Search

Introduction: Impaired expression of emotion through tone, loudness, rate, and rhythm of speech (affective prosody) is common after right hemisphere (RH) stroke and impedes all social interactions. Hypothesis: Abnormal patterns of acoustic features correlate with listener judgment of affective prosody and are associated with infarcts of specific RH gray and white matter regions. Methods: Forty acute ischemic RH stroke patients had MRI DWI and described a picture within 48 hours of onset. Affective prosody of picture descriptions was rated by 21 healthy volunteers (1-7 scale). We identified acoustic features that correlated with listener ratings with Spearman correlations and with linear regression to identify independent predictors. A neurologist identified percent damage to each of 9 regions after co-registration of DWI to an atlas. We identified lesions associated with abnormalities in important acoustic features using logistic regression. Results: Listener ratings of prosody correlated with duration of voiced segments divided by total duration of speech segments(DurV/Dur) (rho=0.63; p2 =27; p=0.0081). Sex, lesion volume, damage to inferior frontal gyrus pars opercularis, inferior fronto-occipital fasciculus, superior longitudinal fasciculus (SLF), and uncinate were the only independent predictors. The same variables predicted CoV (X 2 =33; p=0.0005); age and damage to supramarginal gyrus and SLF were the only independent predictors. The same variables plus education predicted low DurV/Dur (X 2 =25; p=0.02). Conclusions: Impaired emotional expression after RH stroke is due to changes in specific acoustic features caused by infarct in right pars opercularis or supramarginal gyrus, or associated white matter tracts.

Despite its basic and translational importance, the neural circuitry supporting the perception of emotional faces remains incompletely understood. Functional imaging studies and chronic lesion studies indicate distinct roles of the amygdala and insula in recognition of fear and disgust in facial expressions, whereas intracranial encephalography studies, which are not encumbered by variations in human anatomy, indicate a somewhat different role of these structures. In this article, we leveraged lesion-mapping techniques in individuals with acute right hemisphere stroke to investigate lesions associated with impaired recognition of prototypic emotional faces before significant neural reorganization can occur during recovery from stroke. Right hemisphere stroke patients were significantly less accurate than controls on a test of emotional facial recognition for both positive and negative emotions. Patients with right amygdala or anterior insula lesions had significantly lower scores than other right hemisphere stroke patients on recognition of angry and happy faces. Lesion volume within several regions, including the right amygdala and anterior insula, each independently contributed to the error rate in recognition of individual emotions. Results provide additional support for a necessary role of the right amygdala and anterior insula within a network of regions underlying recognition of facial expressions, particularly those that have biological importance or motivational relevance and have implications for clinical practice.

Background: Communication deficits are common and disabling after both left hemisphere (LH) and right hemisphere (RH) stroke, and can be quantified by the number of Content Units (CU; concepts mentioned by healthy speakers) in describing the cookie theft picture from the NIHSS. In LH and RH stroke, CU correlates with lesion volume. Hypothesis: Communication recovery in LH and RH stroke is influenced by % damage to specific areas or vascular territories, independently of lesion volume and initial severity. Methods: 25 acute ischemic RH (n=9) and LH (n=16) stroke patients were evaluated with DWI and described the NIHSS picture Results: Together, age, lesion volume, initial CU, and % damage to each cortical/subcortical area were strongly associated with best recovery (F(9, 15) = 12.55; p< 0.00001; r 2 = 0.88), but only initial severity (CU; t=-4.95; p2 = 0.88), but only initial CU (t=-4.56; p50% damage to BG and had cortical hypoperfusion at Day 1. We speculate that good recovery was due to cortical reperfusion, but repeat PWI scans were not obtained. Conclusions: Patients who had the most room to improve on our measure of communication showed the most recovery. Independently of initial severity, more damage to left or right BG was associated with best recovery.

Consider consumption of annonacin-containing plant products, including pawpaw, as a possible environmental risk factor for atypical parkinsonism.

OBJECTIVE Awareness of motor functioning is most likely a complex process that requires integration of sensory-motor feedback to constantly update the system on the functioning of the limb during motor behavior. Using lesion mapping procedures and behavioral measures, the current study aimed to evaluate neural correlates of anosognosia for hemiplegia (AHP) in the acute stage (first 48 hr) of right hemisphere stroke. METHOD Thirty-five individuals with right hemisphere stroke who presented to an urban medical center within 24 hr of symptom onset were included in the study. All 35 individuals had hemiplegia, and 8 of these individuals exhibited AHP. RESULTS Fisher's exact test statistical map of lesion-deficit association (range is between-log(p) 4 to 11) found maximal value of 10.9 located in pars orbitalis (Brodmann's Area 47; BA). In this selected location, 6 out of 8 patients with AHP had tissue abnormality, whereas none of the unaffected subjects had tissue abnormality in BA 47. Right BA 44/45 was also found to be lesioned more frequently in individuals with AHP (75%) than without AHP (11%). CONCLUSIONS The current study findings provide preliminary support for unique involvement of the right inferior frontal gyrus (IFG), pars orbitalis (BA 47) in AHP. The current data suggest that frontal operculum may play a key role in awareness of limb functioning.

