desynchronization/synchronization during a memory task in humans

Event-related desynchronization (ERD) and event-related synchronization (ERS) of the 1-20Hz EEG frequencies were studied using wavelet transforms in young (n = 10, mean age 22) and elderly subjects (n = 10, mean age 65) performing an auditory Sternberg memory task with words as stimuli. In both age groups, encoding of the four-word memory set elicited ERS in the theta and alpha frequency range. Theta ERS, and ERD in the alpha and beta bands were observed during retrieval. During encoding, the elderly showed greater alpha ERS and smaller theta ERS. During retrieval, smaller alpha ERD and theta ERS was found in the elderly subjects. Also, in the elderly, beta ERD was elicited in the late time window during retrieval. The statistically significant differences between the age groups were more marked during retrieval than during encoding. The results indicate that although the two groups performed equally well behaviorally in the task and the elderly subjects were cognitively intact, normal aging affects oscillatory theta, alpha and beta responses particularly during retrieval from working memory. The ERD/ERS patterns of the elderly resemble those of children found in a recent study, which might suggest that those memory-related brain processes that evolve later in childhood are the first to be affected in older age.     

Directionality of EEG synchronization in Alzheimer's disease subjects

Is directionality of electroencephalographic (EEG) synchronization abnormal in amnesic mild cognitive impairment (MCI) and Alzheimer's disease (AD)? EEG data were recorded in 64 normal elderly (Nold), 69 amnesic MCI, and 73 mild AD subjects at rest condition (closed eyes). Direction of information flux within EEG functional coupling at electrode pairs was performed by directed transfer function (DTF) at delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10 Hz), alpha 2 (10-12 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz). Parietal to frontal direction of the information flux within EEG functional coupling was stronger in Nold than in MCI and/or AD subjects, namely for alpha and beta rhythms. In contrast, the directional flow within inter-hemispheric EEG functional coupling did not discriminate among the three groups. These results suggest that directionality of parieto-to-frontal EEG synchronization is abnormal not only in AD but also in amnesic MCI.     

Value of event-related P300 subcomponents in the clinical diagnosis of mild cognitive impairment and Alzheimer's Disease

Accurate and early diagnosis of Alzheimer's Disease (AD) with reliable and noninvasive methods is of great importance for clinical practice as effective and specific antidementive therapies become available. The aim of the study was to evaluate the clinical relevance of event-related P300 in the early diagnosis of AD. Thirty patients with AD, 26 patients with mild cognitive impairment (MCI) from our Memory Clinic and 26 age-matched healthy controls (HC) were studied with event-related P300 potentials. Amplitudes of temporo-basal dipoles (TB-P300) were significantly diminished in AD compared to HC and MCI. Furthermore, latencies of temporo-superior dipoles (TS-P300) were significantly prolonged in AD compared with HC. Sensitivity was 90.0% for the differentiation of patients with AD from HC (specificity 79.1%) using reduced TB-P300 amplitudes and prolonged TS-P300 latencies. Similar results were found using Pz amplitudes as well as Fz latencies. Our data suggest that TB-P300 amplitudes and TS-P300 latencies may be an accurate clinically available, nonexpensive, noninvasive, and reliable marker for AD.     

Disruption of early event-related theta synchronization of human EEG in alexithymics viewing affective pictures

The 62-channel EEG was recorded while control non-alexithymic (n=21) and alexithymic (n=20) participants viewed sequentially presented neutral, pleasant and unpleasant pictures and subjectively rated them after each presentation. The event-related synchronization (ERS) to these stimuli was assessed in the theta-1 (4-6 Hz) and theta-2 (6-8 Hz) frequency bands. The obtained findings indicate that alexithymia influences perception of only emotional stimuli. Over anterior cortical regions alexithymia vs. control individuals in response to both pleasant and unpleasant stimuli manifested decreased left hemisphere ERS in the early test period of 0-200 ms along with enhanced ERS in response to negative vs. positive and neutral stimuli in the right hemisphere at 200-600 ms after stimulus onset. The findings provide the first EEG evidence that alexithymia construct, associated with a cognitive deficit in initial evaluation of emotion, is indexed by disrupted early frontal synchronization in the upper theta band that can be best interpreted to reflect disregulation during appraisal of emotional stimuli.     

