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</a></div></div></div></div><div class="right-panel-container"><div class="user-content-wrapper"><div class="uploads-container" id="social-redesign-work-container"><div class="upload-header"><h2 class="ds2-5-heading-sans-serif-xs">Uploads</h2></div><div class="documents-container backbone-social-profile-documents" style="width: 100%;"><div class="u-taCenter"></div><div class="profile--tab_content_container js-tab-pane tab-pane active" id="all"><div class="profile--tab_heading_container js-section-heading" data-section="Papers" id="Papers"><h3 class="profile--tab_heading_container">Papers by Jason Berwick</h3></div><div class="js-work-strip profile--work_container" data-work-id="28000543"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/28000543/Decreased_haemodynamic_response_and_decoupling_of_cortical_gamma_band_activity_and_tissue_oxygen_perfusion_after_striatal_interleukin_1_injection"><img alt="Research paper thumbnail of Decreased haemodynamic response and decoupling of cortical gamma-band activity and tissue oxygen perfusion after striatal interleukin-1 injection" class="work-thumbnail" src="https://attachments.academia-assets.com/48308307/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/28000543/Decreased_haemodynamic_response_and_decoupling_of_cortical_gamma_band_activity_and_tissue_oxygen_perfusion_after_striatal_interleukin_1_injection">Decreased haemodynamic response and decoupling of cortical gamma-band activity and tissue oxygen perfusion after striatal interleukin-1 injection</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://manchester.academia.edu/IngoSchiessl">Ingo Schiessl</a> and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/JasonBerwick">Jason Berwick</a></span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Background Neurovascular coupling describes the mechanism by which the energy and oxygen demand a...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Background<br />Neurovascular coupling describes the mechanism by which the energy and oxygen demand arising from neuronal activity is met by an increase in regional blood flow, known as the haemodynamic response. Interleukin 1 (IL-1) is a pro-inflammatory cytokine and an important mediator of neuronal injury, though mechanisms through which IL-1 exerts its effects in the brain are not fully understood. In this study, we set out to investigate if increased cerebral levels of IL-1 have a negative effect on the neurovascular coupling in the cortex in response to sensory stimulation.<br /><br />Methods<br />We used two approaches to measure the neuronal activity and haemodynamic changes in the anaesthetised rat barrel somatosensory cortex in response to mechanical whisker stimulation, before and for 6 h after intra-striatal injection of interleukin-1β or vehicle. First, we used two-dimensional optical imaging spectroscopy (2D-OIS) to measure the size of the functional haemodynamic response, indicated by changes of oxyhaemoglobin (HbO2) and total haemoglobin (HbT) concentration. In the same animals, immunostaining of immunoglobulin G and SJC-positive extravasated neutrophils was used to confirm the pro-inflammatory effects of interleukin-1β (IL-1β). Second, to examine the functional coupling between neuronal activity and the haemodynamic response, we used a ‘Clark-style’ electrode combined with a single sharp electrode to simultaneously record local tissue oxygenation (partial pressure oxygen, pO2) in layer IV/V of the stimulated barrel cortex and multi-unit activity (MUA) together with local field potentials (LFPs), respectively.<br /><br />Results<br />2D-OIS data revealed that the size of the haemodynamic response to mechanical whisker stimulation declined over the 6 h following IL-1β injection whereas the vehicle group remained stable, significant differences being seen after 5 h. Moreover, the size of the transient increases of neuronal LFP activity in response to whisker stimulation decreased after IL-1β injection, significant changes compared to vehicle being seen for gamma-band activity after 1 h and beta-band activity after 3 h. The amplitude of the functional pO2 response similarly decreased after 3 h post-IL-1β injection, whereas IL-1β had no significant effect on the peak of whisker-stimulation-induced MUA. The stimulation-evoked increases in gamma power and pO2 correlated significantly throughout the 6 h in the vehicle group, but such a correlation was not observed in the IL-1β-injected group.<br /><br />Conclusions<br />We conclude that intra-striatal IL-1β decouples cortical neuronal activity from its haemodynamic response. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="30876944"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/30876944/Concurrent_optical_imaging_spectroscopy_laser_Doppler_flowmetry_and_magnetic_resonance_imaging_in_the_investigation_of_the_relative_intra_and_extra_vascular_contributions_to_the_BOLD_signal"><img alt="Research paper thumbnail of Concurrent optical imaging spectroscopy, laser Doppler flowmetry and magnetic resonance imaging in the investigation of the relative intra and extra vascular contributions to the BOLD signal" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/30876944/Concurrent_optical_imaging_spectroscopy_laser_Doppler_flowmetry_and_magnetic_resonance_imaging_in_the_investigation_of_the_relative_intra_and_extra_vascular_contributions_to_the_BOLD_signal">Concurrent optical imaging spectroscopy, laser Doppler flowmetry and magnetic resonance imaging in the investigation of the relative intra and extra vascular contributions to the BOLD signal</a></div><div class="wp-workCard_item"><span>Biomedical Topical Meeting</span><span>, 2004</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">ABSTRACT</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="30876944"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="30876944"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 30876944; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=30876944]").text(description); $(".js-view-count[data-work-id=30876944]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 30876944; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='30876944']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="30876943"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/30876943/Comparison_of_stimulus_evoked_cerebral_hemodynamics_in_the_awake_mouse_and_under_a_novel_anesthetic_regime"><img alt="Research paper thumbnail of Comparison of stimulus-evoked cerebral hemodynamics in the awake mouse and under a novel anesthetic regime" class="work-thumbnail" src="https://attachments.academia-assets.com/51303003/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/30876943/Comparison_of_stimulus_evoked_cerebral_hemodynamics_in_the_awake_mouse_and_under_a_novel_anesthetic_regime">Comparison of stimulus-evoked cerebral hemodynamics in the awake mouse and under a novel anesthetic regime</a></div><div class="wp-workCard_item"><span>Scientific reports</span><span>, Jan 28, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Neural activity is closely followed by a localised change in cerebral blood flow, a process terme...