Functional outcome measures in stroke rehabilitation

I examine statistical considerations in the analysis of functional outcome following stroke and discuss the mathematical relation between improvement in function and discharge functional score. I demonstrate mathematically that the predictor variables of improvement and discharge functional score are the same and that the regression coefficients for improvement and discharge functional score will be equal, except for the admission functional score, for which a mathematically defined relation exists. I argue that the relation between admission functional score and discharge functional score must be positive and strong and that the relation between admission functional score and improvement must be negative for the stroke population. I believe that an ignorance of statistical concepts, especially confounding, and of the differences between raw correlations, partial correlations, and predictors have led to much confusion in functional outcome research.     

增强现实技术在卒中后上肢功能康复中的研究进展

增强现实技术作为一项康复新技术,目前在卒中患者上肢功能康复中的应用处于萌芽阶段.应用于上肢的增强现实关键技术包括跟踪注册技术、显示技术和交互技术.增强现实技术对卒中上肢功能的康复原理主要包括:通过功能训练重塑正常的左右制衡模式;通过高强度、可重复、任务导向性的功能性运动促进卒中患者脑的可塑性和功能重组.目前常见应用于卒...     

The use of the Theory of Planned Behavior to predict engagement in functional behaviors in schizophrenia

In schizophrenia, low motivation may play a role in the initiation and frequency of functional behaviors. Several reviews support the efficacy of the Theory of Planned Behavior (TPB) to predict engagement in various behaviors, but little research has utilized the TPB to explain functional behavior in schizophrenia. This study tested the TPB for predicting prospective engagement in functional behaviors in a sample of 64 individuals with schizophrenia. Participants completed questionnaires assessing their attitudes toward, social norms regarding, perceived behavioral control over, and intention to engage in various functional behaviors during the upcoming week. Follow-up questionnaires assessed engagement in functional behaviors. Zero-order correlations indicated that positive attitudes, social norms, and perceived behavioral control were positively correlated with intentions to engage in functional behaviors. In turn, intentions were positively correlated with engagement in functional behaviors. Using path analysis, social norms and control were significantly related to intentions, which in turn predicted greater engagement in functional behaviors. Results suggest that patients with schizophrenia make reasoned decisions for or against engaging in functional behaviors. Skills training interventions that also target components of the TPB may be effective for increasing motivation to engage in learned behaviors.     

Cognitive and functional changes with aging in schizophrenia.

The variation in functional outcome in schizophrenia appears to be exaggerated in late life. The cognitive and functional deficits commonly seen in younger schizophrenic patients appear to worsen in some cases in late life, while others patients appear to have a stable course of illness without functional decline, and still other patients have been reported to have essentially no residual symptoms in their later years. Cognitive and functional deficits appear to worsen more significantly in patients with a lifetime course of severe functional deficit. Despite the profound functional and cognitive deficits in these patients, neuropathologic studies have found no evidence of typical causes of severe cognitive impairments. This paper reviews the current findings on cognitive and functional changes in aging in schizophrenia, with a specific focus on patients with a poor lifetime functional outcome.     

Functional asymmetry in the cerebellum: A brief review

Recent discoveries on the way in which the cerebellum carries out higher non-motor functions, have stimulated a proliferation of researches into functional integration and neural mechanisms in the cerebellum. Cerebellar functional asymmetry is a special characteristic of cerebellar functional organization and the cerebro-cerebellar circuitry that underlies task performance. Multi-level neuroimaging studies demonstrate that cerebellar functional asymmetry has a rather complex pattern, and may be correlated with practice or certain disorders. In this review, we summarize some new and important advances in the understanding of functional laterality of the cerebellum in primary motor and higher cognitive functions, and highlight the differences in the patterns of cerebellar functional asymmetry in the various functional domains. We propose that cerebellar functional asymmetry may be associated with the pattern of connectivity between a large number of widely distributed brain areas and between special cerebellar functional regions. It is suggested that cerebro-cerebellar circuits in particular play an important role in cerebellar functional asymmetry. Finally, we propose that multi-scale connectivity analyses and careful studies of high-level cerebellar functional asymmetry would make an important contribution to the understanding of the human cerebellum and cerebral neural networks.     

