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Maze training in mice induces MRI-detectable brain shape changes specific to the type of learning

NEUROimage 2011年第3期54卷 2086-2095页

作者： Lerch, Jason P. Yiu, Adelaide P. Martinez-Canabal, Alonso Pekar, Tetyana Bohbot, Veronique D. Frankland, Paul W. Henkelman, R. Mark Josselyn, Sheena A. Sled, John G. Hosp Sick Children Mouse Imaging Ctr Toronto ON M5T 3H7 Canada Univ Toronto Dept Med Biophys Toronto ON Canada Hosp Sick Children Program Neurosci & Mental Hlth Toronto ON M5T 3H7 Canada Univ Toronto Dept Physiol Toronto ON Canada Univ Toronto Inst Med Sci Toronto ON M5S 1A1 Canada McGill Univ Dept Psychiat Verdun PQ H4H 1R3 Canada

Multiple recent human imaging studies have suggested that the structure of the brain can change with learning. To investigate the mechanism behind such structural plasticity, we sought to determine whether maze learning in mice induces brain shape changes that are detectable by MRI and whether such changes are specific to the type of learning. Here we trained inbred mice for 5 days on one of three different versions of the Morris water maze and, using high-resolution MRI, revealed specific growth in the hippocampus of mice trained on a spatial variant of the maze, whereas mice trained on the cued version were found to have growth in the striatum. The structure-specific growth found furthermore correlated with GAP-43 staining, a marker of neuronal process remodelling, but not with neurogenesis nor neuron or astrocyte numbers or sizes. Our findings provide evidence that brain morphology changes rapidly at a scale detectable by MRI and furthermore demonstrate that specific brain regions grow or shrink in response to the changing environmental demands. The data presented herein have implications for both human imaging as well as rodent structural plasticity research, in that it provides a tool to screen for neuronal plasticity across the whole brain in the mouse while also providing a direct link between human and mouse studies. (C) 2010 Elsevier Inc. All rights reserved.

关键词： Animals Biological Markers Brain/anatomy & histology Brain/growth & development Brain/physiology Cell Count Cell Count Corpus Striatum/anatomy & histology Corpus Striatum/physiology Cues GAP-43 Protein/metabolism Hippocampus/anatomy & histology Hippocampus/physiology image processing, computer-assisted Immunohistochemistry Immunohistochemistry Magnetic Resonance Imaging Male Maze Learning/physiology Mice Mice, Inbred C57BL Neuronal Plasticity/physiology

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Advances in Structural and Functional Analysis of Membrane Proteins by Electron Crystallography

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STRUCTURE 2011年第10期19卷 1381-1393页

作者： Wisedchaisri, Goragot Reichow, Steve L. Gonen, Tamir Howard Hughes Med Inst Ashburn VA 20147 USA

Electron crystallography is a powerful technique for the study of membrane protein structure and function in the lipid environment. When well-ordered two-dimensional crystals are obtained the structure of both protein and lipid can be determined and lipid-protein interactions analyzed. Protons and ionic charges can be visualized by electron crystallography and the protein of interest can be captured for structural analysis in a variety of physiologically distinct states. This review highlights the strengths of electron crystallography and the momentum that is building up in automation and the development of high throughput tools and methods for structural and functional analysis of membrane proteins by electron crystallography.

关键词： Aquaporin 1/chemistry Archaea/chemistry Automatic Data processing Bacteriorhodopsins/chemistry Cell Membrane/chemistry Cell Membrane/physiology Cryoelectron Microscopy Crystallography/instrumentation Crystallography/methods Detergents/chemistry Dialysis/instrumentation Humans image processing, computer-assisted Lipid Bilayers/chemistry Membrane Proteins/chemistry Membrane Proteins/physiology Membrane Transport Proteins/chemistry Protein Conformation Static Electricity Static Electricity

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Triangulating the Neural, Psychological, and Economic Bases of Guilt Aversion

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NEURON 2011年第3期70卷 560-572页

作者： Chang, Luke J. Smith, Alec Dufwenberg, Martin Sanfey, Alan G. Univ Arizona Dept Psychol Tucson AZ 85721 USA Univ Arizona Dept Econ Tucson AZ 85721 USA Radboud Univ Nijmegen Donders Inst Brain Mind & Behav NL-6525 EN Nijmegen Netherlands Radboud Univ Nijmegen Inst Behav Sci NL-6525EN Nijmegen Netherlands CALTECH Pasadena CA 91125 USA Univ Gothenburg S-40530 Gothenburg Sweden

