GABAergic inhibition shapes behavior and neural dynamics in human visual working memory.

Neuronal inhibition, primarily mediated by GABAergic neurotransmission, is crucial for brain development and healthy cognition. Gamma-aminobutyric acid concentration levels in sensory areas have been shown to correlate with hemodynamic and oscillatory neuronal responses. How these measures relate to one another during working memory, a higher-order cognitive process, is still poorly understood. We address this gap by collecting magnetoencephalography, functional magnetic resonance imaging, and Flumazenil positron emission tomography data within the same subject cohort using an n-back working-memory paradigm. By probing the relationship between GABAA receptor distribution, neural oscillations, and Blood Oxygen Level Dependent (BOLD) modulations, we found that GABAA receptor density in higher-order cortical areas predicted the reaction times on the working-memory task and correlated positively with the peak frequency of gamma power modulations and negatively with BOLD amplitude. These findings support and extend theories linking gamma oscillations and hemodynamic responses to gamma-aminobutyric acid neurotransmission and to the excitation-inhibition balance and cognitive performance in humans. Considering the small sample size of the study, future studies should test whether these findings also hold for other, larger cohorts as well as to examine in detail how the GABAergic system and neural fluctuations jointly support working-memory task performance.

Influence of the human body odor compound HMHA on face perception.

Body odors convey information about the individuals, but the mechanisms are not fully understood yet. As far as human reproduction is concerned, molecules that are produced in sexually dimorphic amounts could be possible chemosignals. 3-hydroxy-3-methylhexanoic acid (HMHA) is one of them-more typical of men. Here, we investigated the possibility that the perception of gender and attractiveness in human faces could be implicitly influenced by this compound. Clearly feminine, ambiguous and clearly masculine faces were primed with an odor of HMHA, a control odor or air. Based on 100-ms face presentation, 40 raters had to identify the face's gender as quickly as possible and provide attractiveness evaluations. 3-hydroxy-3-methylhexanoic acid tended to be perceived as less pleasant and induced lower sniff duration in women compared with men. As to the effects of HMHA on face perception (vs. control conditions), we found that gender identification and the associated response time were unaffected by HMHA. Attractiveness of the faces, however, increased in presence of HMHA, but not in a sex-specific manner and only for unattractive faces with ambiguous gender. In sum, this study found no evidence in favor of a possible role of this sexually dimorphic compound in intrasexual competition nor in intersexual attraction.

When do we become more distractible? Progressive evolution of different components of distractibility from early to late adulthood.

Distractibility determines the propensity to have one's attention captured by irrelevant information; it relies on a balance between voluntary and involuntary attention. We report a cross-sectional study that uses the competitive attention test to characterize patterns of attention across the adult life span from 21 to 86 years old. Several distractibility components were measured in 186 participants distributed within seven age groups. Results indicate that distractibility components follow distinct trajectories with aging: Voluntary orienting remains stable from 21 to 86 years old, sustained attention decreases after 30 years old, distraction progressively increases between 26 and 86 years old, and impulsivity is lower in older compared to younger adults. Increased distractibility in older age thus seems to result from a dominance of involuntary over voluntary attention processes, whose detrimental effect on performance is partly compensated by enhanced motor control. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Subject-Specific Activation of Central Respiratory Centers during Breath-Holding Functional Magnetic Resonance Imaging.

BACKGROUND: Voluntary breath-holding (BH) triggers responses from central neural control and respiratory centers in order to restore breathing. Such responses can be observed using functional MRI (fMRI). OBJECTIVES: We used this paradigm in healthy volunteers with the view to develop a biomarker that could be used to investigate disorders of the central control of breathing at the individual patient level. METHOD: In 21 healthy human subjects (mean age±SD, 32.8 ± 9.9 years old), fMRI was used to determine, at both the individual and group levels, the physiological neural response to expiratory and inspiratory voluntary apneas, within respiratory control centers in the brain and brainstem. RESULTS: Group analysis showed that expiratory BH, but not inspiratory BH, triggered activation of the pontine respiratory group and raphe nuclei at the group level, with a significant relationship between the levels of activation and drop in SpO2. Using predefined ROIs, expiratory BH, and to a lesser extent, inspiratory BH were associated with activation of most respiratory centers. The right ventrolateral nucleus of the thalamus, right pre-Bötzinger complex, right VRG, right nucleus ambiguus, and left Kölliker-Fuse-parabrachial complex were only activated during inspiratory BH. Individual analysis identified activations of cortical/subcortical and brainstem structures related to respiratory control in 19 out of 21 subjects. CONCLUSION: Our study shows that BH paradigm allows to reliably trigger fMRI response from brainstem and cortical areas involved in respiratory control at the individual level, suggesting that it might serve as a clinically relevant biomarker to investigate conditions associated with an altered central control of respiration.

