Fundamentally altered global- and microstate EEG characteristics in Huntington's disease.

OBJECTIVE: Huntington's disease (HD) is characterized by psychiatric, cognitive, and motor disturbances. The study aimed to determine electroencephalography (EEG) global state and microstate changes in HD and their relationship with cognitive and behavioral impairments. METHODS: EEGs from 20 unmedicated HD patients and 20 controls were compared using global state properties (connectivity and dimensionality) and microstate properties (EEG microstate analysis). For four microstate classes (A, B, C, D), three parameters were computed: duration, occurrence, coverage. Global- and microstate properties were compared between groups and correlated with cognitive test scores for patients. RESULTS: Global state analysis showed reduced connectivity in HD and an increasing dimensionality with increasing HD severity. Microstate analysis revealed parameter increases for classes A and B (coverage), decreases for C (occurrence) and D (coverage and occurrence). Disease severity and poorer test performances correlated with parameter increases for class A (coverage and occurrence), decreases for C (coverage and duration) and a dimensionality increase. CONCLUSIONS: Global state changes may reflect higher functional dissociation between brain areas and the complex microstate changes possibly the widespread neuronal death and corresponding functional deficits in brain regions associated with HD symptomatology. SIGNIFICANCE: Combining global- and microstate analyses can be useful for a better understanding of progressive brain deterioration in HD.

Zazen meditation and no-task resting EEG compared with LORETA intracortical source localization.

Meditation is a self-induced and willfully initiated practice that alters the state of consciousness. The meditation practice of Zazen, like many other meditation practices, aims at disregarding intrusive thoughts while controlling body posture. It is an open monitoring meditation characterized by detached moment-to-moment awareness and reduced conceptual thinking and self-reference. Which brain areas differ in electric activity during Zazen compared to task-free resting? Since scalp electroencephalography (EEG) waveforms are reference-dependent, conclusions about the localization of active brain areas are ambiguous. Computing intracerebral source models from the scalp EEG data solves this problem. In the present study, we applied source modeling using low resolution brain electromagnetic tomography (LORETA) to 58-channel scalp EEG data recorded from 15 experienced Zen meditators during Zazen and no-task resting. Zazen compared to no-task resting showed increased alpha-1 and alpha-2 frequency activity in an exclusively right-lateralized cluster extending from prefrontal areas including the insula to parts of the somatosensory and motor cortices and temporal areas. Zazen also showed decreased alpha and beta-2 activity in the left angular gyrus and decreased beta-1 and beta-2 activity in a large bilateral posterior cluster comprising the visual cortex, the posterior cingulate cortex and the parietal cortex. The results include parts of the default mode network and suggest enhanced automatic memory and emotion processing, reduced conceptual thinking and self-reference on a less judgmental, i.e., more detached moment-to-moment basis during Zazen compared to no-task resting.

Functionally aberrant electrophysiological cortical connectivities in first episode medication-naive schizophrenics from three psychiatry centers.

Functional dissociation between brain processes is widely hypothesized to account for aberrations of thought and emotions in schizophrenic patients. The typically small groups of analyzed schizophrenic patients yielded different neurophysiological findings, probably because small patient groups are likely to comprise different schizophrenia subtypes. We analyzed multichannel eyes-closed resting EEG from three small groups of acutely ill, first episode productive schizophrenic patients before start of medication (from three centers: Bern N = 9; Osaka N = 9; Berlin N = 12) and their controls. Low resolution brain electromagnetic tomography (LORETA) was used to compute intracortical source model-based lagged functional connectivity not biased by volume conduction effects between 19 cortical regions of interest (ROIs). The connectivities were compared between controls and patients of each group. Conjunction analysis determined six aberrant cortical functional connectivities that were the same in the three patient groups. Four of these six concerned the facilitating EEG alpha-1 frequency activity; they were decreased in the patients. Another two of these six connectivities concerned the inhibiting EEG delta frequency activity; they were increased in the patients. The principal orientation of the six aberrant cortical functional connectivities was sagittal; five of them involved both hemispheres. In sum, activity in the posterior brain areas of preprocessing functions and the anterior brain areas of evaluation and behavior control functions were compromised by either decreased coupled activation or increased coupled inhibition, common across schizophrenia subtypes in the three patient groups. These results of the analyzed three independent groups of schizophrenics support the concept of functional dissociation.