Homocysteine and electroencephalographic rhythms in Alzheimer disease: a multicentric study

High plasma concentration of homocysteine is an independent risk factor for Alzheimer’s disease (AD), due to microvascular impairment and consequent neural loss [Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, Wilson PW, Wolf PA (2002) Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 346(7):476–483]. Is high plasma homocysteine level related to slow electroencephalographic (EEG) rhythms in awake resting AD subjects, as a reflection of known relationships between cortical neural loss and these rhythms? To test this hypothesis, we enrolled 34 mild AD patients and 34 subjects with mild cognitive impairment (MCI). Enrolled people were then subdivided into four sub-groups of 17 persons: MCI and AD subjects with low homocysteine level (MCI− and AD−, homocysteine level <11 μmol/l); MCI and AD subjects with high homocysteine level (MCI+ and AD+, homocysteine level ≥11 μmol/l). Resting eyes-closed EEG data were recorded. EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), and beta 2 (20–30 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Results showed that delta (frontal and temporal), theta (central, frontal, parietal, occipital, and temporal), alpha 1 (parietal, occipital, and temporal), and alpha 2 (parietal and occipital) sources were stronger in magnitude in AD+ than AD− group. Instead, no difference was found between MCI− and MCI+ groups. In conclusion, high plasma homocysteine level is related to unselective increment of cortical delta, theta, and alpha rhythms in mild AD, thus unveiling possible relationships among that level, microvascular concomitants of advanced neurodegenerative processes, and synchronization mechanisms generating EEG rhythms.     

Electrophysiological correlates of memory processing in early Finnish–Swedish bilinguals

Event-related desynchronization (ERD) and event-related synchronization (ERS) of the 1–30 EEG frequencies were studied in eight early Finnish–Swedish bilinguals during an auditory bilingual Sternberg memory task using Finnish–Swedish cognates as stimuli. Only subtle differences between languages were expected, since cognates have been assumed to have shared conceptual representations in the bilingual memory. Encoding elicited theta and alpha frequency ERS and beta frequency ERD responses in both languages. Retrieval elicited theta ERS and alpha and beta ERD responses. Some statistically significant differences between encoding and retrieval in Finnish versus Swedish emerged: greater theta and alpha ERS responses were observed during encoding in Swedish than during encoding in Finnish. During between-language retrieval, later-appearing theta ERS and alpha ERD responses were elicited as compared to within-language retrieval. These delayed oscillatory responses might reflect the involvement of central executive attentional functions in relation to language switching.     

Brain oscillatory 1-30 Hz EEG ERD/ERS responses during the different stages of an auditory memory search task

Event-related desynchronization (ERD) and event-related synchronization (ERS) responses of 1-30 Hz EEG frequencies during the different stages of an auditory Sternberg memory task were examined. The ERD/ERS responses were examined separately for successive memory set items (four) and for the two recognition conditions (YES/NO). The presentation of the memory set elicited ERS responses in the theta and alpha frequencies, and also beta ERD responses. These ERD/ERS responses elicited during encoding were found to evolve with successive memory set item presentation. The ERD/ERS responses elicited during the presentation of the probe dissociated significantly between the two recognition conditions (YES/NO). When the probe was included in the memory set (YES condition), recognition elicited stronger alpha and beta frequency ERD responses as compared to the NO condition. The findings from the current study verify that alpha ERD/ERS responses robustly dissociate between auditory encoding and recognition. The increasing alpha ERS responses with increasing memory set item presentation during encoding may be correlates of the functioning phonological loop, active memory maintenance and/or attention. The alpha ERD responses during recognition are undoubtedly associated with auditory memory search processes and distinguish between previously presented versus not presented verbal material. We propose that alpha ERD/ERS responses reflect explicitly auditory memory processes, discriminating between auditory encoding and recognition. Theta ERS responses may be associated with working memory processes, and possibly more specifically with the functioning of the central executive. Beta ERD/ERS responses may reflect also cognitive and/or memory processing, rather than merely the activity of the motor cortices.     

Quantitative electroencephalography in mild cognitive impairment: longitudinal changes and possible prediction of Alzheimer's disease

The present study evaluated the clinical course of patients with mild cognitive impairment (MCI), the pattern of electroencephalography (EEG) changes following cognitive deterioration, as well as the potential of neurophysiological measures in predicting dementia. Twenty-seven subjects with MCI were followed for a mean follow up period of 21 months. Fourteen subjects (52%) progressed (P MCI) to clinically manifest Alzheimer's disease (AD), and 13 (48%) remained stable (S MCI). The two MCI subgroups did not differ in baseline EEG measures between each other and the healthy controls (n = 16), but had significantly lower theta relative power at left temporal, temporo-occipital, centro-parietal, and right temporo-occipital derivation when compared to the reference AD group (n = 15). The P MCI baseline alpha band temporo-parietal coherence, alpha relative power values at left temporal and temporo-occipital derivations, theta relative power values at frontal derivations, and the mean frequency at centro-parietal and temporo-occipital derivations overlapped with those for AD and control groups. After the follow-up, the P MCI patients had significantly higher theta relative power and lower beta relative power and mean frequency at the temporal and temporo-occipital derivations. A logistic regression model of baseline EEG values adjusted for baseline Mini-Mental Test Examination showed that the important predictors were alpha and theta relative power and mean frequency from left temporo-occipital derivation (T5-O1), which classified 85% of MCI subjects correctly.     

