Evolution of cortical activation during recovery from corticospinal tract infarction

BACKGROUND AND PURPOSE: Recovery from hemiparesis due to corticospinal tract infarction is well documented, but the mechanism of recovery is unknown. Functional MRI (fMRI) provides a means of identifying focal brain activity related to movement of a paretic hand. Although prior studies have suggested that supplementary motor regions in the ipsilesional and contralesional hemisphere play a role in recovery, little is known about the time course of cortical activation in these regions as recovery proceeds. METHODS: Eight patients with first-ever corticospinal tract lacunes causing hemiparesis had serial fMRIs within the first few days after stroke and at 3 to 6 months. Six healthy subjects were used as controls. Statistically significant voxels during a finger-thumb opposition task were identified with an automated image processing program. An index of ipsilateral versus contralateral activity was used to compare relative contributions of the 2 hemispheres to motor function in the acute and chronic phases after stroke. RESULTS: Controls showed expected activation in the contralateral sensorimotor cortex (SMC), premotor, and supplementary motor areas. Stroke patients differed from control patients in showing greater activation in the ipsilateral SMC, ipsilateral posterior parietal, and bilateral prefrontal regions. Compared with the nonparetic hand, the ratio of contralateral to ipsilateral SMC activity during movement of the paretic hand increased significantly over time as the paretic hand regained function. CONCLUSIONS: The evolution of activation in the SMC from early contralesional activity to late ipsilesional activity suggests that a dynamic bihemispheric reorganization of motor networks occurs during recovery from hemiparesis.     

A compensatory mechanism in unilateral akinetic-rigid syndrome: an fMRI study

The motor mechanisms of a patient with unilateral hand clumsiness in the early stages of akinetic-rigid syndrome were assessed by functional magnetic resonance imaging (fMRI). Movements of the unaffected hand produced activation in the contralateral sensorimotor cortex (SMC) and ipsilateral SMC and superior parietal lobule (SPL). The affected hand activated the bilateral SMCs, supplementary motor areas, and SPLs. We speculated that the bilateral activation indicated recruitment of a pre-existing bilaterally organized large-scale neural network to perform the motor task.     

Reorganization of the motor cortex in a patient with congenital hemiparesis and mirror movements

Abnormal branching of corticospinal fibers from the unaffected motor cortex is responsible for mirror movements in patients with congenital hemiparesis, but it is unknown which mechanisms enable these patients to lateralize motor activity. Using multiunit electromyographic analysis and transcranial magnetic stimulation, the authors provide evidence for nonbranched crossed and uncrossed corticospinal projections and intracortical inhibition of the mirror hand. They propose that this remarkable reorganization of the unaffected motor cortex helps these patients to reduce mirror movements.     

Transcallosal motor pathway from affected motor cortex to affected hand in a patient with corona radiata infarct A diffusion tensor tractography and transcranial magnetic stimulation study

The mechanisms of motor recovery through the transcallosal pathway remain poorly understood.The present study reports on a hemiplegic patient with corona radiata infarct; it attempts to confirm motor recovery through the transcallosal motor pathway, from the affected motor cortex to the affected hand, using diffusion tensor tractography and transcranial magnetic stimulation. A 54-year-old, male patient and eight age-matched, normal subjects were enrolled in the study. The patient's right hand was initially completely paralyzed, but slowly recovered over 6 months. In the control subjects and the unaffected hemisphere (right) of the patient, the corticospinal tracts originated from the motor cortex and descended along the known corticospinal tract pathway.However, the corticospinal tract of the affected hemisphere was disrupted at the upper pons.Following transcranial stimulation of the affected (left) motor cortex, motor evoked potential from the affected (right) abductor pollicis brevis muscle exhibited longer latency than opposite motor evoked potential. Results from the present study suggest that motor function of the affected (right) hand recovered via the transcallosal motor pathway from the affected (left) motor cortex in this patient.     

