Ankle dorsiflexion as an fMRI paradigm to assay motor control for walking during rehabilitation

The ability to walk independently with the velocity and endurance that permit home and community activities is a highly regarded goal for neurological rehabilitation after stroke. This pilot study explored a functional magnetic resonance imaging (fMRI) activation paradigm for its ability to reflect phases of motor learning over the course of locomotor rehabilitation-mediated functional gains. Ankle dorsiflexion is an important kinematic aspect of the swing and initial stance phase of the gait cycle. The motor control of dorsiflexion depends in part on descending input from primary motor cortex. Thus, an fMRI activation paradigm using voluntary ankle dorsiflexion has face validity for the serial study of walking-related interventions. Healthy control subjects consistently engaged contralateral primary sensorimotor cortex (S1M1), supplementary motor area (SMA), premotor (PM) and cingulate motor (CMA) cortices, and ipsilateral cerebellum. Four adults with chronic hemiparetic stroke evolved practice-induced representational plasticity associated with gains in speed, endurance, motor control, and kinematics for walking. For example, an initial increase in activation within the thoracolumbar muscle representation of S1M1 in these subjects was followed by more focused activity toward the foot representation with additional pulses of training. Contralateral CMA and the secondary sensory area also reflected change with practice and gains. We demonstrate that the supraspinal sensorimotor network for the neural control of walking can be assessed indirectly by ankle dorsiflexion. The ankle paradigm may serve as an ongoing physiological assay of the optimal type, duration, and intensity of rehabilitative gait training.     

Approaching an ecologically valid functional anatomy of spontaneous "willed" action

We used functional magnetic resonance imaging of healthy subjects to investigate the neural basis for spontaneous "willed" action. We hypothesised that such action involves prefrontal cortex (PFC) and supplementary motor area (SMA), in addition to primary motor cortex. Furthermore, we predicted that PFC and SMA would demonstrate similar temporal response dynamics, distinct from primary motor cortex. Specifically, we predicted earlier activation in PFC and SMA, manifest as shorter response latencies compared with primary motor cortex. Six right-handed males participated in an event-related design and were required to generate spontaneous motor acts inside the scanner. By deciding "which" of two buttons to press, and "when" to press them, subjects generated sequences of action that were of high information content ("novelty" or "randomness"). Utilising a short repetition time (1 s), we acquired functional images that covered most of the frontal and parietal cortices. The onset of action was associated with significant activation in bilateral PFC, left primary motor cortex, and, close to the midline, SMA. Following action, mean time to half-maximum blood oxygenation level-dependent response was significantly earlier in left PFC and SMA than primary motor cortex. Our findings suggest that neural correlates of spontaneous willed action are distributed in executive and motor centres, and that temporal response dynamics differentiate "higher" regions from subordinate motor areas.     

Motor imagery of walking following training in locomotor attention. The effect of "the tango lesson"

The hypothesis of this study is that focusing attention on walking motor schemes could modify sensorimotor activation of the brain. Indeed, gait is a learned automated process, mostly regulated by subcortical and spinal structures. We examined the functional changes in the activity of the cerebral areas involved in locomotor imagery tasks, before and after one week of training consisting of physical and mental practice. The aim of the training was to focus the subject's conscious attention on the movements involved in walking. In our training, subjects were asked to perform basic tango steps, which require specific ways of walking; each tango lesson ended with motor imagery training of the performed steps. The results show that training determines an expansion of active bilateral motor areas during locomotor imagery. This finding, together with a reduction of visuospatial activation in the posterior right brain, suggests a decreased role of visual imagery processes in the post-training period in favor of motor-kinesthetic ones.     

