Social cognition and its relationship to functional outcomes in patients with sustained acquired brain injury

Deficits in social cognition are common after traumatic brain injury (TBI). However, little is known about how such deficits affect functional outcomes. The purpose of this study was to investigate the relationship between social cognition and functional outcomes in patients with TBI. We studied this relationship in 20 patients with TBI over the course of 1 year post-injury. Patients completed neurocognitive assessments and social cognition tasks. The social cognition tasks included an emotion-perception task and three theory of mind tasks: the Faux Pas test, Reading the Mind in the Eyes (Eyes) test, and the Moving-Shapes paradigm. The Craig Handicap Assessment and Reporting Technique was used to assess functional outcomes. Compared with our database of normal subjects, patients showed impairments in all social cognition tasks. Multiple regression analysis revealed that theory of mind ability as measured by the Eyes test was the best predictor of the cognitive aspects of functional outcomes. The findings of this pilot study suggest that the degree to which a patient can predict what others are thinking is an important measure that can estimate functional outcomes over 1 year following TBI

Reduced gray matter volume is correlated with frontal cognitive and behavioral impairments in Parkinson\u27s disease

Objective: To identify the brain-volume reductions associated with frontal cognitive and behavioral impairmentsin Parkinson\u27s disease (PD).Methods: Forty PD patients without dementia or amnesia (Hoehn and Yahr stage 3) and 10 age-matched controlsunderwent brain magnetic resonance imaging. Cognitive and behavioral impairments were assessed by using theFrontal Assessment Battery (FAB) and Frontal Systems Behavioral Scale (FrSBe), respectively. We applied voxelbasedmorphometry to investigate the correlations of regional gray matter volume with FAB, FrSBe, and physicaldisability.Results: FAB was significantly lower in PD than in controls. FrSBe was significantly higher after PD onset thanbefore, notably in the apathy subscale. FAB and FrSBe were significantly intercorrelated. In PD patients, leftinferior frontal volume was positively correlated with FAB, whereas right precentral volume was negativelycorrelated with FrSBe total score. The brain volumes in both of these regions were not correlated with theUnified PD Rating Scale III.Conclusion: Behavioral impairments in PD tended to coexist with progression of frontal cognitive impairment.Regional atrophy within the frontal lobe was associated with both frontal cognitive and behavioral impairments.However, the specific region responsible for behavioral impairment differed from that for frontal cognitiveimpairment. These associations were independent of physical disability

Frontal assessment battery and frontal atrophy in amyotrophic lateral sclerosis

Objectives: To determine the potential utility of the frontal assessment battery (FAB)in assessing cognitive impairments in amyotrophic lateral sclerosis (ALS), we investigatedthe association between the FAB score and regional gray matter volume, andascertained whether the regional brain alterations related to cognitive impairmentsoccur in relatively mild stage of ALS.Materials and Methods: Twenty-fourALS patients with a Mini-MentalStateExamination score of >23, a normal score on the Self-RatingDepression Scale, little orno disturbance in speech and handling utensils on the ALS Functional Rating Scale(ALSFRS), and normal measures on respiratory tests (respiratory function test and arterialblood gas analysis), and two age-matchednormal control groups (one for FABassessment and the other for brain morphometry) underwent FAB testing and structuralmagnetic resonance imaging. We applied voxel-basedmorphometry to investigatethe relationship between the FAB score and regional brain alteration, andassessed the relationship between the altered regional brain volume and ALSFRS orrespiratory tests.Results: Frontal assessment battery scores were significantly lower in ALS patientsthan in normal controls. Volume reduction in the right orbitofrontal gyrus in ALS wascorrelated with a lower FAB score. There was no correlation between the right orbitofrontalgyrus volume and ALSFRS or respiratory tests.Conclusions: The results suggest that the FAB is an adequate tool for detecting cognitiveimpairments related to frontal lobe pathology in the relatively mild stage of ALS,independent of physical dysfunctions

Correlation of frontal atrophy with behavioral changes in amyotrophic lateral sclerosis

