Frontal Cerebral Cortex Research Articles

SEXUAL DIMORPHISM OF THE EXTERNAL STRUCTURE OF CORPUS CALLOSUM BODY OF MIDDLE-AGED PEOPLE

The influence of ischemia-reperfusion of the brain up on Bcl-2+ morphometric parameters of the nerve and glial cells of the frontal cerebral lobe cortex of rats with diabetes mellitus has been studied. Bilateral carotid ischemia-reperfusion in animals with out disorders of carbohydrate metabolism has been found to disturb Bcl-2+ morphometric parameters of glial cells of the frontal cerebral lobe cortex on the 12th day of ischemicreperfusion period. In rats with three-month diabetes mellitus morphometric parameters of Bcl-2+-nerve cells undergo changes. Three-month streptozotocininduced diabetes modifies the reaction of morphometric parameters of Bcl-2+-nerve cells of the frontal lobe cortex in the early term of observation at the expense of changes of the coefficients of their shape and elongation, in the late one – at the expense of the latter; glial cells reaction is modified in the early term at the expense of cellular area, their coefficients of their shape and elongation, in the late one – at the expense of the area.

Cerebellar Amyloid-β Plaques: How Frequent Are They, and Do They Influence 18F-Florbetaben SUV Ratios?

Using immunohistochemistry to demonstrate Aβ plaques and vascular deposits, and using the Bielschowsky method to demonstrate neuritic plaques, we performed a neuropathologic assessment of the frontal, occipital, anterior cingulate, and posterior cingulate cerebral cortices and the cerebellar cortex of 87 end-of-life patients (64 with AD, 14 with other types of dementia, and 9 nondemented aged volunteers; mean age ± SD, 80.4 ± 10.2 y) who had undergone 18F-florbetaben PET before death. The lesions were rated as absent (none or sparse) or present (moderate or frequent). Mean cortical SUVRs were compared among cases with different cerebellar Aβ loads. None of the 83 evaluable cerebellar samples showed frequent diffuse Aβ or neuritic plaques; 8 samples showed frequent vascular Aβ deposits. Diffuse Aβ plaques were rated as absent in 78 samples (94%) and present in 5 samples (6%). Vascular Aβ was rated as absent in 62 samples (74.7%) and present in 21 samples (25.3%). No significant differences in cerebellar SUVs were found among cases with different amounts or types of Aβ deposits in the cerebral cortex. Both diffuse and neuritic plaques were found in the cerebral cortex of 26-44 cases. No significant SUVR differences were found between these brains with different cerebellar Aβ loads. The effect of cerebellar plaques on cortical 18F-florbetaben SUVRs appears to be negligible even in advanced stages of AD with a higher cerebellar Aβ load.

PlanHab: hypoxia exaggerates the bed-rest-induced reduction in peak oxygen uptake during upright cycle ergometry.

The study examined the effects of hypoxia and horizontal bed rest, separately and in combination, on peak oxygen uptake (V̇o2 peak) during upright cycle ergometry. Ten male lowlanders underwent three 21-day confinement periods in a counterbalanced order: 1) normoxic bed rest [NBR; partial pressure of inspired O2 (PiO2 ) = 133.1 ± 0.3 mmHg]; 2) hypoxic bed rest (HBR; PiO2 = 90.0 ± 0.4 mmHg), and 3) hypoxic ambulation (HAMB; PiO2 = 90.0 ± 0.4 mmHg). Before and after each confinement, subjects performed two incremental-load trials to exhaustion, while inspiring either room air (AIR), or a hypoxic gas (HYPO; PiO2 = 90.0 ± 0.4 mmHg). Changes in regional oxygenation of the vastus lateralis muscle and the frontal cerebral cortex were monitored with near-infrared spectroscopy. Cardiac output (CO) was recorded using a bioimpedance method. The AIR V̇o2 peak was decreased by both HBR (∼13.5%; P ≤ 0.001) and NBR (∼8.6%; P ≤ 0.001), with greater drop after HBR (P = 0.01). The HYPO V̇o2 peak was also reduced by HBR (-9.7%; P ≤ 0.001) and NBR (-6.1%; P ≤ 0.001). Peak CO was lower after both bed-rest interventions, and especially after HBR (HBR: ∼13%, NBR: ∼7%; P ≤ 0.05). Exercise-induced alterations in muscle and cerebral oxygenation were blunted in a similar manner after both bed-rest confinements. No changes were observed in HAMB. Hence, the bed-rest-induced decrease in V̇o2 peak was exaggerated by hypoxia, most likely due to a reduction in convective O2 transport, as indicated by the lower peak values of CO.