The functional neuroanatomy of simple calculation and number repetition: A parametric PET activation study

We examined cerebral activation patterns with positron emission tomography (PET) in 12 right-handed normal volunteers while they were completing simple calculation tasks or merely repeating numbers. Using a parametric experimental design, during calculation we found activation in the medial frontal/cingulate gyri, left dorsolateral prefrontal cortex, left anterior insular cortex and right anterior insular cortex/putamen, left lateral parietal cortex, and the medial thalamus. Number repetition engaged bilateral inferior sensorimotor cortex, bilateral temporal areas, and left inferior frontal cortex. These results suggest a functional anatomical network for simple calculation, which includes aspects of attention, auditory, and motor processing and the phonological store and articulatory loop components of working memory; they add some support for a special role of the parietal cortex in calculation tasks.     

Effects of robot-aided bilateral force-induced isokinetic arm training combined with conventional rehabilitation on arm motor function in patients with chronic stroke

OBJECTIVE: To analyze the effects of conventional rehabilitation combined with bilateral force-induced isokinetic arm movement training on paretic upper-limb motor recovery in patients with chronic stroke. DESIGN: Single-cohort, pre- and postretention design. SETTING: Rehabilitation department at a medical university. PARTICIPANTS: Twenty subjects who had unilateral strokes at least 6 months before enrolling in the study. INTERVENTION: A training program (40min/session, 3 sessions/wk for 8wk) consisting of 10 minutes of conventional rehabilitation and 30 minutes of robot-aided, bilateral force-induced, isokinetic arm movement training to improve paretic upper-limb motor function. MAIN OUTCOME MEASURES: The interval of pretest, post-test, and retention test was set at 8 weeks. Clinical arm motor function (Fugl-Meyer Assessment [FMA], upper-limb motor function, Frenchay Arm Test, Modified Ashworth Scale), paretic upper-limb strength (grip strength, arm push and pull strength), and reaching kinematics analysis (peak velocity, percentage of time to peak velocity, movement time, normalized jerk score) were used as outcome measures. RESULTS: After comparing the sets of scores, we found that the post-test and retention test in arm motor function significantly improved in terms of grip (P=.009), push (P=.001), and pull (P=.001) strengths, and FMA upper-limb scale (P<.001). Reaching kinematics significantly improved in terms of movement time (P=.015), peak velocity (P=.035), percentage of time to peak velocity (P=.004), and normalized jerk score (P=.008). Improvement in reaching ability was not sustained in the retention test. CONCLUSIONS: Preliminary results showed that conventional rehabilitation combined with robot-aided, bilateral force-induced, isokinetic arm training might enhance the recovery of strength and motor control ability in the paretic upper limb of patients with chronic stroke.     

Cortical mechanisms for acquisition and performance of bimanual motor sequences

We used functional magnetic resonance imaging to investigate the cortical mechanisms contributing to the acquisition and performance of a complex, bimanual motor sequence. To that aim, five subjects were trained on a difficult, asymmetrical finger opposition task. Their performance rate almost doubled in the course of training and approached the performance rate in an untrained, symmetrical finger opposition task. Before training, performance of the asymmetrical sequence was associated with activity in M1, premotor cortex, supplementary motor cortex, and parietal cortex. After training, performance of the asymmetrical sequence was associated mainly with activity in M1, and little activity outside M1 remained. The latter pattern of cortical activation resembled that observed during the execution of symmetrical sequences, which was unaffected by practice with the asymmetrical sequence. The activation pattern obtained with the symmetrical bimanual sequence was indistinguishable from the combined activation measured in contralateral hemispheres during unimanual control sequences. The data indicate that cortical regions previously implicated in the acquisition of difficult unimanual motor sequences also contribute to the acquisition of asymmetrical bimanual sequences. We found no evidence for an expansion of activity in M1 after acquisition of the asymmetrical sequence (while this has been reported after acquisition of unimanual sequences). In the context of existing literature, the data suggest that the acquisition of unimanual and bimanual motor sequences may rely on similar cortical mechanisms, but that the formation of long-term, procedural memories for the two types of sequences might at least in part depend on different mechanisms.     

