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activation in the right operculum, right insular, and the right inferior prefrontal cortices was seen in HC, but not in AD. Unilateral activation was observed in HC in the occipital cortex (left) and the supramarginal gyrus (right); these regions were bilaterally activated in AD. The AD group also showed increased activation in the right dorsal medial portion of the frontal pole, which was not observed in the HC group. Conclusions: Subjects with early AD did not involve certain key structures in normal episodic memory processing as seen in HC, but recruited additional neural circuits especially in the prefrontal cortex. Our study provides the firstMEG dataset confirming a possible neuropathological and neurocompensatory interplay in early AD.

information than traditional biomarkers. These features were used in generating the highand low-risk profile groups, which could aid in establishing individual prognoses. P3-211 A COMPARISON OF GENERAL PRACTITIONERS’ PERSPECTIVES ON NEUROIMAGING IN DEMENTIA IN IRELAND AND NORTH WALES Aurelia Ciblis, Catherine Quinn, Marie-Louise Butler, Arun Bokde, Paul Mullins, Jonathan McNulty, University College Dublin, Dublin, Ireland; Bangor University, Gwynedd, United Kingdom; Trinity College Dublin, Dublin, Ireland; Bangor University, Bangor, United Kingdom. Contact e-mail: aurelia.ciblis@ucd.ie

With the advent of new analysis methods in neuroimaging that involve independent component analysis (ICA) and dynamic causal modelling (DCM), investigations have focused on measuring both the activity and connectivity of specific brain networks. In this study we combined DCM with spatial ICA to investigate network switching in the brain. Using time courses determined by ICA in our dynamic causal models, we focused on the dynamics of switching between the default mode network (DMN), the network which is active when the brain is not engaging in a specific task, and the central executive network (CEN), which is active when the brain is engaging in a task requiring attention. Previous work using Granger causality methods has shown that regions of the brain which respond to the degree of subjective salience of a stimulus, the salience network, are responsible for switching between the DMN and the CEN (Sridharan et al., 2008). In this work we apply DCM to ICA time courses representing these networks in resting state data. In order to test the repeatability of our work we applied this to two independent datasets. This work confirms that the salience network drives the switching between default mode and central executive networks and that our novel technique is repeatable. © 2014 .

Alzheimer’s disease (AD) is sometimes preceded by a stage known as amnestic mild cognitive impairment (aMCI), which is characterised by memory deficits abnormal for age in the absence of dementia. Although not in itself a diagnostic entity, because individuals with aMCI are at a greatly increased risk of developing AD there is an interest in characterising brain changes associated with the syndrome as compared to healthy ageing. In the current study we investigated the resting state functional connectivity (FC) of two important subcortical brain structures, the hippocampus and thalamus using functional magnetic resonance imaging (fMRI) in a group of 15 aMCI subjects and 16 healthy controls (HC). The groups were matched for age, gender and education level. Compared to the HC, the aMCI group showed significantly reduced FC of the hippocampus and thalamus to a number of brain regions (p < 0.05 corrected in all cases), particularly in the frontal and parietal cortex. FC was reduced between both right and left thalamus and bilateral supramarginal gyrus and inferior frontal gyrus (IFG) and left cerebellum; and between both right and left hippocampus and areas of frontal, temporal and parietal cortex. This study is being conducted as part of a wider project which incorporates diffusion imaging tractography of limbic white matter pathways. In the same cohort there was found to be almost no difference in white matter indices of the fornix, which directly connects the hippocampus and thalamus, suggesting that FC may be an earlier biomarker for connectivity changes in aMCI.

