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Article
| Open AccessReconciling persistent and dynamic hypotheses of working memory coding in prefrontal cortex
Working memory (WM) is represented in persistent activity of single neurons as well as a dynamic population code. Here, the authors find that neurons flexibly switch their coding according to current attention while those with stable resting activity maintain WM representations through dynamic activity patterns.
- Sean E. Cavanagh
- , John P. Towers
- & Steven W. Kennerley
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Article
| Open AccessThe sulfite oxidase Shopper controls neuronal activity by regulating glutamate homeostasis in Drosophila ensheathing glia
In Drosophila, ensheathing glia encase the neuropil but their function is not well understood. Here the authors show a surprising role of ensheathing glia in regulating glutamate homeostasis and locomotion which is controlled by the sulfite oxidase Shopper.
- Nils Otto
- , Zvonimir Marelja
- & Christian Klämbt
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Article
| Open AccessRevisiting the functional significance of binocular cues for perceiving motion-in-depth
The presence of opposite horizontal motion in the two eyes is a cue for perceiving motion-in-depth, but also leads to suppressed motion sensitivity. Here, the authors address this paradox and show that spatial and interocular integration mechanisms, distinct from the extraction of motion-in-depth, drive suppression.
- Peter J. Kohler
- , Wesley J. Meredith
- & Anthony M. Norcia
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Article
| Open AccessIntrinsic neuronal dynamics predict distinct functional roles during working memory
Prefrontal neurons exhibit both transient and persistent firing in working memory tasks. Here the authors report that the intrinsic timescale of neuronal firing outside the task is predictive of the temporal dynamics of coding during working memory in three frontoparietal brain areas.
- D. F. Wasmuht
- , E. Spaak
- & M. G. Stokes
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Article
| Open AccessArgininosuccinic aciduria fosters neuronal nitrosative stress reversed by Asl gene transfer
Patients with mutations in the ASL gene present with argininosuccinic aciduria characterised by hyperammonaemia and cognitive impairment. Here, the authors show that cerebral disease involves neuronal nitrosative/oxidative stress that is not induced by hyperammonaemia, and that it can be reversed using AAV-ASL directed to liver and brain in mice.
- Julien Baruteau
- , Dany P. Perocheau
- & Simon N. Waddington
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Article
| Open AccessPsychophysical reverse correlation reflects both sensory and decision-making processes
Reverse correlation is a psychophysics technique used to infer sensory filter properties by measuring how changes in stimuli influence behavior. Here, the authors show that reverse correlation is shaped by both sensory and decision-making processes, and validate a method to partition their contributions.
- Gouki Okazawa
- , Long Sha
- & Roozbeh Kiani
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Article
| Open AccessMAP1B mutations cause intellectual disability and extensive white matter deficit
Intellectual disability (ID) is characterized by an intelligence quotient of below 70 and impaired adaptive skills. Here, analyzing whole genome sequences from 31,463 Icelanders, Walters et al. identify variants in MAP1B associated with ID and extensive brain-wide white matter deficits.
- G. Bragi Walters
- , Omar Gustafsson
- & Kari Stefansson
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Article
| Open AccessLRRK2 kinase regulates α-synuclein propagation via RAB35 phosphorylation
Mutations in LRRK2 kinase are associated with Parkinson’s disease. Here the authors show that LRRK2 modulates propagation of α-synuclein, using rodent and C. elegans models, and show that this is dependent on phosphorylation of one of its substrates, RAB35.
- Eun-Jin Bae
- , Dong-Kyu Kim
- & Seung-Jae Lee
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Article
| Open AccessVti1a/b regulate synaptic vesicle and dense core vesicle secretion via protein sorting at the Golgi
Vti1a and Vti1b are SNARE proteins implicated in regulated secretion. Here the authors show that Vti1a and Vti1b control protein sorting at the Golgi, and targeting to the axon, and thereby indirectly control regulated secretion at the synapse.
- Javier Emperador-Melero
- , Vincent Huson
- & Matthijs Verhage
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Article
| Open AccessReciprocal control of excitatory synapse numbers by Wnt and Wnt inhibitor PRR7 secreted on exosomes
Wnts are important for synapse formation and maintenance. Here, the authors show that proline-rich 7 (PRR7) is a Wnt inhibitor that is secreted via exosomes to regulate excitatory synapse numbers.
