Cameron Davis

Neural substrates of visuospatial processing in distinct reference frames: Evidence from unilateral spatial neglect

There is evidence for different levels of visuospatial processing with their own frames of reference: viewer-centered, stimulus-centered, and object-centered. The neural locus of these levels can be explored by examining lesion location in subjects with unilateral spatial neglect (USN) manifest in these reference frames. Most studies regarding the neural locus of USN have treated it as a homogenous syndrome, resulting in conflicting results. In order to further explore the neural locus of visuospatial processes differentiated by frame of reference, we presented a battery of tests to 171 subjects within 48 hr after right supratentorial ischemic stroke before possible structural and/or functional reorganization. The battery included MR perfusion weighted imaging (which shows hypoperfused regions that may be dysfunctional), diffusion weighted imaging (which reveals areas of infarct or dense ischemia shortly after stroke onset), and tests designed to disambiguate between various types of neglect. Results were consistent with a dorsal/ventral stream distinction in egocentric/allocentric processing. We provide evidence that portions of the dorsal stream of visual processing, including the right supramarginal gyrus, are involved in spatial encoding in egocentric coordinates, whereas parts of the ventral stream (including the posterior inferior temporal gyrus) are involved in allocentric encoding.

Neural regions essential for reading and spelling of words and pseudowords

To identify dysfunctional brain regions critical for impaired reading/spelling of words/pseudowords by evaluating acute stroke patients on lexical tests and magnetic resonance imaging, before recovery or reorganization of structure–function relationships.

Speech and language functions that require a functioning Broca's area

A number of previous studies have indicated that Brocas area has an important role in understanding and producing syntactically complex sentences and other language functions. If Brocas area is critical for these functions, then either infarction of Brocas area or temporary hypoperfusion within this region should cause impairment of these functions, at least while the neural tissue is dysfunctional. The opportunity to identify the language functions that depend on Brocas area in a particular individual was provided by a patient with hyperacute stroke who showed selective hypoperfusion, with minimal infarct, in Brocas area, and acutely impaired production of grammatical sentences, comprehension of semantically reversible (but not non-reversible) sentences, spelling, and motor planning of speech articulation. When blood flow was restored to Brocas area, as demonstrated by repeat perfusion weighted imaging, he showed immediate recovery of these language functions. The identification of language functions that were impaired when Brocas area was dysfunctional (due to low blood flow) and recovered when Brocas area was functional again, provides evidence for the critical role of Brocas area in these language functions, at least in this individual.

Unilateral neglect is more severe and common in older patients with right hemispheric stroke

Introduction: Unilateral neglect after acute right hemispheric stroke significantly impedes poststroke recovery. We studied patients with right hemispheric stroke to determine whether increasing age was associated with more frequent or more severe neglect. Methods: Eight neglect tests within 5 days of symptom onset (and within 24 hours of admission) were administered to 204 subjects with acute right hemispheric stroke. Size of infarct was measured, and neglect tests were scored as percent error. “Any neglect” was defined by an elevated neglect test score, standardized relative to a group of normal controls. Results: When tested for neglect soon after acute stroke admission, 69.6% of subjects older than 65 years had “any neglect” (defined by comparison to a group of normal controls), compared with 49.4% of subjects aged 65 years and younger (p = 0.008). For every additional 10 years of age, patients were 1.83 times as likely to have neglect, even after adjusting for diffusion-weighted imaging (DWI) infarct volume and NIH Stroke Scale (NIHSS) score (95% CI 1.38–2.43). In addition, DWI volume and NIHSS independently predicted neglect. Score on virtually all of the neglect tests worsened as an effect of age. Percentage error on a line cancellation task was 3.8% higher for every additional 10 years of age, after adjustment for DWI volume and NIHSS (p = 0.006). Similar results were found for other neglect tests. Conclusions: Increasing age in patients with acute right hemispheric stroke significantly increases the odds of unilateral neglect as well as severity of neglect, independently of size of the stroke or NIH Stroke Scale score. The reason for this finding in older patients may be because they have more brain atrophy and may be less able to compensate for cerebral infarction, or because they tend to have more cardioembolic strokes, which may be more cortically based.

