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S Knecht

Publications and source records attributed to S Knecht.

At least 19 recordsLinked to original sources

Language lateralization in healthy right-handers.

Our knowledge about the variability of cerebral language lateralization is derived from studies of patients with brain lesions and thus possible secondary reorganization of cerebral functions. In healthy right-handed subjects 'atypical', i.e. right hemisphere language dominance, has generally been assumed to be exceedingly rare. To test this assumption we measured language lateralization in 188 healthy subjects with moderate and strong right-handedness (59% females) by a new non-invasive, quantitative technique previously validated by direct comparison with the intracarotid amobarbital procedure. During a word generation task the averaged hemispheric perfusion differences within the territories of the middle cerebral arteries were determined. (i) The natural distribution of language lateralization was found to occur along a bimodal continuum. (ii) Lateralization was equivalent in men and women. (iii) Right hemisphere dominance was found in 7.5% of subjects. These findings indicate that atypical language dominance in healthy right-handed subjects of either sex is considerably more common than previously suspected.

Adolescent

Cortical asymmetries of the human somatosensory hand representation in right- and left-handers.

Hemispheric asymmetry is known for higher brain functions like language and attention. We tested whether such an asymmetry also exists in the representation of elementary sensory functions. Magnetic source imaging was used to compare the cortical somatosensory hand representation in seven right- and five left-handed individuals. In all right-handers the representation of the dominant hand was larger than the contralateral one in the corresponding hemispheres. In contrast, only two out of five left-handers revealed a larger representation of the dominant left hand compared to the right one. In agreement with previous findings on the lateralization of language and attention, there is a strong correlation between handedness and the extent of the cortical hand representation in right-, but not in left-handers. We conclude that a profound functional hemispheric asymmetry also exists in primary sensory cortices.

Adult

Cortical tuning: a function of anticipated stimulus intensity.

We investigated the activation of the brain during anticipation of tactile stimuli by continuous cerebral blood flow velocity (CBFV) monitoring with bilateral transcranial Doppler sonography. A forced choice paradigm was performed where a first group of subjects (n=16) was expecting suprathreshold and a second group (n=19) was anticipating threshold tactile stimuli to the index finger after a cueing tone. During the anticipation of suprathreshold stimuli the CBFV always exhibited a significantly stronger increase in the right hemisphere than in the left, even when stimuli were anticipated at the right index finger. Conversely when stimuli at perception threshold were expected, the respective contralateral hemisphere showed a significantly stronger perfusion increase. These data show that preparatory activation of the brain during stimulus anticipation is dependant on the expected stimulus intensity.

Acoustic Stimulation

[Neuronal plasticity exemplified by the somatosensory system].

The mammalian brain is capable of a substantial functional reorganization, manifesting on a cortical somatotopical and on a behavioral level. Possible mechanisms are reviewed based on the work by others and ourselves on somatosensory reorganization in humans. The somatosensory system is characterized by divergent projections from the periphery to the cerebral cortex. Changes in synaptic weights allow for reorganization of sensory processing: On one side, limb amputation will result in a representational "invasion" of the differentiated cortex from neighboring regions with concomitant perceptual changes. On the other side, sensorimotor training can increase the representational cortical zone of a limb. Plastic changes can be temporary or persistent. Modulating factors like pain and certain drugs seem to induce a permissive state in the cortex resulting in enhanced reorganization. Thus, specific physical training combined with pharmacoceutical modulation holds promise to improve functional recovery after brain lesions.

Afferent Pathways

Clinical applications of functional MRI at 1.0 T: motor and language studies in healthy subjects and patients.

In this article we describe clinical applications of functional MRI (fMRI) at 1.0 T. All experiments were performed on a commercially available 1.0-T system (Magnetom Impact Expert, Siemens AG, Erlangen, Germany) using a blood oxygen level-dependent (BOLD)-sensitive multi-slice EPI technique (TE 66 ms, 4 mm slice thickness, 210 mm field of view, 64 x 64 acquisition matrix). Different paradigms for localization of the motor cortex and for language lateralization were tested in healthy subjects and patients. Methodological considerations concerning the development of the paradigms are also described. In all healthy subjects, motor activation elicited BOLD signal changes in the sensorimotor cortex, permitting identification of primary motor and sensory cortical areas. Furthermore, focal activation of different cortical areas by a language task was possible in 6 of 10 subjects. Nineteen motor studies were performed in 18 patients with supratentorial lesions, in most cases prior to neurosurgical procedures. In 14 studies, fMRI results demonstrated the localization of the motor hand areas relative to the lesion. The results proved valuable for preoperative planning and contributed to therapeutical decisions. We conclude that functional MRI for clinically relevant applications, such as localization of motor and language function, is feasible even at a field strength of 1.0 T without dedicated equipment.

