References of "Bahri, Mohamed Ali"
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See detailNeuro-functional correlates of the protective effects of exercise against cocaine sensitization and dopamine D2 receptors density: a [18F]Fallypride microPET study.
Becker, Guillaume ULiege; Lespine, Louis-Ferdinand ULiege; Serrano Navacerrada, Maria Elisa ULiege et al

in Molecular Imaging and Biology (in press)

Preclinical studies suggest that free access to a running wheel can attenuate behavioural effects of addictive drugs such as psychomotor sensitization to cocaine in rodents. This phenomenon has an ... [more ▼]

Preclinical studies suggest that free access to a running wheel can attenuate behavioural effects of addictive drugs such as psychomotor sensitization to cocaine in rodents. This phenomenon has an integral role in the process of drug addiction in craving and relapse (Steketee and Kalivas, 2011). Free wheel-running was recently shown to be efficacious at preventing the initiation or the long-term expression of psychomotor sensitization to cocaine in mice or rats (Diaz et al., 2013; Geuzaine and Tirelli, 2014). In the present study, we investigated the neuro-functional correlates of the protection against psychomotor sensitization to cocaine afforded by free wheel-running on dopaminergic neurotransmission, using microPET imaging with [18F]Fallypride, a Dopamine 2 receptor (D2R) antagonist. Sixty-four 28-day-old female C57BL/6J mice were randomly assigned to one of the two housing conditions, defined by the presence or the absence of a running wheel in the cage over a 6-week pre-testing period. Since mice from the two types of housing received either saline (controls) or cocaine (8 mg/kg, i.p.) during testing (9 once-daily sessions to establish sensitization plus 1 single session to test its expression), a basic 2x2 randomized blocks design was generated (2-way ANOVA and planned comparisons; n=10). Experimentation lasted 85 days, with a 42-day period of pre-testing and a 3-week interval preceding the test for long-term expression of sensitization (LTES). All mice underwent a microPET (Focus 120, Siemens) the day after the LTES. The microPET protocol consisted of a 60 min. dynamic acquisition after the injection of 10 MBq of [18F]Fallypride in the tail vein. Wheel-running strongly and significantly attenuated LTES (interaction) to cocaine (Cohen’s d=1.63; t(21)=3.75, p<.001) and cocaine-treated mice exhibited a clear-cut and significant increase (main effect) of the [18F]Fallypride BP (d=0.88, t(31)=2.45, p =.02). Wheel-running induced an overall moderate-sized decrease (main effect) of the [18F]Fallypride BP, but without achieving statistical significance (d=0.64, t(31)=1.79, p =.08). These findings suggest that LTES is associated with an increase of the [18F]Fallypride BP in the mouse striatum, probably reflecting an increase in postsynaptic D2R density in this region. Also, the protecting effect of free running on psychomotor sensitization goes together with a decrease in D2R density in the striatum of exercised mice. We intend to complement the present study with an identical experiment to reach a total number of 80 mice (n=20). This will confer to our study a sufficient power (80%) for the main effect of wheel-running exercise on [18F]Fallypride BP to be detected at an alpha-level of 5%. Finally, autoradiography studies, performed on the same mice with [18F]Fallypride, will strengthen our in vivo results. [less ▲]

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See detailEvaluating the In Vivo Specificity of [18F]UCB-H for the SV2A Protein, Compared with SV2B and SV2C in Rats Using microPET.
Serrano Navacerrada, Maria Elisa ULiege; Becker, Guillaume ULiege; Bahri, Mohamed Ali ULiege et al

in Molecules (2019), 24(9), 1705

The synaptic vesicle protein 2 (SV2) is involved in synaptic vesicle trafficking. The SV2A isoform is the most studied and its implication in epilepsy therapy led to the development of the first SV2A PET ... [more ▼]

The synaptic vesicle protein 2 (SV2) is involved in synaptic vesicle trafficking. The SV2A isoform is the most studied and its implication in epilepsy therapy led to the development of the first SV2A PET radiotracer [18F]UCB-H. The objective of this study was to evaluate in vivo, using microPET in rats, the specificity of [18F]UCB-H for SV2 isoform A in comparison with the other two isoforms (B and C) through a blocking assay. Twenty Sprague Dawley rats were pre-treated either with the vehicle, or with specific competitors against SV2A (levetiracetam), SV2B (UCB5203) and SV2C (UCB0949). The distribution volume (Vt, Logan plot, t* 15 min) was obtained with a population-based input function. The Vt analysis for the entire brain showed statistically significant differences between the levetiracetam group and the other groups (p < 0.001), but also between the vehicle and the SV2B group (p < 0.05). An in-depth Vt analysis conducted for eight relevant brain structures confirmed the statistically significant differences between the levetiracetam group and the other groups (p < 0.001) and highlighted the superior and the inferior colliculi along with the cortex as regions also displaying statistically significant differences between the vehicle and SV2B groups (p < 0.05). These results emphasize the in vivo specificity of [18F]UCB-H for SV2A against SV2B and SV2C, confirming that [18F]UCB-H is a suitable radiotracer for in vivo imaging of the SV2A proteins with PET. [less ▲]

