Content validity of the Brief and Comprehensive ICF Core Sets for common disabling conditions in a developing country.

The International Classification of Functioning, Disability and Health (ICF) features associated tools, the Brief and Comprehensive ICF Core Sets. These are designed to be universally applicable, but have limited evidence of content validity (i.e. comprehensiveness and relevance) in low income, non-Western countries. In this cross-sectional study, we aimed to assess the content validity of the ICF Core Sets in Nepal. We interviewed 161 participants with stroke, spinal cord injury (SCI), chronic obstructive pulmonary disease (COPD), and musculoskeletal conditions and asked them to identify activities they had difficulty performing due to their health condition. We mapped 544 participant responses to the ICF and assessed if these ICF categories were represented in the respective ICF core sets. The Comprehensive Core Sets for stroke, COPD, SCI, and musculoskeletal conditions contained more items identified by participants than the respective Brief Core Sets (e.g., 89% vs. 26% in stroke). Among ICF categories that represented at least 5% of participants' responses, the Brief Core Sets covered 40%-71% of participants' responses whereas the Comprehensive Core Sets covered 67%-100% of responses. This is the first study to evaluate the content validity of the ICF Brief and Comprehensive core sets in Nepali individuals with stroke, SCI, MSK conditions, and COPD. The Comprehensive Core Sets for stroke, COPD, and SCI have adequate content validity for use in clinical practice and research in Nepal; the Brief Core Sets may not adequately meet local and individual needs unless supplemented with additional ICF categories.

Independent component analysis for brain fMRI does not select for independence.

InfoMax and FastICA are the independent component analysis algorithms most used and apparently most effective for brain fMRI. We show that this is linked to their ability to handle effectively sparse components rather than independent components as such. The mathematical design of better analysis tools for brain fMRI should thus emphasize other mathematical characteristics than independence.

Identification of a nephritogenic immunodominant B and T cell epitope in experimental autoimmune glomerulonephritis.

Experimental autoimmune glomerulonephritis (EAG) can be induced in Wistar Kyoto (WKY) rats by immunization with the non-collagenous domain (NC1) of the alpha 3 chain of type IV collagen, alpha3(IV)NC1. In patients with Goodpasture's disease, the major B cell epitope is located at the N-terminus of alpha3(IV)NC1. In order to investigate whether B and T cell responses in EAG are directed towards immunodominant peptides within the same region of rat alpha3(IV)NC1, we immunized WKY rats with recombinant rat alpha3(IV)NC1 (positive control) and five 15-mer overlapping synthetic peptides from the N-terminus of rat alpha3(IV)NC1: pCol(17-31), pCol(24-38), pCol(31-45), pCol(38-52) and pCol(45-59). Positive control animals immunized with alpha3(IV)NC1 produced an antibody response directed towards alpha3(IV)NC1 and pCol(24-38). Splenic T cells from these animals proliferated in response to alpha3(IV)NC1 and pCol(24-38). No significant antibody or T cell responses were observed to the other peptides examined. Animals immunized with pCol(24-38) developed linear deposits of immunoglobulin G on the glomerular basement membrane, albuminuria and focal necrotizing glomerulonephritis with crescent formation by week 6 after immunization. Circulating antibodies from these animals recognized pCol(24-38) and alpha3(IV)NC1, and their T cells proliferated in response to pCol(24-38) and alpha3(IV)NC1. Animals immunized with the other peptides developed no significant immune response to alpha3(IV)NC1 and no disease. In conclusion, these results demonstrate that a 15-mer peptide from the N-terminus of alpha3(IV)NC1 [pCol(24-38)] is recognized by B and T cells from rats immunized with recombinant alpha3(IV)NC1, and that the same peptide is capable of inducing crescentic glomerulonephritis. Identification of this immunodominant peptide will be of value in designing new therapeutic strategies for inducing mucosal tolerance in EAG, which may be applicable to patients with glomerulonephritis.

Distributed and overlapping representations of faces and objects in ventral temporal cortex.