Adult

Molecular characterization of a novel, widespread nuclear protein that colocalizes with spliceosome components.

We report the identification and molecular characterization of a novel type of constitutive nuclear protein that is present in diverse vertebrate species, from Xenopus laevis to human. The cDNA-deduced amino acid sequence of the Xenopus protein defines a polypeptide of a calculated mass of 146.2 kDa and a isoelectric point of 6.8, with a conspicuous domain enriched in the dipeptide TP (threonine-proline) near its amino terminus. Immunolocalization studies in cultured cells and tissues sections of different origin revealed an exclusive nuclear localization of the protein. The protein is diffusely distributed in the nucleoplasm but concentrated in nuclear speckles, which represent a subnuclear compartment enriched in small nuclear ribonucleoprotein particles and other splicing factors, as confirmed by colocalization with certain splicing factors and Sm proteins. During mitosis, when transcription and splicing are downregulated, the protein is released from the nuclear speckles and transiently dispersed throughout the cytoplasm. Biochemical experiments have shown that the protein is recovered in a approximately 12S complex, and gel filtration studies confirm that the protein is part of a large particle. Immunoprecipitation and Western blot analysis of chromatographic fractions enriched in human U2 small nuclear ribonucleoprotein particles of distinct sizes (12S, 15S, and 17S), reflecting their variable association with splicing factors SF3a and SF3b, strongly suggests that the 146-kDa protein reported here is a constituent of the SF3b complex.

Amino Acid Sequence

Plasticity of plasticity? Changes in the pattern of perceptual correlates of reorganization after amputation.

We report a follow-up study on seven arm amputees in whom magnetic source imaging had originally revealed a strong correlation between the amount of cortical invasion of the deafferented cortex and the amount of pain evoked sensation mislocalized to the phantom limb. This re-examination was performed in order to corroborate the phenomenon of mislocalization. On follow-up examination for mislocalization 4 weeks later, a close correlation had remained between the original amount of cortical representational reorganization of the amputation zone (at the first examination) and the number of sites from where painful stimuli evoked sensations referred to the phantom limb, i.e. the amount of perceptual mislocalization, at the second examination. However, contrary to our expectation, the topography of referred sensation had completely changed in every patient. These results suggest that while the overall extent of reorganization is a rather stable phenomenon, the concomitant changes in the pattern of sensory processing are not. This may be due to the fact that alterations of sensory processing are not hardwired, but are rather mediated by an extensive and interconnected neural network with fluctuating synaptic strengths. This mechanism may be of importance for neurological rehabilitation.

Accidents

Cerebral hemodynamic response to generalized spike-wave discharges.

PURPOSE: Data in the literature concerning metabolic demand during generalized spike-wave activity (gSW) are conflicting. We investigated instantaneous changes in cerebral blood flow velocities (CBFV) in both middle cerebral arteries (MCAs) by transcranial Doppler sonography (TCD) during gSW paroxysms recorded by scalp EEG. METHODS: In 13 patients, CBFVs in both MCAs were averaged, time-locked to the occurrence of the gSW; respiratory rate (RR) and end-expiratory pco2 were measured in one patient. RESULTS: Nine patients showed significant changes in CBFV during gSW. Four had biphasic flow changes with an initial increase (p < 0.05) and a subsequent decrease (p < 0.01). This was partially paralleled by an increase in RR (p < 0.01) and a decrease in pco2 (p < 0.01). In three patients, an increase in CBFV that preceded the onset of gSW by several seconds was observed, followed by a decrease in CBFV. Two patients showed a significant decrease only of CBFV. Only gSWs of a median duration of >0.8 s were associated with significant changes in CBFV. CONCLUSIONS: We were able to demonstrate that gSWs of several seconds duration lead to cortical perfusion changes. We suggest that the initial increase of CBFV demonstrated in some patients reflects neuronal activation, whereas the subsequent decrease might in part be due to hyperventilation-induced hypocapnia.

Adult

Noninvasive determination of language lateralization by functional transcranial Doppler sonography: a comparison with the Wada test.