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Neural activity is closely followed by a localised change in cerebral blood flow, a process termed neurovascular coupling. These hemodynamic changes form the basis of contrast in functional magnetic resonance imaging (fMRI) and are used as a correlate for neural activity. Anesthesia is widely employed in animal fMRI and neurovascular studies, however anesthetics are known to profoundly affect neural and vascular physiology, particularly in mice. Therefore, we investigated the efficacy of a novel &#39;modular&#39; anesthesia that combined injectable (fentanyl-fluanisone/midazolam) and volatile (isoflurane) anesthetics in mice. To characterize sensory-evoked cortical hemodynamic responses, we used optical imaging spectroscopy to produce functional maps of changes in tissue oxygenation and blood volume in response to mechanical whisker stimulation. Following fine-tuning of the anesthetic regime, stimulation elicited large and robust hemodynamic responses in the somatosensory cortex, ch...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="14cfe9324ed9f3eb6e4ae116eb877b81" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":51303003,"asset_id":30876943,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/51303003/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="30876943"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="30876943"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 30876943; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="30876942"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/30876942/LRP_1_mediated_intracellular_antibody_delivery_to_the_Central_Nervous_System"><img alt="Research paper thumbnail of LRP-1-mediated intracellular antibody delivery to the Central Nervous System" class="work-thumbnail" src="https://attachments.academia-assets.com/51303005/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/30876942/LRP_1_mediated_intracellular_antibody_delivery_to_the_Central_Nervous_System">LRP-1-mediated intracellular antibody delivery to the Central Nervous System</a></div><div class="wp-workCard_item"><span>Scientific Reports</span><span>, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Here we report the engineering of pH-sensitive polymersomes (synthetic vesicles formed by amphiph...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Here we report the engineering of pH-sensitive polymersomes (synthetic vesicles formed by amphiphilic copolymers) that exploit endogenous transport mechanisms to traverse the BBB, enabling delivery of large macromolecules into both the CNS parenchyma and CNS cells. We achieve this by targeting the Low Density Lipoprotein Receptor-Related Protein 1 (LRP-1) receptor. We show that LRP-1 is associated with endothelial transcytosis that does not involve acidification of cargo in membranetrafficking organelles. By contrast, this receptor is also associated with traditional endocytosis in CNS cells, thus aiding the delivery of relevant cargo within their cytosol. We prove this using IgG as a model cargo, thus demonstrating that the combination of appropriate targeting combined with pHsensitive polymersomes enables the efficient delivery of macromolecules into CNS cells.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="fa3083e12f2d7659c15344276bc6373b" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":51303005,"asset_id":30876942,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/51303005/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="30876942"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="30876942"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 30876942; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="30876941"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/30876941/Long_Latency_Reductions_in_Gamma_Power_Predict_Hemodynamic_Changes_That_Underlie_the_Negative_BOLD_Signal"><img alt="Research paper thumbnail of Long-Latency Reductions in Gamma Power Predict Hemodynamic Changes That Underlie the Negative BOLD Signal" class="work-thumbnail" src="https://attachments.academia-assets.com/51303004/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/30876941/Long_Latency_Reductions_in_Gamma_Power_Predict_Hemodynamic_Changes_That_Underlie_the_Negative_BOLD_Signal">Long-Latency Reductions in Gamma Power Predict Hemodynamic Changes That Underlie the Negative BOLD Signal</a></div><div class="wp-workCard_item"><span>The Journal of neuroscience : the official journal of the Society for Neuroscience</span><span>, Jan 18, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Studies that use prolonged periods of sensory stimulation report associations between regional re...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Studies that use prolonged periods of sensory stimulation report associations between regional reductions in neural activity and negative blood oxygenation level-dependent (BOLD) signaling. However, the neural generators of the negative BOLD response remain to be characterized. Here, we use single-impulse electrical stimulation of the whisker pad in the anesthetized rat to identify components of the neural response that are related to &quot;negative&quot; hemodynamic changes in the brain. Laminar multiunit activity and local field potential recordings of neural activity were performed concurrently with two-dimensional optical imaging spectroscopy measuring hemodynamic changes. Repeated measurements over multiple stimulation trials revealed significant variations in neural responses across session and animal datasets. Within this variation, we found robust long-latency decreases (300 and 2000 ms after stimulus presentation) in gamma-band power (30-80 Hz) in the middle-superficial cor...