Cortical reorganization associated with motor recovery in hemiparetic stroke patients

We investigated the cortical activation changes associated with motor recovery in eight hemiparetic patients with cerebral infarct by using functional MRI (fMRI), which was performed at 1.5 T in parallel with finger flexion-extension movements at a fixed rate. The first fMRI was performed when the patient was able to flex and extend fingers of the affected hand against gravity, and the second fMRI was done when the motor function of the affected hand showed definite improvement. The main cortical activation changes that occurred with motor recovery were an increment in the affected and a decrement in the unaffected primary sensori-motor cortex (SMC) activities. In conclusion, it seems that cortical reorganization occurred in parallel with motor recovery in hemiparetic patients with cerebral infarct.     

Treatment-induced cortical reorganization after stroke in humans

BACKGROUND AND PURPOSE: Injury-induced cortical reorganization is a widely recognized phenomenon. In contrast, there is almost no information on treatment-induced plastic changes in the human brain. The aim of the present study was to evaluate reorganization in the motor cortex of stroke patients that was induced with an efficacious rehabilitation treatment. METHODS: We used focal transcranial magnetic stimulation to map the cortical motor output area of a hand muscle on both sides in 13 stroke patients in the chronic stage of their illness before and after a 12-day-period of constraint-induced movement therapy. RESULTS: Before treatment, the cortical representation area of the affected hand muscle was significantly smaller than the contralateral side. After treatment, the muscle output area size in the affected hemisphere was significantly enlarged, corresponding to a greatly improved motor performance of the paretic limb. Shifts of the center of the output map in the affected hemisphere suggested the recruitment of adjacent brain areas. In follow-up examinations up to 6 months after treatment, motor performance remained at a high level, whereas the cortical area sizes in the 2 hemispheres became almost identical, representing a return of the balance of excitability between the 2 hemispheres toward a normal condition. CONCLUSIONS: This is the first demonstration in humans of a long-term alteration in brain function associated with a therapy-induced improvement in the rehabilitation of movement after neurological injury.     

Neurophysiological follow-up of motor cortical output in stroke patients.

BACKGROUND AND PURPOSE: Transcranial magnetic stimulation (TMS) has been employed in following up a population of 20 stroke patients in a post-acute, apparently stabilized stage. Neurophysiological and clinical data were recorded in 5 different recording sessions, from the beginning of a neuro-rehabilitation treatment (T0, at about 5 weeks from the ictal event.), followed up for about 4 months (T4), with the purpose to study any modification of the cortical motor output in the course of a neuro-rehabilitation treatment. METHODS: Motor evoked potentials (MEPs) were simultaneously recorded from 10 muscles of both upper limbs (affected and not-affected); meanwhile, clinical and functional scores were gathered. Spinal responsiveness was investigated via H-reflex and F-wave recordings. RESULTS: We describe a pattern of improving changes still taking place four months after the stroke, even if the maximal amelioration burden was concentrated between T0 and T1 and T1 and T2 recording sessions (T0/admission to T2/42 days from T0=about 80 days from stroke occurrence). In particular, the excitability threshold (ETh) was progressively decreasing in the affected hemisphere (AH; P<0.001 between T0 and T4), while MEPs amplitude and latency tended toward normality, more in the resting state than during voluntary contraction. Slopes of neurophysiological and clinical data evolution were taken and trends of amelioration described. CONCLUSIONS: These findings suggest that rearrangements of motor cortical neural circuitries are still operating after several months from an acute vascular monohemispheric insult, coupled with a clinical improvement in disability and neurological scores. The steepest part of the slopes were evident in the first 80 days, suggesting that this period is the one in which plastic changes of cortical motor areas are mainly active.     

Anodal cerebellar stimulation increases cortical activation: Evidence for cerebellar scaffolding of cortical processing

While the cerebellum contributes to nonmotor task performance, the specific contributions of the structure remain unknown. One possibility is that the cerebellum allows for the offloading of cortical processing, providing support during task performance, using internal models. Here we used transcranial direct current stimulation to modulate cerebellar function and investigate the impact on cortical activation patterns. Participants (n = 74; 22.03 ± 3.44 years) received either cathodal, anodal, or sham stimulation over the right cerebellum before a functional magnetic resonance imaging scan during which they completed a sequence learning and a working memory task. We predicted that cathodal stimulation would improve, and anodal stimulation would hinder task performance and cortical activation. Behaviorally, anodal stimulation negatively impacted behavior during late‐phase sequence learning. Functionally, we found that anodal cerebellar stimulation resulted in increased bilateral cortical activation, particularly in parietal and frontal regions known to be involved in cognitive processing. This suggests that if the cerebellum is not functioning optimally, there is a greater need for cortical resources.     