Executive control functioning and functional ability in older adults

The manner in which executive control functioning exerts its influence on functional tasks was investigated. Sixty older adults were administered neuropsychological tasks tapping into four domains of executive control function, including working memory, planning, fluency, and flexibility. A test of performance-based functional ability also was administered. Correlational analyses demonstrated that working memory was most strongly associated with performance-based functional ability; however, impairment in planning appeared to best predict performance-based functional decrement in simultaneous regression models. Results highlight the role of planning in the maintenance of functional ability, as measured by performance-based functional measures.     

Executive Control Functioning and Functional Ability in Older Adults

The manner in which executive control functioning exerts its influence on functional tasks was investigated. Sixty older adults were administered neuropsychological tasks tapping into four domains of executive control function, including working memory, planning, fluency, and flexibility. A test of performance-based functional ability also was administered. Correlational analyses demonstrated that working memory was most strongly associated with performance-based functional ability; however, impairment in planning appeared to best predict performance-based functional decrement in simultaneous regression models. Results highlight the role of planning in the maintenance of functional ability, as measured by performance-based functional measures.     

Functional communication and executive function in aphasia

The purpose of this exploratory study was to investigate the relationship between functional communication and executive function ability in aphasia. Twenty-five participants with aphasia underwent examination with an extensive test battery including measures of functional communication, executive function ability, and language impairment. Compared to published norms, most participants did not perform within normal limits on the executive function tests. As expected, the correlation between severity of language impairment and functional communication ratings exceeded that among the executive functioning and functional communication measures. Eight of ten correlation coefficients for the relationship between executive functioning and functional communication reached statistical significance suggesting a clear relationship between scores on the executive functioning measures and functional communication ability. Based on these results, it appears that decreased executive functioning ability may coincide with decreased functional communication ability in persons with aphasia.     

Functional communication and executive function in aphasia

The purpose of this exploratory study was to investigate the relationship between functional communication and executive function ability in aphasia. Twenty‐five participants with aphasia underwent examination with an extensive test battery including measures of functional communication, executive function ability, and language impairment. Compared to published norms, most participants did not perform within normal limits on the executive function tests. As expected, the correlation between severity of language impairment and functional communication ratings exceeded that among the executive functioning and functional communication measures. Eight of ten correlation coefficients for the relationship between executive functioning and functional communication reached statistical significance suggesting a clear relationship between scores on the executive functioning measures and functional communication ability. Based on these results, it appears that decreased executive functioning ability may coincide with decreased functional communication ability in persons with aphasia.     

Changes in local brain function in mild cognitive impairment due to semantic dementia

AimsMild cognitive impairment due to semantic dementia represents the preclinical stage, involving cognitive decline dominated by semantic impairment below the semantic dementia standard. Therefore, studying mild cognitive impairment due to semantic dementia may identify changes in patients before progression to dementia. However, whether changes in local functional activity occur in preclinical stages of semantic dementia remains unknown. Here, we explored local functional changes in patients with mild cognitive impairment due to semantic dementia using resting‐state functional MRI.MethodsWe administered a battery of neuropsychological tests to twenty‐two patients with mild cognitive impairment due to semantic dementia (MCI‐SD group) and nineteen healthy controls (HC group). We performed structural MRI to compare gray matter volumes, and resting‐state functional MRI with multiple sub‐bands and indicators to evaluate functional activity.ResultsNeuropsychological tests revealed a significant decline in semantic performance in the MCI‐SD group, but no decline in other cognitive domains. Resting‐state functional MRI revealed local functional changes in multiple brain regions in the MCI‐SD group, distributed in different sub‐bands and indicators. In the normal band, local functional changes were only in the gray matter atrophic area. In the other sub‐bands, more regions with local functional changes outside atrophic areas were found across various indicators. Among these, the degree centrality of the left precuneus in the MCI‐SD group was positively correlated with general semantic tasks (oral sound naming, word‐picture verification).ConclusionOur study revealed local functional changes in mild cognitive impairment due to semantic dementia, some of which were located outside the atrophic gray matter. Driven by functional connectivity changes, the left precuneus might play a role in preclinical semantic dementia. The study proved the value of frequency‐dependent sub‐bands, especially the slow‐2 and slow‐3 sub‐bands.     

