Dyslexic children lack word selectivity gradients in occipito-temporal and inferior frontal cortex.

fMRI studies using a region-of-interest approach have revealed that the ventral portion of the left occipito-temporal cortex, which is specialized for orthographic processing of visually presented words (and includes the so-called "visual word form area", VWFA), is characterized by a posterior-to-anterior gradient of increasing selectivity for words in typically reading adults, adolescents, and children (e.g. Brem et al., 2006, 2009). Similarly, the left inferior frontal cortex (IFC) has been shown to exhibit a medial-to-lateral gradient of print selectivity in typically reading adults (Vinckier et al., 2007). Functional brain imaging studies of dyslexia have reported relative underactivity in left hemisphere occipito-temporal and inferior frontal regions using whole-brain analyses during word processing tasks. Hence, the question arises whether gradient sensitivities in these regions are altered in dyslexia. Indeed, a region-of-interest analysis revealed the gradient-specific functional specialization in the occipito-temporal cortex to be disrupted in dyslexic children (van der Mark et al., 2009). Building on these studies, we here (1) investigate if a word-selective gradient exists in the inferior frontal cortex in addition to the occipito-temporal cortex in normally reading children, (2) compare typically reading with dyslexic children, and (3) examine functional connections between these regions in both groups. We replicated the previously reported anterior-to-posterior gradient of increasing selectivity for words in the left occipito-temporal cortex in typically reading children, and its absence in the dyslexic children. Our novel finding is the detection of a pattern of increasing selectivity for words along the medial-to-lateral axis of the left inferior frontal cortex in typically reading children and evidence of functional connectivity between the most lateral aspect of this area and the anterior aspects of the occipito-temporal cortex. We report absence of an IFC gradient and connectivity between the lateral aspect of the IFC and the anterior occipito-temporal cortex in the dyslexic children. Together, our results provide insights into the source of the anomalies reported in previous studies of dyslexia and add to the growing evidence of an orthographic role of IFC in reading.

Attention to single letters activates left extrastriate cortex.

Brain imaging studies examining the component processes of reading using words, non-words, and letter strings frequently report task-related activity in the left extrastriate cortex. Processing of these linguistic materials involves varying degrees of semantic, phonological, and orthographic analysis that are sensitive to individual differences in reading skill and history. In contrast, single letter processing becomes automatized early in life and is not modulated by later linguistic experience to the same degree as are words. In this study, skilled readers attended to different aspects (single letters, symbols, and colors) of an identical stimulus set during separate sessions of functional magnetic resonance imaging (fMRI). Whereas activation in some portions of ventral extrastriate cortex was shared by attention to both alphabetic and non-alphabetic features, a letter-specific area was identified in a portion of left extrastriate cortex (Brodmann's Area 37), lateral to the visual word form area. Our results demonstrate that while minimizing activity related to word-level lexical properties, cortical responses to letter recognition can be isolated from figural and color characteristics of simple stimuli. The practical utility of this finding is discussed in terms of early identification of reading disability.

Hypersexuality and hemiballism due to subthalamic infarction.

OBJECTIVE: A 70-year-old right-handed man presented with a subthalamic infarction followed by persistent hypersexuality and hemiballism. A lacunar infarction 1 cm in diameter was observed on magnetic resonance imaging. We hypothesized that metabolic abnormalities would be detected in cortical areas related to his neurobehavioral symptoms. BACKGROUND: Statistical validation of the regional metabolic changes that may relate to neuropsychiatric symptoms has been elusive. Relating metabolic changes to neuropsychiatric symptoms is especially important in unique neurobehavioral cases. METHOD: Quantitative fluorodeoxyglucose positron emission tomography was obtained for a single-subject comparison with scans from 60 healthy subjects. RESULTS: Substantial glucose hypometabolism (p <0.001, uncorrected; [df = 56]) was identified in the subthalamic nucleus at the site of the lacunar infarction. Hypermetabolism (p <0.01) was identified within the basal forebrain and temporal lobes, anterior cingulate and medial prefrontal cortices (areas previously associated with hypersexuality), and striatum (p <0.001) ipsilateral to the stroke (areas known to relate to hemiballism). CONCLUSIONS: Single-subject statistical parametric mapping may improve our understanding of unique neurobehavioral cases.