Ipsilateral cortical connections of motor, premotor, frontal eye, and posterior parietal fields in a prosimian primate, Otolemur garnetti

The ipsilateral connections of motor areas of galagos were determined by injecting tracers into primary motor cortex (M1), dorsal premotor area (PMD), ventral premotor area (PMV), supplementary motor area (SMA), and frontal eye field (FEF). Other injections were placed in frontal cortex and in posterior parietal cortex to define the connections of motor areas further. Intracortical microstimulation was used to identify injection sites and map motor areas in the same cases. The major connections of M1 were with premotor cortex, SMA, cingulate motor cortex, somatosensory areas 3a and 1, and the rostral half of posterior parietal cortex. Less dense connections were with the second (S2) and parietal ventral (PV) somatosensory areas. Injections in PMD labeled neurons across a mediolateral belt of posterior parietal cortex extending from the medial wall to lateral to the intraparietal sulcus. Other inputs came from SMA, M1, PMV, and adjoining frontal cortex. PMV injections labeled neurons across a large zone of posterior parietal cortex, overlapping the region projecting to PMD but centered more laterally. Other connections were with M1, PMD, and frontal cortex and sparsely with somatosensory areas 3a, 1-2, S2, and PV. SMA connections were with medial posterior parietal cortex, cingulate motor cortex, PMD, and PMV. An FEF injection labeled neurons in the intraparietal sulcus. Injections in posterior parietal cortex revealed that the rostral half receives somatosensory inputs, whereas the caudal half receives visual inputs. Thus, posterior parietal cortex links visual and somatosensory areas with motor fields of frontal cortex.     

Cortical connections of area 2 and posterior parietal area 5 in macaque monkeys

The overarching goal of the current investigation was to examine the connections of anterior parietal area 2 and the medial portion of posterior parietal area 5 in macaque monkeys; two areas that are part of a network involved reaching and grasping in primates. We injected neuroanatomical tracers into specified locations in each field and directly related labeled cells to histologically identified cortical field boundaries. Labeled cells were counted so that the relative density of projections to areas 2 and 5 from other cortical fields could be determined. Projections to area 2 were restricted and were predominantly from other somatosensory areas of the anterior parietal cortex (areas 1, 3b, and 3a), the second somatosensory area (S2), and from medial and lateral portions of area 5 (5M and 5L respectively). On the other hand, area 5M had very broadly distributed projections from a number of cortical areas including anterior parietal areas, from primary motor cortex (M1), premotor cortex (PM), the supplementary motor area (SMA), cortex on the medial wall, and from posterior parietal areas 5L and 7b. The more restricted pattern of connections of area 2 indicates that it processes somatic inputs locally and provides proprioceptive information to area 5M. 5M, which at least partially overlaps with functionally defined area MIP, receives inputs from somatosensory (predominantly from area 2), posterior parietal and motor cortex, which could provide the substrate for representing multiple coordinate systems necessary for planning ethologically relevant movements, particularly those involving the hand.     

Interhemispheric visuo-motor integration in humans: the role of the superior parietal cortex

We used event-related functional magnetic resonance imaging (fMRI) to investigate the neural correlates of basic interhemispheric visuo-motor integration. In a simple reaction time task, subjects responded to lateralized left and right light flashes with unimanual left and right hand responses. Typically, reaction times are faster for uncrossed responses (that is, visual stimulus and response hand on the same side) than for crossed responses (that is, visual stimulus and response hand on opposite sides). The chronometric difference between crossed and uncrossed responses is called crossed-uncrossed difference (CUD) and it is typically taken to represent a behavioral estimate of interhemispheric transfer time. The fMRI results obtained in normal right-handers show that the crossed conditions yielded greater activity, compared to the uncrossed conditions, in bilateral prefrontal, bilateral dorsal premotor, and right superior parietal areas. These results suggest that multiple transfers between the hemispheres occur in parallel at the functional levels of sensory-motor integration (posterior parietal), decision-making (prefrontal) and preparation of motor response (premotor). To test the behavioral significance of these multiple transfers, we correlated the individual CUDs with the difference in signal intensity between crossed and uncrossed responses in the prefrontal, dorsal premotor, and right superior parietal activated areas. The analyses demonstrated a strong correlation between the CUD and signal intensity difference between crossed and uncrossed responses in the right superior parietal cortex. These data suggest a critical role of the superior parietal cortex in interhemispheric visuo-motor integration.     

