[Neurofeedback-based motor imagery training for rehabilitation after stroke]. / Neurofeedback-gestütztes Bewegungsvorstellungstraining zur Rehabilitation nach einem Schlaganfall.

Mental training, including motor observation and motor imagery, has awakened much academic interest. The presumed functional equivalence of motor imagery and motor execution has given hope that mental training could be used for motor rehabilitation after a stroke. Results obtained from randomized controlled trials have shown mixed results. Approximately half of the studies demonstrate positive effects of motor imagery training but the rest do not show an additional benefit. Possible reasons why motor imagery training has so far not become established as a robust therapeutic approach are discussed in detail. Moreover, more recent approaches, such as neurofeedback-based motor imagery or closed-loop systems are presented and the potential importance for motor learning and rehabilitation after a stroke is discussed.

[Driving ability with multiple sclerosis]. / Fahreignung bei Multipler Sklerose.

Driving is an important issue for young patients, especially for those whose walking capacity is impaired. Driving might support the patient's social and vocational participation. The question as to whether a patient with multiple sclerosis (MS) is restricted in the ability to drive a car depends on neurological and neuropsychological deficits, self-awareness, insight into deficits and ability to compensate for loss of function. Because of the enormous variability of symptoms in MS the question is highly individualized. A practical driving test under supervision of a driving instructor (possibly accompanied by a neuropsychologist) might be helpful in providing both patient and relatives adequate feedback on driving abilities.

Motor imagery in stroke patients, or plegic patients with spinal cord or peripheral diseases.

OBJECTIVES: When motor imagery (MI) is impaired in stroke patients, it is not clear, whether this is caused by the central lesion with a disruption of networks or this may be due to inactivity/lack of practice following hemiparesis. To answer this question, we investigated MI in two groups of patients: stroke patients and patients with no central lesion, who suffered high-grade tetraparesis caused by myopathy or spinal muscular atrophy. MATERIALS AND METHODS: The first study measured MI in 31 sub-acute and chronic stroke patients with hand paresis. We used self-assessment questionnaires [Kinaesthetic and Visual Imagery Questionnaire (KVIQ), the Vividness of Motor Imagery Questionnaire (VMIQ)] as well as a new chronometric test (mental version and normal/physical version of Box and Block Test). The second study assessed MI in 10 patients without a central lesion, but with severe tetraparesis of peripheral origin. They were incapable of performing the requested task physically. RESULTS: MI in patients was better (i) for the third-person (VMIQ(3.P) ) compared to the first-person perspective (VMIQ(1.P) ), (ii) in patients without sensory impairment compared to those with impaired proprioception, (iii) in patients with light paresis compared to severe paresis and (iv) for the non-affected than the affected hand (KVIQ-10). Patients with severe tetraparesis were able to imagine another person's knee bends, but were not capable of imagining themselves performing knee bends. CONCLUSIONS: MI may be hampered on the affected side in severely paretic patients, particularly in the presence of impaired proprioception. Remarkably, the second study illustrates that motor experiences shape MI. This confirms the close relationship between MI and movement execution. The study advocates the careful use of test batteries for assessment of MI when investigating mental training in clinical trials. Not all patients might benefit to the same extent from MI training. This is possibly contingent on intact proprioception and preserved MI.

Endurance exercise improves walking distance in MS patients with fatigue.

OBJECTIVES: Effects of endurance training in multiple sclerosis (MS) patients complaining of motor fatigue. MATERIALS AND METHODS: Thirty MS patients complaining of fatigue with low to moderate disabilities randomly allocated to the intervention (thrice weekly 45-min intervals of endurance exercise) or control treatment (three 45-min episodes of stretching, balance training and coordination), both as 'add-on' therapy for 3 weeks during inpatient rehabilitation. RESULTS: Maximal walking distance before intervention averaged 1043 +/- 568 and 1163 +/- 750 m in the two groups. The intervention group increased its maximal walking distance by 650 +/- 474 m. The control group extended its walking distance by 96 +/- 70 m. CONCLUSIONS: The present data confirm a strong effect of endurance exercise on maximal walking distance. Remarkably, there were no parallel improvements on the Modified Fatigue Impact Scale, the Beck Depression Inventory and the Hamburg Quality of Life Questionnaire for MS.

A blueprint for movement: functional and anatomical representations in the human motor system.

