Biomedical subjects

Matthias Weisbrod

Publications and source records attributed to Matthias Weisbrod.

At least 19 recordsLinked to original sources

PubMed2006

Stereotyped topography of different elevated contingent negative variation components in children with migraine without aura points towards a subcortical dysfunction.

Increased negativity during contingent negative variation (CNV) is thought to reflect abnormal neural activation in adult migraineurs' attention related processing. Findings in childhood and adolescence have yielded less clear results. This study characterizes the age-dependent development of CNV topography in migraine during childhood in order to elucidate the origin and cerebral generators of described CNV elevations. A large sample of children with primary headache (migraine with/without aura, tension type headache) and healthy controls aged 6-18 years was examined in a CNV paradigm using 64-channel high resolution DC-EEG. Patients were tested for diagnose-related topographic group differences of initial CNV (iCNV), late CNV (lCNV) and postimperative negative variation (PINV). All three CNV components of 6-11-year-old migraineurs without aura showed elevated negativity over the supplementary motor area (SMA) and around the vertex. Migraine children lacked age-dependent development of late CNV around Cz as previously reported. However, they showed a normal development of late CNV over pre-/primary motor cortex (MI). There was no marked elevation of iCNV amplitude over frontal areas (orienting reaction) nor specific amplitude elevations over "motor" or "sensory" areas during sustained attention (late CNV). Additional "pre-mature" activation e.g., in the locus coeruleus (leading to diffuse cortical activation summing up to a maximum over the vertex) or the basal ganglia (interacting with SMA) explained the rather stereotyped CNV elevation around the vertex better than a specific implication of the cortical systems responsible for orienting, motor preparation or sensory attention.

Brain Mapping↗

PubMed2006

Frontal lobe involvement in the processing of meaningful auditory stimuli develops during childhood and adolescence.

Auditory event-related N1b reflects attention-related processing in bilateral temporal auditory cortex. Frontal contributions indicating an orienting reaction have been suggested. We analyzed the maturation of frontal contributions to the auditory event-related potential following the warning stimulus in a contingent negative variation (CNV) task by high-resolution current source density mapping and spatio-temporal source analysis in 80 healthy subjects and 121 primary headache patients (migraine with/without aura, tension type headache) from 6 to 18 years; as increased orienting responses and disturbed maturation have been described in migraineurs. A selective local increase of N1b with age occurred at mid-frontocentral leads. This increase could not be explained sufficiently by overlapping bilateral temporal sources but pointed towards additional frontal activation over the supplementary motor area (SMA) in adolescents which was absent in children. A second frontal N1 component peaked about 50 ms later, showed an earlier maturation and has been suggested to reflect early response selection processes in the anterior cingulate. Primary headache patients showed the same component structure and developmental trajectory as healthy subjects without significant influences of differential diagnosis. We conclude that: (1) Brain maturation crucially influences N1b. (2) Two frontal lobe N1 components can be dissociated in their maturational trajectory. (3) Early SMA activation could be elicited by rare auditory stimuli from about 12 years on, allowing fast sensory-motor coupling without previous categorical stimulus classification. (4) Primary headache patients did not differ in their maturation of frontal or temporal contributions to N1b when elicited by moderately loud short tone bursts.

Acoustic Stimulation↗

PubMed2006

Stroop performance in depressive patients: a preliminary report.

BACKGROUND: The Stroop interference test requires executive control functions, in particular inhibition of a learned routine (in this case word reading). Depressive patients show deficits on tests of executive function. However, the impact of confounding variables like type of depression and anxiety level is not yet elucidated for depressive patients. This is of clinical importance, since executive functions seem to play an important role in predicting treatment response and functional outcome. METHODS: 23 depressive patients and 27 healthy subjects performed a computerized mixed trial Stroop task. Depressive patients were divided according to DSM-IV diagnosis into melancholic and non-melancholic subgroups. Furthermore the level of anxiety was assessed in all subjects. RESULTS: When depressed patients were analyzed as a whole group, they showed only a trend towards higher Stroop interference effect at the beginning of the task. When analysis was performed using according to DSM-IV defined melancholic and non-melancholic subgroups, only non-melancholic patients were impaired in the Stroop task compared to melancholic patients and healthy subjects. LIMITATIONS: The sample size was small resulting in low statistical power. Furthermore, the patients were medicated. CONCLUSIONS: The unexpected result that melancholic patients perform better than non-melancholic ones may be due to their more pronounced rigidity, which makes them more resistant against distraction. Hence, more detailed psychopathological assessment is desirable for future investigations in executive functions of melancholic patients.