Electrophysiological markers of skill-related neuroplasticity

Neuroplasticity involved in acquiring a new cognitive skill was investigated with standard time domain event-related potentials (ERPs) of scalp-recorded electroencephalographic (EEG) activity and frequency domain analysis of EEG oscillations looking at the event-related synchronization (ERS) and desynchronization (ERD) of neural activity. Electroencephalographic activity was recorded before and after practice, while participants performed alphabet addition (i.e., E + 3 = G, true or false?). Participant's performance became automated with practice through a switch in cognitive strategy from mentally counting-up in the alphabet to retrieving the answer from memory. Time domain analysis of the ERPs revealed a prominent positive peak at ∼300 ms that was not reactive to problem attributes but was reduced with practice. A second prominent positive peak observed at ∼500 ms was found to be larger after practice, mainly for problems presented with correct answers. Frequency domain spectral analyses yielded two distinct findings: (1) a frontal midline ERS of theta activity that was greater after practice, and (2) a beta band ERD that increased with problem difficulty before, but not after practice. Because the EEG oscillations were not phase locked to the stimulus, they were viewed as being independent of the time domain results. Consequently, use of time and frequency domain analyses provides a more comprehensive account of the underlying electrophysiological data than either method alone. When used in combination with a well-defined cognitive/behavioral paradigm, this approach serves to constrain the interpretations of EEG data and sets a new standard for studying the neuroplasticity involved in skill acquisition.     

Early event-related potentials changes during simple mental calculation in Chinese older adults with mild cognitive impairment: A case–control study

The aim was to examine early event-related potential (ERP) changes during mental arithmetic calculation task in mild cognitive impairment patients compared to healthy elderly. 16 mild cognitive impairment (MCI) subjects and 16 healthy Chinese older adults were studied. Event-related potentials were elicited using a simple mental calculation task. Performance on arithmetic calculation task, and the latency and amplitude of early event-related potential components (N1, P1, N170, and P2) were compared between the two groups. The reaction time of MCI group was significantly longer than that of control group (1691.03 ± 94.59 vs. 1539.55 ± 27.76, P < 0.01). The correct rate of MCI group (0.9463 ± 0.04) was significantly lower than that of control group (0.9776 ± 0.02, P < 0.01). The latency of temporal–occipital N170 and central–prefrontal P2 of MCI group were significantly prolonged compared to controls. MCI subjects presented significantly higher P2 amplitude. Compared with healthy controls, N170 was significantly lower at left temporal–occipital region and higher at right temporal–occipital region in mild cognitive impairment. Mild cognitive impairment patients had deficit on simple calculation. The early arithmetic calculation processing mechanism of mild cognitive impairment patients may be different from normal people.     

Event-related beta EEG changes during wrist movements induced by functional electrical stimulation of forearm muscles in man

Event-related beta electroencephalographic (EEG) changes were studied during wrist movements induced by functional electrical stimulation (FES) of the appropriate forearm muscles in healthy volunteers. Active and passive hand movements were investigated as control conditions. Significant EEG changes with respect to a pre-movement period were analyzed by calculating time-frequency maps of event-related (de-)synchronization (ERD/ERS) for 32 EEG channels recorded from sensorimotor and premotor areas. Immediately after the beginning of the FES movement, a prominent ERD was found, followed by a beta ERS similar to that observed after active or passive wrist movements. Both changes were maximal over the contralateral primary hand area. The main difference between active and stimulation-induced movements was that in the latter case no ERD was detectable prior to movement-onset. These findings suggest that the sensorimotor processing during FES involves some of the processes which are also involved in voluntary hand movements.     

Variability and Reliability of Paired-Pulse Depression and Cortical Oscillation Induced by Median Nerve Stimulation

Paired-pulse depression (PPD) has been widely used to investigate the functional profiles of somatosensory cortical inhibition. However, PPD induced by somatosensory stimulation is variable, and the reasons for between- and within-subject PPD variability remains unclear. Therefore, the purpose of this study was to clarify the factors influencing PPD variability induced by somatosensory stimulation. The study participants were 19 healthy volunteers. First, we investigated the relationship between the PPD ratio of each component (N20m, P35m, and P60m) of the somatosensory magnetic field, and the alpha, beta, and gamma band changes in power [event-related desynchronization (ERD) and event-related synchronization (ERS)] induced by median nerve stimulation. Second, because brain-derived neurotrophic factor (BDNF) gene polymorphisms reportedly influence the PPD ratio, we assessed whether BDNF genotype influences PPD ratio variability. Finally, we evaluated the test–retest reliability of PPD and the alpha, beta, and gamma ERD/ERS induced by somatosensory stimulation. Significant positive correlations were observed between the P60m_PPD ratio and beta power change, and the P60m_PPD ratio was significantly smaller for the beta ERD group than for the beta ERS group. P35m_PPD was found to be robust and highly reproducible; however, P60m_PPD reproducibility was poor. In addition, the ICC values for alpha, beta, and gamma ERD/ERS were 0.680, 0.760, and 0.552 respectively. These results suggest that the variability of PPD for the P60m deflection may be influenced by the ERD/ERS magnitude, which is induced by median nerve stimulation.     