EARLY AND DELAYED REACTION OF BCL-2+ PROTEIN IN THE NERVE AND GLIAL CELLS OF THE FRONTAL LOBE CEREBRAL CORTEX IN RATS WITH EXPERIMENTAL DIABETES MELLITUS ON ACUTE CIRCULATORY

The activity of antiapoptotic processes in neurons and glial cell sof the frontal lobe cerebral cortex has been studied according to the change sof Bcl-2+ protein content in rats with streptosotocin induced diabetes mellitus in the dynamics of ischemic-reperfusion cerebral injury. 20 minute ischemia with one hour reperfusion in animals without diabetes mellitus concerning the control has been found to intensify antiapoptotic potential of the nerve cells of the frontal lobe cortex at the expense of increased general content of Bcl-2+ protein, and glial cells — at the expense of increased amount of Bcl-2+-cells. On the 12th day of the post-ischemic period the activity of antiapoptotic processes in the nerve cells remains increased, and in glial cells it decreases by means of reducing concentration of Bcl-2+ protein. Streptosotocin induced diabetes during three months does not affect the areal density of Bcl-2+-nerve cells and the content of Bcl-2+ protein in them, although it increases the areal density of Bcl-2+-glial cells considerably with less substantial decrease of Bcl-2+ protein content in them as compared to the appropriate indices in rats without this pathology. The nerve cells of the frontal lobe cerebral cortex of rats with diabetes mellitus in early and delayed ischemic-reperfusion periods present the activation of antiapoptotic mechanisms at the expense of increase of both the number of Bcl-2+-cells and the content of Bcl-2+ protein in them; in Bcl-2+-glial cells on the 12th day of the experiment the content of Bcl-2+ protein decreases inconsiderably against their unchanged amount.

Persistent Impact of In utero Irradiation on Mouse Brain Structure and Function Characterized by MR Imaging and Behavioral Analysis.

Prenatal irradiation is known to perturb brain development. Epidemiological studies revealed that radiation exposure during weeks 8–15 of pregnancy was associated with an increased occurrence of mental disability and microcephaly. Such neurological deficits were reproduced in animal models, in which rodent behavioral testing is an often used tool to evaluate radiation-induced defective brain functionality. However, up to now, animal studies suggested a threshold dose of around 0.30 Gray (Gy) below which no behavioral alterations can be observed, while human studies hinted at late defects after exposure to doses as low as 0.10 Gy. Here, we acutely irradiated pregnant mice at embryonic day 11 with doses ranging from 0.10 to 1.00 Gy. A thorough investigation of the dose-response relationship of altered brain function and architecture following in utero irradiation was achieved using a behavioral test battery and volumetric 3D T2-weighted magnetic resonance imaging (MRI). We found dose-dependent changes in cage activity, social behavior, anxiety-related exploration, and spatio-cognitive performance. Although behavioral alterations in low-dose exposed animals were mild, we did unveil that both emotionality and higher cognitive abilities were affected in mice exposed to ≥0.10 Gy. Microcephaly was apparent from 0.33 Gy onwards and accompanied by deviations in regional brain volumes as compared to controls. Of note, total brain volume and the relative volume of the ventricles, frontal and posterior cerebral cortex, cerebellum, and striatum were most strongly correlated to altered behavioral parameters. Taken together, we present conclusive evidence for persistent low-dose effects after prenatal irradiation in mice and provide a better understanding of the correlation between their brain size and performance in behavioral tests.

Dexmedetomidine Postconditioning Reduces Brain Injury after Brain Hypoxia-Ischemia in Neonatal Rats.

