Parietotemporal Cortex Research Articles

The Disconnection Hypothesis inAlzheimer's Disease Studied Through Multimodal Magnetic Resonance Imaging: Structural, Perfusion, and Diffusion Tensor Imaging.

According to the so-called disconnection hypothesis, the loss of synaptic inputs from the medial temporal lobes (MTL) in Alzheimer's disease (AD) may lead to reduced activity of target neurons in cortical areas and, consequently, to decreased cerebral blood flow (CBF) in those areas. The aim of this study was to assess whether hypoperfusion in parietotemporal and frontal cortices of patients with mild cognitive impairment who converted to AD (MCI-c) and patients with mild AD is associated with atrophy in the MTL and/or microstructural changes in the white matter (WM) tracts connecting these areas. We assessed these relationships by investigating correlations between CBF in hypoperfused areas, mean cortical thickness in atrophied regions of the MTL, and fractional anisotropy (FA) in WM tracts. In the MCI-c group, a strong correlation was observed between CBF of the superior parietal gyri and FA in the parahippocampal tracts (left: r = 0.90, p < 0.0001; right: r = 0.597, p = 0.024), and between FA in the right parahippocampal tract and the right precuneus (r = 0.551, p = 0.041). No significant correlations between CBF in hypoperfused regions and FA in the WM tract were observed in the AD group. These results suggest an association between perfusion deficits and altered WM tracts in prodromal AD, while microvasculature impairments may have a greater influence in more advanced stages. We did not find correlations between cortical thinning in the medial temporal lobes and decreased FA in the WM tracts of the limbic system in either group.

Lipopolysaccharide preconditioning prevents acceleration of kindling epileptogenesis induced by traumatic brain injury

10–20% of symptomatic epilepsies are post-traumatic. We examined effect of LPS preconditioning on epileptogenesis after controlled cortical impact (CCI). LPS (0.01, 0.1 and 0.5mg/kg) was injected i.p. to rats 5days before induction of CCI to parieto-temporal cortex. Kindling started 24h after CCI by i.p. injection of 30mg/kg of pentylenetetrazole every other day until manifestation of 3 consecutive generalized seizures. CCI injury accelerated the rate of kindled seizures acquisition. LPS (0.1 and 0.5mg/kg) prevented the acceleration of kindling. LPS preconditioning significantly decreased IL-1β and TNF-α over-expression and the number of damaged neurons in the hippocampus of traumatic rats.

Cognitive dysfunction in patients with very mild Alzheimer's disease and amnestic mild cognitive impairment showing hemispheric asymmetries of hypometabolism on ¹⁸F-FDG PET.

We investigated cognitive dysfunction in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) who present hemispheric asymmetries of cerebral metabolic rate of glucose (CMRglc) decrease on (18) F-fluorodeoxyglucose positron emission tomography. Based on the hemispheric asymmetries of CMRglc decrease in the posterior cingulate cortex, precuneus, and parietotemporal cortex, the patients were divided into three groups (a left-dominant hypometabolism group, a right-dominant hypometabolism group, and a non-dominant hypometabolism group). CMRglc decrease in the whole brain was controlled among the three groups. All the patients underwent mini-mental state examination (MMSE), Wechsler Memory Scale-Revised (WMS-R), and Wechsler Adult Intelligent Scale-Third (WAIS-III). There were no significant differences in MMSE and WAIS-III scores among the three groups. In WMS-R, the results indicated that the left-dominant group demonstrated significantly lower scores in verbal memory than the other two groups. Furthermore, the left-dominant group had a greater tendency to be diagnosed with AD rather than aMCI. Patients with AD and aMCI showing left-dominant hypometabolism tend to show severer impairment in verbal memory function and to be diagnosed with AD dementia.

Dissecting the function of networks underpinning language repetition.

