Melissa Newhart

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.

Restoring Cerebral Blood Flow Reveals Neural Regions Critical for Naming

We identified areas of the brain that are critical for naming pictures of objects, using a new methodology for testing which components of a network of brain regions are essential for that task. We identified areas of hypoperfusion and structural damage with magnetic resonance perfusion- and diffusion-weighted imaging immediately after stroke in 87 individuals with impaired picture naming. These individuals were reimaged after 3–5 d, after a subset of patients underwent intervention to restore normal blood flow, to determine areas of the brain that had reperfused. We identified brain regions in which reperfusion was associated with improvement in picture naming. Restored blood flow to left posterior middle temporal/fusiform gyrus, Brocas area, and/or Wernickes area accounted for most acute improvement after stroke. Results show that identifying areas of reperfusion that are associated with acute improvement of a function can reveal the brain regions essential for that function.

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.

Neural networks essential for naming and word comprehension

Lesion/deficit association studies of aphasia commonly focus on one brain region as primarily responsible for a particular language deficit. However, functional imaging and some lesion studies indicate that multiple brain regions are likely necessary for any language task. We tested 156 acute stroke patients on basic language tasks (naming and spoken and written word comprehension) and magnetic resonance diffusion and perfusion imaging to determine the relative contributions of various brain regions to each task. Multivariate linear regression analysis indicated that the error rate on each task was best predicted by dysfunction in several perisylvian regions, with both common and distinct regions for the 3 tasks.

Naming and comprehension in primary progressive aphasia: The influence of grammatical word class

Background: Various clinical types of primary progressive aphasia have been associated with distinct areas of atrophy and pathological changes. Therefore, differences in the patterns of language deterioration in the various types might reveal the types of language processes and representations that depend on the areas of brain that are disproportionately affected. Aims: To test the hypotheses (1) that individuals with progressive nonfluent aphasia (associated with left posterior, inferior frontal, and insular atrophy) show progressive motor speech impairment and disproportionate deterioration in naming actions relative to objects, and (2) that individuals with semantic dementia (associated with anterior and inferior temporal atrophy) show disproportionate deterioration in semantic representations of objects relative to actions. Methods & Procedures: The study population consisted of 56 participants with primary progressive aphasia, including 27 with progressive nonfluent aphasia, 16 with semantic dementia, and 13 with amyotrophic lateral sclerosis‐frontotemporal dementia (ALS‐FTD). Participants were given tests of oral and written naming and tests of picture and word association with object and action stimuli. Differences across tests within each group were evaluated. Associations between motor speech impairment (based on a clinical motor speech examination) and naming impairment in each grammatical word class were evaluated. Outcomes & Results: Participants with progressive nonfluent aphasia and ALS‐FTD showed significantly more impairment in naming actions than objects. In contrast, participants with semantic dementia were significantly more impaired in naming objects than actions, and more impaired on semantic tests of objects relative to actions. In all groups, all participants who were more impaired in naming actions also had impaired motor speech (dysarthria and/or apraxia of speech). Conclusions: Distinct patterns of deterioration across grammatical word classes in these clinical subtypes were documented. Together with evidence that these clinical subtypes are associated with different areas of brain atrophy in other studies, our results are consistent with a role of posterior inferior frontal cortex and insula in motor speech and naming actions, as well as the essential role of anterior temporal lobes in semantic representation of objects.