Motor extinction in distinct reference frames: a double dissociation.

OBJECTIVE: Test the hypothesis that right hemisphere stroke can cause extinction of left hand movements or movements of either hand held in left space, when both are used simultaneously, possibly depending on lesion site. METHODS: 93 non-hemiplegic patients with acute right hemisphere stroke were tested for motor extinction by pressing a counter rapidly for one minute with the right hand, left hand, or both simultaneously with their hands held at their sides, or crossed over midline. RESULTS: We identified two distinct types of motor extinction in separate patients; 20 patients extinguished left hand movements held in left or right space (left canonical body extinction); the most significantly associated voxel cluster of ischemic tissue was in the right temporal white matter. Seven patients extinguished either hand held in left space (left space extinction), and the most significantly associated voxel cluster of ischemic tissue was in right parietal white matter. CONCLUSIONS: There was a double dissociation between left canonical body extinction and left space motor extinction. Left canonical body extinction seems to be associated with more dorsal (parietal) ischemia, and left canonical body extinction seems to be associated with more ventral (temporal) ischemia.

Patterns of breakdown in spelling in primary progressive aphasia.

INTRODUCTION: The objective of this study is to determine which cognitive processes underlying spelling are most affected in the three variants of primary progressive aphasia (PPA): Logopenic variant primary progressive aphasia (lvPPA), Semantic variant primary progressive aphasia (svPPA), and Nonfluent variant primary progressive aphasia (nfvPPA). METHODS: 23 PPA patients were administered The Johns Hopkins Dysgraphia Battery to assess spelling. Subtests evaluate for effects of word frequency, concreteness, word length, grammatical word class, lexicality (words vs pseudowords), and "regularity" by controlling for the other variables. Significant effects of each variable were identified with chi square tests. Responses on all spelling to dictation tests were scored by error type. 16 of the 23 subjects also had a high resolution MRI brain scan to identify areas of atrophy. RESULTS: We identified 4 patterns of spelling that could be explained by damage to one or more cognitive processes underlying spelling. Nine patients (3 unclassifiable, 4 with lvPPA, 2 with svPPA) had dysgraphia explicable by impaired access to lexical representations, with reliance on sublexical phonology-to-orthography conversion (POC). Two patients (with nfvPPA) showed dysgraphia explicable by impaired access to lexical representations and complete disruption of sublexical POC. Seven patients (4 with lvPPA, 1 with svPPA, 2 unclassifiable) showed dysgraphia explicable by impaired access to lexical-semantic representations and/or lexical representations with partially spared sublexical POC mechanisms. Five patients (1 with nfvPPA, 2 with svPPA, 1 with lvPPA, and 1 unclassifiable) showed dysgraphia explicable by impairment of the graphemic buffer. CONCLUSIONS: Any cognitive process underlying spelling can be affected in PPA. Predominance of phonologically plausible errors, more accurate spelling of regular words than irregular words, and more accurate spelling of pseudowords than words (indicating spared POC mechanisms) may indicate a low probability of progression to nfvPPA.

Neuroanatomical correlates of oral reading in acute left hemispheric stroke.

Oral reading is a complex skill involving the interaction of orthographic, phonological, and semantic processes. Functional imaging studies with nonimpaired adult readers have identified a widely distributed network of frontal, inferior parietal, posterior temporal, and occipital brain regions involved in the task. However, while functional imaging can identify cortical regions engaged in the process under examination, it cannot identify those brain regions essential for the task. The current study aimed to identify those neuroanatomical regions critical for successful oral reading by examining the relationship between word and nonword oral reading deficits and areas of tissue dysfunction in acute stroke. We evaluated 91 patients with left hemisphere ischemic stroke with a test of oral word and nonword reading, and magnetic resonance diffusion-weighted and perfusion-weighted imaging, within 24-48h of stroke onset. A voxel-wise statistical map showed that impairments in word and nonword reading were associated with a distributed network of brain regions, including the inferior and middle frontal gyri, the middle temporal gyrus, the supramarginal and angular gyri, and the middle occipital gyrus. In addition, lesions associated with word deficits were found to be distributed more frontally, while nonword deficits were associated with lesions distributed more posteriorly.