Evidence of cortical reorganization in hemiparetic patients

We studied the mechanisms underlying the recovery of motor function of the hand using a bidimensional xenon-133 inhalation technique to measure regional cerebral blood flow at rest and during the performance of a motor task (test condition). The regional cerebral blood flow patterns under rest and test conditions were compared in normal control and in stroke patients with either a cortico-subcortical or a deep-seated lesion. Functional recovery appears to depend upon cortical reorganization involving both hemispheres, particularly in both parietal regions in the subgroup of patients with cortico-subcortical lesions.     

Rapid motor cortical reorganization following subacute spinal cord dysfunction

ObjectiveDamage to the spinal cord is known to be associated with a posterior shift of the motor cortical upper limb representation, i.e. towards the somatosensory cortex. Due to missing pre-traumatic data, knowledge resulted from comparing findings between patients and healthy subjects. Here, we present a case of transient spinal cord injury resulting in a left-sided hemiparesis for 4 weeks. By chance, this patient had a pre-lesional navigated transcranial magnetic stimulation (nTMS) motor mapping 2 years before. Hence, nTMS mapping was repeated during the acute (after 1 day), sub-acute (after 10 days) and chronic (after 2 years) phase to trace the cortical reorganization following this incident.MethodsAcute clinical work-up included magnetic resonance imaging and navigated transcranial magnetic stimulation (nTMS). Motor mapping was performed with 110% of the abductor pollicis brevis muscle (APB) resting motor threshold (rMT). Amplitudes and latencies of the motor-evoked potential (MEPs) were recorded and analyzed. In addition, motor function was evaluated by the Medical Research Council (MRC) scale, a standard Purdue Pegboard test and by a reaction time (RT) task.ResultsMRI revealed no aberrant findings. nTMS mapping, however, showed a posterior shift of the APB representation from the anatomical hand knob towards the somatosensory cortex in the acute in comparison to the pre-lesional phase. Concomitantly, there was an increase of rMT (6%). Within 10 days, there was an incomplete reversal of the posterior shift in parallel with improvement of the clinical motor function. Long-term follow-up revealed a complete restitution of nTMS cortical mapping and motor function.ConclusionThe present case report thoroughly documents a rapid cortical reorganization within a few days after a transient spinal shock. Our data adds further evidence to the literature suggesting a posterior shift of motor cortical representation following spinal cord injury. For the first time, 52 cortical reorganization was shown idiosyncratically in a single patient arising from the fortuitous fact of having a pre - lesional nTMS map.     

Movement-related cortical potentials in patients with cerebellar degeneration

We studied the topographic distribution of scalp-recorded, averaged movement-related cortical potentials occurring immediately before and after the onset of voluntary movements in six patients with cerebellar degenerative disease. We placed 26 electrodes on the scalp overlying the sensorimotor area and recorded cortical potentials related to abduction of the index finger. The amplitudes and latencies of the potentials were normal in all patients except two, in whom the negative slope (NS') was absent. All patients had an abnormal topographic pattern of potentials compared with normal subjects. The initial slope of motor potential (isMP), which was focal and contralateral in the normal subjects, was diffuse and bilateral in the patients. The topography of the frontal peak of motor potential (fpMP) was more posterior in the patients than in normal subjects. The patterns found in this preliminary study indicate a derangement of sensorimotor cortex activity in voluntary movement as a consequence of cerebellar dysfunction.     

Functional reorganization of the cerebral motor system after stroke

PURPOSE OF REVIEW: Recovery of function after stroke is now widely considered to be a consequence of central nervous system reorganization. Non-invasive techniques such as functional magnetic resonance imaging, transcranial magnetic stimulation, electroencephalography and magnetoencephalography now allow the study of the working human brain. Studies in stroke patients can now address how cerebral networks in the human brain respond to focal injury and whether these changes are related to functional recovery. This understanding may in turn lead to the development of techniques that will drive cerebral reorganization in a way that promotes functional improvement. RECENT FINDINGS: The relationship between cerebral reorganization and functional recovery has been examined in both cross-sectional and longitudinal studies. It appears that the motor system reacts to damage in a way that attempts to generate motor output through surviving brain regions and networks. There are changes in cortical excitability after stroke that may provide the substrate whereby the effects of motor practice or experience can be more effective in driving long lasting changes in motor networks. This will be particularly important in intact portions of neural networks subserving motor skills learning. SUMMARY: Functionally relevant adaptive changes occur in the human brain following focal damage. A greater understanding of how these changes are related to the recovery process will allow the development of novel therapeutic techniques that are based on neurobiological principles and which are designed to minimize impairment in appropriately targeted patients suffering from stroke.     