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See detailTumor modifications recorded with IVIM and DCE-MRI after Neoadjuvant radiotherapy.
LALLEMAND, François ULiege; LEROI, Natacha ULiege; Bahri, Mohamed Ali ULiege et al

in Radiotherapy and Oncology (2019, April), 133(Supplement 1), 284-285

Purpose or Objective Neoadjuvant radiotherapy (NeoRT) improves tumor local control and facilitates tumor resection in many cancers. We hypothesized anti-cancer treatments (i.e. radiotherapy) modify tumor ... [more ▼]

Purpose or Objective Neoadjuvant radiotherapy (NeoRT) improves tumor local control and facilitates tumor resection in many cancers. We hypothesized anti-cancer treatments (i.e. radiotherapy) modify tumor microenvironment and could potentially impact distant metastases occurrence. Previously, we developed a pre-clinical model demonstrating an impact of NeoRT schedule and the timing of surgery on metastatic spreading (Leroi et al. Oncotarget 2015). Here, we aim to identify by fMRI noninvasive markers reflecting NeoRT related tumor microenvironment modifications that could predict the best timing for performing surgery and avoiding tumor spreading. Material and Methods To briefly delineate the NeoRT model, MDA-MB 231 tumor cells implanted in the flank of SCID mice were locally irradiated with 2x5Gy when tumor reached 100mm3 and then surgically removed at different time points. We performed fMRI, Diffusion Weighted (DW) and Dynamic Contract enhancement (DCE) – MRI, before RT and every 2 days between RT and surgery. We acquired 8 slices of 1 mm thickness and 0.5 mm gap with an “in plane voxel resolution” of 0.5 mm. For DW-MRI, we performed FSEMS (Fast Spin Echo MultiSlice) sequences, with 9 different Bvalue (from 40 to 1000) and B0. We performed IVIM (IntraVoxel Incoherent Motion) analysis to obtain information on intravascular diffusion, related to perfusion (F: perfusion factor) and subsequently tumor vessels perfusion. For DCE-MRI, we performed a T1 mapping with multiple TR and DCE acquisition with 200 repetitions of 3 sec each and gadolinium IV injection after 10 repetitions. We performed semi-quantitative analysis. We validated tumor perfusion by immunochemistry with injection of FITC-dextran IV 3 min before surgery and CD31 labelling. Human Ki67 was used for lung metastases labelling and quantification. Results After the tumor irradiation, we observed a significant and transient increase at day 6 (60% of the basal value (n=6, p<0,05)) of F and D* parameters related to perfusion. The other parameters of the DW-MRI, ADC and D presented no modifications. The sham irradiated tumors used as control showed no modifications of all fMRI parameters. At the same timing, 6 days post-radiotherapy, DCE-MRI significantly demonstrated a WhashinSlope (n=13, p<0,05) increase. Immunochemistry confirmed the increase of tumor perfusion when surgery is performed at day 6. The sham irradiated tumors never demonstrated such changes. Finally, when surgery is performed on tumor increased perfusion measured by fMRI, it demonstrated a burst of lung metastasis compared to the other timings. Conclusion We showed a significant difference in perfusion-related parameters with fMRI and immunochemistry at a specific time point after NeoRT. These modifications are correlated with an increase of metastasis spreading related to surgery procedure. These results open new perspectives in the personalized medicine and MRI guided surgery timing after NeoRT. [less ▲]

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See detailIs auditory localization a sign of consciousness? Evidence from neuroimaging and electrophysiology
Carrière, Manon ULiege; Cassol, Helena ULiege; Aubinet, Charlène ULiege et al

Conference (2019, March 16)

Background Auditory localization is often part of the clinical evaluation of patients recovering from coma. There is however no clear consensus whether it should be considered as a reflex or as a ... [more ▼]