The nature of naming errors in primary progressive aphasia versus acute post-stroke aphasia.

OBJECTIVE: To compare the distribution of error types across subgroups of primary progressive aphasia and poststroke aphasia in different vascular locations. METHOD: We analyzed naming errors in 49 individuals with acute left hemisphere ischemic stroke and 55 individuals with three variants of primary progressive aphasia. Location of atrophy or ischemic stroke was characterized using MRI. RESULTS: We found that distribution of error types was very similar across all subgroups, irrespective of the site or etiology of the lesion. The only significant difference across groups was the percentage of circumlocutions (F(7, 96) = 3.02, p = .005). Circumlocution errors were highest among logopenic variant PPA (24%) and semantic variant PPA (24%). Semantic coordinate errors were common in all groups, probably because they can arise from disruption of different cognitive processes underlying naming and, therefore, from different locations of brain damage. CONCLUSIONS: Semantic errors are common among all types of primary progressive aphasia and poststroke aphasia, and the type of error depends in part on the location of damage.

The NIHSS-plus: improving cognitive assessment with the NIHSS.

BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS) has been criticized for limited representation of cognitive dysfunction and bias towards dominant hemisphere functions. Patients may therefore receive a low NIHSS score despite a fairly large stroke. A broader scale including simple cognitive tests would improve the clinical and research utility of the NIHSS. METHODS: We studied 200 patients with acute non-dominant hemispheric stroke who underwent cognitive testing and had MRI with diffusion-weighted imaging (DWI) within 5 days of presentation. We measured DWI volumes and retrospectively calculated NIHSS scores. We used linear regression to determine the role of selected cognitive tests, when added to the NIHSS, in predicting DWI volume. RESULTS: The NIHSS predicted DWI volume in a univariate analysis, as did total line cancellation and a visual perception task. In a multivariate model, using log-transformed variables, the NIHSS (p=0.0002), line cancellation errors (p=0.02) and visual perception (p=0.004) each improved prediction of total infarct volume. CONCLUSION: The addition of line cancellation and visual perception tasks significantly adds to the model of NIHSS alone in predicting DWI volume. We propose that these two cognitive tests, which together can be completed in 2-3 minutes, could be combined with the NIHSS to create an "NIHSS-plus" that more accurately represents a patient's ischemic tissue volume after a stroke. This scale requires further validation in a prospective study.

Acute recovery of oral word production following stroke: patterns of performance as predictors of recovery.

BACKGROUND: Impairments in oral word production are common at the onset of stroke. The identification of factors that predict early recovery has important implications for identifying those at greater risk of continued impaired functioning, and the management of the patient's care following discharge. AIMS: To identify patterns of performance that are predictors of acute recovery of oral word production abilities following stroke; to identify any association between early and more chronic recovery. METHOD AND PROCEDURES: Acute stroke patients were administered oral word production tasks within 1-2 days of hospital admission, with repeat testing by 7 days; a subset of patients had repeat testing between three weeks to one year later. Performance was examined for error rate and type to identify potential predictors of early recovery. OUTCOME AND RESULTS: The proportion of circumlocution and no response errors at initial testing were associated with the magnitude of recovery of language functioning within the first week following stroke. Patient characteristics of age and gender were found to have no influence on the degree of early recovery observed. None of the examined factors predicted late recovery. The degree of early recovery was not associated with the degree of later recovery. CONCLUSIONS: The current study identified patterns of task performance that increase our understanding of how oral word production recovers following acute stroke. The finding that the degree of early recovery does not predict the degree of later recovery is consistent with the hypothesis that early and late recovery are due to different mechanisms (restored blood flow in acute stroke, and reorganization in later recovery).

Severity of hypoperfusion in distinct brain regions predicts severity of hemispatial neglect in different reference frames.