Radiological diagnosis is based on subjective judgment by radiologists. The reasoning behind this process is difficult to document and share, which is a major obstacle in adopting evidence-based medicine in radiology. We report our attempt to use a comprehensive brain parcellation tool to systematically capture image features and use them to record, search, and evaluate anatomical phenotypes. Anatomical images (T1-weighted MRI) were converted to a standardized index by using a high-dimensional image transformation method followed by atlas-based parcellation of the entire brain. We investigated how the indexed anatomical data captured the anatomical features of healthy controls and a population with Primary Progressive Aphasia (PPA). PPA was chosen because patients have apparent atrophy at different degrees and locations, thus the automated quantitative results can be compared with trained clinicians' qualitative evaluations. We explored and tested the power of individual classifications and of performing a search for images with similar anatomical features in a database using partial least squares-discriminant analysis (PLS-DA) and principal component analysis (PCA). The agreement between the automated z-score and the averaged visual scores for atrophy (r = 0.8) was virtually the same as the inter-evaluator agreement. The PCA plot distribution correlated with the anatomical phenotypes and the PLS-DA resulted in a model with an accuracy of 88% for distinguishing PPA variants. The quantitative indices captured the main anatomical features. The indexing of image data has a potential to be an effective, comprehensive, and easily translatable tool for clinical practice, providing new opportunities to mine clinical databases for medical decision support., Highlights • Brain parcellation tools define structures automatically and convert images into standardized and quantitative matrices. • We tested if an automated tool and the resultant vector of structural volumes can accurately capture anatomical phenotypes. • The agreement between visual and automated atrophy detection was virtually the same as the inter-evaluator agreement. • The quantitative indices captured the main anatomical features in brains with atrophy in different degrees and location. • The image quantification has potential to be an effective, comprehensive, and easily translatable tool for clinical practice.

Background: Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia affecting the elderly. The GGGGCC hexanucleotide expansion mutation at the C9orf72 locus has been identified as a major cause of amyotrophic lateral sclerosis and frontotemporal dementia, raising the question of whether this mutation is a factor in DLB. Furthermore, a small number of clinically diagnosed DLB patients have previously been reported to carry the pathologic C9orf72 hexanucleotide repeat expansion. Objective: To explore whether the C9orf72 mutation is present in pathologically confirmed DLB patients. Methods: We screened a cohort of 111 definite DLB cases with extensive Lewy body pathology for the C9orf72 hexanucleotide repeat expansion using the repeat-primed polymerase chain reaction assay. Results: No pathogenic expansions of the C9orf72 hexanucleotide repeat were found, suggesting that there is no causal relationship between C9orf72 and DLB. Conclusion: Our data illustrate that C9orf72 screening of clinically diagnosed DLB patients should only be considered in cases with a family history of motor neuron disease or frontotemporal dementia to distinguish between mimic diseases.

Individuals with "minor stroke" lack a dense hemiparesis or aphasia; however, commonly endorse persistent cognitive and motor problems despite low NIHSS scores. They also report problems with mood, energy, and the ability to think clearly that are less well characterized. Socioeconomic factors and stroke severity can influence patient-reported outcomes. In this study we explore patient-reported outcomes and the influence of these factors after minor stroke.Patients returning to clinic post-stroke with an NIHSS of ≤ 4 were administered a scale to quantify problems with daily activities and resulting functional burden, along with measures of fatigue and depression. T-tests, chi square analysis, and linear regression were used to compare functional outcomes of patients to controls (TIA or stroke mimic (n = 40)), and evaluate the association between patient-reported outcomes, stroke characteristics, and socioeconomic factors.151 stroke patients were seen a mean 83.6 days post-infarct. Patients reported more problems (11.7 versus 6.9, p = 0.02), resulting in higher functional burden (26.5 versus 12.3, p = 0.01), increased depression (p = 0.07), and greater fatigue (p = 0.02) compared to controls. There was no relationship between stroke characteristics (other than NIHSS), baseline education, income, marital status, or living situation and perception of recovery; however, those actively working prior to their stroke reported better outcomes across all categories (p for each0.02), and differences persisted in multivariable regression models.Prior occupational status may represent an important prognostic indicator for patients with minor stroke. Individuals working at the time of their infarct report better functional outcomes irrespective of age or stroke severity.

Transcranial magnetic stimulation (TMS) is an accessible, non-invasive technique to study cortical function in vivo. TMS studies have provided important pathophysiological insights across a range of neurodegenerative disorders and enhanced our understanding of brain reorganisation after stroke. In neurodegenerative disease, TMS has provided novel insights into the function of cortical output cells and the related intracortical interneuronal networks. Characterisation of cortical hyperexcitability in amyotrophic lateral sclerosis and altered motor cortical function in frontotemporal dementia, demonstration of cholinergic deficits in Alzheimer’s disease and Parkinson’s disease are key examples where TMS has led to advances in understanding of disease pathophysiology and potential mechanisms of propagation, with the potential for diagnostic applications. In stroke, TMS methodology has facilitated the understanding of cortical reorganisation that underlie functional recovery. These insights are critical to the development of effective and targeted rehabilitation strategies in stroke. The present review will provide an overview of cortical function measures obtained using TMS and how such measures may provide insight into brain function. Through an improved understanding of cortical function across a range of neurodegenerative disorders, and identification of changes in neural structure and function associated with stroke that underlie clinical recovery, more targeted therapeutic approaches may now be developed in an evolving era of precision medicine.

