scholarly journals Forgot what you like? Evidence for hippocampal dependence of value-based decisions

2017 ◽  
Author(s):  
A. Z. Enkavi ◽  
B. Weber ◽  
I. Zweyer ◽  
J. Wagner ◽  
C.E. Elger ◽  
...  
Keyword(s):  
Medial Temporal Lobe ◽  
Critical Role ◽  
Brain Regions ◽  
Comparison Task ◽  
Behavioral Decision ◽  
Open Questions ◽  
Preference Construction ◽  
Number Comparison ◽  
Binary Choices ◽  
Processing Network

AbstractConsistent decisions are intuitively desirable and theoretically important for utility maximization. Neuroeconomics has established the neurobiological substrate of value representation, but brain regions that provide input to the value-processing network is less explored. The constructed-preference tradition within behavioral decision research gives a critical role to cognitive processes that rely on associations, suggesting a role for the hippocampus in making decisions and to do so consistently. We compared the performance of 31 patients with mediotemporal lobe (MTL) epilepsy and hippocampal lesions, 30 patients with extratemporal lobe epilepsy, and 30 healthy controls on two tasks: binary choices between candy bars based on their preferences and a number-comparison control task where the larger number is chosen. MTL patients make more inconsistent choices than the other two groups for the value-based choice but not the number-comparison task. These inconsistencies increase with the volume of compromised hippocampal tissue. These results suggest a critical involvement of the MTL in preference construction and value-based choices.SignificanceOur days are full of choices that reflect our preferences. Economics lays out models of how to optimally make these decisions. Neuroeconomics has identified a cortical value-processing network whose activity correlates with constructs related to valuation and choice in economic models. However open questions remain: How are these value signals formed, and what regions might be necessary for retrieving and computing these value signals? Inspired by cognitive models calling on associative processes in value-based decisions, this paper uses unique neuropsychological data to establish the critical role of the medial temporal lobe in making consistent choices and further informs our understanding of the value-processing network.

scholarly journals In vivo synaptic density relates to glucose metabolism at rest in healthy subjects, but is strongly modulated by regional differences

2021 ◽  
pp. 0271678X2098150
Author(s):  
June van Aalst ◽  
Jenny Ceccarini ◽  
Stefan Sunaert ◽  
Patrick Dupont ◽  
Michel Koole ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Medial Temporal Lobe ◽  
Regional Differences ◽  
Specific Binding ◽  
Aerobic Glycolysis ◽  
Glucose Consumption ◽  
Brain Regions ◽  
Synaptic Density ◽  
Energy Demands

Preclinical and postmortem studies have suggested that regional synaptic density and glucose consumption (CMRGlc) are strongly related. However, the relation between synaptic density and cerebral glucose metabolism in the human brain has not directly been assessed in vivo. Using [11C]UCB-J binding to synaptic vesicle glycoprotein 2 A (SV2A) as indicator for synaptic density and [18F]FDG for measuring cerebral glucose consumption, we studied twenty healthy female subjects (age 29.6 ± 9.9 yrs) who underwent a single-day dual-tracer protocol (GE Signa PET-MR). Global measures of absolute and relative CMRGlc and specific binding of [11C]UCB-J were indeed highly significantly correlated ( r > 0.47, p < 0.001). However, regional differences in relative [18F]FDG and [11C]UCB-J uptake were observed, with up to 19% higher [11C]UCB-J uptake in the medial temporal lobe (MTL) and up to 17% higher glucose metabolism in frontal and motor-related areas and thalamus. This pattern has a considerable overlap with the brain regions showing different levels of aerobic glycolysis. Regionally varying energy demands of inhibitory and excitatory synapses at rest may also contribute to this difference. Being unaffected by astroglial and/or microglial energy demands, changes in synaptic density in the MTL may therefore be more sensitive to early detection of pathological conditions compared to changes in glucose metabolism.

scholarly journals Analysis of Urban Effects in Oklahoma City using a Dense Surface Observing Network

2016 ◽  
Vol 55 (3) ◽  
pp. 723-741 ◽  
Author(s):  
Xiao-Ming Hu ◽  
Ming Xue ◽  
Petra M. Klein ◽  
Bradley G. Illston ◽  
Sheng Chen
Keyword(s):  
Metropolitan Area ◽  
Land Surface ◽  
Critical Role ◽  
Central Business District ◽  
Temperature Inversion ◽  
Oklahoma City ◽  
Near Surface ◽  
Open Questions ◽  
The Stability ◽  
Business District