BACKGROUND AND PURPOSE: Hemispatial neglect is among the most common and disabling consequences of right hemisphere stroke. A variety of variables have been associated with the presence or severity of neglect but have not evaluated the independent effects of location, severity, and volume of ischemia. Few have determined areas involved in different types of neglect. We identified the contributions of these variables to severity of viewer-centered versus stimulus-centered neglect in acute ischemic right hemisphere stroke. METHODS: We studied 137 patients within 24 hours of stroke onset with MR diffusion- and perfusion-weighted imaging and a test of hemispatial neglect that distinguishes between viewer-centered and stimulus-centered neglect. Using multivariable linear regression, we identified the independent contributions of severity of ischemia in specific locations, volume of ischemia, and age in accounting for severity of each neglect type. RESULTS: Severity of hypoperfusion in angular gyrus was the only variable that significantly and independently contributed to severity of viewer-centered neglect. Volume of dysfunctional tissue and hypoperfusion in posterior frontal cortex also accounted for some variability in severity of viewer-centered neglect. Severity of hypoperfusion of superior temporal cortex was the only variable that independently and significantly contributed to severity of stimulus-centered neglect. CONCLUSIONS: Location, severity, and volume of ischemia together determine the type and severity of neglect after right hemisphere stroke. Results also show that perfusion-weighted MRI can be used as a semiquantitative measure of tissue dysfunction in acute stroke and can account for a substantial proportion of the variability in functional deficits in the acute stage.

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.

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.

Hemispherectomy sustained before adulthood does not cause persistent hemispatial neglect.

INTRODUCTION: Hemispatial neglect has been well established in adults following acute ischemic stroke, but has rarely been investigated in children and young adults following brain injury. It is known that young brains have a tremendous potential for reorganization; however, there is controversy as to whether functions are assumed by the opposite hemisphere, or perilesional areas in the same hemisphere. Patients with intractable epilepsy who undergo hemispherectomy for treatment are missing the entire cortex on one side following surgery. In these patients, only the opposite hemisphere is available to assume function. Therefore, they provide the unique opportunity to determine in what cases the left or right hemisphere can take over the spatial attention functions of the opposite hemisphere following damage. The objective of this study was to determine the incidence and types of hemispatial neglect in children and young adults following both right- and left-sided hemispherectomy; which types of spatial attention functions can be assumed by the opposite hemisphere; and whether factors like their age at time of surgery, handedness, or gender influence recovery. METHODS: Thirty-two children and young adults who had previously undergone hemispherectomy were administered two tests to evaluate for two types of hemispatial neglect: a gap detection test and a line cancellation test. Egocentric neglect was defined as significantly more omissions of targets on the contralesional versus ipsilesional side of the page (by chi square analysis; p<.05). Allocentric neglect was defined as significantly more errors in detecting contralesional versus ipsilesional gaps in circles. RESULTS: Only one of the patients displayed statistically significant hemispatial egocentric neglect on the line cancellation test, and none of the patients displayed statistically significant egocentric or allocentric neglect on the gap detection test. CONCLUSIONS: These results imply that reorganization to the contralateral hemisphere occurs peri-hemispherectomy, as there are no perilesional areas to assume function.

Where (in the brain) do semantic errors come from?

BACKGROUND: Semantic errors result from the disruption of access either to semantics or to lexical representations. One way to determine the origins of these errors is to evaluate comprehension of words that elicit semantic errors in naming. We hypothesized that in acute stroke there are different brain regions where dysfunction results in semantic errors in both naming and comprehension versus those with semantic errors in oral naming alone. METHODS: A consecutive series of 196 patients with acute left hemispheric stroke who met inclusion criteria were evaluated with oral naming and spoken word/picture verification tasks and magnetic resonance imaging within 48 h of stroke onset. We evaluated the relationship between tissue dysfunction in 10 pre-specified Brodmann's areas (BA) and the production of coordinate semantic errors resulting from (1) semantic deficits or (2) lexical access deficits. RESULTS: Semantic errors arising from semantic deficits were most associated with tissue dysfunction/infarct of left BA 22. Semantic errors resulting from lexical access deficits were associated with hypoperfusion/infarct of left BA 37. CONCLUSION: Our study shows that semantic errors arising from damage to distinct cognitive processes reflect dysfunction of different brain regions.

