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Functional imaging of motor recovery after stroke: Remaining challenges
Abstract
Stroke is a leading cause of disability in the United States and is likely to have an increasing impact on disability worldwide. In order to develop more effective rehabilitation techniques, it is critical to understand the mechanisms underlying the mature brain's capacity to reorganize and restore neurologic function. Over the past decade, functional brain imaging has been a principal investigational tool in elucidating mechanisms of stroke recovery. Functional imaging studies of motor performance in patients with stroke consistently demonstrate areas of brain activation not present in healthy subjects. The role of these additional areas in recovery after stroke remains uncertain. This review discusses methodologic and theoretical issues that impact on interpreting functional imaging studies of motor recovery after stroke.
... In the context of stroke recovery, it has been suggested that functional reorganization can be detected as a change in such correlations/functional connectivity patterns (11). Specifically, for poststroke recovery of hemiparesis, the advantage of task-free resting-state over task-based fMRI is that it avoids the performance confound (12,13); the connectivity measures are not biased by the inability of patients to match control performance. ...
It has been proposed that a form of cortical reorganization (changes in functional connectivity between brain areas) can be assessed with resting-state (rs) functional MRI (fMRI). Here, we report a longitudinal data set collected from 19 patients with subcortical stroke and 11 controls. Patients were imaged up to five times over 1 year. We found no evidence, using rs-fMRI, for longitudinal poststroke cortical connectivity changes despite substantial behavioral recovery. These results could be construed as questioning the value of resting-state imaging. Here, we argue instead that they are consistent with other emerging reasons to challenge the idea of motor-recovery-related cortical reorganization poststroke when conceived of as changes in connectivity between cortical areas.
NEW & NOTEWORTHY We investigated longitudinal changes in functional connectivity after stroke. Despite substantial motor recovery, we found no differences in functional connectivity patterns between patients and controls, nor any changes over time. Assuming that rs-fMRI is an adequate method to capture connectivity changes between cortical regions after brain injury, these results provide reason to doubt that changes in cortico-cortical connectivity are the relevant mechanism for promoting motor recovery.
... In the context of stroke 80 recovery, it has been suggested that reorganization can be detected as a change in such 81 correlations/functional connectivity patterns (van Meer et al., 2010). Specifically, for post-stroke 82 recovery of hemiparesis, the advantage of task-free resting-state over task-based fMRI is that it 83 avoids the performance confound (Krakauer, 2004(Krakauer, , 2007; the connectivity measures are not 84 biased by the inability of patients to match control performance due to motor impairment. 85 ...
Cortical reorganization has been suggested as mechanism for recovery after stroke. It has been proposed that a form of cortical reorganization (changes in functional connectivity between brain areas) can be assessed with resting-state fMRI. Here we report the largest longitudinal data-set in terms of overall sessions in 19 patients with subcortical stroke and 11 controls. Patients were imaged up to 5 times over one year. We found no evidence for post-stroke cortical reorganization despite substantial behavioral recovery. These results could be construed as questioning the value of resting-state imaging. Here we argue instead that they are consistent with other emerging reasons to challenge the idea of motor recovery-related cortical reorganization post-stroke when conceived as changes in connectivity between cortical areas.
... Neurophysiological and neuroimaging studies have provided an improved understanding of the neurobiological processes underlying the brain's ability to restore function by capitalizing on residual networks after stroke (Krakauer, 2004;Ward, 2004;Nudo, 2006;Murphy and Corbett, 2009;Dimyan and Cohen, 2011;Boyd et al., 2017;Sampaio-Baptista et al., 2018). One approach for improving chronic upper limb deficits is to augment this capacity to reorganize, referred to as plasticity. ...
