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1.  Aphasia or Neglect after Thalamic Stroke: The Various Ways They may be Related to Cortical Hypoperfusion 
Although aphasia and hemispatial neglect are classically labeled as cortical deficits, language deficits or hemispatial neglect following lesions to subcortical regions have been reported in many studies. However, whether or not aphasia and hemispatial neglect can be caused by subcortical lesions alone has been a matter of controversy. It has been previously shown that most cases of aphasia or hemispatial neglect due to acute non-thalamic subcortical infarcts can be accounted for by concurrent cortical hypoperfusion due to arterial stenosis or occlusion, reversible by restoring blood flow to the cortex. In this study, we evaluated whether aphasia or neglect occur after acute thalamic infarct without cortical hypoperfusion due to arterial stenosis or occlusion. Twenty patients with isolated acute thalamic infarcts (10 right and 10 left) underwent MRI scanning and detailed cognitive testing. Results revealed that 5/10 patients with left thalamic infarcts had aphasia and only 1 had cortical hypoperfusion, whereas 2/10 patients with right thalamic infarcts had hemispatial neglect and both had cortical hypoperfusion. These findings indicate that aphasia was observed in some cases of isolated left thalamic infarcts without cortical hypoerfusion due to arterial stenosis or occlusion (measured with time-to-peak delays), but neglect occurred after isolated right thalamic infarcts only when there was cortical hypoperfusion due to arterial stenosis or occlusion. Therefore, neglect after acute right thalamic infarct should trigger evaluation for cortical hypoperfusion that might improve with restoration of blood flow. Further investigation in a larger group of patients and with other imaging modalities is warranted to confirm these findings.
doi:10.3389/fneur.2014.00231
PMCID: PMC4237053  PMID: 25477859
acute thalamic stroke; aphasia; neglect; cortical hypoperfusion; diaschisis
2.  Acute lesions that impair affective empathy 
Brain  2013;136(8):2539-2549.
Functional imaging studies of healthy participants and previous lesion studies have provided evidence that empathy involves dissociable cognitive functions that rely on at least partially distinct neural networks that can be individually impaired by brain damage. These studies converge in support of the proposal that affective empathy—making inferences about how another person feels—engages at least the following areas: prefrontal cortex, orbitofrontal gyrus, anterior insula, anterior cingulate cortex, temporal pole, amygdala and temporoparietal junction. We hypothesized that right-sided lesions to any one of these structures, except temporoparietal junction, would cause impaired affective empathy (whereas bilateral damage to temporoparietal junction would be required to disrupt empathy). We studied 27 patients with acute right hemisphere ischaemic stroke and 24 neurologically intact inpatients on a test of affective empathy. Acute impairment of affective empathy was associated with infarcts in the hypothesized network, particularly temporal pole and anterior insula. All patients with impaired affective empathy were also impaired in comprehension of affective prosody, but many patients with impairments in prosodic comprehension had spared affective empathy. Patients with impaired affective empathy were older, but showed no difference in performance on tests of hemispatial neglect, volume of infarct or sex distribution compared with patients with intact affective empathy.
doi:10.1093/brain/awt177
PMCID: PMC3722353  PMID: 23824490
empathy; stroke; emotion perception; magnetic resonance imaging; prosody
3.  Right hemisphere dysfunction is better predicted by emotional prosody impairments as compared to neglect 
Background
Neurologists generally consider hemispatial neglect to be the primary cognitive deficit following right hemisphere lesions. However, the right hemisphere has a critical role in many cognitive, communication and social functions; for example, in processing emotional prosody (tone of voice). We tested the hypothesis that impaired recognition of emotional prosody is a more accurate indicator of right hemisphere dysfunction than is neglect.
Methods
We tested 28 right hemisphere stroke (RHS) patients and 24 hospitalized age and education matched controls with MRI, prosody testing and a hemispatial neglect battery. Emotion categorization tasks assessed recognition of emotions from prosodic cues. Receiver operating characteristic (ROC) analyses were used to compare tests in their ability to distinguish stroke patients from controls.