In the nineteenth century, ground-breaking observations on aphasia by Broca (1865) and Wernicke (1906) suggested that language function depends on the activity of the cerebral cortex. At the same time, Wernicke (1906) and Lichtheim (1885) also elaborated the first large-scale network model of language which incorporated long-range and short-range (transcortical connections) white matter pathways in language processing. The arcuate fasciculus (dorsal stream) was traditionally viewed as the major language pathway for repetition, but scientists also envisioned that white matter tracts traveling through the insular cortex (ventral stream) and transcortical connections may take part in language processing. Modern cognitive neuroscience has provided tools, including neuroimaging, which allow the in vivo examination of short- and long-distance white matter pathways binding cortical areas essential for verbal repetition. However, this state of the art on the neural correlates of language repetition has revealed contradictory findings, with some researchers defending the role of the dorsal and ventral streams, whereas others argue that only cortical hubs (Sylvian parieto-temporal cortex [Spt]) are crucially relevant. An integrative approach would conceive that the interaction between these structures is essential for verbal repetition. For instance, different sectors of the cerebral cortex (e.g., Spt, inferior frontal gyrus/anterior insula) act as hubs dedicated to short-term storage of verbal information or articulatory planning and these areas in turn interact through forward and backward white matter projections. Importantly, white matter pathways should not be considered mere cable-like connections as changes in their microstructural properties correlate with focal cortical activity during language processing tasks. Despite considerable progress, many outstanding questions await response. The articles in this Research Topic tackle many different and critical new questions, including: (1) how white matter pathways instantiate dialogues between different cortical language areas; (2) what are the specific roles of different white matter pathways in language functions in normal and pathological conditions; (3) what are the language consequences of discrete damage to branches of the dorsal and ventral streams; (4) what are the consequences (e.g., release from inhibition) of damage to the left white matter pathways in contralateral ones and viceversa; (5) how these pathways are reorganized after brain injury; (5) can the involvement/sparing of white matter pathways be used in outcome prediction and treatment response; and (5) can the microstructure of white matter pathways be remodeled with intensive rehabilitation training or biological approaches. This Research Topic includes original studies, and opinion and review articles which describe new data as well as provocative and insightful interpretations of the recent literature on the role of white matter pathways in verbal repetition in normal and pathological conditions. A brief highlight summary of each is provided below.

Activity of P-Glycoprotein, a β-Amyloid Transporter at the Blood-Brain Barrier, Is Compromised in Patients with Mild Alzheimer Disease.

Studies in animals and postmortem human brain tissue support a role for P-glycoprotein in clearance of cerebral β-amyloid across the blood-brain barrier (BBB). We tested the hypothesis that BBB P-glycoprotein activity is diminished in Alzheimer disease (AD) by accounting for an AD-related reduction in regional cerebral blood flow (rCBF). We compared P-glycoprotein activity in mild-AD patients (n = 9) and cognitively normal, age-matched controls (n = 9) using PET with a labeled P-glycoprotein substrate, (11)C-verapamil, and (15)O-water to measure rCBF. BBB P-glycoprotein activity was expressed as the (11)C-verapamil radioactivity extraction ratio ((11)C-verapamil brain distributional clearance, K1/rCBF). Compared with controls, BBB P-glycoprotein activity was significantly lower in the parietotemporal, frontal, and posterior cingulate cortices and hippocampus of mild AD subjects. BBB P-glycoprotein activity in brain regions affected by AD is reduced and is independent of rCBF. This study improves on prior work by eliminating the confounding effect that reduced rCBF has on assessment of BBB P-glycoprotein activity and suggests that impaired P-glycoprotein activity may contribute to cerebral β-amyloid accumulation in AD. P-glycoprotein induction or activation to increase cerebral β-amyloid clearance could constitute a novel preventive or therapeutic strategy for AD.

PET Approaches for Diagnosis of Dementia

There is increasing use of neuroimaging modalities, including PET, for diagnosing dementia. For example, FDG-PET demonstrates hypometabolic regions in the posterior cingulate gyri, precuneus, and parietotemporal association cortices, while amyloid PET indicates amyloid deposition in Alzheimer disease and mild cognitive impairment due to Alzheimer disease. Furthermore, the use of combination PET with structural MR imaging can improve the diagnostic accuracy of dementia. In other neurodegenerative dementias, each disease exhibits a specific metabolic reduction pattern. In dementia with Lewy bodies, occipital glucose metabolism is decreased, while in frontotemporal dementia, frontal and anterior temporal metabolism is predominantly decreased. These FDG-PET findings and positive or negative amyloid deposits are important biomarkers for various neurodegenerative dementias.

