[Time perception in functional brain imaging]. / Vnímání casu ve funkcním zobrazení mozku.

BACKGROUND: Knowledge of physiological mechanisms underlying time perception is still rather limited. The aim of our study was to search for a 'time accumulator', i.e. the part of the brain where information on the duration of time is stored. METHODS AND RESULTS: Nine healthy volunteers were given a time reproduction task during event-related fMRI. Subjects were instructed to retain the duration of the stimulus presented (presentation phase) and then to reproduce it by pressing a button (reproduction phase). Two different analyses were made: event-related (P < 0.05, FWR corrected) and parametric (BOLD signal increase/decrease during the presentation/reproduction phases correlated with the time intervals; P < 0.01, FDR corrected). When the event-related approach was employed, activation was noted bilaterally in the inferior prefrontal cortex (IPFC), supplementary motor area (SMA), precuneus and secondary visual cortex. On the right, there was activation in the dorsolateral prefrontal cortex (DLPFC), gyrus cinguli and inferior parietal lobule. On the left, the primary sensory-motor cortex was activated. While during the presentation phase the left DLPFC activity inversely correlated with the presented duration, a nearly identical area showed positive correlation in the reproduction phase. CONCLUSIONS: The event-related analysis did not allow distinguishing the process of time perception from many cognitive processes running simultaneously. In turn, the parametric analysis was based on visualizing regions, in which the signal correlated with the varying duration of the time interval provided the level of attention, decision-making and the processes of behavioral response planning and execution were constant. Moreover, the right and left DLPFC seem to play different roles in time perception. While the left one is functioning as a "time accumulator", the right one is rather involved in the recognition of previously perceived intervals.

Dimensional complexity of EEG brain mechanisms in untreated schizophrenia.

The dimensional complexity of left temporal-parietal and parietal-occipital electroencephalographic (EEG) recordings was assessed by computing the correlation dimension during 20 sec in six recording conditions from 15 first-episode acute schizophrenics before medication, 12 other medication-free individuals clinically and socially remitted after a first schizophrenic episode, 17 medication-free neurotics and 17 controls. The correlation dimension of the temporal-parietal EEG differed between groups [analysis of variance (ANOVA)] (p < 0.004), whereas neurotics (different from schizophrenics at p < 0.002) and remitted schizophrenics showed intermediate values. There was no overall significant difference between groups in the parietal-occipital EEG. Differences of the correlation dimension of the temporal-parietal versus the parietal-occipital EEG were significant between groups (ANOVA p < 0.05); first-episode schizophrenics differed from controls (p < 0.002) and remitted patients (p < 0.08). Increased dimensional complexity of schizophrenic EEG was found in one of two examined brain regions. The higher dimensional complexity of functional brain mechanisms in schizophrenics versus normals is reminiscent of the loosened organization of thought, and of suggestions of certain superior abilities in the patients.

Global, regional, and local measures of complexity of multichannel electroencephalography in acute, neuroleptic-naive, first-break schizophrenics.

BACKGROUND: Schizophrenic symptoms commonly are felt to indicate a loosened coordination, i.e. a decreased connectivity of brain processes. METHODS: To address this hypothesis directly, global and regional multichannel electroencephalographic (EEG) complexities (omega complexity and dimensional complexity) and single channel EEG dimensional complexities were calculated from 19-channel EEG data from 9 neuroleptic-naive, first-break, acute schizophrenics and 9 age- and sex-matched controls. Twenty artifact-free 2 second EEG epochs during resting with closed eyes were analyzed (2-30 Hz bandpass, average reference for global and regional complexities, local EEG gradient time series for single channels). RESULTS: Anterior regional Omega-Complexity was significantly increased in schizophrenics compared with controls (p < 0.001) and anterior regional Dimensional Complexity showed a trend for increase. Single channel Dimensional Complexity of local gradient waveshapes was prominently increased in the schizophrenics at the right precentral location (p = 0.003). CONCLUSIONS: The results indicate a loosened cooperativity or coordination (vice versa: an increased independence) of the active brain processes in the anterior brain regions of the schizophrenics.

Multichannel EEG fields during and without visual input: frequency domain model source locations and dimensional complexities.

27-Channel EEG potential map series were recorded from 12 normals with closed and open eyes. Intracerebral dipole model source locations in the frequency domain were computed. Eye opening (visual input) caused centralization (convergence and elevation) of the source locations of the seven frequency bands, indicative of generalized activity; especially, there was clear anteriorization of alpha-2 (10.5-12 Hz) and beta-2 (18.5-21 Hz) sources (alpha-2 also to the left). Complexity of the map series' trajectories in state space (assessed by Global Dimensional Complexity and Global OMEGA Complexity) increased significantly with eye opening, indicative of more independent, parallel, active processes. Contrary to PET and fMRI, these results suggest that brain activity is more distributed and independent during visual input than after eye closing (when it is more localized and more posterior).