Stroke is a leading cause of disability worldwide, and in approximately 60% of individuals, upper limb deficits persist 6 months after stroke. These deficits adversely affect the functional use of the upper limb and restrict participation in day to day activities. An important goal of stroke rehabilitation is to improve the quality of life by enhancing functional independence and participation in activities. Since upper limb deficits are one of the best predictors of quality of life after stroke, effective interventions targeting these deficits may represent a means to improve quality of life. An increased understanding of the neurobiological processes underlying stroke recovery has led to the development of targeted approaches to improve motor deficits. One such targeted strategy uses brief bursts of Vagus Nerve Stimulation (VNS) paired with rehabilitation to enhance plasticity and support recovery of upper limb function after chronic stroke. Stimulation of the vagus nerve triggers release of plasticity promoting neuromodulators, such as acetylcholine and norepinephrine, throughout the cortex. Timed engagement of neuromodulators concurrent with motor training drives task-specific plasticity in the motor cortex to improve function and provides the basis for paired VNS therapy. A number of studies in preclinical models of ischemic stroke demonstrated that VNS paired with rehabilitative training significantly improved the recovery of forelimb motor function compared to rehabilitative training without VNS. The improvements were associated with synaptic reorganization of cortical motor networks and recruitment of residual motor neurons controlling the impaired forelimb, demonstrating the putative neurobiological mechanisms underlying recovery of motor function. These preclinical studies provided the basis for conducting two multi-site, randomized controlled pilot trials in individuals with moderate to severe upper limb weakness after chronic ischemic stroke. In both studies, VNS paired with rehabilitation improved motor deficits compared to rehabilitation alone. The trials provided support for a 120-patient pivotal study designed to evaluate the efficacy of paired VNS therapy in individuals with chronic ischemic stroke. This manuscript will discuss the neurobiological rationale for VNS therapy, provide an in-depth discussion of both animal and human studies of VNS therapy for stroke, and outline the challenges and opportunities for the future use of VNS therapy.
... Moreover, in healthy individuals, SMA activation seems highly correlated with successful motor skill learning suggesting a key role of the SMA in the correct acquisition of a new motor skill (184). Since the more similar the reconfigured network is to the original undamaged network, the better the recovery (17,185,186), stimulating areas that are spontaneously involved during motor skill learning in healthy individuals such as the SMA could be an effective option for enhancing motor recovery. ...
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method to modulate the local field potential in neural tissue and consequently, cortical excitability. As tDCS is relatively portable, affordable, and accessible, the applications of tDCS to probe brain–behavior connections have rapidly increased in the last 10 years. One of the most promising applications is the use of tDCS to modulate excitability in the motor cortex after stroke and promote motor recovery. However, the results of clinical studies implementing tDCS to modulate motor excitability have been highly variable, with some studies demonstrating that as many as 50% or more of patients fail to show a response to stimulation. Much effort has therefore been dedicated to understand the sources of variability affecting tDCS efficacy. Possible suspects include the placement of the electrodes, task parameters during stimulation, dosing (current amplitude, duration of stimulation, frequency of stimulation), individual states (e.g., anxiety, motivation, attention), and more. In this review, we first briefly review potential sources of variability specific to stroke motor recovery following tDCS. We then examine how the anatomical variability in tDCS placement [e.g., neural target(s) and montages employed] may alter the neuromodulatory effects that tDCS exerts on the post-stroke motor system.
Objectives
This is a protocol for a Cochrane Review (intervention). The objectives are as follows:
To assess the effectiveness and safety of vagus nerve stimulation as an add‐on treatment to rehabilitate people with post‐stroke motor function impairments and activity limitations.
Functional magnetic resonance imaging (fMRI) has been widely employed to study stroke pathophysiology. In particular, analyses of fMRI signals at rest were directed at quantifying the impact of stroke on spatial features of brain networks. However, brain networks have intrinsic time features that were, so far, disregarded in these analyses. In consequence, standard fMRI analysis failed to capture temporal imbalance resulting from stroke lesions, hence restricting their ability to reveal the interdependent pathological changes in structural and temporal network features following stroke. Here, we longitudinally analyzed hemodynamic-informed transient activity in a large cohort of stroke patients (n = 103) to assess spatial and temporal changes of brain networks after stroke. Metrics extracted from the hemodynamic-informed transient activity were replicable within- and between-individuals in healthy participants, hence supporting their robustness and their clinical applicability. While large-scale spatial patterns of brain networks were preserved after stroke, their durations were altered, with stroke subjects exhibiting a varied pattern of longer and shorter network activations compared to healthy individuals. Specifically, patients showed a longer duration in the lateral precentral gyrus and anterior cingulum, and a shorter duration in the occipital lobe and in the cerebellum. These temporal alterations were associated with white matter damage in projection and association pathways. Furthermore, they were tied to deficits in specific behavioral domains as restoration of healthy brain dynamics paralleled recovery of cognitive functions (attention, language and spatial memory), but was not significantly correlated to motor recovery. These findings underscore the critical importance of network temporal properties in dissecting the pathophysiology of brain changes after stroke, thus shedding new light on the clinical potential of time-resolved methods for fMRI analysis.