Event-related potentials correlate with task-dependent glucose metabolism.

Cognitive processing is associated with brain electrical activity that is reflected in event-related potentials (ERP). ERP during a target detection task, and regional cerebral glucose metabolism (CMRglc) measured simultaneously, may be influenced by the same neurophysiologic processes. We tested the hypothesis that ERP factors could be directly correlated with CMRglc to derive functional brain maps of brain activity at 120, 160, 200, 280, and 400 ms following stimulus presentation in a target detection task. We controlled for the potential confounding effects of age, sex, and task accuracy, and correlate target-related and nontarget-related ERP separately. Increases and decreases in CMRglc at each time point were identified with statistical parametric mapping (P < 0.001, uncorrected). The 120- and 160-ms maps were the same for target and nontarget processing, while maps for 280 and 400 ms clearly distinguished between targets and nontargets. Extrinsic (early) cognitive processes that depend mainly on stimulus characteristics show less variation based on stimulus meaning (i.e., letter vs shape; target vs nontarget) than later (intrinsic) cognitive processes. These early effects are lateralized to the left hemisphere, for negative ERP factors, and positive ERP-PET correlations are more likely than negative ERP-PET correlations. Thus, brain areas related to task processing impact both ERP and CMRglc measures, suggesting a shared neurophysiologic mechanism for negative ERP factors and increased CMRglc. Direct statistical analysis of these two measures using statistical parametric mapping provides high spatial and temporal resolution in multisubject experiments, while requiring only a single (18)FDG PET scan per subject.

Cortical activity related to accuracy of letter recognition.

Previous imaging and neurophysiological studies have suggested that the posterior inferior temporal region participates in tasks requiring the recognition of objects, including faces, words, and letters; however, the relationship between accuracy of recognition and activity in that region has not been systematically investigated. In this study, positron emission tomography was used to estimate glucose metabolism in 60 normal adults performing a computer-generated letter-recognition task. Both a region of interest and a voxel-based method of analysis, with subject state and trait variables statistically controlled, found task accuracy to be: (1) negatively related to metabolism in the left ventrolateral inferior temporal occipital cortex (Brodmann's area 37, or ventrolateral BA 37) and (2) positively related to metabolism in a region of the right ventrolateral frontal cortex (Brodmann's areas 47 and 11, or right BA 47/11). Left ventrolateral BA 37 was significantly related both to hits and to false alarms, whereas the right BA 47/11 finding was related only to false alarms. The results were taken as supporting an automaticity mechanism for left ventrolateral BA 37, whereby task accuracy was associated with automatic letter recognition and in turn to reduced metabolism in this extrastriate area. The right BA 47/11 finding was interpreted as reflecting a separate component of task accuracy, associated with selectivity of attention broadly and with inhibition of erroneous responding in particular. The findings are interpreted as supporting the need for control of variance due to subject and task variables, not only in correlational but also in subtraction designs.

Evaluation of brain activity in FDG PET studies.

PURPOSE: A tool (Gemini) was developed for quantifying regions of interest (ROIs) in registered MR and PET data. Its use was validated through phantom and simulated studies. METHOD: Hot spheres were imaged in a phantom (3:1 and 5:1 target-to-nontarget ratios). The computerized 3D Hoffman brain phantom was used to simulate PET studies. Spherical local activity features of two diameters (4 and 10 mm) and five intensities (5, 15, 25, 50, and 100% increase over gray matter) were added to the data in the thalamus and Brodmann area 37. The data were reprojected into sinograms and blurred with a 7 mm kernel. Poisson noise was added, and the sinograms were then reconstructed and analyzed using both SPM96 and Gemini spherical ROIs. RESULTS: Based on phantom and simulated data, the 95th percentile of intensity within a Gemini ROI afforded a reasonable joint optimization of variance (reliability) and accuracy (validity). SPM96 and Gemini results were similar for the larger (10 mm) feature, but in this application, Gemini was more sensitive than SPM96 for the small feature (4 mm). CONCLUSION: Gemini, a tool for display and measurement of spherical ROIs in registered PET and MR data, is precise and accurate for testing hypotheses of differences in localized brain activity, comparing favorably with SPM96.