BACKGROUND: Apoptosis plays an important pathophysiologic role in neuronal cell loss and associated neurologic deficits following traumatic brain injury (TBI). DNA fragmentation represents one of the characteristic biochemical features of neuronal apoptosis and is observed after experimental TBI. DFF45 and DFF40 are essential for DNA fragmentation in various models of apoptosis. MATERIALS AND METHODS: We used mice deficient in DFF45 and wild-type controls. Oligonucleosomal DNA fragmentation induced by TBI was analyzed using in vivo and in vitro assays. Expression and integrity of DFF45 and DFF40 proteins was assessed by Western analysis. Other outcome measurements included neurologic scoring, learning/memory tests, lesion volume measurements (MRI), and assessment of cell viability in vitro among others. RESULTS: We compared the effects of controlled cortical impact (CCI) trauma in DFF45 knockout mice and wild-type controls. Analysis of TBI-induced DNA fragmentation in brain cortex from wild-type and DFF45 knockout mice indicates that, although somewhat delayed, oligonucleosomal cleavage of DNA occurs after TBI in DFF45 knockout mice. DFF45 knockouts showed no significant differences in behavioral outcomes or lesion volumes after TBI as compared to wild-type controls. Using an in vitro reconstitution system, we also demonstrated that cleavage of DFF45 by caspase-3 is not sufficient for DNA fragmentation induced by protein extracts from rat brain cortex. We found that endonuclease activity induced in rat brain cortex following TBI depends on the presence of Mg2+ and Ca2+, but is not inhibited by Zn2+. Primary neuronal cultures from DFF45 knockouts failed to show DNA laddering in response to staurosporine, but did show prominent, albeit delayed, DNA fragmentation following treatment with etoposide. In contrast, primary neurons from wild-type animals demonstrated marked DNA fragmentation following treatment with staurosporine or etoposide. CONCLUSIONS: The results of this study suggest that, in addition to DFF45/40, other endonucleases may be essential for chromatin degradation during neuronal apoptosis in adult brain after TBI.

The effects of selective blockade of group I metabotropic glutamate receptor subtype 1 (mGluR1) on neuronal cell survival and post-traumatic recovery was examined using rat in vitro and in vivo trauma models. The selective mGluR1 antagonists (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA), 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt), and (S)-(+)-alpha-amino-4-carboxy-2-methylbezeneacetic acid (LY367385) provided significant neuroprotection in rat cortical neuronal cultures subjected to mechanical injury, in both pretreatment or posttreatment paradigms. Administration of the antagonists also attenuated glutamate-induced neuronal cell death in the cultures. Coapplication of these antagonists with the N-methyl-d-aspartate (NMDA) receptor antagonist (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) had additive neuroprotective effects in glutamate injured cultures. Intracerebroventricular administration of AIDA to rats markedly improved recovery from motor dysfunction after lateral fluid percussion induced traumatic brain injury (TBI). Treatment with mGluR1 antagonists also significantly reduced lesion volumes in rats after TBI, as evaluated by MRI. It appears that these compounds mediate their neuroprotective effect through an mGluR1 antagonist action, as demonstrated by inhibition of agonist induced phosphoinositide hydrolysis in our in vitro system. Moreover, AIDA, CPCCOEt, and LY367385, at concentrations shown to be neuroprotective, had no significant effects on the steady state NMDA evoked whole cell current. Taken together, these data suggest that modulation of mGluR1 activity may have substantial therapeutic potential in brain injury.

Ischaemic preconditioning in rats was studied using MRI. Ischaemic preconditioning was induced, using an intraluminal filament method, by 30 min middle cerebral artery occlusion (MCAO), and imaged 24 h later. The secondary insult of 100 min MCAO was induced 3 days following preconditioning and imaged 24 and 72 h later. Twenty-four hours following ischaemic preconditioning most rats showed small sub-cortical hyperintense regions not seen in sham-preconditioned rats. Twenty-four hours and 72 h following the secondary insult preconditioned animals showed significantly smaller lesions (24 h = 112 +/- 31 mm(3), mean +/- standard error; 72 h = 80 +/- 35 mm(3)), which were confined to the striatum, than controls (24 h = 234 +/- 32 mm(3), p = 0.026; 72 h = 275 +/- 37 mm(3), p = 0.003). In addition during lesion maturation from 24 to 72 h post-secondary MCAO, preconditioned rats displayed an average reduction in lesion size as measured by MRI whereas sham-preconditioned rats displayed increases in lesion size; this is the first report of such differential lesion volume evolution in cerebral ischaemic preconditioning.

Magic-angle spinning (MAS) has recently been shown to enhance spectral resolution in NMR examinations of intact biological tissue ex vivo. This work demonstrates that freezing certain tissue samples before examination by 1H MAS NMR can have a marked effect on their spectra. Spectra of rat kidney after freezing in liquid nitrogen, compared with spectra before freezing, showed a significant increase in signal intensities from alanine (>100%), glutamine (>40%), and glycine (>100%), and a decrease in signals assigned to lipids and other macromolecules. Some resonances--such as from leucine, valine, isoleucine, and aspartate--only became visible after freezing the tissue. These observations suggest that low temperature storage of tissue necropsies or biopsies might affect the results of a MAS NMR analysis, possibly resulting in the misinterpretation of metabolite changes to pathogen or disease effects.

