Uwe Knorr

Inter-subject variability of cerebral activations in acquiring a motor skill: a study with positron emission tomography

Cerebral structures activated during sequential right-hand finger movements were mapped with regional cerebral blood flow (rCBF) measurements by positron emission tomography (PET) in individual subjects. Nine healthy volunteers were examined twice; after initial learning and after practicing the finger movement sequence for more than 1 h. Task-specific activation sites were identified by statistical distributions of maximal activity and region size in rCBF subtraction images. A consistent task specific activation in all nine subjects was detected in the contralateral sensorimotor cortex at an average movement rate of 3.2 Hz reached after practice. This corresponded to a significant increase of the mean rCBF in the left primary sensorimotor cortex in spatially standardised and averaged PET images. Additional task specific activation sites detected by individual analysis were found in the lateral and medial premotor, parietal, and cingulate areas, and in subcortical structures including the basal ganglia of both cerebral hemispheres. These activations showed no or little spatial overlap from subject to subject, thus being obscured in the analysis of pooled data. The observed activity patterns were related to movement rate and accuracy in individual subjects. It is suggested that the rCBF changes associated with acquisition of a motor skill in individual humans may correspond to plasticity of sensorimotor representations reported in monkeys.

Large-scale plasticity of the human motor cortex

The adult primate brain is capable of modifying rapidly the size of cortical receptive fields or motor output modules in response to altered synaptic input. We used positron emission tomography (PET) to map the regional cerebral blood flow changes related to voluntary finger movements in patients with tumours occupying the hand area of motor cortex. All patients showed activations solely outside the tumour. Compared with the unaffected side, the activations were shifted by 9-43 mm either along the mediolateral body representation of motor cortex or into premotor or parietal somatosensory cortex. These results provide evidence that slowly developing lesions can induce large-scale reorganization that is not confined to changes within the somatotopic body representation in motor cortex.

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.

Precentral Glioma Location Determines the Displacement of Cortical Hand Representation

OBJECTIVE Low-grade brain tumors may remain asymptomatic in contrast to malignant gliomas. The mechanisms underlying the preservation of cerebral function in such gliomas are not well understood. METHODS We used positron emission tomography and transcranial magnetic stimulation for presurgical monitoring of motor hand function in six patients with gliomas of the precentral gyrus. All patients were able to perform finger movements of the contralesional hand. RESULTS Movement-related increases of the regional cerebral blood flow occurred only outside the tumor in surrounding brain tissue. Compared with the contralateral side, these activations were shifted by 20 +/- 13 mm (standard deviation) within the dorsoventral dimension of the precentral gyrus. This shift of cortical hand representation could not be explained by the deformation of the central sulcus as determined from the spatially aligned magnetic resonance images but was closely related to the location of the maximal tumor growth. Dorsal tumor growth resulted in ventral displacement of motor hand representation, leaving the motor cortical output system unaffected, whereas ventral tumor growth leading to dorsal displacement of motor hand representation compromised the motor cortical output, as evident from transcranial magnetic stimulation. In two patients, additional activation of the supplementary motor area was present. CONCLUSION Our data provide evidence for the reorganization of the human motor cortex to allow for preserved hand function in Grade II astrocytomas.

Representations of graphomotor trajectories in the human parietal cortex: Evidence for controlled processing and automatic performance

The aim of this study was to identify the cerebral areas activated during kinematic processing of movement trajectories. We measured regional cerebral blood flow (rCBF) during learning, performance and imagery of right‐hand writing in eight right‐handed volunteers. Compared with viewing the writing space, increases in rCBF were observed in the left motor, premotor and frontomesial cortex, and in the right anterior cerebellum in all movement conditions, and the increases were related to mean tangential writing velocity. No rCBF increases occurred in these areas during imagery. Early learning of new ideomotor trajectories and deliberately exact writing of letters both induced rCBF increases in the cortex lining the right intraparietal sulcus. In contrast, during fast writing of overlearned trajectories and in the later phase of learning new ideograms the rCBF increased bilaterally in the posterior parietal cortex. Imagery of ideograms that had not been practised previously activated the anterior and posterior parietal areas simultaneously. Our results provide evidence suggesting that the kinematic representations of graphomotor trajectories are multiply represented in the human parietal cortex. It is concluded that different parietal subsystems may subserve attentive sensory movement control and whole‐field visuospatial processing during automatic performance.

Multimodal output mapping of human central motor representation on different spatial scales

1 Non‐invasive mapping by focal transcranial magnetic stimulation (TMS) is frequently used to investigate cortical motor function in the intact and injured human brain. We examined how TMS‐derived maps relate to the underlying cortical anatomy and to cortical maps generated by functional imaging studies. 2 The centres of gravity (COGs) of TMS maps of the first dorsal intersosseus muscle (FDI) were integrated into 3‐D magnetic resonance imaging (MRI) data sets in eleven subjects. In seven of these subjects the TMS‐derived COGs were compared with the COG of regional cerebral blood flow increases using positron emission tomography (PET) in an index finger flexion protocol. 3 Mean TMS‐derived COG projections were located on the posterior lip of the precentral gyrus and TMS‐derived COG projections were in close proximity to the mean PET‐derived COG, suggesting that the two methods reflect activity of similar cortical elements. 4 Criteria for a reliable assessment of the COG and the number of positions with a minimum amplitude of two‐thirds of the maximum motor‐evoked potential (T3Ps) were determined as a function of the number of stimuli and extension of the stimulation field. COGs and T3Ps were compared with an estimate of the size of the human motor cortex targeting α‐motoneurons of forearm muscles. This comparison suggests that TMS can retrieve spatial information on cortical organization below the macroanatomic scale of cortical regions. 5 Finally, we studied the cortical representation of hand muscles in relation to facial and foot muscle representations and investigated hemispherical asymmetries. We did not find any evidence for a different ipsi‐ or contralateral representation of the mentalis muscle. Also, no difference was found between FDI representations on the dominant versus the non‐dominant hemisphere.