Assessing direct paths of intracortical causal information flow of oscillatory activity with the isolated effective coherence (iCoh).

Functional connectivity is of central importance in understanding brain function. For this purpose, multiple time series of electric cortical activity can be used for assessing the properties of a network: the strength, directionality, and spectral characteristics (i.e., which oscillations are preferentially transmitted) of the connections. The partial directed coherence (PDC) of Baccala and Sameshima (2001) is a widely used method for this problem. The three aims of this study are: (1) To show that the PDC can misrepresent the frequency response under plausible realistic conditions, thus defeating the main purpose for which the measure was developed; (2) To provide a solution to this problem, namely the "isolated effective coherence" (iCoh), which consists of estimating the partial coherence under a multivariate autoregressive model, followed by setting all irrelevant associations to zero, other than the particular directional association of interest; and (3) To show that adequate iCoh estimators can be obtained from non-invasively computed cortical signals based on exact low resolution electromagnetic tomography (eLORETA) applied to scalp EEG recordings. To illustrate the severity of the problem with the PDC, and the solution achieved by the iCoh, three examples are given, based on: (1) Simulated time series with known dynamics; (2) Simulated cortical sources with known dynamics, used for generating EEG recordings, which are then used for estimating (with eLORETA) the source signals for the final connectivity assessment; and (3) EEG recordings in rats. Lastly, real human recordings are analyzed, where the iCoh between six cortical regions of interest are calculated and compared under eyes open and closed conditions, using 61-channel EEG recordings from 109 subjects. During eyes closed, the posterior cingulate sends alpha activity to all other regions. During eyes open, the anterior cingulate sends theta-alpha activity to other frontal regions.

sLORETA intracortical lagged coherence during breath counting in meditation-naïve participants.

We investigated brain functional connectivity comparing no-task resting to breath counting (a meditation exercise but given as task without referring to meditation). Functional connectivity computed as EEG coherence between head-surface data suffers from localization ambiguity, reference dependence, and overestimation due to volume conduction. Lagged coherence between intracortical model sources addresses these criticisms. With this analysis approach, experienced meditators reportedly showed reduced coherence during meditation, meditation-naïve participants have not yet been investigated. 58-channel EEG from 23 healthy, right-handed, meditation-naïve males during resting [3 runs] and breath counting [2 runs] was computed into sLORETA time series of intracortical electrical activity in 19 regions of interest (ROI) corresponding to the cortex underlying 19 scalp electrode sites, for each of the eight independent EEG frequency bands covering 1.5-44 Hz. Intracortical lagged coherences and head-surface conventional coherences were computed between the 19 regions/sites. During breath counting compared to resting, paired t-tests corrected for multiple testing revealed four significantly lower intracortical lagged coherences, but four significantly higher head-surface conventional coherences. Lowered intracortical lagged coherences involved left BA 10 and right BAs 3, 10, 17, 40. In conclusion, intracortical lagged coherence can yield results that are inverted to those of head-surface conventional coherence. The lowered functional connectivity between cognitive control areas and sensory perception areas during meditation-type breath counting compared to resting conceivably reflects the attention to a bodily percept without cognitive reasoning. The reductions in functional connectivity were similar but not as widespread as the reductions reported during meditation in experienced meditators.

EEG source imaging during two Qigong meditations.

