Functional brain reorganization in children

Developmental brain plasticity in association with focal brain injury is dependent on a number of factors, including age of the individual at the time of injury, size and topography of the brain lesion, maturational state of the brain system injured, integrity of brain areas surrounding and contralateral to the lesion, presence and duration of epilepsy, and medication effects. Recently developed functional neuroimaging tools now make it possible to study non-invasively several aspects of human brain functional reorganization in response to injury. Clinical models which are suitable for the study of developmental brain plasticity include patients who have undergone cortical resections for the alleviation of intractable epilepsy, patients who have sustained unilateral cerebrovascular insults at various periods of development, patients with chronic progressive unilateral brain injury such as in the Sturge-Weber syndrome, and patients with early sensory deprivation such as blind or deaf subjects. Although evidence of functional brain reorganization can be demonstrated in these models, it is emphasized that the neurobiological rules that govern intrahemispheric versus interhemispheric reorganization of function in the brain are, at present, poorly understood.     

Training and stimulation in post stroke recovery brain reorganization

In both animal and clinical studies, training or rehabilitation increases cortical representation with subsequent functional recovery, whereas a lack of rehabilitation or training decreases cortical representation and delays recovery. Animals exposed to enriched environments post stroke have improved functional outcomes compared with animals exposed to nonenriched environments. In humans, stroke units may be the closest approximation there is to an enriched environment. However, studies indicate that patients spend the majority of time being inactive and alone while on a stroke unit. Given the animal evidence (which emphasizes increased stimulation and increased activity), there is clearly an opportunity for improving the stroke rehabilitation experience to maximize post stroke recovery.     

纹状体内囊梗死34例患者临床和影像特征

目的 分析纹状体内囊梗死(SCI)的临床和影像特征并探讨其发病机制.方法 回顾分析34例SCI患者的临床及影像资料.将患者分为皮质型SCI(CSCI)和非皮质型SCI(NCSCI)2组,进行临床和影像资料的对比分析.结果 CSCI 23例,NCSCI 11例.CT血管成像共检出大脑中动脉和颈内动脉狭窄或闭塞25例.CT脑灌注成像检出26例大脑中动脉供血区内血流灌注减低,其中19例累及广泛的大脑中动脉供血区.CSCI患者中检出上述动脉狭窄或闭塞21例,明显高于NCSCI患者中的4例(χ~2=3.27,P=0.020),CSCI患者中检出MCA供血区内血流减低区21例,明显高于NCSCI患者中的5例(χ~2=8.62,P=0.007).结论 SCI有临床和影像特征,大部分由于MCA原位病变所致.动脉病变和其造成的灌注减低是发生皮质症状的重要原因.     

Distinct clinical expressions of striatocapsular infarction according to cortical manifestations

Striatocapsular infarction is known to have various neurologic manifestations including cortical symptoms. However, striatocapsular infarction patients without cortical dysfunctions can be easily found. Therefore, we tried to evaluate the properties and pathogenesis of two distinct expressions of striatocapsular infarction, striatocapsular infarction with and without cortical dysfunctions respectively. Forty-eight patients were divided into two groups according to their initial manifestations. Forty-eight patients with striatocapsular infarction were divided into cortical type of striatocapsular infarction (CSCI) and non-cortical type (NCSCI) according to their initial manifestations. We compared the properties such as stroke risk factors, laboratory data, and clinical features and assessed magnetic resonance imaging (MRI) and MR angiography for possible mechanisms in each type of striatocapsular infarction. Patients with CSCI and those with NCSCI had similar characteristics, laboratory data and morphologic findings in MRI. CSCI patients had more profound initial neurologic manifestations [Both National Institutes of Health Stroke Scale (NIHSS) score and Barthel index]. In MR angiography, patients with CSCI showed more frequent single middle cerebral artery (MCA) stenosis, whereas NCSCI patients had findings that were more heterogeneous. In conclusion, we found that not all the patients with striatocapsular infarction had cortical dysfunctions. It is possible for lesions with similar size and location to have different manifestations (cortical or non-cortical) according to their vascular integrity.     

