R.J. Seitz

A parieto-premotor network for object manipulation: evidence from neuroimaging.

Abstract Functional magnetic resonance imaging (fMRI) was used to assess cerebral activation during manipulation of various complex meaningless objects as compared to manipulation of a single simple object (a sphere). Significant activation was found bilaterally in the ventral premotor cortex (Brodmann’s area 44), in the cortex lining the anterior part of the intraparietal sulcus (most probably corresponding to monkey anterior intraparietal area, AIP), in the superior parietal lobule and in the opercular parietal cortex including the secondary somatosensory area (SII). We suggest that the cortex lining the anterior part of the intraparietal sulcus and area 44 are functionally connected and mediate object manipulation in humans.

The Role of Diaschisis in Stroke Recovery

BACKGROUND AND PURPOSE Recovery from hemiparesis after stroke has been shown to involve reorganization in motor and premotor cortical areas. However, whether poststroke recovery also depends on changes in remote brain structures, ie, diaschisis, is as yet unresolved. To address this question, we studied regional cerebral blood flow in 7 patients (mean+/-SD age, 54+/-8 years) after their first hemiparetic stroke. METHODS We analyzed imaging data voxel by voxel using a principal component analysis by which coherent changes in functional networks could be disclosed. Performance was assessed by a motor score and by the finger movement rate during the regional cerebral blood flow measurements. RESULTS The patients had recovered (P<0. 001) from severe hemiparesis after on average 6 months and were able to perform sequential finger movements with the recovered hand. Regional cerebral blood flow at rest differentiated patients and controls (P<0.05) by a network that was affected by the stroke lesion. During blindfolded performance of sequential finger movements, patients were differentiated from controls (P<0.05) by a recovery-related network and a movement-control network. These networks were spatially incongruent, involving motor, sensory, and visual cortex of both cerebral hemispheres, the basal ganglia, thalamus, and cerebellum. The lesion-affected and recovery-related networks overlapped in the contralesional thalamus and extrastriate occipital cortex. CONCLUSIONS Motor recovery after hemiparetic brain infarction is subserved by brain structures in locations remote from the stroke lesion. The topographic overlap of the lesion-affected and recovery-related networks suggests that diaschisis may play a critical role in stroke recovery.

Activation of frontoparietal cortices during memorized triple-step sequences of saccadic eye movements: an fMRI study

To determine the cortical areas controlling memory‐guided sequences of saccadic eye movements, we performed functional magnetic resonance imaging (fMRI) in six healthy adults. Subjects had to perform a memorized sequence of three saccades in darkness, after a triple‐step stimulus of successively flashed laser targets. To assess the differential contribution of saccadic subfunctions, we applied several control conditions, such as central fixation with or without triple‐step visual stimulation, self‐paced saccades in darkness, visually guided saccades and single memory‐guided saccades. Triple‐step saccades strongly activated the regions of the frontal eye fields, the adjacent ventral premotor cortex, the supplementary eye fields, the anterior cingulate cortex and several posterior parietal foci in the superior parietal lobule, the precuneus, and the middle and posterior portion of the intraparietal sulcus, the probable location of the human parietal eye field. Comparison with the control conditions showed that the right intraparietal sulcus and parts of the frontal and supplementary eye fields are more involved in the execution of triple‐step saccades than in the other saccade tasks. In accordance with evidence from clinical lesion studies, we propose that the supplementary eye field essentially controls the triggering of memorized saccadic sequences, whereas activation near the middle portion of the right intraparietal sulcus appears to reflect the necessary spatial computations, including the use of extraretinal information (efference copy) about a saccadic eye displacement for updating the spatial representation of the second or third target of the triple‐step sequence.

Action observation activates premotor and parietal areas in a somatotopic manner: an fMRI study: Cortical activation during action observation

Functional magnetic resonance imaging (fMRI) was used to localize brain areas that were active during the observation of actions made by another individual. Object‐ and non‐object‐related actions made with different effectors (mouth, hand and foot) were presented. Observation of both object‐ and non‐object‐related actions determined a somatotopically organized activation of premotor cortex. The somatotopic pattern was similar to that of the classical motor cortex homunculus. During the observation of object‐related actions, an activation, also somatotopically organized, was additionally found in the posterior parietal lobe. Thus, when individuals observe an action, an internal replica of that action is automatically generated in their premotor cortex. In the case of object‐related actions, a further object‐related analysis is performed in the parietal lobe, as if the subjects were indeed using those objects. These results bring the previous concept of an action observation/execution matching system (mirror system) into a broader perspective: this system is not restricted to the ventral premotor cortex, but involves several somatotopically organized motor circuits.

Systemic Thrombolysis With Recombinant Tissue Plasminogen Activator and Tirofiban in Acute Middle Cerebral Artery Occlusion

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 ≥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.