Experienced Qigong meditators who regularly perform the exercises "Thinking of Nothing" and "Qigong" were studied with multichannel EEG source imaging during their meditations. The intracerebral localization of brain electric activity during the two meditation conditions was compared using sLORETA functional EEG tomography. Differences between conditions were assessed using t statistics (corrected for multiple testing) on the normalized and log-transformed current density values of the sLORETA images. In the EEG alpha-2 frequency, 125 voxels differed significantly; all were more active during "Qigong" than "Thinking of Nothing," forming a single cluster in parietal Brodmann areas 5, 7, 31, and 40, all in the right hemisphere. In the EEG beta-1 frequency, 37 voxels differed significantly; all were more active during "Thinking of Nothing" than "Qigong," forming a single cluster in prefrontal Brodmann areas 6, 8, and 9, all in the left hemisphere. Compared to combined initial-final no-task resting, "Qigong" showed activation in posterior areas whereas "Thinking of Nothing" showed activation in anterior areas. The stronger activity of posterior (right) parietal areas during "Qigong" and anterior (left) prefrontal areas during "Thinking of Nothing" may reflect a predominance of self-reference, attention and input-centered processing in the "Qigong" meditation, and of control-centered processing in the "Thinking of Nothing" meditation.

Reduced functional connectivity between cortical sources in five meditation traditions detected with lagged coherence using EEG tomography.

Brain functional states are established by functional connectivities between brain regions. In experienced meditators (13 Tibetan Buddhists, 15 QiGong, 14 Sahaja Yoga, 14 Ananda Marga Yoga, 15 Zen), 19-channel EEG was recorded before, during and after that meditation exercise which their respective tradition regards as route to the most desirable meditative state. The head surface EEG data were recomputed (sLORETA) into 19 cortical regional source model time series. All 171 functional connectivities between regions were computed as 'lagged coherence' for the eight EEG frequency bands (delta through gamma). This analysis removes ambiguities of localization, volume conduction-induced inflation of coherence, and reference-dependence. All significant differences (corrected for multiple testing) between meditation compared to no-task rest before and after meditation showed lower coherence during meditation, in all five traditions and eight (inhibitory as well as excitatory) frequency bands. Conventional coherence between the original head surface EEG time series very predominantly also showed reduced coherence during meditation. The topography of the functional connectivities was examined via PCA-based computation of principal connectivities. When going into and out of meditation, significantly different connectivities revealed clearly different topographies in the delta frequency band and minor differences in the beta-2 band. The globally reduced functional interdependence between brain regions in meditation suggests that interaction between the self process functions is minimized, and that constraints on the self process by other processes are minimized, thereby leading to the subjective experience of non-involvement, detachment and letting go, as well as of all-oneness and dissolution of ego borders during meditation.

EEG sLORETA functional imaging during hypnotic arm levitation and voluntary arm lifting.

This study (N = 37 with high, medium, and low hypnotizables) evaluated depth reports and EEG activity during both voluntary and hypnotically induced left-arm lifting with sLORETA functional neuroimaging. The hypnotic condition was associated with higher activity in fast EEG frequencies in anterior regions and slow EEG frequencies in central-parietal regions, all left-sided. The voluntary condition was associated with fast frequency activity in right-hemisphere central-parietal regions and slow frequency activity in left anterior regions. Hypnotizability did not have a significant effect on EEG activity, but hypnotic depth correlated with left hemisphere increased anterior slow EEG and decreased central fast EEG activity. Hypnosis had a minimal effect on depth reports among lows, a moderate one among mediums, and a large one among highs. Because only left-arm data were available, the full role of the hemispheres remains to be clarified.

Assessing interactions in the brain with exact low-resolution electromagnetic tomography.

Scalp electric potentials (electroencephalogram; EEG) are contingent to the impressed current density unleashed by cortical pyramidal neurons undergoing post-synaptic processes. EEG neuroimaging consists of estimating the cortical current density from scalp recordings. We report a solution to this inverse problem that attains exact localization: exact low-resolution brain electromagnetic tomography (eLORETA). This non-invasive method yields high time-resolution intracranial signals that can be used for assessing functional dynamic connectivity in the brain, quantified by coherence and phase synchronization. However, these measures are non-physiologically high because of volume conduction and low spatial resolution. We present a new method to solve this problem by decomposing them into instantaneous and lagged components, with the lagged part having almost pure physiological origin.