Functional magnetic resonance imaging (fMRI) has been widely employed to study stroke pathophysiology. In particular, analyses of fMRI signals at rest were directed at quantifying the impact of stroke on spatial features of brain networks. However, brain networks have intrinsic time features that were, so far, disregarded in these analyses. In consequence, standard fMRI analysis failed to capture temporal imbalance resulting from stroke lesions, hence restricting their ability to reveal the interdependent pathological changes in structural and temporal network features following stroke. Here, we longitudinally analyzed hemodynamic-informed transient activity in a large cohort of stroke patients (n = 103) to assess spatial and temporal changes of brain networks after stroke. While large-scale spatial patterns of these networks were preserved after stroke, their durations were altered, with stroke subjects exhibiting a varied pattern of longer and shorter network activations compared to healthy individuals. These temporal alterations were associated with white matter damage and were behavior-specific. Specifically, restoration of healthy brain dynamics paralleled recovery of cognitive functions, but was not significantly correlated to motor recovery. These findings underscore the critical importance of network temporal properties in dissecting the pathophysiology of brain changes after stroke, thus shedding new light on the clinical potential of time-resolved methods for fMRI analysis.
Significance Statement
Understanding the pathophysiology of a disorder is pivotal to design effective treatment. In this regard, recent advances in stroke research settled a new clinical concept: connectional diaschisis , which suggested that post-stroke impairments arise from both focal structural changes (tied to the injury) and widespread alterations in functional connectivity. fMRI time-resolved methods consider structural and temporal properties of brain networks as interdependent features. They are, thus, better suited to capture the intertwine between structural and functional changes. Here we leveraged a dynamic functional connectivity framework based on the clustering of hemodynamic-informed transients in a large and heterogeneous stroke population assessed longitudinally. We showed that lesions led to an unbalance in the brain dynamics that was associated with white matter fibers disruption and was restored as deficits recovered. Our work showed the potential of a time-resolved method to reveal clinically relevant dynamics of large-scale brain networks.
The underlying mechanisms of the unilateral spatial neglect (USN), a highly prevalent and disabling consequence of stroke that responds poorly to existing interventions, remain unclear. Animal research suggests that post-stroke USN may be related in part to a disruption of visual attention mediated through the midbrain superior colliculi (SC). However, little attention has been placed on studying this mechanism in humans with post-stroke USN. The first manuscript of this thesis presents a literature review on the implications of the SC in USN and reviews the rationale and potential for USN treatments aimed at involving the SC. Overall, 21 animal research studies and 24 human research studies were retrieved. Animal studies suggest a direct involvement of the SC in USN presentation and alleviation through a number of interconnections. It proposes that when the ipsilateral SC is deactivated, the animal presents with USN of the contralesional hemispace where the ipsilateral SC is found to be hypoactive, and the contralateral SC is hyperactive. This activity imbalance is restored after the contralateral SC is also deactivated, leading to USN alleviation. Nonetheless, given the paucity of human studies that were found, the contribution of the SC in USN, while plausible, remains to be confirmed. While intervention studies were retrieved where eye patching, with SC activity rationale, was used as a treatment for USN, several methodological issues were identified for future research in his area. Overall, it is suggested that further exploration of the mechanisms involved and their impact on USN in humans will help develop theoretically based intervention strategies