Why do people often choose to cooperate when they can better serve their interests by acting selfishly? One potential mechanism is that the anticipation of guilt can motivate cooperative behavior. We utilize a formal model of this process in conjunction with fMRI to identify brain regions that mediate cooperative behavior while participants decided whether or not to honor a partner's trust. We observed increased activation in the insula, supplementary motor area, dorsolateral prefrontal cortex (PEG), and temporal parietal junction when participants were behaving consistent with our model, and found increased activity in the ventromedial PFC, dorsomedial PEG, and nucleus accumbens when they chose to abuse trust and maximize their financial reward. This study demonstrates that a neural system previously implicated in expectation processing plays a critical role in assessing moral sentiments that in turn can sustain human cooperation in the face of temptation.

关键词： Adolescent Brain Mapping Brain Mapping Cerebral Cortex/blood supply Cerebral Cortex/physiology Economics Female Genetic Testing Genetic Testing Guilt Humans image processing, computer-assisted Magnetic Resonance Imaging Male Models, Psychological Morals Morals Motivation Neuropsychological Tests Oxygen/blood Regression Analysis Reward Young Adult

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Characterization of the anterior cingulate's role in the at-risk mental state using graph theory

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NEUROimage 2011年第3期56卷 1531-1539页

作者： Lord, Louis-David Allen, Paul Expert, Paul Howes, Oliver Lambiotte, Renaud McGuire, Philip Bose, Subrata K. Hyde, Samuel Turkheimer, Federico E. Univ London Imperial Coll Sci Technol & Med Dept Expt Med London England Kings Coll London Inst Psychiat London WC2R 2LS England Univ London Imperial Coll Sci Technol & Med Inst Math Sci London England Hammersmith Hosp MRC Ctr Clin Sci London England Harvard Univ Massachusetts Gen Hosp Sch Med Athinoula Martinos Ctr Biomed Imaging Boston MA USA

The onset of positive symptoms in schizophrenia is often preceded by a prodromal phase characterized by neurocognitive abnormalities as well as changes in brain structure and function. Increasing efforts have been made to identify individuals at elevated risk of developing schizophrenia, as early intervention may help prevent progression towards psychosis. The present study uses functional MRI and graph theoretical analysis to characterize the organization of a functional brain network in at-risk mental state patients with varying symptoms assessed with the PANSS and healthy volunteers during performance of a verbal fluency task known to recruit frontal lobe networks and to be impaired in psychosis. We first examined between-groups differences in total network connectivity and global network compactness/efficiency. We then addressed the role of specific brain regions in the network organization by calculating the node-specific "betweeness centrality", "degree centrality" and "local average path length" metrics: different ways of assessing a region's importance in a network. We focused our analysis on the anterior cingulate cortex (ACC): a region known to support executive function that is structurally and functionally impaired in at-risk mental state patients. Although global network connectivity and efficiency were maintained in at-risk patients relative to the controls, we report a significant decrease in the contribution of the ACC to task-relevant network organization in at risk subjects with elevated symptoms (PANSS 45) relative to both the controls and the less symptomatic at-risk subjects, as reflected by a reduction in the topological centrality of the ACC. These findings provide evidence of network abnormalities and anterior cingulate cortex dysfunction in people with prodromal signs of schizophrenia. (C) 2011 Elsevier Inc. Alrrights reserved.

关键词： Adult Algorithms Gyrus Cinguli/pathology Gyrus Cinguli/physiopathology Humans image processing, computer-assisted Intelligence Tests Magnetic Resonance Imaging Mental Disorders/pathology Mental Disorders/physiopathology Nerve Net/physiopathology Neural Pathways/physiopathology Neuropsychological Tests Risk Schizophrenia/pathology Schizophrenia/physiopathology Schizophrenic Psychology

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Retinal Vascular Tortuosity, Blood Pressure, and Cardiovascular Risk Factors

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OPHTHALMOLOGY 2011年第5期118卷 812-818页