- Sang H. Lee
- , Seung Min Shin
- & Qing-song Liu
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Article
| Open AccessHuman neuroepithelial stem cell regional specificity enables spinal cord repair through a relay circuit
The optimal type or regional origin of stem cells for regenerative applications in the nervous system has not yet been established. Here the authors show that human neuroepithelial stem cells from the developing spinal cord, but not those from the developing cortex, show good host-graft interaction when transplanted to rodent models of spinal cord injury.
- Maria Teresa Dell’Anno
- , Xingxing Wang
- & Stephen M. Strittmatter
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Article
| Open AccessSimultaneous dendritic voltage and calcium imaging and somatic recording from Purkinje neurons in awake mice
Dendritic integration is important for information processing in the brain. Here, in awake mice, authors combine simultaneous dendritic recording of voltage and calcium signals, with somatic recording from Purkinje neurons, enabling characterization of dendritic spiking, action potential backpropagation, and ‘hotspots’ in spiny dendrites.
- Christopher J. Roome
- & Bernd Kuhn
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Article
| Open AccessAxonal G3BP1 stress granule protein limits axonal mRNA translation and nerve regeneration
G3BP1 is RasGAP SH3 domain binding protein 1 that interacts with 48S pre-initiation complex when translation is stalled. Here, Twiss and colleagues show that neuronal G3BP1 can negatively regulate axonal mRNA translation, and inhibit axonal regeneration after injury.
- Pabitra K. Sahoo
- , Seung Joon Lee
- & Jeffery L. Twiss
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Article
| Open AccessExperience-dependent structural plasticity targets dynamic filopodia in regulating dendrite maturation and synaptogenesis
During development, dendrites display structural plasticity, as reflected in the appearance of long, thin and highly motile dendritic filopodia. Here, the authors examine dendritic dynamics of ventral lateral neurons in the developing Drosophila larva, and identify Amphiphysin as an important regulator of this process.
- Chengyu Sheng
- , Uzma Javed
- & Quan Yuan
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Article
| Open AccessV2a interneuron diversity tailors spinal circuit organization to control the vigor of locomotor movements
Locomotor circuits in the spinal cord produce precise movements with variations in timing and vigor. Here, the authors report that such motor flexibility is generated through the specificity of connections between subtypes of V2a interneurons and motoneuron populations and their distinct plasticity mechanisms.
- Jianren Song
- , Elin Dahlberg
- & Abdeljabbar El Manira
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Article
| Open AccessRegion-specific and state-dependent action of striatal GABAergic interneurons
Striatal GABAergic interneurons regulate the influence of cortical inputs on striatal projection neurons through feedforward inhibition. Here, the authors report that this inhibition is mediated mainly by PV interneurons in the dorsolateral striatum and SOM interneurons in the dorsomedial striatum.
- Elodie Fino
- , Marie Vandecasteele
- & Laurent Venance
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Article
| Open AccessLgl1 controls NG2 endocytic pathway to regulate oligodendrocyte differentiation and asymmetric cell division and gliomagenesis
Oligodendrocyte progenitor cells (OPCs) undergo asymmetric cell division, and disruption of such mechanism can generate oligodendroglioma precursors. Here, Daynac and colleagues show that Lgl1 regulates asymmetric division and differentiation of OPCs by interfering with the endocytosis pathway, and that Lgl1 knockout can lead to gliomagenesis.
- Mathieu Daynac
- , Malek Chouchane
- & Claudia K. Petritsch
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Article
| Open AccessEpigenetic regulation of the circadian gene Per1 contributes to age-related changes in hippocampal memory
Circadian rhythms are known to modulate memory, but it’s not known whether clock genes in the hippocampus are required for memory consolidation. Here, the authors show that epigenetic regulation of clock gene Period1 in the hippocampus regulates memory and contributes to age-related memory decline, independent of circadian rhythms.
- Janine L. Kwapis
- , Yasaman Alaghband
- & Marcelo A. Wood
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Article
| Open AccessSmooth tracking of visual targets distinguishes lucid REM sleep dreaming and waking perception from imagination
When tracking a moving object, our eyes make smooth pursuit movements; however, tracking an imaginary object produces jerky saccadic eye movements. Here, the authors show that during lucid dreams, the eyes smoothly follow dreamed objects. In this respect, dream imagery is more similar to perception than imagination.
