EMERGING IDEAS IN NEURAL SCIENCE

Prediction of Cognitive decline via PET of Brain β-Amyloid and Tau Levels in Adults With Down Syndrome

brainchemist — Wed, 15 Feb 2012 02:14:51 +0000

Positron Emission Tomography of Brain β-Amyloid and Tau Levels in Adults With Down Syndrome

Science daily article

Dr. Linda D. Nelson, PhD, Dr. Prabha Siddarth, PhD, Dr. Vladimir Kepe, PhD, Mr. Kevin E. Scheibel, BS, Dr. S. C. Huang, PhD, Dr. Jorge R. Barrio, PhD, and Dr. Gary W. Small, MD

Departments of Psychiatry and Biobehavioral Sciences (Drs Nelson, Siddarth, and Small), Molecular and Medical Pharmacology (Drs Kepe, Huang, and Barrio), and Neurology (Mr Scheibel), Semel Institute for Neuroscience and Human Behavior (Drs Nelson, Siddarth, and Small), Brain Research Institute (Dr Nelson), UCLA Intellectual and Developmental Disabilities Research Center (Dr Nelson), Mary S. Easton Center for Alzheimer’s Disease Research (Drs Kepe and Small), and UCLA Center on Aging (Dr Small), University of California, Los Angeles

strong>ABSTRACT

Objectives
To determine the neuropathological load in the living brain of nondemented adults with Down syndrome using positron emission tomography with 2-(1-{6-[(2-fluorine 18–labeled fluoroethyl)methylamino]-2-napthyl}ethylidene) malononitrile ([18F]FDDNP) and to assess the influence of age and cognitive and behavioral functioning. For reference, [18F]FDDNP binding values and patterns were compared with those from patients with Alzheimer disease and cognitively intact control participants.
Design
Cross-sectional clinical study.
Participants
Volunteer sample of 19 persons with Down syndrome without dementia (mean age, 36.7 years), 10 patients with Alzheimer disease (mean age, 66.5 years), and 10 controls (mean age, 43.8 years).
Main Outcome Measures
Binding of [18F]FDDNP in brain regions of interest, including the parietal, medial temporal, lateral temporal, and frontal lobes and posterior cingulate gyrus, and the average of all regions (global binding).
Results
The [18F]FDDNP binding values were higher in all brain regions in the Down syndrome group than in controls. Compared with the Alzheimer disease group, the Down syndrome group had higher [18F]FDDNP binding values in the parietal and frontal regions, whereas binding levels in other regions were comparable. Within the Down syndrome group, age correlated with [18F]FDDNP binding values in all regions except the posterior cingulate, and several measures of behavioral dysfunction showed positive correlations with global, frontal, parietal, and posterior cingulate [18F]FDDNP binding.
Conclusions
Consistent with neuropathological findings from postmortem studies, [18F]FDDNP positron emission tomography shows high binding levels in Down syndrome comparable to Alzheimer disease and greater levels than in members of a control group. The positive associations between [18F]FDDNP binding levels and age as well as behavioral dysfunction in Down syndrome are consistent with the age-related progression of Alzheimer-type neuropathological findings in this population.

Weight loss can be Socially contagious

brainchemist — Wed, 15 Feb 2012 02:08:51 +0000

NPG Article

Weight Loss Can Be Contagious

Young adults’ performance in a low intensity weight loss campaign.

Gokee Larose J, Leahey TM, Weinberg BM, Kumar R, Wing RR.
Source

1] Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University [2] Weight Control and Diabetes Research Center, the Miriam Hospital.
Abstract

Young adults (YA) are underrepresented in behavioral weight loss programs and achieve poorer outcomes than older adults (OA). There has been a call to develop programs specifically targeting this age group. This study examined the performance of YA enrolled in a low intensity, team-based weight loss campaign and compared their outcomes to OA to determine the utility of such an approach for weight loss in this population. Shape Up Rhode Island 2009 was a 12-week online team-based weight loss and exercise competition (N=6795, 81% female, 94% White, age=44.7±11.2, BMI=29.4±5.9). YA was defined as 18-35 years and OA as >35 years; YA and OA were compared on enrollment, retention, weight loss and change in steps. A total of 1562 YA enrolled and 715 completed the program. Fewer YA completed compared with OA (46% vs. 62%, p<.001). However, among completers, YA achieved greater percent weight loss (-4.5±4.0% vs. -3.8±3.2%) and greater daily step change (+1578.2±3877.2 vs. +1342.2±3645.7) than OA (p's<.001). Further, more YA completers achieved a ≥5% weight loss (40% vs. 29%, p<.001). Findings were consistent in the overweight/obese subsample, and using ≤25 years of age as the cut off for YA. Weight losses among YA in this low-intensity weight loss campaign were quite promising, with over 700 YA completing the program and on average achieving a 4.5% weight loss. Indeed, the potential public health impact of such an approach is substantial; future efforts to develop programs for this age group may benefit from using a low intensity, team-based approach.