At least three distinct variants of primary progressive aphasia (PPA) have been described, but they are difficult to distinguish early in the course, when individuals experience primarily anomia. People with svPPA are often the hardest to care for, because they have impaired comprehension of words and objects and often have negative changes in comportment. We sought to identify an early marker of semantic variant primary progressive aphasia (svPPA) and to enhance the understanding of the semantic deficit in svPPA. We hypothesized that the pattern of eye tracking in a word picture matching task can differentiate svPPA from other variants and can predict which participants with unclassifiable PPA will progress to svPPA. We tested 19 individuals with PPA on a word picture matching task with eye tracking. We found that individuals with svPPA were less accurate than other variants when the foils were semantic coordinates (horse-cow) or schematically related (horse-saddle), but not when they were thematically related (saw-horse) or unrelated. Moreover, even in the condition in which they were highly accurate (unrelated foils) they looked much more often to the foils and for longer, than other variants or controls. Unclassifiable PPA participants who eventually developed svPPA showed the same pattern. This abnormal pattern was associated with atrophy in bilateral temporal poles.

Aphasia is among the most debilitating outcomes of stroke. Aphasia is a language disorder occurring in 10-30% of stroke survivors. Speech and Language Therapy (SLT) is the gold standard, mainstay treatment for aphasia, but gains from SLT may be incomplete. Pharmaceutical and noninvasive brain stimulation (NIBS) techniques may augment the effectiveness of SLT. Areas covered: Herein reviewed are studies of the safety and efficacy of these adjunctive interventions for aphasia, including randomized placebo-controlled and open-label trials, as well as case series from Pubmed, using search terms 'pharmacological,' 'tDCS' or 'TMS' combined with 'aphasia' and 'stroke.' Expert commentary: Relatively small studies have included participants with a range of aphasia types and severities, using inconsistent interventions and outcome measures. Results to-date have provided promising, but weak to moderate evidence that medications and/or NIBS can augment the effects of SLT for improving language outcomes. We end with recommendations for future approaches to studying these interventions, with multicenter, double-blind, randomized controlled trials.

Behavioral assessment has been investigated in frontotemporal lobar degeneration and Alzheimer's disease, but has not been explored extensively in subtypes of primary progressive aphasia (PPA). We explored the ability of a modified version of the Frontal Behavioral Inventory (FBI-mod) to discriminate between patients with distinct subtypes of PPA and patients with mild cognitive impairment (MCI). We hypothesized that individuals with nonfluent agrammatic PPA (nfaPPA) would have higher negative behavior scores than other groups and that individuals with semantic variant PPA (svPPA) would have higher disinhibition scores than other groups. Family members and/or caregivers of 120 individuals with PPA and MCI (mean age 69.54+8.75 years; 65 (54%) female; education 16.06±2.68 years; disease duration 46.47±34.26 months) completed the FBI-mod [logopenic PPA (lvPPA) n = 40. nfaPPA n = 29, svPPA n = 27, MCI n = 24]. The groups were not significantly different in age, gender, education, or disease duration. There were no significant differences between the groups for negative behaviors (p = 0.72) and disinhibition scores (p = 0.14). When comparing negative and disinhibition scores (in percent), negative scores were significantly higher in all groups (p < 0.001). When comparing subtest items, there was a pairwise difference between lvPPA and svPPA for restlessness (lvPPA < svPPA, p = 0.02, after adjusting for multiple between-group comparisons). There was a significant difference in the proportion of severe neglect between the groups with lvPPA having a lower proportion than the other two variants (p = 0.05), and there was a significant difference in the proportion of severe poor judgment between the groups with lvPPA also having a lower proportion than nfaPPA (p = 0.04). This study reveals the greater negative behavioral disturbance than disinhibition in the PPA and MCI groups of similar age and duration since onset and identifies different profiles for some specific behaviors for the PPA groups. These findings may have clinical and practical implications.

Cognitive neuropsychology (CN) has had an immense impact on the understanding of the normal cognitive processes underlying reading, spelling, spoken language comprehension and production, spatial attention, memory, visual perception, and orchestration of actions, through detailed analysis of behavioural performance by neurologically impaired individuals. However, there are other domains of cognition and communication that have rarely been investigated with this approach. Many cognitive neuropsychologists have extended their work in language, perception, or attention by turning to functional neuroimaging or lesion-symptom mapping to identify the neural mechanisms underlying the cognitive mechanisms they have identified. Another approach to extending one's research in CN is to apply the methodology to other cognitive functions. We briefly review the domains evaluated using methods of CN to develop cognitive architectures and computational models and the domains that have used functional neuroimaging and other brain mapping approaches in healthy controls to identify the neural substrates involved in cognitive tasks over the past 20 years. We argue that in some domains, neuroimaging studies have preceded the careful analysis of the cognitive processes underlying tasks that are studied, with the consequence that results are difficult to interpret. We use this analysis as the basis for discussing opportunities for expanding the field.

An intact orthographic processing system is critical for normal reading and spelling. Here we investigate the neural changes associated with impairment and subsequent recovery of the orthographic lexical processing system in an individual with an ischemic left posterior cerebral artery (PCA) stroke. This work describes a longitudinal case study of a patient, whose initials are MMY, with impairments in orthographic lexical processing for reading and spelling at stroke onset, and who recovered these skills within 1 year post stroke. We tested the hypothesis that this acute impairment to reading and spelling would be associated with a selective loss of neural activation in the left fusiform gyrus (FG), and that subsequent recovery would be associated with a gain of neural activation in this region. MMY's case provided a unique opportunity to assess the selectivity of neural changes because she demonstrated a behavioral recovery of naming as well; i.e., if there is neural recovery for reading and spelling, but not naming, then these neural changes are selective to the recovery of orthographic processing. To test our hypothesis, we examined longitudinal behavioral and functional magnetic resonance imaging (fMRI) data of reading, spelling, and visual object naming acquired acutely, 3 weeks, 5 months, and one year post stroke. In confirmation of our hypothesis, the loss and subsequent gain of orthographic lexical processing was associated with up-regulation of neural activation in areas previously associated with orthographic lexical processing: i.e., the left mid-FG and inferior frontal junction (IFJ). Furthermore, these neural changes were found to be selective to orthographic processing, as they were observed for reading and spelling, but not for visual object naming within the left mid-FG. This work shows that left PCA stroke can temporarily and selectively disrupt the orthographic lexical processing system, not only in the posterior region adjacent to the stroke, but also in relatively distant frontal orthographic processing regions.

