Argye E. Hillis

Classification of primary progressive aphasia and its variants

This article provides a classification of primary progressive aphasia (PPA) and its 3 main variants to improve the uniformity of case reporting and the reliability of research results. Criteria for the 3 variants of PPA—nonfluent/agrammatic, semantic, and logopenic—were developed by an international group of PPA investigators who convened on 3 occasions to operationalize earlier published clinical descriptions for PPA subtypes. Patients are first diagnosed with PPA and are then divided into clinical variants based on specific speech and language features characteristic of each subtype. Classification can then be further specified as “imaging-supported” if the expected pattern of atrophy is found and “with definite pathology” if pathologic or genetic data are available. The working recommendations are presented in lists of features, and suggested assessment tasks are also provided. These recommendations have been widely agreed upon by a large group of experts and should be used to ensure consistency of PPA classification in future studies. Future collaborations will collect prospective data to identify relationships between each of these syndromes and specific biomarkers for a more detailed understanding of clinicopathologic correlations.

The multiple semantics hypothesis: Multiple confusions?

Abstract In this paper we discuss the issue of multiple versus unitary semantics. We argue that the notion of multiple semantics (as currently articulated) does not, in fact, represent a theory of semantic organisation but is, instead, an arbitrary conjunction of a set of independent assumptions which are either unmotivated or, if motivated, equally compatible with a unitary semantics hypothesis. Furthermore, the empirical evidence that has been cited as support for this hypothesis is equally compatible with variants of the unitary semantics hypothesis. A model of semantic processing—the Organised Unitary Content Hypothesis (O.U.C.H.)—that is able to account for reported patterns of dissociation of performance is discussed briefly.

DTI tractography based parcellation of white matter: application to the mid-sagittal morphology of corpus callosum.

Morphology of the corpus callosum (CC) at the mid-sagittal level has been a target of extensive studies. However, the lack of internal structures and its polymorphism make it a challenging task to quantitatively analyze shape differences among subjects. In this paper, diffusion tensor Imaging (DTI) and tract tracing technique were applied to incorporate cortical connectivity information to the morphological study. The CC was parcellated into six major subdivisions based on trajectories to different cortical areas. This subdivision was performed for eight normal subjects and one stroke patient. The parcellated CCs of the normal subjects were normalized for morphological analysis. When comparing the stroke patient to the normal population, we detected significant atrophy in the motor and sensory areas of the patient CC, in line with the clinical deficits. This approach provides a new tool to investigate callosal morphology and functional relationships.

Selective impairment of semantics in lexical processing

Abstract We report the performance of a neurologically impaired patient, KE, whose frequent errors in reading, writing, naming, and comprehension were nearly always semantically related to the target response. To quantify this pattern, a large number of items were presented for tasks of verbal and written naming, oral reading, writing to dictation, word/picture matching, and naming from tactile exploration. Detailed analyses of his performance on these tasks show very similar rates and types of errors, regardless of the modality of stimulus or response. KEs homogeneous pattern of semantic errors across modalities is interpreted as evidence for selective damage to a semantic system common to all lexical processes. In addition, although KE demonstrated some spared knowledge of all items in response to picture stimuli, we were able to interpret all aspects of his performance without resorting to a proposal that there are modality-specific semantic systems. Finally, we show that our interpretation, which ass...

Anatomy of Spatial Attention: Insights from Perfusion Imaging and Hemispatial Neglect in Acute Stroke

The site of lesion responsible for left hemispatial neglect after stroke has been intensely debated recently. Some studies provide evidence that right angular lesions are most likely to cause left neglect, whereas others indicate that right superior temporal lesions are most likely to cause neglect. We examine two potential accounts of the conflicting results: (1) neglect could result from cortical dysfunction beyond the structural lesion in some studies; and (2) different forms of neglect with separate neural correlates have been included in different proportions in separate studies. To evaluate these proposals, we studied 50 patients with acute right subcortical infarcts using tests of hemispatial neglect and magnetic resonance diffusion-weighted and perfusion-weighted imaging performed within 48 h of onset of symptoms. Left “allocentric” neglect (errors on the left sides of individual stimuli, regardless of location with respect to the viewer) was most strongly associated with hypoperfusion of right superior temporal gyrus (Fishers exact test; p < 0.0001), whereas left “egocentric” neglect (errors on the left of the viewer) was most strongly associated with hypoperfusion of the right angular gyrus (p < 0.0001). Patients without cortical hypoperfusion showed no hemispatial neglect. Because the patients did not have cortical infarcts, our data show that neglect can be caused by hypoperfused dysfunctional tissue not detectable by structural magnetic resonance imaging. Moreover, different forms of neglect were associated with different sites of cortical hypoperfusion. Results help explain conflicting results in the literature and contribute to the understanding of spatial attention and representation in the human brain.

Levels of representation, co-ordinate frames, and unilateral neglect

Abstract We describe the performance of a brain-damaged subject, NG, who made reading errors only on the right half of words. This problem persisted even when the subject had demonstrated accurate recognition of die letters in a stimulus through naming all the letters. Furthermore, the spatially determined reading impairment was unaffected by topographic transformations of stimuli: identical performance was obtained for stimuli presented in horizontal, vertical, and mirror-reversed form. The same pattern of errors was also obtained in all forms of spelling tasks: written spelling, oral spelling, and backward oral spelling. The performance of the subject is interpreted in the context of a multi-stage model of the word recognition process. It is concluded that the locus of the deficit responsible for NGs reading impairment is at a stage of processing where word-centred grapheme representations are computed. The spatially determined pattern of performance reported for NG, as well as other patterns observed ...