作者： Cheung, Carol Yim-lui Zheng, Yingfeng Hsu, Wynne Lee, Mong Li Lau, Qiangfeng Peter Mitchell, Paul Wang, Jie Jin Klein, Ronald Wong, Tien Yin Singapore Eye Res Inst Singapore Natl Eye Ctr Singapore 168751 Singapore Natl Univ Singapore Sch Comp Singapore 117548 Singapore Univ Sydney Ctr Vis Res Sydney NSW 2006 Australia Univ Melbourne Royal Victorian Eye & Ear Hosp Ctr Eye Res Australia Melbourne Vic 3010 Australia Univ Wisconsin Dept Ophthalmol Madison WI USA Natl Univ Singapore Yong Loo Lin Sch Med Dept Ophthalmol Singapore 117595 Singapore

Objective: To examine the relationship of retinal vascular tortuosity to age, blood pressure, and other cardiovascular risk factors. Design: Population-based, cross-sectional study. Participants: A total of 3280 participants aged 40 to 80 years from the Singapore Malay Eye Study (78.7% response rate). Methods: Retinal arteriolar and venular (vascular) tortuosity were quantitatively measured from fundus images using a computer-assisted program. Retinal vascular tortuosity was defined as the integral of the curvature square along the path of the vessel, normalized by the total path length. Data on blood pressure and major cardiovascular disease (CVD) risk factors were collected from all participants. Mean Outcome Measures: Retinal arteriolar and venular tortuosity. Results: A total of 2915 participants contributed data to this study. The mean (standard deviation) and median were 2.99 (1.40) and 2.73 for retinal arteriolar tortuosity (x10(4)), and 4.64 (2.39) and 4.19 for retinal venular tortuosity (x10(4)), respectively. Retinal venules were significantly more tortuous than retinal arterioles (P < 0.001). In multivariable-adjusted linear regression models, less arteriolar tortuosity was independently associated with older age, higher blood pressure, higher body mass index (BMI), and narrower retinal arteriolar caliber (all P < 0.05);greater venular tortuosity was independently associated with younger age, higher blood pressure, lower high-density lipoprotein (HDL) cholesterol level, and wider retinal venular caliber (all P < 0.05). Conclusions: Retinal arteriolar tortuosity was associated with older age and higher levels of blood pressure and BMI, whereas venular tortuosity was also associated with lower HDL level. The quantitative assessment of retinal vascular tortuosity from retinal images may provide further information regarding effects of cardiovascular risk factors on the retinal vasculature. Financial Disclosure(s): The author(s) have no proprietary or commerc

关键词： Adult Age Factors Aged Aged, 80 and over Asian Continental Ancestry Group/ethnology Blood Pressure/physiology Cardiovascular Diseases/ethnology Cardiovascular Diseases/physiopathology Cross-Sectional Studies Female Humans Hypertension/physiopathology image processing, computer-assisted Male Middle Aged Retinal Diseases/diagnosis Retinal Diseases/ethnology Retinal Vessels/pathology Risk Factors Singapore/epidemiology Urban Population/statistics & numerical data

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CNS activation maps in awake rats exposed to thermal stimuli to the dorsum of the hindpaw

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NEUROimage 2011年第2期54卷 1355-1366页

作者： Becerra, L. Chang, P. C. Bishop, J. Borsook, D. Massachusetts Gen Hosp PAIN Grp AA Martinos Ctr Dept Radiol Boston MA 02114 USA Harvard Univ Sch Med Cambridge MA 02138 USA

Imaging pain pathways in rats offers a tool to investigate CNS systems in acute and chronic rodent models of pain, neural plasticity associated with the latter, and the opportunity to evaluate pharmacological effects of analgesics on these systems. Furthermore, the evaluation of CNS circuits (e.g., sensory, emotional, endogenous analgesic) offers the potential for defining the complexity of circuit-based behaviors that are difficult to evaluate in current preclinical behavioral models of pain. In these studies, we performed functional MRI in trained, acclimated, awake rats to define neural systems activated by noxious thermal stimuli. Analysis revealed activation in response to a 48 degrees C stimuli in cortical, subcortical and brainstem areas, known to be substrates of the pain pathways. Our results demonstrate the ability to characterize CNS patterns of activation in response to pain in rodents while avoiding the potential complicating effects of anesthesia. (C) 2010 Elsevier Inc. All rights reserved.

