H. Branch Coslett

Frontotemporal dementia: clinicopathological correlations.

Frontotemporal lobar degeneration (FTLD) is characterized by impairments in social, behavioral, and/or language function, but postmortem studies indicate that multiple neuropathological entities lead to FTLD. This study assessed whether specific clinical features predict the underlying pathology.

Reversal of the concreteness effect in a patient with semantic dementia

Abstract Normal subjects are better at identifying and remembering concrete as compared to abstract words (the concreteness effect). We present data on a patient, DM, who shows the opposite pattern. DM has a progressive semantic loss due to atrophic changes in his temporal lobes, particularly on the left. His semantic impairment predominantly involves object terms, with relative sparing of abstract nouns and most aspects of verb meaning. DM showed an advantage for abstract words on a wide range of tasks (e.g. producing definitions, synonymy judgments). These data challenge accounts that attribute the concreteness effect to a quantitative superiority at the level of the underlying conceptual representations. We suggest that there are qualitative differences between abstract and concrete concepts, and that, in particular, concrete concepts are more dependent on perceptual attributes that were disproportionately impaired in DM. We propose, further, that perceptual components of semantic representations are a...

Evidence for Multiple, Distinct Representations of the Human Body

Previous data from single-case and small group studies have suggested distinctions among structural, conceptual, and online sensorimotor representations of the human body. We developed a battery of tasks to further examine the prevalence and anatomic substrates of these body representations. The battery was administered to 70 stroke patients. Fifty-one percent of the patients were impaired relative to controls on at least one body representation measure. Further, principal components analysis of the patient data as well as direct comparisons of patient and control performance suggested a triple dissociation between measures of the 3 putative body representations. Consistent with previous distinctions between the what and how pathways, lesions of the left temporal lobe were most consistently associated with impaired performance on tasks assessing knowledge of the shape or lexical-semantic information about the body, whereas lesions of the dorsolateral frontal and parietal regions resulted in impaired performance on tasks requiring on-line coding of body posture.

Comprehension of affective and nonaffective prosody

We studied patients with damage of either the right (RHD) or left hemisphere (LHD) and control subjects to determine whether the RHD patients had a global or limited prosodic defect. Compared with LHD patients and controls, RHD subjects had decreased comprehension of emotional prosody. Both LHD and RHD groups had more impaired comprehension of propositional prosody than controls, but the RHD and LHD groups did not differ. The right hemisphere, therefore, seems to be dominant for comprehending emotional prosody but not propositional prosody.

Localizing interference during naming: convergent neuroimaging and neuropsychological evidence for the function of Broca's area.

To produce a word, the intended word must be selected from a competing set of other words. In other domains where competition affects the selection process, the left inferior frontal gyrus (LIFG) responds to competition among incompatible representations. The aim of this study was to test whether the LIFG is necessary for resolution of competition in word production. Using a methodological approach applying the same rigorous analytic methods to neuropsychological data as is done with neuroimaging data, we compared brain activation patterns in normal speakers (using fMRI) with the results of lesion-deficit correlations in aphasic speakers who performed the same word production task designed to elicit competition during lexical selection. The degree of activation of the LIFG in normal speakers and damage to the LIFG in aphasic speakers was associated with performance on the production task. These convergent findings provide strong support for the hypothesis that the region of cortex commonly known as Brocas area (i.e., the posterior LIFG) serves to bias competitive interactions during language production.

Anterior temporal involvement in semantic word retrieval: voxel-based lesion-symptom mapping evidence from aphasia

Analysis of error types provides useful information about the stages and processes involved in normal and aphasic word production. In picture naming, semantic errors (horse for goat) generally result from something having gone awry in lexical access such that the right concept was mapped to the wrong word. This study used the new lesion analysis technique known as voxel-based lesion-symptom mapping to investigate the locus of lesions that give rise to semantic naming errors. Semantic errors were obtained from 64 individuals with post-stroke aphasia, who also underwent high-resolution structural brain scans. Whole brain voxel-based lesion-symptom mapping was carried out to determine where lesion status predicted semantic error rate. The strongest associations were found in the left anterior to mid middle temporal gyrus. This area also showed strong and significant effects in further analyses that statistically controlled for deficits in pre-lexical, conceptualization processes that might have contributed to semantic error production. This study is the first to demonstrate a specific and necessary role for the left anterior temporal lobe in mapping concepts to words in production. We hypothesize that this role consists in the conveyance of fine-grained semantic distinctions to the lexical system. Our results line up with evidence from semantic dementia, the convergence zone framework and meta-analyses of neuroimaging studies on word production. At the same time, they cast doubt on the classical linkage of semantic error production to lesions in and around Wernickes area.