A Neuromagnetic Study of the Functional Organization of the Sensorimotor Cortex

Movement‐related neuromagnetic fields from eight healthy human subjects were investigated in a Bereitschaftspotential paradigm. The three conditions studied were right‐sided mouth, index finger and foot movement. The neuromagnetic field patterns corresponding to the motor field and the movement‐evoked field I were analysed using a moving dipole model. For both components a somatotopic organization was found: the estimated dipole locations for the mouth were more lateral and those for the foot more medial than the estimated dipole positions for the index finger movement. With regard to possible clinical applications, e.g. non‐invasive mapping of the sensorimotor cortex and studies of plasticity of the motor function, the present results suggest that the investigation of movement‐evoked field I for the index finger condition is most likely to yield further results.

Individual somatotopy of primary sensorimotor cortex revealed by intermodal matching of MEG, PET, and MRI.

SummaryA method for comparing estimated magnetoencephalographic (MEG) dipole localizations with regional cerebral blood flow (rCBF) activation areas is presented. This approach utilizes individual intermodal matching of MEG data, of rCBF measurements with [15O]-butanol and positron emission tomography (PET), and of anatomical information obtained from magnetic resonance (MR) images. The MEG data and the rCBF measurements were recorded in a healthy subject during right-sided simple voluntary movements of the foot, thumb, index finger, and mouth. High resolution 3D-FLASH MR images of the brain consisting of 128 contiguous sagittal slices of 1.17-mm thickness were used. MEG/MR integration was performed by superimposing the 3D head coordinate system constructed during the MEG measurement onto the MR image data using identical anatomical landmarks as references. PET/MR integration was achieved by a phantom-validated iterative front-to-back-projection algorithm resulting in one integrated MEG/PET/MR image. The estimated dipole locations followed the somatotopic organisation of the task-specific rCBF increases as evident from PET, although they did not match point-to-point. Our results demonstrate that intermodal matching of MEG, PET and MR data provides a tool for relating estimated neuromagnetic field locations to task-specific rCBF changes in individual subjects. Our method offers the perspective of refined dipole modelling.

Individual Integration of Positron Emission Tomography and High-Resolution Magnetic Resonance Imaging

We have developed, validated, and employed a technique of retrospective spatial alignment and integrated display of positron emission tomographic (PET) and high-resolution magnetic resonance (MR) brain images. The method was designed to improve the anatomical evaluation of functional images obtained from single subjects. In the first computational step, alignment of PET and MR data sets is achieved by iteratively matching in three orthogonal views the outermost scalp contours derived from front-to-back projections of each data set. This procedure avoids true three-dimensional modeling, runs without user interaction, and tolerates missing parts of the head circumference in the image volume, as usually the case with PET. Thereafter, high-resolution MR sections corresponding to the PET slices are reconstructed from the spatially transformed MR data. In a phantom study of this method, PET/MR alignment of the phantoms surface was accurate with average residual misfits of 2.17 to 2.32 mm as determined in three orthogonal planes. In-plane alignment of the phantoms insertion holes was accurate with an average residual misfit of 2.30 mm. In vivo application in six subjects allowed the individual anatomical localization of regional CBF (rCBF) responses obtained during unilateral manual exploration. In each subject, the maxima of the rCBF activations in the hand area were precisely allocated to gray matter in the anterior or posterior wall of the central sulcus. The configuration of the rCBF responses closely followed the gyral structures. The technique provided a better topographical understanding of rCBF changes in subtraction images of PET activation studies. It opens the perspective for studies of structural–functional relationships in individual subjects.

Identification of task-specific rCBF changes in individual subjects: validation and application for PET.

Objective A method for identification and quantitative evaluation of task-specific changes of the regional cerebral blood flow (rCBF) measured with PET in activation studies of individual subjects is presented. The method is based on the statistical distributions of the quantitative and spatial information of regions of interest in rCBF subtraction images. Methods For validation, a cylindrical phantom of 20 cm diameter containing six spheres of 10–30 mm in diameter was used. The spheres representing the specific signals were filled with 18F, while one-tenth of this activity concentration was filled into the background compartment of the phantom representing “noise.” Of a sequence of dynamically recorded frames, subtraction images with different signal-to-noise ratios were calculated. Results In these subtraction images, our method allowed us to identify the larger spheres accurately and to quantify the signals. Comparison with t map analysis in averaged subtraction images revealed a high correspondence with the results obtained by our method in individual subtraction images. Based on this phantom validation, the method was applied for mapping of rCBF changes in humans. The rCBF was measured with [15O]butanol in four subjects during unilateral somatosensory discrimination and during rest. Conclusion The method proved to be capable of identifying task-specific rCBF changes in the contralateral motor, premotor, and sensory cortex accurately and with high quantitative and anatomical precision in each subject.