LOC689986, a unique gene showing specific expression in restricted areas of the rodent neocortex

BackgroundThe neocortex is a highly specialised and complex brain structure, involved in numerous tasks, ranging from processing and interpretation of somatosensory information, to control of motor functions. The normal function linked to distinct neocortical areas might involve control of highly specific gene expression, and in order to identify such regionally enriched genes, we previously analysed the global gene expression in three different cortical regions (frontomedial, temporal and occipital cortex) from the adult rat brain. We identified distinct sets of differentially expressed genes. One of these genes, namely the hypothetical protein LOC689986 (LOC689986), was of particular interest, due to an almost exclusive expression in the temporal cortex.ResultsDetailed analysis of LOC689986 in the adult rat brain confirmed the expression in confined areas of parieto-temporal cortex, and revealed highly specific expression in layer 4 of the somatosensory cortex, with sharp borders towards the neighbouring motor cortex. In addition, LOC689986 was found to be translated in vivo, and was detected in the somatosensory cortex and in the Purkinje cells of the cerebellar cortex. The protein was present in neuronal dendrites and also in astrocyte cells. Finally, this unique gene is apparently specific for, and highly conserved in, the vertebrate lineage.ConclusionsIn this study, we have partially characterised the highly conserved LOC689986 gene, which is specific to the vertebrate linage. The gene displays a distinct pattern of expression in layer 4 of the somatosensory cortex, and areas of the parieto-temporal cortex in rodents.

Complexes of beta-amyloid peptides and of intracellular proteins in cerebrospinal fluid: New biomarkers of Alzheimer's disease?

Background: Insulin resistance, as seen in type 2 diabetes, has been shown to increase the risk of late onset Alzheimer’s Disease (AD) by as much as two-fold. In AD patients, characteristic findings are seen with structural magnetic resonance imaging (MRI) including global atrophy as well as regional reductions in gray matter volume (GMV) in the hippocampus, precuneus, posterior cingulate gyrus, parietotemporal, prefrontal, and orbitofrontal cortices. Additionally, negative correlations between peripheral insulin levels and regional GMV are seen in insulin resistant subjects in the middle temporal gyrus.The current study investigated whether elevated fasting glucose (FSG) levels were associated with lower GMV in brain areas that have been preferentially affected by AD. This association difference was further investigated between carrier and non-carrier (NC) groups of the apolipoprotein E (APOE) e4 allele, a genetic risk factor for late onset AD. Methods: Statistical Parametric Mapping (SPM), an automated brain imaging analysis computer package, was used to spatially normalize individual brains to a standard brain template, to obtain GMV maps from structural MRI, and to examine the correlations between higher FSG levels and lower structural MRI GMV measurements in 118 cognitively normal, non-diabetic individuals 6466 years of age (59e4 carriers and 59 NCs). A significance threshold of p 1⁄4 .005 was set for all imaging related analyses. Results: As predicted, significant correlations were seen between higher levels of FSG and lower GMV in AD-affected regions including the left inferior orbitofrontal cortex, parietal, and occipital lobes and the left and right frontal and temporal lobes. Negative correlations between FSG and regional GMV in the middle temporal gyri confirmed findings seen in insulin resistant subjects. Additionally, these associations in AD-related areas are seen in both carriers and NC. Conclusions: Higher FSG levels in cognitively normal, non-diabetic, older adults are associated with lower GMV in AD related brain areas, confirming that elevated FSG may be associated with AD risk, independent of APOEe4 status. Lastly, this study encourages the consideration of elevated FSG and other indicators of glucose control as targets for AD prevention trials, complementing the findings previously established with fluorodeoxyglucose positron emission tomography neuroimaging.

Topography of brain damage in metabolic hypoglycaemia is determined by age at which hypoglycaemia occurred.