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="393bba370bf921296da2afb1dc07daa5" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":51303004,"asset_id":30876941,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/51303004/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="30876941"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="30876941"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 30876941; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="30876876"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/30876876/Inter_trial_variability_in_sensory_evoked_cortical_hemodynamic_responses_the_role_of_the_magnitude_of_pre_stimulus_fluctuations"><img alt="Research paper thumbnail of Inter-trial variability in sensory-evoked cortical hemodynamic responses: the role of the magnitude of pre-stimulus fluctuations" class="work-thumbnail" src="https://attachments.academia-assets.com/51302952/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/30876876/Inter_trial_variability_in_sensory_evoked_cortical_hemodynamic_responses_the_role_of_the_magnitude_of_pre_stimulus_fluctuations">Inter-trial variability in sensory-evoked cortical hemodynamic responses: the role of the magnitude of pre-stimulus fluctuations</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/MylesJones1">Myles Jones</a>, <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/JasonBerwick">Jason Berwick</a>, and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/MohamadSaka">Mohamad Saka</a></span></div><div class="wp-workCard_item"><span>Frontiers in neuroenergetics</span><span>, 2012</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Brain imaging techniques utilize hemodynamic changes that accompany brain activation. However, st...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Brain imaging techniques utilize hemodynamic changes that accompany brain activation. However, stimulus-evoked hemodynamic responses display considerable inter-trial variability and the sources of this variability are poorly understood. One of the sources of this response variation could be ongoing spontaneous hemodynamic fluctuations. We recently investigated this issue by measuring cortical hemodynamics in response to sensory stimuli in anesthetized rodents using 2-dimensional optical imaging spectroscopy. We suggested that sensory-evoked cortical hemodynamics displayed distinctive response characteristics and magnitudes depending on the phase of ongoing fluctuations at stimulus onset due to a linear superposition of evoked and ongoing hemodynamics (Saka et al., 2010). However, the previous analysis neglected to examine the possible influence of variability of the size of ongoing fluctuations. Consequently, data were further analyzed to examine whether the size of pre-stimulus hem...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="05a70209991f02315f22829e665793cd" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":51302952,"asset_id":30876876,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/51302952/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="30876876"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="30876876"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 30876876; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="30876940"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/30876940/Spectroscopic_investigation_of_reflectance_changes_in_the_barrel_cortex_following_whisker_stimulation"><img alt="Research paper thumbnail of Spectroscopic investigation of reflectance changes in the barrel cortex following whisker stimulation" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/30876940/Spectroscopic_investigation_of_reflectance_changes_in_the_barrel_cortex_following_whisker_stimulation">Spectroscopic investigation of reflectance changes in the barrel cortex following whisker stimulation</a></div><div class="wp-workCard_item"><span>Advances in experimental medicine and biology</span><span>, 1998</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="30876940"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="30876940"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 30876940; 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</script> <div class="js-work-strip profile--work_container" data-work-id="30876939"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/30876939/Research_report_Integration_of_neural_responses_originating_from_different_regions_of_the_cortical_somatosensory_map"><img alt="Research paper thumbnail of Research report Integration of neural responses originating from different regions of the cortical somatosensory map" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/30876939/Research_report_Integration_of_neural_responses_originating_from_different_regions_of_the_cortical_somatosensory_map">Research report Integration of neural responses originating from different regions of the cortical somatosensory map</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The neural pathways responsible for detecting peripheral tactile stimuli are well known; however,...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The neural pathways responsible for detecting peripheral tactile stimuli are well known; however, the interactions between different somatosensory regions have been less well investigated. This study demonstrates how the contralateral sensory response of rat barrel cortex to whisker stimulation is affected by stimulation of contralateral forepaw and ipsilateral whisker and forepaw. The barrel cortex in the right hemisphere was located</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="30876939"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="30876939"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 30876939; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=30876939]").text(description); $(".js-view-count[data-work-id=30876939]").attr('title', description).tooltip(); 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</script> <div class="js-work-strip profile--work_container" data-work-id="30876930"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/30876930/A_mathematical_model_of_the_neurovascular_coupling_suggesting_both_vasodilation_and_vasoconstriction"><img