AbstractMany studies have investigated urban heat island (UHI) intensity for cities around the world, which is normally quantified as the temperature difference between urban location(s) and rural location(s). A few open questions still remain regarding the UHI, such as the spatial distribution of UHI intensity, temporal (including diurnal and seasonal) variation of UHI intensity, and the UHI formation mechanism. A dense network of atmospheric monitoring sites, known as the Oklahoma City (OKC) Micronet (OKCNET), was deployed in 2008 across the OKC metropolitan area. This study analyzes data from OKCNET in 2009 and 2010 to investigate OKC UHI at a subcity spatial scale for the first time. The UHI intensity exhibited large spatial variations over OKC. During both daytime and nighttime, the strongest UHI intensity is mostly confined around the central business district where land surface roughness is the highest in the OKC metropolitan area. These results do not support the roughness warming theory to explain the air temperature UHI in OKC. The UHI intensity of OKC increased prominently around the early evening transition (EET) and stayed at a fairly constant level throughout the night. The physical processes during the EET play a critical role in determining the nocturnal UHI intensity. The near-surface rural temperature inversion strength was a good indicator for nocturnal UHI intensity. As a consequence of the relatively weak near-surface rural inversion, the strongest nocturnal UHI in OKC was less likely to occur in summer. Other meteorological factors (e.g., wind speed and cloud) can affect the stability/depth of the nighttime boundary layer and can thus modulate nocturnal UHI intensity.

The melanocortin-3 receptor is a pharmacological target for the regulation of anorexia

2021 ◽  
Vol 13 (590) ◽  
pp. eabd6434
Author(s):  
Patrick Sweeney ◽  
Michelle N. Bedenbaugh ◽  
Jose Maldonado ◽  
Pauline Pan ◽  
Katelyn Fowler ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Feeding Behavior ◽  
Critical Role ◽  
Brain Regions ◽  
Sexually Dimorphic ◽  
Male And Female ◽  
Female Mice ◽  
Bidirectional Regulation ◽  
Fear And Anxiety ◽  
Agouti Related Protein

Ablation of hypothalamic AgRP (Agouti-related protein) neurons is known to lead to fatal anorexia, whereas their activation stimulates voracious feeding and suppresses other motivational states including fear and anxiety. Despite the critical role of AgRP neurons in bidirectionally controlling feeding, there are currently no therapeutics available specifically targeting this circuitry. The melanocortin-3 receptor (MC3R) is expressed in multiple brain regions and exhibits sexual dimorphism of expression in some of those regions in both mice and humans. MC3R deletion produced multiple forms of sexually dimorphic anorexia that resembled aspects of human anorexia nervosa. However, there was no sexual dimorphism in the expression of MC3R in AgRP neurons, 97% of which expressed MC3R. Chemogenetic manipulation of arcuate MC3R neurons and pharmacologic manipulation of MC3R each exerted potent bidirectional regulation over feeding behavior in male and female mice, whereas global ablation of MC3R-expressing cells produced fatal anorexia. Pharmacological effects of MC3R compounds on feeding were dependent on intact AgRP circuitry in the mice. Thus, the dominant effect of MC3R appears to be the regulation of the AgRP circuitry in both male and female mice, with sexually dimorphic sites playing specialized and subordinate roles in feeding behavior. Therefore, MC3R is a potential therapeutic target for disorders characterized by anorexia, as well as a potential target for weight loss therapeutics.

APOE ɛ4 Allele Moderates the Association Between Basal Forebrain Nuclei Volumes and Allocentric Navigation in Older Adults Without Dementia

2022 ◽  
pp. 1-17
Author(s):  
Ondrej Lerch ◽  
Martina Pařízková ◽  
Martin Vyhnálek ◽  
Zuzana Nedelská ◽  
Jakub Hort ◽  
...  
Keyword(s):  
Older Adults ◽  
Basal Forebrain ◽  
Medial Temporal Lobe ◽  
Structural Equation ◽  
Brain Aging ◽  
Late Onset ◽  
Brain Regions ◽  
Real Space ◽  
Complex Model ◽  
E4 Allele