Cross-modal plasticity for sensory and motor activation patterns in blind subjects

Experimental data on cortical reorganization in blind subjects using H(2)(15)O positron emission tomography and functional magnetic resonance imaging (fMRI) showed activation of the visual cortex related to Braille reading and tactile discrimination tasks in congenitally and early blind subjects. The purpose of our study was to differentiate whether occipital activation of blind subjects during Braille reading is task specific or only triggered by sensory or motor area activation. Twelve congenitally and early-onset blind subjects were studied with fMRI during Braille reading, discriminating nonsense dots, sensory stimulation with electromagnetic pulses, and finger tapping. All experiments were performed utilizing a block design with 6 active epochs alternating with 6 rest conditions lasting 34 s each. Echo-planar imaging sequences with 34 transversal slices were performed on a 1.5-T MR scanner. All blind individuals reading Braille and discriminating nonsense dots showed robust activation of the primary, secondary, and higher visual cortex. Application of peripheral electrical stimuli to the reading hand revealed expected sensory activation of the primary somatosensory cortex, but no activation in the visual cortex. Pure motor activation during finger tapping with the reading hand showed expected precentral activation and no activation of visual cortex. In conclusion, occipital activation during Braille reading and discrimination tasks is not due to plasticity of sensory or motor function; pure motor or sensory tasks do not lead to an activation of striate cortex. The brain learns to differentiate between "finger touching" and "finger reading." Our results suggest that activation of the visual cortex in blind subjects is related to higher and more complex brain functions.     

Neural substrates of visuomotor learning based on improved feedback control and prediction

Motor skills emerge from learning feedforward commands as well as improvements in feedback control. These two components of learning were investigated in a compensatory visuomotor tracking task on a trial-by-trial basis. Between-trial learning was characterized with a state-space model to provide smoothed estimates of feedforward and feedback learning, separable from random fluctuations in motor performance and error. The resultant parameters were correlated with brain activity using magnetic resonance imaging. Learning related to the generation of a feedforward command correlated with activity in dorsal premotor cortex, inferior parietal lobule, supplementary motor area and cingulate motor area, supporting a role of these areas in retrieving and executing a predictive motor command. Modulation of feedback control was associated with activity in bilateral posterior superior parietal lobule as well as right ventral premotor cortex. Performance error correlated with activity in a widespread cortical and subcortical network including bilateral parietal, premotor and rostral anterior cingulate cortex as well as the cerebellar cortex. Finally, trial-by-trial changes of kinematics, as measured by mean absolute hand acceleration, correlated with activity in motor cortex and anterior cerebellum. The results demonstrate that incremental, learning-dependent changes can be modeled on a trial-by-trial basis and neural substrates for feedforward control of novel motor programs are localized to secondary motor areas.     

Arm Training Induced Brain Plasticity in Stroke Studied with Serial Positron Emission Tomography

We used serial positron emission tomography (PET) to study training-induced brain plasticity after severe hemiparetic stroke. Ten patients were randomized to either task-oriented arm training or to a control group and scanned before and after 22.6 ± 1.6 days of treatment using passive movements as an activation paradigm. Increases of regional cerebral blood flow (rCBF) were assessed using statistical parametric mapping (SPM99). Before treatment, all stroke patients revealed bilateral activation of the inferior parietal cortex (IPC). After task-oriented arm training, activation was found bilaterally in IPC and premotor cortex, but also in the contralateral sensorimotor cortex (SMC). The control group only showed weak activation of the ipsilateral IPC. After treatment, the training group revealed relatively more activation bilaterally in IPC, premotor areas, and in the contralateral SMC. Five normal subjects showed no statistical significant differences between two separate PET studies. In this group of patients, task-oriented arm training induced functional brain reorganization in bilateral sensory and motor systems.     

