Impaired frontal synchronization of spontaneous magnetoencephalographic activity in patients with bipolar disorder

Recent functional imaging studies demonstrated that brain exhibit coherent, synchronized activities during resting state and the dynamics may be impaired in various psychiatric illnesses. In order to investigate the change of neural dynamics in bipolar disorder, we used a new nonlinear measurement "similarity index" to analyze the magnetoencephalography (MEG) recordings and test the hypothesis that there are synchronization changes within different frequency bands in the frontal cortex of patients with bipolar disorder. Ten patients with bipolar I disorder during euthymic phase and ten normal controls underwent 2min eye-closed resting recording with a whole-head 306-channel MEG system. Eleven channels of MEG data from frontal area were selected for analysis. Synchronization level in the delta (2-4Hz), theta (4-8Hz), alpha (8-12Hz) and beta (12-24Hz) bands was calculated for each subject and compared across group. The results showed that significant dynamic changes in bipolar patients can be characterized by increased synchronization of slow frequency oscillations (delta) and decreased synchronization of fast frequency oscillations (beta). Furthermore, the positive correlation between beta synchronization level and preservative errors in Wisconcin card sorting task was found which would implicate the deficit of executive function in bipolar patients. Our findings indicate that analysis of spontaneous MEG recordings at resting state using nonlinear dynamic approaches may disclose the subtle regional changes of neural dynamics in BD.     

Evoked Synchronization/Desynchronization of Cortical Electrical Activity in Response to Facial Stimuli during Formation of a Set to an Emotionally Negative Expression

Evoked EEG theta and alpha rhythm synchronization/desynchronization responses to facial stimuli were studied in healthy subjects (n = 35) in an experiment involving formation of a set to an emotionally negative facial expression. The magnitude of the evoked theta activity synchronization response in the group of subjects with the plastic type of set was greater and the latent period was shorter than in the group with the rigid type of set. These differences were particularly clear in the temporal and parietal-occipital areas. A sufficiently high level of the phasic theta potentials synchronization response, reflecting the level of activity of the corticohippocampal feedback system during the perception of facial stimuli, was required for rapid substitution of the set to facial expressions. In subjects with plastic sets, the evoked low-frequency alpha potentials response was apparent as synchronization, while that in subjects of the “rigid” group consisted of desynchronization. These results were interpreted in terms of the concept of Klimesch (2007) that the evoked alpha potentials synchronization response is a measure of inhibition in cognitive activity. The alpha potentials synchronization response reflects the process of inhibitory control, which plays an important coordinating role in organizing the plastic properties of the set in relation to its inhibition when it ceases to correspond to new stimuli. The involvement of the tonic and phasic forms of cortical activation, mediated by the corticohippocampal and frontothalamic brain systems, in the functional organization of the cognitive set to an emotionally negative facial expression is discussed.     

Analysis of Evoked EEG Synchronization and Desynchronization in Conditions of Emotional Activation in Humans: Temporal and Topographic Characteristics

Studies in 20 healthy right-handed subjects analyzed evoked EEG synchronization and desynchronization in the delta, theta1, theta2, alpha1, alpha2, beta1, beta2, beta3, and gamma ranges in response to sequential presentation of stimuli from the International Affective Picture System (IAPS) with low, medium, and high emotional activation impact. Each signal presentation was accompanied by subjective scaling of the extent of its emotional impact. EEG traces were recorded in 62 channels as signals were presented. These experiments showed that the degree of emotional impact of the signal was significantly associated with increases in evoked synchronization in the delta, theta1, theta2, beta1, beta3, and gamma ranges and with the effects of combined changes in evoked synchronization and desynchronization in the alpha2 frequency range. The interhemisphere distribution of evoked changes in power provided evidence that not only the posterior areas of the right hemisphere were involved in analyzing the emotional significance of images, as indicated by changes in evoked theta1 and theta2 synchronization and alpha2 desynchronization, but also the anterior areas of the left hemisphere, as indicated by changes in evoked theta2 synchronization. From the standpoint of affective chronometry, the earliest discrimination of the emotional content of stimuli, regardless of the sign of the emotion, occurred in the lower theta range and was seen at 0-600 msec after the start of stimulus presentation. This process was delayed 600-1000 msec in the theta2, alpha2, and gamma ranges.     