Introduction: Previous studies indicate that anodal transcranial Direct Current Stimulation (A-tDCS) to left hemisphere or cathodal tDCS (C-tDCS) to right hemisphere might augment aphasia therapy to facilitate language recovery after chronic stroke and that cerebellar tDCS can augment verbal fluency and learning in healthy controls. Hypothesis: A-tDCS or C-tDCS) plus naming therapy results in improved naming performance for trained and untrained items from baseline to post-treatment compared to sham plus naming therapy in chronic aphasia. Methods: Six patients with large, chronic left middle cerebral artery (MCA) ischemic stroke and one patient with large bilateral MCA strokes participated in a randomized, double-blind, sham controlled, within-subject crossover trial (15 sessions of sham + naming therapy and 15 sessions of tDCS + naming therapy, in random order, separated by 2 months). 4 patients were randomly assigned to A-tDCS and 3 patients were assigned to C-tDCS. We used 2 mA for stimulation over right cerebellum for the first 20 minutes of computer-delivered naming therapy. Within-subjects within-treatments analysis using McNemar’s test for correlated responses to evaluate gains from each of the treatment conditions. An alpha level of p Results: tDCS + naming treatment produced significant gains in naming of both trained and untrained items in 3/4 patients with anodal stimulation and 3/3 patients with cathodal treatment. Sham + naming treatment produced gains for only trained items, and only in 4/7 participants. Discussion: A-tDCS or C-tDCS improved generalization of improvements to untrained stimuli after naming therapy for most patients. Results indicate potential usefulness of right cerebellar tDCS to augment naming therapy after chronic post stroke aphasia with large left or bilateral lesions.

People with post-stroke aphasia may have some degree of chronic deficit for which current rehabilitative treatments are variably effective. Accumulating evidence suggests that transcranial direct current stimulation (tDCS) may be useful for enhancing the effects of behavioral aphasia treatment. However, it remains unclear which brain regions should be stimulated to optimize effects on language recovery. Here, we report on the therapeutic potential of right cerebellar tDCS in augmenting language recovery in SMY, who sustained bilateral MCA infarct resulting in aphasia and anarthria. We investigated the effects of 15 sessions of anodal cerebellar tDCS coupled with spelling therapy using a randomized, double-blind, sham controlled, within-subject crossover trial. We also investigated changes in functional connectivity using resting state functional magnetic resonance imaging before and 2 months post treatment. Both anodal and sham treatments resulted in improved spelling to dictation for trained and untrained words immediately after and 2 months post treatment. However, there was greater improvement with tDCS than with sham, especially for untrained words. Further, generalization to written picture naming was only noted during tDCS but not with sham. The resting state functional connectivity data indicate that improvement in spelling was accompanied by an increase in cerebro-cerebellar network connectivity. These results highlight the therapeutic potential of right cerebellar tDCS to augment spelling therapy in an individual with large bilateral chronic strokes.

Structural imaging has not been used previously to predict the effect of treatment in primary progressive aphasia (PPA).This study examined relationships between baseline brain volume and the effects of phonological and orthographic treatments for anomia in PPA. It was predicted that lower baseline volume would be associated with lower post-treatment naming accuracy for treated items and smaller generalization effects.Twenty-one individuals with PPA participated. The treatment stimuli consisted of nouns that were consistently named correctly at baseline (Prophylaxis items) and/or nouns that were consistently named incorrectly at baseline (Remediation items). All 21 participants had Prophylaxis items, while 10 participants had Remediation items. Naming accuracy for untrained and trained items (Exemplar set 1) was measured. In addition, stimulus generalization was examined by having participants name an alternative exemplar of each untrained and trained item (Exemplar set 2). Correlational analyses focused on the relationships between naming accuracy and volume of regions previously identified as having a role in naming and semantic processing.Unexpectedly, there were no significant correlations between baseline volume and post-treatment accuracy for treated items. However, baseline volume within the left temporal pole was positively correlated with post-treatment accuracy for Untrained Exemplar set 2 Prophylaxis items, while baseline volume in the left inferior temporal gyrus was positively correlated with post-treatment accuracy for Untrained Exemplar set 1 Remediation items.These findings suggest that lower volume in the left temporal pole is associated with decline for Untrained items, while lower volume in the left inferior temporal gyrus is associated with a lack of improvement for Untrained items. Possible explanations for the different patterns observed across Exemplar sets are discussed.

