Brain-machine interfaces for rehabilitation of poststroke hemiplegia.

Noninvasive brain-machine interfaces (BMIs) are typically associated with neuroprosthetic applications or communication aids developed to assist in daily life after loss of motor function, eg, in severe paralysis. However, BMI technology has recently been found to be a powerful tool to promote neural plasticity facilitating motor recovery after brain damage, eg, due to stroke or trauma. In such BMI paradigms, motor cortical output and input are simultaneously activated, for instance by translating motor cortical activity associated with the attempt to move the paralyzed fingers into actual exoskeleton-driven finger movements, resulting in contingent visual and somatosensory feedback. Here, we describe the rationale and basic principles underlying such BMI motor rehabilitation paradigms and review recent studies that provide new insights into BMI-related neural plasticity and reorganization. Current challenges in clinical implementation and the broader use of BMI technology in stroke neurorehabilitation are discussed.

Sensorimotor event-related desynchronization represents the excitability of human spinal motoneurons.

Amplitudes of mu and beta (7-26Hz) oscillations measured by electroencephalography over the sensorimotor areas are suppressed during motor imagery as well as during voluntary movements. This phenomenon is referred to as event-related desynchronization (ERD) and is known to reflect motor cortical excitability. The increased motor cortical excitability associated with ERD during hand motor imagery would induce a descending cortical volley to spinal motoneurons, resulting in facilitation of spinal motoneuronal excitability. Therefore, in the present study, we tested the association of ERD during motor imagery with the excitability of spinal motoneurons in 15 healthy participants. Spinal excitability was tested using the F-wave recorded from the right abductor pollicis brevis muscle. The F-wave results from antidromic activation of spinal motoneurons and is induced by peripheral nerve stimulation. Participants performed 5s of motor imagery of right thumb abduction following 7s of rest. The right median nerve was stimulated at wrist level when the ERD magnitude of the contralateral hand sensorimotor area exceeded predetermined thresholds during motor imagery. The results showed ERD magnitude during hand motor imagery was associated with an increase in F-wave persistence, but not with the response average of F-wave amplitude or F-wave latency. These findings suggest that the ERD magnitude may be a biomarker representing increases in the excitability of both cortical and spinal levels.

EEG-EMG coherence changes in postural tasks.

PURPOSE: Recent studies have investigated the possible function of synchronous oscillatory activity within the sensorimotor cortex of monkeys and humans that is thought to arise from synchronous discharge of large numbers of cortical neurons. There has been found clear task-dependent changes in 15-30 Hz oscillations. In leg muscles, coherence also occurs in the same frequency band during voluntary static contraction. Therefore we investigated changes in coherence in leg muscles during several postural tasks. METHODS: We examined the coherence between EEGs and soleus EMGs during voluntary contraction and in various postural tasks. RESULTS: There was a significant coherence during voluntary static contraction, but not during standing, forward bending, or standing on one foot; whereas, there was significant coherence during stamping the ground. CONCLUSION: These results suggest that the coherence at 15-30 Hz originates from the motor cortex during voluntary contraction, not when doing postural tasks. Coherence analysis indicates that during postural tasks the motor cortex would not produce the synchronous discharge of large numbers of cortical neurons or might not induce soleus EMG activity.

Post-activation depression of the soleus H-reflex in stroke patients.

PURPOSE: We examined post-activation depression in 35 stroke patients and 10 healthy subjects, and investigated whether their clinical symptoms were correlated to post-activation depression. METHODS: Post-activation depression of the soleus H-reflex evoked by electrical stimulation of the common peroneal nerve with supramaximal intensity of motor response on the tibialis anterior muscle. RESULTS: Post-activation depression was decreased on the affected side of the stroke patients. There was a significant difference between the affected and unaffected sides of the patients with post-activation depression, but no difference between the unaffected sides of the patients and healthy subjects. The presence of ankle clonus and the decrease in post-activation depression were correlated. CONCLUSION: Decreased post-activation depression in stroke patients suggests that a mechanism other than postsynaptic inhibition, such as reciprocal Ia inhibition and Ib inhibition, and presynaptic inhibition, may contribute to the exaggerated stretch reflexes, in particular, the manifestation of clonus.

Changes of reflex size in upper limbs using wrist splint in hemiplegic patients.

