[Evidence-based rehabilitation of mobility after stroke]. / Evidenzbasierte Rehabilitation der Mobilität nach Schlaganfall.

BACKGROUND: Approximately two thirds of stroke patients initially suffer from at least impaired mobility. Various rehabilitation concepts have been proposed. OBJECTIVE: Based on the current literature, which rehabilitation methods can be recommended for improvement of gait, gait velocity, gait distance and balance? METHODS: A systematic literature search was carried out for randomized clinical studies and reviews with clinically relevant outcome variables. Formulation of recommendations, separated for target variables and time after stroke. RESULTS: Restoration and improvement of gait function relies on a high number of repetitions of gait movements, which for more severely affected patients is preferentially machine-based. For improvement of gait velocity for less severely affected patients intensive gait training does not necessarily rely on mechanical support. Gait distance can be improved by aerobic endurance exercises with a cardiovascular effect, which have to be performed in a functional context. Improvement of balance should be achieved by intensive functional gait training. Additional stimulation techniques are only effective when included in a functionally relevant training program. DISCUSSION: These guidelines not only provide recommendations for action but also provide pathophysiological insights into functional restoration of stance and gait after stroke.

Conscious and subconscious sensorimotor synchronization--prefrontal cortex and the influence of awareness.

One of the most compelling challenges for modern neuroscience is the influence of awareness on behavior. We studied prefrontal correlates of conscious and subconscious motor adjustments to changing auditory rhythms using regional cerebral blood flow measurements. At a subconscious level, movement adjustments were performed employing bilateral ventral mediofrontal cortex. Awareness of change without explicit knowledge of the nature of change led to additional ventral prefrontal and premotor but not dorsolateral prefrontal activations. Only fully conscious motor adaptations to a changing rhythmic pattern showed prominent involvement of anterior cingulate and dorsolateral prefrontal cortex. These results demonstrate that while ventral prefrontal areas may be engaged in motor adaptations performed subconsciously, only fully conscious motor control which includes motor planning will involve dorsolateral prefrontal cortex.

Control of action as mediated by the human frontal lobe.

Conscious control of action involves the voluntary initiation and the continuous adjustment of motor activity. Neuroimaging data provide evidence that the plan for a movement is developed with respect to the behavioral context in prefrontal cortex, while the synergies of a motor program are coded by premotor cortex and the specific movement parameters by the motor cortex. It is suggested that the initiational aspects of conscious motor activity are implemented in a medial system of information flow and the integrative aspects in a lateral system of the human frontal lobe.

Broca's region subserves imagery of motion: a combined cytoarchitectonic and fMRI study.

Broca's region in the dominant cerebral hemisphere is known to mediate the production of language but also contributes to comprehension. Here, we report the differential participation of Broca's region in imagery of motion in humans. Healthy volunteers were studied with functional magnetic resonance imaging (fMRI) while they imagined movement trajectories following different instructions. Imagery of right-hand finger movements induced a cortical activation pattern including dorsal and ventral portions of the premotor cortex, frontal medial wall areas, and cortical areas lining the intraparietal sulcus in both cerebral hemispheres. Imagery of movement observation and of a moving target specifically activated the opercular portion of the inferior frontal cortex. A left-hemispheric dominance was found for egocentric movements and a right-hemispheric dominance for movement characteristics in space. To precisely localize these inferior frontal activations, the fMRI data were coregistered with cytoarchitectonic maps of Broca's areas 44 and 45 in a common reference space. It was found that the activation areas in the opercular portion of the inferior frontal cortex were localized to area 44 of Broca's region. These activations of area 44 can be interpreted to possibly demonstrate the location of the human analogue to the so-called mirror neurones found in inferior frontal cortex of nonhuman primates. We suggest that area 44 mediates higher-order forelimb movement control resembling the neuronal mechanisms subserving speech.

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

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.

Cerebral midline structures in bimanual coordination.

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.

The role of ventral medial wall motor areas in bimanual co-ordination. A combined lesion and activation study.