Perinatal asphyxia can lead to death and severe disability. Brain hypoxia-ischemia (HI) injury is the major pathophysiology contributing to death and severe disability after perinatal asphyxia. Here, seven-day old Sprague-Dawley rats were subjected to left brain HI. Dexmedetomidine was given intraperitoneally after the brain HI. Yohimbine or atipamezole, two α2 adrenergic receptor antagonists, were given 10min before the dexmedetomidine injection. Neurological outcome was evaluated 7 or 28days after the brain HI. Frontal cerebral cortex was harvested 6h after the brain HI. Left brain HI reduced the left cerebral hemisphere weight assessed 7days after the brain HI. This brain tissue loss was dose-dependently attenuated by dexmedetomidine. Dexmedetomidine applied within 1h after the brain HI produced this effect. Dexmedetomidine attenuated the brain HI-induced brain tissue and cell loss as well as neurological and cognitive dysfunction assessed from 28days after the brain HI. Dexmedetomidine postconditioning-induced neuroprotection was abolished by yohimbine or atipamezole. Brain HI increased tumor necrosis factor α and interleukin 1β in the brain tissues. This increase was attenuated by dexmedetomidine. Atipamezole inhibited this dexmedetomidine effect. Our results suggest that dexmedetomidine postconditioning reduces HI-induced brain injury in the neonatal rats. This effect may be mediated by α2 adrenergic receptor activation that inhibits inflammation in the ischemic brain tissues.

Delirium symptoms’ development during the intensive care unit post-surgery staying is related with reduced intraoperative cerebral oxygen saturation in the elderly subjected to cardiac surgery

Goal of studyOur aim was to examine whether cerebral frontal cortex O2 desaturation may be related with the development of delirium symptoms’ after cardiac surgery in the elderly during the intensive care unit (ICU) staying.Materials and methodsA prospective, before and after, longitudinal study in II-IV ASA class patients scheduled for cardiac surgery and undergoing intravenous general anesthesia with remifentanil plus propofol was done. Clinical and surgical parameters, cardiopulmonary function, intraoperative cerebral oxygen saturation (rSO2) and bispectral index were continuously recorded and corrected throughout the surgery. Severity of delirium was represented as a score of the Intensive Care Delirium Screening Checklist (ICDSC) during the patients’ stay in the ICU under the assumption that higher ICDSC score indicated severe delirium.Results and discussionPatients, n = 44, 77.3% male, aged 59.9 ± 1.9 years old, scheduled to coronary (36.4%), aortic valve replacement (18.2%), mitral valve replacement (13.6%), coronary plus valve replacement (13.6%) and others (18.2%) surgery, on pump 98.4% were enrolled. A reduction of the rSO2 higher than 10% at the end of the surgery compared with basal values was detected in a 46.5% of the patients. Reduction of rSO2 higher than 10% at the end of the surgery was related with significantly higher values of delirium symptoms’ development during the intensive care unit post-surgery staying (rSO2 higher ≥ 10% 68.8 vs. rSO2 higher < 10% 31.3%, P < 0.05).ConclusionDelirium symptoms’ development during the intensive care unit post-surgery staying is related with reduced intraoperative cerebral oxygen saturation in the elderly subjected to cardiac surgery.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Valproic acid stimulates proliferation of glial precursors during cortical gliogenesis in developing rat.