Despite a clear somatotopic organization of the motor cortex, a movement can be learned with one extremity and performed with another. This suggests that there exists a limb-independent coding for movements. To dissociate brain regions coding for movement parameters from those relevant to the chosen effector, subjects wrote their signature with their dominant index finger and ipsilateral big toe, and we determined those areas activated by both conditions using functional magnetic resonance imaging. The results show that movement parameters for this highly trained movement are stored in secondary sensorimotor cortices of the extremity with which it is usually performed, i.e., the dominant hand, including dorsal and ventral lateral premotor cortices. These areas can be accessed by the foot and are therefore functionally independent from the primary representation of the effector. Thus, somatotopy in secondary structures in the human motor system seems to be defined functionally, and not on the basis of anatomical representations.

PET study of changes in local brain hemodynamics and oxygen metabolism after unilateral middle cerebral artery occlusion in baboons.

Local cerebral hemodynamics and oxygen metabolism were measured by positron emission tomography (PET) with the oxygen-15 (15O) steady-state method in baboons, immediately before (T0), 1 (T1), and 3-4 (T2) h after permanent middle cerebral artery occlusion (MCAO). At T1, there was a marked fall in both cerebral blood flow (CBF) and the CBF/cerebral blood volume (CBV) ratio in the occluded territory; these changes were sustained at T2, indicating stable reduction in cerebral perfusion pressure and lack of spontaneous reperfusion within this time range. Compared with preocclusion conditions, the oxygen extraction fraction (OEF) in the occluded territory was elevated at both T1 and T2, indicative of a persistent oligemia/ischemia for up to 3 h after MCAO. At T2, however, this OEF increase had lessened, concomitantly with a decline in cerebral metabolic rate of oxygen (CMRO2). This impairment of oxidative metabolism occurred earlier in the deep, compared with the cortical, MCA territories; in the latter, the CMRO2 was essentially preserved at T1 and only moderately reduced at T2, possibly suggesting prolonged viability. Finally, no significant changes in CBF or CMRO2 were observed in the contralateral MCA territory in this time range after MCAO. Despite methodological limitations (mainly partial volume effects related to PET imaging, which may have resulted in an underestimation of true changes and an overlooking of heterogeneous changes) our study demonstrates the feasibility of the combined PET-MCAO paradigm in baboons; this experimental approach should be valuable in investigating the pathophysiology and therapy of acute stroke.

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.

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.

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).

Human cerebral activity with increasing inspiratory force: a study using positron emission tomography.

Human cerebral activity with increasing inspiratory force: a study using positron emission tomography. J. Appl. Physiol. 81(3): 1295-1305, 1996.--The major aim of this study was to use positron emission tomography (PET) to assess dose-dependent effects of inspiratory loads on relative regional cerebral blood flow as an indication of neuronal activation and recruitment. Six normal men underwent H2 15O-PET scanning during unloaded breathing and with external inspiratory loads (generating mouth pressures of -5, -10, and -15 cmH2O); positive-pressure ventilation against relaxed respiratory muscles acted as control. During unloaded breathing, the supplementary motor area was significantly activated. With the addition of the smallest load, activations also occurred in the right premotor area and bilaterally in the superolateral motor cortex (MI) in areas previously shown to be activated with deeper breathing. There was little further change in these areas with greater loads. Additional force-related activations occurred in the inferolateral sensorimotor cortex, parietal cortex, and midbrain/hypothalamus. The results suggest that volitionally induced increases in inspiratory muscle force are achieved via a complex integration of neuronal activations in cortical and subcortical regions associated with motor control.

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.

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.

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.

Abnormal motor cortex organization contralateral to early upper limb amputation in humans.

We performed both a functional magnetic resonance imaging (fMRI) study using single slice FLASH technique and an investigation with transcranial magnetic stimulation (TMS) in a 21-year-old patient. He had suffered a left upper extremity amputation at age 7. Anteflexion of the amputation stump produced an unusual, broad activation contralateral to the movement. TMS revealed an enlarged cortical motor output area of the deltoid muscle at the amputation stump. Application of paired magnetic stimulation demonstrated decreased intracortical inhibition (ICI). A T1-weighted image indicated a lack of the characteristic shape of the central sulcus contralateral to the amputation. In addition to previous functional studies, these new structural data suggest that maturation of the central sulcus develops in response to daily practice of the contralateral hand, possibly until adolescence.