We evaluated the effect of prolonged wrist extension on H reflex in the flexor carpi radialis (FCR) muscle and tendon jerk (T) reflex in the biceps brachii (BB) muscle of 17 chronic hemiplegic patients. H reflex of the FCR and T reflex of the BB were assessed every 5 minutes within 20 minutes during prolonged wrist extension and post-20 minutes after the extension. As a result, H reflex in the FCR was reduced by passive wrist stretch in 82% of the spastic limbs. The effect was larger in the higher spastic group. In 45% of the spastic limbs, T reflex in the BB also was reduced by passive wrist stretch. The inhibitory effects had a tendency to strengthen in accordance with the grade of muscle tone. We considered from these results, prolonged wrist extension generated inhibitory projections via probably group II afferents of the FCR in the homonym and in the transjoint in spastic limbs.

Integration-plot test for peri-stimulus time histograms in human motor units.

A statistical test is proposed for peri-stimulus time histograms in human motor units for the case where a test stimulus is delivered at a constant interval after a previous discharge. This mathematically described test included the notion of the multiple comparison and thus achieved higher sensitivity than the previously proposed method. With regard to data acquisition, the interval from a sham stimulus to the next discharge was acquired as a control, and the total number of samples was set to be four times as large as that in the test situation to reduce the statistical scattering noise. A newly defined statistical object, the integration plot (timewise accumulation of the test histogram without control subtraction) was used for this statistical test. The integration plot had less noise than the cumulative sum (CUSUM) plot (1/square root(2) in theory) and thus represented the neural effect. To compare this integration-plot test with that of the CUSUM, a simulation experiment that compared two sample histograms (one of which had a faint structural change from 20 ms) was conducted. As a result, the present test succeeded in detecting the onset of the change point earlier (23 ms on average) than the CUSUM test (27 ms on average), and the detection probability was also higher (9 out of 10) than the CUSUM (6 out of 10). It was therefore confirmed experimentally that the present statistical test had higher sensitivity than that of the CUSUM proposed previously.

Cortical neuromagnetic activity associated with cutaneomuscular reflex.

Cortical activity related to the late component of the cutanomuscular reflex was studied by measuring somatosensory evoked magnetic fields (SEFs) during isometric contraction of the reflex-induced muscle. After electrical stimulation to the index finger with intensity of three times of the perception threshold, three peaks of the cortical activity were detected within the somato-sensory area contralaterally to the stimulation site. Three dimentional location and the amplitude of the equivalent current dipoles for each peak were compared to that of observed SEF without muscle contraction. Significantly increased third component of SEFs (the latency of about 50 ms) always preceeded ca 20 ms against the peak of the late component of the cutaneomusucular reflex observed in the first dorsal interosseous (1DI) muscle. The conduction delay from the primary somatomotor cortex to the 1DI was determined as also ca 20 ms according to the result of the transcranial magnetic stimulation. We conclude from these evidences that all or part of the ingredient of the third component of SEFs may contribute to inducement of the late excitatory component of the cutaneomuscular reflex.

Motor strategies for initiating downward-oriented movements during standing in adults.

Sitting down and squatting are routine activities in daily living that lower the body mass by flexing the trunk and legs, but they obviously require different motor strategies for each goal posture. The former action must transfer the supporting surface onto a seat, whereas the latter must maintain the center of mass within the same base of both feet. By comparing the performance of both maneuvers, the mechanisms involved in initiating the downward-oriented movements and the process of optimizing the performance during their repetitions were studied. Twelve healthy subjects were asked to perform sitting-down and squatting actions immediately when a light cue was given, but at a natural speed. Electromyograms, angular movements of the joints of the right leg, and center of pressure (COP) displacement were recorded before and during each task. The initial mechanisms to initiate the break from the upright posture and the changes of postural adjustments during repetitive movements were analyzed separately. The sitting-down movement was achieved by a stereotyped motor strategy characterized by a gastrocnemius muscle burst coupled with deactivation of the erector spinae muscle. The former produced a transient COP displacement in the forward direction, and simultaneous unlocking of the trunk prevented a fall backward. By contrast, because of the absence of any need to produce momentum in a given direction, a variety of motor strategies were available to initiate squatting. The direction of initial COP displacement to initiate squatting varied with the muscles involved in unlocking the upright posture. During repetition of sitting down, the average COP position of the initial standing posture in the preparatory period was immediately shifted forward after the second trial. Simultaneously, the erector spinae muscle was deactivated earlier in the later trials. These resulted in a decreased momentum in the backward direction while the subjects were transferring themselves onto the seat. In the squatting task, however, these changes could not be identified, except for a slight flexed position of the knee during standing in the first trial. These findings suggest that in the case of transferring the body-mass to another supporting base the central nervous system immediately adjusts the size of the initial impetus to optimize the performance.