Theta burst transcranial magnetic stimulation is associated with increased EEG synchronization in the stimulated relative to unstimulated cerebral hemisphere

Theta burst transcranial magnetic stimulation (TBS) may induce behavioural changes that outlast the stimulation period. The neurophysiological basis of these behavioural changes are currently under investigation. Given the evidence that cortical information processing relies on transient synchronization and desynchronization of neuronal assemblies, we set out to test whether TBS is associated with changes of neuronal synchronization as assessed by surface EEG. In four healthy subjects one TBS train of 600 pulses (200 bursts, each burst consisting of 3 pulses at 30 Hz, repeated at intervals of 100 ms) was applied over the right frontal eye field and EEG synchronization was assessed in a time-resolved manner over 60 min by using a non-overlapping moving window. For each time step the linear cross-correlation matrix for six EEG channels of the right and for the six homotopic EEG channels of the left hemisphere were computed and their largest eigenvalues used to assess changes of synchronization. Synchronization was computed for broadband EEG and for the delta, theta, alpha, beta and gamma frequency bands. In all subjects EEG synchronization of the stimulated hemisphere was significantly and persistently increased relative to EEG synchronization of the unstimulated hemisphere. This effect occurred immediately after TBS for the theta, alpha, beta and gamma frequency bands and 10-20 min after TBS for broadband and delta frequency band EEG. Our results demonstrate that TBS is associated with increased neuronal synchronization of the cerebral hemisphere ipsilateral to the stimulation site relative to the unstimulated hemisphere. We speculate that enhanced synchronization interferes with cortical information processing and thus may be a neurophysiological correlate of the impaired behavioural performance detected previously.     

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.     

Comparative analysis of the EEG in babies in the first month of life with gestation periods of 30–42 weeks

The aim of the present work was to compare measures of the power spectra, indexes, and coherence of the EEG in term and preterm infants in the first month of life. Six groups of children were investigated, born at 1) 30-32, 2) 33-34, 3) 35-36, 4) 37-38, 5) 39-40, and 6) 41-42 weeks of gestation; there were 10 in each group. The power of the delta frequencies was maximal in group 5. The power of theta frequencies was greatest in group 3. The theta frequencies index was higher in groups 2, 3, and 4. Alpha frequency power was greater in group 2. The index of alpha frequencies was greater in groups 1, 2, and 3. The indexes of beta1 and beta2 frequencies was greater in groups 1, 2, and 4. The largest number of coherence links in the delta, theta, and alpha frequencies were seen in group 6. Group 2, as compared with group 5, had more coherence links in the delta frequencies in the posterior and posterocentral areas, as well as more intrahemisphere synchronization in the theta and alpha frequencies. The results obtained here showed that EEG power spectra, indexes, and coherence depended on the gestation age at the time of birth, though this relationship was nonlinear.     

Spectral characteristics and linear-nonlinear synchronization changes of different EEG frequency bands during the CNV

During the CNV recorded in a simple auditory working memory task, task-specific decrease of the relative delta band and a transient increase of the absolute theta band were seen, accompanied by an increase of the absolute alpha1 and alpha2 bands in the posterior region. The decreased delta power probably corresponds to increased task-evoked arousal, whereas the transient theta power increase corresponds to working memory demand and possibly to the orienting response. The increased alpha1 and alpha2 power may be a manifestation of a top-down mechanism revealing control over the execution of a response. The area-specific, task-related, and frequency-dependent changes of EEG complexity measures indicate frontally increasing complexity during the early part of the CNV in the beta frequency bands, which underscores the importance of this region in the mechanisms of anticipatory behavior.     

Effects of stimulant medications on the EEG of children with Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive type.

Stimulant medications are the most commonly-used treatments for Attention-Deficit/Hyperactivity Disorder (ADHD) in North America and Australia, although it is still not entirely known how these medications work. This study investigated the effects of stimulant medications on the EEG of children with the Inattentive type of ADHD. An initial EEG was recorded during an eyes-closed resting condition and Fourier transformed to provide absolute and relative power estimates for the delta, theta, alpha and beta bands. Theta/alpha and theta/beta ratios were also calculated. Subjects were placed on a 6-month trial of a stimulant and a second EEG was recorded at the end of the trial. Subjects were included in this study only if they showed a good clinical response during the trial. The unmedicated ADHD group had significantly greater absolute and relative theta, less relative alpha, and higher theta/alpha and theta/beta ratios than the control group. The stimulant medications resulted in a normalisation of the EEG, with changes in the theta, alpha and beta bands being most evident. These results suggest that stimulants act to increase cortical arousal in children with ADHD, normalising their EEG.     