Synapse-Specific Modulation of Synaptic Responses by Brain States in Hippocampal Pathways.

Synaptic changes play a major role in memory processes. Modulation of synaptic responses by brain states remains, however, poorly understood in hippocampal networks, even in basal conditions. We recorded evoked synaptic responses at five hippocampal pathways in freely moving male rats. We showed that, at the perforant path to dentate gyrus (PP-DG) synapse, responses increase during wakefulness compared with sleep. At the Schaffer collaterals to CA1 (SC-CA1) synapse, responses increase during non-REM sleep (NREM) compared with the other states. During REM sleep (REM), responses decreased at the PP-DG and SC-CA1 synapses compared with NREM, while they increased at the fornix to nucleus accumbens synapse (Fx-NAc) during REM compared with the other states. In contrast, responses at the fornix to medial PFC synapse (Fx-PFC) and at the fornix to amygdala synapse (Fx-Amy) were weakly modulated by vigilance states. Extended sleep periods led to synaptic changes at PP-DG and Fx-Amy synapses but not at the other synapses. Synaptic responses were also linked to local oscillations and were highly correlated between Fx-PFC and Fx-NAc but not between Fx-Amy and these synapses. These results reveal synapse-specific modulations that may contribute to memory consolidation during the sleep-wake cycle.SIGNIFICANCE STATEMENT Surprisingly, the cortical network dynamics remains poorly known at the synaptic level. We tested the hypothesis that brain states would modulate synaptic changes in the same way at different cortical connections. To tackle this issue, we implemented an approach to explore the synaptic behavior of five connections upstream and downstream the rat hippocampus. Our study reveals that synaptic responses are modulated in a highly synapse-specific manner by wakefulness and sleep states as well as by local oscillations at these connections. Moreover, we found rapid synaptic changes during wake and sleep transitions as well as synaptic down and upregulations after extended periods of sleep. These synaptic changes are likely related to the mechanisms of sleep-dependent memory consolidation.

Epileptic spasms are associated with increased stereo-electroencephalography derived functional connectivity in tuberous sclerosis complex.

OBJECTIVE: Epileptic spasms (ES) are common in tuberous sclerosis complex (TSC). However, the underlying network alterations and relationship with epileptogenic tubers are poorly understood. We examined interictal functional connectivity (FC) using stereo-electroencephalography (SEEG) in patients with TSC to investigate the relationship between tubers, epileptogenicity, and ES. METHODS: We analyzed 18 patients with TSC who underwent SEEG (mean age = 11.5 years). The dominant tuber (DT) was defined as the most epileptogenic tuber using the epileptogenicity index. Epileptogenic zone (EZ) organization was quantitatively separated into focal (isolated DT) and complex (all other patterns). Using a 20-min interictal recording, FC was estimated with nonlinear regression, h2 . We calculated (1) intrazone FC within all sampled tubers and normal-appearing cortical zones, respectively; and (2) interzone FC involving connections between DT, other tubers, and normal cortex. The relationship between FC and (1) presence of ES as a current seizure type at the time of SEEG, (2) EZ organization, and (3) epileptogenicity was analyzed using a mixed generalized linear model. Spike rate and distance between zones were considered in the model as covariates. RESULTS: Six patients had ES as a current seizure type at time of SEEG. ES patients had a greater number of tubers with a fluid-attenuated inversion recovery hypointense center (p < .001), and none had TSC1 mutations. The presence of ES was independently associated with increased FC within both intrazone (p = .033) and interzone (p = .011) networks. Post hoc analyses identified that increased FC was associated with ES across tuber and nontuber networks. EZ organization and epileptogenicity biomarkers were not associated with FC. SIGNIFICANCE: Increased cortical synchrony among both tuber and nontuber networks is characteristic of patients with ES and independent of both EZ organization and tuber epileptogenicity. This further supports the prospect of FC biomarkers aiding treatment paradigms in TSC.