Background Auditory localization is often part of the clinical evaluation of patients recovering from coma. There is however no clear consensus whether it should be considered as a reflex or as a conscious behavior. For example, auditory localisation corresponds to the diagnosis of unresponsive wakefulness syndrome (UWS) in the Coma Recovery Scale-Revised, while it is considered a sign of consciousness in other post-coma scales. This study aims to determine if auditory localization reflects conscious processing in patients with disorders of consciousness. Methods We first evaluated the proportion of patients with and without auditory localisation in 186 patients with severe brain injury, including 64 UWS, 28 minimally conscious minus (MCS-), 71 minimally conscious plus (MCS+), i.e., language relatively preserved) and 23 who emerged from MCS (EMCS). We then measured brain metabolism using fluorine-18 fluorodeoxyglucose positron emission tomography, functional connectivity using magnetic resonance imaging (MRI) and high-density electroencephalography (EEG) in patients in UWS with and without auditory localization. Findings Auditory localization was observed in 12% of patients in UWS, 46% of patients in MCS-, 62% of patients in MCS+ and 78% of patients in EMCS. Brain metabolism of patients in UWS without auditory localization was mostly restricted to primary areas, whereas a more widespread activity, including associative areas, was observed in patients in UWS with auditory localisation. Brain functional connectivity was also higher in patients in UWS with auditory localisation in the frontoparietal fMRI resting state network, along with higher EEG connectivity in alpha frequency band, compared to patients without auditory localization. Finally, differences were also found regarding the outcome, as the survival rate at two years appeared to be significantly higher in UWS patients with auditory localization as compared to those without auditory localization. Interpretation. Both clinical data in post-comatose patients and neuroimaging examinations in UWS patients with and without auditory localization support the idea that auditory localization should be considered as a sign of consciousness. [less ▲]

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See detailQuantification of [18F]UCB-H Binding in the Rat Brain: From Kinetic Modelling to Standardised Uptake Value
Serrano Navacerrada, Maria Elisa ULiege; Bahri, Mohamed Ali ULiege; Becker, Guillaume ULiege et al

in Molecular Imaging and Biology (2018)

Purpose: [18F]UCB-H is a specific positron emission tomography (PET) biomarker for the Synaptic Vesicle protein 2A (SV2A), the binding site of the antiepileptic drug levetiracetam. With a view to ... [more ▼]

Purpose: [18F]UCB-H is a specific positron emission tomography (PET) biomarker for the Synaptic Vesicle protein 2A (SV2A), the binding site of the antiepileptic drug levetiracetam. With a view to optimising acquisition time and simplifying data analysis with this radiotracer, we compared two parameters: the distribution volume (Vt) obtained from Logan graphical analysis using a Population-Based Input Function, and the Standardised Uptake Value (SUV). Procedures: Twelve Sprague Dawley male rats, pre-treated with three different doses of levetiracetam were employed to develop the methodology. Three additional kainic acid (KA) treated rats (temporal lobe epilepsy model) were also used to test the procedure. Image analyses focused on: (i) length of the dynamic acquisition (90 versus 60 min); (ii) correlations between Vt and SUV over 20-min consecutive time-frames; (iii) and (iv) evaluation of differences between groups using the Vt and the SUV; and (v) preliminary evaluation of the methodology in the KA epilepsy model. Results: A large correlation between the Vt issued from 60 to 90-min acquisitions was observed. Further analyses highlighted a large correlation (r 9 0.8) between the Vt and the SUV. Equivalent differences between groups were detected for both parameters, especially in the 20–40 and 40– 60-min time-frames. The same results were also obtained with the epilepsy model. Conclusions: Our results enable the acquisition setting to be changed from a 90-min dynamic to a 20-min static PET acquisition. According to a better image quality, the 20–40-min time-frame appears optimal. Due to its equivalence to the Vt, the SUV parameter can be considered in order to quantify [18F]UCB-H uptake in the rat brain. This work, therefore, establishes a starting point for the simplification of SV2A in vivo quantification with [18F]UCB-H, and represents a step forward to the clinical application of this PET radiotracer. [less ▲]

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See detailSleep fragmentation is associated with brain tau but not amyloid-β burden in healthy older adults
Chylinski, Daphné ULiege; Rudzik, Franziska; Coppieters't Wallant, Dorothe ULiege et al

Conference (2018, November 09)

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See detailArousals during sleep are associated with brain tau burden in healthy older individuals
Chylinski, Daphné ULiege; Rudzik, Franziska; Coppieters't Wallant, Dorothe ULiege et al

Poster (2018, October 19)