alt="Research paper thumbnail of A mathematical model of the neurovascular coupling suggesting both vasodilation and vasoconstriction" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/30876930/A_mathematical_model_of_the_neurovascular_coupling_suggesting_both_vasodilation_and_vasoconstriction">A mathematical model of the neurovascular coupling suggesting both vasodilation and vasoconstriction</a></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="30876930"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="30876930"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 30876930; 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</script> <div class="js-work-strip profile--work_container" data-work-id="29125061"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29125061/Cocaine_administration_produces_a_protracted_decoupling_of_neural_and_haemodynamic_responses_to_intense_sensory_stimuli"><img alt="Research paper thumbnail of Cocaine administration produces a protracted decoupling of neural and haemodynamic responses to intense sensory stimuli" class="work-thumbnail" src="https://attachments.academia-assets.com/49571602/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29125061/Cocaine_administration_produces_a_protracted_decoupling_of_neural_and_haemodynamic_responses_to_intense_sensory_stimuli">Cocaine administration produces a protracted decoupling of neural and haemodynamic responses to intense sensory stimuli</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/PaulOverton">Paul Overton</a>, <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/AneurinKennerley">Aneurin Kennerley</a>, and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/JasonBerwick">Jason Berwick</a></span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Evidence suggests that for relatively weak sensory stimuli, cocaine elevates background haemodyna...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Evidence suggests that for relatively weak sensory stimuli, cocaine elevates background haemodynamic parameters but still allows enhanced neural responses to be reflected in enhanced haemodynamic responses. The current study investigated the possibility that for more intense stimuli, the raised background may produce a protracted attenuation of the haemodynamic response. Three experiments were performed to measure effects of i.v. cocaine administration (0.5 mg/kg) or saline on responses in rat barrel cortex to electrical stimulation of the whisker pad. The first experiment used optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) to measure haemodynamic changes. Cocaine caused an increase in baseline blood flow (peak approximately 90%), which lasted for the duration of the test period (25 min). Haemodynamic responses to whisker stimulation were substantially reduced throughout. The second experiment used a 16-channel multi-electrode to measure evoked potentials at 100 m intervals through the barrel cortex. Summed neural responses (collapsed across the spatial dimension) after cocaine administration were similar to those after saline. The third experiment extended experiment 1 by examining the effects of cocaine on whisker sensory responses using functional magnetic resonance imaging (and concurrent OIS or LDF). Cocaine caused a similar increase in baseline and reduction in the evoked response to that seen in experiment 1. Together, the results of these three experiments show that cocaine produces a protracted decoupling of neural activity and haemodynamic responses to intense sensory stimulation, which suggests that imaging techniques based on changes in haemodynamic parameters may be unsuitable for studying the effects of cocaine on sensory processing in humans. (J. Berwick). Abbreviations: BF, basal forebrain; BOLD, blood oxygen level dependent; CBF, cerebral blood flow; CMRO 2 , cerebral metabolic rate of oxygen consumption; CSD, current source density; ECOG, electrocorticogram; fMRI, functional magnetic resonance imaging; HbO 2 , time series of oxyhaemoglobin; Hbr, time series of deoxyhaemoglobin; Hbt, total blood volume; LDF, laser Doppler flowmetry; ⌺NA, summed neural activity; NO, nitric oxide; NOS, nitric oxide synthase; OIS, optical imaging spectroscopy; PLSA, path length scaling algorithm; VPM, ventral posterior medial.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="c2ae31b0289f7d1f9bab1a2f7fde5515" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":49571602,"asset_id":29125061,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/49571602/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29125061"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29125061"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29125061; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29125061]").text(description); $(".js-view-count[data-work-id=29125061]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29125061; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29125061']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "c2ae31b0289f7d1f9bab1a2f7fde5515" } } $('.js-work-strip[data-work-id=29125061]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29125061,"title":"Cocaine administration produces a protracted decoupling of neural and haemodynamic responses to intense sensory stimuli","translated_title":"","metadata":{"grobid_abstract":"Evidence suggests that for relatively weak sensory stimuli, cocaine elevates background haemodynamic parameters but still allows enhanced neural responses to be reflected in enhanced haemodynamic responses. The current study investigated the possibility that for more intense stimuli, the raised background may produce a protracted attenuation of the haemodynamic response. Three experiments were performed to measure effects of i.v. cocaine administration (0.5 mg/kg) or saline on responses in rat barrel cortex to electrical stimulation of the whisker pad. The first experiment used optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) to measure haemodynamic changes. Cocaine caused an increase in baseline blood flow (peak approximately 90%), which lasted for the duration of the test period (25 min). Haemodynamic responses to whisker stimulation were substantially reduced throughout. The second experiment used a 16-channel multi-electrode to measure evoked potentials at 100 m intervals through the barrel cortex. Summed neural responses (collapsed across