Aims: We developed a cross-culturally valid short form of the Pyramids and Palm Trees Test to assess object semantic memory. We investigated its clinical utility in differentiating the semantic variant of primary progressive aphasia, from the logopenic and nonfluent agrammatic variants. Areas of atrophy associated with poor performance were identified. Fil: Breining, Bonnie L.. University Johns Hopkins; Estados Unidos Fil: Lala, Trisha. University Johns Hopkins; Estados Unidos Fil: Martínez Cuitiño Carricaburo, María Macarena. Universidad de Buenos Aires; Argentina. Universidad Favaloro; Argentina. Instituto de Neurología Cognitiva; Argentina Fil: Manes, Facundo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Australian Research Council Centre Of Excellence In Cognition And Its Disorders; Australia. Universidad Diego Portales; Chile. Universidad Favaloro; Argentina. Instituto de Neurología Cognitiva; Argentina Fil: Peristeri, Eleni. Aristotle University Of Thessaloniki. Thessaloniki; Grecia Fil: Tsapkini, Kyrana. University Johns Hopkins; Estados Unidos Fil: Faria, Andreia V.. University Johns Hopkins; Estados Unidos Fil: Hillis, Argye E.. University Johns Hopkins; Estados Unidos

Background and Purpose— Early blood–brain barrier damage after acute ischemic stroke has previously been qualitatively linked to subsequent intracranial hemorrhage (ICH). In this quantitative study, it was investigated whether the amount of blood–brain barrier damage evident on pre–tissue-type plasminogen activator MRI scans was related to the degree of post–tissue-type plasminogen activator ICH in patients with acute ischemic stroke. Methods— Analysis was performed on a database of patients with acute ischemic stroke provided by the Stroke Imaging Repository (STIR) and Virtual International Stroke Trials Archive (VISTA) Imaging Investigators. Patients with perfusion-weighted imaging lesions >10 mL and negative gradient-recalled echo imaging before intravenous tissue-type plasminogen activator were included. Postprocessing of the perfusion-weighted imaging source images was performed to estimate changes in blood–brain barrier permeability within the perfusion deficit relative to the unaffected hemisphere. Follow-up gradient-recalled echo images were reviewed for evidence of ICH and divided into 3 groups according to European Cooperative Acute Stroke Study (ECASS) criteria: no hemorrhage, hemorrhagic infarction, and parenchymal hematoma. Results— Seventy-five patients from the database met the inclusion criteria, 28 of whom experienced ICH, of which 19 were classified as hemorrhagic infarction and 9 were classified as parenchymal hematoma. The mean permeability (±SDs), expressed as an index of contrast leakage, was 17.0±8.8% in the no hemorrhage group, 19.4±4.0% in the hemorrhagic infarction group, and 24.6±4.5% in the parenchymal hematoma group. Permeability was significantly correlated with ICH grade in univariate ( P= 0.007) and multivariate ( P= 0.008) linear regression modeling. Conclusions— A perfusion-weighted imaging–derived index of blood–brain barrier damage measured before intravenous tissue-type plasminogen activator is given is associated with the severity of ICH after treatment in patients with acute ischemic stroke.

We evaluated the hypothesis that Brodmann's area (BA) 37 within left occipitotemporal cortex has at least two important functions in lexical processing. One role is the computation of case-, font-, location-, and orientation-independent grapheme descriptions for written word recognition and production (reading and spelling). This role may depend on the medial part of BA 37, in left midfusiform gyrus. The second role is in accessing modality-independent lexical representations for output, for naming and for reading and spelling of irregular or exception words. This role may depend on the lateral part of BA 37 in inferior temporal cortex. We tested these hypotheses in 234 participants with acute left hemisphere ischaemic stroke who underwent magnetic resonance imaging (MRI) and language testing within 48 hours of onset of stroke symptoms.

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

We aimed to identify neural regions where ischemia acutely after stroke is associated with impairment in phoneme discrimination, and to determine whether such deficits are associated with impairment of spoken word comprehension. We evaluated 33 patients within 48 h of left hemisphere ischemic stroke onset with tests of phoneme discrimination and word-picture matching. We identified Pearson correlations between accuracy in phoneme discrimination and accuracy of word comprehension and identified areas where the percentage of infarcted tissue was associated with severity of phoneme discrimination deficit. We found that 54% had deficits in phoneme discrimination relative to healthy controls. Accuracy in phoneme discrimination correlated with accuracy on word comprehension tests. Damage to left intraparietal sulcus and hypoperfusion and/or infarct of left superior temporal gyrus were associated with phoneme discrimination deficits acutely, although patients with these lesions showed improvement or resolution of the deficit by six months.

Molecular genetic research provides unprecedented opportunities to examine genotype-phenotype correlations underlying complex syndromes. To investigate pathogenic mutations and genotype-phenotype relationships in diverse neurodegenerative conditions, we performed a rare variant analysis of damaging mutations in autopsy-confirmed neurodegenerative cases from the Johns Hopkins Brain Resource Center (n = 1243 patients). We used NeuroChip genotyping and C9orf72 hexanucleotide repeat analysis to rapidly screen our cohort for disease-causing mutations. In total, we identified 42 individuals who carried a pathogenic mutation in LRRK2, GBA, APP, PSEN1, MAPT, GRN, C9orf72, SETX, SPAST, or CSF1R, and we provide a comprehensive description of the diverse clinicopathological features of these well-characterized cases. Our study highlights the utility of high-throughput genetic screening arrays to establish a molecular diagnosis in individuals with complex neurodegenerative syndromes, to broaden disease phenotypes and to provide insights into unexpected disease associations.