Gender differences in unilateral spatial neglect within 24 hours of ischemic stroke.

Hemispatial neglect is a common and disabling consequence of stroke. Previous reports examining the relationship between gender and the incidence of unilateral spatial neglect (USN) have included either a large numbers of patients with few neglect tests or small numbers of patients with multiple tests. To determine if USN was more common and/or severe in men or women, we examined a large group of patients (312 right-handed) within 24 hours of acute right hemisphere ischemic stroke. Multiple spatial neglect tasks were used to increase the sensitivity of neglect detection. No differences based upon gender were observed for the prevalence, severity, or a combined task measure of USN.

Distinctions between the dementia in amyotrophic lateral sclerosis with frontotemporal dementia and the dementia of Alzheimer's disease.

The clinical entity of Amyotrophic Lateral Sclerosis with Frontotemporal Dementia (ALS-FTD) has only recently been recognized as an important neurodegenerative disease. As in isolated FTD, the behavioral and personality changes in ALS-FTD might be more characteristic than its cognitive changes. We aimed to characterize the behavioral and cognitive deficits in ALS-FTD, and contrast this profile with that of the most common form of dementia, AD, to assist ALS clinicians in recognizing the syndrome early in its course. Specifically, we hypothesized that a modified version of the Frontal Behavioral Inventory (FBI-mod), a brief questionnaire self-administered by a caregiver, along with just a few cognitive tests, would be clinically useful in distinguishing the dementia in ALS-FTD from the dementia of AD. We administered a battery of neuropsychological tests to 15 patients who met established criteria for Amyotrophic Lateral Sclerosis with Frontotemporal Dementia and to 30 patients who met established criteria for probable Alzheimer's disease. The FBI-mod was completed by caregivers. We found that the FBI-mod, age-corrected Z scores for the Mini-Mental State Examination (MMSE), a test of delayed recall, and a word fluency measure together discriminated between ALS-FTD and AD. ALS-FTD was characterized by more abnormal FBI scores and poor word fluency, in the presence of relatively normal overall cognitive status (MMSE) and/or delayed recall.

Characteristics and reversibility of dementia in Normal Pressure Hydrocephalus.

Studies of the cognitive outcome after shunt insertion for treatment of Normal Pressure Hydrocephalus have reported widely mixed results. We prospectively studied performance of 60 patients with Normal Pressure Hydrocephalus on a comprehensive battery of neuropsychological tests before and after shunt surgery to determine which cognitive functions improve with shunt insertion. We also administered a subset of cognitive tests before and after temporary controlled drainage of cerebrospinal fluid to determine if change on this brief subset of tests after drainage could predict which patients would show cognitive improvement three to six months after shunt insertion. There was a significant improvement in learning, retention, and delayed recall of verbal memory three to six months after surgery (using paired t-tests). The majority (74%) of patients showed significant improvement (by at least one standard deviation) on at least one of the memory tests. Absence of improvement on verbal memory after temporary drainage of cerebrospinal fluid had a high negative predictive value for improvement on memory tests at 3-6 months after surgery (96%; p=0.0005). Also, the magnitude of improvement from Baseline to Post-Drainage on few specific tests of learning and recall significantly predicted the magnitude of improvement after shunt surgery on the same tests (r2=0.32-0.58; p=0.04-0.001). Results indicate that testing before and after temporary drainage may be useful in predicting which patients are less likely to improve in memory with shunting.

Neural regions essential for reading and spelling of words and pseudowords.