The functional architecture of the object vision pathway in the human brain was investigated using functional magnetic resonance imaging to measure patterns of response in ventral temporal cortex while subjects viewed faces, cats, five categories of man-made objects, and nonsense pictures. A distinct pattern of response was found for each stimulus category. The distinctiveness of the response to a given category was not due simply to the regions that responded maximally to that category, because the category being viewed also could be identified on the basis of the pattern of response when those regions were excluded from the analysis. Patterns of response that discriminated among all categories were found even within cortical regions that responded maximally to only one category. These results indicate that the representations of faces and objects in ventral temporal cortex are widely distributed and overlapping.

A parametric fMRI study of overt and covert shifts of visuospatial attention.

It has recently been demonstrated that a cortical network of visuospatial and oculomotor control areas is active for covert shifts of spatial attention (shifts of attention without eye movements) as well as for overt shifts of spatial attention (shifts of attention with saccadic eye movements). Studies examining activity in this visuospatial network during attentional shifts at a single rate have given conflicting reports about how the activity differs for overt and covert shifts. To better understand how the network subserves attentional shifts, we performed a parametric study in which subjects made either overt attentional shifts or covert attentional shifts at three different rates (0.2, 1.0, and 2.0 Hz). At every shift rate, both overt and covert shifts of visuospatial attention induced activations in the precentral sulcus, intraparietal sulcus, and lateral occipital cortex that were of greater amplitude for overt than during covert shifting. As the rate of attentional shifts increased, responses in the visuospatial network increased in both overt and covert conditions but this parametric increase was greater during overt shifts. These results confirm that overt and covert attentional shifts are subserved by the same network of areas. Overt shifts of attention elicit more neural activity than do covert shifts, reflecting additional activity associated with saccade execution. An additional finding concerns the anatomical organization of the visuospatial network. Two distinct activation foci were observed within the precentral sulcus for both overt and covert attentional shifts, corresponding to specific anatomical landmarks. We therefore reappraise the correspondence of these two precentral areas with the frontal eye fields.

Overall vigilance and sustained attention decrements in healthy aging.

Age differences in sustained attention were investigated using a high-event rate digit-discrimination task at 6 levels of stimulus degradation (lasting 8.1 min each). Twenty-one young, 21 middle-aged, and 20 old healthy subjects were studied. Overall sensitivity (d') was equivalent in all groups. Although all subjects showed a sensitivity decrement over blocks, there were no age-related differences in sustained attention capacity. All subjects had larger decrements in d' over blocks at higher degradation levels. However, the performance decrement at higher degradation levels was equivalent in all groups, indicating similar decrement rates in sensitivity with increasing demands on effortful processing. These results indicate that overall levels of vigilance and the ability to sustain attention over time are equivalent in all groups under conditions requiring both automatic (low-degradation) and effortful (high-degradation) stimulus processing.

Cholinergic enhancement and increased selectivity of perceptual processing during working memory.

Using functional magnetic resonance imaging, we investigated the mechanism by which cholinergic enhancement improves working memory. We studied the effect of the cholinesterase inhibitor physostigmine on subcomponents of this complex function. Cholinergic enhancement increased the selectivity of neural responses in extrastriate cortices during visual working memory, particularly during encoding. It also increased the participation of ventral extrastriate cortex during memory maintenance and decreased the participation of anterior prefrontal cortex. These results indicate that cholinergic enhancement improves memory performance by augmenting the selectivity of perceptual processing during encoding, thereby simplifying processing demands during memory maintenance and reducing the need for prefrontal participation.

A functional MRI case study of acquired cerebral dyschromatopsia.