Adult↗

PubMed2006

Cortical motor areas are activated early in a characteristic sequence during post-movement processing.

During motor learning in goal-directed reactions, a specific movement has to be associated with feedback about the movement's success. Such feedback often follows when the movement is already over. We investigated the time-course of post-movement cortical motor processing by high-resolution analysis of lateralized post-movement potentials in forewarned and simple reaction time tasks. In both paradigms we could separate a post-movement component (motor postimperative negative variation-mPINV) peaking about 500 ms after the button press (confirmed by electromyogram and accelerometer). mPINV could not be sufficiently explained by motor cortex activity related to EMG output and/or by sensory feedback. mPINV was enhanced by long intertrial intervals and its lateralization changed with response movement side. Its scalp potential distribution resembled (pre-)motor cortex activity during preceding movement stages and differed from the frontal motor potential peak (proprioceptive and somatosensory reafferent feedback); suggesting post-movement activation of pre-/primary motor cortex. Dipole source analysis yielded a single radial source near premotor cortex which explained lateralized mPINV almost completely. mPINV was present in simple reaction time tasks, indicating that mPINV is an independent component and does not represent delayed resolution of pre-movement negativity. An equivalent of "classical" PINV (cPINV) occurred later over prefrontal and anterior temporal sites in simple and forewarned reaction time tasks. Our results suggest that high-resolution analysis of lateralized movement-related potentials allows to image post-movement motor cortex activity and might provide insights into basic mechanisms of motor learning: A characteristic sequence might involve motor cortex activation (mPINV) before "higher order associative areas" come into play (cPINV).

Adult↗

PubMed2006

Dopaminergic modulation of semantic priming in healthy volunteers.

BACKGROUND: Semantic priming is a function related to prefrontal cortical (PFC) networks and is lateralized. There is evidence that semantic priming underlies dopaminergic modulation. It is known that the D1-receptor is more abundant in prefrontal networks; however, until now there have been no studies investigating the selective modulation of semantic priming with dopamine agonists. Furthermore, D1 receptor dysfunction has been described in schizophrenia, and patients with formal thought disorder seem to have disturbed focusing of associations and increased indirect priming. METHODS: With a subtraction design, we compared the influence of pergolide (D1/D2 agonist) with bromocriptine (D2 agonist) and placebo, in a randomized, double-blind, crossover design in 40 healthy male volunteers. Subjects performed a lateralized lexical decision task including direct and indirect related prime-target pairs (stimulus onset asynchrony = 750 msec). RESULTS: Only on pergolide a decrease of the indirect priming in the left hemisphere presentations was found. CONCLUSIONS: These findings point to a potential selective modulation of agonists with a D1 component on the focusing of semantic associations. The clinical relevance of this study is that it might help the development of therapeutic strategies for treating cognitive deficits in schizophrenia and Parkinson's disease, which are highly relevant to the functional outcome.

Adult↗

PubMed2005

N2 event-related potential correlates of response inhibition in an auditory Go/Nogo task.

The aim of this study was to investigate the event-related potential correlates of response inhibition in the N2 time window, specifically in the auditory modality. A paired tone Go/Nogo paradigm elicited an enhanced fronto-central negativity in the Nogo condition, which was accompanied by a concurring inferior fronto-temporal positivity. In contrast to most previous studies our data provide evidence for a fronto-central Nogo-N2 component in the auditory modality.

Adult↗

PubMed2005

How do children prepare to react? Imaging maturation of motor preparation and stimulus anticipation by late contingent negative variation.

