Bilateral medullary pyramid infarction.
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Biomedical subjects
Publications and source records attributed to Rüdiger J Seitz.
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Both optokinetic nystagmus (OKN) and smooth-pursuit eye movements (SPEM) are subclasses of so-called slow eye movements. However, optokinetic responses are reflexive whereas smooth pursuit requires the voluntary tracking of a moving target. We used functional magnetic resonance imaging (fMRI) to determine the neural basis of OKN and SPEM, and to uncover whether the two underlying neural systems overlap or are independent at the cortical level. The results showed a largely overlapping neural circuitry. A direct comparison between activity during the execution of OKN and SPEM yielded no oculomotor-related area exclusively dedicated to one or the other eye movement type. Furthermore, the performance of SPEM evoked a bilateral deactivation of the human equivalent of the parietoinsular vestibular cortex. This finding might indicate that the reciprocally inhibitory visual-vestibular interaction involves not only OKN but also SPEM, which are both linked with the encoding of object-motion and self-motion. Moreover, we could show differential activation patterns elicited by look-nystagmus and stare-nystagmus. Look-nystagmus is characterized by large amplitudes and low-frequency resetting eye movements rather resembling SPEM. Look-nystagmus evoked activity in cortical oculomotor centers. By contrast, stare-nystagmus is usually characterized as being more reflexive in nature and as showing smaller amplitudes and higher frequency resetting eye movements. Stare-nystagmus failed to elicit significant signal changes in the same regions as look-nystagmus/SPEM. Thus, less reflexive eye movements correlated with more pronounced signal intensity. Finally, on the basis of a general investigation of slow eye movements, we were interested in a cortical differentiation between subtypes of SPEM. We compared activity associated with predictable and unpredictable SPEM as indicated by appropriate visual cues. In general, predictable and unpredictable SPEM share the same neural network, yet information about the direction of an upcoming target movement reduced the cerebral activity level.
The concept of cerebral plasticity suggests that the hand representation in somatosensory cortex is abnormal in congenital malformation disorders. To investigate this issue we studied 11 subjects with different degrees of upper extremity dysmelia due to thalidomide embryopathy in comparison to 10 control subjects. In the affected subjects fingers are typically missing in radio-ulnar order beginning with the thumb. Haemodynamic responses to electrical stimulation of the radial-most and ulnar-most fingers were measured in each subject using functional magnetic resonance tomography. The size of the hand area in the primary somatosensory cortex was estimated by calculating the Euclidian distance between corresponding activation peaks on the lateral postcentral gyrus. The cortical somatosensory hand representation was found to be significantly smaller in dysmelic subjects as compared with the control subjects (P <0.001). The shrinkage of the hand area was not proportional to the number of missing fingers. Furthermore, the cortical representation of the ulnar fingers in the dysmelic subjects was shifted towards the cortical thumb representation of the control group. We suggest that the unproportional reduction of the hand area together with the observed shift may reflect use-dependent rather than malformation-induced reorganization of the somatosensory hand area.
BACKGROUND: The BOLD signal in functional MRI (fMRI) is closely related to neural activity. OBJECTIVE: To investigate if this relationship is disrupted after ischemic stroke. METHODS: BOLD activity during tactile exploration of objects was measured with fMRI at 1 week (subacute), 2 to 4 weeks (early chronic), and after 1 month (chronic) after the first completed brain infarction affecting the sensorimotor cortex in eight patients. Functional integrity of the motor cortical output system was assessed with transcranial magnetic stimulation (TMS). RESULTS: Early after infarction the BOLD-response occurred in the adjacent cortical vicinity related to finger movements of the affected hand. However, during the early chronic stage there was a transient lack of this activation despite clinical improvement of hand function and preserved motor evoked potentials. The BOLD activity reappeared after further improvement in the chronic stage. CONCLUSIONS: Our findings suggest a transient hemodynamic-electrical decoupling in the post-ischemic cerebral cortex during the early phase of spontaneous clinical recovery.
The effect of peripheral lesions on cerebral somatosensory representations is well studied for experimentally induced amputations and deafferentations acquired later in life. However, few studies have investigated the brain's capacity for plastic changes in congenital malformations. We studied somatosensory-evoked fields to electrical stimulation of the bordering fingers in 10 subjects with upper extremity dysmelia in comparison with 10 control subjects using a 122-channel whole-head magnetometer. The number of developed fingers varied between two and four in the affected subjects. We localized finger representations in the primary somatosensory cortex and calculated Euclidian distances to estimate the size of the somatosensory hand area. Euclidian distances were significantly smaller in dysmelic subjects (5.7 mm) than in control subjects (11.6 mm) and were related to the number of the developed fingers on the contralateral hand. In contrast, individual finger representations were not found to be reduced. We suggest that the shrinkage of the somatosensory hand area might be related to the congenital nature of the malformation, to the smaller anatomical hand size in the affected subjects, and/or to use-dependent effects due to impaired hand function.