BACKGROUND AND PURPOSE: Functional transcranial Doppler ultrasonography (fTCD) can assess event-related changes in cerebral blood flow velocities and, by comparison between sides, can provide a measure of hemispheric perfusional lateralization. It is easily applicable, insensitive to movement artifacts, and can be used in patients with less than perfect cooperation. In the present study we investigated the validity of fTCD in determining the hemispheric dominance for language by direct comparison of fTCD with intracarotid amobarbital anesthesia (Wada test). METHODS: fTCD and the Wada test were performed in 19 patients evaluated for epilepsy surgery. By the Wada test, 13 patients were classified as left-hemisphere dominant and 6 as right-hemisphere dominant for language. fTCD was based on the continuous bilateral measurements of blood flow velocities in the middle cerebral arteries and event-related averaging during a cued word generation task previously shown to activate lateralized language areas in normal adults. RESULTS: In 4 patients fTCD assessment was not possible because of lack of an acoustic temporal bone window. In the remaining 15 candidates, determination of language dominance was concordant with the Wada test in every case. Moreover, the correlation of the lateralization measures from both procedures was highly significant (r=.92, P<.0001). CONCLUSIONS: This strong correlation validates fTCD as a noninvasive and practical tool for the determination of language lateralization that can be applied for clinical and investigative purposes.

Adolescent

Reproducibility of functional transcranial Doppler sonography in determining hemispheric language lateralization.

BACKGROUND AND PURPOSE: Since functional transcranial Doppler ultrasonography (fTCD) allows convenient and fully automated quantification of language lateralization, it seems ideal for longitudinal studies of perfusion changes during deterioration as well as recovery of language functions. However, during serial examinations, the technical, stochastic, and physiological variabilities of cerebral blood flow velocities (CBFV) have to be considered. Therefore, before fTCD is accepted as a tool for evaluation of changes in lateralization in the diseased state, its reliability in healthy subjects needs to be determined. METHODS: We performed fTCD during a word generation task based on a previously validated technique with automated calculation of the averaged CBFV differences in the middle cerebral arteries providing an index of lateralization (LI). RESULTS: (1) The accuracy of the LI as assessed by the confidence interval was better than 1% of the mean hemispheric difference. (2) On repeated examination, LIs obtained from 10 subjects showed a high test-retest reproducibility (Pearson product moment correlation coefficient r = 0.95, P < 0.0001). (3) On 10 repeated assessments of LI in the same subject, no practice effects were detected. CONCLUSIONS: Functional TCD is a suitable and very robust tool for the longitudinal quantitative measurement of cerebral language lateralization.

Adult

AVERAGE: a Windows program for automated analysis of event related cerebral blood flow.

Functional transcranial Doppler sonography (fTCD) is used to measure changes in brain perfusion during different states of brain activity by evaluating flow velocities within the major brain arteries. We developed a computer program called AVERAGE which can be used with various TCD devices and allows for subtle quantitative off-line analysis of Doppler flow signals. AVERAGE supports data transformation, heart beat analysis, noise reduction, trigger signal and marker modification, artifact analysis and artifact rejection, as well as data reduction. Perfusion differences and their time course within two different arteries can be analyzed by parametric and non parametric statistical methods. This is important, for instance, in studies on hemispherical dominance during mental task processing. Each data processing step is supported by graphical output. If investigated bilaterally with interhemispheric analysis even minimal activations can reliably be detected and quantified with a sensitivity known from positron emission tomography approaches.

Attention

Influence of afferent feedback on isometric fine force resolution in humans.

The influence of afferent feedback on isometric fine force resolution was studied in humans. Subjects performed the smallest possible isometric flexion force increments with the index finger while visual, cutaneous, and muscle spindle feedback conditions were varied. In the control conditions with visual feedback, isometric force resolution was finest and independent of cutaneous or muscle spindle feedback. In the absence of visual cues, force resolution was significantly coarser. When agonist muscle spindles were vibrated (100 Hz and 150 Hz), fine force resolution capabilities declined further. Diminution of cutaneous feedback per se did not affect fine force resolution. However, the effect of agonist vibration was attenuated when full cutaneous feedback was available. We conclude that in voluntary isometric contractions the degree of fine force resolution depends on the type of afferent feedback available for calibrating central motor commands. Visual feedback is more powerful than spindle feedback, which is more efficient than cutaneous feedback. The extent to which the central motor command itself contributes to the sensation of force is indirectly implied by reproducible, yet coarser force resolution levels when peripheral information is minimized.

Adult

Regional cerebral blood flow increases during preparation for and processing of sensory stimuli.