The role of the unaffected hemisphere in motor recovery after stroke

The contribution of the ipsilateral (nonaffected) hemisphere to recovery of motor function after stroke is controversial. Under the assumption that functionally relevant areas within the ipsilateral motor system should be tightly coupled to the demand we used fMRI and acoustically paced movements of the right index finger at six different frequencies to define the role of these regions for recovery after stroke. Eight well‐recovered patients with a chronic striatocapsular infarction of the left hemisphere were compared with eight age‐matched participants. As expected the hemodynamic response increased linearly with the frequency of the finger movements at the level of the left supplementary motor cortex (SMA) and the left primary sensorimotor cortex (SMC) in both groups. In contrast, a linear increase of the hemodynamic response with higher tapping frequencies in the right premotor cortex (PMC) and the right SMC was only seen in the patient group. These results support the model of an enhanced bihemispheric recruitment of preexisting motor representations in patients after subcortical stroke. Since all patients had excellent motor recovery contralesional SMC activation appears to be efficient and resembles the widespread, bilateral activation observed in healthy participants performing complex movements, instead of reflecting maladaptive plasticity. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Ipsilateral motor pathway without contralateral motor pathway in a stroke patient

The ipsilateral motor pathway from the unaffected motor cortex to the affected extremity is one of the mechanisms of motor recovery following stroke. We report on a stroke patient who showed the ipsilateral motor pathway without the contralateral motor pathway on functional MRI and diffusion tensor tractography. A 53-year-old left hemiparetic patient with an infarct in the right middle cerebral artery territory was evaluated. During a period of three months after onset, motor function of the affected (left) hand had recovered slowly, to the extent that the patient was able to overcome gravity. FMRI showed that only the unaffected (left) primary sensorimotor cortex was activated by movements of the unaffected (right) hand or of the affected (left) hand. On diffusion tensor tractography, the corticospinal tract of the left hemisphere originated from the primary sensori-motor cortex and descended through the known corticospinal tract pathway. By contrast, the right corticospinal tract showed a disruption with Wallerian degeneration to the upper medulla. We conclude that the motor function of the affected (left) hand appeared to be controlled only by the ipsilateral motor pathway from the left motor cortex to the left hand. Motor function of the affected hand appeared to have been reorganized to the ipsilateral motor pathway from the unaffected motor cortex to the affected hand.     

Involvement of area MT in bimanual finger movements in left-handers: an fMRI study

The ease with which humans are able to perform symmetric movements of both hands has traditionally been attributed to the preference of the motor system to activate homologous muscles. Recently, we have shown in right-handers, however, that bimanual index finger adduction and abduction movements in incongruous hand orientations (one palm down/other up) preferentially engaged parietal perception-associated brain areas. Here, we used functional magnetic resonance imaging to investigate the influence of hand orientation in left-handers on cerebral activation during bimanual index finger movements. Performance in incongruous orientation of either hand yielded activations involving right and left motor cortex, supplementary motor area in right superior frontal gyrus (SMA and pre-SMA), bilateral premotor cortex, prefrontal cortex, bilateral somatosensory cortex and anterior parietal cortex along the intraparietal sulcus. In addition, the occipito-temporal cortex corresponding to human area MT (hMT) in either hemisphere was activated in relation to bimanual index finger movements in the incongruous hand orientation as compared with the same movements in the congruous hand orientation or with simply viewing the pacing stimuli. Comparison with the same movement condition in right-handed subjects from a former study support these hMT activations exclusively for left-handed subjects. These results suggest that left-handers use visual motion imagery in guiding incongruous bimanual finger movements.     

Effects of subthalamic nucleus stimulation on actual and imagined movement in Parkinson's disease : a PET study