Valproic acid (VPA) is a neurotherapeutic drug prescribed for seizures, bipolar disorder, and migraine, including women of reproductive age. VPA is a well-known teratogen that produces congenital malformations in many organs including the nervous system, as well as later neurodevelopmental disorders, including mental retardation and autism. In developing brain, few studies have examined VPA effects on glial cells, particularly astrocytes. To investigate effects on primary glial precursors, we developed new cell culture and in vivo models using frontal cerebral cortex of postnatal day (P2) rat. In vitro, VPA exposure elicited dose-dependent, biphasic effects on DNA synthesis and proliferation. In vivo VPA (300mg/kg) exposure from P2 to P4 increased both DNA synthesis and cell proliferation, affecting primarily astrocyte precursors, as >75% of mitotic cells expressed brain lipid-binding protein. Significantly, the consequence of early VPA exposure was increased astrocytes, as both S100-β+ cells and glial fibrillary acidic protein were increased in adolescent brain. Molecularly, VPA served as an HDAC inhibitor in vitro and in vivo as enhanced proliferation was accompanied by increased histone acetylation, whereas it elicited changes in culture in cell-cycle regulators, including cyclin D1 and E, and cyclin-dependent kinase (CDK) inhibitors, p21 and p27. Collectively, these data suggest clinically relevant VPA exposures stimulate glial precursor proliferation, though at higher doses can elicit inhibition through differential regulation of CDK inhibitors. Because changes in glial cell functions are proposed as mechanisms contributing to neuropsychiatric disorders, these observations suggest that VPA teratogenic actions may be mediated through changes in astrocyte generation during development. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 780-798, 2016.

EPID-03MENINGIOANGIOMATOSIS ASSOCIATED WITH MICROCEPHALY AND DEVELOPMENTAL DELAY IN A PEDIATRIC PATIENT

BACKGROUND: Meningioangiomatosis is a rare benign lesion of the central nervous system characterized by focal leptomeningeal and meningovascular proliferation most commonly in the frontal and temporal cerebral cortex. Typically meningioangiomatosis presents with seizures and much less commonly headache, visual disturbance, limb weakness and personality change. Genetic mutations in Microcephalin1 (MCPH1) and ASPM (abnormal spindle like microcephaly) cause primary microcephaly and their role in carcinogenesis is being elucidated. CASE REPORT: A boy with global developmental delay due to microcephaly of undetermined etiology and vesicoureteral reflux presented with a new onset generalized tonic clonic seizure. He had a family history of developmental delay in male relatives (maternal uncle and brother) and a family history (maternal) of malignancy in female relatives (breast, mesothelioma, ovarian and uterine cancer). He had large low set ears, prominent jaw and normal testicles. MRI demonstrated a minimally enhancing vascular 1.9 x 1.9 x 1.5 cm lesion in the mesial right inferior frontal lobe predominantly in the superficial cortical gray matter. The lesion had a low intensity T2 signal and dense calcification along the periphery and a central zone of linear vascular enhancement. There was no associated vasogenic edema or any other abnormal MRI findings. The lesion was totally resected under image guidance. Histopathological examination showed meningoendothelial proliferation without atypical features. Intervening neurons immunoreactive with synaptophysin, GFAP and NeuN were seen. The final diagnosis was frontal lobe meningioangiomatosis. Fragile X syndrome testing was negative (FMR gene CGG repeat number: 32) and chromosomal microarray analysis was normal. Follow up MRIs have not demonstrated recurrence of the meningioangiomatosis and he has been seizure free on Levetiracetam/Topiramate therapy. CONCLUSION: We speculate that there is a genetic basis to the microcephaly and meningioangiomatosis in our patient perhaps involving genes in the X chromosome, MPCH1 or ASPM genes. Further testing is warranted.

Progressive Dopamine Transporter Binding Loss in Autopsy-Confirmed Corticobasal Degeneration

Corticobasal degeneration (CBD) is characterized by neuronal and glial deposition of 4-repeat tau in the frontal and parietal cerebral cortex, white matter and striatum. There is neuronal loss in affected cortical regions and in the substantia nigra (SN). Recent single photon emission tomography (SPECT) studies have reported normal striatal dopamine transporter (DAT) binding in individual patients with CBD. To study the pattern and course of DAT binding loss in CBD. We retrospectively analyzed DAT SPECT studies in two patients presenting with a corticobasal syndrome in whom a diagnosis of CBD was later confirmed pathologically. Baseline scans at 1.5 years after symptom onset revealed only mild abnormalities (reduced uptake in one putamen). Follow up scans at 4.5 years (Case 1) and 5 years (Case 2) after symptom onset showed a marked decline of striatal DAT binding. In both cases, there was a 37% binding reduction from the age-expected striatal binding value. Asymmetry of striatal DAT binding had increased from mild in the first SPECT studies to moderate at the time of their final imaging. CBD patients can have delayed neuronal loss in the SN. Follow up DAT imaging may be of value in patients with possible CBD and a normal baseline scan.