Results
ROC analyses revealed that the Prosody Score was more effective than the Neglect Battery Score in distinguishing stroke patients from controls, as measured by area under the curve (AUC); Prosody Score = 0.84; Neglect Battery Score =0. 57. The Prosody Score correctly classified 78.9%, while Neglect Score correctly classified 55.8% of participants as patients versus controls. The Prosody Score was similar to the total NIH Stroke Scale in identifying RHS patients (AUC=0.86, correctly classifying 80.1% of patients versus controls), but the tests only partially overlapped in the patients identified.
Conclusions
Severe prosody impairment may be a better indicator of right hemisphere dysfunction than neglect. Larger studies are needed to determine if including a bedside test of Prosody with the NIH Stroke Scale would most efficiently and reliably identify right hemisphere ischemia.
PMCID: PMC4059678  PMID: 24945016
prosody; neglect; emotions; stroke; right hemisphere; communication
4.  Motor Extinction in Distinct Reference Frames: A Double Dissociation 
Behavioural neurology  2013;26(1):111-119.
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.
doi:10.3233/BEN-2012-110254
PMCID: PMC3459173  PMID: 22713397
extinction; left body; left space; bimanual motor
5.  Disentangling the Neuroanatomical Correlates of Perseveration from Unilateral Spatial Neglect 
Behavioural neurology  2013;26(1):131-138.
Perseverative behavior, manifest as re-cancelling or re-visiting targets, is distinct from spatial neglect. Perseveration is thought to reflect frontal or parietal lobe dysfunction, but the neuroanatomical correlates remain poorly defined and the interplay between neglect and perseveration is incompletely understood. We enrolled 87 consecutive patients with diffusion-weighted, perfusion-weighted imaging, and spatial neglect testing within 24 hours of right hemisphere ischemic stroke. The degrees of spatial neglect and perseveration were analyzed. Perseveration was apparent in 46% (40/87) of the patients; 28% (24/87) showed perseveration only; 18% (16/87) showed both perseveration and neglect; and 3% (3/87) showed neglect only. Perseverative behaviors occur in an inverted “U” shape: little neglect was associated with few perseverations; moderate neglect with high perseverations; and in severe neglect targets may not enter consciousness and perseverative responses decrease. Brodmann areas of dysfunction, and the caudate and putament, were assessed and volumetrically measured. In this study, the caudate and putamen were not associated with perseveration. After controlling for neglect, and volume of dysfunctional tissue, only Brodmann area 46 was associated with perseveration. Our results further support the notion that perseveration and neglect are distinct entities; while they often co-occur, acute dorsolateral prefrontal cortex ischemia is associated with perseveration specifically.
doi:10.3233/BEN-2012-110235
PMCID: PMC3459288  PMID: 22713393
Perseveration; Neglect; Acute Stroke; Diffusion-weighted imaging; Perfusion-weighted imaging
6.  Patterns of Dysgraphia in Primary Progressive Aphasia Compared to Post-Stroke Aphasia 
Behavioural neurology  2013;26(0):21-34.
We report patterns of dysgraphia in participants with primary progressive aphasia that can be explained by assuming disruption of one or more cognitive processes or representations in the complex process of spelling. These patterns are compared to those described in participants with focal lesions (stroke). Using structural imaging techniques, we found that damage to the left extrasylvian regions, including the uncinate, inferior fronto-occipital fasciculus, and sagittal stratum (including geniculostriate pathway and inferior longitudinal fasciculus), as well as other deep white and grey matter structures, was significantly associated with impairments in access to orthographic word forms and semantics (with reliance on phonology-to-orthography to produce a plausible spelling in the spelling to dictation task). These results contribute not only to our understanding of the patterns of dysgraphia following acquired brain damage but also the neural substrates underlying spelling.
doi:10.3233/BEN-2012-110237
PMCID: PMC3620674  PMID: 22713396
dysgraphia; primary progressive aphasia; phonology; orthography; MRI
7.  Reperfusion of Specific Cortical Areas is Associated with Improvement in Distinct Forms of Hemispatial Neglect 
Objective
To test the hypothesis that restoring blood flow to specific right cortical regions in acute stroke results in improvement in distinct forms of hemispatial neglect distinguished by reference frame: viewer-centered versus stimulus-centered neglect.
