Generalizing post-stroke prognoses from research data to clinical data.

Around a third of stroke survivors suffer from acquired language disorders (aphasia), but current medicine cannot predict whether or when they might recover. Prognostic research in this area increasingly draws on datasets associating structural brain imaging data with outcome scores for ever-larger samples of stroke patients. The aim is to learn brain-behaviour trends from these data, and generalize those trends to predict outcomes for new patients. The practical significance of this work depends on the expected breadth of that generalization. Here, we show that these models can generalize across countries and native languages (from British patients tested in English to Chilean patients tested in Spanish), across neuroimaging technology (from MRI to CT), and from scans collected months or years after stroke for research purposes, to scans collected days or weeks after stroke for clinical purposes. Our results suggest one important confound, in attempting to generalize from research data to clinical data, is the delay between scan acquisition and language assessment. This delay is typically small for research data, where scans and assessments are often acquired contemporaneously. But the most natural, clinical application of these predictions will employ acute prognostic factors to predict much longer-term outcomes. We mitigated this confound by projecting the clinical patients' lesions from the time when their scans were acquired, to the time when their language abilities were assessed; with this projection in place, there was strong evidence that prognoses derived from research data generalized equally well to research and clinical data. These results encourage attention to the confounding role that lesion growth may play in other types of lesion-symptom analysis.

How doctors diagnose diseases and prescribe treatments: an fMRI study of diagnostic salience.

Understanding the brain mechanisms involved in diagnostic reasoning may contribute to the development of methods that reduce errors in medical practice. In this study we identified similar brain systems for diagnosing diseases, prescribing treatments, and naming animals and objects using written information as stimuli. Employing time resolved modeling of blood oxygen level dependent (BOLD) responses enabled time resolved (400 milliseconds epochs) analyses. With this approach it was possible to study neural processes during successive stages of decision making. Our results showed that highly diagnostic information, reducing uncertainty about the diagnosis, decreased monitoring activity in the frontoparietal attentional network and may contribute to premature diagnostic closure, an important cause of diagnostic errors. We observed an unexpected and remarkable switch of BOLD activity within a right lateralized set of brain regions related to awareness and auditory monitoring at the point of responding. We propose that this neurophysiological response is the neural substrate of awareness of one's own (verbal) response. Our results highlight the intimate relation between attentional mechanisms, uncertainty, and decision making and may assist the advance of approaches to prevent premature diagnostic closure.

How doctors generate diagnostic hypotheses: a study of radiological diagnosis with functional magnetic resonance imaging.

BACKGROUND: In medical practice, diagnostic hypotheses are often made by physicians in the first moments of contact with patients; sometimes even before they report their symptoms. We propose that generation of diagnostic hypotheses in this context is the result of cognitive processes subserved by brain mechanisms that are similar to those involved in naming objects or concepts in everyday life. METHODOLOGY AND PRINCIPAL FINDINGS: To test this proposal we developed an experimental paradigm with functional magnetic resonance imaging (fMRI) using radiological diagnosis as a model. Twenty-five radiologists diagnosed lesions in chest X-ray images and named non-medical targets (animals) embedded in chest X-ray images while being scanned in a fMRI session. Images were presented for 1.5 seconds; response times (RTs) and the ensuing cortical activations were assessed. The mean response time for diagnosing lesions was 1.33 (SD ±0.14) seconds and 1.23 (SD ±0.13) seconds for naming animals. 72% of the radiologists reported cogitating differential diagnoses during trials (3.5 seconds). The overall pattern of cortical activations was remarkably similar for both types of targets. However, within the neural systems shared by both stimuli, activation was significantly greater in left inferior frontal sulcus and posterior cingulate cortex for lesions relative to animals. CONCLUSIONS: Generation of diagnostic hypotheses and differential diagnoses made through the immediate visual recognition of clinical signs can be a fast and automatic process. The co-localization of significant brain activation for lesions and animals suggests that generating diagnostic hypotheses for lesions and naming animals are served by the same neuronal systems. Nevertheless, diagnosing lesions was cognitively more demanding and associated with more activation in higher order cortical areas. These results support the hypothesis that medical diagnoses based on prompt visual recognition of clinical signs and naming in everyday life are supported by similar brain systems.

An anatomical signature for literacy.

Language is a uniquely human ability that evolved at some point in the roughly 6,000,000 years since human and chimpanzee lines diverged. Even in the most linguistically impoverished environments, children naturally develop sophisticated language systems. In contrast, reading is a learnt skill that does not develop without intensive tuition and practice. Learning to read is likely to involve ontogenic structural brain changes, but these are nearly impossible to isolate in children owing to concurrent biological, environmental and social maturational changes. In Colombia, guerrillas are re-integrating into mainstream society and learning to read for the first time as adults. This presents a unique opportunity to investigate how literacy changes the brain, without the maturational complications present in children. Here we compare structural brain scans from those who learnt to read as adults (late-literates) with those from a carefully matched set of illiterates. Late-literates had more white matter in the splenium of the corpus callosum and more grey matter in bilateral angular, dorsal occipital, middle temporal, left supramarginal and superior temporal gyri. The importance of these brain regions for skilled reading was investigated in early literates, who learnt to read as children. We found anatomical connections linking the left and right angular and dorsal occipital gyri through the area of the corpus callosum where white matter was higher in late-literates than in illiterates; that reading, relative to object naming, increased the interhemispheric functional connectivity between the left and right angular gyri; and that activation in the left angular gyrus exerts top-down modulation on information flow from the left dorsal occipital gyrus to the left supramarginal gyrus. These findings demonstrate how the regions identified in late-literates interact during reading, relative to object naming, in early literates.