the spatial dimension) after cocaine administration were similar to those after saline. The third experiment extended experiment 1 by examining the effects of cocaine on whisker sensory responses using functional magnetic resonance imaging (and concurrent OIS or LDF). Cocaine caused a similar increase in baseline and reduction in the evoked response to that seen in experiment 1. Together, the results of these three experiments show that cocaine produces a protracted decoupling of neural activity and haemodynamic responses to intense sensory stimulation, which suggests that imaging techniques based on changes in haemodynamic parameters may be unsuitable for studying the effects of cocaine on sensory processing in humans. (J. Berwick). Abbreviations: BF, basal forebrain; BOLD, blood oxygen level dependent; CBF, cerebral blood flow; CMRO 2 , cerebral metabolic rate of oxygen consumption; CSD, current source density; ECOG, electrocorticogram; fMRI, functional magnetic resonance imaging; HbO 2 , time series of oxyhaemoglobin; Hbr, time series of deoxyhaemoglobin; Hbt, total blood volume; LDF, laser Doppler flowmetry; ⌺NA, summed neural activity; NO, nitric oxide; NOS, nitric oxide synthase; OIS, optical imaging spectroscopy; PLSA, path length scaling algorithm; VPM, ventral posterior medial.","grobid_abstract_attachment_id":49571602},"translated_abstract":null,"internal_url":"https://www.academia.edu/29125061/Cocaine_administration_produces_a_protracted_decoupling_of_neural_and_haemodynamic_responses_to_intense_sensory_stimuli","translated_internal_url":"","created_at":"2016-10-13T06:52:26.008-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54959992,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[{"id":25081355,"work_id":29125061,"tagging_user_id":54959992,"tagged_user_id":null,"co_author_invite_id":5565682,"email":"i***e@pharm.ox.ac.uk","display_order":0,"name":"I. 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</script> </div><div class="profile--tab_content_container js-tab-pane tab-pane" data-section-id="6387011" id="papers"><div class="js-work-strip profile--work_container" data-work-id="28000543"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/28000543/Decreased_haemodynamic_response_and_decoupling_of_cortical_gamma_band_activity_and_tissue_oxygen_perfusion_after_striatal_interleukin_1_injection"><img alt="Research paper thumbnail of Decreased haemodynamic response and decoupling of cortical gamma-band activity and tissue oxygen perfusion after striatal interleukin-1 injection" class="work-thumbnail" src="https://attachments.academia-assets.com/48308307/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/28000543/Decreased_haemodynamic_response_and_decoupling_of_cortical_gamma_band_activity_and_tissue_oxygen_perfusion_after_striatal_interleukin_1_injection">Decreased haemodynamic response and decoupling of cortical gamma-band activity and tissue oxygen perfusion after striatal interleukin-1 injection</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://manchester.academia.edu/IngoSchiessl">Ingo Schiessl</a> and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/JasonBerwick">Jason Berwick</a></span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Background Neurovascular coupling describes the mechanism by which the energy and oxygen demand a...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Background<br />Neurovascular coupling describes the mechanism by which the energy and oxygen demand arising from neuronal activity is met by an increase in regional blood flow, known as the haemodynamic response. Interleukin 1 (IL-1) is a pro-inflammatory cytokine and an important mediator of neuronal injury, though mechanisms through which IL-1 exerts its effects in the brain are not fully understood. In this study, we set out to investigate if increased cerebral levels of IL-1 have a negative effect on the neurovascular coupling in the cortex in response to sensory stimulation.<br /><br />Methods<br />We used two approaches to measure the neuronal activity and haemodynamic changes in the anaesthetised rat barrel somatosensory cortex in response to mechanical whisker stimulation, before and for 6 h after intra-striatal injection of interleukin-1β or vehicle. First, we used two-dimensional optical imaging spectroscopy (2D-OIS) to measure the size of the functional haemodynamic response, indicated by changes of oxyhaemoglobin (HbO2) and total haemoglobin (HbT) concentration. In the same animals, immunostaining of immunoglobulin G and SJC-positive extravasated neutrophils was used to confirm the pro-inflammatory effects of interleukin-1β (IL-1β). Second, to examine the functional coupling between neuronal activity and the haemodynamic response, we used a ‘Clark-style’ electrode combined with a single sharp electrode to simultaneously record local tissue oxygenation (partial pressure oxygen, pO2) in layer IV/V of the stimulated barrel cortex and multi-unit activity (MUA) together with local field potentials (LFPs), respectively.<br /><br />Results<br />2D-OIS data revealed that the size of the haemodynamic response to mechanical whisker stimulation declined over the 6 h following IL-1β injection whereas the vehicle group remained stable, significant differences being seen after 5 h. Moreover, the size of the transient increases of neuronal LFP activity in response to whisker stimulation decreased after IL-1β injection, significant changes compared to vehicle being seen for gamma-band activity after 1 h and beta-band activity after 3 h. The amplitude of the functional pO2 response similarly decreased after 3 h post-IL-1β injection, whereas IL-1β had no significant effect on the peak of whisker-stimulation-induced MUA. The stimulation-evoked increases in gamma power and pO2 correlated significantly throughout the 6 h in the vehicle group, but such a correlation was not observed in the IL-1β-injected group.<br /><br />Conclusions<br />We conclude that intra-striatal IL-1β decouples cortical neuronal activity from its haemodynamic response. This finding may have implications for neurological conditions where IL-1β plays a part, especially those involving reductions in cerebral blood flow (such as stroke).