Functional disability in primary progressive aphasia

Background: In primary progressive aphasia (PPA), assessment of language predominates over assessment of functional impairment in activities of daily living (ADLs) in clinical and research environments. Most of the knowledge on functional disability in PPA relies largely on anecdotal experience and limited numbers of studies published to date.

Aims: (1) To describe the different patterns of ADL functional disability in the main PPA variants: semantic variant, nonfluent aphasia, and the more recently defined logopenic variant; (2) to draw relations between functional disability, cognitive, and behavioural symptoms in the PPAs; (3) to examine the impact of functional disability on carer burden, and (4) to provide specific strategies to address the described problems.

Main Contribution: Profiles of disease progression are described from a functional perspective, as well as the relationship (or lack thereof) between functional disability and cognitive and behavioural symptoms. Dementia-management strategies for carers and professionals in overcoming day-to-day difficulties are provided, and the impact of functional deficits on those around the patient, including their spouses and children, are discussed.

Conclusions: Patterns of ADL functional disability and their progression vary between PPA subtypes. Understanding these different profiles of impairment is critical to the development of tailored interventions. There is a range of therapeutic strategies which can be trialled to promote improved ADL functioning, which in turn may also help in reducing levels of carer burden in PPA.     

Widespread functional disconnectivity in schizophrenia with resting-state functional magnetic resonance imaging

Using resting-state functional magnetic resonance imaging, we examined the functional connectivity throughout the entire brain in schizophrenia. The abnormalities in functional connectivity were identified by comparing the correlation coefficients of each pair of 116 brain regions between 15 patients and 15 controls. Then, the global distribution of the abnormal functional connectivities was examined. Experimental results indicated, in general, a decreased functional connectivity in schizophrenia during rest, and such abnormalities were widely distributed throughout the entire brain rather than restricted to a few specific brain regions. The results provide a quantitative support for the hypothesis that schizophrenia may arise from the disrupted functional integration of widespread brain areas.     

Functional and anatomical connectivity abnormalities in left inferior frontal gyrus in schizophrenia

Functional studies in schizophrenia demonstrate prominent abnormalities within the left inferior frontal gyrus (IFG) and also suggest the functional connectivity abnormalities in language network including left IFG and superior temporal gyrus during semantic processing. White matter connections between regions involved in the semantic network have also been indicated in schizophrenia. However, an association between functional and anatomical connectivity disruptions within the semantic network in schizophrenia has not been established. Functional (using levels of processing paradigm) as well as diffusion tensor imaging data from 10 controls and 10 chronic schizophrenics were acquired and analyzed. First, semantic encoding specific activation was estimated, showing decreased activation within the left IFG in schizophrenia. Second, functional time series were extracted from this area, and left IFG specific functional connectivity maps were produced for each subject. In an independent analysis, tract‐based spatial statistics (TBSS) was used to compare fractional anisotropy (FA) values between groups, and to correlate these values with functional connectivity maps. Schizophrenia patients showed weaker functional connectivity within the language network that includes left IFG and left superior temporal sulcus/middle temporal gyrus. FA was reduced in several white matter regions including left inferior frontal and left internal capsule. Finally, left inferior frontal white matter FA was positively correlated with connectivity measures of the semantic network in schizophrenics, but not in controls. Our results indicate an association between anatomical and functional connectivity abnormalities within the semantic network in schizophrenia, suggesting further that the functional abnormalities observed in this disorder might be directly related to white matter disruptions. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Reduced specificity of functional connectivity in the aging brain during task performance

