Toward a reliable,automated method of individual alpha frequency (IAF) quantification

Individual alpha frequency (IAF) is a promising electrophysiological marker of interindividual differences in cognitive function. IAF has been linked with trait‐like differences in information processing and general intelligence, and provides an empirical basis for the definition of individualized frequency bands. Despite its widespread application, however, there is little consensus on the optimal method for estimating IAF, and many common approaches are prone to bias and inconsistency. Here, we describe an automated strategy for deriving two of the most prevalent IAF estimators in the literature: peak alpha frequency (PAF) and center of gravity (CoG). These indices are calculated from resting‐state power spectra that have been smoothed using a Savitzky‐Golay filter (SGF). We evaluate the performance characteristics of this analysis procedure in both empirical and simulated EEG data sets. Applying the SGF technique to resting‐state data from n = 63 healthy adults furnished 61 PAF and 62 CoG estimates. The statistical properties of these estimates were consistent with previous reports. Simulation analyses revealed that the SGF routine was able to reliably extract target alpha components, even under relatively noisy spectral conditions. The routine consistently outperformed a simpler method of automated peak detection that did not involve spectral smoothing. The SGF technique is fast, open source, and available in two popular programming languages (MATLAB, Python), and thus can easily be integrated within the most popular M/EEG toolsets (EEGLAB, FieldTrip, MNE‐Python). As such, it affords a convenient tool for improving the reliability and replicability of future IAF‐related research.     

Pupillometry as a measure of cognitive effort in younger and older adults

Two experiments examined the effectiveness of the pupillary response as a measure of cognitive load in younger and older adults. Experiment 1 measured the change in pupil size of younger and older adults while they listened to spoken digit lists that varied in length and retained them briefly for recall. In Experiment 2 changes in relative pupil size were measured while younger and older adults listened to sentences for later recall that varied in syntactic complexity and sentence length. Both age groups' pupil sizes were sensitive to the size of the memory set in Experiment 1 and sentence length in Experiment 2, with the older adults showing a larger effect of the memory load on a normalized measure of pupil size relative to the younger adults. By contrast, only the younger adults showed a difference in the pupillary response to a change in syntactic complexity, even with an adjustment for the reduced reactivity of the older pupil.     

Prefrontal cortex: links between low frequency delta EEG in sleep and neuropsychological performance in healthy,older people

Low frequency (< 1 Hz) delta EEG in sleep is of increasing interest as it indicates cortical reorganization, especially in the prefrontal cortex (PFC). Other research shows that delta power in sleep is positively linked to waking cerebral metabolic rate. Such findings suggest that < 1 Hz activity may reflect waking performance at neuropsychological tests specific to the PFC. We investigated this unexplored area. Sleep EEGs (Fp1-F3, Fp2-F4, O1-P3, O2-P4) were recorded in 24 healthy 61-75-year-olds. We found significant associations between 0.5-1.0 Hz power from the left frontal EEG channel, in the first non-REM period, and performance at tasks more specific to the left PFC (e.g., nonverbal planning and verbal fluency). This association was absent from the posterior channels. Neither age nor response times were confounding factors. This potential sleep EEG marker for PFC neuropsychological function in healthy, older people also points to further uses of the sleep EEG in understanding the role of sleep.     

Global EEG coherence as a marker for cognition in older adults at risk for dementia

