Publications by authors named "Charles-Francois Latchoumane"

11 Publications

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Engineered glycomaterial implants orchestrate large-scale functional repair of brain tissue chronically after severe traumatic brain injury.

Sci Adv 2021 Mar 5;7(10). Epub 2021 Mar 5.

Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.

Severe traumatic brain injury (sTBI) survivors experience permanent functional disabilities due to significant volume loss and the brain's poor capacity to regenerate. Chondroitin sulfate glycosaminoglycans (CS-GAGs) are key regulators of growth factor signaling and neural stem cell homeostasis in the brain. However, the efficacy of engineered CS (eCS) matrices in mediating structural and functional recovery chronically after sTBI has not been investigated. We report that neurotrophic factor functionalized acellular eCS matrices implanted into the rat M1 region acutely after sTBI significantly enhanced cellular repair and gross motor function recovery when compared to controls 20 weeks after sTBI. Animals subjected to M2 region injuries followed by eCS matrix implantations demonstrated the significant recovery of "reach-to-grasp" function. This was attributed to enhanced volumetric vascularization, activity-regulated cytoskeleton (Arc) protein expression, and perilesional sensorimotor connectivity. These findings indicate that eCS matrices implanted acutely after sTBI can support complex cellular, vascular, and neuronal circuit repair chronically after sTBI.
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http://dx.doi.org/10.1126/sciadv.abe0207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935369PMC
March 2021

Neurostimulation and Reach-to-Grasp Function Recovery Following Acquired Brain Injury: Insight From Pre-clinical Rodent Models and Human Applications.

Front Neurol 2020 21;11:835. Epub 2020 Jul 21.

Regenerative Bioscience Center, University of Georgia, Athens, GA, United States.

Reach-to-grasp is an evolutionarily conserved motor function that is adversely impacted following stroke and traumatic brain injury (TBI). Non-invasive brain stimulation (NIBS) methods, such as transcranial magnetic stimulation and transcranial direct current stimulation, are promising tools that could enhance functional recovery of reach-to-grasp post-brain injury. Though the rodent literature provides a causal understanding of post-injury recovery mechanisms, it has had a limited impact on NIBS protocols in human research. The high degree of homology in reach-to-grasp circuitry between humans and rodents further implies that the application of NIBS to brain injury could be better informed by findings from pre-clinical rodent models and neurorehabilitation research. Here, we provide an overview of the advantages and limitations of using rodent models to advance our current understanding of human reach-to-grasp function, cortical circuitry, and reorganization. We propose that a cross-species comparison of reach-to-grasp recovery could provide a mechanistic framework for clinically efficacious NIBS treatments that could elicit better functional outcomes for patients.
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http://dx.doi.org/10.3389/fneur.2020.00835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396659PMC
July 2020

Extracellular Vesicles Mediate Neuroprotection and Functional Recovery after Traumatic Brain Injury.

J Neurotrauma 2020 06 10;37(11):1358-1369. Epub 2020 Feb 10.

Regenerative Bioscience Center, University of Georgia, Athens, Georgia, USA.

The lack of effective therapies for moderate-to-severe traumatic brain injuries (TBIs) leaves patients with lifelong disabilities. Neural stem cells (NSCs) have demonstrated great promise for neural repair and regeneration. However, direct evidence to support their use as a cell replacement therapy for neural injuries is currently lacking. We hypothesized that NSC-derived extracellular vesicles (NSC EVs) mediate repair indirectly after TBI by enhancing neuroprotection and therapeutic efficacy of endogenous NSCs. We evaluated the short-term effects of acute intravenous injections of NSC EVs immediately following a rat TBI. Male NSC EV-treated rats demonstrated significantly reduced lesion sizes, enhanced presence of endogenous NSCs, and attenuated motor function impairments 4 weeks post-TBI, when compared with vehicle- and TBI-only male controls. Although statistically not significant, we observed a therapeutic effect of NSC EVs on brain lesion volume, nestin expression, and behavioral recovery in female subjects. Our study demonstrates the neuroprotective and functional benefits of NSC EVs for treating TBI and points to gender-dependent effects on treatment outcomes, which requires further investigation.
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http://dx.doi.org/10.1089/neu.2019.6443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249471PMC
June 2020

The rostroventral part of the thalamic reticular nucleus modulates fear extinction.

