Jennifer Heidler-Gary

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.

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.

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.

Utility of Behavioral versus Cognitive Measures in Differentiating between Subtypes of Frontotemporal Lobar Degeneration and Alzheimer’s Disease

We hypothesized that a modified version of the Frontal Behavioral Inventory (FBI-mod), along with a few cognitive tests, would be clinically useful in distinguishing between clinically defined Alzheimer’s disease (AD) and subtypes of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (dysexecutive type), progressive nonfluent aphasia, and semantic dementia. We studied 80 patients who were diagnosed with AD (n = 30) or FTLD (n = 50), on the basis of a comprehensive neuropsychological battery, imaging, neurological examination, and history. We found significant between-group differences on the FBI-mod, two subtests of the Rey Auditory Verbal Learning Test (verbal learning and delayed recall), and the Trail Making Test Part B (one measure of ‘executive functioning’). AD was characterized by relatively severe impairment in verbal learning, delayed recall, and executive functioning, with relatively normal scores on the FBI-mod. Frontotemporal dementia was characterized by relatively severe impairment on the FBI-mod and executive functioning in the absence of severe impairment in verbal learning and recall. Progressive nonfluent aphasia was characterized by severe impairment in executive functioning with relatively normal scores on verbal learning and recall and FBI-mod. Finally, semantic dementia was characterized by relatively severe deficits in delayed recall, but relatively normal performance on new learning, executive functioning, and on FBI-mod. Discriminant function analysis confirmed that the FBI-mod, in conjunction with the Rey Auditory Verbal Learning Test, and the Trail Making Test Part B categorized the majority of patients as subtypes of FTLD or AD in the same way as a full neuropsychological battery, neurological examination, complete history, and imaging. These tests may be useful for efficient clinical diagnosis, although progressive nonfluent aphasia and semantic dementia are likely to be best distinguished by language tests not included in standard neuropsychological test batteries.