</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="10dde57f87cfe32e0843e6bd425e9de8" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":48308307,"asset_id":28000543,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/48308307/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="28000543"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="28000543"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 28000543; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="30876943"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/30876943/Comparison_of_stimulus_evoked_cerebral_hemodynamics_in_the_awake_mouse_and_under_a_novel_anesthetic_regime"><img alt="Research paper thumbnail of Comparison of stimulus-evoked cerebral hemodynamics in the awake mouse and under a novel anesthetic regime" class="work-thumbnail" src="https://attachments.academia-assets.com/51303003/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/30876943/Comparison_of_stimulus_evoked_cerebral_hemodynamics_in_the_awake_mouse_and_under_a_novel_anesthetic_regime">Comparison of stimulus-evoked cerebral hemodynamics in the awake mouse and under a novel anesthetic regime</a></div><div class="wp-workCard_item"><span>Scientific reports</span><span>, Jan 28, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Neural activity is closely followed by a localised change in cerebral blood flow, a process terme...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Neural activity is closely followed by a localised change in cerebral blood flow, a process termed neurovascular coupling. These hemodynamic changes form the basis of contrast in functional magnetic resonance imaging (fMRI) and are used as a correlate for neural activity. Anesthesia is widely employed in animal fMRI and neurovascular studies, however anesthetics are known to profoundly affect neural and vascular physiology, particularly in mice. Therefore, we investigated the efficacy of a novel &#39;modular&#39; anesthesia that combined injectable (fentanyl-fluanisone/midazolam) and volatile (isoflurane) anesthetics in mice. To characterize sensory-evoked cortical hemodynamic responses, we used optical imaging spectroscopy to produce functional maps of changes in tissue oxygenation and blood volume in response to mechanical whisker stimulation. Following fine-tuning of the anesthetic regime, stimulation elicited large and robust hemodynamic responses in the somatosensory cortex, ch...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="14cfe9324ed9f3eb6e4ae116eb877b81" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":51303003,"asset_id":30876943,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/51303003/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="30876943"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="30876943"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 30876943; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="30876942"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/30876942/LRP_1_mediated_intracellular_antibody_delivery_to_the_Central_Nervous_System"><img alt="Research paper thumbnail of LRP-1-mediated intracellular antibody delivery to the Central Nervous System" class="work-thumbnail" src="https://attachments.academia-assets.com/51303005/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/30876942/LRP_1_mediated_intracellular_antibody_delivery_to_the_Central_Nervous_System">LRP-1-mediated intracellular antibody delivery to the Central Nervous System</a></div><div class="wp-workCard_item"><span>Scientific Reports</span><span>, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Here we report the engineering of pH-sensitive polymersomes (synthetic vesicles formed by amphiph...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Here we report the engineering of pH-sensitive polymersomes (synthetic vesicles formed by amphiphilic copolymers) that exploit endogenous transport mechanisms to traverse the BBB, enabling delivery of large macromolecules into both the CNS parenchyma and CNS cells. We achieve this by targeting the Low Density Lipoprotein Receptor-Related Protein 1 (LRP-1) receptor. We show that LRP-1 is associated with endothelial transcytosis that does not involve acidification of cargo in membranetrafficking organelles. By contrast, this receptor is also associated with traditional endocytosis in CNS cells, thus aiding the delivery of relevant cargo within their cytosol. We prove this using IgG as a model cargo, thus demonstrating that the combination of appropriate targeting combined with pHsensitive polymersomes enables the efficient delivery of macromolecules into CNS cells.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="fa3083e12f2d7659c15344276bc6373b" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":51303005,"asset_id":30876942,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/51303005/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="30876942"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="30876942"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 30876942; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=30876942]").text(description); $(".js-view-count[data-work-id=30876942]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 30876942; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='30876942']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="30876941"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/30876941/Long_Latency_Reductions_in_Gamma_Power_Predict_Hemodynamic_Changes_That_Underlie_the_Negative_BOLD_Signal"><img alt="Research paper thumbnail of Long-Latency Reductions in Gamma Power Predict Hemodynamic Changes That Underlie the Negative BOLD Signal" class="work-thumbnail" src="https://attachments.academia-assets.com/51303004/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/30876941/Long_Latency_Reductions_in_Gamma_Power_Predict_Hemodynamic_Changes_That_Underlie_the_Negative_BOLD_Signal">Long-Latency Reductions in Gamma Power Predict Hemodynamic Changes That Underlie the Negative BOLD Signal</a></div><div class="wp-workCard_item"><span>The Journal of neuroscience : the official journal of the Society for Neuroscience</span><span>, Jan 18, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Studies that use prolonged periods of sensory stimulation report associations between regional re...