Driving plasticity in the motor cortex in recurrent low back pain

The sensory and motor systems can reorganise following injury and learning of new motor skills. Recently we observed adaptive changes in motor cortical organisation in patients with recurrent low back pain (LBP), which are linked to altered motor coordination. Although changes in motor coordination can be trained and are associated with improved symptoms and function, it remains unclear whether these training‐induced changes are related to reorganisation of the motor cortex. This was investigated using the model of a delay in postural activation of the deep abdominal muscle, transversus abdominis (TrA) in 20 individuals with recurrent LBP. Subjects were allocated to either motor skill training that involved isolated voluntary contractions of TrA, or a control intervention of self‐paced walking exercise for 2 weeks. Electromyographic (EMG) activity was recorded from TrA bilaterally using intramuscular fine‐wire electrodes. Motor cortical organisation using transcranial magnetic stimulation (TMS) and postural activation associated with single rapid arm movements were investigated before and after training. Motor skill training induced an anterior and medial shift in motor cortical representation of TrA, towards that observed in healthy individuals from our previous study. This shift was associated with earlier postural activation of TrA. Changes were not observed following unskilled walking exercise. This is the first observation that motor training can reverse reorganisation of neuronal networks of the motor cortex in people with recurrent pain. The observed relationship between cortical reorganisation and changes in motor coordination following motor training provides unique insight into potential mechanisms that underlie recovery.     

Functional dominance of finger flexion over extension, expressed in left parietal activation

Sensory stimuli may elicit a widely distributed parietal-premotor circuitry underlying task-related movements such as grasping. These stimuli include the visual presentation of an object to be grasped, as well as the observation of grasping performed by others. In this study, we used functional Magnetic Resonance Imaging (fMRI) to test whether the performance of simple finger flexion, contrasted to extension, might similarly activate higher-order circuitry associated with grasping. Statistical Parametric Mapping (SPM) showed that flexion, compared to extension, was related with significant activation of the left posterior parietal cortex and posterior insula, bilaterally. This pattern supported our hypothesis that simple finger flexion has a specific relation with circuitry involved in preparing manual tasks. Although the two motor conditions showed major overlap in the primary motor cortex, increased flexion-related activation at the precentral motor-premotor junction further supported its association with higher-order motor control.     

Reactivation of motor brain areas during explicit memory for actions

Recent functional brain imaging studies have shown that sensory-specific brain regions that are activated during perception/encoding of sensory-specific information are reactivated during memory retrieval of the same information. Here we used PET to examine whether verbal retrieval of action phrases is associated with reactivation of motor brain regions if the actions were overtly or covertly performed during encoding. Compared to a verbal condition, encoding by means of overt as well as covert activity was associated with differential activity in regions in contralateral somatosensory and motor cortex. Several of these regions were reactivated during retrieval. Common to both the overt and covert conditions was reactivation of regions in left ventral motor cortex and left inferior parietal cortex. A direct comparison of the overt and covert activity conditions showed that activation and reactivation of left dorsal parietal cortex and right cerebellum was specific to the overt condition. These results support the reactivation hypothesis by showing that verbal-explicit memory of actions involves areas that are engaged during overt and covert motor activity.     

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.     

GABAergic inhibitory mechanisms for repetition-adaptivity in large-scale brain systems

Molecular mechanisms for systems level adaptivity of brain activation are largely unknown but a key role for active inhibition by gamma-aminobutyric acid (GABA) is plausible. We used functional magnetic resonance imaging to contrast the modulatory effects on brain adaptivity to task repetition and task difficulty of two GABAergic drugs, lorazepam and flumazenil. In a working memory paradigm, occipitotemporal regions clearly demonstrated attenuation of activation as a function of within-session task repetition or practice in data acquired following placebo, but this spatiotemporal pattern of repetition adaptivity was abolished by both lorazepam and flumazenil. However, in other brain systems flumazenil enhanced repetition adaptivity compared to placebo: in frontal cortex, flumzenil induced attenuation of signal related to task repetition and in hippocampus it exaggerated normal enhancement of signal with repetition. In contrast, there were no significant effects of either flumazenil or lorazepam on areas of frontal cortex which normally demonstrated significant neurocognitive load response or adaptivity to task difficulty. We argue that repetition adaptivity of large-scale brain systems is regulated by GABAergic inhibitory mechanisms and that expression of repetition adaptivity in a given brain system may show an "inverted-U" form of relationship with pharmacologically manipulable levels of GABAergic inhibitory tone.     