Regeneration After a Stroke Requires Intact Communication Channels Between Brain Hemispheres

brainchemist — Wed, 23 Nov 2011 04:29:07 +0000

Degeneration of corpus callosum and recovery of motor function after stroke: A multimodal magnetic resonance imaging study.

Hum Brain Mapp. 2011 Oct 22. doi: 10.1002/hbm.21417. [Epub ahead of print]
Degeneration of corpus callosum and recovery of motor function after stroke: A multimodal magnetic resonance imaging study.
Wang LE, Tittgemeyer M, Imperati D, Diekhoff S, Ameli M, Fink GR, Grefkes C.
Source
Cognitive Neurology Section, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, Germany; International Graduate School of Neuroscience and Research School, Ruhr University Bochum, Germany; Neuromodulation and Neurorehabilitation Section, Max Planck Institute for Neurological Research, Cologne, Germany; Division of Speech and Hearing Sciences, Faculty of Education, The University of Hong Kong, China.
Abstract
Animal models of stroke demonstrated that white matter ischemia may cause both axonal damage and myelin degradation distant from the core lesion, thereby impacting on behavior and functional outcome after stroke. We here used parameters derived from diffusion magnetic resonance imaging (MRI) to investigate the effect of focal white matter ischemia on functional reorganization within the motor system. Patients (n = 18) suffering from hand motor deficits in the subacute or chronic stage after subcortical stroke and healthy controls (n = 12) were scanned with both diffusion MRI and functional MRI while performing a motor task with the left or right hand. A laterality index was employed on activated voxels to assess functional reorganization across hemispheres. Regression analyses revealed that diffusion MRI parameters of both the ipsilesional corticospinal tract (CST) and corpus callosum (CC) predicted increased activation of the unaffected hemisphere during movements of the stroke-affected hand. Changes in diffusion MRI parameters possibly reflecting axonal damage and/or destruction of myelin sheath correlated with a stronger bilateral recruitment of motor areas and poorer motor performance. Probabilistic fiber tracking analyses revealed that the region in the CC correlating with the fMRI laterality index and motor deficits connected to sensorimotor cortex, supplementary motor area, ventral premotor cortex, superior parietal lobule, and temporoparietal junction. The results suggest that degeneration of transcallosal fibers connecting higher order sensorimotor regions constitute a relevant factor influencing cortical reorganization and motor outcome after subcortical stroke. Hum Brain Mapp, 2011. © 2011 Wiley-Liss, Inc.

Influencia del grado de somnolencia, cantidad y calidad de sueño sobre el rendimiento académico en adolescentes.

brainchemist — Wed, 23 Nov 2011 02:32:53 +0000

Adolescents Who Sleep Better Score Higher in Math and Physical Education

http://www.sciencedaily.com/releases/2011/10/111020025758.htm

University of Granada (2011, October 20). Adolescents who sleep better score higher in math and physical education. ScienceDaily. Retrieved November 22, 2011, from http://www.sciencedaily.com /releases/2011/10/111020025758.htm

PDF

http://redalyc.uaemex.mx/src/inicio/ArtPdfRed.jsp?iCve=33715423004

Development of Human Brain Wiring Continues into Adulthood – a longitudinal DTI study

brainchemist — Fri, 23 Sep 2011 15:28:06 +0000

Longitudinal Development of Human Brain Wiring Continues from Childhood into Adulthood

Catherine Lebel and Christian Beaulieu

Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta T6G 2V2, Canada
Author contributions: C.L. and C.B. designed research; C.L. and C.B. performed research; C.L. and C.B. analyzed data; C.L. and C.B. wrote the paper.

