Altered effective connectivity during working memory performance in schizophrenia: a study with fMRI and structural equation modeling

The present study aimed to explore altered effective connectivity in schizophrenic patients while performing a 2-back working memory task. Twelve right-handed, schizophrenic patients treated with typical or atypical antipsychotics and 6 healthy control subjects were studied with fMRI while performing a "2-back" working memory task. Effective connectivity within a cortical-subcortical-cerebellar network for mnemonic information processing was assessed and compared between both groups. The path model included cortico-cortical connections comprising the parietal association cortex, ventrolateral prefrontal cortex (VLPFC), and the dorsolateral prefrontal cortex (DLPFC) as well as a cortico-cerebellar feedback loop comprising prefrontal cortex, contralateral cerebellum, and thalamus. Group differences were analyzed with a stacked models approach. Relative to normal controls, both patient groups revealed a pattern of reduced connectivity within the prefrontal-cerebellar and the cerebellar-thalamic limbs but enhanced connectivity in the thalamo-cortical limb of the cortical-cerebellar circuit. Moreover, a direct comparison of both treatment groups revealed enhanced connectivity in the interhemispheric connections between the cortical association areas in patients treated with atypical antipsychotics. However, right prefrontal and left parieto-frontal path coefficients were lower in the patient group receiving atypical antispychotic drugs. The findings suggest that the relationship between pathology in cortical-subcortical cerebellar networks and associated functional connectivity is complex and may include aspects of increased and decreased levels of connectivity consistent with the notion of "cognitive dysmetria" in schizophrenia. The observed pronounced connectivity within thalamo-cortical projections could be attributed to a compensatory increase of thalamic input in the presence of disrupted effective connectivity within the preceding limb of the cortical-cerebellar circuitry. The study demonstrated the feasibility of structural equation modeling for the investigation of group and treatment-related differences in effective connectivity and provides a promising approach to further disentangle the relationship between altered functional capacity and associated fMRI signal changes.     

Fetal surgery for repair of myelomeningocele allows normal development of anal sphincter muscles in sheep

One major problem for patients with myelomeningocele (MMC) is fecal incontinence. To prevent this problem, fetal surgery for repair of MMC has been recently undertaken. The strategy behind this surgery is to allow normal development of anal sphincter muscles. The purpose of this study was to determine whether fetal surgery for repair of MMC allows normal development of anal sphincter muscles. Myelomeningocele was surgically created in fetal sheep at 75 days of gestation. At 100 days of gestation, fetal surgery for repair of the MMC lesion was performed. Three repair methods were used: standard neurosurgical repair (4 fetal sheep), covering the MMC lesion with Alloderm (2 fetal sheep), and covering the MMC lesion with Gore-Tex (2 fetal sheep). After the sheep were delivered (140 days of gestation), external and internal anal sphincter muscles were analyzed histopathologically. In control fetal sheep (not repaired) anal sphincter muscles did not develop normally. In contrast, in fetal sheep that underwent repair of the MMC, the external and internal anal sphincter muscles developed normally. Histopathologically, in the external sphincter muscles, muscle fibers were dense. In the internal sphincter muscles, endomysial spaces were small, myofibrils were numerous, and fascicular units were larger than those in unrepaired fetal sheep. There was no difference in muscle development for the repair methods. Fetal surgery for repair of MMC allows normal development of anal sphincter muscles.     

Diagnosis of interstitial lung disease in children

Chronic interstitial lung disease (ILD) in infants and children is a challenging diagnostic clinical problem. There are many unresolved and controversial issues in the diagnosis of this heterogeneous group of uncommon disorders in children. Diagnosis requires a high index of suspicion as the initial clinical manifestations are subtle, highly variable and non-specific. There is no consensus for the clinical diagnostic criteria of paediatric ILD. The spectrum of clinical findings is highly variable. The diagnostic evaluation of a child with suspected ILD includes a comprehensive history, physical examination, oxygen saturation (at rest, during exercise or during feeding), a plain chest x ray and a high-resolution thin-cut tomography scan of the chest. Pulmonary function studies can be useful in older children; these typically show a restrictive pattern with a decreased forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and total lung capacity, but normal FEV(1)/FVC. A systematic approach to diagnosis is useful in the evaluation of an infant or child with suspected chronic ILD. Due to the rarity of most of these disorders, multi-centre collaboration is needed to improve our understanding of this orphan lung disease.     

Epidermal growth factor receptor and activated epidermal growth factor receptor expression in gastrointestinal carcinoids and pancreatic endocrine carcinomas.

The epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of many tumors. To analyze the expression of EGFR and activated EGFR in well-differentiated neuroendocrine carcinomas including primary and metastatic gastrointestinal carcinoid tumors and pancreatic endocrine tumors (PET), we examined 58 gastrointestinal carcinoid tumors and 48 PET using immunohistochemistry, Western blotting, and RT-PCR. EGFR and activated EGFR (P-EGFR) were expressed by both gastrointestinal carcinoids and PET in primary and metastatic tumors, although a higher percentage of gastrointestinal carcinoid tumors expressed EGFR and activated EGFR. Western blotting detected a 170 kDa band for both EGFR and activated EGFR in three primary carcinoid tumors and two metastatic carcinoid tumors to the liver. RT-PCR analysis confirmed the expression of EGFR mRNA in both primary and metastatic carcinoid tumors. Patients with activated EGFR expression in their primary PET had a significantly worse prognosis compared to those who did not express activated-EGFR (P = 0.043). These results indicate that gastrointestinal carcinoid tumors as well as PET express EGFR and activated EGFR, and that expression is more common in gastrointestinal carcinoid tumors compared to pancreatic endocrine tumors. These findings implicate the EGFR and P-EGFR signal transduction pathway in the pathogenesis of these neuroendocrine tumors and suggest that targeted therapy directed against the EGFR tyrosine kinase domain may be a useful therapeutic approach in patients with unresectable metastatic gastrointestinal carcinoid tumors and pancreatic endocrine tumors.     

Covert attention in touch: behavioral and ERP evidence for costs and benefits

To investigate the mechanism underlying tactile spatial attention, reaction times (RTs) and event-related potentials (ERPs) were recorded in response to mechanical stimuli delivered to the hands. At the start of each trial cues indicated either the correct (valid) or incorrect (invalid) tactile stimulus location or were uninformative (neutral). RT costs (suppression of invalid compared to neutral trials) were found to be larger than benefits (enhancement of valid compared to neutral trials). ERPs showed that costs and benefits contribute equally to attentional modulations of the somatosensory N140 component, whereas these were largely due to costs at longer latencies. These results differ from the pattern of attentional ERP modulations previously found for vision and audition, where costs precede benefits, and therefore suggest that the mechanisms of attentional selectivity in touch might be different from attentional processes in other modalities.