Ryuta Kinno

Neural Correlates of Noncanonical Syntactic Processing Revealed by a Picture-Sentence Matching Task

It remains controversial whether the left inferior frontal gyrus subserves syntactic processing or short‐term memory demands. Here we devised a novel picture‐sentence matching task involving Japanese sentences with different structures to clearly contrast syntactic reanalysis processes. Using event‐related functional magnetic resonance imaging (fMRI), activations under three main conditions were directly compared: a canonical/subject‐initial active sentence (AS), a noncanonical/subject‐initial passive sentence (PS), and a noncanonical/object‐initial scrambled sentence (SS). We found that activation in the dorsal region of the left inferior frontal gyrus (dF3t) was enhanced more by the noncanonical processing under the PS and SS conditions than by the canonical processing under the AS condition, and this enhancement was independent of domain‐general factors, such as general memory demands and task difficulty. Moreover, the left posterior superior/middle temporal gyrus (pSTG/MTG) showed more enhanced responses to object‐initial sentences under the SS condition than to subject‐initial sentences under the AS and PS conditions, which were not significantly affected by task difficulty. Furthermore, activation in the left lateral premotor cortex (LPMC) increased under the AS, PS, and SS conditions, in that order. It is possible that task difficulty affects the left LPMC, but the three distinct activations patterns suggest that these frontal and temporal regions work in concert to process syntactic structures, with their respective contributions dynamically regulated by linguistic requirements. Hum Brain Mapp 2008.

Differential reorganization of three syntax-related networks induced by a left frontal glioma

The opercular/triangular parts of the left inferior frontal gyrus and the left lateral premotor cortex are critical in syntactic processing. We have recently indicated that a glioma in one of these regions is sufficient to cause agrammatic comprehension. In the present study, we aimed to show how normally existing syntax-related networks are functionally reorganized by a lesion. Twenty-one patients with a left frontal glioma preoperatively performed a picture-sentence matching task, and underwent functional magnetic resonance imaging scans in an event-related design. We established two qualitatively different types of agrammatic comprehension, depending on glioma location. Patients with a glioma in the left lateral premotor cortex had a more profound deficit in the comprehension of scrambled sentences than that of active and passive sentences. In contrast, patients with a glioma in the opercular/triangular parts of the left inferior frontal gyrus had a more profound deficit in the comprehension of passive and scrambled sentences than that of active sentences. Moreover, we found dramatic changes in the activation patterns in these two patient groups, which accompanied abnormal overactivity and/or underactivity in the syntax-related regions. Furthermore, by examining functional connectivity in the normal brain, we identified three syntax-related networks among those regions, and anatomically visualized connections within individual networks by using diffusion tensor imaging. The first network consists of the opercular/triangular parts of the left inferior frontal gyrus, left intraparietal sulcus, right frontal regions, presupplementary motor area, and right temporal regions. These regions were overactivated in the patients with a glioma in the left lateral premotor cortex only for correct responses, indicating a cognitive change. The second network consists of the left lateral premotor cortex, left angular gyrus, lingual gyrus, and cerebellar nuclei. These regions were overactivated in the patients with a glioma in the opercular/triangular parts of the left inferior frontal gyrus for both correct and incorrect responses, indicating a neuronal change. The third network consists of the left ventral frontal and posterior temporal regions. These regions were underactivated in the patients with a glioma in the opercular/triangular parts of the left inferior frontal gyrus, indicating another neuronal change. These results demonstrate that agrammatic comprehension is associated with the global reorganization of functionally distinct networks, which indeed reflects a differential change in the relative contribution of these three networks to normal syntax-related functions.