Abstract

Healthy human brain development is a complex process that continues during childhood and adolescence, as demonstrated by many cross-sectional and several longitudinal studies. However, whether these changes end in adolescence is not clear. We examined longitudinal white matter maturation using diffusion tensor tractography in 103 healthy subjects aged 5–32 years; each volunteer was scanned at least twice, with 221 total scans. Fractional anisotropy (FA) and mean diffusivity (MD), parameters indicative of factors including myelination and axon density, were assessed in 10 major white matter tracts. All tracts showed significant nonlinear development trajectories for FA and MD. Significant within-subject changes occurred in the vast majority of children and early adolescents, and these changes were mostly complete by late adolescence for projection and commissural tracts. However, association tracts demonstrated postadolescent within-subject maturation of both FA and MD. Diffusion parameter changes were due primarily to decreasing perpendicular diffusivity, although increasing parallel diffusivity contributed to the prolonged increases of FA in association tracts. Volume increased significantly with age for most tracts, and longitudinal measures also demonstrated postadolescent volume increases in several association tracts. As volume increases were not directly associated with either elevated FA or reduced MD between scans, the observed diffusion parameter changes likely reflect microstructural maturation of brain white matter tracts rather than just gross anatomy.

Novel Cryo-Imaging technique of GBM’s Microenvironment Reveals Migration and Dispersal Pathways in Vivid 3D Detail

brainchemist — Sun, 28 Aug 2011 13:45:28 +0000

Novel Cryo-Imaging of the Glioma Tumor Microenvironment Reveals Migration and Dispersal Pathways in Vivid Three-Dimensional Detail

Susan M. Burden-Gulley1, Mohammed Q. Qutaish2, Kristin E. Sullivant2, Hong Lu2, Jing Wang2, Sonya E.L. Craig1, James P. Basilion2,4, David L. Wilson2, and Susann M. Brady-Kalnay1,3

Departments of 1Molecular Biology and Microbiology, 2Biomedical Engineering, 3Neuroscience, 4NFCR Center for Molecular Imaging, and Radiology, Case Western Reserve University, Cleveland, Ohio

Abstract
Traditional methods of imaging cell migration in the tumor microenvironment include serial sections of xenografts and standard histologic stains. Current molecular imaging techniques suffer from low resolution and difficulty in imaging through the skull. Here we show how computer algorithms can be used to reconstruct images from tissue sections obtained from mouse xenograft models of human glioma and can be rendered into three-dimensional images offering exquisite anatomic detail of tumor cell dispersal. Our findings identify human LN-229 and rodent CNS-1 glioma cells as valid systems to study the highly dispersive nature of glioma tumor cells along blood vessels and white matter tracts in vivo. This novel cryo-imaging technique provides a valuable tool to evaluate therapeutic interventions targeted at limiting tumor cell invasion and dispersal.

Latitudinal variation in light levels drives human visual system size (Northern Humans Had Bigger Brains)

brainchemist — Sun, 07 Aug 2011 17:06:10 +0000

Latitudinal variation in light levels drives human visual system size
Eiluned Pearce* and Robin Dunbar

Institute of Cognitive and Evolutionary Anthropology, University of Oxford, 64 Banbury Road, Oxford OX2 6PN, UK

Ambient light levels influence visual system size in birds and primates. Here, we argue that the same is true for humans. Light levels, in terms of both the amount of light hitting the Earth’s surface and day length, decrease with increasing latitude. We demonstrate a significant positive relationship between absolute latitude and human orbital volume, an index of eyeball size. Owing to tight scaling between visual system components, this will translate into enlarged visual cortices at higher latitudes. We also show that visual acuity measured under full-daylight conditions is constant across latitudes, indicating that selection for larger visual systems has mitigated the effect of reduced ambient light levels. This provides, to our knowledge, the first support that light levels drive intraspecific variation in visual system size in the human population.

Science daily

“This study adds weight to other research that has looked at the links between eye size and light levels. Other studies have already shown that birds with relatively bigger eyes are the first to sing at dawn in low light. The eyeball size across all primates has been found to be associated with when they choose to eat and forage — with species with the largest eyes being those that are active at night.”

Life at the Top: Alpha males exhibit much higher stress hormone levels

brainchemist — Mon, 18 Jul 2011 16:18:52 +0000

Life at the Top: Rank and Stress in Wild Male Baboons

Laurence R. Gesquiere1,*, Niki H. Learn1, M. Carolina M. Simao1, Patrick O. Onyango1, Susan C. Alberts2,3 Jeanne Altmann

1 Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544. USA.
2 Department of Biology, Duke University, Durham, NC, USA.
3 Institute of Primate Research, National Museums of Kenya, Nairobi, Kenya.
4 Department of Veterinary Anatomy and Physiology, University of Nairobi, Chiromo Campus, Post Office Box 30197 00100, Nairobi, Kenya.