Multi-modal representation of effector modality in frontal cortex during rule switching.

We report a functional magnetic resonance imaging (fMRI) study which investigated whether brain areas involved in updating task rules within the frontal lobe of the cerebral cortex show activity related to the modality of motor response used in the task. Participants performed a rule switching task using different effector modalities. In some blocks participants responded with left/right button presses, whilst in other blocks left/right saccades were required. The color of a Cue event instructed a left or right response based upon a rule, followed by a Feedback which indicated whether the rule was to stay the same or “Flip” on the next trial. The findings revealed variation in the locus of activity within the ventrolateral frontal cortex dependent upon effector modality. Other frontal areas showed no significant difference in activity between response epochs but changed their pattern of connectivity with posterior cortical areas dependent upon response. Multivariate analysis revealed that the pattern of activity evoked by Flip rule Feedbacks within an apparently supra modal frontal region (dorsolateral frontal cortex) discriminated between response epochs. The results are consistent with the existence of multi-modal representations of stimulus-response (SR) rules within the frontal cerebral cortex.

The Possible Damaged Mechanism and the Preventive Effect of Monosialotetrahexosylganglioside in a Rat Model of Cerebral Ischemia-Reperfusion Injury

The pathogenesis of cerebral ischemia-reperfusion injury (CIRI) is not completely clear and therapies are limited now. Therefore, our study aimed to investigate the possible pathogenesis and preventive approach of CIRI through analyzing changes of aspartate (Asp), glutamate (Glu), mitochondrial calcium (MCa), calmodulin (CaM), and malondialdehyde (MDA) contents and ultramicropathology in hippocampus and cerebral cortex of ischemic susceptible injured regions and the effect of monosialotetrahexosylganglioside (GM1) in the rat model of CIRI. Contents of Asp, Glu, MCa, CaM, and MDA in hippocampus and cerebral cortex tissues were measured by a high-performance liquid chromatography, atomic absorption spectrophotometer, and ordinary spectrophotometer, respectively, changes of ultramicrostructure in neurons of the hippocampus CA1 region and frontal cerebral cortex were observed by a transmission electron microscope. Contents of Asp and Glu in hippocampus and cerebral cortex tissues of CIRI groups significantly decreased and contents of MCa, CaM, and MDA significantly increased than those in control groups, and the ultramicrostructure in neurons of the hippocampus CA1 region and frontal cerebral cortex revealed a significant damaged change, and GM1 significantly ameliorated changes of Asp, Glu, MCa, CaM, and MDA contents in hippocampus and ultrastructural changes in neurons of the hippocampus CA1 region and frontal cerebral cortex. Our findings further support that the abnormal release and/or reuptake of excitatory amino acid neurotransmitters, the disordered calcium homeostasis and the excessive production and/or reduced elimination of reactive oxygen species contribute to the pathogenesis of CIRI, and GM1 can partially prevent these pathogenesises to exert the protective effect on CIRI.

A Study of the Effect of Iron and Silicon As Cement Components on Cerebral and Cerebellar cortices of Albino Rats and the Possible Protective Role of Omega 3: A Toxicological and Histological Study