Agrammatic comprehension caused by a glioma in the left frontal cortex

It has been known that lesions in the left inferior frontal gyrus (L. IFG) do not always cause Brocas aphasia, casting doubt upon the specificity of this region. We have previously devised a picture-sentence matching task for a functional magnetic resonance imaging (fMRI) study, and observed that both pars triangularis (L. F3t) of L. IFG (extending to pars opercularis (L. F3op)) and the left lateral premotor cortex (L. LPMC) are selectively involved in syntactic processing. The present study with lesion-symptoms mapping was conducted to examine whether the function of these regions is indeed critical for syntactic comprehension. Using the same picture-sentence matching task, we examined 21 patients with a glioma in the left frontal cortex but with no apparent disability in verbal/written communication or intelligence quotient. This task included three main conditions of sentence types: canonical/subject-initial active sentences, non-canonical/subject-initial passive sentences, and non-canonical/object-initial scrambled sentences. The patients preoperatively underwent a high-resolution 3D-MRI, and voxel-based lesion-symptom mapping was employed for the error rates data. We found that the patients with a lesion in L. F3op/F3t or L. LPMC showed differential patterns of condition-selective deficits in the comprehension of sentences. More specifically, the L. F3op/F3t-damaged patients had more profound deficits in the comprehension of non-canonical sentences, whereas the L. LPMC-damaged patients had more profound deficits in the comprehension of object-initial scrambled sentences. These results establish that a lesion in L. F3op/F3t or L. LPMC is sufficient to cause agrammatic comprehension.

Prevalence and Clinical Implication of Microbleeds in Dementia with Lewy Bodies in Comparison with Microbleeds in Alzheimer's Disease

Background: Cerebral microbleeds (MBs) have been well investigated in Alzheimers disease (AD), but not very extensively in non-AD dementias or in dementia with Lewy bodies (DLB). Aims: To elucidate the clinical significance of MBs in DLB. Methods: We compared the prevalence, locations and risk factors for MBs in 59 DLB and 81 AD patients. We visually counted MBs in each of the cortical and subjacent areas (frontal, temporal, parietal and occipital), the basal ganglia and the thalamus, and the brainstem and the cerebellar hemispheres on 1.5-tesla T2*-weighted gradient-recalled-echo MRI images. White matter lesions were semiquantified in fluid-attenuated inversion recovery images according to the Fazekas rating scale. Results: While the prevalence of MBs was comparable, MBs tended to be more abundant in DLB than in AD in all brain areas with the exception of the occipital lobes. The number of MBs was positively associated with the severity of white matter lesions but not with other vascular risk factors in either AD or DLB. The presence of MBs could be associated with cognitive impairment at onset. MB-positive DLB patients showed less impairment on 123I-metaiodobenzylguanidine myocardial scintigraphy (MIBG scintigraphy) images, supporting the notion of an inverse relationship between vascular lesions and Lewy body pathology. Conclusion: It was suggested that an intricate association between Lewy body pathology, AD-type pathologies and vascular lesions seems to be related to the initial symptoms and results of MIBG scintigraphy in DLB.

Can the 'head-turning sign' be a clinical marker of Alzheimer's disease?

Aims: To investigate the incidence and severity of the ‘head-turning sign’ (HTS), i.e. turning the head back to the caregiver(s) for help, in patients with various dementias and discuss its clinical specificity in Alzheimer’s disease (AD). Methods: We investigated the incidence and severity of HTS while administering a short cognitive test (the revised Hasegawa Dementia Rating Scale: HDSR) in outpatients with AD [125 patients, including 4 with AD + vascular dementia (VaD)], 8 with amnestic mild cognitive impairment (aMCI), 34 with dementia with Lewy bodies (DLB), 8 with progressive supranuclear palsy (PSP) and 6 with VaD. Results: Significant differences were found among the 5 disease groups in the incidence and severity of HTS, and HDSR scores. Given the significant differences between AD and DLB in post hoc analyses, patients were dichotomized into AD-related (AD and aMCI) and AD-nonrelated (PSP, DLB and VaD) groups. Both incidence (41 vs. 17%, p = 0.002) and severity of HTS (0.80 ± 1.13 vs. 0.21 ± 0.60, p = 0.001) were significantly higher in the AD-related group, while average age and HDSR scores were comparable between both groups. AD-related disease, female gender and low HDSR score contributed significantly to the occurrence and severity of HTS. Conclusions: HTS can be a clinical marker of AD and aMCI, and may represent a type of excuse behavior as well as a sign of dependency on and trust in the caregivers.