Cognitive decline in Parkinson's disease is associated with slowing of resting-state brain activity: a longitudinal study

The pathophysiological mechanisms of Parkinson's disease (PD)-related dementia (PDD) are still poorly understood. Previous studies using electroencephalography (EEG) and magnetoencephalography (MEG) have demonstrated widespread slowing of oscillatory brain activity as a neurophysiological characteristic of PD-related dementia. Here, we use MEG to longitudinally study early changes in oscillatory brain activity in initially nondemented PD patients that may be associated with cognitive decline. Using a longitudinal design, resting-state MEG recordings were performed twice at an approximate 4-year interval in 14 healthy controls and 49 PD patients. Changes in peak frequency and in relative spectral power for 10 brain regions were analyzed in relation to clinical measures of cognitive and motor function. In contrast to healthy controls, PD patients showed a slowing of the dominant peak frequency. Furthermore, analysis per frequency band revealed an increase in theta power over time, along with decreases in alpha1 and alpha2 power. In PD patients, decreasing cognitive performance was associated with increases in delta and theta power, as well as decreases in alpha1, alpha2, and gamma power, whereas increasing motor impairment was associated with a theta power increase only. The present longitudinal study revealed widespread progressive slowing of oscillatory brain activity in initially nondemented PD patients, independent of aging effects. The slowing of oscillatory brain activity strongly correlated with cognitive decline and therefore holds promise as an early marker for the development of dementia in PD.     

Synchronization of EEG Theta and Alpha Rhythms in an Unconscious Set to the Perception of an Emotional Facial Expression

Coherence functions in cortical electrical potentials in the theta (4–7 Hz) and alpha ranges (8–13 Hz) recorded during the formation and testing stages of a visual set to facial images bearing an emotional expression (an angry face) were studied in healthy adult subjects (n = 35). Differences in the spatial synchronization between theta and alpha potentials were seen, especially in rigid forms of the set, in which cases of erroneous perception of facial expressions were seen with contrast and assimilative illusions. This group of subjects (n = 23) showed increases in theta potentials between the dorsolateral areas of the frontal cortex (the orbitofrontal cortex) and the temporal area in the right hemisphere. A mechanism is proposed for the development of visual illusions. Analysis of the coherence functions of cortical potentials in the theta and alpha ranges generates a “window” which can be used to study the operation of the two functional systems integrating brain activity, i.e., the corticohippocampal and frontothalamic, in the perception of a facial expression. The frontothalamic system is associated with more diffuse types of cortical activation, especially in its anterior areas. The theta rhythm system evidently facilitates integration of the frontal cortex with the temporal area in the right hemisphere and the connections of the latter with the parietal and central zones in both hemispheres.     

EEG correlates (event-related desynchronization) of emotional face elaboration: a temporal analysis

An EEG frequency band analysis was conducted, in order to explore the significance of brain oscillations (delta, theta, alpha and beta) for emotional face comprehension during different post-stimulus time intervals (50-150; 150-250; 250-350; and 350-450 ms). The study was conducted on twenty adults who looked at emotional (happy, sad, angry, fearful) or neutral faces. The results showed that motivational significance of the stimulus can modulate the power synchronization (event-related desynchronization (ERD) decrease) within the frequency band of delta and theta. We propose that delta and theta respond to variations in processing stage of emotional face: whereas, delta reflects updating of the stimulus, theta responds to the emotional significance of face. The findings revealed that emotional discrimination by theta is observable mainly within 150-250 time interval and that it is more distributed on anterior regions, whereas delta is maximally synchronized within 250-350 interval and more posteriorly distributed for all the stimulus type. Finally, a right-hemisphere dominance was found for theta during emotional face comprehension.     

EEG spectral power analysis of phasic and tonic REM sleep in young and older male subjects

EEG spectral power was studied during periods of rapid eye movements (REMs) and tonic intervals in REM sleep of 7 young and 7 older male subjects. Significant symmetrical decreases in alpha and beta1 power at central and occipital sites, concurrent with an increase in frontal theta power, were observed during the production of REMs. The former findings are discussed as sleep analogues to changes in alpha and beta1 during waking, showing increased information processing and behavioural activation, and that of theta is tentatively presented as reflecting an increase in afferent thresholds. Independent of the phasic-tonic REM distinction, total EEG power markedly decreased as a function of time of night and did not interact with age. Significant age differences in the overall spectral composition of the EEG were obtained, namely, a lower level of delta power and a relative shift towards more power in frequencies above 12 Hz for the older group. Further, older subjects also demonstrated a more uniform topographical distribution of alpha and sigma power.     