关键词： Animals Brain/physiopathology Brain Mapping Brain Mapping Consciousness Forelimb/innervation Hot Temperature image processing, computer-assisted Magnetic Resonance Imaging Male Pain/physiopathology Rats Rats, Sprague-Dawley

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Cortical processing of head- and eye-gaze cues guiding joint social attention

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NEUROimage 2011年第2期54卷 1643-1653页

作者： Laube, Inga Kamphuis, Simone Dicke, Peter W. Thier, Peter Univ Tubingen Dept Cognit Neurol Hertie Inst Clin Brain Res Tubingen Germany Univ Queensland Queensland Brain Inst Brisbane Qld 4072 Australia

Previous fMRI experiments showed an involvement of the STS in the processing of eye-gaze direction in joint attention. Since head-gaze direction can also be used for the assessment of another person's attentional focus, we compared the mechanisms underlying the processing of head- and eye-gaze direction using a combined psychophysical and fMRI approach. Subjects actively followed the head- or eye-gaze direction of a person in a photograph towards one of seven possible targets by moving their eyes. We showed that the right posterior superior temporal sulcus (STS) as well as the right fusiform gyrus (FSG) were involved in both processing of head- as well as eye-gaze direction. Another finding was a bilateral deactivation of a distinct area in the middle STS (mSTS) as well as the left anterior STS (aSTS), that was stronger when subjects followed eye-gaze direction than when they followed head-gaze direction. We assume that this deactivation is based on an active suppression of information arising from the distracting other directional cue, i.e. head-gaze direction in the eye-gaze direction task and eye-gaze direction in the head-gaze direction task. These results further support the hypothesis that the human equivalent of the gaze sensitive area in monkeys lies in more anterior parts of the STS than previously thought. (C) 2010 Elsevier Inc. All rights reserved.

关键词： Adult Attention/physiology Cerebral Cortex/physiology Cues Eye Female Fixation, Ocular Head Humans image processing, computer-assisted Magnetic Resonance Imaging Male Visual Perception/physiology Young Adult

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Parsing decision making processes in prefrontal cortex: Response inhibition, overcoming learned avoidance, and reversal learning

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NEUROimage 2011年第2期54卷 1432-1441页

作者： Greening, Steven G. Finger, Elizabeth C. Mitchell, Derek G. V. Univ Western Ontario Dept Psychiat London ON N6A 5A5 Canada Univ Western Ontario Dept Anat & Cell Biol London ON N6A 5A5 Canada Univ Western Ontario Schulich Sch Med & Dent London ON N6A 5A5 Canada Univ Western Ontario Dept Psychol London ON N6A 5A5 Canada

Reversal learning refers to the ability to inhibit or switch responding to an object when the object-reward contingency changes. Deficits in this process are related to social abnormalities, impulsiveness, and a number of psychiatric disorders. A range of neural regions play a role in this process, including dorsolateral prefrontal cortex (dlPFC), dorsomedial prefrontal cortex (dmPFC), and inferior frontal gyrus (IFG). However, determining the specific functional contribution of each region has proved difficult, in part because reversal learning involves multiple cognitive subprocesses such as error detection, inhibiting responding to formerly rewarded stimuli, and overcoming avoidance of previously punished stimuli. We used fMRI and an experimental task adapted from a recent neurochemical study in marmosets to parse neural responding to subprocesses of reversal learning during choice and feedback trial components. Error-feedback processing was associated with increased activity in dmPFC, dlPFC, and IFG whether participants were overcoming avoidance, inhibiting responding, or performing classic response reversal. Reduced activity in medial prefrontal cortex (mPFC) was associated with error-feedback processing for response inhibition but not overcoming avoidance. Conversely, there was significantly greater activity in anterior dmPFC during error-feedback processing in overcoming avoidance compared to response inhibition. A conjunction analysis confirmed that a striking overlap in activity was observed across the three conditions in IFG, dlPFC, and dmPFC. The results are consistent with conceptualizations of IFG function that emphasize modulating stimulus-response maps rather than purely response inhibition. The approach has implications for models of prefrontal function and neurocognitive perspectives on a range of behavioural abnormalities associated with impairments in decision making. (C) 2010 Elsevier Inc. All rights reserved.