MRS) was used to acquire in vivo spectra from the bilateral anterior cingulate of 10 healthy subjects while they received a subanesthetic dose of either placebo or ketamine, an NMDAR antagonist. Assessments given before and after ketamine or placebo administration included the Brief Rating Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, the Clinician-Administered Dissociative States Scale, and the Stroop task. Results: As predicted, there was a significant increase in anterior cingulate glutamine, a putative marker of glutamate neurotransmitter release, with ketamine administration. This increase was not related to schizophrenia-like positive or negative symptoms but was marginally related to Stroop performance. Conclusions: In humans as in animals, an acute hypofunctional NMDAR state is associated with increased glutamatergic activity in the anterior cingulate. (Am J Psychiatry 2005; 162:394–396) A ccording to the N-methyl-D-aspartate receptor (NMDAR) hypofunction model of schizophrenia (1, 2), NMDAR blockade results in inhibition of γ-aminobutyric acid neurons, causing disinhibition of glutamatergic neurons that converge onto pyramidal neurons in widely distributed cortical regions. NMDAR hypofunction and/or the downstream surge of glutamate in corticolimbic regions may be related to positive and negative symptoms in schizophrenia. Directly supporting this hypothesis, extracellular glutamate concentrations in the prefrontal cortex were found to increase in awake rats when they were given ketamine, an NMDAR antagonist (3). However, to our knowledge, no studies assessing the effects of NMDAR antagonism on glutamatergic activity in humans have been reported. The current study investigated the effects of ketamine on anterior cingulate glutamatergic activity and the relationship to ketamine-induced schizophrenia-like features in healthy humans. Glutamine, the major metabolite of synaptic glutamate (4, 5), was measured with 4-T 1 H proton magnetic resonance spectroscopy ( 1 H-MRS). We hypothesized that there would be a significant increase in anterior cingulate glutamine with ketamine administration, and that this increase would be directly related to schizophrenia-like positive and negative symptoms.

Elevated brain water is a common finding in individuals with severe forms of altitude illness. However, the location, nature, and a causative link between brain edema and symptoms of acute mountain sickness such as headache remains unknown. We examined indices of brain white matter water mobility in 13 participants after 2 and 10 hours in normoxia (21% O2) and hypoxia (12% O2) using magnetic resonance imaging. Using a whole-brain analysis (tract-based spatial statistics (TBSS)), mean diffusivity was reduced in the left posterior hemisphere after 2 hours and globally reduced throughout cerebral white matter by 10 hours in hypoxia. However, no changes in T2 relaxation time (T2) or fractional anisotropy were observed. The TBSS identified an association between changes in mean diffusivity, fractional anisotropy, and T2 both supra and subtentorially after 2 and 10 hours, with headache score after 10 hours in hypoxia. Region of interest-based analyses generally confirmed these results. These data indicate that acute periods of hypoxemia cause a shift of water into the intracellular space within the cerebral white matter, whereas no evidence of brain edema (a volumetric enlargement) is identifiable. Furthermore, these changes in brain water mobility are related to the intensity of high-altitude headache.

A movable, actively decoupled surface coil has been employed to obtain a localized 1H NMR spectrum from the lumbosacral spinal cord of a live Lewis rat. A volume selective 'VOSY' normally spelled out as 'volume selective spectroscopy' spectroscopy pulse sequence that incorporates 'phase ramped' selective RF pulses, has been used to minimize random phase jitter in the NMR signal as a result of the large frequency shifts required to locate the voxel in the center of the cord while using intense gradient pulses. Spectra from 13-microliters voxels in healthy rats and in rats inoculated with guinea pig spinal cord and complete Freund's adjuvant, resulting in experimental autoimmune encephalomyelitis, are shown.

