Tau PET imaging with 18F-PI-2620 in aging and neurodegenerative diseases
Elizabeth C. MorminoTyler N. TouegE. Carmen AzevedoJessica B. CastilloWanjia GuoAyesha NadiadwalaNicole K. CorsoJacob HallAudrey P. FanAlexandra N. TrelleMarc HarrisonMadison P. HuntSharon J. ShaGayle K. DeutschMichelle L. JamesCarolyn A. FredericksMary Ellen I. KoranMichael ZeinehKathleen L. PostonMichael D. GreiciusMehdi KhalighiGuido DavidzonBin ShenGreg ZaharchukAnthony D. WagnerFrederick T. Chin
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Posterior cingulate
Temporal cortex
Primary progressive aphasia
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Abstract Activity and reactivity of the default mode network in the brain was studied using functional magnetic resonance imaging (fMRI) in 28 nondemented individuals with mild cognitive impairment (MCI), 18 patients with mild Alzheimer's disease (AD), and 41 healthy elderly controls (HC). The default mode network was interrogated by means of decreases in brain activity, termed deactivations, during a visual encoding task and during a nonspatial working memory task. Deactivation was found in the default mode network involving the anterior frontal, precuneus, and posterior cingulate cortex. MCI patients showed less deactivation than HC, but more than AD. The most pronounced differences between MCI, HC, and AD occurred in the very early phase of deactivation, reflecting the reactivity and adaptation of the network. The default mode network response in the anterior frontal cortex significantly distinguished MCI from both HC (in the medial frontal) and AD (in the anterior cingulate cortex). The response in the precuneus could only distinguish between patients and HC, not between MCI and AD. These findings may be consistent with the notion that MCI is a transitional state between healthy aging and dementia and with the proposed early changes in MCI in the posterior cingulate cortex and precuneus. These findings suggest that altered activity in the default mode network may act as an early marker for AD pathology. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
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Recently there has been a great emphasis put on finding early imaging markers for Alzheimer's Disease (AD). In previous imaging studies, abnormal magnetic resonance spectroscopic signals have been found to be limited to the posterior cingulate regions (Kantarci et al, 2000). These studies did not examine other cortical areas. In early AD, executive function has been shown to be deteriorated when compared to normal age matched subjects. We hypothesized that frontal metabolic abnormalities demonstrated by magnetic resonance spectroscopy (MRS) might actually exceed those demonstrated for posterior cingulated cortex. MRS was performed in the left Brodman area (Ba) 44 (inferior frontal gyrus), left Ba 37 (posterior temporal), and left precuneus (this included the mid posterior cingulate gyrus and precuneus areas) in 10 normal elderly controls (NEC) (mean age = 77.9, 4M : 6F, mean MMSE = 27.56) and 6 mild AD patients (mean age = 81.5, 5M : 1F, mean MMSE = 24.00). The N–acetylaspartate and N–acetylaspartylglutamate (NAA+NAAG) / Creatine (Cr) ratios were calculated for these three areas. There was no significant difference found in the Ba 37 region between normal and AD subjects. The precuneus area had minimal significance (p<0.061). The Ba 44 region showed the most significant (p<0.01) difference between AD patients and NEC subjects. MRS performed in the frontal area might demonstrate earlier changes in mild AD patients and may prove to be useful in prognostication. Frontal cortex MRS should be assessed in a pre–dementia state such as Mild Cognitive Impairment (MCI).
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Functional neuroimaging studies provide converging evidence for existence of intrinsic brain networks activated during resting states and deactivated with selective cognitive demands. Whether task-related deactivation of the default mode network signifies depressed activity relative to the remaining brain or simply lower activity relative to its resting state remains controversial. We employed 3D arterial spin labeling imaging to examine regional cerebral blood flow (CBF) during rest, a spatial working memory task, and a second rest. Change in regional CBF from rest to task showed significant normalized and absolute CBF reductions in posterior cingulate, posterior-inferior precuneus, and medial frontal lobes . A Statistical Parametric Mapping connectivity analysis, with an a priori seed in the posterior cingulate cortex, produced deactivation connectivity patterns consistent with the classic "default mode network" and activation connectivity anatomically consistent with engagement in visuospatial tasks. The large task-related CBF decrease in posterior-inferior precuneus relative to its anterior and middle portions adds evidence for the precuneus' heterogeneity. The posterior cingulate and posterior-inferior precuneus were also regions of the highest CBF at rest and during task performance. The difference in regional CBF between intrinsic (resting) and evoked (task) activity levels may represent functional readiness or reserve vulnerable to diminution by conditions affecting perfusion.
