Publications by authors named "Julien Vezoli"

15 Publications

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Cortical hierarchy, dual counterstream architecture and the importance of top-down generative networks.

Neuroimage 2021 01 21;225:117479. Epub 2020 Oct 21.

Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France; Institute of Neuroscience, State Key Laboratory of Neuroscience, Chinese Academy of Sciences (CAS) Key Laboratory of Primate Neurobiology, CAS, Shanghai 200031, China. Electronic address:

Hierarchy is a major organizational principle of the cortex and underscores modern computational theories of cortical function. The local microcircuit amplifies long-distance inter-areal input, which show distance-dependent changes in their laminar profiles. Statistical modeling of these changes in laminar profiles demonstrates that inputs from multiple hierarchical levels to their target areas show remarkable consistency, allowing the construction of a cortical hierarchy based on a principle of hierarchical distance. The statistical modeling that is applied to structure can also be applied to laminar differences in the oscillatory coherence between areas thereby determining a functional hierarchy of the cortex. Close examination of the anatomy of inter-areal connectivity reveals a dual counterstream architecture with well-defined distance-dependent feedback and feedforward pathways in both the supra- and infragranular layers, suggesting a multiplicity of feedback pathways with well-defined functional properties. These findings are consistent with feedback connections providing a generative network involved in a wide range of cognitive functions. A dynamical model constrained by connectivity data sheds insight into the experimentally observed signatures of frequency-dependent Granger causality for feedforward versus feedback signaling. Concerted experiments capitalizing on recent technical advances and combining tract-tracing, high-resolution fMRI, optogenetics and mathematical modeling hold the promise of a much improved understanding of lamina-constrained mechanisms of neural computation and cognition. However, because inter-areal interactions involve cortical layers that have been the target of important evolutionary changes in the primate lineage, these investigations will need to include human and non-human primate comparisons.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244994PMC
January 2021

Transplantation in the nonhuman primate MPTP model of Parkinson's disease: update and perspectives.

Primate Biol 2017 11;4(2):185-213. Epub 2017 Oct 11.

Ernst Strüngmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society, 60528 Frankfurt, Germany.

In order to calibrate stem cell exploitation for cellular therapy in neurodegenerative diseases, fundamental and preclinical research in NHP (nonhuman primate) models is crucial. Indeed, it is consensually recognized that it is not possible to directly extrapolate results obtained in rodent models to human patients. A large diversity of neurological pathologies should benefit from cellular therapy based on neural differentiation of stem cells. In the context of this special issue of Primate Biology on NHP stem cells, we describe past and recent advances on cell replacement in the NHP model of Parkinson's disease (PD). From the different grafting procedures to the various cell types transplanted, we review here diverse approaches for cell-replacement therapy and their related therapeutic potential on behavior and function in the NHP model of PD.
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http://dx.doi.org/10.5194/pb-4-185-2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041537PMC
October 2017

Prefrontal Markers and Cognitive Performance Are Dissociated during Progressive Dopamine Lesion.

PLoS Biol 2016 Nov 8;14(11):e1002576. Epub 2016 Nov 8.

University of Lyon, Université Claude Bernard Lyon 1, INSERM, Stem Cell and Brain Research Institute U1208, Lyon, France.

Dopamine is thought to directly influence the neurophysiological mechanisms of both performance monitoring and cognitive control-two processes that are critically linked in the production of adapted behaviour. Changing dopamine levels are also thought to induce cognitive changes in several neurological and psychiatric conditions. But the working model of this system as a whole remains untested. Specifically, although many researchers assume that changing dopamine levels modify neurophysiological mechanisms and their markers in frontal cortex, and that this in turn leads to cognitive changes, this causal chain needs to be verified. Using longitudinal recordings of frontal neurophysiological markers over many months during progressive dopaminergic lesion in non-human primates, we provide data that fail to support a simple interaction between dopamine, frontal function, and cognition. Feedback potentials, which are performance-monitoring signals sometimes thought to drive successful control, ceased to differentiate feedback valence at the end of the lesion, just before clinical motor threshold. In contrast, cognitive control performance and beta oscillatory markers of cognitive control were unimpaired by the lesion. The differing dynamics of these measures throughout a dopamine lesion suggests they are not all driven by dopamine in the same way. These dynamics also demonstrate that a complex non-linear set of mechanisms is engaged in the brain in response to a progressive dopamine lesion. These results question the direct causal chain from dopamine to frontal physiology and on to cognition. They imply that biomarkers of cognitive functions are not directly predictive of dopamine loss.
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http://dx.doi.org/10.1371/journal.pbio.1002576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100991PMC
November 2016

[The brain uses different frequency channels to communicate].

