Altered topological properties of the cortical motor‐related network in patients with subcortical stroke revealed by graph theoretical analysis

Cerebral neuroplasticity after stroke has been elucidated by functional neuroimaging. However, little is known concerning how topological properties of the cortical motor‐related network evolved following subcortical stroke. In the present study, we investigated 24 subcortical stroke patients with only left motor pathway damaged and 24 matched healthy controls. A cortical motor‐related network consisting of 20 brain regions remote from the primary lesion was constructed using resting‐state functional MRI datasets. We subsequently used graph theoretical approaches to analyze the topological properties of this network in both stroke patients and healthy controls. In addition, we divided the stroke patients into two subgroups according to their outcomes in hand function to explore relationships between topological properties of this network and outcomes in hand function. Although we observed that the cortical motor‐related network in both healthy controls and stroke patients exhibited small‐world topology, the local efficiency of this network in stroke patients is higher than and global efficiency is lower than those in healthy controls. In addition, striking alterations in the betweenness centrality of regions were found in stroke patients, including the contralesional supplementary motor area, dorsolateral premotor cortex, and anterior inferior cerebellum. Moreover, we observed significant correlations between betweenness centrality of regions and Fugl‐Meyer assessment scores. A tendency for the cortical motor‐related network to be close to a regular configuration and altered betweenness centrality of regions were demonstrated in patients with subcortical stroke. This study provided insight into functional organization after subcortical stroke from the viewpoint of network topology. Hum Brain Mapp 35:3343–3359, 2014. © 2013 Wiley Periodicals, Inc .     

Evaluation of the motor cortical excitability changes after ischemic stroke

Background:

We evaluated progressive changes in excitability of motor cortex following ischemic stroke using Transcranial Magnetic Stimulation (TMS).

Materials and Methods:

Thirty-one patients (24 men, 7 women; age 37.3 ± 8.2 years) were recruited and TMS was performed using Magstim 200 stimulator and a figure-of-eight coil. Resting motor threshold (RMT) was recorded from affected and unaffected hemispheres and motor evoked potential (MEP) was recorded from contralateral FDI muscle. Central motor conduction time (CMCT) was calculated using F wave method. All measurements were done at baseline (2^nd), 4^th, and 6^th week of stroke.

Results: Affected hemisphere:

MEP was recordable in 3 patients at baseline (all had prolonged CMCT). At 4 weeks, MEP was recordable in one additional patient and CMCT remained prolonged. At 6 weeks, CMCT normalized in one patient. RMT was recordable (increased) in 3 patients at baseline, in one additional patient at 4 weeks, and reduced marginally in these patients at 6 weeks.

Unaffected hemisphere:

MEP was recordable in all patients at baseline, and reduced significantly over time (2^nd week 43.52 ± 9.60, 4^th week 38.84 ± 7.83, and 6^th week 36.85 ± 7.27; P < 0.001). The CMCT was normal and remained unchanged over time.

Conclusion:

The increase in excitability of the unaffected motor cortex suggests plasticity in the post-stroke phase.     

Dynamic brain structural changes after left hemisphere subcortical stroke

This study aimed to quantify dynamic structural changes in the brain after subcortical stroke and identify brain areas that contribute to motor recovery of affected limbs. High‐resolution structural MRI and neurological examinations were conducted at five consecutive time points during the year following stroke in 10 patients with left hemisphere subcortical infarctions involving motor pathways. Gray matter volume (GMV) was calculated using an optimized voxel‐based morphometry technique, and dynamic changes in GMV were evaluated using a mixed‐effects model. After stroke, GMV was decreased bilaterally in brain areas that directly or indirectly connected with lesions, which suggests the presence of regional damage in these “healthy” brain tissues in stroke patients. Moreover, the GMVs of these brain areas were not correlated with the Motricity Index (MI) scores when controlling for time intervals after stroke, which indicates that these structural changes may reflect an independent process (such as axonal degeneration) but cannot affect the improvement of motor function. In contrast, the GMV was increased in several brain areas associated with motor and cognitive functions after stroke. When controlling for time intervals after stroke, only the GMVs in the cognitive‐related brain areas (hippocampus and precuneus) were positively correlated with MI scores, which suggests that the structural reorganization in cognitive‐related brain areas may facilitate the recovery of motor function. However, considering the small sample size of this study, further studies are needed to clarify the exact relationships between structural changes and recovery of motor function in stroke patients. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Early motor network connectivity after stroke: An interplay of general reorganization and state‐specific compensation