Quantitative electroencephalography (EEG) provides useful information about neurophysiological health of the aging brain. Current studies investigating EEG coherence and power for specific brain areas and frequency bands have yielded inconsistent results. This study assessed EEG coherence and power indices at rest measured over the whole skull and for a wide frequency range as global EEG markers for cognition in a sample at risk for dementia. Since global markers are more reliable and less error-prone than region- and frequency-specific indices they might help to overcome previous inconsistencies. Global EEG coherence (1–30 Hz) and an EEG slowing score were assessed. The EEG slowing score was calculated by low-frequency power (1–8 Hz) divided by high-frequency power (9–30 Hz). In addition, the prognostic value of the two EEG indices for cognition and cognitive decline was assessed in a 5-year follow-up pilot study. Baseline global coherence correlated positively with cognition at baseline, but not with cognitive decline or with cognition at the 5-year follow-up. The EEG slowing ratio showed no significant association, neither with cognition at baseline or follow-up, nor with cognitive decline over a period of 5 years. The results indicate that the resting state global EEG coherence might be a useful and easy to assess electrophysiological correlate for neurocognitive health in older adults at risk for dementia. Because of the small statistical power for the follow-up analyses, the prognostic value of global coherence could not be determined in the present study. Future studies should assess its prognostic value with larger sample sizes.     

Perfectionism and other related trait measures as predictors of mortality in diabetic older adults: a six-and-a-half-year longitudinal study

After baseline assessment of health and perfectionism trait measures, 385 diabetic older adults were followed for six-and-a-half years. We hypothesized that the potential for increased stress associated with perfectionism leads to an increased risk of impending mortality for diabetics. Contrary to our hypothesis, mortality risk was 29 percent lower for high scorers on the perfectionism (self-oriented) dimension, compared to low scorers. In contrast, Cox regression analysis showed that high scores on measures of dysfunctional perfectionistic attitudes and dysfunctional dependency, which in many respects parallel the perfectionism (self-oriented) measure, were associated with an increased risk of mortality. Implications of findings are discussed.     

The effects of a single aerobic exercise session on mood and neural emotional reactivity in depressed and healthy young adults: A late positive potential study

Depression has been characterized by lowered mood and unfavorable changes in neural emotional reactivity (altered brain responses to emotional stimuli). Physical exercise is a well-established strategy to improve the mood of healthy and depressed individuals. Increasing evidence suggests that exercise might also improve emotional reactivity in healthy adults by increasing or decreasing brain responses to positive or negative stimuli, respectively. It is unknown, however, if exercise could also benefit emotional reactivity in depressed individuals. We investigated the effects of a single aerobic exercise session on mood and emotional reactivity in 24 depressed and 24 matched healthy young adults. Self-reported mood and neural reactivity to emotional pictures (indexed by the EEG late positive potential, LPP) were assessed before and after two experimental protocols: exercise (36 min of moderate-intensity exercise at 75% of maximal heart rate) and seated rest condition (36 min). In the healthy control group, exercise improved self-reported mood and neural emotional reactivity (increasing LPP to positive pictures). In the depressed group, exercise improved self-reported mood; however, it did not affect neural emotional reactivity. Additional analyses performed on both groups revealed that exercise-induced changes in emotional reactivity are associated with the severity of depressive symptoms: the effectiveness of exercise in improving emotional reactivity decreases with the severity of depressive symptoms. Overall, the study further strengthens the claim of a beneficial role of exercise on mood and emotional reactivity. It also suggests that a single aerobic exercise session might have a limited influence on neural emotional reactivity in depressed individuals.     

Frailty as a predictor of adverse outcomes in hospitalized older adults: A systematic review and meta-analysis

Frailty syndrome is prevalent among hospitalized older adults as are the occurrence of adverse outcomes. This systematic review and meta-analysis investigated whether frailty in older adults at hospital admission predicts adverse outcomes. Manual (ProQuest, conferences annals and references) and electronic searches (PUBMED, EMBASE, Web of Science, Lilacs, CINAHL, PsycINFO and Google Scholar) were performed. We included prospective studies of hospitalized older adults. Primary outcomes were functional decline at hospital discharge and mortality after discharge. Other data were considered secondary outcomes. Methodological quality was evaluated by the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Twenty-eight papers were included, corresponding to 19 cohorts (5 cohorts for functional decline and 16 for mortality), with moderate to good methodological quality. Being frail [RR: 1.32 (95%CI: 1.04; 1.67)] and pre-frail [RR: 1.51 (95%CI: 1.05; 2.17)] are risk factors for functional decline compared with being nonfrail. Frail individuals had a relative risk for in-hospital mortality and mortality in medium- and long-term compared to nonfrail (in-hospital RR: 8.20, medium RR: 9.49 and long RR: 7.94) and pre-frail (in-hospital RR: 3.19, medium RR: 3.31 and long RR: 3.72). The overall mortality risk in frail individuals is 3.49 and 2.14 times compared to nonfrail and pre-frail, respectively. Length of hospital stay was higher for frail older adults (13.5 days) compared with pre-frail (10.5 days) and nonfrail (8.3 days). Therefore, being frail at hospital admission is a risk factor for in-hospital mortality, long hospital stay, functional decline at hospital discharge, and mortality in the medium- and long-term.     