When you look into a mirror and move your eyes left to right, you will see that you cannot observe your own eye movements. This demonstrates the phenomenon of saccadic suppression: during saccadic eye movements, visual sensitivity is much reduced. Given that humans make more than 100,000 eye movements each day, it is clear why suppression is needed: without it, the motion on the retina would prevent us from seeing anything at all. Psychophysical data show that suppression is stimulus selective: it is strongest for the kind of stimuli that preferentially activate magnocellular thalamic neurons. This has led to the hypothesis that saccadic suppression selectively targets the magnocellular stream. We used fMRI to find brain areas with a stimulus-selective suppression of the BOLD signal that matches the psychophysical data. We found such a neural correlate of saccadic suppression in the dorsal stream (hMT+, V7) and in ventral area V4. These areas receive magnocellular input; hence our findings are consistent with the magnocellular hypothesis. The range of effects in our data and in single cell data, however, argues against a single thalamic mechanism that suppresses all cortical input. Instead, we speculate that saccadic suppression relies on multiple mechanisms operating in different cortical areas.
BACKGROUND AND PURPOSE: In acute ischemic stroke, thrombolytic treatment with recombinant tissue plasminogen activator (rtPA) is limited by a concomitant activation of the coagulatory system, leading to incomplete or delayed reperfusion, microcirculatory disturbances, or even repeated vessel occlusions. Our pilot study sought to assess the therapeutic potential of a new treatment strategy combining rtPA at reduced dosages with a platelet glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitory agent in acute middle cerebral artery occlusion. METHODS: Nineteen patients suffering from acute middle cerebral artery occlusion (Thrombolysis in Myocardial Infarction [TIMI] flow grade 0 to 1) underwent combined intravenous thrombolytic treatment using rtPA at reduced dosages and the GPIIb/IIIa antagonist tirofiban. Stroke MRI (diffusion- and perfusion-weighted imaging) and MR angiography were performed at baseline and between days 1 and 2 after treatment. Clinical scores (National Institutes of Health Stroke Scale and modified Rankin Scale) were assessed at baseline and after 1 week. RESULTS: Middle cerebral artery recanalization (TIMI flow grade 2 and 3) occurred in 13 of 19 patients (68%). The ischemic lesion on follow-up MRI was significantly smaller in patients with recanalization compared with those without recanalization (P=0.001). Only patients with recanalization improved neurologically (P<0.001). Because no symptomatic hemorrhage was observed, the power of our study to detect a symptomatic bleeding rate of > or =8% was at least 80%. CONCLUSIONS: Combined thrombolysis with a GPIIb/IIIa antagonist and rtPA at reduced dosages is promising but cannot be recommended for general use before prospective randomized clinical trials are completed.
What mechanisms allow us to direct a precise saccade to a remembered target position in space? The cerebellum has been proposed to be involved not only in motor and oculomotor control, but also in perceptual and cognitive functions. We used functional MRI (Echoplanar imaging at 1.5 T) to investigate the role of the cerebellum in the control of externally triggered and internally generated saccadic eye movements of high and low memory impact, in six healthy volunteers. Memory-guided saccades to remembered locations of 3 targets (triple-step saccades) in contrast to either central fixation or to visually guided saccades activated the cerebellar hemispheres predominantly within lobuli VI-crus I. The same areas were activated when an analogous visuospatial working memory task was contrasted to the triple-step saccades. Visually guided saccades activated the posterior vermis and the triple-step saccades, contrasted to the working memory task, activated predominantly the posterior vermis and paravermal regions. Our data confirm the primary involvement of the posterior vermis for visually-triggered saccadic eye movements and present novel evidence for a role of the cerebellar hemispheres in the mnemonic and visuospatial control of memory-guided saccades.
PURPOSE: To investigate the development of ischemic brain lesions, as present in the acute stroke phase, by diffusion-weighted magnetic resonance imaging (DWI), and in the subacute and chronic phases until up to four months after stroke, in fluid-attenuated inversion recovery (FLAIR)- and T2-weighted (T2W) magnetic resonance (MR) images. MATERIALS AND METHODS: Twelve consecutive patients with their first middle cerebral artery (MCA) infarction were included. Lesion volumes were assessed on T2W images recorded with a turbo spin echo (TSE) and on images recorded with the FLAIR sequence on average on day 8 and after about four months. They were compared with acute lesion volumes in perfusion and DWI images taken within 24 hours of stroke onset. RESULTS: On day 8, lesion volumes in images obtained with FLAIR exceeded the acute infarct volumes in DWI. The chronic lesion volumes were almost identical in T2W and FLAIR images but significantly reduced compared with the acute DWI lesions. The lesion volumes assessed on DWI images correlated highly with the lesions in the images obtained with TSE or FLAIR, as did the lesions in the images obtained with FLAIR and TSE. The secondary lesion shrinkage was accompanied by ventricular enlargement and perilesional sulcal widening, as most clearly visible in the images obtained with FLAIR. CONCLUSION: Our results show that the acute DWI lesions are highly predictive for the infarct lesion in the chronic stage after stroke despite a dynamic lesion evolution most evident in MR images obtained with FLAIR.