Having previously shown that comorbidity is a major determinant of neurological sequelae in hypoglycaemia, our aim was to describe the neuroimaging patterns of brain damage in different hypoglycaemic situations and to elucidate the factors that determine lesion topography. We reviewed 50 patients (31 females, 19 males) with symptomatic hypoglycaemia (<2.8 mmol/L) occurring between 1 day and 5 years of age (median 4 d) who had undergone magnetic resonance imaging (MRI; at least axial T2-weighted, sagittal T1-weighted, and coronal fluid-attenuated inversion recovery [FLAIR]-weighted imaging). MRI was performed during the follow-up examination at least 1 month after the occurrence of symptomatic hypoglycaemia, i.e. between 1 month and 5 years of age (median 3 mo). Hypoglycaemia resulted from three inborn errors of metabolism: congenital hyperinsulinism (33 patients), fatty acid β-oxidation disorders (13 patients), or glycogen storage disease type I (four patients). We selected the patients with clear MRI abnormalities and analysed their topography according to aetiology and age at occurrence of the lesion. The topography of the brain lesions depended on age: from the neonatal period to 6 months of age, lesions predominantly involved the posterior white matter; between 6 and 22 months the basal ganglia, and after 22 months the parietotemporal cortex (p=0.04). The relationship between brain lesions and age could reflect the maturation sequence of the brain.

Effects of early rolipram treatment on histopathological outcome after controlled cortical impact injury in mice

Traumatic brain injury (TBI) pathology includes contusions, cavitation, cell death, all of which can be exacerbated by inflammation. We hypothesized that an anti-inflammatory drug, rolipram, may reduce pathology after TBI, since in several CNS injury models rolipram reduces inflammation and improves cell survival and functional recovery. Adult male C57BL/6 mice received a craniotomy over the right parietotemporal cortex. Vertically directed controlled cortical impact (CCI) injury was delivered. Naïve controls were used for comparison. At 30min post-surgery, animals were treated with vehicle or rolipram (1mg/kg), and then once per day for 3 days. On day 3, the brains were systematically sectioned and stained to visualize the resulting pathology using hematoxylin and eosin (H&E) staining and NeuN immunocytochemistry. Total parietotemporal cortical contusion and cavity volume were significantly increased in rolipram-treated as compared to vehicle-treated CCI animals. Contusion areas at specific bregma levels indicated a significant effect of drug across bregma levels. Neuronal cell loss in the dentate hilus and area CA3 of the hippocampus were similar between vehicle and rolipram-treated animals. Although rolipram is well known to reduce pathology and inflammation in several other CNS injury models, the pathology resulting from CCI was worsened with rolipram at this particular dose and administration schedule. These studies suggest that consideration of the unique characteristics of TBI pathology is important in the extrapolation of promising therapeutic interventions from other CNS injury models.

Dissociable dorsal and ventral frontostriatal working memory circuits: Evidence from subthalamic stimulation in Parkinson's disease

In this study, we investigated the neural substrates involved in visual working memory (WM) and the resulting effects of subthalamic nucleus (STN) stimulation in Parkinson's disease (PD). Cerebral activation revealed by positron emission tomography was compared among Parkinson patients with (PD-ON) or without (PD-OFF) STN stimulation, and a group of control subjects (CT) in two visual WM tasks with spatial (SP) and nonspatial (NSP) components. PD-OFF patients displayed significant reaction time (RT) deficits for both memory tasks. Although there were no significant differences in RT between patients with PD-ON and -OFF stimulation, patients with PD-ON stimulation performed comparably to controls. The memory tasks were executed with normal error rates in PD-ON and -OFF stimulation. In contrast to these behavioral results, whether the corresponding prefrontal activation was differentially affected by deep brain stimulation status in patients depended on whether the WM modality was SP versus NSP. Thus, SP WM was associated with (1) abnormal reduction in dorsolateral prefrontal activity in PD-OFF and -ON stimulation and (2) abnormal overactivation in parieto-temporal cortex in PD-OFF and in limbic circuits in PD-ON stimulation. In NSP WM, normal activation of the ventral prefrontal cortex was restored in PD-ON stimulation. In both visual modalities the posterior cerebral regions including fusiform cortex and cerebellum, displayed abnormally reduced activity in PD. These results indicate that PD induces a prefrontal hypoactivation that STN stimulation can partially restore in a modality selective manner by additional recruitment of limbic structures in SP WM or by recovery of the ventral prefrontal activation in NSP WM.