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Abstract Purpose To characterize, using functional MRI (fMRI), the pattern of active brain regions in the resting state in patients with epilepsy. Materials and Methods We studied 28 patients with epilepsy, divided into a partial seizure (PS; N = 9) and a generalized seizure group (GS; N = 19), and 34 control subjects. Resting state fMRI was performed using a GE 3T scanner by collecting 200 volumes of echo‐planar imaging (EPI) images with subjects relaxed, eyes closed. Data were processed using a modification of the method of Fransson (Hum Brain Mapp 2005;26:15–29), which reveals information on regional low‐frequency Blood Oxygenation Level Dependent (BOLD) signal oscillations in the resting state without any a priori hypothesis. The significant active areas in brain were identified with both individual and group analysis. Results Controls showed active regions in the precuneus/posterior cingulate cortex (PCC) and medial prefrontal cortex (MPFC)/ventral anterior cingulate cortex (vACC), theregions associated with the brain “default mode.” Similar active regions were observed in PS, whereas GS showed no significant activation of precuneus/PCC. Conclusion In GS, the lack of activation in precuneus/PCC may partly account for their more severe interictal deficits, compared to PS, in cognitive functions such as concentration and memory. J. Magn. Reson. Imaging 2008;27:1214–1220. © 2008 Wiley‐Liss, Inc.
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We have investigated functional connectivity of the default mode network (DMN) in normal aging and Alzheimer's disease (AD) using resting state fMRI at 3T. Images from young and elderly controls, and patients with AD were processed using spatial independent component analysis to identify the DMN. Functional connectivity was quantified using integration and indices derived from graph theory. Four DMN sub-systems were identified: Frontal (medial frontal, superior frontal), Parietal (precuneus-posterior cingulate, lateral parietal), Temporal (medial temporal cortices), and Hippocampal (left and right). There was a decrease in antero-posterior interactions (lower global efficiency), but increased interactions within the Frontal and Parietal sub-systems (higher local clustering) in elderly compared to young controls. The decreased antero-posterior integration was more pronounced in AD patients compared to elderly controls, particularly in the precuneus-posterior cingulate region. The approach allows for a complete characterization of connectivity changes and could be applied to other resting state networks and pathologies.
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The precuneus/posterior cingulate cortex, which has been associated with pain sensitivity, plays a pivotal role in the default mode network. However, information regarding migraine-related alterations in resting-state brain functional connectivity in the default mode network and in local regional spontaneous neuronal activity is not adequate. This study used functional magnetic resonance imaging to acquire resting-state scans in 22 migraineurs without aura and in 22 healthy matched controls. Independent component analysis, a data-driven method, was used to calculate the resting-state functional connectivity of the default mode network in the patient and healthy control groups. Regional homogeneity (ReHo) was used to analyse the local features of spontaneous resting-state brain activity in the migraineurs without aura. Compared with the healthy controls, migraineurs without aura showed increased functional connectivity in the left precuneus/posterior cingulate cortex within the default mode network and significant increase in ReHo values in the bilateral precuneus/posterior cingulate cortex, left pons and trigeminal nerve entry zone. In addition, functional connectivity was decreased between the areas with abnormal ReHo (using the peaks in the precuneus/posterior cingulate cortex) and other brain areas. The abnormalities in the precuneus/posterior cingulate cortex suggest that migraineurs without aura may exhibit information transfer and multimodal integration dysfunction and that pain sensitivity and pian processing may also be affected.
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