As acute ethanol exposure inhibits N-methyl-D-aspartate glutamate (Glu) receptors, sudden withdrawal from chronic alcohol use may lead to an increased activation of these receptors with excitotoxic effects. In the longer term, brain levels of Glu and its metabolites, such as glutamine (Gln), are likely to be chronically altered by alcohol, possibly providing a measure of overall abnormal Glu-Gln cycling. However, few studies have assessed concentrations of these metabolites in clinical populations of individuals with alcohol use disorders. Glu and Gln levels were compared in groups of 17 healthy controls and in 13 participants with alcohol dependence. Within the alcohol-dependent group, seven participants had current alcohol use disorder (AUD), and six had AUD in remission for at least 1 year (AUD-R). Neurometabolite concentrations were measured with proton magnetic resonance spectroscopy ((1)H-MRS) in a predominantly gray matter voxel that included the bilateral anterior cingulate gyri. Tissue segmentation provided an assessment of the proportion of gray matter in the (1)H-MRS voxel. The Drinker Inventory of Consequences (DrInC) and Form-90 were administered to all participants to quantify alcohol consequences and use. Glu level was lower and Gln level was higher in the AUD and AUD-R groups relative to the control group; creatine, choline, myo-inositol, and total N-acetyl groups, primarily N-acetylaspartate did not differ across groups. These results were not confounded by age, sex, or proportion of gray matter in the (1)H-MRS voxel. Neurometabolite concentrations did not differ between AUD and AUD-R groups. Subsequent regressions in the combined clinical group, treating voxel gray matter proportion as a covariate, revealed that total score on the DrInC was positively correlated with Gln but negatively correlated with both Glu and gray matter proportion. Regression analyses, including DrInC scores and smoking variables, identified a marginal independent effect of smoking on Gln. The current findings of higher Gln and lower Glu in the combined AUD and AUD-R groups might indicate a perturbation of the Glu-Gln cycle in alcohol use disorders. The absence of differences in mean Glu and Gln between the AUD and AUD-R groups suggests that altered Glu-Gln metabolism may either predate the onset of abuse or persist during prolonged abstinence.

Objective.Studies that have examined abnormalities in cerebral blood flow (CBF) in patients with systemic lupus erythematosus (SLE) reported CBF relative to a region assumed to be normal in the brain. We examined the absolute differences in both regional CBF and cerebral blood volume (CBV) between patients with SLE and healthy controls.Methods.CBF and CBV were measured with dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI), a technique that provides an alternative to radionuclide perfusion studies and permits quantitative anatomic, CBF, and CBV imaging in a single scanning session. CBF and CBV were measured in lesions and in normal-appearing tissue in the major cerebral and subcortical brain regions. Unlike most perfusion studies in SLE, CBF and CBV values were not normalized to a region of the brain assumed to be healthy.Results.CBF and CBV within MRI-visible lesions were markedly reduced relative to surrounding normal-appearing white matter. CBF and CBV in normal-appearing tissue were both higher in SLE patient groups, with or without lesions, relative to the control group.Conclusion.DSC MRI, without normalization to a region presumed to be healthy, revealed that CBF and CBV in normal-appearing tissue in patients with SLE was higher than CBF and CBV in controls. Since this finding was made in subgroups of patients with and without lesions, the higher CBF and CBV appear to precede lesion pathology.

Background Cognitive deficits in schizophrenia may be related to glutamatergic dysfunction, but in vivo measurement of glutamate metabolism has been challenging. We examined the relationship between glutamate metabolism and cognitive function in schizophrenia. Methods Thirty subjects with DSM-IV schizophrenia and 28 healthy volunteers were studied using 4 Tesla proton echo planar spectroscopic imaging. Glutamate plus glutamine (Glx), N-acetylaspartate compounds, and Inositol concentrations in gray and white matter and broad neuropsychological function were assessed in all subjects. Results Glutamate plus glutamine was positively correlated with overall cognitive performance in the schizophrenia group ( p = .0006), accounting for about 36% of the variance. No correlation was found in control subjects. Group-averaged Glx levels were similar in schizophrenia and control subjects. N-acetylaspartate compounds were reduced in cortical gray matter in the younger schizophrenia subjects (age p = .04) compared with age-matched control subjects. Inositol was increased in cortical gray ( p = .002) and white matter ( p = .02) in the older schizophrenia subjects (age > 30) compared with age-matched control subjects. Conclusions Although not reduced in schizophrenia as a group, lower Glx levels correlates with impaired cognition in the illness. This suggests heterogeneity in mechanisms that regulate glutamate function in schizophrenia. Patients with reduced glutamatergic reserves may be rendered into a more severe hypoglutamatergic state with cognitive consequences. Reduced cortical gray matter N-acetylaspartate compound concentration early in the illness with normalization in older subjects is consistent with a process of early dendritic retraction with subsequent increased neuronal packing. Later in the illness, Inositol elevation suggests glial involvement.