Neural Correlates of Modality-specific Spatial Extinction

Sites of lesions responsible for visual, tactile, and/or motor extinction have not been clearly identified. We sought to determine the frequency of extinction in various modalities immediately after acute ischemic stroke, the rate of co-occurrence of extinction across modalities, and areas of infarct and/or hypoperfusion associated with each modality of extinction. A total of 148 patients with right supratentorial stroke were studied. In Study 1, 88 patients without hemiplegia, hemianesthesia, or visual field cuts were tested within 24 hours of onset for visual, tactile, and motor extinction, and underwent magnetic resonance diffusion and perfusion imaging. Associations between modality of extinction and areas of neural dysfunction (hypoperfusion/infarct) were identified. Of the 88 patients, 19 had only tactile extinction, 8 had only visual extinction, 12 had only motor extinction, 14 had extinction in two or more modalities, and 35 had no extinction. Tactile extinction was associated with neural dysfunction in the inferior parietal lobule; visual extinction was associated with dysfunction in the visual association cortex; and motor extinction was associated with neural dysfunction in the superior temporal gyrus. In Study 2, data from 60 patients who were excluded from Study 1 because of motor deficits were analyzed in the same way to determine whether frontal lesions contributed to visual or tactile extinction. Results again demonstrated that tactile extinction is associated with inferior parietal dysfunction, and visual extinction is associated with dysfunction of the visual association cortex. Potential accounts of the results, based on the hemisphere rivalry model of extinction and the limited attentional capacity model, are considered.

Therapy for naming deficits in two variants of primary progressive aphasia

Background: Primary progressive aphasia (PPA) refers to a progressive and selective decline in language due to neurodegenerative disease. There are three variants of PPA, progressive nonfluent aphasia (PNFA), semantic dementia (SD), and logopaenic progressive aphasia (LPA). All variants include impaired object naming, but distinct underlying deficits might interfere with naming. Therefore, individuals with different types of PPA may respond differently to naming therapy. Aims: To identify differences in patterns of success and generalisation in response to the same treatment in patient with LPA and a patient with SD. Furthermore, we wished to identify whether the treatment effect was item specific (trained words) or generalised to untrained words in trained or untrained categories. Methods & Procedures: Participants included an individual with LPA and one with SD. An assessment of lexical processing was administered before and after a naming treatment to assess underlying deficits and generalisation effects. Therapy consisted of a cueing hierarchy treatment. Treatment items consisted of pictured objects in the categories of fruits/vegetables and clothing. Outcomes & Results: Two different patterns of performance were observed. The LPA participant improved in naming of treated items and untreated items in both treated and untreated categories. The participant with SD improved in naming treated items only, but showed less deterioration in untreated items in treated than untreated categories. Conclusions: Individuals with PPA can show improved naming (at least temporarily) with therapy, but generalisation to untrained items may depend on the underlying cause of the naming deficit, which may differ across subtypes.

Ischemia in broca area is associated with broca aphasia more reliably in acute than in chronic stroke.

Background and Purpose— We aimed to determine if ischemia involving Broca area predicts Broca aphasia more reliably in acute or chronic stroke. Methods— We included consecutive right-hand-dominant patients with left hemisphere ischemic stroke (<48 hours from onset for acute stroke or >6 months after stroke for chronic stroke). MRI scans were analyzed for ischemic lesions or hypoperfusion in Broca area (Brodmann areas 44 and 45). Patients were scored on the Western Aphasia Battery to classify aphasia syndromes; &khgr;2 tests were used to identify significant associations. Results— The presence of infarct involving any part of Broca area and the presence of Broca or global aphasia was much stronger in acute (&khgr;2=38.1; df1; P<0.0001) than in chronic stroke (&khgr;2=0.54; df1; P=0.46; not significant). The association between infarct or hypoperfusion covering all of Broca area and the presence of Broca or global aphasia was much stronger in acute (&khgr;2=35.8; df1; P<0.0001) than in chronic stroke (&khgr;2=1.2; df1; p=0.27; not significant). In a subset of 20 patients studied longitudinally, the associations were significant only acutely, not chronically (&khgr;2=20; df1; P<0.0001 vs. &khgr;2=0; df1; p=1; not significant for ischemia involving part of Broca area, and &khgr;2=16.4; df1; P<0.0001 vs &khgr;2=3.2; df1; p=0.08; not significant for ischemia covering all of Broca area). Conclusions— Broca aphasia is more reliably associated with infarct/ hypoperfusion of Broca area in acute stroke. Many chronic stroke patients with damage to part or all of Broca area had neither Broca nor global aphasia. Broca or global aphasia was sometimes present initially in these patients but resolved by 6 months. Our results indicate that the acute aphasia syndrome may allow the clinician to predict the compromised vascular territory, even when structural imaging shows only a small (or no) infarct.

