The Decay and Consolidation of Effector-Independent Motor Memories

Abstract Learning a motor adaptation task produces intrinsically unstable or transient motor memories. Despite the presence of effector-independent motor memories following the learning of novel environmental dynamics, it remains largely unknown how those memory traces decay in different contexts and whether an “offline” consolidation period protects memories against decay. Here, we exploit inter-effector transfer to address these questions. We found that newly-acquired motor memories formed with one effector could be partially retrieved by the untrained effector to enhance its performance when the decay occurred with the passage of time or “washout” trials on which error feedback was provided. The decay of motor memories was slower following “error-free” trials, on which errors were artificially clamped to zero or removed, compared with “washout” trials. However, effector-independent memory components were abolished following movements made in the absence of performance error, resulting in no transfer gains. The brain can consolidate motor memories during daytime wakefulness. We found that 6 hours of wakeful resting increased the resistance of effector-independent memories to decay across all contexts. Collectively, our results suggest that the decay of effector-independent motor memories is context dependent and offline processing preserves those memories against decay, leading to improvements of the subsequent inter-effector transfer.

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Molecular Mechanisms of Drug Resistance in Glioblastoma

International Journal of Molecular Sciences ◽

10.3390/ijms22126385 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6385

Author(s):

Maya A. Dymova ◽

Elena V. Kuligina ◽

Vladimir A. Richter

Keyword(s):

Drug Resistance ◽

Brain Tumor ◽

Molecular Mechanisms ◽

Primary Brain Tumor ◽

Therapeutic Resistance ◽

Molecular Characteristics ◽

Blood Brain ◽

Conventional Radiation ◽

The Brain ◽

Made In

Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and is not amenable to effective surgical resection. The present review summarizes recent advances in our understanding of the molecular mechanisms of therapeutic resistance of GBM to already known drugs, the molecular characteristics of glioblastoma cells, and the barriers in the brain that underlie drug resistance. We also discuss the progress that has been made in the development of new targeted drugs for glioblastoma, as well as advances in drug delivery across the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB).

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Inducing human motor adaptation without explicit error feedback: A motor cost approach

IEEE Transactions on Neural Systems and Rehabilitation Engineering ◽

10.1109/tnsre.2021.3096516 ◽

2021 ◽

pp. 1-1

Author(s):

Yangmengfei Xu ◽

Vincent Crocher ◽

Justin Fong ◽

Ying Tan ◽

Denny Oetomo

Keyword(s):

Motor Adaptation ◽

Error Feedback ◽

Cost Approach ◽

Human Motor ◽

Human Motor Adaptation

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Context-Dependent Modulation of Early Visual Cortical Responses to Numerical and Nonnumerical Magnitudes

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_01774 ◽

2021 ◽

pp. 1-12

Author(s):

Joonkoo Park ◽

Sonia Godbole ◽

Marty G. Woldorff ◽

Elizabeth M. Brannon

Keyword(s):

Visual Processing ◽

Context Dependency ◽

Numerical Magnitude ◽

Continuous Variables ◽

Processing Stream ◽

Cortical Responses ◽

Early Visual Cortex ◽

Context Dependent ◽

Visual Cortical ◽

The Brain

Abstract Whether and how the brain encodes discrete numerical magnitude differently from continuous nonnumerical magnitude is hotly debated. In a previous set of studies, we orthogonally varied numerical (numerosity) and nonnumerical (size and spacing) dimensions of dot arrays and demonstrated a strong modulation of early visual evoked potentials (VEPs) by numerosity and not by nonnumerical dimensions. Although very little is known about the brain's response to systematic changes in continuous dimensions of a dot array, some authors intuit that the visual processing stream must be more sensitive to continuous magnitude information than to numerosity. To address this possibility, we measured VEPs of participants viewing dot arrays that changed exclusively in one nonnumerical magnitude dimension at a time (size or spacing) while holding numerosity constant and compared this to a condition where numerosity was changed while holding size and spacing constant. We found reliable but small neural sensitivity to exclusive changes in size and spacing; however, changing numerosity elicited a much more robust modulation of the VEPs. Together with previous work, these findings suggest that sensitivity to magnitude dimensions in early visual cortex is context dependent: The brain is moderately sensitive to changes in size and spacing when numerosity is held constant, but sensitivity to these continuous variables diminishes to a negligible level when numerosity is allowed to vary at the same time. Neurophysiological explanations for the encoding and context dependency of numerical and nonnumerical magnitudes are proposed within the framework of neuronal normalization.

