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Danielle Wasserman,1,2,* Dorothea Bindman,1,* Alexander D Nesbitt,1– 3 Diana Cash,4 Milan Milosevic,5 Paul T Francis,6 K Ray Chaudhuri,7 Guy D Leschziner,1,2 Luigi Ferini-Strambi,8 Clive Ballard,9 Amy Eccles,10 Ivana Rosenzweig1,2 1Sleep and Brain Plasticity Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, UK; 2Sleep Disorders Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, UK; 3Headache Group, Department of Clinical Neurosciences, King’s College Hospital NHS Foundation Trust, London, UK; 4BRAIN, Department of Neuroimaging, King’s College London, London, UK; 5School of Public Health “Andrija Stampar“, University of Zagreb School of Medicine, Zagreb, Croatia; 6Wolfson Centre for Age-Related Diseases, King’s College London, London, UK; 7Movement Disorders Unit, King’s College Hospital, Department of Clinical and Basic Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, Parkinson Foundation Centre of Excellence, King’s College London, London, UK; 8Sleep Disorders Center, Department of Clinical Neurosciences, Università Vita-Salute San Raffaele, Milan, Italy; 9Medical School, University of Exeter, Exeter, UK; 10Department of Nuclear Medicine, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK*These authors contributed equally to this workCorrespondence: Ivana RosenzweigSleep and Brain Plasticity Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, Box 089, De Crespigny Park, London SE5 8AF, UKEmail ivana.1.rosenzweig@kcl.ac.ukIntroduction: Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is increasingly recognised as an important precursor disease state of alpha-synucleinopathies. This parasomnia is characterized by a history of recurrent nocturnal dream enactment behaviour, loss of skeletal muscle atonia, and increased phasic muscle activity during REM sleep. Neuroimaging studies of striatal dopamine transporter uptake tracer signaling suggest increasing dopaminergic deficit across the continuum of the alpha-synucleinopathies, with early sleep dysfunction suggestive of early caudate dysfunction. Henceforth, we set out to investigate the relationship between early sleep changes and the striatal dopaminergic availability in iRBD.Methods: Twelve patients with iRBD, who had undergone a video polysomnography and a neuroimaging assessment of striatal dopamine transporter (DaT) uptake tracer signaling, and 22 matched controls who had similarly undergone a video polysomnography were retrospectively identified. Data were statistically analyzed to identify altered sleep parameters and correlate them with striatal dopamine transporter uptake tracer signaling.Results: The iRBD patients exhibited an increased number of periodic limb movements during sleep (P=0.001), compared to 22 age-matched healthy subjects. In addition, several significant links were found between regional DaT-uptakes and sleep architecture. Correlational analyses suggested a strong positive association between sleep fragmentation and dopamine deficiency in left caudate (r=− 0.630, P=0.028), whilst an increased uptake in the whole striatum was strongly linked to the sleep efficiency, and to a lesser degree to the length of sleep duration.Discussion: To the best of our knowledge, this is the first demonstration of a close relationship between dopaminergic availability in striatum and the quality of sleep in iRBD. Taken together, our exploratory findings suggest that subtle but functionally significant striatal changes in early stages of iRBD may contribute to the further shaping of sleep architecture.Keywords: isolated rapid eye movement behaviour disorder, polysomnography, sleep architecture, striatum, striatal dopamine transporter uptake tracer signalling imaging, DaTSCAN