S.07.03 Brain activation associated with attentional bias in smokers is modulated by a dopamine antagonist

Attention deficit hyperactivity disorder (ADHD) in medication-naïve children has been associated with reduced activation in inferior/medial prefrontal, striatal and parieto-temporal cortices during inhibitory control and attention allocation. Functional magnetic resonance imaging (fMRI) studies in adult ADHD, however, have been inconsistent and confounded by medication-history and the need for a retrospective diagnosis of childhood ADHD. We used fMRI combined with a Simon task that measured interference inhibition and controlled for and co-measured attention allocation to compare brain function in 11 medication-naïve adults with persistent inattentive/hyperactive behaviours, followed up from childhood ADHD, and 15 age-matched controls. Despite comparable task performance, patients showed reduced activation compared to controls in left orbital/medial frontal cortex and striatum during interference inhibition and in left lateral inferior/dorsolateral prefrontal cortex during attention allocation. Whole-brain regression analyses within patients showed a negative correlation between symptom severity and fronto-striatal, temporo-parietal and cerebellar brain activation. The findings demonstrate that the typical fronto-striatal dysfunction observed in children with ADHD during interference inhibition and attention allocation is also observed in adults grown up from childhood ADHD with persistent symptoms. Furthermore, they show that functional deficits in adult ADHD are not related to chronic stimulant medication given that this sample was medication-naive.

Evolution of source EEG synchronization in early Alzheimer's disease

Alzheimer's disease (AD) disrupts functional connectivity in distributed cortical networks. We analyzed changes in the S-estimator, a measure of multivariate intraregional synchronization, in electroencephalogram (EEG) source space in 15 mild AD patients versus 15 age-matched controls to evaluate its potential as a marker of AD progression. All participants underwent 2 clinical evaluations and 2 EEG recording sessions on diagnosis and after a year. The main effect of AD was hyposynchronization in the medial temporal and frontal regions and relative hypersynchronization in posterior cingulate, precuneus, cuneus, and parietotemporal cortices. However, the S-estimator did not change over time in either group. This result motivated an analysis of rapidly progressing AD versus slow-progressing patients. Rapidly progressing AD patients showed a significant reduction in synchronization with time, manifest in left frontotemporal cortex. Thus, the evolution of source EEG synchronization over time is correlated with the rate of disease progression and should be considered as a cost-effective AD biomarker.

P3‐338: Beneficial effects of IVIg in the triple transgenic mouse model of Alzheimer's disease

Background: Intravenous immunoglobulin preparation (IVIg) is composed of >98% human IgG obtained from the plasma of healthy donors. It is approved for the treatment of immunodeficiency and autoimmune diseases and is under study in Alzheimer disease (AD) as well. Understanding the mechanisms of action of IVIg in AD would allow a more rational use of this product and may lead to the development of replacement therapies. Methods: To this aim, we investigated the effects of IVIg treatment in 3xTg-AD mice, which reproduce both As and tau pathologies. 3xTg-AD mice and non-transgenic controls were injected twice weekly with IVIg (or vehicle) for 1 or 3 months. Results: IVIg did not induce a significant immune response and was detected in the serum (ELISA: 22.2 mg/mL 6 0.7, mean 6 SEM), on splenocytes (flow cytometry: mean fluorescence index: 28.2 6 1.2 versus 7.5 6 0.3. Mean 6 SEM in IVIg and vehicle 3xTg-AD mice, respectively. p<0.0001) and in the parieto-temporal cortex (ELISA: 22.6 6 1.4 ng/mg tissue. Mean 6 SEM) of IVIg-injected mice. Furthermore, following IVIg injections, a significant reduction of behavioral deficits was observed in the object recognition (OR) test (OR index: 0.67 6 0.03 versus 0.55 6 0.03; mean 6 SEM in IVIg and vehicle 3xTg-AD mice, respectively; p1⁄40.0096) but not in the Barnes Maze. IVIg treatment also led to a 22% reduction of the soluble Ab42/Ab40 ratio versus vehicle (p1⁄40.025). Conclusions: Such beneficial effects of IVIg on cognition and Ab42/Ab40 ratio in 3xTgAD mice support the use of this model to further investigate the mechanisms of action of IVIg in AD.