Over the last few years, several functionally distinct subregions of the posterior parietal cortex (PPC) have been shown to subserve oculomotor control. Since these areas seem to overlap with regions whose activation is related to attention, we used functional magnetic resonance imaging to compare the cerebral activation pattern evoked by eye movements with different attentional loads, i.e., oscillatory saccades with different frequencies, as well as predictable, and unpredictable saccades. Our results show activation in largely overlapping networks with differing strength of activity and symmetry of involved areas. Predictable saccades having the shortest saccadic latency led to the most pronounced cerebral activity both in terms of cortical areas involved and signal intensity. Predictable and unpredictable saccades were dominated by activation within the right hemisphere, whereas oscillatory saccades showing the longest saccadic latency were dominated by activation within the left hemisphere. In all tasks, the centers of gravity of activation occurred within the posterior part of the intraparietal sulcus (IPS), while the predictable saccades additionally activated its anterior part. The enhanced activity during the execution of predictable saccades was probably related to top-down processing and/or the preparation of the upcoming eye movement. The hemispheric difference could arise from a predominant role of the right PPC for shifting spatial attention and the left PPC for shifting temporal attention. The differential encoding of saccadic eye movements within IPS indicates that the PPC splits up into different functional modules related to the particular demands of a saccade.
Following up on an earlier positron emission tomography (PET) experiment (Indefrey et al., 2001), we used a scene description paradigm to investigate whether a posterior inferior frontal region subserving syntactic encoding for speaking is also involved in syntactic parsing during listening. In the language production part of the experiment, subjects described visually presented scenes using either sentences, sequences of noun phrases, or sequences of syntactically unrelated words. In the language comprehension part of the experiment, subjects were auditorily presented with the same kinds of utterances and judged whether they matched the visual scenes. We were able to replicate the previous finding of a region in caudal Broca's area that is sensitive to the complexity of syntactic encoding in language production. In language comprehension, no hemodynamic activation differences due to syntactic complexity were found. Given that correct performance in the judgment task did not require syntactic processing of the auditory stimuli, the results suggest that the degree to which listeners recruit syntactic processing resources in language comprehension may be a function of the syntactic demands of the task or the stimulus material.
The cerebral control of bimanual movements is not completely understood. We investigated a 59-year-old, right-handed man who presented with an acute bimanual coordination deficit. Magnetic resonance imaging showed a lesion involving the entire corpus callosum, which was found on stereotactic biopsy to be an ischemic infarct. Paired-pulse transcranial magnetic stimulation indicated that the patient had a lack of interhemispheric inhibition, while intracortical inhibition in motor cortex of either side was normal. Functional magnetic resonance imaging showed activation of the left SMA, the bilateral motor cortex and anterior cerebellum during spontaneous bimanual thumb-index oppositions, which were uncoupled as evident from simultaneous electromyographic recordings. In contrast, when the bimanual thumb-index oppositions were cued by a visual stimulus, the movements of both hands were tightly correlated. This synchronized activity was accompanied by additional activations bilateral in lateral occipital cortex, dorsal premotor cortex and cerebellum. The data suggest that the visually cued movements of both hands were recoupled by action of a bihemispheric motor network.
BACKGROUND AND PURPOSE: The most important effect of cerebral ischemia is brain infarction. In this magnetic resonance imaging (MRI) study, the authors aimed at assessing postischemic brain atrophy. METHODS: Ten patients suffering from their first acute cerebral ischemia in the territory of the middle cerebral artery were studied retrospectively. Three-dimensional MRI volume scans were recorded in the acute and chronic stage after infarction and analyzed voxel by voxel intraindividually with the newly developed voxel-guided morphometry. RESULTS: Shrinkage of brain tissue was detected in all patients, not only in the perilesional cortical structures but also in contralateral homolog cortex areas and subcortically in the striatum and thalamus. This secondary shrinkage was not related to the size of the infarcts or to the clinical outcome of patients. CONCLUSIONS: Our study suggests that delayed brain atrophy after acute ischemic stroke involved areas anatomically connected with the ischemic brain lesion but nevertheless was accompanied by a simultaneous improvement of the neurological deficit.