Po-Wah So,1 Antigoni Ekonomou,1 Kim Galley,1 Leigh Brody,2 Meliz Sahuri-Arisoylu,2 Ivan Rattray,3 Diana Cash,1 Jimmy D Bell2 1King’s College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Neuroimaging, London, UK; 2University of Westminster, Research Centre for Optimal Health, London, UK; 3King’s College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Basic and Clinical Neuroscience, London, UK Background: Ischemic stroke is a devastating condition, with metabolic derangement and persistent inflammation enhancing the initial insult of ischaemia. Recombinant tissue plasminogen remains the only effective treatment but limited as therapy must commence soon after the onset of symptoms.Purpose: We investigated whether acetate, which modulates many pathways including inflammation, may attenuate brain injury in stroke. As acetate has a short blood half-life and high amounts irritate the gastrointestinal tract, acetate was administered encapsulated in a liposomal nanoparticle (liposomal-encapsulated acetate, LITA).Methods: Transient ischemia was induced by 90 mins middle-cerebral artery occlusion (MCAO) in Sprague-Dawley rats, and LITA or control liposomes given intraperitoneally at occlusion and daily for up to two weeks post-MCAO. Magnetic resonance imaging (MRI) was used to estimate lesion volume at 24 h, 1 and 2 weeks post-MCAO and anterior lateral ventricular volume (ALVv) at 2 weeks post-MCAO. Locomotive behaviour was tested prior to the final MRI scan. After the final scan, brains were collected, and immunohistochemistry was performed. Results: Lesion volumes were decreased by ~80% from 24 h to one-week post-MCAO, in both control and LITA groups (P

As for standard positron emission tomography (PET) scanners, MR-compatible PET scanners will require gamma shielding to suppress the influence of activity outside the PET field of view (FOV). Suitable materials must have very specific properties, including magnetic properties close to those of water, high density, high atomic number, and ideally a low conductivity. In order to identify potential suitable materials, we have selected several heavy-metal-based candidates based on the available data for magnetic and shielding properties. These materials include several nonferromagnetic metals and metal oxides, two scintillating crystals (bismuth germanate and lead tungstate) and two metal/epoxy compounds. The magnetic resonance imaging (MRI) compatibility of these materials was assessed under various conditions, both on a human and a small-animal MRI scanner. In parallel, we assessed the shielding efficiency at 661 kev of the most promising candidates. These experiments showed that there is a range of possibilities for the design of MR-compatible gamma shields. Lead has acceptable magnetic compatibility but can induce significant conductivity-related artefacts. Heavy-metal-based minerals are fully insulating and hot-pressed lead monoxide showed good MR compatibility combined with good shielding properties. Other possibilities include the use of lead based powders and heavy-metal oxide composites. Index Terms--Magnetic resonance imaging (MRI), positron emission tomography (PET), shielding.

Surveys of labor educators and academic librarians, designed to study library usage by participants in labor education, indicate that a lack of communication and understanding exists between the two departments at many institutions. Increased cooperation and library utilization are recommended. Twenty-seven references are listed, and the questionnaires are appended. (Author/MES)

'Shoshone' sainfoin (Onobrychis viciifolia Scop.) (Reg. no. CV-258, PI 639688) was developed by the Wyoming Agricultural Experiment Station and jointly released with Montana Agricultural Experiment Station and the United States [...]

Complementary and alternative medicine (CAM) has been gaining interest among individuals with serious mental illnesses. Yet, very little is known about how CAM may be beneficial to mental health. This study explored the specific benefits attributed to CAM by a national sample of 255 individuals with a serious mental illness who experienced CAM as having a positive impact on their mental health. Data about the CAM benefits were gathered through open-ended questions embedded in a mail survey that examined the patterns of CAM use in this population. Qualitative analysis revealed a wide spectrum of benefits that encompassed all major areas of human functioning, including physical, emotional, cognitive, self, social, spiritual, and overall functioning, and addressed both the improvement of psychiatric symptomatology and the promotion of functional recovery. Study findings provide useful information that can guide both everyday clinical practice and future research on the efficacy of CAM for psychiatric populations. [ABSTRACT FROM AUTHOR]