Preparing for and processing of sensory stimuli are energy-requiring processes. We attempted to assess the relative contributions of these processes to increases in regional cerebral perfusion. Nineteen healthy right-handed subjects were examined while they were engaged in detecting tactile stimuli to the index finger 5 s after a cueing tone. Cerebral blood flow velocity (CBFV) modulations in the middle cerebral arteries (MCAs) were continuously measured by bilateral simultaneous transcranial Doppler ultrasonography. Tactile stimuli well above threshold per se did not produce a significant, relative CBFV increase in the contralateral MCA. However, when subjects were expecting a threshold tactile stimulus, there was a significant regional increase in CBFV in the hemisphere contralateral to the attended index finger for approximately 15 s, starting within the first seconds after the cueing. This increase was present even before the tactile stimulus was applied and also in sessions when the stimulus was omitted. We conclude that preparation of the cortex causes a stronger regional cerebral blood flow increase than the processing of the tactile stimulus itself.

Adult

Input-increase and input-decrease types of cortical reorganization after upper extremity amputation in humans.

A plastic remodeling of regions in somatosensory cortex has previously been observed to occur in separate experimental paradigms in response to loss of somatosensory input and to increase in input. In this study, both types of cortical reorganization have been observed to occur concurrently in the same adult human nervous system as a result of a single intervention. Following upper extremity amputation, magnetic source imaging revealed that tactile stimulation of the lip evoked responses not only in the area of the somatosensory cortex corresponding to the face, but also within the cortical region that would normally correspond to the now absent hand. This "invasion" of the cortical amputation zone was accompanied by a significant increase in the size of the representation of the digits of the intact hand, presumably as a result of an increased importance of sensory stimulation consequent to increased dependence on that hand imposed by the loss of the contralateral extremity.

Adolescent

Persistent unihemispheric perceptual impairments in humans following focal seizures.

Perception has been linked to a highly coordinated activation of cortical regions whose functional organization and performance is subject to plastic changes. We tested whether chronic repetitive disturbances of the brain by focal epileptic activity have a long-standing detrimental effect on the perceptual performance in the affected hemisphere. Nine patients were examined who had a history of complex partial seizures but no structural cerebral damage on magnetic resonance imaging and no evidence of ongoing epileptic activity on scalp electroencephalography and who had clinically been without seizures for at least 3 days. The side of primary epileptic involvement was determined by seizure semiology (n = 2), focal electroencephalographic slowing (n = 3) or focal abnormality during single photon emission topography (SPECT) (n = 4). The computer controlled psychometric assessment of the somesthetic frequency discrimination revealed that the perception in the hand corresponding to the affected hemisphere was impaired relative to the contralateral hand (P < 0.01), and to the performance of a group of normal controls (P < 0.01). We conclude that mechanisms related to focal epileptic activity can result in regional perceptual decrements even when there is no clinical or surface-electroencephalographic evidence of epileptic discharges. This in turn suggests that somatosensory testing may be of help in localizing, or at least lateralizing an epileptic focus.

Adult

Successive activation of both cerebral hemispheres during cued word generation.

Most humans have a left hemispheric dominance for language. However, during diagnostic language testing there also is activation of the right hemisphere, which is probably related to attention. To investigate further the role of attention during language production we monitored cerebral blood flow velocities in the middle cerebral arteries by continuous bilateral transcranial Doppler ultrasonography (TCD) in nine right-handed subjects. During cued word generation, a successive activation of the right hemisphere in the preparatory phase, and of the left hemisphere during word searching was demonstrated. These findings indicate that attentional processes precede verbal activation and that the two procedures can be separated by comparative blood flow velocity measurement.

Acoustic Stimulation

Parallel and serial processing of haptic information in man: effects of parietal lesions on sensorimotor hand function.

Recent animal studies have shown that there is an evolutionary shift within the order of primates from parallel to serial processing of haptic information. In an attempt to determine whether there is also evidence of serial processing in humans 10 patients with parietal cortical lesions, three patients with subcortical lesions and one patient after hemispherectomy, were examined. Case-by-case and across subject analysis of lesion type, sensorimotor profile and electrophysiological findings showed that in unihemispheric lesions: (a) there is little impairment of thermesthesia, nociception and vibration sense: (b) two-point discrimination and integrity of the N20 somatosensory component are highly correlated; (c) a loss of the N20 component is accompanied by a severe impairment of stereognosis; (d) conversely, in more posterior lesions astereognosis can occur with an intact N20 component; and (e) if the lesion is in the right hemisphere there is frequently impairment of graphesthesia in both hands. These data are taken to indicate serial processing from SI (as evidenced by an intact N20 component) to posterior parietal cortex allowing progressive spatial and temporal integration. In graphesthesia our data suggest an integrative function of the right parietal cortex for both sides of the body. Other sensory qualities like vibration nociception and thermesthesia are apparently processed in a non-serial, probably parallel way involving both hemispheres. The effects of cerebral lesions in our series suggest parallel as well as serial processing of somesthetic information in man underlying the perception of different haptic features.

Adult