We investigated glutamate-related neuronal dysfunction in the anterior cingulate (AC) early in schizophrenia before and after antipsychotic treatment. A total of 14 minimally treated schizophrenia patients and 10 healthy subjects were studied with single-voxel proton magnetic resonance spectroscopy (1H-MRS) of the AC, frontal white matter and thalamus at 4 T. Concentrations of N-acetylaspartate (NAA), glutamate (Glu), glutamine (Gln) and Gln/Glu ratios were determined and corrected for the partial tissue volume. Patients were treated with antipsychotic medication following a specific algorithm and 1H-MRS was repeated after 1, 6 and 12 months. There were group × region interactions for baseline NAA (P = 0.074) and Gln/Glu (P = 0.028): schizophrenia subjects had lower NAA (P = 0.045) and higher Gln/Glu (P = 0.006) in the AC before treatment. In addition, AC Gln/Glu was inversely related to AC NAA in the schizophrenia (P = 0.0009) but not in the control group (P = 0.92). Following antipsychotic treatment, there were no further changes in NAA, Gln/Glu or any of the other metabolites in any of the regions studied. We conclude that early in the illness, schizophrenia patients already show abnormalities in glutamatergic metabolism and reductions in NAA consistent with glutamate-related excitotoxicity.

Improved detection of J-coupled neurometabolites through the use of modified proton magnetic resonance spectroscopy (1H-MRS) techniques has recently been reported. TE-averaged point-resolved spectroscopy (PRESS) uses the J modulation effects by averaging FIDs with differing echo times to improve detection of glutamate, while standard PRESS detection of glutamate can be improved by using an appropriate single echo determined from J-modulation simulations. In the present study, the reliabilities of TE-averaged PRESS, standard PRESS with TE = 40 ms, and standard PRESS with TE = 30 ms in detecting metabolite levels in the cingulate gyrus of the human brain at 3T were compared in six subjects. TE-averaged PRESS measures showed a mean variability of 9% for N-acetyl aspartate, choline, and creatine, compared with < 4% for the 30- and 40-ms PRESS techniques. The coefficients of variation for glutamate were 10%, 7%, and 5% for TE-averaged, 30-ms, and 40-ms PRESS, respectively. PRESS with a TE of 40 ms also demonstrated improved reliability for GABA and glutamine concentrations. These results show that with the appropriate selection of echo time standard PRESS can be a reliable (1)H-MRS technique for the measurement of J-coupled neurometabolites in the human brain and, moreover, compares favorably with at least one J-edited technique.

The purpose of this study was to examine differences in habituation to heat and cold pain in women with fibromyalgia (FM; n = 33) and in women who were healthy controls (HC; n = 44). Quantitative sensory testing (QST) was used to assess pain thresholds during five consecutive trials of ascending heat and descending cold stimulation. Anxiety, depression, fatigue, and pain during the previous week were assessed using self-report measures. The overall hypotheses were that there would be differences between groups in pain thresholds and in the rate of habituation to heat and cold pain stimuli. Multilevel modeling was used to test the hypotheses. There were large overall differences in pain thresholds, with the FM group showing greater sensitivity to heat and cold pain stimuli compared with the HC group. While habituation occurred in both of the groups for heat pain, the HC group had stronger habituation across trials than the FM group. Conversely, while the HC group habituated to cold pain stimuli, the FM group showed sensitization and had decreased cold pain thresholds across trials (they felt cold pain at higher temperatures). In addition, anxiety, depression, fatigue, and pain were related to decreased heat and cold pain thresholds in the overall sample. However, when group was controlled, none of these variables were related to thresholds or rates of habituation or sensitization. The differences between women with FM and healthy women in habituation and sensitization may have important implications for the etiology, diagnosis, and treatment of FM and other chronic pain conditions.