Methods
Twenty five patients with acute right stroke were evaluated at Day 1 and Day 3-5 with a battery of neglect tests and diffusion- and perfusion-weighted MRI. Multivariate linear regression analysis revealed Brodmann areas where reperfusion predicted degree of improvement in scores on each type of neglect, independently of reperfusion of other areas, total change in the volume of infarct or hypoperfusion, and age.
Results
Reperfusion of dorsal frontoparietal cortex (including Brodmann areas 40, 46, and 4) independently predicted improvement in viewer-centered neglect, such as detecting stimuli on left in line cancellation and scene copying (r=0.951; p<0.0001). Reperfusion of a more ventral temporo-occipital cortex, including right Brodmann areas 37, 38, 21 and 18, independently contributed to improvement in stimulus-centered neglect, such as detecting left gaps in circles (r=0.926; p<0.0001). Reperfusion of right midfusiform gyrus (temporal occipital cortex), change in total volume of ischemia, change in volume of hypoperfusion and age predicted degree of improvement in reading (reduction in “neglect dyslexic” errors; r=0.915; p<0.0001). Results demonstrate that reperfusing specific cortical regions yields improvement in different types of neglect.
doi:10.1016/j.cortex.2011.01.003
PMCID: PMC3125403  PMID: 21345430
8.  Predictors and assessment of cognitive dysfunction resulting from ischaemic stroke 
Lancet neurology  2010;9(9):895-905.
Stroke remains a primary cause of morbidity throughout the world mainly because of its effect on cognition. Individuals can recover from physical disability resulting from stroke, but might be unable to return to their previous occupations or independent life because of cognitive impairments. Cognitive dysfunction ranges from focal deficits, resulting directly from an area of infarction or from hypoperfusion in adjacent tissue, to more global cognitive dysfunction. Global dysfunction is likely to be related to other underlying subclinical cerebrovascular disease, such as white-matter disease or subclinical infarcts. Study of cognitive dysfunction after stroke is complicated by varying definitions and lack of measurement of cognition before stroke. Additionally, stroke can affect white-matter connectivity, so newer imaging techniques, such as diffusion-tensor imaging and magnetisation transfer imaging, that can be used to assess this subclinical injury are important tools in the assessment of cognitive dysfunction after stroke. As research is increasingly focused on the role of preventable risk factors in the development of dementia, the role of stroke in the development of cognitive impairment and dementia could be another target for prevention.
doi:10.1016/S1474-4422(10)70164-2
PMCID: PMC3592203  PMID: 20723846
9.  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.
doi:10.1016/j.cortex.2009.12.001
PMCID: PMC2889229  PMID: 20060967
Primary Progressive Aphasia; dysgraphia; spelling errors; neuroimaging; aphasia
10.  The Nature of Naming Errors in Primary Progressive Aphasia Versus Acute Post-Stroke Aphasia 
Neuropsychology  2010;24(5):581-589.
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.
doi:10.1037/a0020287
PMCID: PMC3085899  PMID: 20804246
naming errors; stroke aphasia; primary progressive aphasia
11.  The function of the left anterior temporal pole: evidence from acute stroke and infarct volume 
Brain  2011;134(10):3094-3105.