Evidence from imaging studies suggests that primary visual cortex and multiple areas in ventral occipitotemporal cortex subserve color perception in humans. To learn more about the organization of these areas, we used structural and functional MRI (fMRI) to examine a patient with damage to ventral cortex. An art professor, KG, suffered a cerebrovascular accident during heart surgery that impaired his ability to perceive color. The Farnsworth-Munsell 100-Hue test was used to assess the extent of his deficit. When tested 12 months after the lesion, KG performed worse than 95% of age-matched normals on the 100-Hue test, but well above chance. Structural and functional MRI studies were conducted 3 years after the lesion to investigate the neuroanatomical correlates of KG'ss remaining color ability. Structural MRI revealed bilateral damage to ventral occipitotemporal cortex. In young and age-matched normal controls, an fMRI version of the 100-Hue reliably activated bilateral, color-selective regions in primary visual cortex and anterior and posterior ventral cortex. In subject KG, color-selective cortex was found in bilateral primary visual cortex. In ventral cortex, no color-selective activity was observed in right ventral cortex, and only a small area of activity was observed in left anterior ventral cortex. However, significant color-selective activity was observed in posterior left ventral cortex spared by the lesion. This posterior left ventral activation was similar in extent, position, and degree of color-selectivity to the posterior left posterior activation observed in normal controls, suggesting that this focus may be the cortical substrate underlying KG's remaining color perception.

Distinguishing the functional roles of multiple regions in distributed neural systems for visual working memory.

We have investigated the human neural systems for visual working memory using functional magnetic resonance imaging to distinguish sustained activity during memory delays from transient responses related to perceptual and motor operations. These studies have identified six distinct frontal regions that demonstrate sustained activity during memory delays. These regions could be distinguished from brain regions in extrastriate cortex that participate more in perception and from brain regions in medial and lateral frontal cortex that participate more in motor control. Moreover, the working memory regions could be distinguished from each other based on the relative strength of their participation in spatial and face working memory and on the relative strength of sustained activity during memory delays versus transient activity related to stimulus presentation. These results demonstrate that visual working memory performance involves the concerted activity of multiple regions in a widely distributed system. Distinctions between functions, such as perception versus memory maintenance, or spatial versus face working memory, are a matter of the degree of participation of different regions, not the discrete parcellation of different functions to different modules.

Distinguishing the functional roles of multiple regions in distributed neural systems for visual working memory.

We have investigated the human neural systems for visual working memory using functional magnetic resonance imaging to distinguish sustained activity during memory delays from transient responses related to perceptual and motor operations. These studies have identified six distinct frontal regions that demonstrate sustained activity during memory delays. These regions could be distinguished from brain regions in extrastriate cortex that participate more in perception and from brain regions in medial and lateral frontal cortex that participate more in motor control. Moreover, the working memory regions could be distinguished from each other based on the relative strength of their participation in spatial and face working memory and on the relative strength of sustained activity during memory delays versus transient activity related to stimulus presentation. These results demonstrate that visual working memory performance involves the concerted activity of multiple regions in a widely distributed system. Distinctions between functions, such as perception versus memory maintenance, or spatial versus face working memory, are a matter of the degree of participation of different regions, not the discrete parcellation of different functions to different modules.

Complementary neural mechanisms for tracking items in human working memory.

Recognition of a specific visual target among equally familiar distracters requires neural mechanisms for tracking items in working memory. Event-related functional magnetic resonance imaging revealed evidence for two such mechanisms: (i) Enhanced neural responses, primarily in the frontal cortex, were associated with the target and were maintained across repetitions of the target. (ii) Reduced responses, primarily in the extrastriate visual cortex, were associated with stimulus repetition, regardless of whether the stimulus was a target or a distracter. These complementary neural mechanisms track the status of familiar items in working memory, allowing for the efficient recognition of a currently relevant object and rejection of irrelevant distracters.

Distributed neural systems for the generation of visual images.

Visual perception of houses, faces, and chairs evoke differential responses in ventral temporal cortex. Using fMRI, we compared activations evoked by perception and imagery of these object categories. We found content-related activation during imagery in extrastriate cortex, but this activity was restricted to small subsets of the regions that showed category-related activation during perception. Within ventral temporal cortex, activation during imagery evoked stronger responses on the left whereas perception evoked stronger responses on the right. Additionally, visual imagery evoked activity in parietal and frontal cortex, but this activity was not content related. These results suggest that content-related activation during imagery in visual extrastriate cortex may be implemented by "top-down" mechanisms in parietal and frontal cortex that mediate the retrieval of face and object representations from long-term memory and their maintenance through visual imagery.