Authors:
Julien Vezoli

Med Sci (Paris) 2016 Oct 19;32(10):823-826. Epub 2016 Oct 19.

Ernst Strüngmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society, Fries Lab, Deutschordenstr. 46, D-60528, Frankfurt am Main, Allemagne.

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http://dx.doi.org/10.1051/medsci/20163210011DOI Listing
October 2016

Alpha-Beta and Gamma Rhythms Subserve Feedback and Feedforward Influences among Human Visual Cortical Areas.

Neuron 2016 Jan;89(2):384-97

1Ernst Strungmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society, Deutschordenstraße 46, 60528 Frankfurt, Germany

Primate visual cortex is hierarchically organized. Bottom-up and top-down influences are exerted through distinct frequency channels, as was recently revealed in macaques by correlating inter-areal influences with laminar anatomical projection patterns. Because this anatomical data cannot be obtained in human subjects, we selected seven homologous macaque and human visual areas, and we correlated the macaque laminar projection patterns to human inter-areal directed influences as measured with magnetoencephalography. We show that influences along feedforward projections predominate in the gamma band, whereas influences along feedback projections predominate in the alpha-beta band. Rhythmic inter-areal influences constrain a functional hierarchy of the seven homologous human visual areas that is in close agreement with the respective macaque anatomical hierarchy. Rhythmic influences allow an extension of the hierarchy to 26 human visual areas including uniquely human brain areas. Hierarchical levels of ventral- and dorsal-stream visual areas are differentially affected by inter-areal influences in the alpha-beta band.
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http://dx.doi.org/10.1016/j.neuron.2015.12.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871751PMC
January 2016

The Effects of Cognitive Control and Time on Frontal Beta Oscillations.

Cereb Cortex 2016 Apr 30;26(4):1715-1732. Epub 2015 Jan 30.

INSERM U846, Stem Cell and Brain Research Institute, Bron 69500, France.

Frontal beta oscillations are associated with top-down control mechanisms but also change over time during a task. It is unclear whether change over time represents another control function or a neural instantiation of vigilance decrements over time, the time-on-task effect. We investigated how frontal beta oscillations are modulated by cognitive control and time. We used frontal chronic electrocorticography in monkeys performing a trial-and-error task, comprising search and repetition phases. Specific beta oscillations in the delay period of each trial were modulated by task phase and adaptation to feedback. Beta oscillations in this same period showed a significant within-session change. These separate modulations of beta oscillations did not interact. Crucially, and in contrast to previous investigations, we examined modulations of beta around spontaneous pauses in work. After pauses, the beta power modulation was reset and the cognitive control effect was maintained. Cognitive performance was also maintained whereas behavioral signs of fatigue continued to increase. We propose that these beta oscillations reflect multiple factors contributing to the regulation of cognitive control. Due to the effect of pauses, the time-sensitive factor cannot be a neural correlate of time-on-task but may reflect attentional effort.
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http://dx.doi.org/10.1093/cercor/bhv006DOI Listing
April 2016

Visual areas exert feedforward and feedback influences through distinct frequency channels.

Neuron 2015 Jan 31;85(2):390-401. Epub 2014 Dec 31.