In this multicenter study, 2D spatial mapping of J-coupled resonances at 3T and 4T was performed using short-TE (15 ms) proton echo-planar spectroscopic imaging (PEPSI). Water-suppressed (WS) data were acquired in 8.5 min with 1-cm(3) spatial resolution from a supraventricular axial slice. Optimized outer volume suppression (OVS) enabled mapping in close proximity to peripheral scalp regions. Constrained spectral fitting in reference to a non-WS (NWS) scan was performed with LCModel using correction for relaxation attenuation and partial-volume effects. The concentrations of total choline (tCho), creatine + phosphocreatine (Cr+PCr), glutamate (Glu), glutamate + glutamine (Glu+Gln), myo-inositol (Ins), NAA, NAA+NAAG, and two macromolecular resonances at 0.9 and 2.0 ppm were mapped with mean Cramer-Rao lower bounds (CRLBs) between 6% and 18% and approximately 150-cm(3) sensitive volumes. Aspartate, GABA, glutamine (Gln), glutathione (GSH), phosphoethanolamine (PE), and macromolecules (MMs) at 1.2 ppm were also mapped, although with larger mean CRLBs between 30% and 44%. The CRLBs at 4T were 19% lower on average as compared to 3T, consistent with a higher signal-to-noise ratio (SNR) and increased spectral resolution. Metabolite concentrations were in the ranges reported in previous studies. Glu concentration was significantly higher in gray matter (GM) compared to white matter (WM), as anticipated. The short acquisition time makes this methodology suitable for clinical studies.

A strategy for using tissue water as a concentration standard in (1)H magnetic resonance spectroscopic imaging studies on the brain is presented, and the potential errors that may arise when the method is used are examined. The sensitivity of the method to errors in estimates of the different water compartment relaxation times is shown to be small at short echo times (TEs). Using data from healthy human subjects, it is shown that different image segmentation approaches that are commonly used to account for partial volume effects (SPM2, FSL's FAST, and K-means) lead to different estimates of metabolite levels, particularly in gray matter (GM), owing primarily to variability in the estimates of the cerebrospinal fluid (CSF) fraction. While consistency does not necessarily validate a method, a multispectral segmentation approach using FAST yielded the lowest intersubject variability in the estimates of GM metabolites. The mean GM and white matter (WM) levels of N-acetyl groups (NAc, primarily N-acetylaspartate), choline (Ch), and creatine (Cr) obtained in these subjects using the described method with FAST multispectral segmentation are reported: GM [NAc] = 17.16 +/- 1.19 mM; WM [NAc] = 14.26 +/- 1.38 mM; GM [Ch] = 3.27 +/- 0.47 mM; WM [Ch] = 2.65 +/- 0.25 mM; GM [Cr] = 13.98 +/- 1.20 mM; and WM [Cr] = 7.10 +/- 0.67 mM.

Glutamate, a major excitatory neurotransmitter, has been implicated as an important mediator in the neurotransmission, potentiation, and negative affect associated with pain. We present results showing that a painful stimulus elicits a dynamic increase in glutamate (9.3% from baseline) concentrations in the anterior cingulate cortex, detectable using proton Magnetic Resonance Spectroscopy ((1)H-MRS). Increases in glutamine levels were also seen, which correlate strongly with the subjective level of pain experienced by participants (r(2) = 0.58, P0.01). These novel findings are the first time a dynamic change in glutamate and glutamine levels from baseline in response to an external stimuli has been measured in a single proton MRS scanning session. As such, this report demonstrates the efficacy of (1)H-MRS as a non-invasive tool for the study of neural responses to pain in vivo. The paradigm used in this study demonstrates that dynamic glutamate/glutamine changes due to stimulation are measurable by proton MRS, and could provide a means of testing novel pharmaceutical agents and other treatments for chronic pain.

Victims of minimal traumatic brain injury (mTBI) do not show clear morphological brain defects, but frequently suffer lasting cognitive deficits, emotional difficulties and behavioral disturbances. In the present study we adopted a non-invasive closed-head weight-drop mouse model to produce mTBI. We examined the effects of 20, 25, or 30 g weight drop 7, 30, 60 and 90 days following injury on mice's ability to perform the Morris water maze. The mice suffered profound long-lasting learning and memory deficits that were force- and time-dependent. Although the injured mice could acquire the task, they could not improve their initial escape latency by more than 50%, while normal mice improved by up to 450% (P