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Krešimir Krnjević (1927–2021) and GABAergic inhibition: a lifetime dedication

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2021-0451 ◽

2021 ◽

pp. 1-4

Author(s):

Yehezkel Ben-Ari ◽

Enrico Cherubini ◽

Massimo Avoli

Keyword(s):

Canadian Journal ◽

Chief Editor ◽

Aminobutyric Acid ◽

Gabaergic Inhibition ◽

Inhibitory Neurotransmitter ◽

Neuroscience Research ◽

Personal Interactions ◽

The Brain ◽

Made In

After over seven decades of neuroscience research, it is now well established that γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. In this paper dedicated to Krešimir Krnjević (1927–2021), a pioneer and leader in neuroscience, we briefly highlight the fundamental contributions he made in identifying GABA as an inhibitory neurotransmitter in the brain and our personal interactions with him. Of note, between 1972 and 1978 Dr. Krnjević was a highly reputed Chief Editor of the Canadian Journal of Physiology and Pharmacology.

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Abstract 306: Alamandine but not angiotensin-(1-7) produces cardiovascular effects in the Insular Cortex

Hypertension ◽

10.1161/hyp.64.suppl_1.306 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Fernanda R Marins ◽

Aline C Oliveira ◽

Fatimunnisa Qadri ◽

Natalia Alenina ◽

Michael Bader ◽

...

Keyword(s):

Brain Region ◽

Insular Cortex ◽

Cardiovascular Effects ◽

Endogenous Ligand ◽

Renal Nerve ◽

Renal Sympathetic Nerve Activity ◽

Equimolar Dose ◽

The Brain ◽

Renal Sympathetic ◽

Made In

In the course of experiments aimed to evaluate the immunofluorescence distribution of MrgD receptors we observed the presence of immunoreactivity for the MrgD protein in the Insular Cortex. In order to evaluate the functional significance of this finding, we investigated the cardiovascular effects produced by the endogenous ligand of MrgD, alamandine, in this brain region. Urethane (1.4g/kg) anesthetized rats were instrumented for measurement of MAP, HR and renal sympathetic nerve activity (RSNA). Unilateral microinjection of alamandine (40 pmol/100nl), Angiotensin-(1-7) (40pmol/100nl), Mas/MrgD antagonista D-Pro7-Ang-1-7 (50pmol/100nl), Mas agonist A779 (100 pmol/100nl) or vehicle (0,9% NaCl) were made in different rats (N=4-6 per group) into posterior insular cortex (+1.5mm rostral to the bregma). Microinjection of alamandine in this region produced a long-lasting (> 18 min) increase in MAP (Δ saline= -2±1 vs. alamandine= 12±2 mmHg, p< 0.05) associated to increases in HR (Δ saline= 2±2 vs. alamandine= 35±5 bpm; p< 0.05) and in the amplitude of renal nerve discharges (Δ saline = -2±1 vs. alamandine= 35±5.5 % of the baseline; p< 0.05). Strikingly, an equimolar dose of angiotensin-(1-7) did not produce any change in MAP or HR (Δ MAP=-0.5±0.3 mmHg and +2.7±1.2 bpm, respectively; p> 0.05) and only a slight increase in RSNA (Δ =7.3±3.2 %) . In keeping with this observation the effects of alamandine were not significantly influenced by A-779 (Δ MAP=+13± 2.5 mmHg, Δ HR= +26±3.6 bpm; Δ RSNA = 25± 3.4%) but completely blocked by the Mas/MrgD antagonist D-Pro7-Ang-(1-7) (Δ MAP=+0 ± 1 mmHg Δ HR= +4±2.6 bpm; Δ RSNA = 0.5± 2.2 %). Therefore, we have identified a brain region in which alamandine/MrgD receptors but not Ang-(1-7)/Mas could be involved in the modulation of cardiovascular-related neuronal activity. This observation also suggests that alamandine might possess unique effects unrelated to Ang-(1-7) in the brain.

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Febrile Convulsions, by J. Gordon Millichap, M.D., M.R.C.P. New York: The Macmillan Company, 1968, 239 pp., $7.95

PEDIATRICS ◽

10.1542/peds.42.2.381 ◽

1968 ◽

Vol 42 (2) ◽

pp. 381-382

Author(s):

Randolph K. Byers

Keyword(s):

New York ◽

Relevant Literature ◽

Febrile Seizures ◽

Cerebral Injury ◽

Extensive Review ◽

Cerebral Disease ◽

Febrile Convulsions ◽

The Individual ◽

The Brain ◽

Made In

This rather modest-looking monograph deals not only with the large experiences of the author in relation to febrile seizures, but also presents an extensive review of the modern relevant literature (266 references in the bibliography). The most useful point made in the book, it seems to me, is that febrile convulsions are just that: i.e., convulsions coinciding with fever, the result of illness not directly involving the brain or its meninges. Such a seizure may be an isolated occurrence in the life of the individual, or it may recur a few times with fever; it may be the first sign of idiopathic chronic epilepsy, or it may be evidence of more or less apparent cerebral injury of a static sort; or, it may be the presenting symptom heralding progressive cerebral disease.