Two patients with midline tumours and disturbances of bimanual co-ordination as the presenting symptoms were examined. Both reported difficulties whenever the two hands had to act together simultaneously, whereas they had no problems with unimanual dexterity or the use of both hands sequentially. In the first patient the lesion was confined to the cingulate gyrus; in the second it also invaded the corpus callosum and the supplementary motor area. Kinematic analysis of bimanual in-phase and anti-phase movements revealed an impairment of both the temporal adjustment between the hands and the independence of movements between the two hands. A functional imaging study in six volunteers, who performed the same bimanual in-phase and anti-phase tasks, showed strong activations of midline areas including the cingulate and ventral supplementary motor area. The prominent activation of the ventral medial wall motor areas in the volunteers in conjunction with the bimanual co-ordination disorder in the two patients with lesions compromising their function is evidence for their pivotal role in bimanual co-ordination.

Human anterior intraparietal area subserves prehension: a combined lesion and functional MRI activation study.

It has been shown in nonhuman primates that the posterior parietal cortex is involved in coordination of arm and eye movements in space, whereas the anterior intraparietal area in the anterior lateral bank of the intraparietal sulcus plays a crucial role in fine finger movements, such as grasping. In this study we show by optoelectronic movement recordings that patients with cortical lesions involving the anterior lateral bank of the intraparietal sulcus have selective deficits in the coordination of finger movements required for object grasping, whereas reaching is much less disturbed. Patients with parietal lesions sparing the cortex lining the anterior intraparietal sulcus showed intact grasping behavior. Complementary evidence was obtained from functional MRI in normal control subjects showing a specific activation of the anterior lateral bank of the intraparietal sulcus during grasping. In conclusion, this combined lesion and activation study suggests that the anterior lateral bank of the intraparietal sulcus, possibly including the human homologue of the anterior intraparietal area, mediates the processing of sensorimotor integration of precisely tuned finger movements in humans.

Anatomy of motor learning. I. Frontal cortex and attention to action.

We used positron emission tomography to study new learning and automatic performance in normal volunteers. Subjects learned sequences of eight finger movements by trial and error. In a previous experiment we showed that the prefrontal cortex was activated during new learning but not during during automatic performance. The aim of the present experiment was to see what areas could be reactivated if the subjects performed the prelearned sequence but were required to pay attention to what they were doing. Scans were carried out under four conditions. In the first the subjects performed a prelearned sequence of eight key presses; this sequence was learned before scanning and was practiced until it had become overlearned, so that the subjects were able to perform it automatically. In the second condition the subjects learned a new sequence during scanning. In a third condition the subjects performed the prelearned sequence, but they were required to attend to what they were doing; they were instructed to think about the next movement. The fourth condition was a baseline condition. As in the earlier study, the dorsal prefrontal cortex and anterior cingulate area 32 were activated during new learning, but not during automatic performance. The left dorsal prefrontal cortex and the right anterior cingulate cortex were reactivated when subjects paid attention to the performance of the prelearned sequence compared with automatic performance of the same task. It is suggested that the critical feature was that the subjects were required to attend to the preparation of their responses. However, the dorsal prefrontal cortex and the anterior cingulate cortex were activated more when the subjects learned a new sequence than they were when subjects simply paid attention to a prelearned sequence. New learning differs from the attention condition in that the subjects generated moves, monitored the outcomes, and remembered the responses that had been successful. All these are nonroutine operations to which the subjects must attend. Further analysis is needed to specify which are the nonroutine operations that require the involvement of the dorsal prefrontal and anterior cingulate cortex.

Recovery from subcortical stroke--PET activation patterns in patients compared with healthy subjects.

The results of experiments with noninvasive monitoring techniques give us ideas about strategies used by the brain during recovery of function. They have their limitations, however, in that they do not allow us to work out underlying mechanism for such recovery. This can only be done by exact physiologic investigations, which can be performed most rigorously in monkeys or other animals. We hope that advances in comparative anatomy and physiology between different primates, including humans, will allow us to combine our knowledge about functional changes in the brain with more fundamental knowledge about their mechanisms. In the future this knowledge may indicate in which way such mechanisms can be modulated either pharmacologically or by physiotherapy to lead to a better outcome for patients.

Transient phase-locking and dynamic correlations: Are they the same thing?