The representation of objects in the human occipital and temporal cortex.

Recently, we identified, using fMRI, three bilateral regions in the ventral temporal cortex that responded preferentially to faces, houses, and chairs [Ishai, A., Ungerleider, L. G., Martin, A., Schouten, J. L., & Haxby, J. V. (1999). Distributed representation of objects in the human ventral visual pathway. Proceedings of the National Academy of Sciences, U.S.A., 96, 9379--9384]. Here, we report differential patterns of activation, similar to those seen in the ventral temporal cortex, in bilateral regions of the ventral occipital cortex. We also found category-related responses in the dorsal occipital cortex and in the superior temporal sulcus. Moreover, rather than activating discrete, segregated areas, each category was associated with its own differential pattern of response across a broad expanse of cortex. The distributed patterns of response were similar across tasks (passive viewing, delayed matching) and presentation formats (photographs, line drawings). We propose that the representation of objects in the ventral visual pathway, including both occipital and temporal regions, is not restricted to small, highly selective patches of cortex but, instead, is a distributed representation of information about object form. Within this distributed system, the representation of faces appears to be less extensive as compared to the representations of nonface objects.

Distinct representations of eye gaze and identity in the distributed human neural system for face perception.

Face perception requires representation of invariant aspects that underlie identity recognition as well as representation of changeable aspects, such as eye gaze and expression, that facilitate social communication. Using functional magnetic resonance imaging (fMRI), we investigated the perception of face identity and eye gaze in the human brain. Perception of face identity was mediated more by regions in the inferior occipital and fusiform gyri, and perception of eye gaze was mediated more by regions in the superior temporal sulci. Eye-gaze perception also seemed to recruit the spatial cognition system in the intraparietal sulcus to encode the direction of another's gaze and to focus attention in that direction.

Are face-responsive regions selective only for faces?

To examine the specificity of face-responsive regions for face processing, we used fMRI to measure the response of the fusiform gyrus and the superior temporal sulcus (STS) to pictures of human faces, animals, faceless animals, and houses. Results indicate that faces, animals, and faceless animals all elicited greater activity than houses, and had identical peaks of activation in the lateral fusiform gyrus, bilaterally, and in the right posterior STS. Moreover, within the lateral fusiform gyrus the responses to faces, animals and faceless animals were all greater than the responses to these stimuli in the medial aspect of the fusiform gyrus, a region that responds more strongly to other objects (e.g. houses). These findings suggest that the neural representation of animals in the fusiform gyrus and the posterior STS relies strongly on the same neural substrates that represent faces.

Attribute-based neural substrates in temporal cortex for perceiving and knowing about objects.

The cognitive and neural mechanisms underlying category-specific knowledge remain controversial. Here we report that, across multiple tasks (viewing, delayed match to sample, naming), pictures of animals and tools were associated with highly consistent, category-related patterns of activation in ventral (fusiform gyrus) and lateral (superior and middle temporal gyri) regions of the posterior temporal lobes. In addition, similar patterns of category-related activity occurred when subjects read the names of, and answered questions about, animals and tools. These findings suggest that semantic object information is represented in distributed networks that include sites for storing information about specific object attributes such as form (ventral temporal cortex) and motion (lateral temporal cortex).

Distributed representation of objects in the human ventral visual pathway.