Background: Recent studies have linked cognitive impairment in amyotrophic lateral sclerosis (ALS) to frontotemporal pathology. Aim: We examined possible associations between behavior changes and regional gray matter volume in early ALS and assessed whether the volume changes were independent of physical impairments. Methods: Seventeen ALS patients with Mini-Mental State Examination ≥24, no need for assistance in daily life, normal respiratory tests (respiratory function test and arterial blood gas analytes), and eleven age-matched controls, underwent structural MRI. Behavioral changes were assessed with family-rating Frontal Systems Behavior Scale (FrSBe). We applied voxel-based morphometry to investigate the correlation between FrSBe and gray matter volume and assessed the correlation of volume with ALS Functional Rating Scale (ALSFRS) and respiratory tests. Results: Current FrSBe were significantly higher than retrospective scores assessing the status before onset, most notably in apathy. The volumes of right middle and left medial frontal gyri in ALS were negatively correlated with FrSBe, whereas they were not correlated with ALSFRS and respiratory tests. The volume of right frontal cluster, but not left medial frontal cluster, was significantly smaller than that of controls. Conclusions: Regional atrophy within frontal lobe was associated with behavioral dysfunction in early ALS, this association was independent of physical factors

Insular gray matter volume and objective quality of life in schizophrenia

Improving quality of life has been recognized as an important outcome for schizophrenia treatment, although the fundamental determinants are not well understood. In this study, we investigated the association between brain structural abnormalities and objective quality of life in schizophrenia patients. Thirty-three schizophrenia patients and 42 age-, sex-, and education-matched healthy participants underwent magnetic resonance imaging. The Quality of Life Scale was used to measure objective quality of life in schizophrenia patients. Voxel-based morphometry was performed to identify regional brain alterations that correlate with Quality of Life Scale score in the patient group. Schizophrenia patients showed gray matter reductions in the frontal, temporal, limbic, and subcortical regions. We then performed voxel-based multiple regression analysis in these regions to identify any correlations between regional gray matter volume and Quality of Life Scale scores. We found that among four subcategories of the scale, the Instrumental Role category score correlated with gray matter volume in the right anterior insula in schizophrenia patients. In addition, this correlation was shown to be mediated by negative symptoms. Our findings suggest that the neural basis of objective quality of life might differ topographically from that of subjective QOL in schizophrenia

Role of the JNK pathway in thrombin-induced ICAM-1 expression in endothelial cells

Objective: Thrombin induces leukocyte adherence to endothelial cells via increased expression of intercellular adhesion molecule-1 (ICAM-1). Although ICAM-1 expression is regulated by NF-kappa B, recent studies have suggested that additional signaling mechanisms may also be involved. The goal of this study was to determine whether mitogen-activated protein (MAP) kinases, including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 MAP kinase (p38), mediate thrombin-induced ICAM-1 expression in endothelial cells.Methods: Western blot analysis using anti-ICAM-1 antibody and luciferase assays were performed in cultured endothelial cells after addition of signal transduction inhibitors or transfection of various gene constructs. JNK kinase activity was determined by a kinase assay using c-Jun as a substrate or by Western blot analysis with anti-phospho-JNK antibody.Results: Treatment of endothelial cells with the JNK-specific inhibitors, SP600125 or JNK inhibitory peptide 1 (JNKI1), resulted in a significant decrease in thrombin-induced ICAM-1 expression as demonstrated by Western blot analysis (67 +/- 3 0x1.535a8bfffb01p-890nd 72 +/- 7%, respectively). In contrast, inhibitors of MEK and p38 had only minimal effect. The combination of SP600125 and the NF-kappa B inhibitor, BAY 11-7082, resulted in complete inhibition of thrombin-induced ICAM-1 expression. The G(alpha q) inhibitor, YM-254890, inhibited thrombin-induced JNK activation and ICAM-1 expression. Dominant-negative Ras and Rac1, but not Rho, inhibited thrombin-induced JNK activation and ICAM-1 promoter activity. Finally, thrombin-induced JNK activation and ICAM-1 promoter activity were inhibited by beta ARK1ct (a G beta gamma subunit scavenger) and Csk.Conclusions: These data suggest that, in concert with NF-kappa B, JNK regulates thrombin-induced ICAM-1 expression by a mechanism that is dependent on G(alpha q), G beta gamma, Ras, Rac1 and the Src kinase family