Intelligence related differences in EEG-bandpower

Several studies on the relationship between event-related desynchronization/synchronization (ERD/ERS) and cognitive performance revealed contradictory results particularly for the alpha band. Studies from our laboratory have shown that good performers show a larger upper alpha ERD (interpreted in terms of larger cortical activation) than bad performers. In contrast, other researchers found evidence for the neural efficiency hypothesis, which states that more intelligent subjects exhibit a smaller extent of cortical activation, which is assumed to be reflected by a smaller upper alpha ERD. Here we address the question whether these divergent results may be due to differences in general task difficulty. Using a modified version of the RAVEN, individually divided into easy and difficult tasks, a group of average and a group of highly intelligent subjects (IQ- and IQ+) have been investigated. While in the theta frequency IQ+ subjects generally exhibited a significantly stronger activation, we found a significant interaction of task difficulty and IQ group in the upper alpha band, indicating both, a weaker activation for the high IQ group during the easy tasks, and a significant increase from easy to difficult tasks for IQ+ only.     

The effects of age and gender on sleep EEG power spectral density in the middle years of life (ages 20-60 years old)

The effects of age and gender on sleep EEG power spectral density were assessed in a group of 100 subjects aged 20 to 60 years. We propose a new statistical strategy (mixed-model using fixed-knot regression splines) to analyze quantitative EEG measures. The effect of gender varied according to frequency, but no interactions emerged between age and gender, suggesting that the aging process does not differentially influence men and women. Women had higher power density than men in delta, theta, low alpha, and high spindle frequency range. The effect of age varied according to frequency and across the night. The decrease in power with age was not restricted to slow-wave activity, but also included theta and sigma activity. With increasing age, the attenuation over the night in power density between 1.25 and 8.00 Hz diminished, and the rise in power between 12.25 and 14.00 Hz across the night decreased. Increasing age was associated with higher power in the beta range. These results suggest that increasing age may be related to an attenuation of homeostatic sleep pressure and to an increase in cortical activation during sleep.     

Mobile phone emission increases inter-hemispheric functional coupling of electroencephalographic alpha rhythms in epileptic patients

It has been reported that GSM electromagnetic fields (GSM-EMFs) of mobile phones modulate - after a prolonged exposure - inter-hemispheric synchronization of temporal and frontal resting electroencephalographic (EEG) rhythms in normal young and elderly subjects (Vecchio et al., 2007, 2010). Here we tested the hypothesis that this can be even more evident in epileptic patients, who typically suffer from abnormal mechanisms governing synchronization of rhythmic firing of cortical neurons. Eyes-closed resting EEG data were recorded in ten patients affected by focal epilepsy in real and sham exposure conditions. These data were compared with those obtained from 15 age-matched normal subjects of the previous reference studies. The GSM device was turned on (45 min) in the "GSM" condition and was turned off (45 min) in the other condition ("sham"). The mobile phone was always positioned on the left side in both patients and control subjects. Spectral coherence evaluated the inter-hemispheric synchronization of EEG rhythms at the following frequency bands: delta (about 2-4 Hz), theta (about 4-6 Hz), alpha1 (about 6-8 Hz), alpha2 (about 8-10 Hz), and alpha3 (about 10-12 Hz). The effects on the patients were investigated comparing the inter-hemispheric EEG coherence in the epileptic patients with the control group of subjects evaluated in the previous reference studies. Compared with the control subjects, epileptic patients showed a statistically significant higher inter-hemispheric coherence of temporal and frontal alpha rhythms (about 8-12 Hz) in the GSM than "Sham" condition. These results suggest that GSM-EMFs of mobile phone may affect inter-hemispheric synchronization of the dominant (alpha) EEG rhythms in epileptic patients. If confirmed by future studies on a larger group of epilepsy patients, the modulation of the inter-hemispheric alpha coherence due to the GSM-EMFs could have clinical implications and be related to changes in cognitive-motor function.     