Brain imaging and electrophysiological recording studies in humans have reported discrete cortical regions in posterior ventral temporal cortex that respond preferentially to faces, buildings, and letters. These findings suggest a category-specific anatomically segregated modular organization of the object vision pathway. Here we present data from a functional MRI study in which we found three distinct regions of ventral temporal cortex that responded preferentially to faces and two categories of other objects, namely houses and chairs, and had a highly consistent topological arrangement. Although the data could be interpreted as evidence for separate modules, we found that each category also evoked significant responses in the regions that responded maximally to other stimuli. Moreover, each category was associated with its own differential pattern of response across ventral temporal cortex. These results indicate that the representation of an object is not restricted to a region that responds maximally to that object, but rather is distributed across a broader expanse of cortex. We propose that the functional architecture of the ventral visual pathway is not a mosaic of category-specific modules but instead is a continuous representation of information about object form that has a highly consistent and orderly topological arrangement.

Functional anatomy of pursuit eye movements in humans as revealed by fMRI.

We have investigated the functional anatomy of pursuit eye movements in humans with functional magnetic imaging. The performance of pursuit eye movements induced activations in the cortical eye fields also activated during the execution of visually guided saccadic eye movements, namely in the precentral cortex [frontal eye field (FEF)], the medial superior frontal cortex (supplementary eye field), the intraparietal cortex (parietal eye field), and the precuneus, and at the junction of occipital and temporal cortex (MT/MST) cortex. Pursuit-related areas could be distinguished from saccade-related areas both in terms of spatial extent and location. Pursuit-related areas were smaller than their saccade-related counterparts, three of eight significantly so. The pursuit-related FEF was usually inferior to saccade-related FEF. Other pursuit-related areas were consistently posterior to their saccade-related counterparts. The current findings provide the first functional imaging evidence for a distinction between two parallel cortical systems that subserve pursuit and saccadic eye movements in humans.

An fMRI version of the Farnsworth-Munsell 100-Hue test reveals multiple color-selective areas in human ventral occipitotemporal cortex.

Studies of patients with cerebral achromatopsia have suggested that ventral occipitotemporal cortex is important for color perception. We created a functional magnetic resonance imaging (fMRI) version of a clinical test commonly used to assess achromatopsia, the Farnsworth-Munsell 100-Hue test. The test required normal subjects to use color information in the visual stimulus to perform a color sequencing task. A modification of the test requiring ordering by luminance was used as a control task. Subjects were also imaged as they passively viewed colored stimuli. A limited number of areas responded more to chromatic than achromatic stimulation, including primary visual cortex. Most color-selective activity was concentrated in ventral occipitotemporal cortex. Several areas in ventral cortex were identified. The most posterior, located in posterior fusiform gyrus, corresponded to the area activated by passive viewing of colored stimuli. More anterior and medial color-selective areas were located in the collateral sulcus and fusiform gyrus. These more anterior areas were not identified in previous imaging studies which used passive viewing of colored stimuli, and were most active in our study when visual color information was behaviorally relevant, suggesting that attention influences activity in color-selective areas. The fMRI version of the Farnsworth-Munsell test may be useful in the study of achromatopsia.

Localization of cardiac-induced signal change in fMRI.

Signal detection in the analysis of blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) may be greatly hindered by cardiac pulsatility artifacts. Vessel pulsation, cerebrospinal fluid movement, and tissue deformation are all associated with the cardiac cycle and all can produce fMRI signal variance. Most cognitive fMRI studies do not utilize a method of cardiac-related noise reduction, in part because of the lack of information on the regional significance and magnitude of cardiac-related signal variance in the brain. In this paper we present a topographical description of the regions showing significant contributions of cardiac-related signal variance. The results are highly consistent across subjects and suggest that reduced sensitivity due to cardiac-induced noise in the BOLD signal is systematically greater in specific areas, typically near major blood vessels. Significant effects of cardiac-related variability were found on average in 27.5 +/- 8.0% of voxels. Strong influences were found along the vertebrobasilar arterial system near the medial areas of the brain, along the middle cerebral artery near the anterior temporal lobes and in the insula, and along the anterior cerebral artery in the anterior interhemispheric fissure in the medial frontal lobes. Significant effects were also observed in the sigmoid transverse and superior sagittal sinus regions. These results identify regions in which fMRI will have reduced sensitivity due to increased signal variation produced by cardiac pulsatility.