Ernst Strüngmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society, Deutschordenstraße 46, 60528 Frankfurt, Germany; Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Kapittelweg 29, 6525 EN Nijmegen, Netherlands. Electronic address:

Visual cortical areas subserve cognitive functions by interacting in both feedforward and feedback directions. While feedforward influences convey sensory signals, feedback influences modulate feedforward signaling according to the current behavioral context. We investigated whether these interareal influences are subserved differentially by rhythmic synchronization. We correlated frequency-specific directed influences among 28 pairs of visual areas with anatomical metrics of the feedforward or feedback character of the respective interareal projections. This revealed that in the primate visual system, feedforward influences are carried by theta-band (∼ 4 Hz) and gamma-band (∼ 60-80 Hz) synchronization, and feedback influences by beta-band (∼ 14-18 Hz) synchronization. The functional directed influences constrain a functional hierarchy similar to the anatomical hierarchy, but exhibiting task-dependent dynamic changes in particular with regard to the hierarchical positions of frontal areas. Our results demonstrate that feedforward and feedback signaling use distinct frequency channels, suggesting that they subserve differential communication requirements.
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http://dx.doi.org/10.1016/j.neuron.2014.12.018DOI Listing
January 2015

Communication through coherence with inter-areal delays.

Curr Opin Neurobiol 2015 Apr 20;31:173-80. Epub 2014 Nov 20.

Ernst Strüngmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society, 60528 Frankfurt, Germany; Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, 6525 EN Nijmegen, Netherlands.

The communication-through-coherence (CTC) hypothesis proposes that anatomical connections are dynamically rendered effective or ineffective through the presence or absence of rhythmic synchronization, in particular in the gamma and beta bands. The original CTC statement proposed that uni-directional communication is due to rhythmic entrainment with an inter-areal delay and a resulting non-zero phase relation, whereas bi-directional communication is due to zero-phase synchronization. Recent studies found that inter-areal gamma-band synchronization entails a non-zero phase lag. We therefore modify the CTC hypothesis and propose that bi-directional cortical communication is realized separately for the two directions by uni-directional CTC mechanisms entailing delays in both directions. We review evidence suggesting that inter-areal influences in the feedforward and feedback directions are segregated both anatomically and spectrally.
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http://dx.doi.org/10.1016/j.conb.2014.11.001DOI Listing
April 2015

Increased DAT binding in the early stage of the dopaminergic lesion: a longitudinal [11C]PE2I binding study in the MPTP-monkey.

Neuroimage 2014 Nov 7;102 Pt 2:249-61. Epub 2014 Aug 7.

INSERM U846, Stem Cell and Brain Research Institute, Bron, France; Université de Lyon, Université Lyon1, Lyon, France.

The delayed appearance of motor symptoms in PD poses a crucial challenge for early detection of the disease. We measured the binding potential of the selective dopamine active transporter (DAT) radiotracer [(11)C]PE2I in MPTP-treated macaque monkeys, thus establishing a detailed profile of the nigrostriatal DA status following MPTP intoxication and its relation to induced motor and non-motor symptoms. Clinical score and cognitive performance were followed throughout the study. We measured longitudinally in vivo the non-displaceable binding potential to DAT in premotor, motor-recovered (i.e. both non-symptomatic) and symptomatic MPTP-treated monkeys. Results show an unexpected and pronounced dissociation between clinical scores and [(11)C]PE2I-BP(ND) during the premotor phase i.e. DAT binding in the striatum of premotor animals was increased around 20%. Importantly, this broad increase of DAT binding in the caudate, ventral striatum and anterior putamen was accompanied by i) deteriorated cognitive performance, showing a likely causal role of the observed hyperdopaminergic state (Cools, 2011; Cools and D'Esposito, 2011) and ii) an asymmetric decrease of DAT binding at a focal point of the posterior putamen, suggesting that increased DAT is one of the earliest, intrinsic compensatory mechanisms. Following spontaneous recovery from motor deficits, DAT binding was greatly reduced as recently shown in-vivo with other radiotracers (Blesa et al., 2010, 2012). Finally, high clinical scores were correlated to considerably low levels of DAT only after the induction of a stable parkinsonian state. We additionally show that the only striatal region which was significantly correlated to the degree of motor impairments is the ventral striatum. Further research on this period should allow better understanding of DA compensation at premature stages of PD and potentially identify new diagnosis and therapeutic index.
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http://dx.doi.org/10.1016/j.neuroimage.2014.07.059DOI Listing
November 2014

Alteration of daily and circadian rhythms following dopamine depletion in MPTP treated non-human primates.

PLoS One 2014 23;9(1):e86240. Epub 2014 Jan 23.