- Stephen LaBerge
- , Benjamin Baird
- & Philip G. Zimbardo
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Article
| Open AccessSleep loss causes social withdrawal and loneliness
Loneliness markedly increases mortality and morbidity, yet the factors triggering loneliness remain largely unknown. This study shows that sleep loss leads to a neurobehavioral phenotype of human social separation and loneliness, one that is transmittable to non-sleep-deprived individuals.
- Eti Ben Simon
- & Matthew P. Walker
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Article
| Open AccessLearning auditory discriminations from observation is efficient but less robust than learning from experience
Many animals can learn, not just by direct experience, but by observing another animal performing a task. Here, the authors show in zebra finches that observer learning is efficient, but differs from direct learning in that it is less generalizable to novel stimuli.
- Gagan Narula
- , Joshua A. Herbst
- & Richard H. R. Hahnloser
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Article
| Open AccessNeonatal brain injury causes cerebellar learning deficits and Purkinje cell dysfunction
Premature infants are vulnerable to hypoxia and thus white matter injury, especially in the cerebellum, which develops during late gestation. Here, the authors test the effects of perinatal hypoxia on motor performance and rescue behavioral deficits using the GABA reuptake inhibitor Tiagabine.
- Aaron Sathyanesan
- , Srikanya Kundu
- & Vittorio Gallo
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Article
| Open AccessItch suppression in mice and dogs by modulation of spinal α2 and α3GABAA receptors
Chronic itch affects about 10% of the general population, however current treatments are largely ineffective. Here, the authors show that targeting of inhibitory α2 and α3GABAA receptors reduces itch in mice and in a canine model, suggesting this a potentially useful therapeutic approach.
- William T. Ralvenius
- , Elena Neumann
- & Hanns Ulrich Zeilhofer
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Article
| Open AccessElongator mutation in mice induces neurodegeneration and ataxia-like behavior
Elp6 is a component of the Elongator complex that regulates tRNAs and translation. Here the authors identify a mutation in the Elp6 gene that contributes to the cerebellar ataxia-like phenotype in a mutant mouse.
- Marija Kojic
- , Monika Gaik
- & Brandon J. Wainwright
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Article
| Open AccessMultiple timescales of normalized value coding underlie adaptive choice behavior
Previous work has shown that the neural representation of value adapts to the recent history of rewards. Here, the authors report that a computational model based on divisive normalization over multiple timescales can explain changes in value coding driven by changes in the reward statistics.
- Jan Zimmermann
- , Paul W. Glimcher
- & Kenway Louie
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Article
| Open AccessCommensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma
Glaucoma is a neurodegenerative disease of which the etiology is still unclear. Here the authors show that elevation of intraocular pressure induces T cell infiltration in the eyes. Furthermore, they show that T cell cross-reactivity between endogenous and commensal antigens contributes to disease onset in mice.
- Huihui Chen
- , Kin-Sang Cho
- & Dong F. Chen
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Article
| Open AccessRole of VTA dopamine neurons and neuroligin 3 in sociability traits related to nonfamiliar conspecific interaction
Individuals with autism spectrum disorder have alteration in social and novelty behaviors. Here, Bellone and colleagues show that chemogenetic inhibition of mouse dopamine neurons in the ventral tegmental area can blunt exploration towards unfamiliar conspecifics, and that these behavioral deficits are recapitulated in mice lacking neuroligin3 gene product.
- Sebastiano Bariselli
- , Hanna Hörnberg
- & Camilla Bellone
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Article
| Open AccessTranscriptional and physiological adaptations in nucleus accumbens somatostatin interneurons that regulate behavioral responses to cocaine
While making up a small percentage of neurons in the nucleus accumbens, somatostatin interneurons may have important function in dopamine- and addiction-related behavior. Here, Ribeiro and colleagues show that somatostatin interneurons regulate behavioral responses to cocaine with physiological and transcriptomic changes.
- Efrain A. Ribeiro
- , Marine Salery
- & Eric J. Nestler
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Article
| Open AccessDevelopmental seizures and mortality result from reducing GABAA receptor α2-subunit interaction with collybistin
The inhibitory synaptic protein collybistin (CB) and GABAAR-α subunits are thought to interact, but strength and specificity are unclear. Here the authors study the CB–α2 interaction and show that a mouse mutated in the CB-binding region of α2 displays a loss of specific synapses and seizure.