Peri-ictal hypoxemia during temporal lobe seizures: A SEEG study.

Focal seizures originating from the temporal lobe are commonly associated with peri-ictal hypoxemia (PIH). During the course of temporal lobe seizures, epileptic discharges often not only spread within various parts of the temporal lobe but also possibly insula and frontal lobe. The link between spatial propagation of the seizure discharges and PIH is still unclear. The present study investigates the involvement of several brain structures including medial temporal structures, temporal pole, anterior insula, and frontal cortex in the occurrence of PIH. Using quantitative indices obtained during SEEG (stereoencephalography) recordings in 38 patients, we evaluated the epileptogenicity, the spatial propagation, and functional connectivity between those structures during seizures leading to PIH. Multivariate statistical analyses of SEEG quantitative indices showed that temporal lobe seizures leading to PIH are characterized by a strong involvement of amygdala and anterior insula during seizure propagation and a more widespread involvement of medial temporal lobe structures, lateral temporal lobe, temporal pole, and anterior cingulate at the end of the seizures. On the contrary, seizure-onset zone was not associated with PIH occurrence. During seizure propagation, anterior insula, temporal pole, and temporal lateral neocortex activities were correlated with intensity of PIH. Lastly, PIH occurrence was also related to a widespread increase of synchrony between those structures. Those results suggest that PIH occurrence during temporal lobe seizures may be related to the activation of a widespread network of cortical structures, among which amygdala and anterior insula are key nodes.

Face-hand sensorimotor interactions revealed by afferent inhibition.

Reorganization of the sensorimotor cortex following permanent (e.g., amputation) or temporary (e.g., local anaesthesia) deafferentation of the hand has revealed large-scale plastic changes between the hand and face representations that are accompanied by perceptual correlates. The physiological mechanisms underlying this reorganization remain poorly understood. The aim of this study was to investigate sensorimotor interactions between the face and hand using an afferent inhibition transcranial magnetic stimulation protocol in which the motor evoked potential elicited by the magnetic pulse is inhibited when it is preceded by an afferent stimulus. We hypothesized that if face and hand representations in the sensorimotor cortex are functionally coupled, then electrocutaneous stimulation of the face would inhibit hand muscle motor responses. In two separate experiments, we delivered an electrocutaneous stimulus to either the skin over the right upper lip (Experiment 1) or right cheek (Experiment 2) and recorded muscular activity from the right first dorsal interosseous. Both lip and cheek stimulation inhibited right first dorsal interosseous motor evoked potentials. To investigate the specificity of this effect, we conducted two additional experiments in which electrocutaneous stimulation was applied to either the right forearm (Experiment 3) or right upper arm (Experiment 4). Forearm and upper arm stimulation also significantly inhibited the right first dorsal interosseous motor evoked potentials, but this inhibition was less robust than the inhibition associated with face stimulation. These findings provide the first evidence for face-to-hand afferent inhibition.

Dynamics of hippocampus and orbitofrontal cortex activity during arousing reactions from sleep: An intracranial electroencephalographic study.

Sleep is punctuated by transient elevations of vigilance level called arousals or awakenings depending on their durations. Understanding the dynamics of brain activity modifications during these transitional phases could help to better understand the changes in cognitive functions according to vigilance states. In this study, we investigated the activity of memory-related areas (hippocampus and orbitofrontal cortex) during short (3 s to 2 min) arousing reactions detected from thalamic activity, using intracranial recordings in four drug-resistant epilepsy patients. The average power of the signal between 0.5 and 128 Hz was compared across four time windows: 10 s of preceding sleep, the first part and the end of the arousal/awakening, and 10 s of wakefulness. We observed that (a) in most frequency bands, the spectral power during hippocampal arousal/awakenings is intermediate between wakefulness and sleep whereas frontal cortex shows an early increase in low and fast activities during non-rapid-eye-movement (NREM) sleep arousals/awakenings; (b) this pattern depends on the preceding sleep stage with fewer modifications for REM than for non-REM sleep arousal/awakenings, potentially reflecting the EEG similarities between REM sleep and wakefulness; (c) a greater activation at the arousing reaction onset in the prefrontal cortex predicts longer arousals/awakenings. Our findings suggest that hippocampus and prefrontal arousals/awakenings are progressive phenomena modulated by sleep stage, and, in the neocortex, by the intensity of the early activation. This pattern of activity could underlie the link between sleep stage, arousal/awakening duration and restoration of memory abilities including dream recall.