Space-oriented EEG segmentation reveals changes in brain electric field maps under the influence of a nootropic drug.

Map landscape-based segmentation of the sequences of momentary potential distribution maps (42-channel recordings) into brain microstates during spontaneous brain activity was used to study brain electric field spatial effects of single doses of piracetam (2.9, 4.8, and 9.6 g Nootropil UCB and placebo) in a double-blind study of five normal young volunteers. Four 15-second epochs were analyzed from each subject and drug condition. The most prominent class of microstates (covering 49% of the time) consisted of potential maps with a generally anterior-posterior field orientation. The map orientation of this microstate class showed an increasing clockwise deviation from the placebo condition with increasing drug doses (Fisher's probability product, p < 0.014). The results of this study suggest the use of microstate segmentation analysis for the assessment of central effects of medication in spontaneous multi-channel electroencephalographic data, as a complementary approach to frequency-domain analysis.

Brain electric correlates of strong belief in paranormal phenomena: intracerebral EEG source and regional Omega complexity analyses.

The neurocognitive processes underlying the formation and maintenance of paranormal beliefs are important for understanding schizotypal ideation. Behavioral studies indicated that both schizotypal and paranormal ideation are based on an overreliance on the right hemisphere, whose coarse rather than focussed semantic processing may favor the emergence of 'loose' and 'uncommon' associations. To elucidate the electrophysiological basis of these behavioral observations, 35-channel resting EEG was recorded in pre-screened female strong believers and disbelievers during resting baseline. EEG data were subjected to FFT-Dipole-Approximation analysis, a reference-free frequency-domain dipole source modeling, and Regional (hemispheric) Omega Complexity analysis, a linear approach estimating the complexity of the trajectories of momentary EEG map series in state space. Compared to disbelievers, believers showed: more right-located sources of the beta2 band (18.5-21 Hz, excitatory activity); reduced interhemispheric differences in Omega complexity values; higher scores on the Magical Ideation scale; more general negative affect; and more hypnagogic-like reveries after a 4-min eyes-closed resting period. Thus, subjects differing in their declared paranormal belief displayed different active, cerebral neural populations during resting, task-free conditions. As hypothesized, believers showed relatively higher right hemispheric activation and reduced hemispheric asymmetry of functional complexity. These markers may constitute the neurophysiological basis for paranormal and schizotypal ideation.

Towards a quantitative characterisation of functional states of the brain: from the non-linear methodology to the global linear description.

The paper traces the development of a global approach to the electric activity of the brain, from its roots in non-linear dynamical approach to the current state of art. The rationale of a three-dimensional system of global multichannel EEG descriptors (sigma, phi and omega) is provided and results obtained by means of the global descriptors in various application areas are summarised. Finally, arguments in favour of a global, 'holistic' assessment of brain functional states are presented. Definitions and properties of the global EEG descriptors are summarised in the Appendix.

Adaptive segmentation of spontaneous EEG map series into spatially defined microstates.

Space-oriented segmentation can decompose multi-channel EEG map series into time segments characterized by quasi-stationary field map configurations. This assesses the dynamics of the underlying processes as activities of different neural generator ensembles. Our method of space-oriented segmentation describes the scalp field at times of maximal field strength (Global Field Power) by the locations of the centroids of positive and negative map areas. A quantitative measure of the simultaneous distance of the centroid locations evaluates the similarity between consecutive maps. A segment is defined as a sequence of maps that do not differ from each other by more than a present value. Finally, the average centroid locations for each segment are entered into an agglomerative clustering procedure to obtain a set of distinct classes of field configurations. Four records of 16 s of 42-channel resting EEG (band-pass filtered 2-16 Hz) from six subjects were analyzed. Average segment duration was 157.9 ms. Most segments belonged to a small number of classes (from 2 to 6, mean 3.7 classes for 90% of analysis time). The most frequent class showed an anterior-posterior field orientation and covered from 45 to 74% (mean 55% across subjects) of total time, with an average duration of 265 ms. The procedure was also tested using temporally and spatially unstructured data (white noise and randomly shuffled EEG) to ascertain that the methods reflect the spatio-temporal structure of the EEG processes.

Single-dose piracetam effects on global complexity measures of human spontaneous multichannel EEG.