Inserm, U846, Stem Cell and Brain Research Institute, Bron, France ; Université de Lyon, Lyon 1, UMR-S 846, Lyon, France.

Disturbances of the daily sleep/wake cycle are common non-motor symptoms of Parkinson's disease (PD). However, the impact of dopamine (DA) depletion on circadian rhythms in PD patients or non-human primate (NHP) models of the disorder have not been investigated. We evaluated alterations of circadian rhythms in NHP following MPTP lesion of the dopaminergic nigro-striatal system. DA degeneration was assessed by in vivo PET ([(11)C]-PE2I) and post-mortem TH and DAT quantification. In a light∶dark cycle, control and MPTP-treated NHP both exhibit rest-wake locomotor rhythms, although DA-depleted NHP show reduced amplitude, decreased stability and increased fragmentation. In all animals, 6-sulphatoxymelatonin peaks at night and cortisol in early morning. When the circadian system is challenged by exposure to constant light, controls retain locomotor rest-wake and hormonal rhythms that free-run with stable phase relationships whereas in the DA-depleted NHP, locomotor rhythms are severely disturbed or completely abolished. The amplitude and phase relations of hormonal rhythms nevertheless remain unaltered. Use of a light-dark masking paradigm shows that expression of daily rest-wake activity in MPTP monkeys requires the stimulatory and inhibitory effects of light and darkness. These results suggest that following DA lesion, the central clock in the SCN remains intact but, in the absence of environmental timing cues, is unable to drive downstream rhythmic processes of striatal clock gene and dopaminergic functions that control locomotor output. These findings suggest that the circadian component of the sleep-wake disturbances in PD is more profoundly affected than previously assumed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0086240PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900505PMC
November 2014

Anatomy of hierarchy: feedforward and feedback pathways in macaque visual cortex.

J Comp Neurol 2014 Jan;522(1):225-59

Stem Cell and Brain Research Institute, INSERM U846, 69500, Bron, France; Université de Lyon, Université Lyon I, 69003, Lyon, France; Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut, 06520-8001, USA.

The laminar location of the cell bodies and terminals of interareal connections determines the hierarchical structural organization of the cortex and has been intensively studied. However, we still have only a rudimentary understanding of the connectional principles of feedforward (FF) and feedback (FB) pathways. Quantitative analysis of retrograde tracers was used to extend the notion that the laminar distribution of neurons interconnecting visual areas provides an index of hierarchical distance (percentage of supragranular labeled neurons [SLN]). We show that: 1) SLN values constrain models of cortical hierarchy, revealing previously unsuspected areal relations; 2) SLN reflects the operation of a combinatorial distance rule acting differentially on sets of connections between areas; 3) Supragranular layers contain highly segregated bottom-up and top-down streams, both of which exhibit point-to-point connectivity. This contrasts with the infragranular layers, which contain diffuse bottom-up and top-down streams; 4) Cell filling of the parent neurons of FF and FB pathways provides further evidence of compartmentalization; 5) FF pathways have higher weights, cross fewer hierarchical levels, and are less numerous than FB pathways. Taken together, the present results suggest that cortical hierarchies are built from supra- and infragranular counterstreams. This compartmentalized dual counterstream organization allows point-to-point connectivity in both bottom-up and top-down directions.
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http://dx.doi.org/10.1002/cne.23458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255240PMC
January 2014

Early presymptomatic and long-term changes of rest activity cycles and cognitive behavior in a MPTP-monkey model of Parkinson's disease.

PLoS One 2011 24;6(8):e23952. Epub 2011 Aug 24.

Inserm, U846, Stem Cell and Brain Research Institute, Bron, France.

Background: It is increasingly recognized that non-motor symptoms are a prominent feature of Parkinson's disease and in the case of cognitive deficits can precede onset of the characteristic motor symptoms. Here, we examine in 4 monkeys chronically treated with low doses of the neurotoxin MPTP the early and long-term alterations of rest-activity rhythms in relationship to the appearance of motor and cognitive symptoms.

