@article {1674, title = {Peripheral inflammation related to lower fMRI activation during a working memory task and resting functional connectivity among older adults: a preliminary study.}, journal = {Int J Geriatr Psychiatry}, volume = {32}, year = {2017}, month = {2017 Mar}, pages = {341-349}, abstract = {

OBJECTIVE: Peripheral inflammation has been associated with adverse effects on cognition and brain structure in late life, a process called {\textquoteright}inflammaging.{\textquoteright} Identifying biomarkers of preclinical cognitive decline is critical in the development of preventative therapies, and peripheral inflammation may be able to serve as an indicator of cognitive decline. However, little is known regarding the relationship between peripheral inflammation and brain structure and function among older adults.

METHODS: Twenty-four older adults (mean age = 78) underwent a functional magnetic resonance imaging (fMRI) resting state functional connectivity scan, and a subset (n = 14) completed the n-Back working memory task in the scanner. All participants completed a blood draw, and inflammation was measured with interleukin 6 (IL-6) and C-Reactive Protein (CRP).

RESULTS: Surprisingly, age was unrelated to measures of inflammation (IL-6, CRP) or brain function (default mode network (DMN) connectivity; working memory performance; blood oxygenation level dependent (BOLD) activation with higher working memory load). However, lower functional connectivity between the left parietal seed and all other DMN regions was associated with higher levels of IL-6 and CRP. Additionally, greater plasma concentration of IL-6 was associated with lower BOLD activation in the left middle frontal gyrus in response to increased working memory load.

CONCLUSIONS: These preliminary findings support the importance of IL-6 and CRP in brain function among older adults. Frontal and parietal regions may be particularly sensitive to the effects of inflammation. Additionally, these findings provide preliminary evidence of inflammatory contributions to level of neural activity, even after accounting for vascular risk factors.

}, keywords = {Aged, Brain Mapping, C-Reactive Protein, Cognition, Cognitive Dysfunction, Female, Frontal Lobe, Humans, Inflammation, Interleukin-6, Magnetic Resonance Imaging, Male, Memory, Short-Term, Parietal Lobe, Rest}, issn = {1099-1166}, doi = {10.1002/gps.4482}, author = {Dev, Sheena I and Moore, Raeanne C and Soontornniyomkij, Benchawanna and Achim, Cristian L and Jeste, Dilip V and Eyler, Lisa T} } @article {125, title = {Paradox of pattern separation and adult neurogenesis: A dual role for new neurons balancing memory resolution and robustness.}, journal = {Neurobiol Learn Mem}, volume = {129}, year = {2016}, month = {2016 Mar}, pages = {60-8}, abstract = {

Hippocampal adult neurogenesis is thought to subserve pattern separation, the process by which similar patterns of neuronal inputs are transformed into distinct neuronal representations, permitting the discrimination of highly similar stimuli in hippocampus-dependent tasks. However, the mechanism by which immature adult-born dentate granule neurons cells (abDGCs) perform this function remains unknown. Two theories of abDGC function, one by which abDGCs modulate and sparsify activity in the dentate gyrus and one by which abDGCs act as autonomous coding units, are generally suggested to be mutually exclusive. This review suggests that these two mechanisms work in tandem to dynamically regulate memory resolution while avoiding memory interference and maintaining memory robustness.

}, issn = {1095-9564}, doi = {10.1016/j.nlm.2015.10.013}, author = {Johnston, Stephen T and Shtrahman, Matthew and Parylak, Sarah and Gon{\c c}alves, J Tiago and Gage, Fred H} } @article {129, title = {Primate-specific ORF0 contributes to retrotransposon-mediated diversity.}, journal = {Cell}, volume = {163}, year = {2015}, month = {2015 Oct 22}, pages = {583-93}, abstract = {

LINE-1 retrotransposons are fast-evolving mobile genetic entities that play roles in gene regulation, pathological conditions, and evolution. Here, we show that the primate LINE-1 5{\textquoteright}UTR contains a primate-specific open reading frame (ORF) in the antisense orientation that we named ORF0. The gene product of this ORF localizes to promyelocytic leukemia-adjacent nuclear bodies. ORF0 is present in more than 3,000 loci across human and chimpanzee genomes and has a promoter and a conserved strong Kozak sequence that supports translation. By virtue of containing two splice donor sites, ORF0 can also form fusion proteins with proximal exons. ORF0 transcripts are readily detected in induced pluripotent stem (iPS) cells from both primate species. Capped and polyadenylated ORF0 mRNAs are present in the cytoplasm, and endogenous ORF0 peptides are identified upon proteomic analysis. Finally, ORF0 enhances LINE-1 mobility. Taken together, these results suggest a role for ORF0 in retrotransposon-mediated diversity.