tailored to USN type. The implication of the collicular pathway has been studied using the spatial summation effect (SSE), where response to bilateral presentations is significantly faster that to unilateral presentations. It has never been directly analyzed in those with post-stroke USN. The objectives of the second manuscript, in which the thesis related study was conducted were twofold: 1. to determine the feasibility of investigating SC contribution using the SSE and, 2. to compare the SC contribution in three groups - individuals with left USN of the near extrapersonal space following right hemisphere stroke, those without USN following a right hemisphere stroke and healthy normal controls. This pilot study included individuals with (n=7) and without (n=10) right hemisphere post-stroke USN and individuals with no history of previous stroke and USN (n=10). All participants were tested on a computer reaction time test under two conditions: using both eyes and using a right monocular eye patch while responding to unilateral and bilateral achromatic stimuli presentations. An eye tracker device was used to control for fixation ability. It was found that the SSE was present in controls under binocular and monocular conditions. In individuals without post-stroke USN, SSE was found abnormal (under binocular and monocular conditions) where reaction times to bilateral stimuli were faster than to the unilateral left stimuli only and not to the unilateral right stimuli presentations. As for the participants with USN, we found that they had poor fixation ability by demonstrating either failure to fixate or several missed fixations (i.e. loosing fixation). Overall, the feasibility of using SSE to investigate the contribution of the SC in post-stroke USN is challenging with this population given poor fixation. Interestingly, the SC are connected to the frontal eye field in directing spatial attention and controlling voluntary and reflexive saccade eye movements that are involved in fixation. This suggests that inability to properly fixate may be associated with SC impairment in individuals with post-stroke USN. Further research is needed to investigate this mechanism and to develop innovative treatment techniques for USN that could potentially involve training of fixation. Les mécanismes neuronaux sous-jacents de la négligence spatiale unilatérale (NSU), une conséquence répandue et invalidante d'un accident vasculaire cérébral (AVC) qui répond pauvrement aux traitements, sont encore mal connus. Des travaux récents sur des animaux suggèrent que la NSU peut être liée en partie à une rupture du contrôle de l'attention visuelle médiée par les collicules supérieurs (CS) du mésencéphale. Toutefois, peu d'attention a été mise sur l'étude de ce mécanisme chez l'homme avec la NSU suite à un AVC. Le premier manuscrit présente une revue de littérature sur les implications des CS dans la NSU et examine la justification et le potentiel, et vise à associer les CS à des traitements pour NSU. Au total, 21 études sur les animaux et 24 études sur l'homme étaient récupérées Les études chez l'animal suggèrent une implication directe des CS dans la présentation et l'allégement de la NSU. Principalement, lorsque la CS ipsilatérale est désactivé, l'animal présente la NSU de l'hémiespace contralésionnelle. Le CS ipsilatéral se trouve être hypoactif, et le CS contralatéral est hyperactif. Ce déséquilibre dans les activités des CS est rétabli suite à la désactivation du CS contralatéral mènant à l'allégement de la NSU. Néanmoins, étant donné la rareté des études sur l'homme qui ont été trouvées, la contribution des CS dans la NSU, tandis que plausible, reste à confirmer. Des études basées sur les connaissances des activités des CS chez l'homme ont été trouvées dans lesquelles la patche de l'il a été utilisée comme un traitement pour la NSU. Néanmoins, plusieurs questions doivent être abordées dans les futures études analysant l'effet de la patche de l'il sur la NSU. Dans l'ensemble, il est suggéré que l'exploration additionnelle et directe des mécanismes en jeu et leur impact sur la NSU chez l'homme contriburent au développement des stratégies d'intervention adaptées aux plusieurs types de NSU. L'implication des parcours