- Rochelle M. Hines
- , Hans Michael Maric
- & Stephen J. Moss
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Article
| Open AccessRegulation of striatal cells and goal-directed behavior by cerebellar outputs
Cerebellar outputs contribute to motor as well as cognitive behaviors. Here, the authors elucidate the connectivity between deep cerebellar nuclei and specific cell types in the striatum via the intralaminar thalamic nucleus and the participation of this circuit in striatum-dependent behavior.
- Le Xiao
- , Caroline Bornmann
- & Peter Scheiffele
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Article
| Open AccessEvaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia
Chromatin accessibility may be altered in disease states. Here the authors carry out ATAC-seq on a large number of samples of dorsolateral prefrontal cortex from individuals with schizophrenia, and healthy controls.
- Julien Bryois
- , Melanie E. Garrett
- & Gregory E. Crawford
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Article
| Open AccessSocial interactions impact on the dopaminergic system and drive individuality
Individual animals differ in behavioral traits, but the mechanisms underlying individuation are unclear. Here, the authors show that mice living in a ‘city’ develop individual behavior differences, associated with changes in dopamine cell firing, that can be reversed on moving them to a different social environment.
- N. Torquet
- , F. Marti
- & P. Faure
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Article
| Open AccessDevelopment of MPFC function mediates shifts in self-protective behavior provoked by social feedback
People insulate themselves against negative social feedback via self-protective behaviors. Here, the authors show that early adolescents react against immediate social feedback, but adults also consider accumulated past negative evaluations, a function mediated by the rostromedial prefrontal cortex (RMPFC).
- Leehyun Yoon
- , Leah H. Somerville
- & Hackjin Kim
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Article
| Open AccessGenome-wide association study results for educational attainment aid in identifying genetic heterogeneity of schizophrenia
Educational attainment and schizophrenia have a negative phenotypic relationship but show positive genetic correlation. Here, the authors study genetic dependence between the two traits and find that multiple genes have pleiotropic effects on both without a systematic pattern of sign concordance.
- V. Bansal
- , M. Mitjans
- & P. D. Koellinger
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Article
| Open AccessSleep-dependent reconsolidation after memory destabilization in starlings
Sleep is important for memory consolidation but its role in reconsolidation is not known. Here, the authors show in starlings that an auditory memory consolidated by sleep can be destabilized by retrieval and impaired by subsequent interference, but the memory recovers and stabilizes after a night of sleep-dependent reconsolidation.
- Timothy P. Brawn
- , Howard C. Nusbaum
- & Daniel Margoliash
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Article
| Open AccessDifferential dynamics of cortical neuron dendritic trees revealed by long-term in vivo imaging in neonates
Layer 4 stellate neurons in barrel cortex have a characteristic dendritic pattern. Here, the authors conduct long-term imaging from postnatal day 3–6 to show that an orientation bias is established through dendritic tree turnover and selective elaboration, which may be induced by biased thalamocortical inputs.
- Shingo Nakazawa
- , Hidenobu Mizuno
- & Takuji Iwasato
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Article
| Open AccessPhosphatidylserine exposure mediated by ABC transporter activates the integrin signaling pathway promoting axon regeneration
Apoptotic cells display surface signals such as phosphatidlyserines that are recognized by phagocytes via engulfment signal receptors. Here, the authors show how one such receptor, transthyretin-like protein 11, plays a role in initiating axon regeneration in the peripheral nervous system.
- Naoki Hisamoto
- , Anna Tsuge
- & Kunihiro Matsumoto
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Article
| Open AccessA novel environment-evoked transcriptional signature predicts reactivity in single dentate granule neurons
Single nuclei RNA-seq has been used to characterize transcriptional signature of environment-related activity in cells of the dentate gyrus. Here the authors use this approach to show that whether a neuron will be reactivated in response to re-exposure to a previous environment can be predicted by its transcriptional signature.
- Baptiste N. Jaeger
- , Sara B. Linker
- & Fred H. Gage
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Article
| Open AccessLocomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination
The contribution of oligodendrocytes to remyelination in functional recovery after spinal cord injury is not fully understood. Here, the authors show that oligodendrocyte progenitor cell differentiation is not required for functional recovery after spinal cord injury in mice.
