Christian Dettmers

Motor cortex plasticity during constraint-induced movement therapy in stroke patients

Stroke patients in the chronic phase received constraint-induced (CI) movement therapy. The motor cortex was spatially mapped using focal transcranial magnetic stimulation (TMS) before and after 2 weeks of treatment. Motor-output areas of the abductor pollicis brevis muscle, motor evoked potential (MEP) amplitudes and location of centre of gravity (CoG) of motor cortex output were studied. After CI therapy, motor performance improved substantially in all patients. There was also an increase of motor output area size and MEP amplitudes, indicating enhanced neuronal excitability in the damaged hemisphere for the target muscles. The mean centre of gravity of the motor output maps was shifted considerably after the rehabilitation, indicating the recruitment of motor areas adjacent to the original location. Thus, even in chronic stroke patients, reduced motor cortex representations of an affected body part can be enlarged and increased in level of excitability by an effective rehabilitation procedure. The data therefore demonstrate a CNS correlate of therapy-induced recovery of function after nervous system damage in humans.

ACTION OBSERVATION HAS A POSITIVE IMPACT ON REHABILITATION OF MOTOR DEFICITS AFTER STROKE

Evidence exists that the observation of actions activates the same cortical motor areas that are involved in the performance of the observed actions. The neural substrate for this is the mirror neuron system. We harness this neuronal system and its ability to re-enact stored motor representations as a means for rehabilitating motor control. We combined observation of daily actions with concomitant physical training of the observed actions in a new neurorehabilitative program (action observation therapy). Eight stroke patients with moderate, chronic motor deficit of the upper limb as a consequence of medial artery infarction participated. A significant improvement of motor functions in the course of a 4-week treatment, as compared to the stable pre-treatment baseline, and compared with a control group have been found. The improvement lasted for at least 8 weeks after the end of the intervention. Additionally, the effects of action observation therapy on the reorganization of the motor system were investigated by functional magnetic resonance imaging (fMRI), using an independent sensorimotor task consisting of object manipulation. The direct comparison of neural activations between experimental and control groups after training with those elicited by the same task before training yielded a significant rise in activity in the bilateral ventral premotor cortex, bilateral superior temporal gyrus, the supplementary motor area (SMA) and the contralateral supramarginal gyrus. Our results provide pieces of evidence that action observation has a positive additional impact on recovery of motor functions after stroke by reactivation of motor areas, which contain the action observation/action execution matching system.

Inhibition of ipsilateral motor cortex during phasic generation of low force

OBJECTIVE To study the effect of different types of unilateral pinch grips on excitability of the ipsilateral motor cortex. METHODS In 9 healthy volunteers, transcranial magnetic stimuli (TMS) were applied over one motor cortex while the subjects performed either phasic or tonic ipsilateral pinch grips with different force levels (range 1-40% maximum voluntary contraction, MVC). Motor evoked potentials (MEP) were recorded from the relaxed contralateral first dorsal interosseous muscle (FDI) and were compared to MEPs obtained during muscle relaxation of both hands. In additional experiments, transcranial electrical stimuli (TES) were administered and F waves were recorded after electrical stimulation of the ulnar nerve. RESULTS Phasic pinch grips with low force (1 and 2% MVC) induced a significant decrease of TMS-induced MEP amplitudes. The effect lasted for about 100 ms after reaching the force level and was similar for both right and left-handed pinch grips. TES-induced MEPs and F waves remained unchanged. In contrast, tonic contractions (20 and 40% MVC) enhanced MEPs in the homologous FDI. CONCLUSIONS Phasic pinch grips with low force inhibit the motor cortex responsible for the contralateral homologous hand muscle. This effect, which is probably mediated transcallosally, might act at the level of the motor cortex.

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 H215O 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.

Increased excitability in the primary motor cortex and supplementary motor area in patients with phantom limb pain after upper limb amputation

Using functional magnetic resonance imaging and single slice FLASH technique, we investigated reorganization of the hand representation of the primary sensorimotor cortex (SMC) in 16 patients with upper extremity amputation. Patients were asked to perform finger tapping with the intact hand, repetitive eye closing and anteflexion of the amputation stump or intact shoulder. Six normal volunteers served as control. In the normal volunteers activations during shoulder anteflexion, finger tapping and eye closure were located within the central sulcus in a medio-lateral fashion. Patients demonstrated invasion of the face or shoulder representation into the hand representation of the amputated limb. Eight phantom limb pain patients showed significantly greater activation in SMC and supplementary motor area (SMA) in contrast to eight patients without phantom limb pain. We conclude, that different parts of the motor system are affected in patients with phantom limb pain--possibly in the sense of an up-regulation of excitability.

Visuomotor control within a distributed parieto-frontal network

The aim of this functional magnetic resonance imaging study was to investigate differences in visuomotor control with increasing task complexity. Twelve righthanded volunteers were asked to perform their signature under different degrees of visual control: internally generated movement with closed eyes, signing with open eyes, tracking the line of the projected signature forwards, and tracking the line of the projected signature backwards. There was a gradual onset and disappearance of activation within a distributed network. Parietal, lateral and medial frontal brain areas were activated during all conditions, confirming the involvement of a parietofrontal system. The weight of activation shifted with increasing task complexity. Internally generated movements activated predominantly the inferior parietal lobule and the ventral premotor cortex, as well as the rostral cingulate area, pre-supplementary motor area (pre-SMA) and SMA proper. Opening the eyes reduced SMA and cingulate activation and activated increasingly the occipito-parietal areas with higher task complexity. Visually guided movements produced an activation predominantly in the superior parietal lobule and dorsal premotor cortex. This study bridges human activation studies with the results of neurophysiological studies with monkeys. It confirms a gradual transition of visuomotor control with increasing task complexity within a distributed parietofrontal network.

Reorganization of the Executive Motor System after Stroke

We wished to characterize changes in function of the executive motor system individually and to correlate these with the degree of recovery from motor disability following stroke. Six male stroke pati

Age-independent activation in areas of the mirror neuron system during action observation and action imagery. A fMRI study

PURPOSE Recent studies have found age-related BOLD signal changes in several areas of the human brain. We investigated whether such changes also occur in brain areas involved in the processing of motor action observation and imagery. METHODS Functional magnetic resonance imaging with an experimental paradigm in which motor acts had to be observed and/or imagined from a first person perspective was performed in twenty-six subjects. RESULTS In line with previous work action observation and imagery induced BOLD signal increases in similar areas, predominantly in the premotor and parietal cortex. In contrast to young subjects the elderly displayed a stronger activity in most activated brain areas indicative of compensatory activity for the age-related decline of neural structures. Importantly, activity in the ventrolateral premotor cortex and inferior parietal cortex, seminal areas of the mirror neuron system, did not exhibit activity changes as a function of age. CONCLUSION These findings suggest that activity within the mirror neuron system is not age dependent and provide a neural basis for therapeutical interventions and novel rehabilitation treatments such as video therapy.

Structural and functional cortical abnormalities after upper limb amputation during childhood

Functional reorganization has been well documented in the human adult brain after amputation of the arm. To assess the effects of amputation on the developing brain, we investigated six patients with upper limb amputation in early childhood and one with right dysmelia. Transcranial magnetic stimulation indicated contralateral cortical disinhibition and enlargement of the excitable area of the stump. FMRI data corroborated these plastic changes and also showed an ipsilateral functional reorganization. In the T1-weighted MRI, we found structural deformities of the contralateral and ipsilateral central sulcus in three patients and a contralateral atrophic parietal lobule in two patients. Therefore, arm amputation in childhood affects functional organization as well as anatomical structure in both hemispheres.