rétino-colliculaires a été étudiée en utilisant l'effet de la sommation spatiale (ESS), mais n'a jamais été directement analysé chez cieux avec de la NSU suite à un AVC. Les objectifs du deuxième manuscrit étaient de déterminer la faisabilité d'enquêter sur l'implication des CS en utilisant l'ESS et d'analyser la contribution des CS chez les individus présentant une NSU gauche de l'espace extrapersonnel près suite à un AVC de l'hémisphère droit (n=7), les personnes sans NSU suite à un AVC de l'hémisphère droit (n=10), et chez des individus sains (n=10). Les participants ont été testés sur une tâche de temps de réaction sur l'ordinateur en utilisant les deux yeux et en utilisant une patche monoculaire sur l'il droit tout en répondant à des présentations achromatique unilatérales et bilatérales. Un dispositif oculomètre a été utilisé pour measurer de la capacité de fixation. Par conséquent, l'ESS était présent chez les individus sains sous conditions binoculaire et monoculaire. Chez les personnes sans NSU, l'ESS était anormal (sous conditions binoculaire et monoculaire), dans lesquelles les temps de réaction aux présentations bilatérales étaient plus rapides qu'aux présentations unilatérales gauches, et pas droites. Les participants avec NSU ont démontré une capacité de fixation faible en démontrant soit une incapacité totale de fixer ou plusieurs pertes de fixation. En conclusion, la possibilité d'utiliser l'ESS pour enquêter sur la contribution des CS dans la NSU suite à un AVC est difficile étant donné une pauvre capacité de fixation. En effet les CS sont liés au domaine il frontal à diriger l'attention spatiale et le contrôle des mouvements oculaires volontaires et réflexes. Nous pouvons donc spéculer que l'incapacité à fixer indique une insuffisance des activités des CS chez des individus avec NSU suite à un AVC. D'autres recherches sur ce sujet sont nécessaires afin de développer des techniques thérapeutique innovantrices qui pourraient impliquer un entraînement à la fixation.
Purpose: This study aimed to identify brain areas with white matter changes that contribute to motor recovery of affected limbs during acute to sub-acute phases of subcortical infarction. Methods: Diffusion tensor imaging was performed 1, 4, and 12 weeks after stroke onset in 18 patients with acute subcortical infarct, and in 18 age- and risk factor-matched controls. Fugl-Meyer scale was used to assess levels of motor impairment, and Statistical Parametric Mapping was applied to determine fractional anisotropy (FA) changes for the entire brain in order to identify areas correlated with motor recovery. Results: Fugl-Meyer scores of patients at 4 and 12 weeks were significantly higher than those at 1 week (all p < 0.01). Accompanying with the progressive decreases of FA in the corticospinal tract above and below the stroke lesion, progressive increases of FA in the contralesional medial frontal gyrus, and thalamocortical connections including projections to the somatosensory cortices, primary motor cortex, and premotor areas, were positively correlated with Fugl-Meyer scores (all p < 0.005) within 12 weeks following acute subcortical infarction. Conclusions: Remodeling of white matter in contralesional brain regions related to motor, cognition, and sensory processing may facilitate early motor recovery in patients with an acute infarct.
Neuroimagery findings have shown similar cerebral networks associated with imagination and execution of a movement. On the other hand, neuropsychological studies of parietal-lesioned patients suggest that these networks may be at least partly distinct. In the present study, normal subjects were asked to either imagine or execute auditory-cued hand movements. Compared with rest, imagination and execution showed overlapping networks, including bilateral premotor and parietal areas, basal ganglia and cerebellum. However, direct comparison between the two experimental conditions showed that specific cortico-subcortical areas were more engaged in mental simulation, including bilateral premotor, prefrontal, supplementary motor and left posterior parietal areas, and the caudate nuclei. These results suggest that a specific neuronal substrate is involved in the processing of hand motor representations.