Motor recovery after stroke relies on functional reorganization of the motor network, which is commonly assessed via functional magnetic resonance imaging (fMRI)‐based resting‐state functional connectivity (rsFC) or task‐related effective connectivity (trEC). Measures of either connectivity mode have been shown to successfully explain motor impairment post‐stroke, posing the question whether motor impairment is more closely reflected by rsFC or trEC. Moreover, highly similar changes in ipsilesional and interhemispheric motor network connectivity have been reported for both rsFC and trEC after stroke, suggesting that altered rsFC and trEC may capture similar aspects of information integration in the motor network reflecting principle, state‐independent mechanisms of network reorganization rather than state‐specific compensation strategies. To address this question, we conducted the first direct comparison of rsFC and trEC in a sample of early subacute stroke patients (n = 26, included on average 7.3 days post‐stroke). We found that both rsFC and trEC explained motor impairment across patients, stressing the clinical potential of fMRI‐based connectivity. Importantly, intrahemispheric connectivity between ipsilesional M1 and premotor areas depended on the activation state, whereas interhemispheric connectivity between homologs was state‐independent. From a mechanistic perspective, our results may thus arise from two distinct aspects of motor network plasticity: task‐specific compensation within the ipsilesional hemisphere and a more fundamental form of reorganization between hemispheres.     

Reduced neural connectivity but increased task‐related activity during working memory in de novo Parkinson patients

Objective: Patients with Parkinson's disease (PD) often suffer from impairments in executive functions, such as working memory deficits. It is widely held that dopamine depletion in the striatum contributes to these impairments through decreased activity and connectivity between task‐related brain networks. We investigated this hypothesis by studying task‐related network activity and connectivity within a sample of de novo patients with PD, versus healthy controls, during a visuospatial working memory task. Methods: Sixteen de novo PD patients and 35 matched healthy controls performed a visuospatial n‐back task while we measured their behavioral performance and neural activity using functional magnetic resonance imaging. We constructed regions‐of‐interest in the bilateral inferior parietal cortex (IPC), bilateral dorsolateral prefrontal cortex (DLPFC), and bilateral caudate nucleus to investigate group differences in task‐related activity. We studied network connectivity by assessing the functional connectivity of the bilateral DLPFC and by assessing effective connectivity within the frontoparietal and the frontostriatal networks. Results: PD patients, compared with controls, showed trend‐significantly decreased task accuracy, significantly increased task‐related activity in the left DLPFC and a trend‐significant increase in activity of the right DLPFC, left caudate nucleus, and left IPC. Furthermore, we found reduced functional connectivity of the DLPFC with other task‐related regions, such as the inferior and superior frontal gyri, in the PD group, and group differences in effective connectivity within the frontoparietal network. Interpretation: These findings suggest that the increase in working memory‐related brain activity in PD patients is compensatory to maintain behavioral performance in the presence of network deficits. Hum Brain Mapp 36:1554–1566, 2015. © 2015 Wiley Periodicals, Inc.     

Corticomuscular coherence in the acute and subacute phase after stroke

Objective

Stroke is one of the leading causes of physical disability due to damage of the motor cortex or the corticospinal tract. In the present study we set out to investigate the role of adaptations in the corticospinal pathway for motor recovery during the subacute phase after stroke.