Introduction Cement industry generates dust during its production. The main route of entry of cement dust particles in the body is the respiratory tract and / or the gastrointestinal tract by inhalation or swallowing, producing both respiratory and non-respiratory systems involvement. Content of Portland cement is a mixture of elements that include iron and silicon. Yet, there is a lack of the studies concerned with the effects of cement on different organs in humans or animals. Therefore, the aim of the present study was to investigate the effect of two of cement components (silicon and iron) on brain tissues and the possible protective effect of omega-3. Material and methods fifty male adult albino rats were divided into three groups; Group I (control group), Group II (treated group) that was subdivided into three subgroups; subgroup IIa, received iron as ferrous chloride, subgroup IIb, received silicon as sodium silicate and subgroup IIc, received both elements orally for two months and Group III (protected group) received iron and silicon, simultaneously with omega- 3. Energy Dispersive X-ray Spectrometry (EDX) analysis was done. Frontal cerebral & cerebellar cortices were subjected for biochemical oxidative assay. Histological study and immunohistochemical staining for Glial fibrillary acidic protein (GFAP) were performed as well as morphometric study. Results cerebral & cerebellar cortices of treated rats (subgroup IIc) showed peaks for iron and silicon. The profile of oxidative stress markers, in group (II), revealed significantly decreased antioxidant enzymes activity, superoxide dismutase (SOD) and catalase (CAT), while malondialdehyde (MDA) level increased significantly as compared with control group. Histological findings of cerebral and cerebellar cortices revealed different degrees of degenerated nerve cells, tissue vacuolation, and degenerated neuropil in group II. Immunohistochemial results showed marked proliferation of astrocytes. The co-administration of omega-3 (group III) showed significant increase of both SOD and CAT activities and significant decrease of MDA. Marked preservation of cerebral and cerebellar cortical tissues was noticed. Conclusion The present work revealed the hazardous effect of cement component (iron and silicon) on cerebral & cerebellar cortices of albino rats. The role of protective effect of omega-3 might find a clinical application against the hazardous effect among the exposed workers. Further studies are needed to magnitude the problem on health.

Cortical EEG components that reflect inverse effectiveness during visuotactile integration processing

Multisensory integration is required to interpret information from multiple senses and then produce the appropriate behavioral output. Inverse effectiveness, a phenomenon in which weaker stimuli induce greater activation of multisensory neurons than do stronger stimuli, is an essential component of multisensory integration. The superior colliculus is especially abundant in multisensory neurons with properties of inverse effectiveness. However, multisensory neurons are distributed throughout the brain, suggesting that a wide range of brain regions are involved in generating multisensory behavior in addition to the superior colliculus. In this study, we aimed to use scalp EEG to elucidate the cortical responses that respond to multisensory stimuli according to the principle of inverse effectiveness. By modulating the intensity of the tactile aspect of a simultaneous visuotactile stimulus, we explored the time–frequency component of scalp EEG waveforms produced during multi-sensory stimulation. Using this method, we determined the relative values and temporal dynamics of the increment of power spectrum (event-related spectrum perturbation) and phase coherence across trials (e.g., inter-trial phase coherency) produced by multisensory stimulation compared to unisensory stimulation. In the somatosensory and anterior cingulate cortices, we observed significant differences in the inter-trial phase coherence of the theta band oscillation 200–400ms post-stimulus, in response to visuotactile (multisensory) and tactile (unisensory) stimulation, while no differences were found in later time windows and other cortical areas. These results suggest that inverse effectiveness is an important aspect of multi-sensory processing in the somato-sensory and frontal cerebral cortices.

Systemic oxidative-nitrosative-inflammatory stress during acute exercise in hypoxia; implications for microvascular oxygenation and aerobic capacity.

Exercise performance in hypoxia may be limited by a critical reduction in cerebral and skeletal tissue oxygenation, although the underlying mechanisms remain unclear. We examined whether increased systemic free radical accumulation during hypoxia would be associated with elevated microvascular deoxygenation and reduced maximal aerobic capacity (V̇O2 max ). Eleven healthy men were randomly assigned single-blind to an incremental semi-recumbent cycling test to determine V̇O2 max in both normoxia (21% O2) and hypoxia (12% O2) separated by a week. Continuous-wave near-infrared spectroscopy was employed to monitor concentration changes in oxy- and deoxyhaemoglobin in the left vastus lateralis muscle and frontal cerebral cortex. Antecubital venous blood samples were obtained at rest and at V̇O2 max to determine oxidative (ascorbate radical by electron paramagnetic resonance spectroscopy), nitrosative (nitric oxide metabolites by ozone-based chemiluminescence and 3-nitrotyrosine by enzyme-linked immunosorbent assay) and inflammatory stress biomarkers (soluble intercellular/vascular cell adhesion1 molecules by enzyme-linked immunosorbent assay). Hypoxia was associated with increased cerebral and muscle tissue deoxygenation and lower V̇O2 max (P<0.05 versus normoxia). Despite an exercise-induced increase in oxidative-nitrosative-inflammatory stress, hypoxia per se did not have an additive effect (P>0.05 versus normoxia). Consequently, we failed to observe correlations between any metabolic, haemodynamic and cardiorespiratory parameters (P>0.05). Collectively, these findings suggest that altered free radical metabolism cannot explain the elevated microvascular deoxygenation and corresponding lower V̇O2 max in hypoxia. Further research is required to determine whether free radicals when present in excess do indeed contribute to the premature termination of exercise in hypoxia.