Following a hemispheric stroke, various degrees of neuronal reorganization around the lesion occur immediately after disease onset and thereafter up to several months. These include transcallosal excitability, changes of the intact motor cortex and ipsilateral motor responses after transcranial magnetic stimulation (TMS) on the intact hemisphere. To elucidate the relationship between lesion localization and motor cortex excitability (intracortical inhibition; ICI) in the intact hemisphere, we applied a paired conditioning‐test TMS paradigm in 12 patients with unilateral cortical stroke (cortical group) and nine patients with subcortical stroke caudal to the corpus callosum (subcortical group), with interstimulus intervals varying from 1 to 10 ms. All patients exhibited unilateral complete hand palsy. ICI was significantly less in the cortical group than in age‐matched healthy control subjects. It was especially more marked in the cortical group patients with a disease duration of less than 4 months after onset. Patients in the cortical group with a duration longer than 4 months showed a tendency for ICI to be normalized, and there was a significant correlation between ICI and disease duration. Patients in the subcortical group showed normal excitability curves. All patients in the cortical group showed no transcallosal inhibition (TCI) in the active unaffected hand muscle after TMS of the affected motor cortex, whereas all the subcortical patients showed some TCI. No ipsilateral motor responses were elicited in the paretic hand in any of the patients. The reduced ICI in the cortical group might have been a result of disruption of TCI. The normalization of ICI in the patients with longer disease duration and the normal ICI in the subcortical group patients do not support the functional significance of motor cortex hyperexcitability in the unaffected hemisphere, at least in a patient population with poor motor recovery.
Brain activation is adaptive to task difficulty and practice. We used functional MRI to map brain systems activated by an object-location learning task in 24 healthy elderly volunteers each scanned following placebo and two of four active drugs studied. We distinguished a fronto-striatal system adaptive to difficulty from a posterior system adaptive to practice. Fronto-striatal response to increased cognitive load was significantly attenuated by scopolamine, sulpiride and methylphenidate; practice effects were not modulated by these drugs but were enhanced by diazepam. We also found enhancement by methylphenidate, and attenuation by sulpiride, of load response in premotor, cingulate and parietal regions comprising a spatial attention network. Difficulty and practice evoke anatomically and pharmacologically dissociable brain activation dynamics, which are probably mediated by different neurotransmitter systems in humans.
The aim of the current study was to assess the reproducibility of functional magnetic resonance imaging (fMRI) brain activation signals in a sensorimotor task in healthy subjects. Because random or systematic changes are likely to happen when movements are repeated over time, the authors searched for time-dependent changes in the fMRI signal intensity and the extent of activation within and between sessions. Reproducibility was studied on a sensorimotor task called "the active task" that includes a motor output and a sensory feedback, and also on a sensory stimulation called "the passive task" that assessed the sensory input alone. The active task consisted of flexion and extension of the right hand. The subjects had performed it several times before fMRI scanning so that it was well learned. The passive task consisted of a calibrated passive flexion and extension of the right wrist. Tasks were 1 Hz-paced. The control state was rest. Subjects naïve to the MRI environment and non–MRI-naïve subjects were studied. Twelve MRI-naïve subjects underwent 3 fMRI sessions separated by 5 hours and 49 days, respectively. During MRI scanning, they performed the active task. Six MRI-naïve subjects underwent 2 fMRI sessions with the passive task 1 month apart. Three non–MRI-naïve subjects performed twice an active 2-Hz self-paced task. The data were analyzed with SPM96 software. For within-session comparison, for active or passive tasks, good reproducibility of fMRI signal activation was found within a session (intra-and interrun reproducibility) whether it was the first, second, or third session. Therefore, no within-session habituation was found with a passive or a well-learned active task. For between-session comparison, for MRI-naïve or non–MRI-naïve subjects, and with the active or the passive task, activation was increased in the contralateral premotor cortex and in ispsilateral anterior cerebellar cortex but was decreased in the primary sensorimotor cortex, parietal cortex, and posterior supplementary motor area at the second session. The lower cortical signal was characterized by reduced activated areas with no change in maximum peak intensity in most cases. Changes were partially reversed at the third session. Part of the test–retest effect may come from habituation of the MRI experiment context. Less attention and stress at the second and third sessions may be components of the inhibition of cortical activity. Because the changes became reversed, the authors suggest that, beyond the habituation process, a learning process occurred that had nothing to do with procedural learning, because the tasks were well learned or passive. A long-term memory representation of the sensorimotor task, not only with its characteristics (for example, amplitude, frequency) but also with its context (fMRI), can become integrated into the motor system along the sessions. Furthermore, the pattern observed in the fMRI signal changes might evoke a consolidation process.Keywords: Active or passive motor task, Cerebral activation, Functional MRI, Healthy subjects, Human, Sensorimotor tasks