Deficits in lexical retrieval are commonly observed in individuals with post-stroke aphasia. Successful lexical retrieval is related to lexical diversity, lexical sophistication, and phonological word properties; however, the crucial brain regions supporting these different features are not fully understood. We performed MRI-based lesion symptom mapping in 58 individuals with a chronic left hemisphere stroke to assess how regional damage relates to spoken discourse-extracted measures of lexical diversity, lexical sophistication, and phonological word properties. For discourse transcription and word feature analysis, we used the Computerized Language Analysis (CLAN) program, Stanford Core Natural Language Processing, Irvine Phonotactic Online Dictionary, Lexical Complexity Analyzer, and Gramulator. Lesions involving the left posterior insula and supramarginal gyri and inferior fronto-occipital fasciculus were significant predictors of utterances with, on average, lower lexical diversity. Low lexical sophistication was associated with damage to the left pole of the superior temporal gyrus. Production of words with lower phonological complexity (fewer phonemes, higher phonological similarity) was associated with damage to the left supramarginal gyrus. Our findings indicate that discourse-extracted features of lexical retrieval depend on the integrity of specific brain regions involving insular and peri-Sylvian areas. The identified regions provide insight into potentially underlying mechanisms of lexically diverse, sophisticated and phonologically complex words produced during discourse., Highlights • Word production in connected speech of individuals with post-stroke aphasia depends on lesion locations • Low lexical diversity is linked to lesions to the left insula, supramarginal gyrus and inferior fronto-occipital fasciculus • Lexical sophistication is linked to lesions to the left pole of the temporal gyrus • Phonological word features are linked to lesions to the left supramarginal gyrus • Features of lexical retrieval in connected speech depend on the integrity of ventral and dorsal language processing streams

Objective To evaluate language deficits after acute stroke and their association with post–acute care at a setting other than home. We hypothesized that deficits in language comprehension would be associated with discharge to a setting other than home after adjustment for physical/occupational therapy (PT/OT) needs. Design Secondary analysis of prospectively collected data. Discharge location, demographic characteristics (age, sex, race), and the presence of PT/OT recommendations were abstracted from the medical record. Setting Acute stroke unit at a tertiary medical center. Participants Left hemispheric stroke patients (N=152) within 24 hours of event. Interventions The following tasks were administered: (a–b) oral and written naming of pictured objects, (c) oral naming with tactile input (tactile naming), (d–f) oral reading, oral spelling, and repetition of words and pseudowords, (g) written spelling to dictation, (h) spoken word-picture verification (ie, auditory comprehension), and (i) written word-picture verification (ie, written word comprehension). Main Outcome Measure Discharge to a setting other than home. Results Of 152 cases, 88 were discharged home and 64 to another setting. Among stroke subjects discharged to a setting other than home, 63.6% had auditory comprehension deficits compared with 42.9% of those discharged home ( P =.03). Deficits in auditory and reading comprehension and oral spelling to dictation were significantly associated with increased odds of discharge to a setting other than home after adjustment for age and PT/OT recommendations. Conclusions Cases with deficits in auditory comprehension, reading comprehension, and oral spelling to dictation had increased odds of being discharged to settings other than home. Early evaluation of these language deficits and prompt treatment may allow patients who would otherwise be discharged to an institution to go home. Further research is needed to design and evaluate individualized treatment protocols and their effect on discharge recommendations.

BACKGROUND Many stroke patients are clinically dehydrated at the time of hospital presentation, which could lead to an increase in blood viscosity and alteration in cerebral perfusion. Impaired cerebral perfusion can cause hemispheric dysfunction, which can be rapidly quantified with bedside tests of hemispatial neglect. We hypothesized that hospitalized patients with laboratory markers consistent with dehydration or a volume contracted state (VCS) would have more severe cerebral dysfunction defined by greater degree of neglect. METHODS Subjects were a consecutive series of right-handed patients with acute right hemispheric stroke admitted within the Johns Hopkins Health System. All participants had clinical syndrome and magnetic resonance imaging consistent with acute infarction. The primary definition of a VCS was a urea/creatinine ratio >15, with secondary definition including urine specific gravity over 1.010. Acute infarct volume was measured on magnetic resonance imaging. Neglect was evaluated using a standardized battery of bedside tests. RESULTS Of 201 patients meeting inclusion criteria, 131/201 (65%) had elevated BUN/creatinine ratios at admission. Approximately 61% (122/201) had some degree of neglect. Elevated BUN/creatinine ratio was associated with an increased odds of severe neglect in unadjusted models (OR=4.1; 95% CI, 1.2, 14.4), with loss of significance in adjusted models (OR=4.43; 95% CI, 0.99, 19.8) after adjustment for age, infarct volume, sex, and NIHSS score. CONCLUSIONS Our data suggest that patients who are in a VCS at the time of stroke may have more frequent and severe neglect, with attenuation of results after adjustment for factors related to stroke size and age. If proven clinically relevant, a formalized rehydration strategy based on objective lab markers may represent an opportunity for improvement in outcome with low-cost, broadly available treatment for acute stroke patients.

Purpose We aimed to: (a) review existing data on the neural basis of affective prosody; (b) test the hypothesis that there are double dissociations in impairments of expression and recognition of affective prosody; and (c) identify areas of infarct associated with impaired expression and/or recognition of affective prosody after acute right hemisphere (RH) ischemic stroke. Methods Participants were tested on recognition of emotional prosody in content-neutral sentences. Expression was evaluated by measuring variability in fundamental frequency. Voxel-based symptom mapping was used to identify areas associated with severity of expressive deficits. Results We found that 9/23 patients had expressive prosody impairments; 5/9 of these patients also had impaired recognition of affective prosody; 2/9 had selective deficits in expressive prosody; recognition was not tested in 2/9. Another 6/23 patients had selective impairment in recognition of affective prosody. Severity of expressive deficits was associated with lesions in right temporal pole; patients with temporal pole lesions had deficits in expression and recognition. Conclusions Expression and recognition of prosody can be selectively impaired. Damage to right anterior temporal pole is associated with impairment of both, indicating a role of this structure in a mechanism shared by expression and production of affective prosody.