Global complexity of 47-channel resting electroencephalogram (EEG) of healthy young volunteers was studied after intake of a single dose of a nootropic drug (piracetam, Nootropil UCB Pharma) in 12 healthy volunteers. Four treatment levels were used: 2.4, 4.8, 9.6 g piracetam and placebo. Brain electric activity was assessed through Global Dimensional Complexity and Global Omega-Complexity as quantitative measures of the complexity of the trajectory of multichannel EEG in state space. After oral ingestion (1-1.5 h), both measures showed significant decreases from placebo to 2.4 g piracetam. In addition, Global Dimensional Complexity showed a significant return to placebo values at 9.6 g piracetam. The results indicate that a single dose of piracetam dose-dependently affects the spontaneous EEG in normal volunteers, showing effects at the lowest treatment level. The decreased EEG complexity is interpreted as increased cooperativity of brain functional processes.

Beyond mapping: estimating complexity of multichannel EEG recordings.

A new measure of complexity of multichannel EEG recordings is proposed. The quantity assesses the diversity of activities of different brain generators contributing to the global dynamics of electric field of brain.

Analysis of complexity of EEG during sleep.

New multichannel descriptors of EEG activity: complexity (omega), total power (zeta) and generalized frequency (phi) were applied to whole night sleep analysis in 11 healthy subjects. The values of omega and phi decreased systematically from waking to slow wave sleep, and increased systematically in consecutive NREM-REM sleep cycles. The changes of zeta were opposite to omega and phi. These descriptors may be an alternative approach to the EEG sleep analysis.

Interhemispheric differences of sleep EEG complexity.

Complexity of EEG (omega), a global measure reflecting degree of spatial synchronization, was computed for whole night recordings of sleep EEG of 10 healthy volunteers, 9 males and 1 female (age 21-53) and 6 depressive patients, 5 males and 1 female (age 23-64). Sleep was scored visually in 20 s epochs, omega was calculated in 2.5 s segments and the median from 8 segments (20 s) was calculated. omega was calculated for the whole field of 21 electrodes and for the left and right hemisphere separately (2 x 8 electrodes). Measure of global power (sigma) and generalized frequency (phi) were also computed for the same data. In healthy subjects the complexity was higher over the right hemisphere during waking, and the difference shifted to higher complexity over the left hemisphere in slow wave sleep (F = 5.15, df1 = 4, df2 = 6856, P < 0.0005). The opposite trend was found in depressives (F = 10.51, df1 = 4, df2 = 3960, P < 0.0001).

Subsecond changes of global brain state in illusory multistable motion perception.

This study explored transient changes in EEG microstates and spatial Omega complexity associated with changes in multistable perception. 21-channel EEG was recorded from 13 healthy subjects viewing an alternating dot pattern that induced illusory motion with ambiguous direction. Baseline epochs with stable motion direction were compared to epochs immediately preceding stimuli that were perceived with changed motion direction ('reference stimuli'). About 750 ms before reference stimuli, Omega complexity decreased as compared to baseline, and two of four classes of EEG microstates changed their probability of occurrence. About 300 ms before reference stimuli, Omega complexity increased and the previous deviations of EEG microstates were reversed. Given earlier results on Omega complexity and microstates, these sub-second EEG changes might parallel longer-lasting fluctuations in vigilance. Assumedly, the discontinuities of illusory motion thus occur during sub-second dips in arousal, and the following reconstruction of the illusion coincides with a state of relative over-arousal.

From the 'EEG age' to a rational scale of brain electric maturation.

The aim of the present study was to propose an improved method of quantitative assessment of EEG age-related changes. 40 EEG recordings of healthy subjects (aged 0.7-78 years) were analysed. Multidimensional scaling of EEG spectral data indicated a presence of an 'age factor' related non-linearly to the chronological age. Relative integrals of FFT spectra in 6 frequency bands were utilized as predictors of age or, alternatively, logarithmized age. Three regression models based on EEG spectral indicators were examined. Regression from logarithmic predictors to logarithm of age performed best in terms of linearity and residual errors. As a result, the Brain Electric Maturation Scale was proposed, being defined by the logarithm of ratio of the age predicted from the EEG data and chronological age. The scale could serve as an objective measure of brain maturation in children, or as an age-independent indicator of slow EEG abnormalities.

Spatial EEG synchronisation over sensorimotor hand areas in brisk and slow self-paced index finger movements.

The changes of spatial EEG synchronisation during brisk and slow voluntary self-paced movements of the right and left index finger were analysed in 12 right-handed and 11 left-handed subjects. EEG was recorded from the left and right sensorimotor area using 24 closely spaced electrodes. A novel measure of spatial EEG synchronisation, omega-complexity, was computed separately for the left and right sensorimotor area in 64 overlapping one-second epochs representing 4.5 s of the pre-movement and 3.5 s of the post-movement period. Omega-complexity was higher, hence spatial synchronisation was lower, in slow than in brisk movements, especially in the right-handed. A sustained increase of omega-complexity was observed during execution of a slow movement. A decrease of omega-complexity which was often associated with a brief burst of spatially synchronised 10-Hz oscillations occurred at the onset of extensor muscle contraction. We suggest that increased spatial EEG synchronisation at movement onset may prevent "spillover" of excitation from the sensorimotor hand area to other cortical regions. During movement, the cortical neuronal assemblies subserve distinct, specialised functions manifesting in increased omega-complexity.