Supratentorial functional disturbances in two children with cerebellar cortical dysplasia

When evaluating children with mental retardation, subtle cerebral and cerebellar morphologic anomalies are often noted at Magnetic Resonance Imaging (MRI). Some, such as cerebellar cortical dysplasia (CCD), have been considered as subtle markers of cerebral dysgenesis. Their functional significance and their effect on brain function, remain unknown. To study supratentorial functional disturbances related to CCD we performed Positron-Emission-Tomography (PET) studies in two children with isolated CCD, in order to investigate the degree of involvement of supratentorial structures. One had developmental delay, motor disturbances and ataxia, and the other one only had mental retardation. PET studies revealed hypoperfusion and hypometabolism within the vermis, thalamus and the right striatum in one case, and hypometabolism in the basal ganglia and cerebellar deep grey nuclei in the other case. Our results could lead to a hypothesis explaining motor disturbances as well as cognitive impairment, and could suggest a pathological functional significance of CCD. Nevertheless, the relationship between these findings and mental retardation needs further investigation.     

Motor recovery and cortical reorganization after constraint-induced movement therapy in stroke patients: a preliminary study

Constraint-induced movement therapy (CIMT) is a physical rehabilitation regime that has been previously shown to improve motor function in chronic hemiparetic stroke patients. However, the neural mechanisms supporting rehabilitation-induced motor recovery are poorly understood. The goal of this study was to assess motor cortical reorganization after CIMT using functional magnetic resonance imaging (fMRI). In a repeated-measures design, 4 incompletely recovered chronic stroke patients treated with CIMT underwent motor function testing and fMRI. Five age-matched normal subjects were also imaged. A laterality index (LI) was determined from the fMRI data, reflecting the distribution of activation in motor cortices contralateral compared with ipsilateral to the moving hand. Pre-intervention fMRI showed a lower LI during affected hand movement of stroke patients (LI = 0.23+/-0.07) compared to controls (LI unaffected patient hand = 0.65+/-0.10; LI dominant normal hand = 0.65+/-0.11; LI nondominant normal hand = 0.69+/-0.11; P < 0.05) due to trends toward increased ipsilateral motor cortical activation. Motor function testing showed that patients made significant gains in functional use of the stroke-affected upper extremity (detected by the Motor Activity Log) and significant reductions in motor impairment (detected by the Fugl-Meyer Stroke Scale and the Wolf Motor Function Test) immediately after CIMT, and these effects persisted at 6-month follow-up. The behavioral effects of CIMT were associated with a trend toward a reduced LI from pre-intervention to immediately post-intervention (LI = -0.01+/-0.06, P = 0.077) and 6 months post-intervention (LI = -0.03+/-0.15). Stroke-affected hand movement was not accompanied by mirror movements during fMRI, and electromyographic measures of mirror recruitment under simulated fMRI conditions were not correlated with LI values. These data provide preliminary evidence that gains in motor function produced by CIMT in chronic stroke patients may be associated with a shift in laterality of motor cortical activation toward the undamaged hemisphere.     

Motor network reorganization after motor imagery training in stroke patients with moderate to severe upper limb impairment

Background

Motor imagery training (MIT) has been widely used to improve hemiplegic upper limb function in stroke rehabilitation. The effectiveness of MIT is associated with the functional neuroplasticity of the motor network. Currently, brain activation and connectivity changes related to the motor recovery process after MIT are not well understood. Aim: We aimed to investigate the neural mechanisms of MIT in stroke rehabilitation through a longitudinal intervention study design with task-based functional magnetic resonance imaging (fMRI) analysis.

Methods

We recruited 39 stroke patients with moderate to severe upper limb motor impairment and randomly assigned them to either the MIT or control groups. Patients in the MIT group received 4 weeks of MIT therapy plus conventional rehabilitation, while the control group only received conventional rehabilitation. The assessment of Fugl-Meyer Upper Limb Scale (FM-UL) and Barthel Index (BI), and fMRI scanning using a passive hand movement task were conducted on all patients before and after treatment. The changes in brain activation and functional connectivity (FC) were analyzed. Pearson's correlation analysis was conducted to evaluate the association between neural functional changes and motor improvement.