Animal experiments suggest that reorganisation of cerebral representations is the neurobiological basis of post-lesional recovery. In human ischemic brain disease recovery is a dynamic and sustained process beginning after stroke manifestation. The mechanisms underlying recovery can be investigated non-invasively in the human brain using functional neuroimaging and transcranial magnetic stimulation (TMS). In the acute stage, the mismatch area of the perfusion deficit and the impaired water diffusion as assessed by magnetic resonance imaging (MRI) shows the brain tissue that potentially can be rescued by thrombolysis or emergency carotid endarterectomy. Since spontaneous motor recovery is a function of the corticospinal tract integrity, early reperfusion of ischemic tissue is critical. In the subacute and chronic stage after stroke, recovery of motor function was shown to take place irrespective of a concomitant affection of the somatosensory system. Functional MRI with simultaneous recordings of the electromyogram provides evidence that the abnormal activation of motor and premotor cortical areas in both hemispheres related to finger movements has a large interindividual variability. As evident from TMS, recovery results from regression of perilesional inhibition and from remote intracortical disinhibition. Repetitive training, constraint induced training and motor imagery can augment recovery promoting a re-emerging activation in the affected hemisphere. Evolution of altered local perilesional and large-scale bihemispheric circuits appears to allow for post-lesional deficit compensation.
We used functional magnetic resonance imaging (fMRI) to explore how guidance of motor acts is influenced by the visually perceived body scheme. We found that when subjects view their hand as their opposite hand, i.e., the right hand is seen as the left hand and vice versa, activation in the visual cortex was lateralized opposite to the seen hand. This demonstrates for the first time that our body scheme to which vision relates our environment is already represented at the level of visual cortex.
Mirror apraxia is a condition in which patients with lesions of the posterior parietal cortex have deficits in reaching to objects presented through a mirror. The aim of the present study was to investigate possible mechanisms underlying this disorder. First, we addressed the question of whether mirror apraxia is exhibited to the same extent in peripersonal and in body space. Four patients with lesions of the posterior parietal lobe on either side and with marked mirror apraxia were required to reach for objects that were presented to them through a mirror and located either in body space (i.e. on the body surface) or in peripersonal space (i.e. in the reaching distance). Whereas reaching for objects located in body space was flawless in all patients, the performance deteriorated when the same objects were transferred to the peripersonal space. Although the objects were located only a few centimetres above the body surface, the patients reached towards the virtual object in the mirror. Based on these results we suggest that mirror apraxia may originate from a dissociation between the representations of body schema and peripersonal space and that objects located on the body surface become integrated into the body schema. In the second part of the study, using positron emission tomography study (PET), we studied the cerebral activation pattern during reaching to objects presented through a mirror in the peripersonal space in healthy subjects. The results show that increased neural activity in the anterior part of the intraparietal sulcus and in the dorsal premotor cortex was bound to the transformation of the target position from the mirror space to the real space. In contrast, the activity related to object localization in the mirror occurred at the parieto-occipital junction. Both mirror and arm transformation involved the medial posterior part of the superior parietal lobule, putatively area V6a. The results demonstrate that acting through a mirror is processed in a number of cortical areas of the dorsal stream.
BACKGROUND AND PURPOSE: We sought to investigate the feasibility of the combined use of low-dose recombinant tissue plasminogen activator (rtPA) and tirofiban, a glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonist, for systemic thrombolysis in acute stroke. METHODS: Consecutive patients who were treated with systemic application of low-dose rtPA and body weight-adjusted tirofiban (rtPA+T group; n=37) were evaluated retrospectively during 1999-2001. Patients in the rtPA+T group were compared with a group of patients treated with a dose of 0.9 mg/kg body weight in a different center (rtPA group; n=119). The 41 patients with infarctions of the middle cerebral artery territory who were not eligible for thrombolytic treatment because of medical contraindications or arrival in the hospital >3 hours after stroke onset served as controls. For matched comparisons, the National Institutes of Health Stroke Scale on admission and the Rankin Scale on discharge 5 days after stroke were used. RESULTS: The patients treated with rtPA+T or rtPA improved (P<0.05) compared with the controls at discharge; patients in the rtPA+T and rtPA groups reached a Rankin Scale score of 0 to 2 in 63% and 55%, respectively, while only 16% of the controls achieved this score. Death rates (8% in rtPA+T group and 5% in rtPA group) were similar among the 2 treatment groups. They included 1 fatal hemorrhage in the rtPA+T group and 4 fatal hemorrhages in the rtPA group. Five percent of the untreated patients developed symptomatic, nonfatal cerebral hemorrhage. CONCLUSIONS: Systemic combined thrombolysis with rtPA+T seems to be a feasible treatment in acute stroke.
We describe a patient with chronic manganism due to intoxication 40 years ago. Whereas previous reports on acute or subacute intoxication have shown no or only small reductions in striatal D2 receptor density, we found markedly decreased D2 receptor density using (18)F-methylspiperone PET in this very late stage of chronic manganism, supporting the hypothesis that manganese intoxication may trigger a neurodegenerative disease process.