Both the motor system and the frontal executive control system show a late maturation in humans which continues into school-age and even adolescence. We investigated the maturation of preparation processes towards a fast motor reaction in 74 healthy right-handed children aged 6 to 18 years and analyzed the topography of the late component of contingent negative variation (lCNV) in a 64-electrode high density sensor array. While adolescents from about 12 years on showed a bilaterally distributed centro-parietal maximum like adults do, younger children almost completely missed the negativity over the left central area contralaterally to the side of the anticipated movement. The reason, as revealed by current source density, was that only adolescents showed significant evoked activity of the left pre-/primary motor and supplementary/cingulate motor areas, while in contrast both age groups displayed significant current sinks over the right (ipsilateral) centro-temporal area and right posterior parietal cortex. Spatio-temporal source analysis confirmed that negativity over the right posterior parietal area could not be explained by a projection via volume conduction from frontal areas involved in motor preparation but represented an independent component with a different maturational course most likely related to sensory attention. Significant event-related desynchronization of alpha-power over the contralateral sensorimotor cortex was found in the younger age group, indicating that also 6- to 11-year-old children were engaged in motor preparation. Thus, the missing current sink over the contalateral sensorimotor cortex during late CNV in 6- to 11-year-old children might reflect the immaturity of a specific subcomponent of the motor preparation system which is related to evoked (late CNV) but not induced activity (alpha-ERD).

Adolescent↗

PubMed2005

Response execution in lexical decision tasks obscures sex-specific lateralization effects in language processing: evidence from event-related potential measures during word reading.

A common hypothesis about sex differences in language processing attributes these differences to a bilateral contribution of language-related brain areas in females and a left-hemispheric dominated activation in males. However, most imaging studies failed to find such a generalized lateralization effect and reported a left-lateralized activation in both sexes instead. In a previous semantic priming study, we found a sustained (approximately 190-640 ms) bilateral positivity in the ERP waveforms, which was larger for the female group. Word reading and lexical decision were confounded in that study. In the present study we used a delayed response to separate semantic processing from response selection and execution. The modification of the task design, together with a dense sensor array, showed that females developed a bilateral sustaining posterior positivity/frontal negativity during reading/semantic processing. In contrast, males showed an attenuated positivity at left posterior sites and an attenuated negativity at right frontal sites. This sex-specific lateralization effect disappeared during response processing, evoking a bilaterally distributed activation for both sexes (frontal negative and posterior positive), which was larger for the female subjects. We conclude that, at least under specific conditions, language processing evokes a bilateral activation in females and a lateralization effect in males. However, the processing of the response, which is dominated by a 'P300-like' component evoked by this process, evokes a larger activation in both sexes which obscures the sex-specific lateralization effect when semantic processing and response processing are not separated.

Brain Mapping↗

PubMed2005

SOA-dependent N400 and P300 semantic priming effects using pseudoword primes and a delayed lexical decision.

In a previous semantic priming study, we found a semantic distance effect on the lexical-decision-related P300 when SOA was short (150 ms) only, but no different RT and N400 priming effects between short and long (700 ms) SOAs. To investigate this further, we separated priming from lexical decision, using a delayed lexical decision in the present study. In the short SOA only, primed targets evoked an early peaking (approximately 480 ms) P300-like component, probably because the subject detected the semantic relationship implicitly. We hypothesize that in tasks requiring an immediate lexical decision, this early P300 and the later lexical decision P300 (approximately 600 ms) are additive. Secondly, we found both a direct and an indirect priming effect for both SOAs for the ERP amplitude of the N400 time window. However the N400 component itself was considerably larger in the long SOA than in the short SOA. We interpreted this finding as an ERP correlate for deeper semantic processing in the long SOA, due to increased attention that was provoked by the use of pseudoword primes. In contrast, in the short SOA, subjects might have used a shallowed semantic processing. N400, P300, and RTs are sensitive to semantic priming-but the modulation patterns are not consistent. This raises the question as to which variable reflects an immediate physiological correlate of semantic priming, and which variable reflects co-occurring processes associated with semantic priming.