Results

The MIT group achieved higher improvements in FM-UL and BI relative to the control group after the treatment. Passive movement of the affected hand evoked an abnormal bilateral activation pattern in both groups before intervention. A significant Group × Time interaction was found in the contralesional S1 and ipsilesional M1, showing a decrease of activation after intervention specifically in the MIT group, which was negatively correlated with the FM-UL improvement. FC analysis of the ipsilesional M1 displayed the motor network reorganization within the ipsilesional hemisphere, which correlated with the motor score changes.

Conclusions

MIT could help decrease the compensatory activation at both hemispheres and reshape the FC within the ipsilesional hemisphere along with functional recovery in stroke patients.     

Motor outcome after subcortical stroke correlates with the degree of cortical reorganization.

OBJECTIVE: The contribution of cortical reorganization to motor recovery after a subcortical stroke is uncertain. The purpose of the study was to investigate the relationship between changes in motor cortex organization, and the degree of motor function after a subcortical stroke. METHODS: Transcranial magnetic stimulation mapping of the corticomotor projection to the hand was performed in 27 patients who had suffered a subcortical ischemic stroke resulting in an upper limb motor deficit up to 23 years previously. Corticospinal conduction was assessed by measurements of motor evoked potential latency, amplitude and threshold. Motor function in the upper limb was assessed using the Motor Assessment Scale for Stroke and measurements of grip strength. RESULTS: Motor maps for the hand were displaced on the affected side relative to the unaffected side in 17 patients. In 10 of these patients in whom corticospinal conduction had normalized, there was a strong positive correlation between the magnitude of the map shift and grip strength in the affected hand (r=0.79; P=0.006). In the other seven patients with a map shift, in whom corticospinal conduction was still impaired, there was a tendency for a larger map area to be associated with better motor function, and in the group as a whole there was a correlation between map area and grip strength (r=0.52; P=0.005). CONCLUSIONS: The present findings provide evidence that the cortical plasticity and reorganization that occurs after a subcortical stroke is functionally significant and contributes to motor outcome.     

Crossed cerebellocerebral diaschisis in patients with cerebellar stroke

Objectives– We performed single‐photon emission computed tomography (SPECT) to investigate crossed cerebellocerebral diaschisis (CCCD) in patients with cerebellar stroke. Material and methods– Fifteen patients with unilateral cerebellar stroke underwent SPECT of the brain with N‐isopropyl‐p‐[¹²³I] iodoamphetamine (¹²³I‐IMP). Regional cerebral blood flow (rCBF) was measured by the autoradiographic method. Regions of interest were defined in the cerebral cortex, striatum, thalamus and cerebellum to compare structures (contralateral to the cerebellar lesion) with counterparts ipsilateral to the stroke. Results– In the frontal and parietal cortices, especially the posterior superior frontal, anterior midfrontal, precentral, postcentral, and supramarginal areas, rCBF contralateral to the lesion was significantly lower than on the side of the lesion (showing CCCD). Conclusion – This CCCD phenomenon is important to be aware of in clinical reading of images.     

The differential roles of contralesional frontoparietal areas in cortical reorganization after stroke

BackgroundStudies examining the contribution of contralesional brain regions to motor recovery after stroke have revealed conflicting results comprising both supporting and disturbing influences. Especially the relevance of contralesional brain regions beyond primary motor cortex (M1) has rarely been studied, particularly concerning the temporal dynamics post-stroke.MethodsWe, therefore, used online transcranial magnetic stimulation (TMS) interference to longitudinally assess the role of contralesional (right) frontoparietal areas for recovery of hand motor function after left hemispheric stroke: contralesional M1, contralesional dorsal premotor cortex (dPMC), and contralesional anterior intraparietal sulcus (IPS). Fourteen stroke patients and sixteen age-matched healthy subjects performed motor tasks of varying complexity with their (paretic) right hand. Motor performance was quantified using three-dimensional kinematic data. All patients were assessed twice, (i) in the first week, and (ii) after more than three months post-stroke.ResultsWhile we did not observe a significant effect of TMS interference on movement kinematics following the stimulation of contralesional M1 and dPMC in the first week post-stroke, we found improvements of motor performance upon interference with contralesional IPS across motor tasks early after stroke, an effect that persisted into the later phase. By contrast, for dPMC, TMS-induced deterioration of motor performance was only evident three months post-stroke, suggesting that a supportive role of contralesional premotor cortex might evolve with reorganization.ConclusionWe here highlight time-sensitive and region-specific effects of contralesional frontoparietal areas after left hemisphere stroke, which may influence on neuromodulation regimes aiming at supporting recovery of motor function post-stroke.     