Absent movement‐related cortical potentials in children with primary motor stereotypies

The underlying pathophysiologic mechanism for complex motor stereotypies in children is unknown, with hypotheses ranging from an arousal to a motor control disorder. Movement‐related cortical potentials (MRCPs), representing the activation of cerebral areas involved in the generation of movements, precede and accompany self‐initiated voluntary movements. The goal of this study was to compare cerebral activity associated with stereotypies to that seen with voluntary movements in children with primary complex motor stereotypies. Electroencephalographic (EEG) activity synchronized with video recording was recorded in 10 children diagnosed with primary motor stereotypies and 7 controls. EEG activity related to stereotypies and self‐paced arm movements were analyzed for presence or absence of early or late MRCP, a steep negativity beginning about 1 second before the onset of a voluntary movement. Early MRCPs preceded self‐paced arm movements in 8 of 10 children with motor stereotypies and in 6 of 7 controls. Observed MRCPs did not differ between groups. No MRCP was identified before the appearance of a complex motor stereotypy. Unlike voluntary movements, stereotypies are not preceded by MRCPs. This indicates that premotor areas are likely not involved in the preparation of these complex movements and suggests that stereotypies are initiated by mechanisms different from voluntary movements. Further studies are required to determine the site of the motor control abnormality within cortico‐striatal‐thalamo‐cortical pathways and to identify whether similar findings would be found in children with secondary stereotypies. © 2013 International Parkinson and Movement Disorder Society     

Subdivision of Broca's region based on individual‐level functional connectivity

Broca's region is composed of two adjacent cytoarchitectonic areas, 44 and 45, which have distinct connectivity to superior temporal and inferior parietal regions in both macaque monkeys and humans. The current study aimed to make use of prior knowledge of sulcal anatomy and resting‐state functional connectivity, together with a novel visualization technique, to manually parcellate areas 44 and 45 in individual brains in vivo. One hundred and one resting‐state functional magnetic resonance imaging datasets from the Human Connectome Project were used. Left‐hemisphere surface‐based correlation matrices were computed and visualized in brainGL. By observation of differences in the connectivity patterns of neighbouring nodes, areas 44 and 45 were manually parcellated in individual brains, and then compared at the group‐level. Additionally, the manual labelling approach was compared with parcellation results based on several data‐driven clustering techniques. Areas 44 and 45 could be clearly distinguished from each other in all individuals, and the manual segmentation method showed high test‐retest reliability. Group‐level probability maps of areas 44 and 45 showed spatial consistency across individuals, and corresponded well to cytoarchitectonic probability maps. Group‐level connectivity maps were consistent with previous studies showing distinct connectivity patterns of areas 44 and 45. Data‐driven parcellation techniques produced clusters with varying degrees of spatial overlap with the manual labels, indicating the need for further investigation and validation of machine learning cortical segmentation approaches. The current study provides a reliable method for individual‐level cortical parcellation that could be applied to regions distinguishable by even the most subtle differences in patterns of functional connectivity.     

Non‐invasive brain stimulation for fine motor improvement after stroke: a meta‐analysis

The aim of this study was to determine whether non‐invasive brain stimulation (NIBS) techniques improve fine motor performance in stroke. We searched PubMed, EMBASE, Web of Science, SciELO and OpenGrey for randomized clinical trials on NIBS for fine motor performance in stroke patients and healthy participants. We computed Hedges’ g for active and sham groups, pooled data as random‐effects models and performed sensitivity analysis on chronicity, montage, frequency of stimulation and risk of bias. Twenty‐nine studies (351 patients and 152 healthy subjects) were reviewed. Effect sizes in stroke populations for transcranial direct current stimulation and repeated transcranial magnetic stimulation were 0.31 [95% confidence interval (CI), 0.08–0.55; P = 0.010; Tau², 0.09; I², 34%; Q, 18.23; P = 0.110] and 0.46 (95% CI, 0.00–0.92; P = 0.05; Tau², 0.38; I², 67%; Q, 30.45; P = 0.007). The effect size of non‐dominant healthy hemisphere transcranial direct current stimulation on non‐dominant hand function was 1.25 (95% CI, 0.09–2.41; P = 0.04; Tau², 1.26; I², 93%; Q, 40.27; P < 0.001). Our results show that NIBS is associated with gains in fine motor performance in chronic stroke patients and healthy subjects. This supports the effects of NIBS on motor learning and encourages investigation to optimize their effects in clinical and research settings.     