Adult↗

PubMed2005

Electroencephalographic response to transcranial magnetic stimulation in children: Evidence for giant inhibitory potentials.

The electroencephalographic response to transcranial magnetic stimulation (TMS) recently has been established as a direct parameter of motor cortex excitability. Its N100 component was suggested to reflect an inhibitory response. We investigated influences of cerebral maturation on TMS-evoked N100 in 6- to 10-year-old healthy children. We used a forewarned reaction time (contingent negative variation) task to test the effects of response preparation and sensory attention on N100 amplitude. Single-pulse TMS of motor cortex at 105% motor threshold intensity evoked N100 amplitudes of more than 100 microV in resting children (visible in single trials), which correlated negatively with age and positively with absolute stimulation intensity. During late contingent negative variation, which involves preactivation of the cortical structures necessary for a fast response, N100 amplitude was significantly reduced. We conclude that (1) N100 amplitude reduction during late contingent negative variation provides further evidence that TMS-evoked N100 reflects inhibitory processes, (2) response preparation and attention modulate N100, and (3) TMS-evoked N100 undergoes maturational changes and could serve to test cortical integrity and inhibitory function in children. Parallels between the inhibitory N100 after TMS (provoking massive synchronous excitation) and the inhibitory wave component of epileptic spike wave complexes are suggested.

Adult↗

PubMed2004

Differential dopaminergic modulation of executive control in healthy subjects.

RATIONALE: Executive control (EC) has different subcomponents, e.g., response inhibition (measured, for example, by the Stroop task) and working memory (WM-measured, for example, by delayed response tasks, DRT). EC has been associated with networks involving the prefrontal cortex (PFC). Moreover, there is evidence that dopamine agonists, especially those with a D1 profile, may modulate EC, since in the PFC D1 subtype receptors are more abundant. OBJECTIVE: This study aimed to selectively distinguish whether D1 versus D2 dopamine agonism differentially influences EC related to the inhibition of irrelevant information and WM. Because of its D1 component, we predicted that the administration of pergolide (mixed D1/D2 agonist), in comparison with bromocriptine (D2 selective agonist) and placebo, would enhance performance in both EC tasks. Using a lateralized Stroop task, we predicted a decrease in the interference effect, as well as error rates, while no increase in facilitation effects. For the DRT task, we predicted fewer error scores in the delay condition. METHODS: Forty male healthy subjects participated in this randomized, double-blind, placebo-controlled, crossover study. RESULTS: For the Stroop task no superiority of pergolide was found; however, with bromocriptine, decreased interference was found. No modulation of lateralization effects was shown in interference measures. Moreover, subjects on pergolide showed an absence of facilitation effects. No effects of either agonist were found for the DRT. CONCLUSION: Our findings suggest that dopamine agonists modulate two EC tasks differently. Furthermore, there seems to be a selective modulation of different aspects of the Stroop task.

Adaptation, Psychological↗

PubMed2004

Olfactory impairment in monozygotic twins discordant for schizophrenia.

OBJECTIVE: Several studies demonstrated olfactory dysfunction in patients with schizophrenia, some reported deficient olfaction in unaffected relatives of schizophrenics as well. This study differentially assessed olfactory acuity as well as smell identification and smell discrimination in monozygotic twins discordant for schizophrenia and healthy, monozygotic control twins, to determine the genetic basis of different olfactory modalities and their association to schizophrenia. METHOD: The Sniffin'Sticks test,a comprehensive and standardized olfactory test, was employed to assess the olfactory function of 10 monozygotic twin pairs discordant for schizophrenia versus 10 age- and sexmatched healthy,monozygotic twin pairs. RESULTS: Olfaction of affected monozygotic twins was globally impaired. Partial olfactory impairment of their unaffected co-twins may point to a genetic cause of olfactory impairment in schizophrenia. The influence of genetic factors was most evident for olfactory acuity and least evident for smell identification. All olfactory functions declined with duration of illness. Side of stimulus presentation did not influence olfactory performance. CONCLUSIONS: Genetic factors associated with olfactory dysfunction may contribute to schizophrenia. The degree of the genetic influence on olfaction depends on the olfactory domain under examination.