- Greg J. Duncan
- , Sohrab B. Manesh
- & Wolfram Tetzlaff
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Article
| Open AccessDynamic contrast enhancement and flexible odor codes
Sensory stimuli are encountered in multiple ways necessitating a flexible and adaptive neural population code for identification. Here, the authors show that the dynamics of odor coding in the locust antennal lobe varies with stimulus context so as to enhance the target stimulus representation.
- Srinath Nizampatnam
- , Debajit Saha
- & Baranidharan Raman
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Article
| Open AccessVibration hotspots reveal longitudinal funneling of sound-evoked motion in the mammalian cochlea
Locations along the cochlea are tuned to different sound frequencies, and the individual vibration components are dynamically compressed before being converted to neural activity for further auditory processing. Here, the authors use optical coherence tomography to map sound-evoked vibrations and find a “hotspot” region with larger vibrations.
- Nigel P. Cooper
- , Anna Vavakou
- & Marcel van der Heijden
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Article
| Open AccessTargeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy
Charcot–Marie–Tooth disease 1A (CMT1A) is a peripheral demyelinating disease. Here, the authors demonstrate in a rodent model of CMT1A that Schwann cells have impairments in lipid biosynthesis, and that restoring lipids via diet can reverse the dysmyelinating phenotype in these animals.
- R. Fledrich
- , T. Abdelaal
- & M. W. Sereda
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Article
| Open AccessMultimodal neuromarkers in schizophrenia via cognition-guided MRI fusion
Cognitive impairment is a feature of many psychiatric diseases. Here the authors aimed to identify multimodal neuromarkers that can be used to quantify and predict cognitive performance in individuals with schizophrenia using three different features of MRI and three independent cohorts.
- Jing Sui
- , Shile Qi
- & Vince D. Calhoun
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Article
| Open AccessBrain-controlled modulation of spinal circuits improves recovery from spinal cord injury
Brain–spine interfaces have been used to enable leg movement following spinal cord injury, but movement is either involuntary or not adjustable. Here, the authors show in rats that a proportional stimulation interface permits voluntary movement and augments recovery in conjunction with rehabilitation.
- Marco Bonizzato
- , Galyna Pidpruzhnykova
- & Grégoire Courtine
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Article
| Open AccessOverexpression of endophilin A1 exacerbates synaptic alterations in a mouse model of Alzheimer’s disease
Endophilin A1 protein is known to be elevated in Alzheimer’s disease (AD). Here the authors show that endophilin A1 overexpression exacerbates synaptic deficits in a mouse model of AD.
- Qing Yu
- , Yongfu Wang
- & Shirley ShiDu Yan
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Article
| Open AccessSpontaneous cortical activity transiently organises into frequency specific phase-coupling networks
Coordination of neural activity between distant brain areas is necessary for cognition. Here, the authors report using MEG that various brain networks show dynamic phase coupling through specific frequency bands in the alpha and delta/theta range transiently during the resting state.
- Diego Vidaurre
- , Laurence T. Hunt
- & Mark W. Woolrich
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Article
| Open AccessEpigenome-wide DNA methylation profiling in Progressive Supranuclear Palsy reveals major changes at DLX1
Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by aggregation of Tau, encoded by MAPT. Here, the authors perform an EWAS for PSP in prefrontal lobe tissue and find hypermethylation of DLX1 and its antisense transcript DLX1AS to associate with MAPT expression.
- Axel Weber
- , Sigrid C. Schwarz
- & Ulrich Müller
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Article
| Open AccessSaccade metrics reflect decision-making dynamics during urgent choices
Saccades have been extensively used to report choices in perceptual decision making studies yet little is known about the influence of covert decision-related processes on saccade metrics. Here, the authors demonstrate that saccade kinematics is a reliable tell about the degree of decision certainty.
- Joshua A. Seideman
- , Terrence R. Stanford
- & Emilio Salinas
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Article
| Open AccessBlood–brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound
Magnetic resonance-guided focused ultrasound with injected microbubbles has been used to temporarily open the blood–brain barrier (BBB) in animal models of Alzheimer's disease (AD). Here, the authors use this technology to non-invasively open the BBB in 5 patients with mild-to-moderate AD in a phase I trial, and show that the procedure is safe.
- Nir Lipsman
- , Ying Meng
- & Sandra E. Black
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