Abstract: The loss of dopamine in idiopathic or animal models of Parkinson’s disease induces synchronized low-frequency oscillatory burst-firing in subthalamic nucleus neurones. We sought to establish whether these firing patterns observed in vivo were preserved in slices taken from dopamine-depleted animals, thus establishing a role for the isolated subthalamic–globus pallidus complex in generating the pathological activity. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) showed significant reductions of over 90% in levels of dopamine as measured in striatum by high pressure liquid chromatography. Likewise, significant reductions in tyrosine hydroxylase immunostaining within the striatum (>90%) and tyrosine hydroxylase positive cell numbers (65%) in substantia nigra were observed. Compared with slices from intact mice, neurones in slices from MPTP-lesioned mice fired significantly more slowly (mean rate of 4.2 Hz, cf. 7.2 Hz in control) and more irregularly (mean coefficient of variation of inter-spike interval of 94.4%, cf. 37.9% in control). Application of ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonopentanoic acid (AP5) and the GABAA receptor antagonist picrotoxin caused no change in firing pattern. Bath application of dopamine significantly increased cell firing rate and regularized the pattern of activity in cells from slices from both MPTP-treated and control animals. Although the absolute change was more modest in control slices, the maximum dopamine effect in the two groups was comparable. Indeed, when taking into account the basal firing rate, no differences in the sensitivity to dopamine were observed between these two cohorts. Furthermore, pairs of subthalamic nucleus cells showed no correlated activity in slices from either control (21 pairs) or MPTP-treated animals (20 pairs). These results indicate that the isolated but interconnected subthalamic–globus pallidus network is not itself sufficient to generate the aberrant firing patterns in dopamine-depleted animals. More likely, inputs from other regions, such as the cortex, are needed to generate pathological oscillatory activity. [Copyright &y& Elsevier]

We used the short-lived radionuclide, Br to follow γ-aminobutyrate (GABA) receptor-mediated halide exchange into membrane vesicles from rat cerebral cortex in millisecond and second time regions using quench-flow technique. The radioisotope was prepared by neutron capture [Br(n,γ)Br] on irradiation of a natural isotope of bromine, Br in a neutron flux. Br decays by β-emission with secondary γ-emission. Possible advantages of Br over Cl in anion tracer measurements include, (a) a short lifetime (t = 35.3 hr), which alleviates contamination and disposal problems, (b) high counting efficiency (1.54) due to the secondary radiation, (c) measurement with a γ-counter as well as a β-counter, (d) a simple preparation not requiring subsequent purification steps giving a specific activity depending on the irradiation time. With 6 hr irradiation time the specific activity was sufficient to make measurements with <1 m m Br, which is less than the bromide concentration known to affect the properties of GABA receptor. The radiotracers, Br and Cl could be compared with the same solution composition. In conditions where a direct effect of binding of halide to receptor does not contribute to a difference in measured ion-flux, Br was translocated only marginally faster than Cl. The effect of chlordiazepoxide (CDPX) (2-250 μ m) on the progress of GABA (10 μ m)-mediated Br uptake was measured in a time range of 200 msec to 20 sec using quench-flow technique. The two phases of anion exchange previously reported in this experimental model with GABA alone were observed. The rate of Br exchange was increased 2.3-fold at 30-60 μ m CDPX and was not further increased with increasing [CDPX]. The rate of halide exchange is a measure of open channel concentration. The isotope exchange rate constant, J, in a membrane vesicle preparation, is a measure of the membrane permeability per internal volume/surface area, J = PA/V. Receptor desensitization rate was also increased by CDPX, but unlike the isotope exchange rate, it continued to increase up to at least 250 μ m CDPX. [ABSTRACT FROM AUTHOR]

Chloride-36 exchange into three different membrane vesicle preparations from rat brain homogenate was followed. The different preparations all contained the same sealed vesicular components characterized by their rates of chloride exchange. The GABA-mediated 36Cl- exchange in all the preparations occurred in two phases shown to be mediated by two distinguishable receptors present in the activity ratio of 5:1 as previously described (Cash, D.J., Subbarao, K. 1987. Biochemistry 26:7556, 7562). Reported differences do not result from differences in the membrane preparations used or from the use of a GABA-mimetic instead of GABA, but from experimental differences. The preparations compared were made with mild or vigorous homogenization and with different extents of purification from solutes or membrane components: (i) a synaptoneurosome preparation, (ii) a Ficoll gradient preparation, and (iii) a washed P2 preparation. In each preparation the same four populations of membrane vesicles were characterized by their 36Cl- influx rates: (i) a major population (40-50%) (tau 1/2 = 1.4 min), (ii) a slower exchanging major population (40-55%) (tau 1/2 = 24 min), (iii) a minor population (5-12%) containing active GABA receptor and having the GABA-independent permeability of the slower exchanging population, and (iv) a very small exchange (approximately 2%) (tau 1/2 approximately 0.2 sec). The GABA-independent 36Cl- exchange processes were kinetically first order. The relative quantities of the different vesicle populations varied slightly with the preparation and purification technique. The identity of these components, observed in the different preparations, was attributed to the vesicle formation being dependent on the morphology and properties of the membrane rather than the preparation method. The soluble brain extract was GABA-mimetic with the two observed receptors, causing channel opening and desensitization. But little washing of the membrane was required to observe the function of both receptors. Muscimol was GABA-mimetic with both receptors. With muscimol, channel opening occurred at 2.6-fold lower concentrations while desensitization was unaltered relative to GABA. This is additional evidence that these responses are mediated by different pairs of binding sites. The dependence of desensitization rate on muscimol concentration indicated that there are two binding sites mediating desensitization, as described with GABA. [ABSTRACT FROM AUTHOR]