Nat Commun 2019 10 11;10(1):4637. Epub 2019 Oct 11.

Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon, 305-338, Korea.

The thalamus has been implicated in fear extinction, yet the role of the thalamic reticular nucleus (TRN) in this process remains unclear. Here, in mice, we show that the rostroventral part of the TRN (TRNrv) is critically involved in the extinction of tone-dependent fear memory. Optogenetic excitation of TRNrv neurons during extinction learning dramatically facilitated, whereas the inhibition disrupted, the fear extinction. Single unit recordings demonstrated that TRNrv neurons selectively respond to conditioned stimuli but not to neutral stimuli. TRNrv neurons suppressed the spiking activity of the medial part of the dorsal midline thalamus (dMTm), and a blockade of this inhibitory pathway disrupted fear extinction. Finally, we found that the suppression of dMTm projections to the central amygdala promotes fear extinction, and TRNrv neurons have direct connections to this pathway. Our results uncover a previously unknown function of the TRN and delineate the neural circuit for thalamic control of fear memory.
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http://dx.doi.org/10.1038/s41467-019-12496-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789150PMC
October 2019

Chronic Electrical Stimulation Promotes the Excitability and Plasticity of ESC-derived Neurons following Glutamate-induced Inhibition In vitro.

Sci Rep 2018 Jul 19;8(1):10957. Epub 2018 Jul 19.

Regenerative Bioscience Center, ADS Complex, University of Georgia, Athens, Georgia.

Functional electrical stimulation (FES) is rapidly gaining traction as a therapeutic tool for mediating the repair and recovery of the injured central nervous system (CNS). However, the underlying mechanisms and impact of these stimulation paradigms at a molecular, cellular and network level remain largely unknown. In this study, we used embryonic stem cell (ESC)-derived neuron and glial co-cultures to investigate network maturation following acute administration of L-glutamate, which is a known mediator of excitotoxicity following CNS injury. We then modulated network maturation using chronic low frequency stimulation (LFS) and direct current stimulation (DCS) protocols. We demonstrated that L-glutamate impaired the rate of maturation of ESC-derived neurons and glia immediately and over a week following acute treatment. The administration of chronic LFS and DCS protocols individually following L-glutamate infusion significantly promoted the excitability of neurons as well as network synchrony, while the combination of LFS/DCS did not. qRT-PCR analysis revealed that LFS and DCS alone significantly up-regulated the expression of excitability and plasticity-related transcripts encoding N-methyl-D-aspartate (NMDA) receptor subunit (NR2A), brain-derived neurotrophic factor (BDNF) and Ras-related protein (RAB3A). In contrast, the simultaneous administration of LFS/DCS down-regulated BDNF and RAB3A expression. Our results demonstrate that LFS and DCS stimulation can modulate network maturation excitability and synchrony following the acute administration of an inhibitory dose of L-glutamate, and upregulate NR2A, BDNF and RAB3A gene expression. Our study also provides a novel framework for investigating the effects of electrical stimulation on neuronal responses and network formation and repair after traumatic brain injury.
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http://dx.doi.org/10.1038/s41598-018-29069-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053382PMC
July 2018

Thalamic Spindles Promote Memory Formation during Sleep through Triple Phase-Locking of Cortical, Thalamic, and Hippocampal Rhythms.

Neuron 2017 Jul 6;95(2):424-435.e6. Epub 2017 Jul 6.

Center for Cognition and Sociality, Institute for Basic Science, Yuseong-gu, 34141 Daejeon, Republic of Korea; IBS school, University of Science and Technology, 34113 Daejeon, Republic of Korea. Electronic address:

While the interaction of the cardinal rhythms of non-rapid-eye-movement (NREM) sleep-the thalamo-cortical spindles, hippocampal ripples, and the cortical slow oscillations-is thought to be critical for memory consolidation during sleep, the role spindles play in this interaction is elusive. Combining optogenetics with a closed-loop stimulation approach in mice, we show here that only thalamic spindles induced in-phase with cortical slow oscillation up-states, but not out-of-phase-induced spindles, improve consolidation of hippocampus-dependent memory during sleep. Whereas optogenetically stimulated spindles were as efficient as spontaneous spindles in nesting hippocampal ripples within their excitable troughs, stimulation in-phase with the slow oscillation up-state increased spindle co-occurrence and frontal spindle-ripple co-occurrence, eventually resulting in increased triple coupling of slow oscillation-spindle-ripple events. In-phase optogenetic suppression of thalamic spindles impaired hippocampus-dependent memory. Our results suggest a causal role for thalamic sleep spindles in hippocampus-dependent memory consolidation, conveyed through triple coupling of slow oscillations, spindles, and ripples.
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http://dx.doi.org/10.1016/j.neuron.2017.06.025DOI Listing
July 2017

Arousal Rules: An Empirical Investigation into the Aesthetic Experience of Cross-Modal Perception with Emotional Visual Music.

Front Psychol 2017 4;8:440. Epub 2017 Apr 4.

Communicative Interaction Lab, Graduate School of Culture Technology, Korea Advanced Institute of Science and TechnologyDaejeon, South Korea.

Emotional visual music is a promising tool for the study of aesthetic perception in human psychology; however, the production of such stimuli and the mechanisms of auditory-visual emotion perception remain poorly understood. In Experiment 1, we suggested a literature-based, directive approach to emotional visual music design, and inspected the emotional meanings thereof using the self-rated psychometric and electroencephalographic (EEG) responses of the viewers. A two-dimensional (2D) approach to the assessment of emotion (the valence-arousal plane) with frontal alpha power asymmetry EEG (as a proposed index of valence) validated our visual music as an emotional stimulus. In Experiment 2, we used our synthetic stimuli to investigate possible underlying mechanisms of affective evaluation mechanisms in relation to audio and visual integration conditions between modalities (namely congruent, complementation, or incongruent combinations). In this experiment, we found that, when arousal information between auditory and visual modalities was contradictory [for example, active (+) on the audio channel but passive (-) on the video channel], the perceived emotion of cross-modal perception (visual music) followed the channel conveying the stronger arousal. Moreover, we found that an (heightened and compacted in subjects' emotional responses) in the aesthetic perception of visual music might occur when the two channels contained contradictory arousal information and positive congruency in valence and texture/control. To the best of our knowledge, this work is the first to propose a literature-based directive production of emotional visual music prototypes and the validations thereof for the study of cross-modally evoked aesthetic experiences in human subjects.
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http://dx.doi.org/10.3389/fpsyg.2017.00440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379063PMC
April 2017

Dynamical nonstationarity of resting EEGs in patients with attention-deficit/hyperactivity disorder (AD/HD).

IEEE Trans Biomed Eng 2013 Jan 31;60(1):159-63. Epub 2012 Aug 31.

Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.

This study applied dynamical nonstationarity analysis (DNA) to the resting EEGs of patients with attention-deficit/hyperactivity disorder (AD/HD). We aimed to assess and characterize AD/HD using features based on the local and global duration of dynamical microstate. We hypothesized that AD/HD patients would have difficulties in maintaining stable cognitive states (e.g., attention deficit and impulsivity) and that they would thus exhibit EEGs with temporal dynamics distinct from normal controls, i.e., rapidly and frequently changing dynamics. To test this hypothesis, we recorded EEGs from 12 adolescent subjects with AD/HD and 11 age-matched healthy subjects in the resting state with eyes closed and eyes open. We found that AD/HD patients exhibited significantly faster changes in dynamics than controls in the right temporal region during the eyes closed condition, but slower changes in dynamics in the frontal region during the eyes open condition. AD/HD patients exhibited a disruption in the rate of change of dynamics in the frontotemporal region at rest, probably due to executive and attention processes. We suggest that the DNA using complementary local and global features based on the duration of dynamical microstates could be a useful tool for the clinical diagnosis of subjects with AD/HD.
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http://dx.doi.org/10.1109/TBME.2012.2213598DOI Listing
January 2013

Multiway array decomposition analysis of EEGs in Alzheimer's disease.

J Neurosci Methods 2012 May 28;207(1):41-50. Epub 2012 Mar 28.

Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology-KAIST, Daejeon 305-701, Republic of Korea.