Event-related potentials (ERPs) and intelligence in neonatally identified 47, XXY males

The event-related potentials (ERPs) of 18 extra X males (mean age 18.1 years) were recorded during the course of phonemic and orthographic discrimination tasks. The N2 and P3 latencies and amplitudes of subjects were examined in relation to their verbal and nonverbal intelligence test scores based on assessments at three ages: prior to puberty, during puberty and at sexual maturity. The results indicated that verbal abilities at most test occasions were significantly related to P3 latencies. Nonverbal abilities were largely uncorrelated with ERPs. The findings suggest that the verbal deficits of extra X males are the result of unlateralized individual differences in neural cognitive processing     

Differences in induced gamma and upper alpha oscillations in the human brain related to verbal/performance and emotional intelligence.

Participating in the study were 30 respondents, who could be clustered as high-average verbal/performance intelligent (HIQ/AIQ), or emotionally intelligent (HEIQ/AEIQ). The EEG was recorded while students were performing two tasks: the Raven's advanced progressive matrices (RAPM), and identifying emotions in pictures (IDEM). Significant differences in event-related desynchronization/synchronization (ERD/ERS) related to verbal/performance intelligence were only observed while respondents solved the RAPM. The HIQ and AIQ groups displayed temporal and spatial differently induced gamma band activity. Significant differences in ERD/ERS related to emotional intelligence were only observed for the IDEM task. HEIQ individuals displayed more gamma band ERS and less upper alpha band ERD than did AEIQ individuals. It can be concluded that HIQ and HEIQ individuals employed more adequate strategies for solving the problems at hand. The results further suggest that emotional intelligence and verbal/performance intelligence represent distinct components of the cognitive architecture.     

一种运动想象脑电分类算法的研究

为了解决脑机接口(BCI)中不同意识任务下脑电信号分类问题,针对运动想象脑电(EEG)的事件相关去同步/同步(ERD/ERS)现象,提出一种基于支持向量机(SVM)的实用分类算法。该算法首先对脑电信号进行滤波,获得对运动想象比较敏感的频段,对滤波后的脑电信号,通过去均值减小由于均值不同所造成的误差,然后,再提取基于ERD/ERS的脑电能量场强特征,对提取的特征,运用支持向量机(SVM)进行分类,得到了满意的效果。结果表明,此方法可为脑机接口技术的应用提供有效的手段。     

运动想象脑电的ERD/ERS分析

脑电信号所包含的频率分量及其变化规律是脑-计算机接口(brain- computer interface,BCI)研究的关键之一.事件相关去同步(event- ralated desynchronization,ERD)/同步现象(event- related synchronization,ERS)则是确定EEG频带的基本方法.本文在事件相关现象的神经生理学原理的基础上,利用传统计算方法,提出简单而有效的ERD/ERS波形的拓扑图法;并且对比应用基于匹配追踪法的分解参数,采用平均时间-频率能量分布图的方法,研究ERD/ERS规律.分析实际运动想象脑电MI-EEG时,两种方法的结论可以互相验证,也体现了各自的优点.     

Plasma levels of alpha beta peptides are altered in amnestic mild cognitive impairment but not in sporadic Alzheimer's disease

Plasma alpha beta levels have been examined in sporadic Alzheimer's disease yielding conflicting results; both no difference and an increase in plasma concentrations of alpha beta42 and alpha beta40 in sporadic cases of AD as compared to controls have been reported. Elevated plasma alpha beta42 levels may be detected several years before the onset of symptoms (in mild cognitive impairment stadium). Levels of alpha beta40 and alpha beta42 were measured in plasma from 54 patients with AD, 39 subjects with MCI and 35 controls using a commercially available ELISA. Mean plasma alpha beta42 levels were significantly higher in MCI as compared to both AD (P < 0.001) and control subjects (P < 0.001), while alpha beta40 did not differ between the groups. No correlations were observed between alpha beta levels and age, MMSE scores or gender. According to ROC curve analysis the maximum accuracy in discriminating MCI versus both controls and AD subjects has been achieved using a cut-off value of 3.8.