Aberrant Cortical Morphometry in the 22q11.2 Deletion Syndrome

BackgroundThere is increased risk of developing psychosis in 22q11.2 deletion syndrome (22q11DS). Although this condition is associated with morphologic brain abnormalities, simultaneous examination of multiple high-resolution measures of cortical structure has not been performed. MethodsFifty-three patients with 22q11DS, 30 with psychotic symptoms, were compared with demographically matched nondeleted youths: 53 typically developing and 53 with psychotic symptoms. High-resolution magnetic resonance imaging measures of cerebral volume, cortical thickness, surface area, and an index of local gyrification were obtained and compared between groups. ResultsPatients with 22q11DS demonstrated global increases in cortical thickness associated with reductions in surface area, reduced index of local gyrification, and lower cerebral volumes relative to typically developing controls. Findings were principally in the frontal lobe, superior parietal lobes, and in the paramedian cerebral cortex. Focally decreased thickness was seen in the superior temporal gyrus and posterior cingulate cortex in 22q11DS relative to nondeleted groups. Patterns between nondeleted participants with psychotic symptoms and 22q11DS were similar but with important differences in several regions implicated in schizophrenia. Post hoc analysis suggested that like the 22q11DS group, cortical thickness in nondeleted individuals with psychotic symptoms differed from typically developing controls in the superior frontal gyrus and superior temporal gyrus, regions previously linked to schizophrenia. ConclusionsSimultaneous examination of multiple measures of cerebral architecture demonstrates that differences in 22q11DS localize to regions of the frontal, superior parietal, superior temporal, and paramidline cerebral cortex. The overlapping patterns between nondeleted participants with psychotic symptoms and 22q11DS suggest partially shared neuroanatomic substrates.

Construction and analysis of the protein-protein interaction networks based on gene expression profiles of Parkinson's disease.

BackgroundParkinson's Disease (PD) is one of the most prevailing neurodegenerative diseases. Improving diagnoses and treatments of this disease is essential, as currently there exists no cure for this disease. Microarray and proteomics data have revealed abnormal expression of several genes and proteins responsible for PD. Nevertheless, few studies have been reported involving PD-specific protein-protein interactions.ResultsMicroarray based gene expression data and protein-protein interaction (PPI) databases were combined to construct the PPI networks of differentially expressed (DE) genes in post mortem brain tissue samples of patients with Parkinson's disease. Samples were collected from the substantia nigra and the frontal cerebral cortex. From the microarray data, two sets of DE genes were selected by 2-tailed t-tests and Significance Analysis of Microarrays (SAM), run separately to construct two Query-Query PPI (QQPPI) networks. Several topological properties of these networks were studied. Nodes with High Connectivity (hubs) and High Betweenness Low Connectivity (bottlenecks) were identified to be the most significant nodes of the networks. Three and four-cliques were identified in the QQPPI networks. These cliques contain most of the topologically significant nodes of the networks which form core functional modules consisting of tightly knitted sub-networks. Hitherto unreported 37 PD disease markers were identified based on their topological significance in the networks. Of these 37 markers, eight were significantly involved in the core functional modules and showed significant change in co-expression levels. Four (ARRB2, STX1A, TFRC and MARCKS) out of the 37 markers were found to be associated with several neurotransmitters including dopamine.ConclusionThis study represents a novel investigation of the PPI networks for PD, a complex disease. 37 proteins identified in our study can be considered as PD network biomarkers. These network biomarkers may provide as potential therapeutic targets for PD applications development.