Previous studies have shown that location and direction of injury may affect outcome in experimental models of traumatic brain injury. Significant variability in outcome data has also been noted in studies using the lateral fluid percussion brain injury model (FPI) in rats. In recent studies from our laboratory, we observed considerable variability in localization and severity of tissue damage as a function of small changes in craniotomy position. To further address this issue, we examined the relationship between craniotomy position and brain lesion size/location in rats subjected to moderate FPI (2.28 +/- 0.18 atmospheres). With placement of a 5-mm craniotomy adjacent to the sagittal suture, there was both ipsilateral and contralateral damage as detected at 3 weeks posttrauma using T2-weighted magnetic resonance imaging (MRI). The MRI lesions were generally restricted to the hippocampus and subcortical layers. Shifting of the craniotomy site laterally was associated with increased ipsilateral tissue damage and a greater cortical component that correlated with distance from the sagittal suture. In contrast, the contralateral MRI lesion did not change significantly in size or location unless the center of the craniotomy was placed more than 3.5 mm from the sagittal suture, under which condition contralateral damage could no longer be detected. Ipsilateral tissue damage as determined from the MRI scans was linearly correlated to motor outcome but not with cognitive outcome as assessed by the Morris Water Maze. We conclude that craniotomy position is critical in determining extent and location of tissue injury produced during the lateral FPI model in rats. Addressing such potential variability is essential for studies that address either injury mechanisms or therapeutic treatments.

Background: Impairment in auditory sensory gating (ASG) has been documented in alcohol dependence [1]. Likewise, it has been shown that ASG becomes abnormal during alcohol administration in otherwise healthy individuals [2]. Patterns of gating abnormality associated with alcohol use are likely associated with an alcohol responsive neurochemical like glutamate (Glu), particularly since it is well-established that alcohol affects NMDA receptors and that glutamatergic functioning is abnormal in both acute alcohol use and in alcohol dependence [3]. Hence, a link between Glu metabolite levels and ASG was hypothesized. It was first hypothesized that Glu and ASG abnormality would be found in groups with alcohol dependence. A second hypothesis was that across groups, greater Glu would predict reduced ASG. Methods: Groups were comprised of healthy, non-drinking controls (Controls, N = 4), individuals with current alcohol dependence (AUD-current, N = 6), and with alcohol dependence in remission for at least 1 year (AUD-remission, N = 6). Participants underwent a diagnostic assessment for alcohol consumption, MRI, 1H-MRS for in vivo assessment of Glu and other metabolites, and MEG scanning during a paired click protocol. ASG was computed as the ratio of the source strength of the 50 ms component in the event related field (ERF) to the second click in the pair divided by the source strength of the 50 ms component to the first click in the pair. Results: Univariate MANOVAs controlling for age and gender revealed a significant effect for group on Glu and ASG, such that ASG ratios were significantly elevated, implying weakened gating. Glu concentration was reduced in AUD-current relative to the other two groups. Further analysis revealed that when additionally controlling for the group effect, reduced Glu predicted increasing impairment in ASG. Conclusions: The overall results were consistent with the hypothesis that differences in Glu metabolite levels associated with alcohol dependence result in impaired ASG.

The translation of MRS to clinical practice has been impeded by the lack of technical standardization. There are multiple methods of acquisition, post‐processing, and analysis whose details greatly impact the interpretation of the results. These details are often not fully reported, making it difficult to assess MRS studies on a standardized basis. This hampers the reviewing of manuscripts, limits the reproducibility of study results, and complicates meta‐analysis of the literature. In this paper a consensus group of MRS experts provides minimum guidelines for the reporting of MRS methods and results, including the standardized description of MRS hardware, data acquisition, analysis, and quality assessment. This consensus statement describes each of these requirements in detail and includes a checklist to assist authors and journal reviewers and to provide a practical way for journal editors to ensure that MRS studies are reported in full., This paper sets out the expert consensus on minimum reporting guidelines for MRS studies. It includes a checklist as a practical way for authors and journal editors to ensure that MRS studies are reported appropriately. A common set of reporting standards will greatly increase transparency, rigor, and replicability of MRS studies, and should further the successful integration of MRS into widespread clinical practice.

Health professionals should be aware of medical procedures that cause vascular access complications. This case describes a haemodialysis patient who experienced pain, swelling and bruising over a radiocephalic fistula following MRI. Exactly the same signs and symptoms were evident following a second scan performed 3emsp14;months later. Plausible explanations include a radio frequency-induced electrical current being formed at the arteriovenous fistula, or varying gradients of the MRI sequence stimulating peripheral nerves, leading to a site of increased tissue stimulation. Of note, a juxta-anastomotic venous stenosis was confirmed by fistulogram 4emsp14;days after the second scan, although whether this access failure was due to the MRI scan per se could not be ascertained. Nevertheless, these previously undocumented observations suggest that careful patient and fistula monitoring is required when completing MRI scans in those with an arteriovenous fistula.