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See detailTHE SV2A PROTEIN: IMAGING SYNAPTIC DENSITY DURING THE PROGRESSION OF THE TEMPORAL LOBE EPILEPSY IN THE KASE RAT MODEL
Serrano Navacerrada, Maria Elisa ULiege; Bahri, Mohamed Ali ULiege; Becker, Guillaume ULiege et al

Poster (2018, October 18)

Introduction The temporal lobe epilepsy (TLE) is the most common epileptic disorder. New antiepileptic drugs target the Synaptic Vesicle protein 2A (SV2A) (1). Nevertheless, the prevailing literature ... [more ▼]

Introduction The temporal lobe epilepsy (TLE) is the most common epileptic disorder. New antiepileptic drugs target the Synaptic Vesicle protein 2A (SV2A) (1). Nevertheless, the prevailing literature addressing the relation between this protein and the epilepsy is limited (2, 3). This study provides insights on the role of the SV2A protein during the four stages of TLE (4, 5), throughout its in vivo study with the [18F]UCB-H radiotracer (6). Methods Twenty-four male Sprague-Dawley were subjected to multiple injections (7) of i) Saline (Sham), or ii) 5mg/kg of Kainic Acid (KA). The rats not reacting to KA (NKA) were also scanned. In each TLE stages, a [18F]UCB-H dynamic scan was performed, followed by a T2-structural MRI. EEG recordings were performed to determine the number of crises. Data processing was done with PMOD 3.6. Results were expressed as SUV and statistically analyzed with the SPSS and the SPM. Results During the acute phase, statistically significant differences were found between Sham and KA in striatum, cerebellum, and medulla. In the latent phase, these SUV differences were detected between the NKA and KA in the same regions along with hippocampus and thalamus. When the spontaneous crises started, these group differences became statistically significant in all the regions but the cortex. During the chronic phase, all the regions showed statistically significant differences between groups. Furthermore, the voxel-wise analysis highlighted statistically significant differences in voxels at the level of amygdala and hippocampus. Conclusions These results show that [18F]UCB-H is able to detect early modifications in SV2A expression (3 days after the TLE model creation), in particular in regions implicated in the epileptic process. This radiotracer can potentially be used as a suitable biomarker for the early detection of the epileptic disease, being able to distinguish between stages in this neurodegenerative disease. [less ▲]

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See detailSound production and sonic apparatus in deep-living cusk-eels (Genypterus chilensis and Genypterus maculatus)
Parmentier, Eric ULiege; Bahri, Mohamed Ali ULiege; Plenevaux, Alain ULiege et al

in Deep-Sea Research. Part I, Oceanographic Research Papers (2018)

Cusk-eels (Ophidiidae) are known sound producers, but many species live in deep water where sounds are difficult to record. For these species sonic ability has been inferred from inner anatomy. Genypterus ... [more ▼]

Cusk-eels (Ophidiidae) are known sound producers, but many species live in deep water where sounds are difficult to record. For these species sonic ability has been inferred from inner anatomy. Genypterus (subfamily Ophidiinae) are demersal fishes inhabiting the continental shelf and slope at depths between 50 and 800 m. Males and females G. maculatus have been maintained together in a tank and 9 unsexed specimens of G. chilensis in a second tank, providing a valuable opportunity to record the sounds of living species usually found at great depths. Genypterus chilensis and G. maculatus respectively produced one and two sound types mainly between 7 and 10 pm. Sound 1 in Genypterus maculatus consists of trains of pulses that vary in amplitude and pulse period; call 2 sounded like a growl that results from the rapid emission of pulses that define sound 1. Genypterus chilensis produced a growl having an unusual feature since the first peak of the second pulse has always greater amplitude than all other peaks. These sounds are probably related to courtship behavior since floating eggs are found after night calls. The anatomical structures of the sound-producing organ in both species present an important panel of highly derived characters including three pairs of sonic muscles, a neural arch that pivots on the first vertebral body and a thick swimbladder with unusual features. Sonic structures are similar between species and between sexes. Therefore both biological sexes are capable of sound production although precedent from shallow ophidiids and sonic fishes in general suggests that males are more likely to produce courtship calls. This study reports two main types of information. It demonstrates that two deep-living species are capable of sound production, which is a pioneer step in the acoustic study of deep-sea fauna. Recorded sounds should also help to locate fish in open sea. As these species are currently used to diversify the aquaculture industry in Chile, deeper studies on their acoustic behavior should also help to target spawning period and to identify mature specimens. [less ▲]