Occurrence and Clinicotopographical Correlates of Brainstem Infarction in Patients with Diabetes Mellitus

BACKGROUND The goal of the study was to clarify the association between diabetes mellitus (DM) and brainstem infarctions (BSIs) and to investigate the clinicotopographic characteristics of BSIs in patients with diabetes. METHODS Data were retrospectively reviewed for 1026 consecutive patients admitted to our hospital because of acute cerebral infarctions from January 2004 to August 2010. Acute symptomatic BSIs were explored on radiologic images and classified into multiple infarctions with BSIs, multifocal BSIs, and monofocal BSIs. Isolated BSIs were further classified based on the vertical distribution into midbrain, pontine, and medullary infarctions, and on the horizontal distribution into anterior-dominant, posterior-dominant, and anterior/posterior BSIs. Neurologic symptoms of BSIs and clinical background were compared between DM and non-DM patients. RESULTS The prevalence of BSIs was 2.6-fold higher (P < .0001) in DM patients. Logistic regression analysis including age, sex, smoking, previous stroke, atrial fibrillation, other cardiac diseases, hypertension, hyperlipidemia, and DM showed that DM was independently associated with BSIs (odds ratio [OR] 2.814; 95% confidence interval [CI] 1.936-4.090; P < .0001). Compared with non-DM patients, DM patients showed more frequent monofocal BSIs (P < .0001) and multifocal BSIs (P = .0296). Monofocal BSIs (n = 114) more frequently involved the pons (P < .0001) and medulla (P = .0212). Anterior-dominant BSIs (P < .0001) were more common in DM patients than in non-DM patients. Symptoms of BSIs included more frequent motor paresis (P = .0180) and less frequent diplopia (P = .0298) in DM patients than in non-DM patients. CONCLUSIONS DM is important in the development of BSIs, and the associated clinical characteristics include more frequent motor paresis and less frequent diplopia.

Difficulty in identification of the frontal language area in patients with dominant frontal gliomas that involve the pars triangularis

OBJECTIVE Identification of language areas using functional brain mapping is sometimes impossible using current methods but essential to preserve language function in patients with gliomas located within or near the frontal language area (FLA). However, the factors that influence the failure to detect language areas have not been elucidated. The present study evaluated the difficulty in identifying the FLA in dominant-side frontal gliomas that involve the pars triangularis (PT) to determine the factors that influenced failed positive language mapping. METHODS Awake craniotomy was performed on 301 patients from April 2000 to October 2013 at Tokyo Womens Medical University. Recurrent cases were excluded, and patients were also excluded if motor mapping indicated their glioma was in or around the motor area on the dominant or nondominant side. Eighty-two consecutive cases of primary frontal glioma on the dominant side were analyzed for the present study. MRI was used for all patients to evaluate whether tumors involved the PT and to perform language functional mapping with a bipolar electrical stimulator. Eighteen of 82 patients (mean age 39 ± 13 years) had tumors that showed involvement of the PT, and the detailed characteristics of these 18 patients were examined. RESULTS The FLA could not be identified with intraoperative brain mapping in 14 (17%) of 82 patients; 11 (79%) of these 14 patients had a tumor involving the PT. The negative response rate in language mapping was only 5% in patients without involvement of the PT, whereas this rate was 61% in patients with involvement of the PT. Univariate analyses showed no significant correlation between identification of the FLA and sex, age, histology, or WHO grade. However, failure to identify the FLA was significantly correlated with involvement of the PT (p < 0.0001). Similarly, multivariate analyses with the logistic regression model showed that only involvement of the PT was significantly correlated with failure to identify the FLA (p < 0.0001). In 18 patients whose tumors involved the PT, only 1 patient had mild preoperative dysphasia. One week after surgery, language function worsened in 4 (22%) of 18 patients. Six months after surgery, 1 (5.6%) of 18 patients had a persistent mild speech deficit. The mean extent of resection was 90% ± 7.1%. Conclusions Identification of the FLA can be difficult in patients with frontal gliomas on the dominant side that involve the PT, but the positive mapping rate of the FLA was 95% in patients without involvement of the PT. These findings are useful for establishing a positive mapping strategy for patients undergoing awake craniotomy for the treatment of frontal gliomas on the dominant side. Thoroughly positive language mapping with subcortical electrical stimulation should be performed in patients without involvement of the PT. More careful continuous neurological monitoring combined with subcortical electrical stimulation is needed when removing dominant-side frontal gliomas that involve the PT.