This work represents an attempt to bring together two important themes in neuronal dynamics. The first is the characterization of dynamic correlations in multiunit recordings of spike activity using joint-peri-stimulus time histograms (J-PSTHs) [Aertsen and Preissl, 1991: Non Linear Dynamics and Neural Networks]. The second is transient phase-locking at high (gamma) frequencies, either in terms of spiking in separable spike trains [e.g., Eckhorn et al., 1988: Biol Cybern 60:121-130, Gray and Singer, 1989 Proc Natl Acad Sci USA 86:1698-1702], or using continuous electrical or biomagnetic signals [e.g., Desmedt and Tomberg, 1994 Neurosci Lett 168:126-129]. In this paper we suggest that transient phase-locking is necessary for frequency-specific, dynamic event-related correlations. This point is demonstrated using the gamma-frequency (36 Hz) component of neuromagnetic signals measured in the prefrontal and partial regions of a subject during self-paced movements. A J-PSTH analysis revealed dynamic changes in prefronto-parietal correlations in relation to movement onset. These frequency-specific dynamic correlations were associated with changes in the degree of phase-locking, of the sort reported by Desmedt and Tomberg [1994 Neurosci Lett 168:126-129]. Hum. Brain Mapping 5:48-57, 1997. (c) 1997 Wiley-Liss, Inc.

Dynamic scanning of 15O-butanol with positron emission tomography can identify regional cerebral activations.

To determine task-specific activations of the human brain in individual subjects, we applied pixel-by-pixel t-map statistics to the regional cerebral perfusion data obtained sequentially by dynamic scanning of [15O]-butanol with positron emission tomography (PET). The listmode data were binned into frames of 2 sec, and multiple corresponding pixel-by-pixel activation-minus-control subtractions were used for t-map calculation. The subtraction frames covering 10-40 sec after tracer arrival in the brain showed the activation-related increase of regional cerebral perfusion. A mismatch of the activation and control data by 2 sec resulted in a mean error of <5% of the integrated activity increase. To validate these results, we simulated images with a spatial resolution and signal-to-noise ratio equivalent to that of the [15O]-butanol subtraction images. By means of these simulated images, we determined the minimal data requirements for t-map analysis, the degree of spatial correlations in the image matrix, and the distribution of noise in the t-maps. The simulation results provided a measure to estimate the significance of regional cerebral perfusion changes recorded with [15O]-butanol. The location and spatial extent of regional cerebral activations obtained from dynamic data corresponded closely to those obtained with quantitative measurements of regional cerebral blood flow (rCBF). Our results show that statistical parametric mapping of [15O]-butanol scanning data allows the detection of significant, task-specific brain activations in single activation-control comparisons in individual subjects.

Quantitative comparison of functional magnetic resonance imaging with positron emission tomography using a force-related paradigm.

The intention of our study was to compare functional magnetic resonance imaging (fMRI) with positron emission tomography (PET). We used the same force-related motor paradigm for both techniques, which allows for quantification of stimulus intensity. Regional cerebral blood flow (rCBF) was determined with PET in six male subjects (age 30 +/- 3) using the slow bolus injection technique and oxygen-15-labeled water. Scans were collected during six different conditions: at rest and during repetitive Morse key press at 1 Hz, with the right index finger at a range of different forces. In a second series of experiments fMRI data were acquired under similar conditions in six volunteers in a single slice parallel to and 51 +/- 3 mm dorsal to the anterior and posterior commissure (AC-PC). A conventional 1.5-T clinical magnetic resonance (MR) system and the FLASH technique were used. The data obtained in both series of experiments were subjected to the same statistical analyses. Statistical parametric maps (SPM) were generated by two different approaches: a correlation between peak force and rCBF or fMRI signal and using a categorical comparison of force exerted with rest. SPMs were coregistered with anatomical MR images. PET and fMRI measurements demonstrated activation in the primary motor cortex (M1) and posterior supplementary motor cortex in all subjects. Correlation analysis demonstrated foci in the M1 in four subjects with PET and in only one subject with fMRI. Locations of activation peaks differed by 2 to 8 mm between imaging methods. The relationship between fMRI signal or rCBF and peak force was logarithmic. The maximum increase in fMRI signal was 5.0% +/- 0.9 at 60% of the maximum voluntary contraction while the corresponding increase in rCBF was 13.7% +/- 1.2. The ratio of percentage rCBF change to percentage fMRI signal change was very similar across all force levels. The high degree of correspondence between PET and fMRI data provides good cross-validation for the two techniques.