Background: Cholinergic deficit and medial temporal lobe (MTL) atrophy are hallmarks of Alzheimer’s disease (AD) leading to early allocentric spatial navigation (aSN) impairment. APOE ɛ4 allele (E4) is a major genetic risk factor for late-onset AD and contributes to cholinergic dysfunction. Basal forebrain (BF) nuclei, the major source of acetylcholine, project into multiple brain regions and, along with MTL and prefrontal cortex (PFC), are involved in aSN processing. Objective: We aimed to determine different contributions of individual BF nuclei atrophy to aSN in E4 positive and E4 negative older adults without dementia and assess whether they operate on aSN through MTL and PFC or independently from these structures. Methods: 120 participants (60 E4 positive, 60 E4 negative) from the Czech Brain Aging Study underwent structural MRI and aSN testing in real-space arena setting. Hippocampal and BF nuclei volumes and entorhinal cortex and PFC thickness were obtained. Associations between brain regions involved in aSN were assessed using MANOVA and complex model of mutual relationships was built using structural equation modelling (SEM). Results: Path analysis based on SEM modeling revealed that BF Ch1-2, Ch4p, and Ch4ai nuclei volumes were indirectly associated with aSN performance through MTL (pch1 - 2 = 0.039; pch4p = 0.042) and PFC (pch4ai = 0.044). In the E4 negative group, aSN was indirectly associated with Ch1-2 nuclei volumes (p = 0.015), while in the E4 positive group, there was indirect effect of Ch4p nucleus (p = 0.035). Conclusion: Our findings suggest that in older adults without dementia, BF nuclei affect aSN processing indirectly, through MTL and PFC, and that APOE E4 moderates these associations.

scholarly journals Modeling Causal Relationship Between Brain Regions Within the Drug-Cue Processing Network in Chronic Cocaine Smokers

2015 ◽  
Vol 40 (13) ◽  
pp. 2960-2968 ◽  
Author(s):  
Suchismita Ray ◽  
Margaret Haney ◽  
Catherine Hanson ◽  
Bharat Biswal ◽  
Stephen José Hanson
Keyword(s):  
Causal Relationship ◽  
Brain Regions ◽  
Chronic Cocaine ◽  
Cue Processing ◽  
Processing Network ◽  
Drug Cue

scholarly journals Spatial inhibition of return is impaired in mild cognitive impairment and mild Alzheimer’s disease

2020 ◽  
Author(s):  
Xiong Jiang ◽  
James H. Howard ◽  
G. Wiliam Rebeck ◽  
R. Scott Turner
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Medial Temporal Lobe ◽  
Inhibition Of Return ◽  
Memory Performance ◽  
Brain Regions ◽  
List Type ◽  
Older Individuals

ABSTRACTSpatial inhibition of return (IOR) refers to the phenomenon by which individuals are slower to respond to stimuli appearing at a previously cued location compared to un-cued locations. Here we provide evidence supporting that spatial IOR is mildly impaired in individuals with mild cognitive impairment (MCI) or mild Alzheimer’s disease (AD), and the impairment is readily detectable using a novel double cue paradigm. Furthermore, reduced spatial IOR in high-risk healthy older individuals is associated with reduced memory and other neurocognitive task performance, suggesting that the novel double cue spatial IOR paradigm may be useful in detecting MCI and early AD.SIGNIFICANCE STATEMENTNovel double cue spatial inhibition of return (IOR) paradigm revealed a robust effect IOR deficits in individuals with mild cognitive impairment (MCI) or mild Alzheimer’s disease (AD)Spatial IOR effect correlates with memory performance in healthy older adults at a elevated risk of Alzheimer’s disease (with a family history or APOE e4 allele)The data suggests that double cue spatial IOR may be sensitive to detect early AD pathological changes, which may be linked to disease progress at the posterior brain regions (rather than the medial temporal lobe)

scholarly journals A perspective on therapies for amyotrophic lateral sclerosis: can disease progression be curbed?

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiaojiao Xu ◽  
Dingding Shen ◽  
Yining Gao ◽  
Qinming Zhou ◽  
You Ni ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Disease Progression ◽  
Motor Neurons ◽  
Critical Role ◽  
Cell Therapies ◽  
Gene Therapies ◽  
Open Questions ◽  
Novel Therapeutic Strategies ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons, leading to paralysis and eventually death. Symptomatic treatments such as inhibition of salivation, alleviation of muscle cramps, and relief of spasticity and pain still play an important role in enhancing the quality of life. To date, riluzole and edaravone are the only two drugs approved by the Food and Drug Administration for the treatment of ALS in a few countries. While there is adequate consensus on the modest efficacy of riluzole, there are still open questions concerning the efficacy of edaravone in slowing the disease progression. Therefore, identification of novel therapeutic strategies is urgently needed. Impaired autophagic process plays a critical role in ALS pathogenesis. In this review, we focus on therapies modulating autophagy in the context of ALS. Furthermore, stem cell therapies, gene therapies, and newly-developed biomaterials have great potentials in alleviating neurodegeneration, which might halt the disease progression. In this review, we will summarize the current and prospective therapies for ALS.

