Biomedical subjects

R D Pascual-Marqui

Publications and source records attributed to R D Pascual-Marqui.

At least 19 recordsLinked to original sources

PubMed2001

Source localization of EEG activity during hypnotically induced anxiety and relaxation.

The engagement of different brain regions which implement subjectively experienced emotional states in normals is not completely clarified. Emotional states can conveniently be induced by hypnosis-based suggestions. We studied brain electric activity during hypnotically induced anxiety and relaxation in 11 right-handed normals (5 males, 6 females, mean age 26.5+/-7.6 years). After induction of light hypnosis, anxiety and then relaxation was suggested using a standardized text (reverse sequence in half of the subjects). Nineteen-channel, eyes-closed EEG (20 artifact-free s/subject) was analyzed (source localization using FFT approximation and low resolution electromagnetic tomography, LORETA). Global tests revealed the strongest difference (P<0.005) between EEG source gravity center locations during the two emotional states in the excitatory beta-2 EEG frequency band (18.5-21 Hz). Post hoc tests showed that the sources were located more right during anxiety than during relaxation (P=0.01). LORETA specified that anxiety showed maximally stronger activity than relaxation in right Brodmann area 10, and relaxation showed maximally stronger activity than anxiety in left Brodmann area 22. Clearly, the two induced emotional states were associated with activity of different neural populations. Our results agree with reports on brain activity shifted to the right (especially fronto-temporal) during negative compared with positive emotions, and support the role of beta-2 EEG frequency in emotional states.

Adult↗

PubMed2001

Low-resolution brain electromagnetic tomography revealed simultaneously active frontal and parietal sleep spindle sources in the human cortex.

Analyses of scalp-recorded sleep spindles have demonstrated topographically distinct slow and fast spindle waves. In the present paper, the electrical activity in the brain corresponding to different types of sleep spindles was estimated by means of low-resolution electromagnetic tomography. In its new implementation, this method is based on realistic head geometry and solution space is restricted to the cortical gray matter and hippocampus. In multichannel all-night electroencephalographic recordings, 10-20 artifact-free 1.25-s epochs with frontally, parietally and approximately equally distributed spindles were marked visually in 10 normal healthy subjects aged 20-35years. As a control condition, artifact-free non-spindle epochs 1-3s before or after the corresponding spindle episodes were marked. Low-resolution electromagnetic tomography demonstrated, independent of the scalp distribution, a distributed spindle source in the prefrontal cortex (Brodmann areas 9 and 10), oscillating with a frequency below 13Hz, and in the precuneus (Brodmann area 7), oscillating with a frequency above 13Hz. In extremely rare cases only the prefrontal or the parietal source was active. Brodmann areas 9 and 10 have principal connections to the dorsomedial thalamic nucleus; Brodmann area 7 is connected to the lateroposterior, laterodorsal and rostral intralaminar centrolateral thalamic nuclei. Thus, the localized cortical brain regions are directly connected with adjacent parts of the dorsal thalamus, where sleep spindles are generated. The results demonstrated simultaneously active cortical spindle sources which differed in frequency by approximately 2Hz and were located in brain regions known to be critically involved in the processing of sensory input, which is in line with the assumed functional role of sleep spindles.

Adult↗

PubMed2001

Anterior cingulate activity as a predictor of degree of treatment response in major depression: evidence from brain electrical tomography analysis.

OBJECTIVE: The anterior cingulate cortex has been implicated in depression. Results are best interpreted by considering anatomic and cytoarchitectonic subdivisions. Evidence suggests depression is characterized by hypoactivity in the dorsal anterior cingulate, whereas hyperactivity in the rostral anterior cingulate is associated with good response to treatment. The authors tested the hypothesis that activity in the rostral anterior cingulate during the depressed state has prognostic value for the degree of eventual response to treatment. Whereas prior studies used hemodynamic imaging, this investigation used EEG. METHOD: The authors recorded 28-channel EEG data for 18 unmedicated patients with major depression and 18 matched comparison subjects. Clinical outcome was assessed after nortriptyline treatment. Of the 18 depressed patients, 16 were considered responders 4-6 months after initial assessment. A median split was used to classify response, and the pretreatment EEG data of patients showing better (N=9) and worse (N=9) responses were analyzed with low-resolution electromagnetic tomography, a new method to compute three-dimensional cortical current density for given EEG frequency bands according to a Talairach brain atlas. RESULTS: The patients with better responses showed hyperactivity (higher theta activity) in the rostral anterior cingulate (Brodmann's area 24/32). Follow-up analyses demonstrated the specificity of this finding, which was not confounded by age or pretreatment depression severity. CONCLUSIONS: These results, based on electrophysiological imaging, not only support hemodynamic findings implicating activation of the anterior cingulate as a predictor of response in depression, but they also suggest that differential activity in the rostral anterior cingulate is associated with gradations of response.