BACKGROUND: PET studies in moderately affected Parkinson's disease (PD) patients reveal abnormal cerebral activation during motor execution and imagery, but the effects of subthalamic nucleus (STN) stimulation are not well established. OBJECTIVES: to assess the effect of STN stimulation on cerebral activation during actual and imagined movement in patients with advanced PD. METHODS: seven severely affected PD patients treated with bilateral STN stimulation were studied with PET and H(2)(15)O. The following conditions were investigated: (1). rest; (2). motor execution of a sequential predefined joystick movement with the right hand and (3). motor imagery of the same task. Patients were studied with and without left STN stimulation while right stimulator remained off. RESULTS: Without STN stimulation, the primary motor cortex was activated only during motor execution whereas the dorsolateral prefrontal cortex (DLPFC) was activated only during motor imagery. An activation of the supplementary motor area (SMA) was seen during both motor execution and motor imagery. Left STN stimulation during motor execution increased the regional cerebral blood flow (rCBF) bilaterally in the prefrontal cortex including DLPFC, in the left thalamus and putamen. In addition, a reduction of rCBF was noted in the right primary motor cortex, inferior parietal lobe and SMA. Under left STN stimulation, during motor imagery, rCBF increased bilaterally in the DLPFC and in the left thalamus and putamen and decreased in the left SMA and primary motor cortex. CONCLUSION: STN stimulation during both motor execution and imagery tends to improve the functioning of the frontal-striatal-thalamic pathway and to reduce the recruitment of compensatory motor circuits notably in motor, premotor and parietal cortical areas.     

Preservation of central motor conduction in patients with spinal muscular atrophy type II

We evaluated the central (motor cortex to C8 motoneuron) and peripheral (C8 motoneuron to the muscle) motor conduction in 14 limbs of 7 patients with the intermediate form of spinal muscular atrophy (SMA II). The central motor conduction time (CMCT) was calculated using motor evoked potentials (MEPs) by transcranial magnetic stimulation and the results of a conventional F wave study. Peripheral conduction abnormality was found in 6 median nerves (43%) and 10 ulnar nerves (71%). Even in these patients with peripheral conduction abnormalities, the CMCT was consistently normal whenever the MEP was recorded. These results indicate that the motor conduction of the corticospinal fibers remains normal in SMA II.     

Behavioral recovery and anatomical plasticity in adult rats after cortical lesion and treatment with monoclonal antibody IN-1

We have previously reported that monoclonal antibody (mAb) IN-1 treatment after ischemic infarct in adult rats results in significant recovery of skilled forelimb use. Such recovery was correlated with axonal outgrowth from the intact, opposite motor cortex into deafferented subcortical motor areas. In the present study, we investigated the effects of mAb IN-1 treatment after adult sensorimotor cortex (SMC) aspiration lesion on behavioral recovery and neuroanatomical plasticity in the corticospinal tract. Adult rats underwent unilateral SMC aspiration lesion and treatment with either mAb IN-1 or a control Ab, or no treatment. Animals were then tested over a 6-week period in the skilled forelimb use task and the skilled ladder rung walking task. We found that animals treated with mAb IN-1 after SMC lesion fully recovered the use of forelimb reaching, but showed no improvement in digit grasping as tested in the skilled forelimb use task. The mAb IN-1 treatment group was also significantly improved as compared to control groups in the skilled ladder rung walking test. Furthermore, neuroanatomical tracing revealed a significant increase in the corticospinal projections into the deafferented motor areas of the spinal cord after mAb IN-1 treatment. These results indicate that treatment with mAb IN-1 after cortical aspiration lesion induces remodeling of motor pathways resulting in recovery in only certain behavioral tasks, suggesting that the cause of brain damage influences behavioral recovery after mAb IN-1 treatment.     

Motor sequence complexity and performing hand produce differential patterns of hemispheric lateralization

Studies in brain damaged patients conclude that the left hemisphere is dominant for controlling heterogeneous sequences performed by either hand, presumably due to the cognitive resources involved in planning complex sequential movements. To determine if this lateralized effect is due to asymmetries in primary sensorimotor or association cortex, whole-brain functional magnetic resonance imaging was used to measure differences in volume of activation while healthy right-handed subjects performed repetitive (simple) or heterogeneous (complex) finger sequences using the right or left hand. Advanced planning, as evidenced by reaction time to the first key press, was greater for the complex than simple sequences and for the left than right hand. In addition to the expected greater contralateral activation in the sensorimotor cortex (SMC), greater left hemisphere activation was observed for left, relative to right, hand movements in the ipsilateral left superior parietal area and for complex, relative to simple, sequences in the left premotor and parietal cortex, left thalamus, and bilateral cerebellum. No such volumetric asymmetries were observed in the SMC. Whereas the overall MR signal intensity was greater in the left than right SMC, the extent of this asymmetry did not vary with hand or complexity level. In contrast, signal intensity in the parietal and premotor cortex was greater in the left than right hemisphere and for the complex than simple sequences. Signal intensity in the caudal anterior cerebellum was greater bilaterally for the complex than simple sequences. These findings suggest that activity in the SMC is associated with execution requirements shared by the simple and complex sequences independent of their differential cognitive requirements. In contrast, consistent with data in brain damaged patients, the left dorsal premotor and parietal areas are engaged when advanced planning is required to perform complex motor sequences that require selection of different effectors and abstract organization of the sequence, regardless of the performing hand.     