Autoantibodies against Muscarinic Acetylcholine Receptor on Exocrine Glands in Sjögren Syndrome

These investigations demonstrate that serum antibodies against muscarinic acetylcholine receptors (mAChR) in primary Sjogren syndrome (pSS) and associated Sjogren syndrome (aSS) bind and activate both cholinergic receptors of M3 in salivary gland and M1 in neonatal myocardium and in the cerebral frontal cortex area subtypes; triggering the production of the second messengers and proinflammatory mediators related to mAChR activation. In this way the cholinergic autoantibodies damages these receptors, which thus starts acting as an antigen. On this basis M3 and M1 mAChR IgG can be considered new markers of pSS/aSS allowing the differentiation between dry eye and mouth of autoimmune and non-autoimmune nature. Given that cholinergic autoantibodies also deregulate the parasympathetic system of the target organs, they can also be seen as a new factor contributing to the etiopathology of the syndrome.

Reduced Threshold Potential of the Trigeminal Nerve in Equine Headshaking

AimAlthough the aetiopathogenesis of headshaking remains elusive, trigeminal neuralgia is regarded as the likely explanation of observed clinical signs. The aim of this study was to compare sensory nerve conduction threshold and velocity of the trigeminal nerve using the infraorbital nerve in control and headshaking horses.MethodsControl group (n = 6 horses) and headshaking group (n = 6) were subject to general anaesthesia. A Nicolet Viking IV evoked potential system was used for sensory nerve conduction study. Stimulating, recording and reference electrodes were used. A pair of stimulating electrodes was placed at the gingival mucosa, one each at the rostral and caudal aspects of the maxillary canine tooth. Four pairs of recording electrodes were placed at 4 different points along the tract of the infraorbital nerve (point 1 at infraorbital foramen), maxillary nerve (point 2 at exit of trigeminal canal), spinal somatosensory (point 3 at level of C1 spinal cord segment), and cortical somatosensory evoked potentials (point 4 at level of frontal cerebral cortex). A reference electrode was placed at a distance half way between the stimulating and recording electrodes at point 1. Stimuli were applied at 2.5, 5, 10, 15, 20 mA. The duration of each stimulus was 0.1 ms. Thresholds were recorded and conduction velocities calculated for each group.ResultsThe threshold of sensory nerve action potential occurred at low stimuli (2.5 and 5 mA) in horses with headshaking; and at higher stimuli (10 mA in 3 horses, 15 mA in 1 horse, and 25 mA in 2 horses) in control horses. Although there were differences in conduction velocity between groups, this was not significant.Conclusions and practical significanceHeadshaking horses have a low threshold for inducing sensory action potentials upon minimal stimulation compared with control horses supporting involvement of the trigeminal nerve in the pathogenesis of affected horses.Ethical animal researchStudy approved by the UC Davis IACUC. Sources of funding: Private donation. Competing interests: None.

Learning and switching between stimulus-saccade associations in Parkinson’s disease

Making flexible associations between what we see and what we do is important for many everyday tasks. Previous work in patients with focal lesions has shown that the control of saccadic eye movements in such contexts relies on a network of areas in the frontal cerebral cortex. These regions are reciprocally connected with structures in the basal ganglia although the contribution of these sub-cortical structures to oculomotor control in complex tasks is not well understood. We report the performance of patients with idiopathic Parkinsons disease (PDs) in a test which required learning and switching between arbitrary cue-saccade rules. In Experiment 1 feedback was given following each response which reliably indicated which of the two possible rules was correct. PDs were slower to learn the first cue-saccade association presented, but did not show increased error or reaction time switch costs when switching between two rules within blocks. In a follow up experiment the feedback given by the computer was adjusted to be probabilistic such that executing a response based upon the “correct” rule only resulted in positive feedback on 80% of trials. Under these conditions patients were impaired in terms of response latencies and number of errors. In all conditions PDs showed multi-stepping/hypometria of saccades consistent with a motoric deficit in executing actions based on cognitive cues. The findings are consistent with a role for the nigrostriatal dopamine system in the reinforcement of saccade-response-outcome associations. Intact performance of PDs when associations are not stochastically reinforced suggests that striatal learning systems are complemented by cognitive representations of task rules which are unaffected in the early stages of PD.