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Studies that use prolonged periods of sensory stimulation report associations between regional reductions in neural activity and negative blood oxygenation level-dependent (BOLD) signaling. However, the neural generators of the negative BOLD response remain to be characterized. Here, we use single-impulse electrical stimulation of the whisker pad in the anesthetized rat to identify components of the neural response that are related to &quot;negative&quot; hemodynamic changes in the brain. Laminar multiunit activity and local field potential recordings of neural activity were performed concurrently with two-dimensional optical imaging spectroscopy measuring hemodynamic changes. Repeated measurements over multiple stimulation trials revealed significant variations in neural responses across session and animal datasets. Within this variation, we found robust long-latency decreases (300 and 2000 ms after stimulus presentation) in gamma-band power (30-80 Hz) in the middle-superficial cor...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="393bba370bf921296da2afb1dc07daa5" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":51303004,"asset_id":30876941,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/51303004/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="30876941"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="30876941"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 30876941; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="30876876"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/30876876/Inter_trial_variability_in_sensory_evoked_cortical_hemodynamic_responses_the_role_of_the_magnitude_of_pre_stimulus_fluctuations"><img alt="Research paper thumbnail of Inter-trial variability in sensory-evoked cortical hemodynamic responses: the role of the magnitude of pre-stimulus fluctuations" class="work-thumbnail" src="https://attachments.academia-assets.com/51302952/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/30876876/Inter_trial_variability_in_sensory_evoked_cortical_hemodynamic_responses_the_role_of_the_magnitude_of_pre_stimulus_fluctuations">Inter-trial variability in sensory-evoked cortical hemodynamic responses: the role of the magnitude of pre-stimulus fluctuations</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/MylesJones1">Myles Jones</a>, <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/JasonBerwick">Jason Berwick</a>, and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/MohamadSaka">Mohamad Saka</a></span></div><div class="wp-workCard_item"><span>Frontiers in neuroenergetics</span><span>, 2012</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Brain imaging techniques utilize hemodynamic changes that accompany brain activation. However, st...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Brain imaging techniques utilize hemodynamic changes that accompany brain activation. However, stimulus-evoked hemodynamic responses display considerable inter-trial variability and the sources of this variability are poorly understood. One of the sources of this response variation could be ongoing spontaneous hemodynamic fluctuations. We recently investigated this issue by measuring cortical hemodynamics in response to sensory stimuli in anesthetized rodents using 2-dimensional optical imaging spectroscopy. We suggested that sensory-evoked cortical hemodynamics displayed distinctive response characteristics and magnitudes depending on the phase of ongoing fluctuations at stimulus onset due to a linear superposition of evoked and ongoing hemodynamics (Saka et al., 2010). However, the previous analysis neglected to examine the possible influence of variability of the size of ongoing fluctuations. Consequently, data were further analyzed to examine whether the size of pre-stimulus hem...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="05a70209991f02315f22829e665793cd" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":51302952,"asset_id":30876876,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/51302952/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="30876876"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="30876876"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 30876876; 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however,...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The neural pathways responsible for detecting peripheral tactile stimuli are well known; however, the interactions between different somatosensory regions have been less well investigated. This study demonstrates how the contralateral sensory response of rat barrel cortex to whisker stimulation is affected by stimulation of contralateral forepaw and ipsilateral whisker and forepaw. 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</script> <div class="js-work-strip profile--work_container" data-work-id="29125061"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29125061/Cocaine_administration_produces_a_protracted_decoupling_of_neural_and_haemodynamic_responses_to_intense_sensory_stimuli"><img alt="Research paper thumbnail of Cocaine administration produces a protracted decoupling of neural and haemodynamic responses to intense sensory stimuli" class="work-thumbnail" src="https://attachments.academia-assets.com/49571602/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29125061/Cocaine_administration_produces_a_protracted_decoupling_of_neural_and_haemodynamic_responses_to_intense_sensory_stimuli">Cocaine administration produces a protracted decoupling of neural and haemodynamic responses to intense sensory stimuli</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/PaulOverton">Paul Overton</a>, <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/AneurinKennerley">Aneurin Kennerley</a>, and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/JasonBerwick">Jason Berwick</a></span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Evidence suggests that for relatively weak sensory stimuli, cocaine elevates background haemodyna...