Cerebral artery thrombosis as a cause of striatocapsular infarction. a histopathological case study

Striatocapsular infarction is a distinct form of stroke, but few histopathological studies have been performed concerning acute lesions. We report the postmortem findings of a patient with an infarct who died shortly after onset. A 72-year-old man died of acute myocardial infarction 6 days after the onset of left-sided striatocapsular infarction. Autopsy revealed thrombus formation of the left middle cerebral artery (MCA) trunk. The lateral striate arteries irrigating the area of the infarct branched off distal to the arterial segment occluded with a thrombus. The cortical vessels were perfused by leptomeningeal collaterals. This report histopathologically confirmed thrombus formation of the MCA resulting in striatocapsular infarction.     

Functional reorganization and recovery after constraint-induced movement therapy in subacute stroke: case reports

Preliminary assessments of the feasibility, safety, and effects on neuronal reorganization measured with transcranial magnetic stimulation (TMS) from Constraint-Induced Movement Therapy (CIMT) of the upper extremity were made in eight cases of subacute stroke. Within fourteen days of their stroke, patients were randomly assigned to two weeks of CIMT or traditional therapy. Baseline motor performance and cortical/subcortical representation for movement with TMS were assessed before treatment. Post-treatment assessments were made at the end of treatment and at three months after the stroke. The TMS mapping showed a larger motor representation in the lesioned hemisphere of the CIMT patients as compared to the controls at the three-month follow-up assessment. The enlarged motor representation in the lesioned hemisphere for hand movement correlated with improved motor function of the affected hand, suggesting a link between movement representation size as measured with TMS and functionality. These results suggest that TMS can be safely and effectively used to assess brain function in subacute stroke and further suggest that CIMT may enhance cortical/subcortical motor reorganization and accelerate motor recovery when started within the first two weeks after stroke.     

Functional and effective reorganization of the aging brain during unimanual and bimanual hand movements

Motor performance decline observed during aging is linked to changes in brain structure and function, however, the precise neural reorganization associated with these changes remains largely unknown. We investigated the neurophysiological correlates of this reorganization by quantifying functional and effective brain network connectivity in elderly individuals (n = 11; mean age = 67.5 years), compared to young adults (n = 12; mean age = 23.7 years), while they performed visually‐guided unimanual and bimanual handgrips inside the magnetoencephalography (MEG) scanner. Through a combination of principal component analysis and Granger causality, we observed age‐related increases in functional and effective connectivity in whole‐brain, task‐related motor networks. Specifically, elderly individuals demonstrated (i) greater information flow from contralateral parietal and ipsilateral secondary motor regions to the left primary motor cortex during the unimanual task and (ii) decreased interhemispheric temporo‐frontal communication during the bimanual task. Maintenance of motor performance and task accuracy in elderly was achieved by hyperactivation of the task‐specific motor networks, reflecting a possible mechanism by which the aging brain recruits additional resources to counteract known myelo‐ and cytoarchitectural changes. Furthermore, resting‐state sessions acquired before and after each motor task revealed that both older and younger adults maintain the capacity to adapt to task demands via network‐wide increases in functional connectivity. Collectively, our study consolidates functional connectivity and directionality of information flow in systems‐level cortical networks during aging and furthers our understanding of neuronal flexibility in motor processes.     

Functional properties of sub-bands of oscillatory brain waves to pattern visual stimulation in man.

The scalp recorded transient visual evoked potential (VEP) represents the massed activity of a large number of neurons of the human visual cortex. Animal studies show that intracerebrally-recorded high frequency electrical activity represents binding between neurons participating in a cooperative response. We evaluated the relationship between scalp recorded high frequency activity and transient VEPs elicited by a repetitive (grating) pattern. Stimuli were 1 and 4 cycles/degree sinusoidal gratings, presented in an on/off mode. Following conventional averaging, the discrete wavelet transform (DWT) was applied. Multi-resolution decomposition was used to divide the responses into 6 orthogonal frequency bands. The results show that high frequency oscillatory activity in the beta and gamma frequency range is closely related in time to the N70 peak of the simultaneous VEP. Power in both bands is modulated by spatial frequency. Beta range response to hemifield stimulation recorded over a chain of electrodes over the occipital area lateralizes in the same manner as N70, while gamma range activity is insensitive to lateralization and is more closely linked to foveal stimulation. This dissociation between beta and gamma range activity suggests that different bands of high frequency oscillatory activity in humans, linked to visual stimulation, may represent different aspects of visual processing.     