Cerebral midline structures in bimanual coordination

Abstract In six healthy right-handed volunteers, we compared the cerebral activation pattern related to unimanual right- and left-hand movements and to bimanual in-phase and anti-phase movements using functional magnetic resonance imaging (fMRI). Internally paced unimanual finger-to-thumb opposition movements led to a strong contralateral activation of primary sensorimotor areas in all six subjects. Midline activity was lateralized to the left side during right-hand movements, but to both sides during left-hand movements. Activity patterns of bimanual in-phase movements resembled the combined activity patterns of the two unimanual conditions: right and left hemispheric activations of the primary sensorimotor cortices and predominantly left-sided medial frontal activity. In contrast, during anti-phase movements, we observed a clear increase in activity, in both right and left frontal midline areas and in right hemispheric, mainly dorsolateral premotor areas compared to in-phase movements. These results indicate that frontal midline activity is not specific for bimanual movements per se. It can already be involved during simple unimanual movements but becomes progressively more involved during more complex aspects of movement control.

Mirror agnosia and mirror ataxia constitute different parietal lobe disorders

We describe two new clinical syndromes, mirror agnosia and mirror ataxia, both characterized by the deficit of reaching for an object through a mirror in association with a lesion of either parietal lobe. Clinical investigation of 13 patients demonstrated that the impairments affected both sides of the body. In mirror agnosia, the patients always reached toward the virtual object in the mirror and they were not capable of changing their behavior even after presentation of the position of the object in real visual space. In mirror ataxia (resembling optic ataxia) although some patients initially tended to reach for the virtual object in the mirror, they soon learned to guide their arms toward the real object, all of them producing many directional errors. Both patient groups performed poorly on mental rotation, but only the patients with mirror agnosia were impaired in line orientation. Only 1 of the patients suffered from neglect and 3 from apraxia. Magnetic resonance imaging showed that in mirror agnosia the common zone of lesion overlap was scattered around the posterior angular gyrus/superior temporal gyrus and in mirror ataxia around the postcentral sulcus. We propose that both these clinical syndromes may represent different types of dissociation of retinotopic space and body scheme, or likewise, of allocentric and egocentric space normally adjusted in the parietal lobe. Ann Neurol 1999;46:51–61

Thrombolysis With Recombinant Tissue Plasminogen Activator and Tirofiban in Stroke: Preliminary Observations

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.

Quantitative Assessment of Recovery from Motor Hemineglect in Acute Stroke Patients

Background and Purpose: Motor hemineglect is characterized by an underutilization of one side of the body. It is a higher-order motor disorder that resembles hemiplegia although being substantially different from it due to a preserved motor output system. Its role for poststroke recovery is still unclear. Methods: We studied 52 patients presenting with acute hemiparetic stroke over the first 7 days after symptom onset. Nineteen patients had unilateral motor hemineglect. Impairment was clinically assessed with the European Stroke Scale and a multifactorial motor score. It was further assessed quantitatively, as overall arm activity was measured continuously by Actiwatches. Lesion volumes were measured morphometrically within 24 h on perfusion- and diffusion-weighted magnetic resonance images and on average on day 9 by T2-weighted magnetic resonance imaging. Results: Patients with motor hemineglect were characterized by significantly reduced initial arm activity in comparison to patients without motor hemineglect. This was paralleled by larger brain lesions in the patients with motor hemineglect. Patients with motor neglect either recovered virtually completely (5 cases; 2/5 left hemisphere; 3/5 treated with recombinant tissue plasminogen activator, rt-PA) within 7 days or did not improve at all (14 cases; 3/14 left hemisphere; 3/14 rt-PA treated). Conclusion: Our data reveal a high incidence of motor hemineglect in patients with acute stroke. They further show that these patients are more severely compromised than those without motor hemineglect. A rapid and near complete recovery was observed in about one fourth of the motor hemineglect patients and may be related to involvement of the left hemisphere or to therapy with thrombolysis.

Functional activation within the PI-DWI mismatch region in recovery from ischemic stroke: preliminary observations.

In this study, we sought to investigate if brain tissue affected by ischemia can accommodate areas of activation related to restoration of brain function following ischemic stroke. In two patients perfusion imaging (PI) and diffusion weighted imaging (DWI) obtained in the acute phase after stroke was coregistered with BOLD imaging of brain functions acquired when profound recovery had occurred. Both patients suffered from thrombembolic brain infarction due to dissection of the internal carotid artery (ICA) characterized by a severe PI-DWI mismatch in the acute stage of stroke. Following ICA recanalization and clinical recovery BOLD imaging showed task-specific activation adjacent to the infarct lesion within the former PI-DWI mismatch area. The data in these two stroke patients provide evidence that brain tissue at risk of infarction as shown by the PI-DWI mismatch can survive and, thereby, constitute the major site underlying post-ischemic recovery.