Methodology/principal Findings: Behavioral activity recordings as well as motor and cognitive assessments were carried out continuously and in parallel before, during and for several months following MPTP-treatment (12-56 weeks). Cognitive abilities were assessed using a task that is dependent on the functional integrity of the fronto-striatal axis. Rest-activity cycles were monitored continuously using infrared movement detectors of locomotor activity. Motor impairment was evaluated using standardized scales for primates. Results show that MPTP treatment led to an immediate alteration (within one week) of rest-activity cycles and cognitive deficits. Parkinsonian motor deficits only became apparent 3 to 5 weeks after initiating chronic MPTP administration. In three of the four animals studied, clinical scores returned to control levels 5-7 weeks following cessation of MPTP treatment. In contrast, both cognitive deficits and chronobiological alterations persisted for many months. Levodopa treatment led to an improvement of cognitive performance but did not affect rest-activity rhythms in the two cases tested.

Conclusions/significance: Present results show that i) changes in the rest activity cycles constituted early detectable consequences of MPTP treatment and, along with cognitive alterations, characterize the presymptomatic stage; ii) following motor recovery there is a long-term persistence of non-motor symptoms that could reflect differential underlying compensatory mechanisms in these domains; iii) the progressive MPTP-monkey model of presymptomatic ongoing parkinsonism offers possibilities for in-depth studies of early non-motor symptoms including sleep alterations and cognitive deficits.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0023952PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161087PMC
February 2012

Frontal feedback-related potentials in nonhuman primates: modulation during learning and under haloperidol.

J Neurosci 2009 Dec;29(50):15675-83

Inserm, U846, Stem Cell and Brain Research Institute, 69500 Bron, France.

Feedback monitoring and adaptation of performance involve a medial reward system including medial frontal cortical areas, the medial striatum, and the dopaminergic system. A considerable amount of data has been obtained on frontal surface feedback-related potentials (FRPs) in humans and on the correlate of outcome monitoring with single unit activity in monkeys. However, work is needed to bridge knowledge obtained in the two species. The present work describes FRPs in monkeys, using chronic recordings, during a trial and error task. We show that frontal FRPs are differentially sensitive to successes and failures and can be observed over long-term periods. In addition, using the dopamine antagonist haloperidol we observe a selective effect on FRP amplitude that is absent for pure sensory-related potentials. These results describe frontal dopaminergic-dependent FRPs in monkeys and corroborate a human-monkey homology for performance monitoring signals.
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http://dx.doi.org/10.1523/JNEUROSCI.4943-09.2009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6666180PMC
December 2009

Expectations, gains, and losses in the anterior cingulate cortex.

Cogn Affect Behav Neurosci 2007 Dec;7(4):327-36

Inserm U846, Stem Cell and Brain Research Institute, Bron, France.

The anterior cingulate cortex (ACC) participates in evaluating actions and outcomes. Little is known on how action-reward values are processed in ACC and if the context in which actions are performed influences this processing. In the present article, we report ACC unit activity of monkeys performing two tasks. The first task tested whether the encoding of reward values is co ntext dependent-that is, dependent on the size of theother rewards that are available in the current block of trials. The second task tested whether unexpected events signaling a change in reward are represented. We show that the context created by a block design (i.e., the context of possible alternative rewards) influences the encoding of reward values, even if no decision or choice is required. ACC activity encodes the relative and not absolute expected reward values. Moreover, cingulate activitysignals and evaluates when reward expectations are violated by unexpected stimuli, indicating reward gains or losses.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2271114PMC
http://dx.doi.org/10.3758/cabn.7.4.327DOI Listing
December 2007

Quantitative analysis of connectivity in the visual cortex: extracting function from structure.

Neuroscientist 2004 Oct;10(5):476-82

Cerveau et Vision, INSERM U371, IFNL, Université Claude Bernard Lyon I, Bron, France.

It is generally agreed that information flow through the cortex is constrained by a hierarchical architecture. Lack of precise data on areal connectivity leads to indeterminacy of existing models. The authors introduce two quantitative parameters (SLN and FLN) that hold the promise of resolving such indeterminacy. In the visual system, using a very incomplete database, provisional hierarchies are in line with the recent proposal of higher functions of area V1 and suggest a hitherto unsuspected central function of the frontal eye field.
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http://dx.doi.org/10.1177/1073858404268478DOI Listing
October 2004
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