Effects of cerebellar infarcts on cortical processing of saccades

The objective of the present study was to investigate cerebellar influences on cortical components of saccadic eye movement programming in human subjects. In 24 patients with a localized cerebellar lesion, saccadic eye movements were recorded in different reflexive (step, gap, overlap) and intentional (anti, memory, short memory sequences) tasks and compared to 23 healthy controls. The cerebellar lesions led to impairments in different saccade parameters. Cerebellar patients tended to show hypermetria and increased latencies compared to the control group. In particular, they executed significantly more erroneous saccades specifically in the memory task (suppression errors) but not in the anti task (pro-saccade errors). Moreover, while reproducing short sequences of saccades from memory, patients with cerebellar infarcts made more errors with regard to the sequence order than controls. The influence of cerebellar hemispheric lesions on the saccade latency, the task-specific lesion effects on the frequency of suppression errors, and the effects on the number of order errors suggest that the cerebellum is involved in cortical processes such as target selection and sequence reproduction.     

Motor training‐related brain reorganization in patients with cerebellar degeneration

Cerebellar degeneration progressively impairs motor function. Recent research showed that cerebellar patients can improve motor performance with practice, but the optimal feedback type (visual, proprioceptive, verbal) for such learning and the underlying neuroplastic changes are unknown. Here, patients with cerebellar degeneration (N = 40) and age‐ and sex‐matched healthy controls (N = 40) practiced single‐joint, goal‐directed forearm movements for 5 days. Cerebellar patients improved performance during visuomotor practice, but a training focusing on either proprioceptive feedback, or explicit verbal feedback and instruction did not show additional benefits. Voxel‐based morphometry revealed that after training gray matter volume (GMV) was increased prominently in the visual association cortices of controls, whereas cerebellar patients exhibited GMV increase predominantly in premotor cortex. The premotor cortex as a recipient of cerebellar efferents appears to be an important hub in compensatory remodeling following damage of the cerebro‐cerebellar motor system.     

Unilateral cerebellar stroke disrupts movement preparation and motor imagery.

OBJECTIVE: To assess motor cortex excitability, motor preparation and imagery in patients with unilateral cerebellar stroke with damage of the dentate nucleus by using transcranial magnetic stimulation (TMS). METHOD: Eight patients with unilateral cerebellar lesions due to tromboembolic stroke and 10 age matched healthy subjects were enrolled. Resting (RMT) and active (AMT) motor threshold, cortical and peripheral silent period, evaluation of motor imagery, reaction time and premovement facilitation of motor evoked potential (MEP) were tested bilaterally using TMS. RESULTS: The RMT and AMT were found to be increased contra lateral to the affected cerebellar hemisphere while the cortical silent period was prolonged. In addition the amount of MEP facilitation during motor imagery and the pre-movement facilitation were reduced in the motor cortex contra lateral to the affected cerebellar hemisphere. The reaction time, performed with the symptomatic hand, was slower. CONCLUSIONS: On the whole, our data confirm a role for the cerebellum in maintaining the excitability of primary motor area. Furthermore, patients with unilateral cerebellar stroke exhibit lateralized deficit of motor preparation and motor imagery. SIGNIFICANCE: Our results add to evidence that cerebellum contributes to specific aspects of motor preparation and motor imagery.     

Movement-related cortical potential in patients with cerebellar dentate degeneration]

We reported movement-related cortical potentials (MRCPs) in 11 patients with lesion of the dentate nucleus (Machado-Joseph disease (MJD) 7 cases, dentato-rubro-pallido-luysian atrophy (DRPLA)1, myoclonus epilepsy associated with ragged-red fibers (MERRF)1, dyssynergia cerebellaris myoclonica (DCM) 2), and compared with those of 7 cases of multiple system atrophy (MSA) who were postulated to have mild dentate lesions (striato-nigral degeneration 2 cases, Shy-Drager syndrome 2, sporadic olivo-ponto-cerebellar atrophy 3), and 7 control subjects without any neurological findings. Further we classified the diseases into the following two groups based on the lesion of the dentate nucleus. One was MJD group that had normal or slightly abnormal electroencephalogram (EEG), and the other was DN group (DRPLA, MERRF, DCM) that had markedly abnormal EEG. One of the main findings from this study was smaller slope of the Ns' in the MJD and DN group and normal slope of BP. There was no significant difference in the slope of Ns' between MJD patients and DN patients. This result shows EEG abnormalities have no influence on MRCP recordings. These results suggest that Ns' component may reflect the function in the cerebellar dentate nucleus, and that MRCP is a useful diagnostic method in patients with cerebellar ataxia.