Functional anatomy of motor recovery after early brain damage

Functional magnetic resonance imaging and transcranial magnetic stimulation were used to examine a 34 year-old right-handed patient, who, at the age of 6 years, had experienced sudden right hemiplegia, seizures, and stupor during a bout of measles encephalitis, followed by incomplete distal right motor recovery. Morphological MRI showed massive unilateral enlargement of the left ventricle, associated with extreme thinning of the white and gray matter,with partial preservation of the pyramidal tract. Functional MRI and transcranial magnetic stimulation revealed reorganization of the motor cortices, and integrity of the corticospinal pathway, respectively. Our findings indicate that complete hand motor recovery may require functional connections between the motor cortical areas and cortical-subcortical structures, in addition to the retained integrity of the primary sensorimotor area and pyramidal tract.     

Functional recovery and expression of GDNF seen in photochemically induced cerebral infarction

Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor involved in the survival and proliferation of neurons. However, there have been few reports examining the relationship between GDNF and functional recovery after cerebral infarction. The authors investigated the change in the expression of GDNF proteins during functional recovery in rats following photochemically induced cerebral infarctions. Functional recovery for the first 14 days after the infarction was evaluated using a beam-walking test. The number of GDNF-like immunoreactive cells around the infarction were counted at various times (24 h, 72 h, 7 days, and 14 days) post-infarction. Immunohistochemical analysis of brain sections showed that the expression of GDNF-like immunoreactive cells was significantly increased in the temporal cortex until 7 days on the side ipsilateral to the infarction, and had decreased by 14 days. Likewise, the functional recovery of paralysis was substantial until 7 days post-infarction, after which the improvement was mild. Therefore, the expression of GDNF protein might have some relationship with the functional recovery of paralysis. There are great hopes that GDNF could be used as a therapeutic agent for cerebral infarction.     

Plasticity and reorganization of the uninjured brain

Brain capacity is dependent not so much on the number of neurons but on the number of synaptic connections with functional connections that develop over a lifetime of genetic programming and life experiences. In the uninjured human brain, cortical reorganization that occurs in response to learning and experience is referred to as brain plasticity. Motor learning and complex environments result in a greater number of synapses and an increase in dendritic branching, whereas repetitive movements alone, in the absence of motor learning, do not. Learning and experience lead to an expansion of cortical representation, while failure to maintain training results in a contraction of cortical representation. In animals, loss of sensory peripheral afferent input results in an expansion of the forelimb representation of the intact adjacent cortex. Prolonged periods of peripheral nerve stimulation in both animals and humans can lead to reorganization of related sensorimotor cortical maps.     

Functional reorganization in adult monkey thalamus after peripheral nerve injury.

Large changes in somatotopic organization can be induced in adult primate somatosensory cortex by cutting peripheral afferents. The role, if any, of the thalamus in these changes has not been investigated previously. In the present experiments, electrophysiological recording in the ventroposterior lateral nucleus (VPL) has revealed that not only can reorganization occur in the thalamus, but it may be as extensive as that revealed in the cortex of the same monkeys. Thus, for at least some types of deafferentation, the reorganization revealed in the cortex may depend largely on subcortical changes.     

Middle cerebral artery stenosis is a major clinical determinant in striatocapsular small, deep infarction

BACKGROUND: The significance of the stenotic lesions of the middle cerebral artery (MCA) in Asian patients with striatocapsular small, deep infarctions (SSDIs) remains undetermined. OBJECTIVES: To investigate the frequency of stenotic lesions of the MCA in patients with SSDIs and to evaluate clinical and radiological features in those same patients. SETTING: Acute stroke registry of a university hospital. PATIENTS AND METHODS: One hundred two Korean patients with acute symptomatic SSDIs underwent cerebral angiography or magnetic resonance angiography and echocardiography. We divided these patients into 2 groups-patients with and without MCA occlusive lesions. The clinical and magnetic resonance image features were compared between these 2 groups. RESULTS: Thirty-seven patients (36%) had an ipsilateral proximal MCA lesion, whereas 65 patients (64%) showed no MCA abnormality on cerebral angiography or magnetic resonance angiography. Among 65 patients without an MCA lesion, 18 had an embolic source; the remaining 37 patients had no demonstrable embolic source. There were significant differences in the temporal profile and magnetic resonance imaging findings between the groups. Although the type of lacunar syndrome and the volume of infarcts did not differ between the groups, the unstable temporal profile and magnetic resonance imaging findings of multiple small infarcts in the symptomatic hemisphere were frequently observed in patients with MCA lesions. CONCLUSIONS: The proximal MCA lesion was a common cause of SSDIs in Korean patients. Depending on the existence of an MCA lesion, the clinical course and magnetic resonance imaging feature of the patients with SSDIs were different.     