Natural Course of Choroidal Neovascular Membranes Within the Foveal Avascular Zone in Senile Macular Degeneration

We divided 96 eyes (93 patients) with senile macular degeneration and choroidal neovascular membranes into two groups--those with juxtafoveal membranes (1 to 250 mu from the center of the foveal avascular zone) and those with subfoveal membranes (0 mu from the center of the zone). After an average follow-up period of 21 months, one of 38 eyes in the juxtafoveal group (3%) had improved two or more lines on the Snellen chart, three eyes (8%) had remained the same, and 34 eyes (89%) had lost two or more lines on the Snellen chart. Although 35 of the 38 eyes (92%) had had initial visual acuities of 6/30 (20/100) or better, 27 eyes (71%) had become legally blind. Of the 58 eyes in the subfoveal group, 18 (31%) had remained the same or improved and 40 (69%) had lost two or more lines on the Snellen chart; 41 (70%) had final visual acuities of 6/60 (20/20) or worse. Of the 26 eyes in the subfoveal group that had had initial visual acuities of 6/60 (20/100) or better (45%). four (15%) had stayed the same and 22 (85%) had lost two or more lines on the Snellen chart. Fourteen of the 26 eyes (54%) had final visual acuities of 6/60 (20/200) or worse. Exudative maculopathy developed in the second eye in 13% of patients who initially had unilateral choroidal neovascularization after 12 months, in 22% after 24 months, and in 29% after 36 months, using life table analysis.

Aphasia: progress in the last quarter of a century.

In the last 25 years, characterization of aphasia has shifted from descriptions of the language tasks that are impaired by brain damage to identification of the disrupted cognitive processes underlying language. At the same time advances in technology, including functional imaging, electrophysiologic studies, perfusion imaging, diffusion tensor imaging, and transcranial magnetic stimulation, have led to new insights regarding the relationships between language and the brain. These insights, together with computational models of language processes, converge on the view that a given language task relies on a complex set of cognitive processes and representations carried out by an intricate network of neural regions working together. Recovery from aphasia depends on restoration of tissue function or reorganization of the cognitive/neural network underlying language, which can be facilitated by a number of diverse interventions. The original research by the author reported in this article was supported by NIH R01 DC05375.

A Pilot Randomized Trial of Induced Blood Pressure Elevation: Effects on Function and Focal Perfusion in Acute and Subacute Stroke

Background: Small, unrandomized studies have indicated that pharmacologically induced blood pressure elevation may improve function in ischemic stroke, presumably by improving blood flow to ischemic, but noninfarcted tissue (which may be indicated by diffusion-perfusion mismatch on MRI). We conducted a pilot, randomized trial to evaluate effects of pharmacologically induced blood pressure elevation on function and perfusion in acute stroke. Methods: Consecutive series of patients with large diffusion-perfusion mismatch were randomly assigned to induced blood pressure elevation (‘treated’ patients, n = 9) or conventional management (‘untreated’ patients, n = 6). Results: There were no significant differences between groups at baseline. NIH Stroke Scale (NIHSS) scores were lower (better) in treated versus untreated patients at day 3 (mean 5.6 vs. 12.3; p = 0.01) and week 6–8 (mean 2.8 vs. 9.7; p < 0.04). Treated (but not untreated) patients showed significant improvement from day 1 to day 3 in NIHSS score (from mean 10.2 to 5.6; p < 0.002), cognitive score (from mean 58.7 to 27.9% errors; p < 0.002), and volume of hypoperfused tissue (mean 132 to 58 ml; p < 0.02). High Pearson correlations between the mean arterial pressure (MAP) and accuracy on daily cognitive tests indicated that functional changes were due to changes in MAP. Conclusion: Results warrant a full-scale, double-blind clinical trial to evaluate the efficacy and risk of induced blood pressure elevation in selective patients with acute/subacute stroke.

Hypoperfusion of Wernicke's area predicts severity of semantic deficit in acute stroke

Based on earlier findings that the presence of word comprehension impairment (a deficit in the meaning of words, or lexical semantics) in acute stroke was strongly associated with the presence of hypoperfusion or infarct in Wernickes area, we tested the hypothesis that the severity of word comprehension impairment was correlated with the magnitude of delay in perfusion of Wernickes area on magnetic resonance perfusion‐weighted imaging. Eighty patients were prospectively studied within 24 hours of onset or progression of acute left hemisphere stroke symptoms, with diffusion‐weighted imaging, perfusion‐weighted imaging, and detailed language tests. For 50 patients without infarct in Wernickes area, we found a strong Pearson correlation between the rate of errors on a word comprehension test and the mean number of seconds of delay in time‐to‐peak concentration of contrast in Wernickes area, relative to the homologous region on the right. These results add further evidence for the crucial role of Wernickes area (Brodmanns area 22) in word comprehension and indicate that the magnitude of delay on PWI may be a gross indicator of tissue dysfunction.