The importance of studying connectivity in the aging brain is increasingly recognized. Recent studies have shown that connectivity within the default mode network is reduced with age and have demonstrated a clear relation of these changes with cognitive functioning. However, research on age‐related changes in other functional networks is sparse and mainly focused on prespecified functional networks. Using functional magnetic resonance imaging, we investigated age‐related changes in functional connectivity during a visual oddball task in a range of functional networks. It was found that compared with young participants, elderly showed a decrease in connectivity between areas belonging to the same functional network. This was found in the default mode network and the somatomotor network. Moreover, in all identified networks, elderly showed increased connectivity between areas within these networks and areas belonging to different functional networks. Decreased connectivity within functional networks was related to poorer cognitive functioning in elderly. The results were interpreted as a decrease in the specificity of functional networks in older participants. Hum Brain Mapp 35:319–330, 2014. © 2012 Wiley Periodicals, Inc.     

Malformation of the functional organization of somatosensory cortex in adult ephrin-A5 knock-out mice revealed by in vivo functional imaging.

The molecular mechanisms that coordinate the functional organization of the mammalian neocortex are largely unknown. We tested the involvement of a putative guidance label, ephrin-A5, in the functional organization of the somatosensory cortex by quantifying the functional representations of individual whiskers in vivo in adult ephrin-A5 knock-out mice, using intrinsic signal optical imaging. In wild-type mice ephrin-A5 is expressed in a gradient in the somatosensory cortex during development. In adult ephrin-A5 knock-out mice, we found a spatial gradient of change in the amount of cortical territory shared by individual whisker functional representations across the somatosensory cortex, as well as a gradient of change in the distance between the functional representations. Both gradients of change were in correspondence with the developmental expression gradient of ephrin-A5 in wild-type mice. These changes involved malformations of the cortical spacing of the thalamocortical components, without concurrent malformations of the intracortical components of individual whisker functional representations. Overall, these results suggest that a developmental guidance label, such as ephrin-A5, is involved in establishing certain spatial relationships of the functional organization of the adult neocortex, and they underscore the advantage of investigating gene manipulation using in vivo functional imaging.     

Changes in white matter functional networks during wakefulness and sleep

Blood oxygenation level‐dependent (BOLD) signals in the white matter (WM) have been demonstrated to encode neural activities by showing structure‐specific temporal correlations during resting‐state and task‐specific imaging of fiber pathways with various degrees of correlations in strength and time delay. Previous neuroimaging studies have shown state‐dependent functional connectivity and regional amplitude of signal fluctuations in brain gray matter across wakefulness and nonrapid eye movement (NREM) sleep cycles. However, the functional characteristics of WM during sleep remain unknown. Using simultaneous electroencephalography and functional magnetic resonance imaging data during wakefulness and NREM sleep collected from 66 healthy participants, we constructed 10 stable WM functional networks using clustering analysis. Functional connectivity between these WM functional networks and regional amplitude of WM signal fluctuations across multiple low‐frequency bands were evaluated. In general, decreased WM functional connectivity between superficial and middle layer WM functional networks was observed from wakefulness to sleep. In addition, functional connectivity between the deep and cerebellar networks was higher during light sleep and lower during both wakefulness and deep sleep. The regional fluctuation amplitude was always higher during light sleep and lower during deep sleep. Importantly, slow‐wave activity during deep sleep negatively correlated with functional connectivity between WM functional networks but positively correlated with fluctuation strength in the WM. These observations provide direct physiological evidence that neural activities in the WM are modulated by the sleep–wake cycle. This study provided the initial mapping of functional changes in WM during sleep.     

Impaired functional connectivity at EEG alpha and theta frequency bands in major depression