Functional recovery after brain lesion--contralateral neuromodulation: an fMRI study

Behavioral recovery takes place even after permanent damage to the entire brain region normally controlling sensorimotor hind limb function in the rat. In our study, 2 weeks after full behavioral recovery from an experimental unilateral permanent brain damage, the topographic representation of the previous paretic hindlimb was investigated by fMRI. The analysis showed that during electrical stimulation of the previously paretic hindlimb, two normally inactive brain regions were now being activated. One region was the non-damaged contralateral sensori-motor cortex and the other region was located lateral to the lesion. These results suggest that behavioral recovery can be explained by functional reorganization and neuromodulation of the brain.     

Functional magnetic resonance imaging evaluation of brain function reorganization in cerebral stroke patients after constraint-induced movement therapy

In this study, stroke patients received constraint-induced movement therapy for 3 weeks. Before and after constraint-induced movement therapy, the flexibility of their upper limbs on the affected side was assessed using the Wolf motor function test, and daily use of their affected limbs was assessed using the movement activities log, and cerebral functional reorganization was assessed by functional magnetic resonance imaging. The Wolf motor function test score and the movement activities log quantity and quality scores were significantly increased, while action performance time in the Wolf motor function test was significantly decreased after constraint-induced movement therapy. By functional magnetic resonance imaging examination, only scattered activation points were visible on the affected side before therapy. In contrast, the volume of the activated area was increased after therapy. The activation volume in the sensorimotor area was significantly different before and after therapy, and the activation area increased and appeared adjusted. In addition to the activated area around the lesions being decreased, there were also some new activated areas, including the supplementary movement area, premotor area and the ipsilateral sensorimotor area. Our findings indicate that constraint-induced movement therapy significantly improves the movement ability and daily use of the affected upper limbs in stroke patients and promotes cerebral functional reorganization.     

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.     

Functional reorganization of the auditory pathways following late callosotomy

Injuries at various levels of the auditory system have been shown to lead to functional reorganization of the auditory pathways. In particular, it has recently been shown that such reorganization can occur in callosal agenesis. The pattern of cortical activity following callosotomy is however still unknown, but behavioral results suggest that it could be significantly different from that observed in callosal agenesis. We aimed to confirm this hypothesis by investigating fMRI responses to complex sounds presented binaurally and monaurally in a callosotomized patient. In the binaural condition, the callosotomized subject showed patterns of auditory cortical activation that were similar to those of neurologically intact individuals. However, in both monaural conditions, the callosotomized individual showed a significant increase of the asymmetries favoring the contralateral pathways. Such patterns of cortical responses are only partially consistent with the results obtained from callosal agenesis subjects using the exact same procedure. Indeed, the latter show differences compared with normals in both binaural and monaural conditions. These findings provide neurological evidence that callosotomy could lead to distinctive functional reorganization of the human auditory pathways.     

Functional reorganization of the auditory pathways following late callosotomy

Injuries at various levels of the auditory system have been shown to lead to functional reorganization of the auditory pathways. In particular, it has recently been shown that such reorganization can occur in callosal agenesis. The pattern of cortical activity following callosotomy is however still unknown, but behavioral results suggest that it could be significantly different from that observed in callosal agenesis. We aimed to confirm this hypothesis by investigating fMRI responses to complex sounds presented binaurally and monaurally in a callosotomized patient. In the binaural condition, the callosotomized subject showed patterns of auditory cortical activation that were similar to those of neurologically intact individuals. However, in both monaural conditions, the callosotomized individual showed a significant increase of the asymmetries favoring the contralateral pathways. Such patterns of cortical responses are only partially consistent with the results obtained from callosal agenesis subjects using the exact same procedure. Indeed, the latter show differences compared with normals in both binaural and monaural conditions. These findings provide neurological evidence that callosotomy could lead to distinctive functional reorganization of the human auditory pathways.