Distinct mechanisms and timing of language recovery after stroke

The “language network” is remarkably stable across language tasks but changes in response to injury to specific components or in response to “disconnection” of input to one component. We investigated network changes during language recovery, hypothesizing that language recovery takes place through distinct mechanisms: (a) reperfusion; (b) recovery from diaschisis; (c) recovery from structural disconnection; and (d) “reorganization” of language, whereby various components assume function of a damaged component. We also tested the hypothesis that “reorganization” depends on: the language task, level of performance, size and site of stroke, and time post onset. We tested these hypotheses in five participants who had structural, perfusion, and functional imaging utilizing spelling, reading, word generation, and picture naming tasks at acute and subsequent stages after ischaemic stroke. These cases illustrate different mechanisms of aphasia recovery or illustrate that reorganization of language acutely depends on individual variables in addition to size and site of stroke.

Site of the ischemic penumbra as a predictor of potential for recovery of functions

Background and Purpose: Diffusion–perfusion mismatch has been used to estimate salvageable tissue and predict potential for recovery in acute stroke. Location of the salvageable tissue may be as important as volume or percentage in predicting potential for recovery of specific functions. Impaired naming, a common and disabling deficit after left hemisphere stroke, is often associated with tissue dysfunction of left Brodmann area (BA) 37, posterior inferior temporal cortex. We tested the hypothesis that the presence of diffusion–perfusion mismatch within left BA 37 predicts probability and extent of short-term improvement of naming. Methods: One hundred five patients with acute left hemisphere ischemic stroke had diffusion-weighted imaging, perfusion-weighted imaging, a test of picture naming, and other language tests at admission and 2 to 4 days later. Linear regression was used to determine whether diffusion–perfusion mismatch in any BA in language cortex, total volume of mismatch, or diffusion or perfusion abnormality predicted degree of improvement in naming by days 3 to 5. Results: The presence of >20% diffusion–perfusion mismatch in left BA 37 and total volumes of diffusion and perfusion abnormality at day 1 each independently predicted degree of improvement in naming. Mismatch in this area did not predict the degree of improvement in other language tests or the NIH Stroke Scale in this study. Conclusions/Relevance: Diffusion–perfusion mismatch in left Brodmann area 37 was strongly associated with acute improvement in naming, independently of volume or percentage of total mismatch or diffusion or perfusion abnormality. These data indicate that mismatch in a particular area is a marker of salvageable tissue and an important predictor of potential for recovery of functions that depend on that area. Location of mismatch before treatment may help to predict potential benefits of reperfusion. GLOSSARY: ADC = apparent diffusion coefficient; BA = Brodmann area; DWI = diffusion-weighted imaging; NIHSS = NIH Stroke Scale; PWI = perfusion-weighted imaging; TE = echo time; TR = repetition time; TTP = time to peak.

A neural network critical for spelling

We aimed to identify neuroanatomical regions associated with deficits to the graphemic buffer, a working memory component of the spelling system that holds the sequence of letter identities during production. We evaluated 331 patients with left hemisphere ischemic stroke with various spelling tests and magnetic resonance diffusion‐weighted imaging and perfusion‐weighted imaging, within 48 hours of stroke onset. A voxel‐wise statistical map showed that ischemia in voxels in posterior and inferior frontal and parietal cortex, subcortical white matter underlying prefrontal cortex, lateral occipital gyrus, or caudate was associated with impairment in maintaining the sequence of letter identities while spelling. Ann Neurol 2009;66:249–253