}, keywords = {5{\textquoteright} Untranslated Regions, Amino Acid Sequence, Animals, Base Sequence, Cytoplasm, Humans, Long Interspersed Nucleotide Elements, Molecular Sequence Data, Nuclear Proteins, Open Reading Frames, Pan troglodytes, Retroelements, Ribosomes, RNA Processing, Post-Transcriptional, RNA, Antisense, RNA, Messenger, Sequence Alignment}, issn = {1097-4172}, doi = {10.1016/j.cell.2015.09.025}, author = {Denli, Ahmet M and Narvaiza, I{\~n}igo and Kerman, Bilal E and Pena, Monique and Benner, Christopher and Marchetto, Maria C N and Diedrich, Jolene K and Aslanian, Aaron and Ma, Jiao and Moresco, James J and Moore, Lynne and Hunter, Tony and Saghatelian, Alan and Gage, Fred H} } @article {167, title = {Prospective Optimization.}, journal = {Proc IEEE Inst Electr Electron Eng}, volume = {102}, year = {2014}, month = {2014 May}, abstract = {

Human performance approaches that of an ideal observer and optimal actor in some perceptual and motor tasks. These optimal abilities depend on the capacity of the cerebral cortex to store an immense amount of information and to flexibly make rapid decisions. However, behavior only approaches these limits after a long period of learning while the cerebral cortex interacts with the basal ganglia, an ancient part of the vertebrate brain that is responsible for learning sequences of actions directed toward achieving goals. Progress has been made in understanding the algorithms used by the brain during reinforcement learning, which is an online approximation of dynamic programming. Humans also make plans that depend on past experience by simulating different scenarios, which is called prospective optimization. The same brain structures in the cortex and basal ganglia that are active online during optimal behavior are also active offline during prospective optimization. The emergence of general principles and algorithms for goal-directed behavior has consequences for the development of autonomous devices in engineering applications.

}, issn = {0018-9219}, doi = {10.1109/JPROC.2014.2314297}, author = {Sejnowski, Terrence J and Poizner, Howard and Lynch, Gary and Gepshtein, Sergei and Greenspan, Ralph J} } @article {160, title = {A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale.}, journal = {PLoS Comput Biol}, volume = {5}, year = {2009}, month = {2009 Mar}, pages = {e1000334}, abstract = {

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is critical, however, for both basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brainwide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brainwide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open-access data repository; compatibility with existing resources; and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.

}, keywords = {Animals, Brain, Databases, Factual, Humans, Macaca, Mice, Models, Neurological, Nerve Net, Neuroanatomy, Research Design}, issn = {1553-7358}, doi = {10.1371/journal.pcbi.1000334}, author = {Bohland, Jason W and Wu, Caizhi and Barbas, Helen and Bokil, Hemant and Bota, Mihail and Breiter, Hans C and Cline, Hollis T and Doyle, John C and Freed, Peter J and Greenspan, Ralph J and Haber, Suzanne N and Hawrylycz, Michael and Herrera, Daniel G and Hilgetag, Claus C and Huang, Z Josh and Jones, Allan and Jones, Edward G and Karten, Harvey J and Kleinfeld, David and K{\"o}tter, Rolf and Lester, Henry A and Lin, John M and Mensh, Brett D and Mikula, Shawn and Panksepp, Jaak and Price, Joseph L and Safdieh, Joseph and Saper, Clifford B and Schiff, Nicholas D and Schmahmann, Jeremy D and Stillman, Bruce W and Svoboda, Karel and Swanson, Larry W and Toga, Arthur W and Van Essen, David C and Watson, James D and Mitra, Partha P} }