Organization of corticospinal neurons in the monkey

The retrograde axonal transport method has been employed to identify the cell bodies of cortical neurons projecting directly to the spinal cord in the monkey. The investigation has focused on aspects of the laminar, columnar, and somatotopic organization of corticospinal neurons within each of the cytoarchitectural and functional subdivisions of the sensorimotor cortex. The principle findings of these experiments are that: (i) cortical regions containing cell bodies of corticospinal neurons are the first motor cortex (area 4), the first somatic sensory cortex (areas 3a, 3b, 1, and 2), and part of the immediately adjacent posterior parietal cortex (area 5), the second somatic sensory cortex, the supplementary motor cortex (the medial aspect of area 6), and the medial part of the posterior parietal cortex in a region termed the supplementary sensory area; (ii) corticospinal neurons display a somatotopic organization within each of these functional subdivisions of the sensorimotor cortex; (iii) all corticospinal neurons arise from layer V of the cortex; and (iv) corticospinal neurons within the first motor and first somatic sensory cortex oftern occur in clusters, perhaps reflecting a columnar organization in the sensorimotor cortex. These findings demonstrate the origins of the corticospinal system to be more extensive than previously recognized and show that a number of common features characterize the organization of corticospinal neurons in all cortical areas. Across cortical subdivisions, however, major differences exist in the extent of spinal segmental representations, in the manner in which corticospinal neurons occur in groups, and in the numerical density and sizes of corticospinal neurons. These aspects of the organization of the corticospinal system presumably reflect specialization of the different cortical areas in spinal cord sensory and motor control.     

Evidence for Direct Connections between the Hand Region of the Supplementary Motor Area and Cervical Motoneurons in the Macaque Monkey

In primates the corticospinal neurons of the hand representation of the primary motor cortex (M1) give rise to direct contacts with the cervical motoneurons that control distal forelimb muscles. We investigated, at the light-microscopy level, whether corticospinal cells present in the hand area of the supplementary motor area (SMA) also establish direct connections with cervical motoneurons, particularly those innervating hand and finger muscles. The hand representation of the M1 (two monkeys) or SMA (two monkeys) was located using intracortical microstimulation and injected with the anterograde tracer biotinylated dextran amine to label corticospinal terminals. Forearm muscles acting on the wrist and hand as well as hand muscles acting on the thumb and index finger, thus including those activated by intracortical stimulation, were injected with the retrograde tracer cholera-toxin B subunit, in order to label the motoneurons. A consistent zone of overlap between the two markers was found in the cervical cord. Close appositions between corticospinal axonal terminals and the somata or dendrites of motoneurons were found after injection in the M1, confirming previous observations. The new finding is the observation of similar close appositions after injection in the SMA, suggesting its control of hand movements in parallel with the M1.     

Motor imagery in normal subjects and in asymmetrical Parkinson's disease: a PET study

OBJECTIVE: To investigate, using PET and H2(15)O, brain activation abnormalities of patients with PD during motor imagery. To determine whether motor imagery activation patterns depend on the hand used to complete the task. BACKGROUND: Previous work in PD has shown that bradykinesia is associated with slowness of motor imagery. METHODS: The PET study was performed in eight patients with PD with predominantly right-sided akinesia, and in eight age-matched control subjects, all right-handed. Regional cerebral blood flow was measured by PET and H2(15)O while subjects imagined a predetermined unimanual externally cued sequential movement with a joystick with either the left or the right hand, and during a rest condition. RESULTS: In normal subjects, the prefrontal cortex, supplementary motor area (SMA), superior parietal lobe, inferior frontal gyrus, and cerebellum were activated during motor imagery with either the left or the right hand. Contralateral primary motor cortex activation was noted only when the task was imagined with the right (dominant) hand, whereas activation of the dorsolateral prefrontal cortex was observed only during imagery with the left hand. In patients with PD, motor imagery with the right ("akinetic") hand was characterized by lack of activation of the contralateral primary sensorimotor cortex and the cerebellum, persistent activation of the SMA, and bilateral activation of the superior parietal cortex. Motor imagery with the left ("non-akinetic") hand was also abnormal, with lack of activation of the SMA compared with controls. CONCLUSIONS: In patients with PD with predominantly right-sided akinesia, brain activation during motor imagery is abnormal and may appear even with the less affected hand. In normal subjects, brain activation during motor imagery depends on the hand used in the imagined movement.     