Brain activation related to the change between bimanual motor programs

By using positron emission tomography, we aimed to identify cerebral foci of neuronal activation associated with the initiation of a specific motor program. To that end, a state of repeatedly alternating in- and antiphase of bimanual flexion and extension movements was compared with similar movement responses except phase changing. This comparison provided the opportunity to eliminate confounding effects of attention and simple movements. Change between the two bimanual motor programs was related with activation at the posterior border of the left angular gyrus, the right precuneus, and the right premotor and right medial prefrontal cortex. In a subsequent experiment, with attention and random movements as additional variables, activation at the posterior border of the left angular gyrus was found at the same significance level. This posterior parietal activation may indicate an equivalence with the coding of intention in monkey posterior parietal cortex. Lesion of the left posterior parietal cortex in human gives rise to left-right disorientation and ideomotor apraxia. Our results may support the view that these symptoms reflect the inability to transpose a motor plan to the representation of a personal body scheme. Activation of the right premotor and right medial prefrontal cortex was related both to the change between motor programs and to the condition with strictly regular movement in which no additional responses were made to randomly presented signals. This is consistent with the concept that motor preparation is associated with both the selection of internally instructed movements and the suppression of irrelevant environmental stimuli.     

Age dependency of the hemodynamic response as measured by functional near-infrared spectroscopy

Aging reduces cerebral blood flow in association cortices during rest. However, the influence of age on functional brain activation is still controversial. The aim of our study was to examine age dependency of brain activation in primary and association cortices. Therefore, changes in the concentration of oxy- and deoxyhemoglobin as well as changes in the redox state of cytochrome-c-oxidase (Cyt-Ox) were measured by functional near-infrared spectroscopy (fNIRS) in the lateral prefrontal and motor cortices during an event-related Stroop interference task. Fourteen young (23.9 +/- 3.1 years old) and 14 elderly subjects (65.1 +/- 3.1) participated in the study. Data revealed two effects of aging on brain activation: (1) Elderly and young subjects used the lateral prefrontal cortex to cope with interference during the Stroop task. In young subjects, the vascular response was higher during incongruent than neutral trials in the entire examined lateral prefrontal cortex. However, in the elderly, all lateral prefrontal regions showed a hemodynamic response but not necessarily a specific interference effect. (2) The hemodynamic response was reduced in elderly subjects in the lateral prefrontal association cortex, but obviously not in the motor cortex. We propose that calculating effect sizes is the only reliable approach to analyze age-related effects in fNIRS studies, because they are independent from the assumed differential pathlength factor. In summary, our findings suggest that aging decreases the hemodynamic response in the frontal association cortex during functional activation, omitting the primary motor cortex.     

Imitation and observational learning of hand actions: prefrontal involvement and connectivity

The first aim of this event-related fMRI study was to identify the neural circuits involved in imitation learning. We used a rapid imitation task where participants directly imitated pictures of guitar chords. The results provide clear evidence for the involvement of dorsolateral prefrontal cortex, as well as the fronto-parietal mirror circuit (FPMC) during action imitation when the requirements for working memory are low. Connectivity analyses further indicated a robust connectivity between left prefrontal cortex and the components of the FPMC bilaterally. We conclude that a mechanism of automatic perception-action matching alone is insufficient to account for imitation learning. Rather, the motor representation of an observed, complex action, as provided by the FPMC, only serves as the ‘raw material’ for higher-order supervisory and monitoring operations associated with the prefrontal cortex. The second aim of this study was to assess whether these neural circuits are also recruited during observational practice (OP, without motor execution), or only during physical practice (PP). Whereas prefrontal cortex was not consistently activated in action observation across all participants, prefrontal activation intensities did predict the behavioural practice effects, thus indicating a crucial role of prefrontal cortex also in OP. In addition, whilst OP and PP produced similar activation intensities in the FPMC when assessed during action observation, during imitative execution, the practice-related activation decreases were significantly more pronounced for PP than for OP. This dissociation indicates a lack of execution-related resources in observationally practised actions. More specifically, we found neural efficiency effects in the right motor cingulate-basal ganglia circuit and the FPMC that were only observed after PP but not after OP. Finally, we confirmed that practice generally induced activation decreases in the FPMC during both action observation and imitation sessions and outline a framework explaining the discrepant findings in the literature.     