Auditory event-related potentials and alpha oscillations in the psychosis prodrome: Neuronal generator patterns during a novelty oddball task

Prior research suggests that event-related potentials (ERP) obtained during active and passive auditory paradigms, which have demonstrated abnormal neurocognitive function in schizophrenia, may provide helpful tools in predicting transition to psychosis. In addition to ERP measures, reduced modulations of EEG alpha, reflecting top-down control required to inhibit irrelevant information, have revealed attentional deficits in schizophrenia and its prodromal stage. Employing a three-stimulus novelty oddball task, nose-referenced 48-channel ERPs were recorded from 22 clinical high-risk (CHR) patients and 20 healthy controls detecting target tones (12% probability, 500 Hz; button press) among nontargets (76%, 350 Hz) and novel sounds (12%). After current source density (CSD) transformation of EEG epochs (− 200 to 1000 ms), event-related spectral perturbations were obtained for each site up to 30 Hz and 800 ms after stimulus onset, and simplified by unrestricted time–frequency (TF) principal components analysis (PCA). Alpha event-related desynchronization (ERD) as measured by TF factor 610–9 (spectral peak latency at 610 ms and 9 Hz; 31.9% variance) was prominent over right posterior regions for targets, and markedly reduced in CHR patients compared to controls, particularly in three patients who later developed psychosis. In contrast, low-frequency event-related synchronization (ERS) distinctly linked to novels (260–1; 16.0%; mid-frontal) and N1 sink across conditions (130–1; 3.4%; centro-temporoparietal) did not differ between groups. Analogous time-domain CSD-ERP measures (temporal PCA), consisting of N1 sink, novelty mismatch negativity (MMN), novelty vertex source, novelty P3, P3b, and frontal response negativity, were robust and closely comparable between groups. Novelty MMN at FCz was, however, absent in the three converters. In agreement with prior findings, alpha ERD and MMN may hold particular promise for predicting transition to psychosis among CHR patients.     

IVIG-bound IgG and IgM cloned by phage display from a healthy individual reveal the same restricted germ-line gene origin as in autoimmune thrombocytopenia

Intravenous immunoglobulin preparations (IVIG) have shown positive effects in the treatment of immune defects and autoimmune diseases. It is not clear how IVIG interacts with the components of the immune system. To investigate this, we cloned previously a large number of phage displayed IgG Fab fragments derived from three patients with autoimmune thrombocytopenia (AITP) that were specifically bound by IVIG molecules. Many of these Fabs reacted with platelets. Sequencing revealed that the most frequently used germ-line gene segments of all IVIG-bound Fabs were identical to those observed for many other autoantibodies. Particularly, the loci 3-30 or 3-30/3-30. 5, 3-23 and 3r, 3l, and 2a2 represented the most abundant genes used for the heavy (VH) and light chain V region (VL), respectively. This suggested a specific interaction of IVIG molecules with B cells that present B cell receptors derived from these germ-line genes. In the current study we determined the genetic origin of IVIG-reactive IgG and IgM cloned from a healthy person. A favoured selection of antibodies derived from the same germ-line origins as in AITP was observed. Because 3-30 and 3-23 are the most frequently rearranged VH germ-line gene segments among human B cells, our results suggest that this favoured anti-idiotypic interaction may have an important role for the development and control of the normal B cell repertoire.     