Adult↗

PubMed2004

Reliability of brain volumes from multicenter MRI acquisition: a calibration study.

Multicenter studies can provide additional information over single center studies because of their increased statistical power. Because similar acquisition protocols are being used internationally for structural magnetic resonance imaging (MRI) studies of the human brain, volumetric MRI data studies seem suitable for this purpose. Possible systematic differences between sites should be avoided, however, particularly when subtle differences in tissue volume are being searched for, such as in neuropsychiatric diseases. In this calibration study, the brains of six healthy volunteers were (re)scanned with MR scanners from four different manufacturers at five different sites, using the local acquisition protocols. The images were segmented at a central reference site. The intraclass correlation coefficient (ICC) was determined for the whole brain, gray and white matter, cerebellum, and lateral and third ventricle volumes. When required, the processing algorithms were calibrated for each site. Calibration of the histogram analysis was needed for segmentation of total brain volume at one site and for gray and white matter volume at all sites. No (additional) calibration was needed for cerebellum and ventricle volumes. The ICCs were > or = 0.96 for total brain, > or = 0.92 for cerebellum, > or = 0.96 for lateral ventricle, > or = 0.21 for third ventricle, > or = 0.84 for gray matter, and > or = 0.78 for white matter volume. Calibration of segmentation procedures allows morphologic MRI data acquired at different research sites to be combined reliably in multicenter studies.

Adult↗

PubMed2004

Specific task anticipation versus unspecific orienting reaction during early contingent negative variation.

OBJECTIVE: To investigate whether a warning stimulus in a forewarned reaction time task elicits only an unspecific orienting reaction or task specific motor cortex activity. METHODS: We examined the time-course of alpha event-related desynchronization (ERD) as an indicator for primary motor cortex activation in an auditory contingent negative variation (CNV) paradigm with an interstimulus interval of 3 s in healthy subjects between 6 and 18 years using a 64 channel high-density sensor array. RESULTS: We replicated a wide frontal distribution for the initial CNV component (iCNV), while only during late CNV (lCNV) a centro-parietal negativity resembling the 'Bereitschaftspotential' occurred. However, an early alpha-ERD over the central area contralateral to the side of the response movement followed the imperative stimulus already during the iCNV-interval. This early alpha-ERD was highly significantly lateralised and was even more prominent during iCNV than during lCNV indicating an activation of the contralateral sensorimotor cortex already during iCNV. CONCLUSIONS: We conclude that early task specific preparatory motor processes (which might reflect the retrieval of a motor program from memory) were elicited by the warning stimulus. These preparatory processes clearly exceeded an unspecific orienting reaction as early alpha-ERD was influenced by the side of the anticipated movement.

Acoustic Stimulation↗

PubMed2004

Prefrontal-cingulate activation during executive control: which comes first?

The Stroop test requires executive control functions, in particular inhibition of a learned routine (in this case, word reading). The spatiotemporal analysis of brain activation during Stroop task execution was performed in 16 healthy subjects using high-density event-related potentials (ERPs) and dipole source modeling (BESA software). Scalp ERP analysis revealed the neurophysiological substrate of the interference effect: first, a greater negativity in the incongruent as compared to the congruent and neutral conditions was found between 350 and 450 ms poststimulus over left frontocentral scalp regions. Source analysis of the difference wave (incongruent-congruent) indicated that a generator localized in left prefrontal cortex (PFC) contributed to this effect. Second, immediately after the first effect, a greater positivity in the incongruent as compared to the congruent and neutral conditions developed between 450 and 550 ms poststimulus over midline frontocentral scalp regions. A generator of this effect was located in right anterior cingulate cortex (ACC). ACC activation seems to follow the activation of PFC with some overlap between the two components. Possible interpretation of this finding is that PFC signals ACC when executive control is required and ACC implements the control.

Adult↗

PubMed2004

The similarity of brain morphology in healthy monozygotic twins.