关键词： Avoidance Learning/physiology Brain Mapping Brain Mapping Decision Making/physiology Female Humans image processing, computer-assisted Magnetic Resonance Imaging Male Prefrontal Cortex/physiology Reversal Learning/physiology

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Working memory maintenance of grasp-target information in the human posterior parietal cortex

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NEUROimage 2011年第3期54卷 2401-2411页

作者： Fiehler, Katja Bannert, Michael M. Bischoff, Matthias Blecker, Carlo Stark, Rudolf Vaitl, Dieter Franz, Volker H. Roesler, Frank Univ Marburg D-35032 Marburg Germany Max Planck Inst Biol Cybernet Tubingen Germany Univ Giessen Bender Inst Neuroimaging D-35390 Giessen Germany Univ Hamburg Hamburg Germany Univ Potsdam Potsdam Germany

Event-related functional magnetic resonance imaging was applied to identify cortical areas involved in maintaining target information in working memory used for an upcoming grasping action. Participants had to grasp with their thumb and index finger of the dominant right hand three-dimensional objects of different size and orientation. Reaching-to-grasp movements were performed without visual feedback either immediately after object presentation or after a variable delay of 2-12 s. The right inferior parietal cortex demonstrated sustained neural activity throughout the delay, which overlapped with activity observed during encoding of the grasp target. Immediate and delayed grasping activated similar motor-related brain areas and showed no differential activity. The results suggest that the right inferior parietal cortex plays an important functional role in working memory maintenance of grasp-related information. Moreover, our findings confirm the assumption that brain areas engaged in maintaining information are also involved in encoding the same information, and thus extend previous findings on working memory function of the posterior parietal cortex in saccadic behavior to reach-to-grasp movements. (C) 2010 Elsevier Inc. All rights reserved.

关键词： Adult Brain Mapping Brain Mapping Female Hand Strength/physiology Humans image processing, computer-assisted Magnetic Resonance Imaging Male Memory, Short-Term/physiology Motor Cortex/physiology Orientation/physiology Oxygen/blood Parietal Lobe/physiology Psychomotor Performance/physiology Somatosensory Cortex/physiology Space Perception/physiology Supine Position/physiology Visual Cortex/physiology Visual Perception/physiology Young Adult

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A Neural Signature of Hierarchical Reinforcement Learning

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NEURON 2011年第2期71卷 370-379页

作者： Ribas-Fernandes, Jose J. F. Solway, Alec Diuk, Carlos McGuire, Joseph T. Barto, Andrew G. Niv, Yael Botvinick, Matthew M. Princeton Univ Princeton Neurosci Inst Princeton NJ 08540 USA Champalimaud Fdn Champalimaud Neurosci Programme P-1400038 Lisbon Portugal Univ Penn Dept Psychol Philadelphia PA 19104 USA Univ Massachusetts Dept Comp Sci Amherst MA 01002 USA Princeton Univ Dept Psychol Princeton NJ 08540 USA

Human behavior displays hierarchical structure: simple actions cohere into subtask sequences, which work together to accomplish overall task goals. Although the neural substrates of such hierarchy have been the target of increasing research, they remain poorly understood. We propose that the computations supporting hierarchical behavior may relate to those in hierarchical reinforcement learning (HRL), a machine-learning framework that extends reinforcement-learning mechanisms into hierarchical domains. To test this, we leveraged a distinctive prediction arising from HRL. In ordinary reinforcement learning, reward prediction errors are computed when there is an unanticipated change in the prospects for accomplishing overall task goals. HRL entails that prediction errors should also occur in relation to task subgoals. In three neuroimaging studies we observed neural responses consistent with such subgoal-related reward prediction errors, within structures previously implicated in reinforcement learning. The results reported support the relevance of HRL to the neural processes underlying hierarchical behavior.

关键词： Adolescent Adult Brain/blood supply Brain/physiology Brain Mapping Brain Mapping Brain Waves/physiology computer Simulation Electroencephalography/methods Female Humans image processing, computer-assisted Linear Models Magnetic Resonance Imaging/methods Male Models, Biological Oxygen/blood Psychomotor Performance/physiology Reinforcement (Psychology) Young Adult

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