The role of the anterior temporal lobes in cognition and language has been much debated in the literature over the last few years. Most prevailing theories argue for an important role of the anterior temporal lobe as a semantic hub or a place for the representation of unique entities such as proper names of peoples and places. Lately, a few studies have investigated the role of the most anterior part of the left anterior temporal lobe, the left temporal pole in particular, and argued that the left anterior temporal pole is the area responsible for mapping meaning on to sound through evidence from tasks such as object naming. However, another recent study indicates that bilateral anterior temporal damage is required to cause a clinically significant semantic impairment. In the present study, we tested these hypotheses by evaluating patients with acute stroke before reorganization of structure–function relationships. We compared a group of 20 patients with acute stroke with anterior temporal pole damage to a group of 28 without anterior temporal pole damage matched for infarct volume. We calculated the average percent error in auditory comprehension and naming tasks as a function of infarct volume using a non-parametric regression method. We found that infarct volume was the only predictive variable in the production of semantic errors in both auditory comprehension and object naming tasks. This finding favours the hypothesis that left unilateral anterior temporal pole lesions, even acutely, are unlikely to cause significant deficits in mapping meaning to sound by themselves, although they contribute to networks underlying both naming and comprehension of objects. Therefore, the anterior temporal lobe may be a semantic hub for object meaning, but its role must be represented bilaterally and perhaps redundantly.
doi:10.1093/brain/awr050
PMCID: PMC3187536  PMID: 21685458
anterior temporal lobe; aphasia; acute ischaemic stroke; word naming; comprehension; semantic impairment; infarct volume
12.  Patterns of reading performance in acute stroke: A descriptive analysis 
Behavioural neurology  2010;22(1-2):35-44.
One of the main sources of information regarding the underlying processes involved in both normal and impaired reading has been the study of reading deficits that occur as a result of brain damage. However, patterns of reading deficits found acutely after brain injury have been little explored. The observed patterns of performance in chronic stroke patients might reflect reorganization of the cognitive processes underlying reading or development of compensatory strategies that are not normally used to read.
Method
112 acute left hemisphere stroke patients were administered a task of oral reading of words and pseudowords within 1-2 days of hospital admission; performance was examined for error rate and type, and compared to that on tasks involving visual lexical decision, visual/auditory comprehension, and naming.
Results
Several distinct patterns of performance were identified. Although similarities were found between the patterns of reading performance observed acutely and the classical acquired dyslexias generally identified more chronically, some notable differences were observed. Of interest was the finding that no patient produced any pure semantic errors in reading, despite finding such errors in comprehension and naming.
doi:10.3233/BEN-2009-0258
PMCID: PMC3093311  PMID: 20543457
Dyslexia; Oral Reading; Acute Stroke
13.  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 diffusionand 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/Relevance
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 semi-quantitative measure of tissue dysfunction in acute stroke and can account for substantial proportion of the variability in functional deficits in the acute stage.
doi:10.1161/STROKEAHA.109.561969
PMCID: PMC2790042  PMID: 19762699
14.  A Neural Network Critical for Spelling 
Annals of neurology  2009;66(2):249-253.
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.
doi:10.1002/ana.21693
PMCID: PMC2745512  PMID: 19743449
15.  Acute recovery of oral word production following stroke: Patterns of performance as predictors of recovery 
Behavioural neurology  2009;21(3):145-153.
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).
doi:10.3233/BEN-2009-0245
PMCID: PMC2828045  PMID: 19996511
16.  Gender differences in unilateral spatial neglect within 24 hours of ischemic stroke 
Brain and cognition  2008;68(1):49-52.
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.
doi:10.1016/j.bandc.2008.02.122
PMCID: PMC2582443  PMID: 18406504
Sex differences; spatial neglect; gender differences; spatial cognition; acute stroke
17.  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 hours 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.
doi:10.1016/j.cortex.2008.05.013
PMCID: PMC2659726  PMID: 19084219
aphasia; perfusion-weighted magnetic resonance imaging; semantics; acute ischemic stroke
18.  Voxelwise Bayesian Lesion Deficit Analysis 
NeuroImage  2008;40(4):1633-1642.