Variation in the human lymphocyte sister chromatid exchange frequency as a function of time: results of daily and twice-weekly sampling

The variation in lymphocyte sister chromatid exchange (SCE) frequency was investigated in healthy nonsmokers who were not taking any medication. Two separate studies were undertaken. In the first, blood was drawn from four women twice a week for 8 weeks. These donors recorded the onset and termination of menstruation and times of illness. In the second study, blood was obtained from two women and two men for 5 consecutive days on two separate occasions initiated 14 days apart. One donor participated in both studies. Analysis of the mean SCE frequencies in each study indicated that significant temporal variation occurred in each donor, and that more variation occurred in the longer study. Some of the variation was found to be associated with the menstrual cycle. Peaks in the SCE frequency were observed at times that corresponded approximately to ovulation and to the beginning and end of menstruation. In the daily study, most of the variation appeared to be random, but occasional day-to-day changes occurred that were greater than those expected by chance. To determine how well a single SCE sample estimated the pooled mean for each donor in each study, we calculated the number of samples that encompassed that donor's pooled mean within 1 or more standard errors. For both studies, about 75% of the samples encompassed the pooled mean within 2 standard errors. An analysis of high-frequency cells (HFCs) was also undertaken. The results for each study indicate that the proportion of HFCs, compared with the use of Fisher's Exact test, is significantly more constant than the means, which were compared by using the t-test. These results coupled with our previous work suggest that HFC analysis may be the method of choice when analyzing data from human population studies.     

Perception of structured optic flow and random visual motion in infants and adults: a high-density EEG study

Electroencephalogram (EEG) was used in 8-month-old infants and adults to study brain electrical activity as a function of perception of structured optic flow and random visual motion. A combination of visual evoked potential (VEP) analyses and analyses of temporal spectral evolution (TSE, time-dependent spectral power) was carried out. Significant differences were found for the N2 component of VEP for optic flow versus random visual motion within and between groups. Both adults and infants showed shorter latencies for structured optic flow than random visual motion, and infants showed longer latencies, particularly for random visual motion, and larger amplitudes than adults. Both groups also showed significant differences in induced activity when TSE of the two motion stimuli (optic flow and random visual motion) was compared with TSE of a static dot pattern. Infants showed an induced decrease in the amplitudes in theta-band frequency, while adults showed an induced increase in beta-band frequency. Differences in induced activity for the two motion stimuli could, however, not be observed. Brain activity related to motion stimuli is different for infants and adults and the differences are observed both in VEPs and in induced activity of the EEG. To investigate how changes in locomotor development are related to accompanying changes in brain activity associated with visual motion perception, more data of infants with different experiences in self-produced locomotion are required.     

Fetuin as a marker of cortical plate cells in the fetal cow neocortex: a comparison of the distribution of fetuin, alpha 2HS-glycoprotein, alpha-fetoprotein and albumin during early development

Summary Fetuin, ₂HS-glycoprotein (₂HS), -fetoprotein (AFP) and albumin have been shown to be present in some regions of the neocortex in two early stages of development of the cow brain using PAP immunocytochemistry. In the pre-cortical plate stage fibres of the primordial plexiform layer stained positively for fetuin. No staining was seen for albumin but plasma and cerebrospinal fluid (CSF) were positive for ₂HS and AFP. In the early cortical plate stage the strongest fetuin positive staining was seen in the earliest formed cells of the plate. ₂HS staining was much less intense but similar in distribution. The possible role of fetuin, or related glycoproteins, in cortical plate differentiation is discussed. Staining for AFP and for albumin was seen mainly in the ventricular zone and marginal zone fibres, and had a similar distribution and intensity for both proteins. Plasma and CSF stained for all four proteins. Tests showed some cross-reactivity between fetuin and anti-₂HS and, to a much lesser extent, between antisera to AFP and albumin and antigens denatured by fixation.