Confirmation of CT criteria to distinguish pathophysiologic subtypes of cerebral infarction.

PURPOSE: To determine whether cerebral infarctions classified as embolic or hemodynamic by their appearance on CT scans reflect distinct pathophysiologic entities. METHODS: Cerebral infarctions were retrospectively classified into two groups according to their morphologic appearance on CT scans: territorial infarctions and watershed, or terminal supply area, infarctions. Specific CO2 reactivity for both groups of patients was determined with the xenon-133 method and 32 stationary detectors. Twenty-one patients with unilateral, supratentorial, ischemic cerebral infarctions were selected. CT findings were highly suggestive of a territorial infarction in 14 patients (mean age, 56 years) and of a watershed infarction in seven patients (mean age, 52 years). RESULTS: The initial slope index of the territorial and watershed infarction groups during CO2 inhalation was 55.1 +/- 2.4 sec-1 and 52.0 +/- 1.9 sec-1, respectively, in the infarcted hemispheres and 58.3 +/- 2.3 sec-1 and 55.1 +/- 1.5 sec-1, respectively, in the noninfarcted hemispheres. CO2 reactivity of the unaffected detectors was 1.75 +/- 0.3 sec-1 mm Hg-1 and 1.51 +/- 0.2 sec-1 mm Hg-1 for the territorial and watershed infarction groups, respectively. CO2 reactivity of the affected detectors was 1.75 +/- 0.3 sec-1 mm Hg-1 and 1.27 +/- 0.2 sec-1 mm Hg-1 for the two groups, respectively. The CO2 reactivity difference between affected detectors of the hemodynamic group and age-matched healthy control subjects was significant. CONCLUSIONS: The difference in CO2 reactivity between the two groups supports the concept that CT criteria can identify two pathophysiologic entities. In addition, we conclude that during the chronic stage, lower CO2 reactivity of the watershed infarction indicates that the global hemodynamic situation in these infarcts is more severely compromised than in territorial infarctions.

Hemodynamic sequelae of ventricular tachyarrhythmias on cerebral blood flow.

The present experiments were designed to compare the behavior of cerebral blood flow (CBF) during acute moderate and severe hypotensive episodes induced by either ventricular tachycardias (VT) or by hemorrhage. Using the microsphere method CBF was determined in 20 Sprague-Dawley rats during sinus rhythm (Group A), in 28 animals during high-rate VT (Group B) and in 10 animals after hemorrhage (Group C). According to the decrease in blood pressure and with respect to the lower threshold of cerebral autoregulation Group B was divided into 2 subgroups (B1: 80-130 mmHg; B2: 50-80 mmHg) retrospectively. While CBF remained constant in Group B1 (0.98 +/- 0.3 ml g-1 min-1 vs. 1.01 +/- 0.32 in controls, NS), CBF decreased markedly during severely hypotensive VT in Group B2 (0.52 +/- 0.2 ml g-1 min-1, p < 0.001 vs. A; p < 0.05 vs. C) and during hypovolemic hypotension in Group C (0.77 +/- 0.22 ml g-1 min-1 vs. A; NS). Cerebrovascular resistance and autoregulation indices indicated a maintenance of CBF regulation during hypovolemic hypotension and a failure during normovolemic hypotension. These findings indicate that the autoregulatory ability of the brain is substantially more stable during hypovolemic hypotension than during normovolemic hypotension. Therefore, the hemodynamic sequelae of acute hypotensive episodes on CBF depend on the underlying cause of hypotension.

Effect of flunarizine on cerebral blood flow in baboons with or without focal cerebral ischaemia.

In baboons with or without regional cerebral ischaemia (achieved by transorbital clip of the middle cerebral artery), cerebral blood flow (CBF) was measured using the intra-arterial Xenon-133 technique during steady-state, slight hypotension, and hypocapnia before and after administration of various doses of the calcium antagonist flunarizine (0.5 mg kg-1, 1.0 mg kg-1, or 10 micrograms kg-1 min-1 over 30 min). In normal baboons flunarizine did not alter CBF significantly, but at reduced blood pressure it increased CBF by 19.9% owing to exaggerated vasodilatory autoregulation. During hypocapnia flunarizine impaired the physiological reduction in CBF owing to reduced vasoconstriction. In baboons with cerebral ischaemia, CBF measurements were stable and comparable with those in a control group using an arterial clip unless flunarizine was added. In a group of five flunarizine-treated animals, mean CBF after positioning of the clip was higher than in the control group. However, the increase in mean CBF varied significantly between animals, indicating that a secondary reduction in CBF due to postischaemic pathophysiological processes was not prevented consistently.