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See detailA Heartbeat Away From Consciousness: Heart Rate Variability Entropy can discriminate disorders of consciousness and is correlated with resting-state fMRI brain connectivity of the Central Autonomic Network
Riganello, Francesco ULiege; Larroque, Stephen Karl ULiege; Bahri, Mohamed Ali ULiege et al

Poster (2018, October)

Motivation: Heart rate variability (HRV) reflects the heart-brain two-way dynamic interactions[1-5]. HRV entropy analysis quantifies the unpredictability and complexity of the heart rate beats intervals ... [more ▼]

Motivation: Heart rate variability (HRV) reflects the heart-brain two-way dynamic interactions[1-5]. HRV entropy analysis quantifies the unpredictability and complexity of the heart rate beats intervals and over multiple time scales using multiscale entropy (MSE)[6-8]. The complexity index (CI) provides a score of a system’s complexity by aggregating the MSE measures over a range of time scales[8]. Most HRV entropy studies have focused on acute traumatic patients using task-based designs[9]. We here investigate the CI and its discriminative power in chronic patients with unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) at rest, and its relation to brain functional connectivity. Methods: We investigated the CI in short (CIs) and long (CIl) time scales in 16 UWS and 17 MCS sedated. CI for MCS and UWS groups were compared using a Mann-Whitney exact test. Spearman’s correlation tests were conducted between the Coma Recovery Scale-revised (CRS-R) and both CI. Discriminative power of both CI was assessed with One-R machine learning model. Correlation between CI and brain connectivity (detected with functional magnetic resonance imagery using seed-based and hypothesis-free intrinsic connectivity) was investigated using a linear regression in a subgroup of 12 UWS and 12 MCS patients with sufficient image quality. Results and Discussion: Significant differences were found between MCS and UWS for CIs and CIl (0.0001≤p≤0.006). Significant correlations were found between CRS-R and CIs and CIl (0.0001≤p≤0.026). The One-R classifier selected CIl as the best discriminator between UWS and MCS with 85% accuracy, 19% false positive rate and 12% false negative rate after a 10-fold cross-validation test. Positive correlations were observed between CI and brain areas belonging to the autonomic system. CI was found to be significantly higher in MCS compared to UWS patients, with high discriminative power and lower false negative rate than the reported misdiagnosis rate of human assessors, providing an easy, inexpensive and non-invasive diagnosis tool. CI is correlated to functional connectivity changes in brain regions belonging to the autonomic nervous system, suggesting that CI can provide an indirect way to screen and monitor connectivity changes in this neural system. Future studies should investigate further the extent of CI’s predictive power for other pathologies in the disorders of consciousness spectrum. [less ▲]

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See detailEPILEPSY AND THE SV2A PROTEIN: new insights about the disease.
Serrano Navacerrada, Maria Elisa ULiege; Raedt, Robrecht; Becker, Guillaume ULiege et al

Conference (2018, September 13)

Around two million of people worldwide are affected by neurodegenerative diseases, such as Alzheimer, Parkinson or Epilepsy. Despite the social and the economic impact of these diseases, their causes ... [more ▼]

Around two million of people worldwide are affected by neurodegenerative diseases, such as Alzheimer, Parkinson or Epilepsy. Despite the social and the economic impact of these diseases, their causes still remain unclear. In the case of the epilepsy, for example, around 25% of the patients suffer drug-resistant epilepsy, for which there is no medicament able to mitigate the epileptic crises or the associated symptomatology, such as cognitive problems and mood disorders. In 1974, UCB Pharma synthetized a new antiepileptic drug with a high therapeutic index: the Levetiracetam. The target of this medicament is the Synaptic Vesicle Protein 2A (SV2A) whose specific role in the pathology is still unknown. The main goal of my thesis is to better understand the relationship between this protein and the epilepsy. On the one hand, the production and phenotyping of conditional knockout mice for the SV2A protein allowed us to discover a possible implication of this protein in the spatial memory and anxiety process, an important part of the epileptic symptomatology. On the other hand, the synthesis of the radiotracer [18F]UCB-H, with a high affinity for the SV2A protein, enabled the in vivo evaluation (with the mPET technique) of a rat model of the temporal lobe epilepsy through the disease process. Results showed a strong correlation between the severity of the epilepsy (EEG technique) and the SV2A levels in different brain regions, highlighting the importance of this protein in the development of the disease. In summary, although further studies in humans are necessary, this protein emerges as an important key in clinical diagnosis and medical research, being implicated in all the aspects of the epileptic disease. [less ▲]