Cerebrospinal Fluid Profile in Frontotemporal Dementia and Alzheimer's Disease

We assessed cerebrospinal fluid (CSF) levels of tau and other biomarkers of neurodegenerative disease. CSF tau levels vary widely in reports of frontotemporal dementia (FTD). CSF samples were assayed for tau, amyloid β1‐42 (A1‐42), and the isoprostane 8,12‐iso‐iPF2a‐VI (iP) prospectively in 64 patients with FTD, retrospectively in 26 autopsied cases with FTD or Alzheimers disease (AD), and in 13 healthy seniors. To validate our observations in vivo, we correlated CSF tau levels with cortical atrophy in 17 FTD patients using voxel‐based morphometry analyses of high‐resolution magnetic resonance imaging. CSF levels of tau, Aβ1‐42, and iP differed significantly in FTD compared with AD. Individual patient analyses showed that 34% of FD patients had significantly low levels of CSF tau, although this was never seen in AD. A discriminant analysis based on CSF levels of tau, Aβ1‐42, and iP was able to classify 88.5% of these patients in a manner that corresponds to their clinical or autopsy diagnosis. Magnetic resonance imaging studies showed that CSF tau levels correlate significantly with right frontal and left temporal cortical atrophy, brain regions known to be atrophic in patients with autopsy‐proved FTD. We conclude that CSF tau levels are significantly reduced in many patients with FTD. Ann Neurol 2005;57:721–729

Processing of faces by patients with unilateral hemisphere lesions: I. Dissociation between judgments of facial affect and facial identity

In this study, right-hemisphere-damaged (RHD) subjects performed significantly worse than LHD and NHD controls across a series of seven facial identity and facial affect tasks. Even when the patient groups were statistically equated on a measure of visuoperceptual ability, the RHD group remained impaired on three emotional tasks--naming, picking, and discriminating emotional faces. These findings suggest that the defects shown by RHD patients on facial affect tasks cannot be solely attributed to defects in visuoperceptual processing and that the right-hemisphere superiority for processing facial affect exists above and beyond its superiority for processing facial identity.

Power in Voxel-based Lesion-Symptom Mapping

Lesion analysis in brain-injured populations complements what can be learned from functional neuroimaging. Voxel-based approaches to mapping lesion-behavior correlations in brain-injured populations are increasingly popular, and have the potential to leverage image analysis methods drawn from functional magnetic resonance imaging. However, power is a major concern for these studies, and is likely to vary regionally due to the distribution of lesion locations. Here, we outline general considerations for voxel-based methods, characterize the use of a nonparametric permutation test adapted from functional neuroimaging, and present methods for regional power analysis in lesion studies.

Left inferior parietal representations for skilled hand-object interactions: evidence from stroke and corticobasal degeneration.

Patients with ideomotor apraxia (IM) are frequently more impaired in the production and imitation of object-related (transitive) than non-object-related, symbolic (intransitive) gestures, but reasons for this dissociation, and its anatomical underpinnings, remain unclear. Our theoretical model of praxis (Buxbaum, 2001) postulates that left inferior parietal lobe (IPL) gesture representations store information about postures and movements of the body and hand for skillful manipulation of familiar objects; in contrast, bilateral fronto-parietal dynamic calculations provide constantly-updated information about the current position and movement of the body and hand for both familiar and novel, transitive and intransitive movements. This account predicts distinct patterns of IM in patients with left IPL damage versus bilateral fronto-parietal involvement. Consistent with predictions, 16 stroke patients with left IPL damage were more impaired with transitive than intransitive gestures, whereas 4 patients with bilateral fronto-parietal damage due to corticobasal degeneration (CBD) were not [F (1, 18) = 8.5 p < .01]. Additionally, the hand posture component of transitive gestures was the most impaired aspect of gesture in CVA, but tended to be the least impaired aspect of gesture in CBD [F (3, 54) = 5.1, p < .005]. Finally, CVA patients were more impaired with transitive hand postures than meaningless or intransitive hand postures, whereas CBD patients showed the opposite pattern. These data indicate that the left IPL mediates representations of skilled hand-object interactions, as distinct from dynamic coding of the body in space, and suggest that the IPL maps between representations of object identity in the ventral stream and spatial body representations mediated by the dorsal system.