Meditators and non-meditators: EEG source imaging during resting.

Many meditation exercises aim at increased awareness of ongoing experiences through sustained attention and at detachment, i.e., non-engaging observation of these ongoing experiences by the intent not to analyze, judge or expect anything. Long-term meditation practice is believed to generalize the ability of increased awareness and greater detachment into everyday life. We hypothesized that neuroplasticity effects of meditation (correlates of increased awareness and detachment) would be detectable in a no-task resting state. EEG recorded during resting was compared between Qigong meditators and controls. Using LORETA (low resolution electromagnetic tomography) to compute the intracerebral source locations, differences in brain activations between groups were found in the inhibitory delta EEG frequency band. In the meditators, appraisal systems were inhibited, while brain areas involved in the detection and integration of internal and external sensory information showed increased activation. This suggests that neuroplasticity effects of long-term meditation practice, subjectively described as increased awareness and greater detachment, are carried over into non-meditating states.

Rivastigmine effects on EEG spectra and three-dimensional LORETA functional imaging in Alzheimer's disease.

OBJECTIVE: The objective of the study is to investigate the electrocortical and the global cognitive effects of 3 months rivastigmine medication in a group of mild to moderate Alzheimer's disease patients. MATERIALS AND METHODS: Multichannel EEG and cognitive performances measured with the Mini Mental State Examination in a group of 16 patients with mild to moderate Alzheimer's Disease were collected before and 3 months after the onset of rivastigmine medication. RESULTS: Spectral analysis of the EEG data showed a significant power decrease in the delta and theta frequency bands during rivastigmine medication, i.e., a shift of the power spectrum towards 'normalization'. Three-dimensional low resolution electromagnetic tomography (LORETA) functional imaging localized rivastigmine effects in a network that includes left fronto-parietal regions, posterior cingulate cortex, bilateral parahippocampal regions, and the hippocampus. Moreover, a correlation analysis between differences in the cognitive performances during the two recordings and LORETA-computed intracortical activity showed, in the alpha1 frequency band, better cognitive performance with increased cortical activity in the left insula. CONCLUSION: The results point to a 'normalization' of the EEG power spectrum due to medication, and the intracortical localization of these effects showed an increase of cortical activity in frontal, parietal, and temporal regions that are well-known to be affected in Alzheimer's disease. The topographic convergence of the present results with the memory network proposed by Vincent et al. (J. Neurophysiol. 96:3517-3531, 2006) leads to the speculation that in our group of patients, rivastigmine specifically activates brain regions that are involved in memory functions, notably a key symptom in this degenerative disease.

First valence, then arousal: the temporal dynamics of brain electric activity evoked by emotional stimuli.

The temporal dynamics of the neural activity that implements the dimensions valence and arousal during processing of emotional stimuli were studied in two multi-channel ERP experiments that used visually presented emotional words (experiment 1) and emotional pictures (experiment 2) as stimulus material. Thirty-two healthy subjects participated (mean age 26.8 +/- 6.4 years, 24 women). The stimuli in both experiments were selected on the basis of verbal reports in such a way that we were able to map the temporal dynamics of one dimension while controlling for the other one. Words (pictures) were centrally presented for 450 (600) ms with interstimulus intervals of 1,550 (1,400) ms. ERP microstate analysis of the entire epochs of stimulus presentations parsed the data into sequential steps of information processing. The results revealed that in several microstates of both experiments, processing of pleasant and unpleasant valence (experiment 1, microstate #3: 118-162 ms, #6: 218-238 ms, #7: 238-266 ms, #8: 266-294 ms; experiment 2, microstate #5: 142-178 ms, #6: 178-226 ms, #7: 226-246 ms, #9: 262-302 ms, #10: 302-330 ms) as well as of low and high arousal (experiment 1, microstate #8: 266-294 ms, #9: 294-346 ms; experiment 2, microstate #10: 302-330 ms, #15: 562-600 ms) involved different neural assemblies. The results revealed also that in both experiments, information about valence was extracted before information about arousal. The last microstate of valence extraction was identical with the first microstate of arousal extraction.