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Evidence suggests that for relatively weak sensory stimuli, cocaine elevates background haemodynamic parameters but still allows enhanced neural responses to be reflected in enhanced haemodynamic responses. The current study investigated the possibility that for more intense stimuli, the raised background may produce a protracted attenuation of the haemodynamic response. Three experiments were performed to measure effects of i.v. cocaine administration (0.5 mg/kg) or saline on responses in rat barrel cortex to electrical stimulation of the whisker pad. The first experiment used optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) to measure haemodynamic changes. Cocaine caused an increase in baseline blood flow (peak approximately 90%), which lasted for the duration of the test period (25 min). Haemodynamic responses to whisker stimulation were substantially reduced throughout. The second experiment used a 16-channel multi-electrode to measure evoked potentials at 100 m intervals through the barrel cortex. Summed neural responses (collapsed across the spatial dimension) after cocaine administration were similar to those after saline. The third experiment extended experiment 1 by examining the effects of cocaine on whisker sensory responses using functional magnetic resonance imaging (and concurrent OIS or LDF). Cocaine caused a similar increase in baseline and reduction in the evoked response to that seen in experiment 1. Together, the results of these three experiments show that cocaine produces a protracted decoupling of neural activity and haemodynamic responses to intense sensory stimulation, which suggests that imaging techniques based on changes in haemodynamic parameters may be unsuitable for studying the effects of cocaine on sensory processing in humans. (J. Berwick). Abbreviations: BF, basal forebrain; BOLD, blood oxygen level dependent; CBF, cerebral blood flow; CMRO 2 , cerebral metabolic rate of oxygen consumption; CSD, current source density; ECOG, electrocorticogram; fMRI, functional magnetic resonance imaging; HbO 2 , time series of oxyhaemoglobin; Hbr, time series of deoxyhaemoglobin; Hbt, total blood volume; LDF, laser Doppler flowmetry; ⌺NA, summed neural activity; NO, nitric oxide; NOS, nitric oxide synthase; OIS, optical imaging spectroscopy; PLSA, path length scaling algorithm; VPM, ventral posterior medial.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="c2ae31b0289f7d1f9bab1a2f7fde5515" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":49571602,"asset_id":29125061,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/49571602/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29125061"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29125061"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29125061; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29125061]").text(description); $(".js-view-count[data-work-id=29125061]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29125061; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29125061']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "c2ae31b0289f7d1f9bab1a2f7fde5515" } } $('.js-work-strip[data-work-id=29125061]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29125061,"title":"Cocaine administration produces a protracted decoupling of neural and haemodynamic responses to intense sensory stimuli","translated_title":"","metadata":{"grobid_abstract":"Evidence suggests that for relatively weak sensory stimuli, cocaine elevates background haemodynamic parameters but still allows enhanced neural responses to be reflected in enhanced haemodynamic responses. The current study investigated the possibility that for more intense stimuli, the raised background may produce a protracted attenuation of the haemodynamic response. Three experiments were performed to measure effects of i.v. cocaine administration (0.5 mg/kg) or saline on responses in rat barrel cortex to electrical stimulation of the whisker pad. The first experiment used optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) to measure haemodynamic changes. Cocaine caused an increase in baseline blood flow (peak approximately 90%), which lasted for the duration of the test period (25 min). Haemodynamic responses to whisker stimulation were substantially reduced throughout. The second experiment used a 16-channel multi-electrode to measure evoked potentials at 100 m intervals through the barrel cortex. Summed neural responses (collapsed across the spatial dimension) after cocaine administration were similar to those after saline. The third experiment extended experiment 1 by examining the effects of cocaine on whisker sensory responses using functional magnetic resonance imaging (and concurrent OIS or LDF). Cocaine caused a similar increase in baseline and reduction in the evoked response to that seen in experiment 1. Together, the results of these three experiments show that cocaine produces a protracted decoupling of neural activity and haemodynamic responses to intense sensory stimulation, which suggests that imaging techniques based on changes in haemodynamic parameters may be unsuitable for studying the effects of cocaine on sensory processing in humans. (J. Berwick). 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The current study investigated the possibility that for more intense stimuli, the raised background may produce a protracted attenuation of the haemodynamic response. Three experiments were performed to measure effects of i.v. cocaine administration (0.5 mg/kg) or saline on responses in rat barrel cortex to electrical stimulation of the whisker pad. The first experiment used optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) to measure haemodynamic changes. Cocaine caused an increase in baseline blood flow (peak approximately 90%), which lasted for the duration of the test period (25 min). Haemodynamic responses to whisker stimulation were substantially reduced throughout. The second experiment used a 16-channel multi-electrode to measure evoked potentials at 100 m intervals through the barrel cortex. Summed neural responses (collapsed across the spatial dimension) after cocaine administration were similar to those after saline. The third experiment extended experiment 1 by examining the effects of cocaine on whisker sensory responses using functional magnetic resonance imaging (and concurrent OIS or LDF). Cocaine caused a similar increase in baseline and reduction in the evoked response to that seen in experiment 1. Together, the results of these three experiments show that cocaine produces a protracted decoupling of neural activity and haemodynamic responses to intense sensory stimulation, which suggests that imaging techniques based on changes in haemodynamic parameters may be unsuitable for studying the effects of cocaine on sensory processing in humans. (J. Berwick). 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