Recent reports on functional brain imaging in major depression have lead to an assumption that observed psychopathology might be related to an altered brain functional connectivity. Our hypothesis was that an increase in brain functional connectivity occurs in major depression. As a measure of functional connectivity, the electroencephalogram (EEG) structural synchrony approach was used in 12 medication-free depressive outpatients and 10 control subjects. Differences in the number and strength of structurally synchronized EEG patterns were compared between groups. In depressive patients the number and strength of short cortex functional connections were significantly larger for the left than for the right hemisphere, while the number and strength of long functional connections were significantly larger for the right than for the left hemisphere. Some of the functional connections were positively correlated with the severity of depression, thus being predictive. These were short-range anterior, posterior, and left hemisphere functional connections for the alpha frequency band and short-range anterior functional connections for the theta frequency band. The topology of the most representative functional connections among all patients with major depression indicated that the right anterior and left posterior brain parts may discriminate depressive patients from healthy controls. The obtained data support our hypothesis that there is an increase in brain functional connectivity in major depression. This finding was interpreted within the semantic framework, where different specialization of left (monosemantic context) and right (polysemantic context) hemispheres is functionally insufficient in patients with depression.     

Functional and immunologic protein S in normal pregnant women and in full-term newborns

Total and free protein S antigen and C4b-binding protein (C4bp) were determined by rocket immuno-electrophoresis, and functional protein S was assayed by a coagulation method, throughout pregnancy and normal puerperium and in a group of normal full-term newborns (FTN). The functional protein S assay is based on a modification of the APTT, using a mixture of test sample, protein S deficient plasma, activated protein C, phospholipids and calcium. This protein S functional assay is specific for protein S since the APTT prolongation by normal plasma was abolished by incubation of plasma with monospecific, rabbit anti-protein S IgG. The ratios of functional protein S/free protein S antigen in healthy men (n = 13) and women (n = 14) were 1.0 +/- 0.13 (mean +/- SD) and 1.03 +/- 0.20, respectively. During pregnancy there is a decrease in functional protein S and a progressive decrease in total and free protein S antigen, with a functional/free protein S ratio of 0.75 +/- 0.28 in the third trimester of pregnancy (n = 16). In early puerperium the functional protein S level was lower than the free protein S antigen level (ratio about 0.5). In the FTN group, the free protein S level was 39% and protein S activity was about 70% that of adults, with a functional/free protein S ratio of 1.84 +/- 0.31. C4bp values were 23.5 +/- 10.3% in the FTN group, and crossed immunoelectrophoresis showed that in this group the major protein S peak corresponded to free protein S.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased cortico-subcortical functional connectivity in schizophrenia

It has been widely reported that structural and functional connectivities are disturbed in cortical networks in schizophrenia (SZ). However, much less is known about the structural and functional connectivities between cortical and subcortical regions in SZ. Here, diffusion tensor imaging (DTI) data was used to identify consistent cortico-subcortical structural connection patterns across SZ patients and controls, and thus 13 common cortical Regions of Interest (ROIs) were determined. DTI and resting state fMRI (R-fMRI) datasets were used to assess the structural and functional connectivities between the 13 cortical ROIs and 12 subcortical regions in 8 SZ patients and 10 normal controls. It was found that there are significantly increased functional connectivities for 7 cortico-subcortical connections between the 13 cortical ROIs and 12 subcortical regions. Among most of these connections, the functional connectivity strength was doubled in SZ in comparison to controls. The cortical ROIs with functional hyper-connectivities to subcortical regions are localized in frontal and parietal lobes. However, no significant difference in the structural connectivity between these cortical and subcortical regions was found between SZ and controls. Additional analysis results showed 4 significantly increased and 2 significantly decreased cortico-cortical connections. Our study results suggest the functional hyper-connectivity between cortical and subcortical regions, adding further evidence to literature findings that SZ is a disorder of connectivity between components of large-scale brain networks. The result of either increased or decreased functional connectivities among cortical ROIs exhibits the complex pattern of disturbance of brain networks in SZ.     

Cognitive and behavioural predictors of progression rates in Alzheimer's disease

Cognitive and functional decline in Alzheimer's disease (AD) may show different, yet correlated, rates of progression. Over a 2-year period we investigated the predictive role of neuropsychological and behavioural variables on the cognitive and functional decline of 43 patients with AD. Slow and fast decliners were defined on the basis of cognitive and functional indexes of disease progression. We found that cognitive decline was predicted by diffuse cognitive impairment and functional progression by visuospatial deficits. Psychotic symptoms predicted faster disease progression in both cognitive and functional dimensions.