Relating cognitive deficits to the presence of lesions has been an important means of delineating structure-function associations in the human brain. We propose a voxel-based Bayesian method for lesion-deficit analysis, which identifies complex linear or nonlinear associations among brain-lesion locations, and neurological status. We validated this method using a simulated data set, and we applied this algorithm to data obtained from an acute-stroke study to identify associations among voxels with infarct or hypoperfusion, and impaired word reading. We found that a distributed region involving Brodmann areas (BA) 22, 37, 39, and 40 was implicated in word reading.
doi:10.1016/j.neuroimage.2008.01.014
PMCID: PMC2394734  PMID: 18328733
19.  Right Hemispatial Neglect: Frequency and Characterization Following Acute Left Hemisphere Stroke 
Brain and cognition  2006;64(1):50-59.
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 48 hours 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.
doi:10.1016/j.bandc.2006.10.005
PMCID: PMC1949495  PMID: 17174459
spatial neglect; spatial attention; acute ischemic stroke; global processing; local processing; temporal cortex; parietal cortex
20.  Aphasia: Current Concepts in Theory and Practice 
Recent advances in neuroimaging contribute to a new insights regarding brain-behavior relationships and expand understanding of the functional neuroanatomy of language. Modern concepts of the functional neuroanatomy of language invoke rich and complex models of language comprehension and expression, such as dual stream networks. Increasingly, aphasia is seen as a disruption of cognitive processes underlying language. Rehabilitation of aphasia incorporates evidence based and person-centered approaches. Novel techniques, such as methods of delivering cortical brain stimulation to modulate cortical excitability, such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation, are just beginning to be explored. In this review, we discuss the historical context of the foundations of neuroscientific approaches to language. We sample the emergent theoretical models of the neural substrates of language and cognitive processes underlying aphasia that contribute to more refined and nuanced concepts of language. Current concepts of aphasia rehabilitation are reviewed, including the promising role of cortical stimulation as an adjunct to behavioral therapy and changes in therapeutic approaches based on principles of neuroplasticity and evidence-based/person-centered practice to optimize functional outcomes.
PMCID: PMC4041294  PMID: 24904925
stroke; aphasia; neuroanatomy; dorsal and ventral streams; rehabilitation
21.  Dissociation between Egocentric and Allocentric Visuospatial and Tactile Neglect in Acute Stroke 
Previous investigations provide evidence for distinction between egocentric (viewer-centered) and allocentric (stimulus- or object-centered) hemispatial neglect. However, it has not been determined whether this dissociation is modality-independent or modality-specific. We identify the incidence of egocentric and allocentric neglect in visual and tactile modalities, as well as the frequency of their co-occurrences in each modality.
One-hundred patients with acute, right supratentorial ischemic stroke were administered tests for egocentric and allocentrichemispatial neglect in visual (n = 98) and tactile (n = 58) modalities. The visual test consisted of a page of 30 circles; 10 with no gap, 10 with a gap on the right side, and 10 with a gap on the left. Patients were asked to circle all complete circles and cross out all circles with gaps. A tactile version consisted of the same stimulus types presented as raised circles. Patients were asked to explore the board of circles with their dominant hand and report whether each circle had a gap. To determine the presence of egocentric or allocentric neglect, each test was analyzed for a significantly higher number of errors on the contralesional versus ipsilesional side of the page/board, or of the stimulus, using the Chi square analysis.
On the visual test, 17 patients exhibited egocentric neglect; four exhibited allocentric neglect; and only two exhibited both. In the tactile modality, 19 exhibited egocentric neglect; one exhibited allocentric neglect; and none demonstrated both. Only four patients showed egocentric neglect on both visual and tactile tests. We found one patient with bilateral lesions who showed left egocentric visual neglect and right allocentric tactile neglect.