Statistical test for peri-stimulus time histograms in assessing motor neuron activity.

The peri-stimulus time histogram is a valuable tool for evaluating neural connections in humans. To detect the degree to which a conditioning stimulus to a sensory nerve modulates motor neuron activity, a histogram of motor unit spike intervals after a conditioning stimulus is measured. This histogram allows the effect of the conditioning stimulus to be visualised. By comparison with a reference histogram of motor unit spike intervals after a sham stimulus, the noise caused by spontaneous firing sway can be removed. However, no valid statistical test has yet been developed to separate the physiological effect from the spontaneous sway and statistical noise. A computational method has been proposed to detect modulation caused by a conditioning stimulus. To clarify the effect of a conditioning stimulus, this new method used reference histograms to calculate a confidence interval. A simulated experiment demonstrated that about 2000 re-samplings were sufficient to estimate a confidence interval for a histogram with 1 ms bin width constructed from 300 triggers. Testing of the experimental data, measured from the tibialis anterior muscles during the elicitation of the excitatory spinal reflex, confirmed that significant peaks were produced at 30, 34, 35 and 38ms after the conditioning stimulus. These correspond appropriately to the delay of the spinal reflex.

The results of a primary and staged pantalar arthrodesis and tibiotalocalcaneal arthrodesis in adult patients.

Twenty-three patients (twenty-seven feet) with either a primary or staged pantalar arthrodesis or a tibiotalocalcaneal arthrodesis were evaluated to determine their clinical status. The main indication for the operation was the presence of severe pain unresponsive to non-operative treatment. Fourteen feet (twelve patients) had a pantalar arthrodesis; a fusion of the ankle, subtalar, talonavicular and calcaneocuboid joints. Half the feet in this group had either a triple arthrodesis or an ankle fusion performed at an earlier time. The remaining seven feet had all joints fused during the same operation. Thirteen feet (eleven patients) had a tibiotalocalcaneal arthrodesis. Two of these feet had an ankle arthrodesis performed four and six years previously. The other eleven had the ankle and subtalar joints fused during the same operation. All patients were followed for a mean of fifty-five months (14 to 159 months) from the time of their final arthrodesis procedure. Overall, twenty-three of the twenty-seven feet achieved a solid arthrodesis of all joints operated upon. Four feet had a failure of fusion of only a single joint and all were in the pantalar group. The mean time to radiographic fusion was twenty-three weeks and resulted in a plantigrade foot with an average tibia-floor angle of 87 degrees. Complications occurred in ten feet (37%); of which there were three deep infections; two ankles and one subtalar joint. These arthrodeses procedures resulted in marked relief of the patients' preoperative pain, the main indication for performing the surgery. Postoperatively there was no pain in eleven feet, mild occasional pain in thirteen feet, and moderate pain in only three feet. However, when all parameters of our clinical rating scale were evaluated, only five patients had an excellent clinical result, nine were rated good, three were rated fair and six patients had a poor result. These operations must be considered to be salvage procedures. They are technically difficult to perform and major complications may occur. Pain relief appears to be the main indication for performing these operations, and may account for whatever improvement occurs in the patient's function.

Promoter analysis of genes that are coordinately expressed during pollen development reveals pollen-specific enhancer sequences and shared regulatory elements.

We have investigated the functional organization and properties of cis regulatory elements in the promoter regions of two genes from tomato (LAT52 and LAT59) that are preferentially and coordinately expressed during pollen maturation. Promoter deletion analysis in transgenic plants demonstrated that only minimal (less than 200 bp) promoter proximal regions are required for developmentally regulated expression in pollen and in specific cell types of the sporophyte. Cis-acting regulatory regions of these two promoters and of a third pollen-expressed promoter (LAT56) were characterized in detail using a transient expression assay. We identified two upstream activator regions in the LAT52 promoter and further showed that a 19-bp segment from one of those regions enhanced expression of the heterologous CaMV35S promoter in pollen. Similarities in sequence between crucial cis elements provide evidence that shared regulatory elements are involved in the coordinate expression of the LAT genes during microsporogenesis.