Correlation between disease severity and brain electric LORETA tomography in Alzheimer's disease.

OBJECTIVE: To compare EEG power spectra and LORETA-computed intracortical activity between Alzheimer's disease (AD) patients and healthy controls, and to correlate the results with cognitive performance in the AD group. METHODS: Nineteen channel resting EEG was recorded in 21 mild to moderate AD patients and in 23 controls. Power spectra and intracortical LORETA tomography were computed in seven frequency bands and compared between groups. In the AD patients, the EEG results were correlated with cognitive performance (Mini Mental State Examination, MMSE). RESULTS: AD patients showed increased power in EEG delta and theta frequency bands, and decreased power in alpha2, beta1, beta2 and beta3. LORETA specified that increases and decreases of power affected different cortical areas while largely sparing prefrontal cortex. Delta power correlated negatively and alpha1 power positively with the AD patients' MMSE scores; LORETA tomography localized these correlations in left temporo-parietal cortex. CONCLUSIONS: The non-invasive EEG method of LORETA localized pathological cortical activity in our mild to moderate AD patients in agreement with the literature, and yielded striking correlations between EEG delta and alpha1 activity and MMSE scores in left temporo-parietal cortex. SIGNIFICANCE: The present data support the hypothesis of an asymmetrical progression of the Alzheimer's disease.

Nonsmooth nonnegative matrix factorization (nsNMF).

We propose a novel nonnegative matrix factorization model that aims at finding localized, part-based, representations of nonnegative multivariate data items. Unlike the classical nonnegative matrix factorization (NMF) technique, this new model, denoted "nonsmooth nonnegative matrix factorization" (nsNMF), corresponds to the optimization of an unambiguous cost function designed to explicitly represent sparseness, in the form of nonsmoothness, which is controlled by a single parameter. In general, this method produces a set of basis and encoding vectors that are not only capable of representing the original data, but they also extract highly localized patterns, which generally lend themselves to improved interpretability. The properties of this new method are illustrated with several data sets. Comparisons to previously published methods show that the new nsNMF method has some advantages in keeping faithfulness to the data in the achieving a high degree of sparseness for both the estimated basis and the encoding vectors and in better interpretability of the factors.

Coherence and phase locking in the scalp EEG and between LORETA model sources, and microstates as putative mechanisms of brain temporo-spatial functional organization.

Brain electric mechanisms of temporary, functional binding between brain regions are studied using computation of scalp EEG coherence and phase locking, sensitive to time differences of few milliseconds. However, such results if computed from scalp data are ambiguous since electric sources are spatially oriented. Non-ambiguous results can be obtained using calculated time series of strength of intracerebral model sources. This is illustrated applying LORETA modeling to EEG during resting and meditation. During meditation, time series of LORETA model sources revealed a tendency to decreased left-right intracerebral coherence in the delta band, and to increased anterior-posterior intracerebral coherence in the theta band. An alternate conceptualization of functional binding is based on the observation that brain electric activity is discontinuous, i.e., that it occurs in chunks of up to about 100 ms duration that are detectable as quasi-stable scalp field configurations of brain electric activity, called microstates. Their functional significance is illustrated in spontaneous and event-related paradigms, where microstates associated with imagery- versus abstract-type mentation, or while reading positive versus negative emotion words showed clearly different regions of cortical activation in LORETA tomography. These data support the concept that complete brain functions of higher order such as a momentary thought might be incorporated in temporal chunks of processing in the range of tens to about 100 ms as quasi-stable brain states; during these time windows, subprocesses would be accepted as members of the ongoing chunk of processing.