Functional cortical changes of the sensorimotor network are associated with clinical recovery in multiple sclerosis

OBJECTIVE: To assess the early cortical changes following an acute motor relapse secondary to a pseudotumoral lesion in MS patients, the longitudinal cortical functional correlates of clinical recovery, and the evolution over time of cortical reorganization. METHODS: FMRI during the performance of a simple motor task were obtained from 12 MS patients (after a clinical attack involving the motor system secondary to a pseudotumoral lesion) and 15 matched controls. In six patients and five controls, a longitudinal fMRI study was also performed. RESULTS: In patients, at baseline, the primary sensorimotor cortex (SMC) of the ipsilateral (contralesional) hemisphere was significantly more active during task performance with the impaired than the unimpaired hand. During task performance with the unimpaired hand, the ipsilateral cerebellum and several motor areas in the contralateral hemisphere were significantly more active. Pseudotumoral lesion volume was correlated with activation of the primary SMC bilaterally (r = -0.86 and -0.85) and the nine-hole peg test score with activation of the primary SMC of the affected hemisphere (r = 0.88). A recovery of function of the primary SMC of the affected hemisphere was found in the four patients with clinical improvement. In the two patients without clinical recovery, there was a persistent recruitment of the primary SMC of the unaffected hemisphere. CONCLUSIONS: Pseudotumoral MS lesions affecting the motor system can determine short-term cortical changes characterized by the recruitment of pathways in the unaffected hemisphere. The regain of function of motor areas of the affected hemisphere seems to be a critical factor for a favorable recovery.     

fMRI study of bimanual coordination

Eleven right-handed subjects performed uni- and bimanual tapping tasks. Hemodynamic responses as measured with functional magnetic resonance imaging (fMRI) in the primary somato-motor cortex (SMC) showed that during bimanual activity the SMC contralateral to the hand taking the faster rate was more strongly activated than the SMC contralateral to hand taking the slower rate. There were no asymmetries, left SMC activation during the right fast/left slow tapping condition was comparable to the right SMC activation during the left fast/right slow condition. A given SMC showed similar activation levels for bimanual and unimanual activity (i.e. left SMC activation for right fast/left slow was similar to left SMC activation for the right fast unimanual condition). In contrast, a given supplementary motor area (SMA) showed significantly more activation for the bimanual than for the unimanual activity. In addition, an asymmetry was observed during bimanual activities: during the right fast/left slow activity, the left SMA showed more activation than the right SMA, but during the left fast/right slow activity, the right SMA was not significantly more activated than the left SMA. For unimanual activities, a clear rate effect (greater activation for faster rate) was seen in the SMC but not in the SMA.     

Relation of bimanual coordination to activation in the sensorimotor cortex and supplementary motor area: analysis using functional magnetic resonance imaging

The aim of this study was to analyze how functional activation in the supplementary motor area (SMA) and sensorimotor cortex (SMC) is related to bimanual coordination using functional magnetic resonance imaging. Subjects included 24 healthy volunteers, 15 of whom were right-handed and 9 left-handed. Three kinds of activation tasks, all of which required the repetitive closing and opening of a fist, were performed: unimanual movement of the nonpreferred hand (task A); simultaneous, agonistic movement of both hands (task B); simultaneous, antagonistic movement of both hands (task C). The SMA activation during task C was more pronounced than that during the other two tasks for right and left handers. The results suggested that the activation of the SMA, at least during a simple motion used in the present study, was little influenced by whether the motion was unimanual or bimanual but instead how the bimanual motion was composed of the motion element of a single hand. The SMC activation during task C was significantly larger than that during task B, whereas hemispheric differences in the activation were not found. This indicated that the complexity of the bimanual movement also affected the SMC activation.