Adult↗

PubMed2001

Brain mapping of bilateral visual interactions in children.

Interhemispheric interactions were studied with functional brain mapping of visual processing. Children performed a reaction time task with uni- and bilateral targets and nontargets. The visual evoked potential (VEP) was segmented into P1a, P1b, and N1 microstates using map rather than channel features. Map latencies, amplitudes and sources were tested for bilateral interactions. Bilateral targets yielded shorter VEP map latencies but later response onsets than unilateral ones. Source analyses of the unilateral VEPs indicated a transition from contra- (P1a) to ipsilateral (P1b) visual cortex activation (interhemispheric transfer). Bilateral VEPs were smaller than the summed unilateral VEPs in all microstates. indicating that interhemispheric interactions both precede and follow interhemispheric transfer. Brain mapping of uni- and bilateral VEPs in children thus revealed several distinct forms of interhemispheric interactions in the same, early time range.

Brain Mapping↗

PubMed2000

Effect of the 5-HT(1A) partial agonist buspirone on regional brain electrical activity in man: a functional neuroimaging study using low-resolution electromagnetic tomography (LORETA).

In a double-blind, placebo-controlled study, the effects of 20 mg buspirone - a 5-HT(1A) partial agonist - on regional electrical generators within the human brain were investigated utilizing three-dimensional EEG tomography. Nineteen-channel vigilance-controlled EEG recordings were carried out in 20 healthy subjects before and 1, 2, 4, 6 and 8 h after drug intake. Low-resolution electromagnetic tomography (LORETA; Key Institute for Brain-Mind Research, software: http://www.keyinst.unizh.ch) was computed from spectrally analyzed EEG data, and differences between drug- and placebo-induced changes were displayed as statistical parametric maps. Data were registered to the Talairach-Tournoux human brain atlas available as a digitized MRI (McConnell Brain Imaging Centre: http://www.bic.mni.mcgill.ca). At the pharmacodynamic peak (1st hour), buspirone increased theta and decreased fast alpha and beta sources. Areas of theta increase were mainly the left temporo-occipito-parietal and left prefrontal cortices, which is consistent with PET studies on buspirone-induced decreases in regional cerebral blood flow and fenfluramine-induced serotonin activation demonstrated by changes in regional cerebral glucose metabolism. In later hours (8th hour) with lower buspirone plasma levels, delta, theta, slow alpha and fast beta decreased, predominantly in the prefrontal and anterior limbic lobe. Whereas the results of the 1st hour speak for a slight CNS sedation (more in the sense of relaxation), those obtained in the 8th hour indicate activation. Thus, LORETA may provide useful and direct information on drug-induced changes in central nervous system function in man.

Adult↗

PubMed2000

Mood state and brain electric activity in ecstasy users.

Resting EEG during open and closed eyes and subsequent mood ratings were obtained from 15 Ecstasy users and 14 Ecstasy-naive controls. Absolute spectral power on the scalp, and the three-dimensional, intracerebral distribution of neuroelectric activity using low resolution brain electromagnetic tomography (LORETA) were computed. LORETA revealed global increases of theta, alpha 1 and beta 2/3 power during eyes open in Ecstasy users, and spectral analyses revealed a right-posterior increase of alpha 2 power (confirmed by LORETA) and increased beta band activity during open eyes. Ecstasy users had higher levels of state depressiveness, emotional excitability and a trend-level increase in state anxiety. The observed differences may be related to regular exposure to Ecstasy or other illicit drugs, or may be pre-existing.

Adult↗

PubMed2000

Spatial pattern of cerebral glucose metabolism (PET) correlates with localization of intracerebral EEG-generators in Alzheimer's disease.