Aim of the study was to investigate the degree of similarity of twin brains with respect to their outer shape and gyrification. High resolution MRI was obtained from 26 healthy monozygotic twins (MZ) and three-dimensional renderings of the brains were generated. Similarity was rated by human investigators and by computer analysis. Three different image types were analyzed: whole-brain views, silhouettes and a bird's-eye view of a segment showing the central region. For each of the three image types, 13 tasks (identifying the related twin-pair out of a set of five brains) had to be solved by the human raters. For whole brain, views and silhouettes 66/91(p<0.005) and for segment views 44/91 (p<0.02) correct identifications were made. Using cross correlation coefficients, the computer-based analysis as well significantly often identified related twins. Again correct identification was more likely based on whole-brain views and silhouettes than on segment views of the central region. In conclusion, we found that overall brain shape is probably strongly influenced by genetic effects but the variation in sulcal and gyral patterns is also affected by non-genetic influences to a considerable extent.

Adult↗

PubMed2004

Motor processing after movement execution as revealed by evoked and induced activity.

Event-related synchronization (ERS) in the beta frequency band following movement execution has shown that motor processing is not completed yet when a movement ends. It is known that induced and evoked activities reflect different aspects of cortical processing which may result in different time courses. In the current study, we analyzed topography of postimperative negative variation (PINV) in 39 healthy right-handed adolescents in an acoustic forewarned reaction time (contingent negative variation, CNV) task using a 64-electrode high-density sensor array. We dissociated different PINV components in their time course from postmovement beta ERS in order to provide fundamental knowledge about evoked and induced EEG components after movement execution as a basis for further analysis of postmovement processing. A postmovement negativity occurred from about 500 to 1200 ms after the imperative stimulus (peaking about 600 ms after a right-hand button press) at central electrodes, contralateral to the response movement side. Current source density (CSD) analysis confirmed the current sinks over motor areas [contralateral primary motor/premotor and supplementary/cingulate motor area]. The described DC component (motor PINV, mPINV) differed in time course and localization from later "classical" PINV (cPINV) which is thought to reflect contingency reappraisal. mPINV could also be distinguished topographically from a mere delayed CNV resolution. When mPINV and ERS at the same left central electrode were compared, both parameters showed different time courses. Left central mPINV rather paralleled ERS at midcentral electrodes. Therefore, we suggest that the topography of mPINV provides first hints towards an involvement of contralateral primary motor cortex in postmovement processing beyond a mere idling state as reflected by later beta ERS. mPINV could be a useful tool to investigate the role of primary motor cortex in motor-learning processes. The combined analysis of induced and evoked activities seems to be able to elucidate different aspects of cortical connectivity and motor processes following movement.

Acoustic Stimulation↗

PubMed2004

Pattern-reversal visual-evoked potentials in children with migraine and other primary headache: evidence for maturation disorder?

Recently, evidence for a disturbed maturation of cerebral information processing in migraine came from studies investigating the auditory-evoked contingent negative variation and the auditory-evoked potential from childhood to adulthood. This study is to clarify whether age-dependent development is altered also for the processing of visual stimuli in migraine. Components of pattern-reversal visual-evoked potentials at four different spatial frequencies (which can preferentially activate the magno- and the parvocellular visual system) were compared between children aged 6 and 18 years with primary headache (N = 123; 67 migraine without aura, MO; 32 migraine with aura, MA; 24 tension-type headache, TH) in the headache-free interval and healthy controls (N = 82). Children were divided into two age groups: 6-11 years (pre- and early puberty) and 12-18 years (late and post-puberty). Age-dependent development was normal for N80 and P100 latency in children with primary headache, but altered for N135 latency as indicated by a significant interaction among the factors diagnosis, spatial frequency and age group (P < 0.01). In headache-free controls, N135 latency reduction between pre- and post-puberty age was most pronounced at high spatial frequency. The main 'decline' of N135 latency with increasing age was shifted to lower spatial frequencies in the headache subgroups. The results give evidence that maturation of visual processing is partly disturbed in migraineurs.

Adolescent↗