5-Fluorouracil–induced Leukoencephalopathy with Acute Stroke-like Presentation Fulfilling Criteria for Recombinant Tissue Plasminogen Activator Therapy

A 61-year-old man underwent systemic chemotherapy with intravenous infusion of nedaplatin and 5-fluorouracil. On the day after the final drug administration, he suddenly experienced difficulty in speaking followed by left-sided weakness. His National Institutes of Health Stroke Scale score was 12. A computed tomographic scan of the brain performed 4 hours after symptom onset revealed no abnormalities. Because all eligibility criteria were fulfilled, he immediately underwent intravenous recombinant tissue plasminogen activator therapy. He recovered from neurologic complications on day 14. An initial magnetic resonance imaging scan of his brain revealed a hyperintense area in the bilateral white matter and corpus callosum, and these abnormalities had improved on the follow-up scan. We diagnosed him with 5-fluorouracil-induced leukoencephalopathy with acute stroke-like presentation. Our experience suggests that 5-fluorouracil-induced leukoencephalopathy potentially fulfills all eligibility criteria for recombinant tissue plasminogen activator therapy.

Cerebral microhemorrhage in Marchiafava-Bignami disease detected by susceptibility-weighted imaging.

Marchiafava–Bignami disease (MBD) is a rare alcohol-associated disorder. Clinical features include not only disturbed consciousness, dysarthria, tetraparesis, astasia-abasia, and symptoms of interhemispheric disconnection as initial symptoms but also cognitive deficits as clinical outcomes. The clinical significance of cerebral microhemorrhage (CMH) has been recognized in patients with cognitive deficits; however, the presence of CMH in patients with MBD has not been emphasized. The aim of the present study was to clarify the relationship between CMH and MBD. For this purpose, we report four patients with MBD, who showed asymmetrical hypointense areas in multiple cortico-subcortical regions on susceptibility-weighted imaging (SWI). All cases had a history of chronic alcohol abuse and symmetrical lesions in the entire corpus callosum. These patients’ clinical symptoms included not only coma, dysarthria, and astasia-abasia as initial symptoms but also dementia as a clinical outcome. SWI showed asymmetrical hypointense areas in the multiple cortico-subcortical regions, indicating the presence of CMH. Compared with patients with normal cognitive function, demented patients showed higher severity of CMH. Our report would indicate that CMH is an important factor indicating the severity of dementia in patients with MBD.

Left frontal glioma induces functional connectivity changes in syntax-related networks

BackgroundA glioma leads to a global loss of functional connectivity among multiple regions. However, the relationships between performance/activation changes and functional connectivity remain unclear. Our previous studies (Brain 137:1193–1212; Brain Lang 110:71–80) have shown that a glioma in the left lateral premotor cortex or the opercular/triangular parts of the left inferior frontal gyrus causes agrammatic comprehension accompanied by abnormal activations in 14 syntax-related regions. We have also confirmed that a glioma in the other left frontal regions does not affect task performances and activation patterns.ResultsBy a partial correlation method for the time-series functional magnetic resonance imaging data, we analyzed the functional connectivity in 21 patients with a left frontal glioma. We observed that almost all of the functional connectivity exhibited chaotic changes in the agrammatic patients. In contrast, some functional connectivity was preserved in an orderly manner in the patients who showed normal performances and activation patterns. More specifically, these latter patients showed normal connectivity between the left fronto-parietal regions, as well as normal connectivity between the left triangular and orbital parts of the left inferior frontal gyrus.ConclusionsOur results indicate that these pathways are most crucial among the syntax-related networks. Both data from the activation patterns and functional connectivity, which are different in temporal domains, should thus be combined to assess any behavioral deficits associated with brain abnormalities.