Introduction: Previous studies show that the NIH Stroke Scale (NIHSS) underestimates volume of right hemisphere (RH) relative to left hemisphere stroke. Hypothesis: Analysis of descriptions of the “Cookie Theft” picture from the NIHSS yields quantitative measures of severity of RH cortical deficits that, when added to NIHSS scores, better account for infarct volume than NIHSS score alone in acute RH stroke. Methods: We evaluated 26 patients with acute ischemic RH stroke within 48 hours of onset with NIHSS, analysis of the “Cookie Theft” picture, and DWI, and compared them to 26 age-matched controls. Picture descriptions were evaluated for: total content units (CU; based on published norms), syllables per CU; left CU:right CU; % interpretive CU. A neurologist blinded to clinical data measured lesion volume and % damage to gray and white matter regions of interest (ROI) on DWI after registration to an atlas. Multivariable linear regression was used to generate a model that best predicted stroke volume. Pearson correlations were calculated between behavioral scores and % damage to each ROI. Group means were compared by t-tests. Results: Lesion volume correlated more strongly with syllables per CU (r2 = .39; p=0.0006) than with NIHSS score (r2=.38; p=0.0008). Moreover, lesion volume was best accounted for by a model that included: total CU, syllables per CU, left CU:right CU, % interpretive CU; NIHSS score, and age (r2 =.80; p< Conclusions: Adding picture description scores improves NIHSS in accounting for lesion volume in RH stroke and yields complementary information about lesion localization.

Introduction: Emotional empathy includes emotional contagion (sharing another’s feelings) and perspective-taking (inferring another’s feelings). Earlier studies show that right hemisphere stroke (RHS) can cause impaired perspective-taking. However, studies have not identified stroke lesions associated with impaired emotional contagion. Hypothesis: Acute infarcts in specific frontal, temporal, or limbic regions disrupt emotional contagion, measured with skin conductance response (SCR; a sensitive measure of emotional response), as well as perspective-taking. Methods: Participants (9 acute RHS, 9 age-matched controls) played a “roulette” game and watched a partner play. We measured SCR to winning and losing. They rated the emotions (happy to sad) of themselves and their partner when they won and lost money. A neurologist blind to behavioral responses measured percent damage to 10 frontal, temporal, and limbic regions of interest (ROI) on DWI after registration to an atlas. We evaluated differences in group means with unpaired t-tests and differences between ratings of emotions for wins versus losses with paired t-tests. We evaluated associations between SCR magnitude and percent damage to ROI with Spearman correlations. Results: SCR magnitude was significantly lower in response to both wins and losses in patients with right anterior insula (AI) or inferior frontal gyrus opercularis (IFGop) lesions, compared to those without these lesions, when they played or watched partner play (p=0.0001 to 0.008). SCR to partner winning or losing negatively correlated percent damage to insula (rho=-.64;p=0.005) and IFGop (rho=-.47; p=0.045). Controls and patients without AI or IFGop lesions rated partners and themselves as significantly happier when they won versus lost (p Conclusions: Acute right AI and IFGop infarcts are associated with impaired emotional contagion measured with SCR and perspective-taking.

Introduction: An estimated 44-70% of stroke patients present to the hospital in a dehydrated state. Prior studies suggest that volume contraction contributes to worsened neglect syndromes and reduced chance of early recovery. Thus we hypothesized that patients who were clinically dehydrated at the time of stroke carried a higher probability of worse functional outcome at three months. Methods: We enrolled a consecutive series of ischemic stroke patients who presented to the hospital within 12 hours from stroke symptom onset. Patients were excluded if they had baseline kidney disease, presented with signs of active infection, or were unable to complete MRI. Clinical function was measured via daily NIHSS and 3 month modified Rankin scale (mRS). A priori, we defined a volume contracted state as BUN/creatinine ratio > 15 or urine specific gravity (SG) > 1.010. Results: One hundred and four patients were eligible for inclusion after 1 year of recruitment, of whom 83 (80%) had urinalysis measured and were thus included in this analysis. 62/83 patients (75%) had elevated urine SG consistent with a clinically dehydrated state. Independent of age, sex, and baseline NIHSS score, patients with elevated urine SG > 1.010 had a 3.6 increased odds (95% CI; 1.31-9.93) of being in a higher (worse) modified mRS category (Figure). A combined model defining volume contraction using both elevated BUN/creatinine ratio and urine SG did not demonstrate a statistically meaningful difference in outcomes. Conclusions: Elevated urine specific gravity at the time of ischemic stroke is associated with worse 3 month outcome. This objective marker may represent a readily available, standardized way to measure clinical dehydration syndromes as we attempt to define structured rehydration strategies for this population of patients.