These data provide strong evidence that egocentric and allocentric neglect are distinct syndromes that often dissociate and likely reflect damage to different brain areas. They also show that selective egocentric or allocentric neglect can occur in visual or tactile modalities.
doi:10.1016/j.cortex.2006.02.002
PMCID: PMC4297640  PMID: 18761135
Acute stroke; Cognitive impairment; Hemispatial neglect
22.  Diffusion–Perfusion Mismatch: An Opportunity for Improvement in Cortical Function 
Objective: There has been controversy over whether diffusion–perfusion mismatch provides a biomarker for the ischemic penumbra. In the context of clinical stroke trials, regions of the diffusion–perfusion mismatch that do not progress to infarct in the absence of reperfusion are considered to represent “benign oligemia.” However, at least in some cases (particularly large vessel stenosis), some of this hypoperfused tissue may remain dysfunctional for a prolonged period without progressing to infarct and may recover function if eventually reperfused. We hypothesized that patients with persistent diffusion–perfusion mismatch using a hypoperfusion threshold of 4–5.9 s delay on time-to-peak (TTP) maps at least sometimes have persistent cognitive deficits relative to those who show some reperfusion of this hypoperfused tissue.
Methods: We tested this hypothesis in 38 patients with acute ischemic stroke who had simple cognitive tests (naming or line cancelation) and MRI with diffusion and perfusion imaging within 24 h of onset and again within 10 days, most of whom had large vessel stenosis or occlusion.
Results: A persistent perfusion deficit of 4–5.9 s delay in TTP on follow up MRI was associated with a persistent cognitive deficit at that time point (p < 0.001). When we evaluated only patients who did not have infarct growth (n = 14), persistent hypoperfusion (persistent mismatch) was associated with a lack of cognitive improvement compared with those who had reperfused. The initial volume of hypoperfusion did not correlate with the later infarct volume (progression to infarct), but change in volume of hypoperfusion correlated with change in cognitive performance (p = 0.0001). Moreover, multivariable regression showed that the change in volume of hypoperfused tissue of 4–5.9 s delay (p = 0.002), and change in volume of ischemic tissue on diffusion weighted imaging (p = 0.02) were independently associated with change in cognitive function.
Conclusion: Our results provide additional evidence that non-infarcted tissue with a TTP delay of 4–5.9 s may be associated with persistent deficits, even if it does not always result in imminent progression to infarct. This tissue may represent the occasional opportunity to intervene to improve function even days after onset of symptoms.
doi:10.3389/fneur.2014.00280
PMCID: PMC4294157  PMID: 25642208
diffusion–perfusion mismatch; acute ischemic stroke; penumbra; NIHSS; functional outcome
23.  The Pediatric Intracerebral Hemorrhage Score: A Simple Grading Scale for Intracerebral Hemorrhage in Children 
Background and Purpose
The ICH Score is the most commonly used clinical grading scale for outcome prediction after adult intracerebral hemorrhage (ICH). We created a similar scale in children to inform clinical care and assist in clinical research.
Methods
Children, full-term newborns to 18 years, with spontaneous ICH were prospectively enrolled from 2007-2012 at three centers. The pediatric ICH score was created by identifying factors associated with poor outcome. The score's ability to detect moderate disability or worse and severe disability or death was examined with sensitivity, specificity, and area under the receiver operating characteristic (ROC) curves.
Results
The pediatric ICH score components include ICH volume >2-3.99% of total brain volume (TBV)=1 point, ICH volume ≥4% TBV=2 points; acute hydrocephalus=1 point; herniation=1 point; and infratentorial location=1 point. The score ranges from 0-5. At 3-month follow-up of 60 children, 10 were severely disabled or dead, 30 had moderate disability, and 20 had good recovery. A pediatric ICH score of ≥1 predicted moderate disability or worse with a sensitivity of 75% [95% confidence interval (CI): 59-87%] and a specificity of 70% (95% CI: 46-88%). A pediatric ICH score of ≥2 predicted severe disability or death with a sensitivity and specificity of 90% (95% CI: 55-99%) and 68% (95% CI: 53-80%). The area under the ROC curve for classifying outcome as severe disability or death was 0.88 (95% CI: 0.78-0.97).