Contralateral cerebellar diaschisis 7 hours after MCA-occlusion in primates.

2,3,5-triphenyltetrazoliumchloride (TTC) as an indicator of mitochondrial function in combination with regional cerebral blood flow measurements was used in six baboons 6.9 +/- 1.2 h after permanent occlusion of the left middle cerebral artery. Staining with TTC was compared with blood flow data obtained during normocapnia using the microsphere method. Five animals showed a focal area of unstained tissue in the left middle cerebral artery territory. Mean blood flow in the unstained area was 28.3 +/- 15.4 ml min-1 100 g-1. Five of 6 animals showed a significant decrease of contralateral cerebellar blood flow in the presence of normal TTC staining. We conclude that at this early stage of infarction contralateral cerebellar diaschisis is caused by functional deactivation.

Immersion and perfusion staining with 2,3,5-triphenyltetrazolium chloride (TTC) compared to mitochondrial enzymes 6 hours after MCA-occlusion in primates.

2,3,5-triphenyltetrazolium chloride (TTC) is commonly applied in rodents and cats as a marker of infarcted tissue as early as 20 min after the onset of focal ischaemia. At this stage it is suggested that it reflects hypoperfusion rather than failure of respiratory chain. Immersion of brain slices in TTC solution is preferable in comparison to perfusion with TTC in order to ensure, that enough TTC enters the post-occlusion tissue. We compared immersion technique versus perfusion technique 6 h after permanent occlusion of the left middle cerebral artery in 18 baboons. In addition, we assessed the function of the respiratory chain enzymes of stained and unstained tissue in three baboons. The immersion technique revealed an absence of TTC staining limited to subcortical structures in two animals. In seven experiments TTC indicated involvement of almost the entire MCA territory. The extent of the ischaemic lesion indicated by the perfusion technique was very similar. Tissue samples from the presumed infarcted areas revealed normal mitochondrial function. We conclude that perfusion and immersion technique do not cause significant different ischaemic delineation 6 h after middle cerebral artery occlusion. TTC staining appears to be a reliable method of evaluating volume of infarction in primates. Furthermore, absence of TTC staining 6 h after stroke onset is caused by energy or oxygen depletion rather than by mitochondrial injury.

Case report: regional cerebral hypoperfusion induced by ventricular tachycardia - short-term hippocampal hypoperfusion and its potential relationship to selective neuronal damage.

BACKGROUND: Focussing on regional cerebral hypoperfusion during hemodynamically stable, but borderline hypotensive, sustained ventricular tachycardia (VT) experimental studies show (1) a reduction of cerebral blood flow (CBF) during tachyarrhythmias in contrast to the concept of CBF autoregulation, (2) a mediation of hypoperfusion by neuronal and humoral mechanisms, and (3) an involvment of microcirculation due to an ischemic stress response of the cerebral tissue. The clinical relevance of these observations remains still unclear. CASE REPORTS: Two patients with coronary artery disease, left ventricular dysfunction and sustained monomorphic VT underwent electrophysiological study. VT was induced and the tracer (99m)Tc-HMPAO was injected after 3 minutes of ongoing VT. Regional CBF during this life threatening arrhythmia was determined with brain SPECT. A scanning protocol was performed after termination of VT. The measurements were repeated at baseline during normofrequent sinus rhythm (SR) one week later. CBF during SR was significantly reduced in the temporal lobe in comparison to the conditions during stable VT, particularly in the left hippocampus. CONCLUSION: The reduction of hippocampal CBF due to cerebrovascular vasoconstriction and neuronal reflex mechanism previously observed in experiments during stable, sustained VT can be confirmed in a clinical scenario by high resolution (99m)Tc-HMPAO brain SPECT. This supports the hypothesis that repetitive stable VT can play a role in the pathophysiology of cerebrovascular insufficiency. Further clinical studies are needed to analyze the impact of tachyarrhythmias on cognitive and mnemic function.