Visuospatial deficits in posterior cortical atrophy: structural and functional correlates

ObjectiveTo determine the neural substrates of biased spatial orienting in posterior cortical atrophy (PCA) by using a combined structural and functional neuroimaging approach.BackgroundPatients with spatial neglect typically bisect horizontal long...

Minor adverse effects of galvanic vestibular stimulation in persons with stroke and healthy individuals

Objective: Galvanic vestibular stimulation (GVS) induces polarity-specific activations in the vestibular nerves and upstream in the vestibular and parietotemporal cortices as well as sub-cortical regions. This makes it an attractive technique for cognitive neuromodulation. However, systematic studies regarding adverse effects of GVS are unavailable. Thus, this study assessed adverse effects during and after sub-sensory GVS (mean: 0.6 mA) and GVS with 1.5 mA.Methods: Two hundred and fifty-five GVS sessions delivered to 55 persons with stroke and 30 healthy individuals were analysed using a 34-item-questionnaire including potential symptoms and rating scales for adverse effects.Results: The most frequent symptoms during and after GVS were slight itching (mean: 10.2%) and tingling (mean: 10.7%) underneath the electrodes. Healthy individuals and persons with stroke did not differ in their incidence and rated intensity of adverse effects, nor did persons with or without unilateral spatial neglect. Adverse effects were found more frequently with GVS with 1.5 mA as with sub-sensory GVS. Participants were unable to differentiate real from sham conditions during sub-sensory GVS. Importantly, neither seizures nor vertigo or nausea were observed.Conclusion: Sub-sensory GVS and GVS with 1.5 mA induce very few and mild adverse effects in healthy and persons with stroke and are safe when safety guidelines are followed.

Resting state network abnormalities in Alzheimer's disease: Beyond the default mode network

Background: Several studies of Alzheimer’s disease (AD) patients have demonstrated alterations of the default mode network (DMN). Recent studies suggested that in AD a decreased parieto-temporal functional coactivation is coupled with an increased prefrontal coactivation. To date, how resting state brain networks (RSNs) other than the DMN are affected by AD, and whether their functional changes occur early in the course of the disease have not been fully investigated yet. This study investigated whether RSNs are affected in AD and amnestic mild cognitive impairment (aMCI) patients, and whether they are related to gray matter (GM) atrophy and cognitive functioning.Methods: Using RS functional MRI (fMRI), the coactivation patterns of the DMN, as well as the fronto-parietal, executive, and salience networks were explored in 13 patients with AD and 12 patients with aMCI relative to 13 healthy controls. Results: Compared with healthy controls and aMCI, AD was associated with an opposing coactivation effects in the DMN (decreased) and frontal networks (enhanced). The only RS abnormality found in aMCI patients compared with controls was a precuneus coactivation reduction in the DMN. Results obtained after GM volume correction suggested that GM volume loss accentuated RS fMRI differences between patients and controls, especially in the frontal regions, but most RSN group differences could not be explain by atrophy alone. Cognitive impairment correlated with enhanced executive network coactivation in aMCI patients, and with a reduced coactivation of the same network in AD patients.Conclusions:AD is associated with an alteration of large-scale functional brain networks, which extends well beyond the DMN. The limited resources of the parieto-temporal cortex of AD patients may be paralleled, in an attempt to maintain cognitive efficiency, by an increased prefrontal coactivation. A medial parietal RS fMRI signal change seems to be present since the early phase of AD.

Early changes of cholinergic receptors in hippocampus and parietotemporal cortex of the rat model of sporadic Alzheimer's disease