Methods for the extraction of features from physiological datasets are growing needs as clinical investigations of Alzheimer's disease (AD) in large and heterogeneous population increase. General tools allowing diagnostic regardless of recording sites, such as different hospitals, are essential and if combined to inexpensive non-invasive methods could critically improve mass screening of subjects with AD. In this study, we applied two state of the art multiway array decomposition (MAD) methods to extract unique features from electroencephalograms (EEGs) of AD patients obtained from multiple sites. In comparison to MAD, spectral-spatial average filter (SSFs) of control and AD subjects were used as well as a common blind source separation method, algorithm for multiple unknown signal extraction (AMUSE), and singular value decomposition (SVD) coupled to tensor unfolding. We trained a feed-forward multilayer perceptron (MLP) to validate and optimize AD classification from two independent databases. Using a third EEG dataset, we demonstrated that features extracted from MAD outperformed features obtained from SSFs AMUSE in terms of root mean squared error (RMSE) and reaching up to 100% of accuracy in test condition. We propose that MAD maybe a useful tool to extract features for AD diagnosis offering great generalization across multi-site databases and opening doors to the discovery of new characterization of the disease.
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http://dx.doi.org/10.1016/j.jneumeth.2012.03.005DOI Listing
May 2012

Hemispheric asymmetry in non-linear interdependence of EEG in post-traumatic stress disorder.

Psychiatry Clin Neurosci 2012 Mar;66(2):87-96

Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.

Aim: While volumetric and metabolic imaging on post-traumatic stress disorder (PTSD) patients has been intensively performed, few studies using electroencephalograms (EEG) have been done as yet. The aim of the present study was to investigate abnormalities in functional connectivity of cortical networks in PTSD.

Methods: Non-linear interdependence (NI), a measure of bidirectional, non-linear information transmission between two time series, was used. Resting EEG were recorded for 18 PTSD patients and 18 sex-matched healthy subjects on 16 channels with their eyes closed.

Results: The NI patterns in PTSD patients were hemisphere asymmetric: an increase in NI in the fronto-parieto-temporal regions of the left hemisphere (F7, F3, T3, C3, T5 and P3) and a decrease in the fronto-parieto-occipital regions of the right hemisphere (F4, C4, P4 and O2). The non-linearity of NI in EEG, estimated from the surrogate data method, exhibited an increase in the PTSD patients as compared with that of healthy subjects, particularly in the left hemispheric cortex.

Conclusion: Abnormal functional connectivity in PTSD can be assessed using NI, a measure of multi-channel EEG.
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http://dx.doi.org/10.1111/j.1440-1819.2011.02300.xDOI Listing
March 2012

Quantification of brain macrostates using dynamical nonstationarity of physiological time series.

IEEE Trans Biomed Eng 2011 Apr 30;58(4):1084-93. Epub 2009 Oct 30.

Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.

The brain shows complex, nonstationarity temporal dynamics, with abrupt micro- and macrostate transitions during its information processing. Detecting and characterizing these transitions in dynamical states of the brain is a critical issue in the field of neuroscience and psychiatry. In the current study, a novel method is proposed to quantify brain macrostates (e.g., sleep stages or cognitive states) from shifts of dynamical microstates or dynamical nonstationarity. A ``dynamical microstate'' is a temporal unit of the information processing in the brain with fixed dynamical parameters and specific spatial distribution. In this proposed approach, a phase-space-based dynamical dissimilarity map (DDM) is used to detect transitions between dynamically stationary microstates in the time series, and Tsallis time-dependent entropy is applied to quantify dynamical patterns of transitions in the DDM. We demonstrate that the DDM successfully detects transitions between microstates of different temporal dynamics in the simulated physiological time series against high levels of noise. Based on the assumption of nonlinear, deterministic brain dynamics, we also demonstrate that dynamical nonstationarity analysis is useful to quantify brain macrostates (sleep stages I, II, III, IV, and rapid eye movement (REM) sleep) from sleep EEGs with an overall accuracy of 77%. We suggest that dynamical nonstationarity is a useful tool to quantify macroscopic mental states (statistical integration) of the brain using dynamical transitions at the microscopic scale in physiological data.
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http://dx.doi.org/10.1109/TBME.2009.2034840DOI Listing
April 2011
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