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      Methods matter: A primer on permanent and reversible interference techniques in animals for investigators of human neuropsychology

      research-article
      a , b , * , c , d , e
      Neuropsychologia
      Pergamon Press
      Animal models, TMS, tDCS, Lesion

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The study of patients with brain lesions has contributed greatly to our understanding of the biological bases of human cognition, but this approach also has several unavoidable limitations. Research that uses animal models complements and extends human neuropsychology by addressing many of these limitations. In this review, we provide an overview of permanent and reversible animal lesion techniques for researchers of human neuropsychology, with the aim of highlighting how these methods provide a valuable adjunct to behavioural, neuroimaging, physiological, and clinical investigations in humans. Research in animals has provided important lessons about how the limitations of one or more techniques, or differences in their mechanism of action, has impacted upon the understanding of brain organisation and function. These cautionary tales highlight the importance of striving for a thorough understanding of how any intereference technique works (whether in animal or human), and for how to best use animal research to clarify the precise mechanisms underlying temporary lesion methods in humans.

          Highlights

          • There are many ways to temporarily or permanently disrupt brain function in animals.

          • Temporary vs. permanent disruption can sometimes lead to disparate results.

          • Understanding the mechanisms of a given technique is vital to interpreting results.

          • Here, we review current and emerging lesion techniques in animals.

          • Animal models provide a valuable adjunct to neuropsychological studies in humans.

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          Most cited references99

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          DREADDs for Neuroscientists.

          Bryan Roth (2016)
          To understand brain function, it is essential that we discover how cellular signaling specifies normal and pathological brain function. In this regard, chemogenetic technologies represent valuable platforms for manipulating neuronal and non-neuronal signal transduction in a cell-type-specific fashion in freely moving animals. Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-based chemogenetic tools are now commonly used by neuroscientists to identify the circuitry and cellular signals that specify behavior, perceptions, emotions, innate drives, and motor functions in species ranging from flies to nonhuman primates. Here I provide a primer on DREADDs highlighting key technical and conceptual considerations and identify challenges for chemogenetics going forward.
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            Emotion, decision making and the orbitofrontal cortex.

            The somatic marker hypothesis provides a systems-level neuroanatomical and cognitive framework for decision making and the influence on it by emotion. The key idea of this hypothesis is that decision making is a process that is influenced by marker signals that arise in bioregulatory processes, including those that express themselves in emotions and feelings. This influence can occur at multiple levels of operation, some of which occur consciously and some of which occur non-consciously. Here we review studies that confirm various predictions from the hypothesis. The orbitofrontal cortex represents one critical structure in a neural system subserving decision making. Decision making is not mediated by the orbitofrontal cortex alone, but arises from large-scale systems that include other cortical and subcortical components. Such structures include the amygdala, the somatosensory/insular cortices and the peripheral nervous system. Here we focus only on the role of the orbitofrontal cortex in decision making and emotional processing, and the relationship between emotion, decision making and other cognitive functions of the frontal lobe, namely working memory.
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              Transcranial pulsed ultrasound stimulates intact brain circuits.

              Electromagnetic-based methods of stimulating brain activity require invasive procedures or have other limitations. Deep-brain stimulation requires surgically implanted electrodes. Transcranial magnetic stimulation does not require surgery, but suffers from low spatial resolution. Optogenetic-based approaches have unrivaled spatial precision, but require genetic manipulation. In search of a potential solution to these limitations, we began investigating the influence of transcranial pulsed ultrasound on neuronal activity in the intact mouse brain. In motor cortex, ultrasound-stimulated neuronal activity was sufficient to evoke motor behaviors. Deeper in subcortical circuits, we used targeted transcranial ultrasound to stimulate neuronal activity and synchronous oscillations in the intact hippocampus. We found that ultrasound triggers TTX-sensitive neuronal activity in the absence of a rise in brain temperature (<0.01 degrees C). Here, we also report that transcranial pulsed ultrasound for intact brain circuit stimulation has a lateral spatial resolution of approximately 2 mm and does not require exogenous factors or surgical invasion. Copyright 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Neuropsychologia
                Neuropsychologia
                Neuropsychologia
                Pergamon Press
                0028-3932
                1873-3514
                01 July 2018
                01 July 2018
                : 115
                : 211-219
                Affiliations
                [a ]MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK
                [b ]Department of Experimental Psychology, University of Oxford, Oxford, UK
                [c ]Department of Psychology, University of Bath, Bath, UK
                [d ]Centre for Pain Research, University of Bath, Bath, UK
                [e ]The Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford, UK
                Author notes
                [* ]Corresponding author at: MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK andrew.bell@ 123456psy.ox.ac.uk
                Article
                S0028-3932(17)30345-7
                10.1016/j.neuropsychologia.2017.09.019
                6018620
                28943365
                724dde33-a826-4884-b9bf-e7063b74a857
                © 2017 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 9 July 2017
                : 7 September 2017
                : 19 September 2017
                Categories
                Article

                Neurology
                animal models,tms,tdcs,lesion
                Neurology
                animal models, tms, tdcs, lesion

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