Conclusions
The pediatric ICH score is a simple clinical grading scale that may ultimately be used for risk stratification, clinical care, and research.
doi:10.1161/STROKEAHA.113.003448
PMCID: PMC3910321  PMID: 24281231
intracerebral hemorrhage; outcome; pediatric stroke; hemorrhage
24.  A Comparison of Two Methods for MRI Classification of At-Risk Tissue and Core Infarction 
Objective: To compare how at-risk tissue and core infarction were defined in two major trials that tested the use of MRI in selecting acute stroke patients for endovascular recanalization therapy.
Methods: MRIs from 12 patients evaluated for possible endovascular therapy were processed using the methods published from two major trials, MR RESCUE and DEFUSE 2. Specifically, volumes of at-risk tissue and core infarction were generated from each patient’s MRI. MRIs were then classified as whether or not they met criteria for salvageable tissue: “penumbral pattern” for MR RESCUE and/or “target profile” for DEFUSE 2 as defined by each trial.
Results: Volumes of at-risk tissue measured by the two definitions were correlated (p = 0.017) while the volumes of core infarct were not (p = 0.059). The volume of at-risk tissue was consistently larger when defined by the penumbral pattern than the target profile while the volume of core infarct was consistently larger when defined by the target profile than the penumbral pattern. When these volumes were used to classify the MRI scans, 9 out of 12 patients (75%) were classified as having a penumbral pattern, while only 4 out of 12 patients (33%) were classified as having a target profile. Of the 9 patients classified as penumbral pattern, 5 (55%) were classified differently by the target profile.
Interpretation: Our analysis found that the MR RESCUE trial defined salvageable tissue in a way that made it more likely for patients be labeled as favorable for treatment. For the cohort of patients examined in this study, had they been enrolled in both trials, most of the patients identified as having salvageable tissue by the MR RESCUE trial would not have been considered to have salvageable tissue in the DEFUSE 2 trial. Caution should be taken in concluding that MRI selection for endovascular therapy is not effective as imaging selection criteria were substantially different between the two trials.
doi:10.3389/fneur.2014.00155
PMCID: PMC4153314  PMID: 25232348
MR RESCUE; DEFUSE 2; MRI; penumbra; DWI; PWI; at-risk tissue; core infarction
25.  Quantifying Brain Lesions in Neuroimaging Research Examining Language Recovery after Stroke 
NeuroImage  2012;73:208-214.
New structural and functional neuroimaging methods continue to rapidly develop, offering promising tools for cognitive neuroscientists. In the last 20 years, advanced magnetic resonance imaging (MRI) techniques have provided invaluable insights into how language is represented and processed in the brain and how it can be disrupted by damage to, or dysfunction of, various parts of the brain. Current functional MRI (fMRI) approaches have also allowed researchers to purposefully investigate how individuals recover language after stroke. This paper presents recommendations for quantification of brain lesions derived from discussions among international researchers at the Neuroimaging in Aphasia Treatment Research Workshop held at Northwestern University (Evanston, Illinois, USA). Methods for detailing and characterizing the brain damage that can influence results of fMRI studies in chronic aphasic stroke patients are discussed. Moreover, we aimed to provide the reader with a set of general practical guidelines and references to facilitate choosing adequate structural imaging strategies that facilitate fMRI studies in aphasia treatment research.
doi:10.1016/j.neuroimage.2012.07.044
PMCID: PMC3534842  PMID: 22846659
Structural anatomy; Language recovery; Stroke; Aphasia; Brain lesions

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