Age- and genotype-related neurophysiologic reactivity to oxidative stress in healthy adults

The epsilon4 allele of the apolipoprotein E gene (ApoE), as well as aging increase the risk of Alzheimer's and vascular diseases. Electroencephalogram (EEG) reactivity to hyperventilation (HV) depends on hypocapnia-induced cerebral vasoconstriction, which may be impaired in subjects with subclinical cerebrovascular disease. Quantitative EEG at rest and under 3-minute HV was examined in 125 healthy subjects divided into younger (age range 28-50) and older (age range 51-82) cohorts and stratified by ApoE genotype. The younger ApoE-epsilon4 carriers had excessive EEG reactivity to HV characterized by the manifestation of high-voltage delta, theta activity and sharp waves, and larger HV-induced changes in EEG relative powers than in the younger ApoE-epsilon4 noncarriers. EEG reactivity to HV decreased with aging, and in the ApoE-epsilon4 carriers the decrease was more pronounced than in the ApoE-epsilon4 noncarriers. The older ApoE-epsilon4 carriers had smaller HV-induced changes in EEG relative powers than the older ApoE-epsilon4 noncarriers. A marked decline of EEG reactivity to HV in the older ApoE-epsilon4 carriers suggests the possible impact of vascular factors on the pathogenesis of ApoE-induced Alzheimer disease.     

Electroencephalogram differences in two subtypes of attention-deficit/hyperactivity disorder

This study investigated EEG differences between children with two subtypes of Attention-Deficit/Hyperactivity Disorder (ADHD) and normal control subjects. EEG was recorded during an eyes-closed resting condition and Fourier transformed to provide absolute and relative power estimates for the delta, theta, alpha, and beta bands, and the mean frequency for each band was calculated. Ratio coefficients were also calculated between frequency bands. Mean group differences were found in the theta, alpha, and beta bands between all three groups. Similarly, differences were found between all three groups for the theta/alpha and theta/beta ratios and for the mean frequency of the total EEG. These results support a model of ADHD resulting from a developmental deviation rather than a maturational lag in the central nervous system. Differences between the clinical groups in frontal activity suggest that different neuroanatomical systems are involved in the different subtypes of ADHD.     

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.     

Influences of the Loading on Working Memory on the Spatial Synchronization of Prestimulus Cortical Electrical Activity during Recognition of an Emotional Facial Expression

Experiments using a set to an emotionally negative facial expression were performed in healthy adult subjects (n = 35, 16 males, 19 females) to study the effects of increased loading on working memory (addition of an additional cognitive task to the experimental context) on the spatial synchronization of cortical electrical activity. The EEG theta (4–7 Hz) and alpha (8–13 Hz) frequency ranges were studied, along with the alpha1 (8–10 Hz) and alpha2 (11–13 Hz) ranges. Analysis of coherence functions of cortical potentials was compared with data obtained in experiments without loading. Additional loading on working memory led to increases in the inertia of the set to the facial expression and significantly altered the maps of the spatial synchronization of cortical potentials in the theta and alpha ranges: there were increases in the coherence of theta potentials both between individual frontal areas of the left and right hemispheres and between the frontal and temporal areas. It is hypothesized that the inertia of the set to an emotionally negative facial expression is associated with increased activity in the corticohippocampal system, as indicated by the significant increase in coherence relationships between theta potentials in cortical areas which have key roles in organizing cognitive sets. The increase in the loading on working memory significantly weakened the spatial synchronization of the low-frequency alpha rhythm, evidently reflecting decreases in the role of the frontothalamic selective attention system in the recognition process due to redistribution of attention resources resulting from the additional cognitive task in the context of the subject’s ongoing activity.     

Task-related power and coherence changes in neuromagnetic activity during visuomotor coordination

We analyzed a set of full-head (66 channels, CTF Inc.) magnetoencephalography (MEG) data recorded when 5 subjects performed rhythmic right index-finger flexion and extension movements on the beat (synchronization) or off the beat (syncopation) with a visual metronome at 1 Hz. Neuromagnetic activities in the alpha (8–14 Hz), beta (15–30 Hz) and gamma (30–50 Hz) ranges were shown to correlate with different aspects of the task. Specifically, we found that, compared with the control condition in which subjects only looked at the visual metronome without making any movement, all the movement conditions were accompanied by a decrease of power in the alpha range (8–14 Hz) in sensorimotor channels of both hemispheres, and an increase of coherence among a subset of these channels. The same comparison showed that power changes in the beta range differentiate task conditions by exhibiting power increases for synchronization and power decreases for syncopation. Changes in the gamma range power were found to be related to the kinematics of movement trajectories (flexion versus extension). These results suggest that three important cortical oscillations play different functional roles in a visuomotor timing task. Electronic Publication