Sciencedaily

In social hierarchies, dominant individuals experience reproductive and health benefits, but the costs of social dominance remain a topic of debate. Prevailing hypotheses predict that higher-ranking males experience higher testosterone and glucocorticoid (stress hormone) levels than lower-ranking males when hierarchies are unstable but not otherwise. In this long-term study of rank-related stress in a natural population of savannah baboons (Papio cynocephalus), high-ranking males had higher testosterone and lower glucocorticoid levels than other males, regardless of hierarchy stability. The singular exception was for the highest-ranking (alpha) males, who exhibited both high testosterone and high glucocorticoid levels. In particular, alpha males exhibited much higher stress hormone levels than second-ranking (beta) males, suggesting that being at the very top may be more costly than previously thought.

Milestone: The X-ray Crystal structure of the voltage gated sodium channel

brainchemist — Mon, 18 Jul 2011 14:53:37 +0000

The crystal structure of a voltage-gated sodium channel

Jian Payandeh, Todd Scheuer, Ning Zheng & William A. Catterall

Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA
Jian Payandeh, Todd Scheuer, Ning Zheng & William A. Catterall
Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA
Ning Zheng

Voltage-gated sodium (NaV) channels initiate electrical signalling in excitable cells and are the molecular targets for drugs and disease mutations, but the structural basis for their voltage-dependent activation, ion selectivity and drug block is unknown. Here we report the crystal structure of a voltage-gated Na+ channel from Arcobacter butzleri (NavAb) captured in a closed-pore conformation with four activated voltage sensors at 2.7 Å resolution. The arginine gating charges make multiple hydrophilic interactions within the voltage sensor, including unanticipated hydrogen bonds to the protein backbone. Comparisons to previous open-pore potassium channel structures indicate that the voltage-sensor domains and the S4–S5 linkers dilate the central pore by pivoting together around a hinge at the base of the pore module. The NavAb selectivity filter is short, ~4.6 Å wide, and water filled, with four acidic side chains surrounding the narrowest part of the ion conduction pathway. This unique structure presents a high-field-strength anionic coordination site, which confers Na+ selectivity through partial dehydration via direct interaction with glutamate side chains. Fenestrations in the sides of the pore module are unexpectedly penetrated by fatty acyl chains that extend into the central cavity, and these portals are large enough for the entry of small, hydrophobic pore-blocking drugs. This structure provides the template for understanding electrical signalling in excitable cells and the actions of drugs used for pain, epilepsy and cardiac arrhythmia at the atomic level.

Cortical Neural Prostheses turns memory on an off

brainchemist — Fri, 17 Jun 2011 22:05:30 +0000

A cortical neural prosthesis for restoring and enhancing memory

Theodore W Berger1, Robert E Hampson2, Dong Song1, Anushka Goonawardena2, Vasilis Z Marmarelis1 and Sam A Deadwyler2
1 Depatment of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA
2 Department of Physiology and Pharmacology, Wake Forest University, Winston-Salem, NC, USA

ABSTRACT
A primary objective in developing a neural prosthesis is to replace neural circuitry in the brain that no longer functions appropriately. Such a goal requires artificial reconstruction of neuron-to-neuron connections in a way that can be recognized by the remaining normal circuitry, and that promotes appropriate interaction. In this study, the application of a specially designed neural prosthesis using a multi-input/multi-output (MIMO) nonlinear model is demonstrated by using trains of electrical stimulation pulses to substitute for MIMO model derived ensemble firing patterns. Ensembles of CA3 and CA1 hippocampal neurons, recorded from rats performing a delayed-nonmatch-to-sample (DNMS) memory task, exhibited successful encoding of trial-specific sample lever information in the form of different spatiotemporal firing patterns. MIMO patterns, identified online and in real-time, were employed within a closed-loop behavioral paradigm. Results showed that the model was able to predict successful performance on the same trial. Also, MIMO model-derived patterns, delivered as electrical stimulation to the same electrodes, improved performance under normal testing conditions and, more importantly, were capable of recovering performance when delivered to animals with ensemble hippocampal activity compromised by pharmacologic blockade of synaptic transmission. These integrated experimental-modeling studies show for the first time that, with sufficient information about the neural coding of memories, a neural prosthesis capable of real-time diagnosis and manipulation of the encoding process can restore and even enhance cognitive, mnemonic processes.