BACKGROUND: Since the measurement of human cerebral glucose metabolism (GluM) by positron emission tomography (PET) and that of human cerebral electrical activity by EEG reflect synaptic activity, both methods should be related in their cerebral spatial distribution. Healthy subjects do indeed demonstrate similar metabolic and neuroelectric spatial patterns. OBJECTIVE: The aim of the study was to show that this similarity of GluM and EEG spatial patterns holds true in a population with a high variability of glucose metabolism. METHODS: We investigated healthy control subjects and patients with varying degrees of cognitive dysfunction and varying GluM patterns by applying [18F]FDG PET and EEG. RESULTS: We demonstrated that the localization of intracerebral generators of EEG correlates with spatial indices of GluM. CONCLUSION: These results indicates that EEG provides similar spatial information about brain function as GluM-PET. Since EEG is a non-invasive technique, which is more widely available and can be repeated more often than PET, this may have important implications both for neuropsychiatric research and for clinical diagnosis. However, further studies are required to determine whether equivalent EEG dipole generators can yield a diagnostic specificity and sensitivity similar to that of GluM-PET.

Aged↗

PubMed2000

Face-elicited ERPs and affective attitude: brain electric microstate and tomography analyses.

OBJECTIVES: Although behavioral studies have demonstrated that normative affective traits modulate the processing of facial and emotionally charged stimuli, direct electrophysiological evidence for this modulation is still lacking. METHODS: Event-related potential (ERP) data associated with personal, traitlike approach- or withdrawal-related attitude (assessed post-recording and 14 months later) were investigated in 18 subjects during task-free (i.e. unrequested, spontaneous) emotional evaluation of faces. Temporal and spatial aspects of 27 channel ERP were analyzed with microstate analysis and low resolution electromagnetic tomography (LORETA), a new method to compute 3 dimensional cortical current density implemented in the Talairach brain atlas. RESULTS: Microstate analysis showed group differences 132-196 and 196-272 ms poststimulus, with right-shifted electric gravity centers for subjects with negative affective attitude. During these (over subjects reliably identifiable) personality-modulated, face-elicited microstates, LORETA revealed activation of bilateral occipito-temporal regions, reportedly associated with facial configuration extraction processes. Negative compared to positive affective attitude showed higher activity right temporal; positive compared to negative attitude showed higher activity left temporo-parieto-occipital. CONCLUSIONS: These temporal and spatial aspects suggest that the subject groups differed in brain activity at early, automatic, stimulus-related face processing steps when structural face encoding (configuration extraction) occurs. In sum, the brain functional microstates associated with affect-related personality features modulate brain mechanisms during face processing already at early information processing stages.

Adult↗

PubMed1999

Low resolution brain electromagnetic tomography (LORETA) functional imaging in acute, neuroleptic-naive, first-episode, productive schizophrenia.

Functional imaging of brain electrical activity was performed in nine acute, neuroleptic-naive, first-episode, productive patients with schizophrenia and 36 control subjects. Low-resolution electromagnetic tomography (LORETA, three-dimensional images of cortical current density) was computed from 19-channel electroencephalographic (EEG) activity obtained under resting conditions, separately for the different EEG frequencies. Three patterns of activity were evident in the patients: (1) an anterior, near-bilateral excess of delta frequency activity; (2) an anterior-inferior deficit of theta frequency activity coupled with an anterior-inferior left-sided deficit of alpha-1 and alpha-2 frequency activity; and (3) a posterior-superior right-sided excess of beta-1, beta-2 and beta-3 frequency activity. Patients showed deviations from normal brain activity as evidenced by LORETA along an anterior-left-to-posterior-right spatial axis. The high temporal resolution of EEG makes it possible to specify the deviations not only as excess or deficit, but also as inhibitory, normal and excitatory. The patients showed a dis-coordinated brain functional state consisting of inhibited prefrontal/frontal areas and simultaneously overexcited right parietal areas, while left anterior, left temporal and left central areas lacked normal routine activity. Since all information processing is brain-state dependent, this dis-coordinated state must result in inadequate treatment of (externally or internally generated) information.

Acute Disease↗

PubMed1998

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.

Acute Disease↗

PubMed1998

The continuous performance test revisited with neuroelectric mapping: impaired orienting in children with attention deficits.