P.107 Hippocampal GABA-A 5 receptor subunits are down-regulated in the methylazoxymethanol model of schizophrenia. [Extracted from the article]

A balanced integration of emotional and cognitive information is essential for flexible behaviour, which involves the anterior cingulate cortex (ACC) and the midcingulate cortex (MCC) [1]. Both clinical and preclinical researchers have been interested in studying the role of ACC and MCC in health and disease but preclinical rodent studies so far have suffered from a severe misconception: The definition of ACC/MCC used for rodents is not homologous to the human definition of ACC/MCC. Due to this, numerous findings of rodent studies are not directly translatable to the human situation, an issue that has been addressed in the past [2]. However, the majority of researchers still use the non-homologous definition of rodent ACC/MCC and awareness of the homologous nomenclature needs to be raised. Here, we demonstrate in a series of experiments the value of the homologous rodent ACC/MCC definition for translational research. We conducted a literature review, showing that the non-homologous definition of rodent ACC/MCC does not match human ACC/MCC anatomy and connectivity, while the homologous definition does. We then determined volumes of ACC and MCC in the BALB/cJ mouse, a model demonstrating characteristic symptoms of CD and ADHD (increased aggression and inattention). BALB/cJ mice were tested in the resident-intruder paradigm, demonstrating increased aggression (reduced attack latency: p < 0.01, atypical biting pattern: p < 0.01 and more attacks as well as threats: p < 0.01) compared to BALB/cByJ mice, a non-aggressive genetically relevant substrain. Afterwards, mice were perfused and brains sliced to reconstruct volumes of ACC/MCC, by measuring the surface area of slices containing ACC/MCC, multiplied by the thickness of the slice. BALB/cJ mice demonstrated an increased volume of the ACC (p < 0.01) and a decreased volume of the MCC (p < 0.05), volumetric changes that are also observed in clinical CD and ADHD [3, 4]. A high percentage of the variance in aggressive behaviour was explained by ACC and MCC volumes (all R2 > 0.55 and all p < 0.05). Using the non-homologous definition, no volumetric differences between BALB/cJ and BALB/cByJ mice could be observed (p > 0.05), highlighting the importance of using the homologous ACC/MCC definition. Last, we aimed to validate our histological findings by using voxel-based morphometry (VBM) of structural magnetic resonance imaging (MRI) data to measure ACC/MCC volumes. BALB/cJ and BALB/cByJ mice were tested in the 5-choice serial reaction time task, a task probing attention. BALB/cJ mice showed a global attention deficit, indicated by an increased percentage of omissions compared to BALB/cByJ mice (p < 0.001). Ex-vivo MRI scanning was performed and VBM analysis supported our volumetric findings (p < 0.001). In addition, inattentive behaviour could be partly explained by ACC and MCC volumes (R2 > 0.25 and p < 0.05). Together, these experiments emphasize the value of the homologous definition of ACC and MCC, especially for translational neuroscience. Furthermore, our data demonstrate that structural changes in ACC and MCC in BALB/cJ mice are related to aggression and inattention, mirroring human neuroimaging studies in CD and ADHD patients. [ABSTRACT FROM AUTHOR]