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Forming Diagnostic Opinions

Rhetorik ◽

10.1515/rhet.2018.005 ◽

2018 ◽

Vol 37 (1) ◽

pp. 68-93

Author(s):

Markus H. Woerner ◽

Ricca Edmondson

Keyword(s):

Medical Diagnosis ◽

Rhetorical Analysis ◽

Voluntary Action ◽

Medical Communication ◽

Medical Diagnoses ◽

Textual Evidence ◽

Social And Emotional ◽

Context Dependent ◽

The Brain

Abstract Using an understanding of rhetoric as a method of communicative reasoning capable of providing grounds for conviction in those to whom it is addressed, this article argues that the formation of medical diagnoses shares a structure with Aristotle’s account of the rhetorical syllogism (the enthymeme). Here the argument itself (logos), together with characterological elements (ethos) and emotions (pathos), are welded together so that each affects the operation of the others. In the initial three sections of the paper, we contend, first, that diagnoses, as verdictive performatives, differ from scientific claims in being irreducibly personal and context-dependent; secondly, that they fit the structure of voluntary action as analysed by Aristotle and Aquinas; thirdly, that as practical syllogisms they differ from theoretical syllogisms, for example in taking effect in action, being ›addressed‹, and being intrinsically embedded in wider contexts of medical communication and practices. In the remaining sections we apply this account to textual evidence about diagnosis, drawing on work by the brain surgeon Henry Marsh. A rhetorical analysis of his observations on the formation of diagnostic opinions in situilluminates how moral, social and emotional features are fused with the cognitive aspects of medical judgement, making or marring how diagnoses and treatment are enacted. In other words, a philosophical- rhetorical account of diagnosis can help us to appreciate how medical diagnosis takes effect. We briefly conclude with some implications of our work for how diagnostic processes could in practice be better supported.

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Distributed context-dependent choice information in mouse dorsal-parietal cortex

10.21203/rs.3.rs-288103/v1 ◽

2021 ◽

Author(s):

Javier Orlandi ◽

Mohammad Adbolrahmani ◽

Ryo Aoki ◽

Dmitry Lyamzin ◽

Andrea Benucci

Keyword(s):

Decision Making ◽

Decision Variable ◽

Visual Stream ◽

Posterior Cortex ◽

Neural Data ◽

Context Dependent ◽

Cortical Regions ◽

Low Dimensional ◽

Independent Decision ◽

The Brain

Abstract Choice information appears in the brain as distributed signals with top-down and bottom-up components that together support decision-making computations. In sensory and associative cortical regions, the presence of choice signals, their strength, and area specificity are known to be elusive and changeable, limiting a cohesive understanding of their computational significance. In this study, examining the mesoscale activity in mouse posterior cortex during a complex visual discrimination task, we found that broadly distributed choice signals defined a decision variable in a low-dimensional embedding space of multi-area activations, particularly along the ventral visual stream. The subspace they defined was near-orthogonal to concurrently represented sensory and motor-related activations, and it was modulated by task difficulty and contextually by the animals’ attention state. To mechanistically relate choice representations to decision-making computations, we trained recurrent neural networks with the animals’ choices and found an equivalent decision variable whose context-dependent dynamics agreed with that of the neural data. In conclusion, our results demonstrated an independent decision variable broadly represented in the posterior cortex, controlled by task features and cognitive demands. Its dynamics reflected decision computations, possibly linked to context-dependent feedback signals used for probabilistic-inference computations in variable animal-environment interactions.

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Reward and aversion encoding in the lateral habenula for innate and learned behaviours

Translational Psychiatry ◽

10.1038/s41398-021-01774-0 ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Sarah Mondoloni ◽

Manuel Mameli ◽

Mauro Congiu

Keyword(s):

Animal Species ◽

Brain Structures ◽

Individual Member ◽

Negative Events ◽

Lateral Habenula ◽

Sensory Stimuli ◽

Aversive Events ◽

Evolutionarily Conserved ◽

The Brain ◽

Made In

AbstractThroughout life, individuals experience a vast array of positive and aversive events that trigger adaptive behavioural responses. These events are often unpredicted and engage actions that are likely anchored on innate behavioural programs expressed by each individual member of virtually all animal species. In a second step, environmental cues, that are initially neutral, acquire value through the association with external sensory stimuli, and become instrumental to predict upcoming positive or negative events. This process ultimately prompts learned goal-directed actions allowing the pursuit of rewarding experience or the avoidance of a danger. Both innate and learned behavioural programs are evolutionarily conserved and fundamental for survival. Among the brain structures participating in the encoding of positive/negative stimuli and contributing to innate and learned behaviours is the epithalamic lateral habenula (LHb). The LHb provides top-down control of monoaminergic systems, responds to unexpected appetitive/aversive stimuli as well as external cues that predict the upcoming rewards or punishments. Accordingly, the LHb controls a number of behaviours that are innate (originating from unpredicted stimuli), and learned (stemming from predictive cues). In this review, we will discuss the progresses that rodent’s experimental work made in identifying how LHb activity governs these vital processes, and we will provide a view on how these findings integrate within a complex circuit connectivity.

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