A total of 11 children with attention deficit disorder (ADD) and nine control children performed a continuous performance test (CPT) of the A-X type with concurrent neuroelectric brain mapping to assess preparatory processing, purportedly mediated by the frontal lobes. This cued CPT task proved to be a highly specific task. The groups could be clearly differentiated both at the behavioral and electrophysiological level. ADD children detected fewer signals and made more false alarms. There were no major group differences in topographical distribution of the event-related potential microstates, but ADD children displayed reduced global field power (GFP) in an early CNV/P3 microstate to cues. This indicated that impaired orienting to cues, rather than impaired executive target processing, determines the initial processing stages in ADD. In comparison with data from the same task run in Utrecht, the same orienting deficit in clinically diagnosed ADHD children was demonstrated. Low resolution electromagnetic tomography (LORETA) estimated posterior sources underlying these orienting processes and the orienting deficit. This argued against frontal lobe involvement at this stage and suggested involvement of a posterior attention system.

Arousal↗

PubMed1998

Neuroelectric mapping reveals precursor of stop failures in children with attention deficits.

Children with attention deficit disorders (ADD) may have specific problems with response inhibition in the STOP task. This task requires that subjects stop responses to a primary task if a second signal follows. However, it is unclear whether these problems reflect an impairment of the stopping process per se, whether they are related to reduced frontal lobe activation and whether they are confined to severe and pervasive forms of ADD. In 11 ADD and nine control children, 32 channel event-related EEG potentials (ERPs) were recorded in a STOP and a delayed GO task. Mapping revealed that both tasks evoked a similar sequence of neuroelectric microstates, i.e. of time segments with stable map topography. Adaptive segmentation identified the transition between these microstates. Reliable group differences were found in several microstates and in both tasks despite matched performance. In the GO task, ADD children had topographically altered P2/N2 microstates and attenuated P300-type microstates. In the STOP task, a topographically altered N1 microstate which coincided with the onset of the stop signal preceded the stop failures of ADD children. The timing of this microstate is too early to reflect deficits in actual stop signal processing and instead suggests altered initial orienting of attention to the primary signal in ADD children. Imaging with low resolution tomography (LORETA) during this microstate to stop failures indicated mainly posterior activation for both groups and increased rather than reduced frontal activation in ADD children. For a later microstate (P550), LORETA indicated strong frontal activation after successful stopping, but no group differences. The results suggest that information processing of ADD children deviates during activation of posterior mechanisms which may be related to the orienting of attention and which precedes and partly determines inhibitory control problems in ADD.

Arousal↗

PubMed1998

Differential effects of normal aging on sources of standard N1, target N1 and target P300 auditory event-related brain potentials revealed by low resolution electromagnetic tomography (LORETA).

The P300 event-related potential (ERP) is considered to be closely related to cognitive processes. In normal aging, P300 scalp latencies increase, parietal P300 scalp amplitudes decrease and the scalp potential field shifts to a relatively more frontal distribution. Based on ERPs recorded in 172 normal healthy subjects aged between 20 and 88 years in an auditory oddball paradigm, the effects of age on the electrical activity in the brain corresponding to N1 and P300 components were estimated by means of low resolution electromagnetic tomography (LORETA). This distributed approach directly computes a unique 3-dimensional electrical source distribution by assuming that neighbouring neurons are simultaneously and synchronously active. N1 LORETA generators, located predominantly in both auditory cortices and also symmetrically in prefrontal areas, increased with advancing age for standards but remained stable for targets. P300 LORETA generators, located symmetrically in the prefrontal cortex, in the parieto-occipital junction and in the inferior parietal cortex (supramarginal gyrus) and medially in the superior parietal cortex, were differentially affected by age. While age did not affect parieto-occipital sources, superior parietal and right prefrontal sources decreased pronouncedly. Thus, in normal aging, P300 current density decreased in regions were a fronto-parietal network for sustained attention was localized.

Adult↗

PubMed1998

Three-dimensional tomography of event-related potentials during response inhibition: evidence for phasic frontal lobe activation.