In studies of patients with focal brain lesions, it is often useful to coregister an image of the patient's brain to that of another subject or a standard template. We refer to this process as spatial normalization. Spatial normalization can improve the presentation and analysis of lesion location in neuropsychological studies; it can also allow other data, for example from functional imaging, to be compared to data from other patients or normal controls. In functional imaging, the standard procedure for spatial normalization is to use an automated algorithm, which minimizes a measure of difference between image and template, based on image intensity values. These algorithms usually optimize both linear (translations, rotations, zooms, and shears) and nonlinear transforms. In the presence of a focal lesion, automated algorithms attempt to reduce image mismatch between template and image at the site of the lesion. This can lead to significant inappropriate image distortion, especially when nonlinear transforms are used. One solution is to use cost-function masking—masking the areas used in the calculation of image difference—to exclude the area of the lesion, so that the lesion does not bias the transformations. We introduce and evaluate this technique using normalizations of a selection of brains with focal lesions and normal brains with simulated lesions. Our results suggest that cost-function masking is superior to the standard approach to this problem, which is affine-only normalization; we propose that cost-function masking should be used routinely for normalizations of brains with focal lesions.
The measurement of impairment and disability can improve patient care and is now essential in clinical audit. Practical, useful measures are slowly being developed, both for use in specific diseases and for more general use. This review discusses both new measures and new work on more well-established measures.
We used positron emission tomography (PET) to study organizational changes in the functional anatomy of the brain in 10 patients following recovery from striatocapsular motor strokes. Comparisons of regional cerebral blood flow maps at rest between the patients and 10 normal subjects revealed significantly lower regional cerebral blood flow in the basal ganglia, thalamus, sensorimotor, insular, and dorsolateral prefrontal cortices, in the brainstem, and in the ipsilateral cerebellum in patients, contralateral to the side of the recovered hand. These deficits reflect the distribution of dysfunction caused by the ischemic lesion. Regional cerebral blood flow was significantly increased in the contralateral posterior cingulate and premotor cortices, and in the caudate nucleus ipsilateral to the recovered hand. During the performance of a motor task by the recovered hand, patients activated the contralateral cortical motor areas and ipsilateral cerebellum to the same extent as did normal subjects. However, activation was greater than in normal subjects in both insulae; in the inferior parietal (area 40), prefrontal and anterior cingulate cortices; in the ipsilateral premotor cortex and basal ganglia; and in the contralateral cerebellum. The pattern of cortical activation was also abnormal when the unaffected hand, contralateral to the hemiplegia, performed the task. We showed that bilateral activation of motor pathways and the recruitment of additional sensorimotor areas and of other specific cortical areas are associated with recovery from motor stroke due to striatocapsular infarction. Activation of anterior and posterior cingulate and prefrontal cortices suggests that selective attentional and intentional mechanisms may be important in the recovery process. Our findings suggest that there is considerable scope for functional plasticity in the adult human cerebral cortex.
We have studied regional cerebral blood flow changes in 6 patients after their recovery from a first hemiplegic stroke. All had a single well-defined hemispheric lesion and at least a brachial monoparesis that subsequently recovered. Each patient had 6 measurements of cerebral blood flow by positron tomography with 2 scans at rest, 2 during movement of fingers of the recovered hand, and 2 during movement of fingers of the normal hand. When the normal fingers were moved, regional cerebral blood flow increased significantly in contralateral primary sensorimotor cortex and in the ipsilateral cerebellar hemisphere. When the fingers of the recovered hand were moved, significant regional cerebral blood flow increases were observed in both contralateral and ipsilateral primary sensorimotor cortex and in both cerebellar hemispheres. Other regions, namely, insula, inferior parietal, and premotor cortex, were also bilaterally activated with movement of the recovered hand. We have also demonstrated, by using a new technique of image analysis, different functional connections between the thalamic nuclei and specific cortical and cerebellar regions during these movements. Our results suggest that ipsilateral motor pathways may play a role in the recovery of motor function after ischemic stroke.