Outcomes following kinesthetic feedback for gait training in a direct access environment: A case report on social wellness in relation to gait impairment.

The purpose of this case report was to describe the outcomes following the use of kinesthetic feedback as a primary intervention strategy for gait training. The plan of care for this 22-year-old female addressed the patient's social wellness goal of “walking more normally,” using motor learning principles. At initial examination, the patient demonstrated asymmetries for gait kinematics between the left and right lower extremity (analyzed using video motion analysis), pattern of force distribution at the foot, and activation of specific lower extremity muscles (as measured by surface electromyography). Interventions for this patient consisted of neuromuscular and body awareness training, with an emphasis on kinesthetic feedback. Weekly sessions lasted 30–60 minutes over 4 weeks. The patient was prescribed a home program of walking 30–60 minutes three times/week at a comfortable pace while concentrating on gait correction through kinesthetic awareness of specific deviations. Following intervention, the patient's gait improved across all objective measures. She reported receiving positive comments from others regarding improved gait and a twofold increase in her walking confidence. Outcomes support a broadened scope of practice that incorporates previously unreported integration of a patient's social wellness goals into patient management.     

Outcomes following kinesthetic feedback for gait training in a direct access environment: a case report on social wellness in relation to gait impairment

The purpose of this case report was to describe the outcomes following the use of kinesthetic feedback as a primary intervention strategy for gait training. The plan of care for this 22-year-old female addressed the patient's social wellness goal of "walking more normally," using motor learning principles. At initial examination, the patient demonstrated asymmetries for gait kinematics between the left and right lower extremity (analyzed using video motion analysis), pattern of force distribution at the foot, and activation of specific lower extremity muscles (as measured by surface electromyography). Interventions for this patient consisted of neuromuscular and body awareness training, with an emphasis on kinesthetic feedback. Weekly sessions lasted 30-60 minutes over 4 weeks. The patient was prescribed a home program of walking 30-60 minutes three times/week at a comfortable pace while concentrating on gait correction through kinesthetic awareness of specific deviations. Following intervention, the patient's gait improved across all objective measures. She reported receiving positive comments from others regarding improved gait and a twofold increase in her walking confidence. Outcomes support a broadened scope of practice that incorporates previously unreported integration of a patient's social wellness goals into patient management.     

Dynamic shifts in the organization of primary somatosensory cortex induced by bimanual spatial coupling of motor activity

Previous work has shown that training and learning can induce powerful changes in the homuncular organization of the primary somatosensory cortex (SI). Moreover, a number of studies suggest the existence of short-term adaptation of representational maps in SI. Recently, motor activity has been shown to induce rapid modulation of somatosensory cortical maps. It is hypothesized that there is a task-related influence of motor and premotor areas upon the organization of somatosensory cortex. In order to test this hypothesis, we studied the functional organization of somatosensory cortex by examining coupling effects in a bimanual movement task. Bimanual coupling is known to be related to an activation of the premotor cortex and the supplementary motor area. The functional organization of the somatosensory cortex for known bimanual coupling effects was compared to the organization of the somatosensory cortex during the same movements but with only a small effort in coupling. Topography of the functional organization of the somatosensory cortex was assessed using neuromagnetic source imaging based on tactile stimulation of the first (D1) and fifth digit (D5). We could show that the cortical representations of D1 and D5 moved further apart during the bimanual coupling task in comparison to the same task without coupling and rest. Our data suggest that somatosensory cortical maps undergo fast and dynamic modulation as a result of a task-related influence of motor or premotor areas.