OBJECTIVES: Spatial analysis of the evoked brain electrical fields during a cued continuous performance test (CPT) revealed an extremely robust anteriorization of the positivity of a P300 microstate in the NoGo compared to the Go condition (NoGo-anteriorization in a previous study). To allow a neuroanatomical interpretation the NoGo-anteriorization was investigated with a new three-dimensional source tomography method (LORETA) was applied. METHODS: The CPT contains subsets of stimuli requiring the execution (Go) or the inhibition (NoGo) of a cued motor response which can be considered as mutual control conditions for the event-related potential (ERP) study of inhibitory brain functions 21-channel ERPs were obtained from 10 healthy subjects during a cued CPT, and analyzed with LORETA. RESULTS: Topographic analyses revealed significantly different scalp distributions between the Go and the NoGo conditions in both P100 and P300 microstates, indicating that already at an early stage different neural assemblies are activated. LORETA disclosed a significant hyperactivity located in the right frontal lobe during the NoGo condition in the P300 microstate. CONCLUSIONS: The results indicate that right frontal sources are responsible for the NoGo-anteriorization of the scalp P300 which is consistent with animal and human lesion studies of inhibitory brain functions. Furthermore, it demonstrates that frontal activation is confined to a brief microstate and time-locked to phasic inhibitory motor control. This adds important functional and chronometric specificity to findings of frontal activation obtained with PET and Near-Infrared-Spectroscopy studies during the cued CPT, and suggests that these metabolic results are not due to general task demands.

Adult↗

PubMed1998

Electrical sources of P300 event-related brain potentials revealed by low resolution electromagnetic tomography. 1. Effects of normal aging.

The P300 event-related potential (ERP) is considered to be closely related to cognitive processes. Previous reports regarding major generators contributing to the scalp-recorded P300 suggested widely distributed multiple sources. Based on ERPs recorded in 172 normal healthy subjects aged between 20 and 88 years in an auditory oddball paradigm, electrical activity in the brain corresponding to N1 and P300 components was localized by means of low resolution electromagnetic tomography (LORETA). The N1 LORETA generators, located in both auditory cortices, did not change over age. On the other hand, the P300 LORETA generators, located predominantly in the frontal neocortex and less pronounced in the posterior parietal cortex, decreased over age both in frontal and parietal source strength.

Adult↗

PubMed1998

Electrical sources of P300 event-related brain potentials revealed by low resolution electromagnetic tomography. 2. Effects of nootropic therapy in age-associated memory impairment.

In a double-blind, placebo-controlled study the effects of Actovegin on frontal and parietal electrical P300 sources revealed by low resolution electromagnetic tomography (LORETA) were studied in age-associated memory impairment (AAMI) patients. Actovegin is a protein-free metabolically active hemoderivative improving oxygen and glucose utilization. Each patient had, in randomized order, a treatment of 2 weeks with 250 ml 20% Actovegin and 250 ml placebo daily. Auditory ERPs were recorded before and 5 h after drug administration on day 1 (acute effect) and on day 15 (subacute and superimposed effect). Compared to age- and sex-matched normal controls, AAMI patients showed a trend towards P300 latency prolongation and a significantly reduced P300 global field power (GFP). Maximal LORETA source strength did not differ from controls. After Actovegin parietal P300 scalp amplitudes increased, while frontal and temporal amplitudes decreased as compared to placebo. This increase in hilliness, measured by the GFP, was significant. Moreover, the parietal P300 source strength increased after acute, subacute and superimposed infusion of Actovegin as compared to placebo. This may reflect improved availability of cognitive processing resources in the parietal cortex, an area that on the one hand plays an important role in fundamental aspects of attention and on the other hand has been found to be functionally impaired in dementia.

Aged↗

PubMed1997

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).

Adult↗

PubMed1997

Extracranial localization of intracranial interictal epileptiform activity using LORETA (low resolution electromagnetic tomography).

Besides the standard clinical methods of EEG waveshape analysis, mathematical models for reconstruction of dipolar sources from the digitized surface EEG have been introduced in epilepsy research. Although useful for localizing focal sources, these methods are inadequate for analyzing widespread epileptiform activity. A recently introduced alternative method called LORETA (low resolution electromagnetic tomography, Pascual-Marqui et al., 1994), directly computes the current distribution throughout the full brain volume, assuming that neighboring neuronal populations are simultaneously and synchronously activated. In mathematical terms the method selects the smoothest of all possible 3-dimensional current distributions, inherently introducing a certain amount of dispersion. In 7 patients, undergoing simultaneous EEG recording from 10 intracranial (subdural) and 22 extracranial electrodes, 111 subdural discharges (61 subtemporal and 50 lateral temporal) were identified. The exact time point of maximal intracranial activity was automatically identified, and the LORETA solution at that timepoint was computed from the surface EEG. Statistical comparison revealed significantly higher LORETA current density in the area corresponding to the subdurally recorded spike compared to other areas, and a more anterior and more medial LORETA location for subtemporal compared to lateral temporal spikes. This study indicates that the LORETA technique may become a useful method to localize electrical activity in the brain.

Adolescent↗