disease (AD) and neurodegeneration. VitaminD has been shown to down-regulate the L-type voltage-sensitive calcium channels, LVSCC-A1C and LVSCC-A1D, and up-regulate (nerve growth factor) NGF. However, expression of these proteins when VDR is repressed is unknown. The aim of this study is to investigate LVSCC-A1C, LVSCC-A1D, calbindin-D28k, inducible nitric oxide synthase (iNOS) expressions and NGF release in VDR-silenced primary cortical neurons. Methods: qRT-PCR and western blots were performed to determine VDR, LVSCC-A1C, LVSCC-A1D, calbindin-D28k and iNOS expression levels. NGF and cytotoxicity levels were determined by ELISA. Apoptosis was determined by TUNEL. Results: Our findings illustrate that LVSCC-A1C and iNOS expressions increased rapidly in cortical neurons when VDR is down-regulated, whereas, LVSCC-A1D levels did not change, NGF release calbindin-D28k expression decreased in response to VDR down-regulation. Although vitamin D regulates LVSCC-A1C through VDR, it may not regulate LVSCC-A1D through VDR. Conclusions: Our results indicate that suppression of VDR or vitamin D-VDR pathway disruption disrupts LVSCC-A1C, calbindin-D28k and NGF production and increase oxidative stress. Thus it can make neurons vulnerable to aging and neurodegeneration, and when combined with As toxicity, it is possible to explain some of the events that occur during neurodegeneration.

Leading role of &lt;sup&gt;18&lt;/sup&gt;F-FDG-PET imaging in early diagnosis of Alzheimer&amp;rsquo;s disease: an overview

Leading role of 18F-FDG-PET imaging in early diagnosis of Alzheimer&rsquo;s disease: an overview Ernesto Cason1, Giorgio Treglia2, Giorgio Fagioli11Unit of Nuclear Medicine, Maggiore Hospital of Bologna, Bologna, Italy; 2Institute of Nuclear Medicine, Catholic University of the Sacred Heart, Rome, ItalyAbstract: Early detection of Alzheimer&rsquo;s disease (AD) is important to reveal preclinical pathological alterations, to monitor disease progression, and to evaluate response to therapy. The study of cerebral glucose metabolism through 18F-fluoro-deoxy-glucose positron emission tomography (FDG-PET) plays a leading role in early detection of AD because the decrease of cerebral glucose metabolism largely precedes the onset of AD symptoms. This technique demonstrated high sensitivity in early diagnosis of AD, allowing a qualitative and quantitative estimate of cerebral glucose metabolism. Furthermore FDG-PET imaging may help to discriminate the subjects of a high-risk population (like patients with mild cognitive impairment) who more probably will develop AD: an early stage of AD generally shows hypometabolism of medial temporal lobes and parietotemporal posterior cortices; other cerebral cortices are later involved. The combination of FDG-PET with other biomarkers, such as genotype, cerebrospinal fluid markers, and amyloid plaque imaging, may increase the preclinical diagnostic accuracy and offer promising approaches to assess individual prognosis in AD patients.Keywords: positron emission tomography, dementia, neuroimaging, Alzheimer&rsquo;s disease, 18F-FDG

Phase Advance of the Light-Dark Cycle Perturbs Diurnal Rhythms of Brain-derived Neurotrophic Factor and Neurotrophin-3 Protein Levels, Which Reduces Synaptophysin-positive Presynaptic Terminals in the Cortex of Juvenile Rats

In adult rat brains, brain-derived neurotrophic factor (BDNF) rhythmically oscillates according to the light-dark cycle and exhibits unique functions in particular brain regions. However, little is known of this subject in juvenile rats. Here, we examined diurnal variation in BDNF and neurotrophin-3 (NT-3) levels in 14-day-old rats. BDNF levels were high in the dark phase and low in the light phase in a majority of brain regions. In contrast, NT-3 levels demonstrated an inverse phase relationship that was limited to the cerebral neocortex, including the visual cortex, and was most prominent on postnatal day 14. An 8-h phase advance of the light-dark cycle and sleep deprivation induced an increase in BDNF levels and a decrease in NT-3 levels in the neocortex, and the former treatment reduced synaptophysin expression and the numbers of synaptophysin-positive presynaptic terminals in cortical layer IV and caused abnormal BDNF and NT-3 rhythms 1 week after treatment. A similar reduction of synaptophysin expression was observed in the cortices of Bdnf gene-deficient mice and Ca(2+)-dependent activator protein for secretion 2 gene-deficient mice with abnormal free-running rhythm and autistic-like phenotypes. In the latter mice, no diurnal variation in BDNF levels was observed. These results indicate that regular rhythms of BDNF and NT-3 are essential for correct cortical network formation in juvenile rodents.