Cerebral activation during the exertion of sustained static force in man.

The aim of our study was to determine alterations of cerebral activity during prolonged static force exertion. Regional cerebral blood flow (rCBF) was measured using H2(15)O positron emission tomography (PET) while six male normal subjects pressed a morse-key with their right index finger with a constant force of 20% of their maximal voluntary contraction (MVC) for different periods of time (1.5-4.5 min). Exertion of static force led to activation which was at least as extensive as that during exertion of repetitive dynamic force pulses. Despite a considerable sense of fatigue and increased effort at the end of a 4.5 min key press, no compensatory changes of activity were detected in motor or sensory related structures. The right dorsolateral prefrontal cortex demonstrated a significant correlation between rCBF and duration of key-press, possibly reflecting processes over-riding fatigue. Prominent basal ganglia activation was demonstrated in this static force task, but not in a previous force task involving repetitive dynamic force pulses. This suggests that sustained exertion of a static force is an active process modulated, at least in part, by the basal ganglia.

Motor imagery--anatomical representation and electrophysiological characteristics.

Experience and results of neuropsychological studies have shown that motor imagery can improve motor performance and enhance motor learning. In recent years several electro-physiological and functional imaging studies have investigated the physiological basis for this observation. In the present essay we review two of our recent studies, in which we compared motor imagery with motor preparation and motor execution. In the first we used positron emission tomography to describe their functional anatomy and in the second we employed electromyography, H-reflexes and transcranial magnetic stimulation to delineate their electrophysiological characteristics. Both studies demonstrated that motor imagery shares some characteristics with motor preparation and other, additional ones with motor execution. Thus it can be seen as a special form of motor behaviour, similar but distinct from both motor preparation and execution. This combination of mutual and distinct characteristics may be the key to its successful role in motor learning.

Comparison of regional cerebral blood flow with transcranial magnetic stimulation at different forces.

This study's objective was to investigate regional cerebral blood flow (rCBF) within the primary motor cortex (M1) and to compare it with thresholds of transcranial magnetic stimulation (TMS) and electromyographic recordings during exertion of different force levels with the right index finger. Quantitative electromyographic recordings, TMS, and positron emission tomography scans were performed while five and six volunteers, respectively, pressed a Morse key repetitively or with constant force with the right hand at five different force levels: 5, 10, 20, 40, and 60% of the individual's maximum voluntary contraction (MVC). Although at 5% MVC muscle activity was restricted to the first dorsal interosseus muscle, superficial finger flexors, and extensors, there was progressive involvement of proximal muscles during finger flexion with increasing force. rCBF increased logarithmically in the contralateral M1 with increasing force. In ipsilateral M1, rCBF decreased at 5% MVC and then increased logarithmically at higher force levels. TMS thresholds in the contralateral hemisphere declined logarithmically to reach a plateau at high force levels. The threshold in the ipsilateral hemisphere decreased slightly at high force levels. The logarithmic increase of rCBF and decrease of TMS thresholds in the contralateral hemisphere suggest related underlying physiological phenomena; increased cortical synaptic activity and increased excitability. It suggested that the pronounced ipsilateral rCBF alterations reflect transcallosal inhibition and are more prominent during repetitive movements (as used in the positron emission tomography study) than during the generation of a constant force (as exerted during TMS).

A multivariate analysis of evoked responses in EEG and MEG data.