Global dimensional complexity of multi-channel EEG indicates change of human brain functional state after a single dose of a nootropic drug.

Viewing the multi-channel EEG as a sequence of momentary field maps corresponds to the concept of a trajectory in K-dimensional state space (K = number of channels). This approach permits a quantitative, single value measure of complexity of the brain state trajectory, the global correlation dimension that describes the ensemble characteristics of all recorded channels. In 5 normal volunteers, 4 records of 16-channel resting EEG were obtained during each of 4 randomized sessions (double blind design) after a single dose of placebo or 2.9 g or 4.8 g or 9.6 g piracetam. The global correlation dimension of a 40 sec epoch from each record was estimated, using 50 computational runs with 8192 point pairs. The results were combined for the two intermediate doses and averaged over repeated records. The dimensionality decreased from placebo (median = 5.89) to low dose (median = 5.72) to high dose (median = 5.59), significant in a Friedman ANOVA at P < 0.02, with significant differences between placebo vs. high and low vs. high dose. Thus, the subtle change of brain global functional state after a single dose of piracetam is reflected by the non-linear measure of global dimensional complexity of the multi-channel EEG.

Strictly simultaneous classical eyelid conditioning in man.

Strictly simultaneous eyelid conditioning in human Ss on the one hand and forward (ISI: 0.45 s), backward (ISI: -0.45 s), and pseudoconditioning on the other hand were compared in two different experimental situations: one-session experiment (100 reinforcements, 20 isolated CS randomly interspersed), and ten-sessions experiment (20 reinforcements, 4 isolated CS in each session), UCS was a light flash (0.5 J, 20 microseconds duration), CS a tone (1000 Hz, 50 ms, 73 dB). In both the experiments, strictly simultaneous conditioning was significantly different from pseudoconditioning, but significantly less effective than forward conditioning. In the ten-sessions experiment, it was also less effective than backward conditioning, while in the one-session experiment, it did not differ from backward conditioning. Statistical mixture decomposition method applied to the one-session- and the ten-sessions- experimental samples of individual acquisition curves resulted into the division of both samples into 4 subgroups according to the trend of acquisition curves. A significant positive association between the conditioning procedure and the distribution of individual curves into the four subgroups was found.

Global dimensional complexity of the EEG in healthy volunteers.

In contrast to the single-channel dimensional complexity, the global dimensional complexity is calculated from a multichannel EEG. The intention with the method is to measure the spatial distribution of information processing in the brain. The method seems to be of interest in psychopharmacological research, but the interpretation of the results in physiological terms is rather difficult. To get a more detailed information on the physiological significance of the EEG complexity measures, the influence of well-known physiological factors was studied in a group of 14 healthy subjects aged from 1.5 to 61 years. It was found that the correlation dimension was somewhat higher in older individuals, but the correlation with age was not statistically significant. However, the global correlation dimension was significantly lower during full alertness than during drowsiness. These results might reflect the changes in spatial structure of information processing, a high complexity suggesting a 'disorganisation' during drowsiness. As regards the age-dependent changes of the correlation dimension, the spatial 'flexibility' of information processing was also studied, using the differences between the 'alert' and 'drowsy' parts of the same EEG as indicator. It was found that the differences 'drowsy minus alert' were significantly related to age. A plausible interpretation seems to be that the spatial distribution of information processing is more changeable, or more flexible, in adults than in children.

Statistical mixture decomposition as a method for type analysis of learning curves.

A method for type analysis of learning curves, based on the statistical mixture decomposition, is described. Some critical points in current data-analytic techniques are discussed. The mathematical rationale of the new method is outlined in a brief sketch. The possibilities of the method are documented by two examples. In the first study, done on simulated lata of a known structure (N = 200, 2 classes), it was possible to distinguish, with an average performance of 82%, between two types, and to reproduce their original curves. In the second study data from experiments in classical eye-lid conditioning in man were analysed (N = 80). The decomposition procedure resulted into the classification into four groups, with pronounced inter-class differences in the course of respective learning curves. The variety of class curves ranges from a group with only few CRs (C1, N = 26), through a group with an initial increase and final decrease in CR frequency (C2, N = 16), a group with an apparently biphasic course of CR frequency (C3, N = 20), to a group with a rapid increase of CR and then stable course of CR frequency (C4, N = 18). The results are consistent with earlier findings concerning the existence of distinct types of learning curves. The problem of interpretation is briefly discussed. The method can be applied principally to any problems, where different types of time development trends of an alternative response are to be distinguished.