CINAHL: an exploratory analysis of the current status of nursing theory construction as reflected by the electronic domain.

Since the 1980s the electronic domain has become the primary method for academic and professional communication of research and information. Papers relating to theory construction in nursing are a frequently occurring phenomenon within the electronic domain. Theory construction provides the underpinning for the advancement of professional nursing, facilitating the conceptualization of nursing actions leading to theory-based practice and research. The purpose of this study was to address the research question, 'What are the similarities and differences among theory construction papers that are accessible electronically in nursing literature today?' The Cumulative Index to Nursing and Allied Health Literature (CINAHL) was accessed to obtain a listing of papers from which an overall description of the type of theory construction papers being published in the nursing literature today could be determined. A literature search was conducted using the description 'theory construction'. Papers were limited to publication years from 1990 onwards. A total of 125 papers were obtained and read by one of the six authors. Using grounded theory, categories emerged by identification of similarities and differences among the papers. The findings are discussed here along with suggestions for further study. A second purpose of this paper was to present both traditional and non-traditional methods of tapping into the electronic domain when searching for assistance with theory construction.

Brain basis for dyslexia: a summary of work in progress.

Studies of brain/behavior relations in the last decade have converged to suggest a left-hemisphere functional deficit for dyslexia. The relationship is most convincing at the microscopic level, where anomalous neural organization has been associated with reading, and at the macroscopic level, where several studies find atypical hemispheric symmetry in the language-related temporal region in individuals with dyslexia. Physiological studies measuring brain function during cognitive challenge have now begun to accumulate in support of a left-hemisphere deficit in dyslexia. This article summarizes work in progress on the structure and physiological profiles of reading disability and relates the findings to core left-hemisphere language functions.

Regional cerebral blood flow correlates of language processes in reading disability.

This series of studies tests the hypothesis of abnormal left hemisphere activation in reading-disabled subjects during language task performance. First, a left superotemporal focus of activation, as measured by regional cerebral blood flow, was found to be positively correlated with task accuracy in a group of 69 normal adults. Next, that left superotemporal activation was replicated in a second group of 83 adults whose childhood reading ability was known from standardized tests given in childhood. Finally, in that latter group, childhood reading ability was also found to be inversely correlated with focal activation in a more posterior, temporoparietal area of cortex. Adult reading outcome was statistically unrelated to this finding. The results are interpreted as suggesting a trait anomaly of left hemisphere cerebral activation in adults who were dyslexic as children and as providing an existence proof of individual differences in focal cortical activation sites during constant task demands.

Hypofrontal vs. hypo-Sylvian blood flow in schizophrenia.

Hypofrontality in schizophrenia has been a frequent but not consistent finding in regional cerebral blood flow studies. However, the contributions of subject and state variables such as age, education, task activation, and anxiety, some of which are known to influence blood flow profiles, have not been thoroughly examined in this population. Here, in a sample including 24 normal, 18 schizophrenic, 22 bipolar, and 13 unipolar depressive subjects, narrative prose memory deficit was found to distinguish both schizophrenic and bipolar subjects from normal controls. Further, when these subjects were engaged in repeated trials of a verbal recognition memory task, left hemisphere hypofrontal blood flow in the early stage of learning was related to narrative memory, independent of diagnostic group. In the late stage of learning, state anxiety was significantly associated with left hypofrontality, while right hypofrontality was significantly related to narrative memory--both findings again independent of diagnostic group. A focal suppression of left hemispheric peri-Sylvian activation (in Broca's and Wernicke's areas) uniquely characterized schizophrenia after taking into account variance due to age, education, gender, state anxiety, and verbal memory. It is concluded that a failure of left peri-Sylvian activation during memory task performance reflects a unique language-related focal deficit in schizophrenia.