This paper presents a multivariate analysis of evoked responses and their spatiotemporal dynamics as measured with electro- or magnetoencephalography. This analysis uses standard techniques (ManCova) to make possible statistical inference about differential responses, after the data have been transformed using singular value decomposition. The generality of this approach is limited only by the assumptions implicit in the general linear model and can range from simple analyses like Hotelling's T2 test (in comparing evoked responses among different conditions) to complex analyses of a multivariate regression type (e.g., characterizing the response components associated with a behavioral or psychophysical parameter). To illustrate the technique we have characterized time-dependent changes (both within and between trials) in magnetic fields, evoked by self-paced movements. Our illustrative analysis showed that movement-evoked components were less prone to adaptation than premovement components, suggesting that functionally distinct (preparatory and early executive) biomagnetic signals show differential adaptation.

Averaged and single-trial analysis of cortical activation sequences in movement preparation, initiation, and inhibition.

We compare estimates of three-dimensional brain activity extracted from averaged and from selected single-trial magnetoencephalographic signals, in order to study activation sequences related to motor preparation, inhibition, and movement, cued on two tones (S1 and S2). We studied all possible hand-ear combinations in a right-handed subject in both initiation and inhibition, and found some marked differences between combinations. Averaging revealed activity in the right motor cortex in all combinations requiring movement inhibition, irrespective of laterality of finger and ear, and in the contralateral motor cortex during movement (but considerably reduced for the task with the practiced ear and finger). These activation patterns are seen in single trials with variability of latency but not position. In the average signal, a long silent period between the warning and imperative stimuli is seen; in single trials, however, recurring sequences of activation linking frontal and posterior areas are seen throughout the analysis period in all combinations. These results show that single-trial analysis is needed to understand all the significant neural correlates of this task.

Magnetic field tomography of cortical and deep processes: examples of "real-time mapping" of averaged and single trial MEG signals.

Magnetic field tomography (MFT) provides 3-dimensional estimates of brain activity, from non-contact, non-invasive measurements of the magnetic field generated by coherent electrical activity in the brain. MFT analysis of averaged auditory "odd-ball" data show cortical and deep activation, presumably from the amygdala and hippocampus. These results are compared with MFT estimates obtained from a patient who had undergone lobectomy which removed these structures. The variability from subject to subject is confounded by variability between trials for the same subject; the relationship between the averaged and single trials is probed by bi-hemispheric simultaneous measurements performed under the same odd-ball paradigm and by MFT analysis of auditory evoked data and interictal epileptic activity.

Relation between cerebral activity and force in the motor areas of the human brain.

1. Positron emission tomography (PET) studies were performed in six normal right-handed male volunteers (age 30 +/- 3) to investigate the relationship between cerebral activation as measured by relative regional cerebral blood flow (rCBF) and force peak exerted during right index finger flexion. The purpose was to determine in which central motor structures activity is directly correlated with force for repeatedly executed movements. 2. Twelve PET rCBF measurements were performed in each volunteer with the use of H2(15)O as a perfusion tracer. Volunteers pressed a Morse-key repetitively with their right index finger for 2 min while lying in a supine position in the PET camera. The device was fitted with strain gauges to measure the force peaks exerted upon it. Scans were collected twice each at five different levels of exerted force peak and in a resting state. Individual and group results were co-registered with anatomic magnetic resonance images (MRI). 3. Group analysis revealed four major regions with a high correlation between rCBF and different degrees of repetitively exerted force peaks. One was located in the arm area of the left lateral surface [primary somatosensory and motor cortex (SI, MI)]. The second area was situated on the left mesial surface of the brain, posterior to the anterior commissure (AC) and encompassing the first gyrus dorsal to the cingulate sulcus. This area is thought to be homologous to the posterior part of the supplementary motor area (SMA) in the monkey. The third area was the dorsal bank of the posterior cingulate sulcus. The fourth area showing a significant correlation between rCBF and force peaks was in the cerebellar vermis. 4. Individual PET data were co-registered with each individual's MRI in order to identify precisely the locations of structures demonstrating a positive correlation between rCBF and force peak. Activated areas on the mesial surface consisted of the same two distinct regions seen in the group data. In three subjects the focus on the lateral surface of the cortex appeared to extend into the caudal premotor area; in two it extended into the rostral part of the superior parietal area. In no subject did blood flow in the anterior cingulate areas and anterior SMA show a correlation with the force exerted. Cerebellar correlations were present in the vermis in all subjects.(ABSTRACT TRUNCATED AT 400 WORDS)