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See detailEPILEPSY AND THE SV2A PROTEIN: new insights about the disease.
Serrano Navacerrada, Maria Elisa ULiege; Raedt, Robrecht; Becker, Guillaume ULiege et al

Conference (2018, September 13)

Around two million of people worldwide are affected by neurodegenerative diseases, such as Alzheimer, Parkinson or Epilepsy. Despite the social and the economic impact of these diseases, their causes ... [more ▼]

Around two million of people worldwide are affected by neurodegenerative diseases, such as Alzheimer, Parkinson or Epilepsy. Despite the social and the economic impact of these diseases, their causes still remain unclear. In the case of the epilepsy, for example, around 25% of the patients suffer drug-resistant epilepsy, for which there is no medicament able to mitigate the epileptic crises or the associated symptomatology, such as cognitive problems and mood disorders. In 1974, UCB Pharma synthetized a new antiepileptic drug with a high therapeutic index: the Levetiracetam. The target of this medicament is the Synaptic Vesicle Protein 2A (SV2A) whose specific role in the pathology is still unknown. The main goal of my thesis is to better understand the relationship between this protein and the epilepsy. On the one hand, the production and phenotyping of conditional knockout mice for the SV2A protein allowed us to discover a possible implication of this protein in the spatial memory and anxiety process, an important part of the epileptic symptomatology. On the other hand, the synthesis of the radiotracer [18F]UCB-H, with a high affinity for the SV2A protein, enabled the in vivo evaluation (with the mPET technique) of a rat model of the temporal lobe epilepsy through the disease process. Results showed a strong correlation between the severity of the epilepsy (EEG technique) and the SV2A levels in different brain regions, highlighting the importance of this protein in the development of the disease. In summary, although further studies in humans are necessary, this protein emerges as an important key in clinical diagnosis and medical research, being implicated in all the aspects of the epileptic disease. [less ▲]

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See detailA Heartbeat Away From Consciousness: Heart Rate Variability Entropy Can Discriminate Disorders of Consciousness and Is Correlated With Resting-State fMRI Brain Connectivity of the Central Autonomic Network
Riganello, Francesco ULiege; Larroque, Stephen Karl ULiege; Bahri, Mohamed Ali ULiege et al

in Frontiers in Neurology (2018), 9

Background: Disorders of consciousness are challenging to diagnose, with inconsistent behavioral responses, motor and cognitive disabilities, leading to approximately 40% misdiagnoses. Heart rate ... [more ▼]

Background: Disorders of consciousness are challenging to diagnose, with inconsistent behavioral responses, motor and cognitive disabilities, leading to approximately 40% misdiagnoses. Heart rate variability (HRV) reflects the complexity of the heart-brain two-way dynamic interactions. HRV entropy analysis quantifies the unpredictability and complexity of the heart rate beats intervals. We here investigate the complexity index (CI), a score of HRV complexity by aggregating the non-linear multi-scale entropies over a range of time scales, and its discriminative power in chronic patients with unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), and its relation to brain functional connectivity. Methods: We investigated the CI in short (CIs) and long (CIl) time scales in 14 UWS and 16 MCS sedated. CI for MCS and UWS groups were compared using a Mann-Whitney exact test. Spearman's correlation tests were conducted between the Coma Recovery Scale-revised (CRS-R) and both CI. Discriminative power of both CI was assessed with One-R machine learning model. Correlation between CI and brain connectivity (detected with functional magnetic resonance imagery using seed-based and hypothesis-free intrinsic connectivity) was investigated using a linear regression in a subgroup of 10 UWS and 11 MCS patients with sufficient image quality. Results: Higher CIs and CIl values were observed in MCS compared to UWS. Positive correlations were found between CRS-R and both CI. The One-R classifier selected CIl as the best discriminator between UWS and MCS with 90% accuracy, 7% false positive and 13% false negative rates after a 10-fold cross-validation test. Positive correlations were observed between both CI and the recovery of functional connectivity of brain areas belonging to the central autonomic networks (CAN). Conclusion: CI of MCS compared to UWS patients has high discriminative power and low false negative rate at one third of the estimated human assessors' misdiagnosis, providing an easy, inexpensive and non-invasive diagnostic tool. CI reflects functional connectivity changes in the CAN, suggesting that CI can provide an indirect way to screen and monitor connectivity changes in this neural system. Future studies should assess the extent of CI's predictive power in a larger cohort of patients and prognostic power in acute patients. [less ▲]

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