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia affecting the elderly. The GGGGCC hexanucleotide expansion mutation at the C9orf72 locus has been identified as a major cause of amyotrophic lateral sclerosis and frontotemporal dementia, raising the question of whether this mutation is a factor in DLB. Furthermore, a small number of clinically diagnosed DLB patients have previously been reported to carry the pathologic C9orf72 hexanucleotide repeat expansion.To explore whether the C9orf72 mutation is present in pathologically confirmed DLB patients.We screened a cohort of 111 definite DLB cases with extensive Lewy body pathology for the C9orf72 hexanucleotide repeat expansion using the repeat-primed polymerase chain reaction assay.No pathogenic expansions of the C9orf72 hexanucleotide repeat were found, suggesting that there is no causal relationship between C9orf72 and DLB.Our data illustrate that C9orf72 screening of clinically diagnosed DLB patients should only be considered in cases with a family history of motor neuron disease or frontotemporal dementia to distinguish between mimic diseases.

Hemorrhagic transformation (HT) increases the morbidity and mortality of ischemic stroke. Anticoagulation is often indicated in patients with atrial fibrillation, low ejection fraction, or mechanical valves who are hospitalized with acute stroke, but increases the risk of HT. Risk quantification would be useful. Prior studies have investigated risk of systemic hemorrhage in anticoagulated patients, but none looked specifically at HT. In our previously published work, age, infarct volume, and estimated glomerular filtration rate (eGFR) significantly predicted HT. We created the hemorrhage risk stratification (HeRS) score based on regression coefficients in multivariable modeling and now determine its validity in a prospectively followed inpatient cohort. A total of 241 consecutive patients presenting to 2 academic stroke centers with acute ischemic stroke and an indication for anticoagulation over a 2.75-year period were included. Neuroimaging was evaluated for infarct volume and HT. Hemorrhages were classified as symptomatic versus asymptomatic, and by severity. HeRS scores were calculated for each patient and compared to actual hemorrhage status using receiver operating curve analysis. Area under the curve (AUC) comparing predicted odds of hemorrhage (HeRS score) to actual hemorrhage status was 0.701. Serum glucose (P

Spelling a word involves the retrieval of information about the word's letters and their order from long-term memory as well as the maintenance and processing of this information by working memory in preparation for serial production by the motor system. While it is known that brain lesions may selectively affect orthographic long-term memory and working memory processes, relatively little is known about the neurotopographic distribution of the substrates that support these cognitive processes, or the lesions that give rise to the distinct forms of dysgraphia that affect these cognitive processes. To examine these issues, this study uses a voxel-based mapping approach to analyse the lesion distribution of 27 individuals with dysgraphia subsequent to stroke, who were identified on the basis of their behavioural profiles alone, as suffering from deficits only affecting either orthographic long-term or working memory, as well as six other individuals with deficits affecting both sets of processes. The findings provide, for the first time, clear evidence of substrates that selectively support orthographic long-term and working memory processes, with orthographic long-term memory deficits centred in either the left posterior inferior frontal region or left ventral temporal cortex, and orthographic working memory deficits primarily arising from lesions of the left parietal cortex centred on the intraparietal sulcus. These findings also contribute to our understanding of the relationship between the neural instantiation of written language processes and spoken language, working memory and other cognitive skills.

The most common classification of aphasic individuals in the literature is by clinical syndromes of commonly co-occurring deficits that reflect vascular territories affected by stroke. This classification system is approximately based on the lesion–deficit association logic of the 19th century. The relationship between these syndromes and the associated vascular territories is not always consistent, in part because of individual variability in vasculature and in part because of reorganization of structure–function relationship after injury. Characteristics of vascular syndromes of aphasia are dissociable, because the entire vascular territory is not always damaged and because various symptoms recover at different rates. In this chapter, the vascular syndromes of aphasia are described. The relevance of the vascular syndromes to current concepts of the functional neuroanatomy of language is discussed. The usefulness of vascular syndromes in medical management of stroke versus aphasia research and treatment is considered.

The arcuate fasciculus (AF) is believed to be fundamental to the neural circuitry behind many important cognitive processes. Connecting Wernicke’s and Broca’s area, these fibers are thought to be especially important for repetition. In this case study we present evidence from a patient that set doubt on these assumptions. We present structural imaging, diffusion tensor imaging, and language data on a patient with a large left-sided stroke and severely damaged left AF who showed intact word repetition and relatively intact sentence repetition performance. Specifically, his sentence repetition is more fluent and grammatical, with less hesitation than spontaneous speech, and with rare omissions only during the longest sentences. These results challenge classical theories that maintain the left AF is the dominant language processing pathway or mechanism for repetition.

We investigated the association between yes/no sentence comprehension and dysfunction in anterior and posterior left-hemisphere cortical regions in acute stroke patients. More specifically, we manipulated whether questions were Nonreversible (e.g., Are limes sour?) or Reversible (e.g., Is a horse larger than a dog?) to investigate the regions associated with semantic and syntactic processing. In addition, we administered lexical tasks (i.e., Picture-Word Verification, Picture Naming) to help determine the extent to which deficits in sentence processing were related to deficits in lexical processing. We found that errors on the lexical tasks were associated with ischemia in posterior-temporal Brodmann Areas (BA 21, 22, 37) and inferior parietal regions (BA 39, 40). Nonreversible question comprehension was associated with volume of tissue dysfunction, while Reversible question comprehension was associated with posterior regions (BA 39, 40) as well as one anterior region (BA 6). We conclude that deficits in Nonreversible questions required extensive dysfunction that affected language processing across multiple levels, while Reversible question comprehension was associated with regions involved in semantics as well as working memory that indirectly influenced syntactic processing. Overall, this suggests that yes/no question comprehension relies on multiple regions and that the importance of certain regions increases in relation to semantic, phonological, and syntactic complexity.