OBJECTIVE: 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. METHODS: A series of 106 consenting patients were administered oral reading and spelling tests within 24 hours of left supratentorial stroke onset. Patients underwent diffusion- and perfusion-weighted magnetic resonance examination the same day to identify regions of hypoperfusion/infarct of 16 Brodmann areas. RESULTS: Simultaneous logistic regression analysis demonstrated that dysfunction of left Brodmann areas 40 (supramarginal gyrus) and 37 (posterior-inferior temporal/fusiform gyrus) best predicted impairment in reading words (odds ratio [OR], 6.20 [95% confidence interval (CI), 1.54-24.96] and 2.71 [95% CI, 0.87-8.45], respectively), reading pseudowords (OR, 39.65 [95% CI 3.9-400.78] and 4.41 [95% CI, 1.1-17.51], respectively), spelling words (OR, 14.11 [95% CI 1.37-144.93] and 7.41 [95% CI, 1.48-37.24], respectively), and spelling pseudowords (OR, 4.84 [95% CI, 0.73-32.13] and 7.74 [95% CI, 1.56-38.51], respectively). Whole-brain voxel-wise analyses demonstrated voxel clusters within these regions that were most strongly associated with task deficits. INTERPRETATION: Results indicate that a shared network of regions including parts of left Brodmann areas 37 and 40 is necessary for reading and spelling of words and pseudowords. Further studies may define the precise roles of these brain regions in language. Identification of any neural regions specific to one of these tasks or one type of stimuli will require study of more patients with selective deficits.

Spatial neglect during electrocortical stimulation mapping in the right hemisphere.

Spatial processing was assessed following implantation of subdural electrodes in the nondominant hemisphere with electrocortical stimulation mapping (ESM) in two patients before epilepsy surgery. The first patient had mild hemispatial neglect/extinction during ESM of posterior temporal and inferior parietal areas. These areas were resected, and the patient had postoperative deficits that were similar to those occurring with ESM. The second patient was found to have marked hemispatial neglect during stimulation of parietal areas. These areas were not resected, and the patient had no neglect following surgery. These results suggest that ESM can help predict spatial processing deficits associated with cortical resection, and may help prevent postoperative impairments following resection in right parietal or temporal regions.

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.

Neural regions essential for distinct cognitive processes underlying picture naming.

We hypothesized that distinct cognitive processes underlying oral and written picture naming depend on intact function of different, but overlapping, regions of the left hemisphere cortex, such that the distribution of tissue dysfunction in various areas can predict the component of the naming process that is disrupted. To test this hypothesis, we evaluated 116 individuals within 24 h of acute ischaemic stroke using a battery of oral and written naming and other lexical tests, and with magnetic resonance diffusion and perfusion imaging to identify the areas of tissue dysfunction. Discriminant function analysis, using the degree of hypoperfusion in various Brodmann's areas--BA 22 (including Wernicke's area), BA 44 (part of Broca's area), BA 45 (part of Broca's area), BA 21 (inferior temporal cortex), BA 37 (posterior, inferior temporal/fusiform gyrus), BA 38 (anterior temporal cortex) and BA 39 (angular gyrus)--as discriminant variables, classified patients on the basis of the primary component of the naming process that was impaired (defined as visual, semantics, modality-independent lexical access, phonological word form, orthographic word form and motor speech by the pattern of performance and types of errors across lexical tasks). Additionally, linear regression analysis demonstrated that the areas contributing the most information to the identification of patients with particular levels of impairment in the naming process were largely consistent with evidence for the roles of these regions from functional imaging. This study provides evidence that the level of impairment in the naming process reflects the distribution of tissue dysfunction in particular regions of the left anterior, inferior and posterior middle/superior temporal cortex, posterior inferior frontal and inferior parietal cortex. While occipital cortex is also critical for picture naming, it is likely that bilateral occipital damage is necessary to disrupt visual recognition. These findings provide new evidence that a network of brain regions supports naming, but separate components of this network are differentially required for distinct cognitive processes or representations underlying the complex task of naming pictures.

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.

Right hemispatial neglect: frequency and characterization following acute left hemisphere stroke.

The frequency of various types of unilateral spatial neglect and associated areas of neural dysfunction after left hemisphere stroke are not well characterized. Unilateral spatial neglect (USN) in distinct spatial reference frames have been identified after acute right, but not left hemisphere stroke. We studied 47 consecutive right handed patients within 48h of left hemisphere stroke to determine the frequency and distribution of types of right USN using cognitive testing and MRI imaging. The distribution of USN types was different from the previously reported distribution following acute right hemisphere stroke. In this left hemisphere stroke population, allocentric neglect was more frequent than egocentric neglect.