Cortical reorganization after motor stroke: A pilot study on differences between the upper and lower limbs

Stroke patients suffering from hemiparesis may show substantial recovery in the first months poststroke due to neural reorganization. While reorganization driving improvement of upper hand motor function has been frequently investigated, much less is known about the changes underlying recovery of lower limb function. We, therefore, investigated neural network dynamics giving rise to movements of both the hands and feet in 12 well‐recovered left‐hemispheric chronic stroke patients and 12 healthy participants using a functional magnetic resonance imaging sparse sampling design and dynamic causal modeling (DCM). We found that the level of neural activity underlying movements of the affected right hand and foot positively correlated with residual motor impairment, in both ipsilesional and contralesional premotor as well as left primary motor (M1) regions. Furthermore, M1 representations of the affected limb showed significantly stronger increase in BOLD activity compared to healthy controls and compared to the respective other limb. DCM revealed reduced endogenous connectivity of M1 of both limbs in patients compared to controls. However, when testing for the specific effect of movement on interregional connectivity, interhemispheric inhibition of the contralesional M1 during movements of the affected hand was not detected in patients whereas no differences in condition‐dependent connectivity were found for foot movements compared to controls. In contrast, both groups featured positive interhemispheric M1 coupling, that is, facilitation of neural activity, mediating movements of the affected foot. These exploratory findings help to explain why functional recovery of the upper and lower limbs often develops differently after stroke, supporting limb‐specific rehabilitative strategies.     

Normalized activation in the somatosensory cortex 30 years following nerve repair in children: an fMRI study

The clinical outcome following a peripheral nerve injury in the upper extremity is generally better in young children than in teenagers and in adults, but the mechanism behind this difference is unknown. In 28 patients with a complete median nerve injury sustained at the ages of 1–13 years (n = 13) and 14–20 years (n = 15), the cortical activation during tactile finger stimulation of the injured and healthy hands was monitored at a median time since injury of 28 years using functional magnetic resonance imaging (fMRI) at 3 Tesla. The results from the fMRI were compared with the clinical outcome and electroneurography. The cortical activation pattern following sensory stimulation of the median nerve‐innervated fingers was dependent on the patient's age at injury. Those injured at a young age (1–13 years) had an activation pattern similar to that of healthy controls. Furthermore, they showed a clinical outcome significantly superior (P = 0.001) to the outcome in subjects injured at a later age; however, electroneurographical parameters did not differ between the groups. In subjects injured at age 14–20 years, a more extended activation of the contralateral hemisphere was seen in general. Interestingly, these patients also displayed changes in the ipsilateral hemisphere where a reduced inhibition of somatosensory areas was seen. This loss of ipsilateral inhibition correlated to increasing age at injury as well as to poor recovery of sensory functions in the hand. In conclusion, cerebral changes in both brain hemispheres may explain differences in clinical outcome following a median nerve injury in childhood or adolescence.     

Training‐, muscle‐ and task‐specific up‐ and downregulation of cortical inhibitory processes

Motor cortical contribution was shown to be important for balance control and for ballistic types of movements. However, little is known about the role of cortical inhibitory mechanisms and even less about long(er)‐term adaptations of these inhibitory processes. Therefore, the aim of the present study was to investigate the role of intracortical inhibition before and after four weeks of explosive or balance training. Two groups of subjects participated for four weeks either in an explosive training programme of the plantar flexor muscles or in a balance training programme on unstable devices. Adaptations in short‐interval intracortical inhibition (SICI) were assessed by applying paired‐pulse TMS to the soleus muscle during dynamic plantar flexions, balance perturbations and at rest. Furthermore, SICI was assessed for the untrained tibialis anterior muscle. The results show task‐, muscle‐ and group‐specific adaptations in SICI after the training (p = .021) with significantly increased SICI after balance training in the balance task and decreased SICI after explosive training in the ballistic task. The training also caused task‐ and group‐specific behavioural adaptations indicated by improved balance performance after balance training and increased ballistic performance after explosive training. There were no changes in SICI when measured at rest or in the untrained tibialis anterior muscle. This study shows that long(er)‐term training improves the ability to modulate cortical inhibitory processes in a task‐ and muscle‐specific manner.