Glutamate in the pathophysiology of schizophrenia

2020 ◽  
pp. 287-296
Author(s):  
Daniel C. Javitt
Keyword(s):  
Visual System ◽  
Visual Processing ◽  
Negative Symptoms ◽  
Glutamate Release ◽  
Critical Role ◽  
Brain Regions ◽  
Long Term Memory ◽  
Subcortical Structures ◽  
Impaired Metabolism

Glutamate theories of schizophrenia were first proposed over 30 years ago and since that time have become increasingly accepted. Theories are supported by the ability of N-methyl-D-aspartate receptor (NMDAR) antagonists such as phencyclidine (PCP) or ketamine to induce symptoms that closely resemble those of schizophrenia. Moreover, NMDAR antagonists uniquely reproduce the level of negative symptoms and cognitive deficits observed in schizophrenia, suggesting that such models may be particularly appropriate to poor outcome forms of the disorder. As opposed to dopamine, which is most prominent within frontostriatal brain regions, glutamate neurons are present throughout cortex and subcortical structures. Thus, NMDAR theories predict widespread disturbances across cortical and thalamic pathways, including sensory brain regions. In auditory cortex, NMDAR play a critical role in the generation of mismatch negativity (MMN), which may therefore serve as a translational marker of NMDAR dysfunction across species. In the visual system, NMDAR play a critical role in function of the magnocellular visual system. Deficits in both auditory and visual processing contribute to social and communication deficits, which, in turn, lead to poor functional outcome. By contrast, NMDAR dysfunction within the frontohippocampal system may contribute to well described deficits in working memory, executive processing and long-term memory formation. Deficits in NMDAR function may be driven by disturbances in presynaptic glutamate release, impaired metabolism of NMDAR modulators such as glycine or D-serine, or intrinsic abnormalities in NMDAR themselves.

scholarly journals Thalamic-Medial Temporal Lobe Connectivity Underpins Familiarity Memory

2020 ◽  
Vol 30 (6) ◽  
pp. 3827-3837 ◽  
Author(s):  
Alex Kafkas ◽  
Andrew R Mayes ◽  
Daniela Montaldi
Keyword(s):  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Critical Role ◽  
Dynamic Interaction ◽  
Thalamic Nuclei ◽  
Neural Basis ◽  
General Role ◽  
Anterior Thalamus ◽  
Ventrolateral Thalamus ◽  
Familiarity And Recollection

Abstract The neural basis of memory is highly distributed, but the thalamus is known to play a particularly critical role. However, exactly how the different thalamic nuclei contribute to different kinds of memory is unclear. Moreover, whether thalamic connectivity with the medial temporal lobe (MTL), arguably the most fundamental memory structure, is critical for memory remains unknown. We explore these questions using an fMRI recognition memory paradigm that taps familiarity and recollection (i.e., the two types of memory that support recognition) for objects, faces, and scenes. We show that the mediodorsal thalamus (MDt) plays a material-general role in familiarity, while the anterior thalamus plays a material-general role in recollection. Material-specific regions were found for scene familiarity (ventral posteromedial and pulvinar thalamic nuclei) and face familiarity (left ventrolateral thalamus). Critically, increased functional connectivity between the MDt and the parahippocampal (PHC) and perirhinal cortices (PRC) of the MTL underpinned increases in reported familiarity confidence. These findings suggest that familiarity signals are generated through the dynamic interaction of functionally connected MTL-thalamic structures.

scholarly journals The Medial Temporal Lobe Is Critical for Spatial Relational Perception

2020 ◽  
Vol 32 (9) ◽  
pp. 1780-1795 ◽  
Author(s):  
Nicholas A. Ruiz ◽  
Michael R. Meager ◽  
Sachin Agarwal ◽  
Mariam Aly
Keyword(s):  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Critical Role ◽  
Long Term Memory ◽  
Term Memory ◽  
Cognitive Domains ◽  
Attention Tasks ◽  
Human Participants ◽  
Attention And Perception

The medial temporal lobe (MTL) is traditionally considered to be a system that is specialized for long-term memory. Recent work has challenged this notion by demonstrating that this region can contribute to many domains of cognition beyond long-term memory, including perception and attention. One potential reason why the MTL (and hippocampus specifically) contributes broadly to cognition is that it contains relational representations—representations of multidimensional features of experience and their unique relationship to one another—that are useful in many different cognitive domains. Here, we explore the hypothesis that the hippocampus/MTL plays a critical role in attention and perception via relational representations. We compared human participants with MTL damage to healthy age- and education-matched individuals on attention tasks that varied in relational processing demands. On each trial, participants viewed two images (rooms with paintings). On “similar room” trials, they judged whether the rooms had the same spatial layout from a different perspective. On “similar art” trials, they judged whether the paintings could have been painted by the same artist. On “identical” trials, participants simply had to detect identical paintings or rooms. MTL lesion patients were significantly and selectively impaired on the similar room task. This work provides further evidence that the hippocampus/MTL plays a ubiquitous role in cognition by virtue of its relational and spatial representations and highlights its important contributions to rapid perceptual processes that benefit from attention.

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