Biomedical subjects

S Knecht

Publications and source records attributed to S Knecht.

At least 19 recordsLinked to original sources

PubMed1999

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↗

PubMed1999

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1996

Reorganizational and perceptional changes after amputation.

The demonstration of cortical representational shifts in adult animals subsequent to deafferentation from amputation or dorsal rhizotomy has spurred attempts to elucidate the perceptual correlates of reorganization. Because the hand is flanked by the face and the trunk on the cortical homunculus it has been suggested that cortical remapping in arm amputees leads to a mislocalization of sensations from these sites to the phantom arm in a systematic manner with modality specific one-to-one topographical correspondence. Therefore, we assessed shifts of representational zones by magnetic source imaging in eight arm-amputees and examined them for referred sensation by somaesthetic stimuli of different modalities at standardized sites. It was found that referred phantom sensations can be evoked from sites on the face and the trunk ipsilateral but also contralateral to the amputation and that the extent of physiological reorganization as revealed by magnetic source imaging strongly correlates with the number of sites, be it ipsi- or contralateral, from where painful stimuli evoke referred sensation. Thus, it seems that the extent of reorganization after amputation is closely related to nociceptive inputs. The mislocalization evoked from both sides of the body, suggesting involvement of bilateral pathways, demonstrates that the perceptual changes go beyond what can be explained by shifts in neighbouring cortical representational zones.

Adult↗

PubMed1995

Cortical reorganization in human amputees and mislocalization of painful stimuli to the phantom limb.

In human arm amputees, a significant relationship was found between the amount of reorganization in the primary somato-sensory cortex, and the amount of body surface from which painful stimuli evoked sensations that were perceived to be emanating from the now missing extremity, i.e. the phantom limb. This mislocalization could be evoked almost equally from stimulation of either side of the body. Based on these findings obtained by magnetic source imaging and psychophysical testing in eight amputees, it is concluded that the extent of the generally known cortical reorganization contralateral to the amputation is an indicator of more widespread plastic changes in the brain involving bilateral pathways.

Adult↗

PubMed1995

Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation.

Although phantom-limb pain is a frequent consequence of the amputation of an extremity, little is known about its origin. On the basis of the demonstration of substantial plasticity of the somatosensory cortex after amputation or somatosensory deafferentation in adult monkeys, it has been suggested that cortical reorganization could account for some non-painful phantom-limb phenomena in amputees and that cortical reorganization has an adaptive (that is, pain-preventing) function. Theoretical and empirical work on chronic back pain has revealed a positive relationship between the amount of cortical alteration and the magnitude of pain, so we predicted that cortical reorganization and phantom-limb pain should be positively related. Using non-invasive neuromagnetic imaging techniques to determine cortical reorganization in humans, we report a very strong direct relationship (r = 0.93) between the amount of cortical reorganization and the magnitude of phantom limb pain (but not non-painful phantom phenomena) experienced after arm amputation. These data indicate that phantom-limb pain is related to, and may be a consequence of, plastic changes in primary somatosensory cortex.

Adult↗

PubMed1995

Altered force release control in Parkinson's disease.

Isometric force tracking and force aiming modified by visual feed-back was investigated in Parkinsonian (PD) and control subjects. Production and maintenance of isometric force, production and release of isotonic force, and maximum force were tested. Statistical analysis revealed that the PD patients could perform most force tasks in a similar manner to that of control subjects. However, PD patients had difficulties in sustaining target force over a 30-s period and in performing rapid alternating movements. The major finding in PD patients was an inability to precisely release a target force. Overall these data suggest that the release of a produced force is a sensitive motor control parameter in Parkinson's disease.

Adult↗