Why Are Children So Distractible? Development of Attention and Motor Control From Childhood to Adulthood.

Distractibility is the propensity to behaviorally react to irrelevant information. Although children are more distractible the younger they are, the precise contribution of attentional and motor components to distractibility and their developmental trajectories have not been characterized yet. We used a new behavioral paradigm to identify the developmental dynamics of components contributing to distractibility in a large cohort of French participants balanced, between age groups, in gender and socioeconomic status (N = 352; age: 6-25). Results reveal that each measure of these components, namely voluntary attention, distraction, impulsivity, and motor control, present a distinct maturational timeline. In young children, increased distractibility is mostly the result of reduced sustained attention capacities and enhanced distraction, whereas in teenagers, it is the result of decreased motor control and increased impulsivity.

Relation between coffee consumption and risk of seizure-related respiratory dysfunction in patients with drug-resistant focal epilepsy.

OBJECTIVE: Caffeine is an antagonist of the adenosine pathway, which is involved in regulation of breathing. Extracellular concentrations of adenosine are increased in the immediate aftermath of a seizure. Seizure-related overstimulation of adenosine receptors might promote peri-ictal apnea. However, the relation between caffeine consumption and risk of seizure-related respiratory dysfunction in patients with drug-resistant focal epilepsy remains unknown. METHODS: We performed a cross-sectional analysis of data collected in patients included in the SAVE study in Lyon's epilepsy monitoring unit at the Adult Epilepsy Department of the Lyon University Hospital between February 2016 and October 2018. The video-electroencephalographic recordings of 156 patients with drug-resistant focal epilepsy included in the study were reviewed to identify those with ≥1 focal seizure (FS), valid pulse oximetry (SpO2 ) measurement, and information about usual coffee consumption. This latter was collected at inclusion using a standardized self-questionnaire and further classified into four groups: none, rare (≤3 cups/week), moderate (4 cups/week to 3 cups/day), and high (≥4 cups/day). Peri-ictal hypoxemia (PIH) was defined as SpO2 < 90% for at least 5 s occurring during the ictal period, the post-ictal period, or both. RESULTS: Ninety patients fulfilled inclusion criteria, and 323 seizures were analyzed. Both the level of usual coffee consumption (p = .033) and the level of antiepileptic drug withdrawal (p = .004) were independent risk factors for occurrence of PIH. In comparison with FS in patients with no coffee consumption, risk of PIH was four times lower in FS in patients with moderate consumption (odds ratio [OR] = .25, 95% confidence interval [CI] = .07-.91, p = .036) and six times lower in FS in patients with high coffee consumption (OR = .16, 95% CI = .04-.66, p = .011). However, when PIH occurred, its duration was longer in patients with moderate or high consumption than in those with no coffee consumption (p = .042). SIGNIFICANCE: Coffee consumption may be a protective factor for seizure-related respiratory dysfunction, with a dose-dependent effect.

Automatic analysis of single-channel sleep EEG in a large spectrum of sleep disorders.

STUDY OBJECTIVES: To assess the performance of the single-channel automatic sleep staging (AS) software ASEEGA in adult patients diagnosed with various sleep disorders. METHODS: Sleep recordings were included of 95 patients (38 women, 40.5 ± 13.7 years) diagnosed with insomnia (n = 23), idiopathic hypersomnia (n = 24), narcolepsy (n = 24), and obstructive sleep apnea (n = 24). Visual staging (VS) was performed by two experts (VS1 and VS2) according to the American Academy of Sleep Medicine rules. AS was based on the analysis of a single electroencephalogram channel (Cz-Pz), without any information from electro-oculography nor electromyography. The epoch-by-epoch agreement (concordance and Conger's coefficient [κ]) was compared pairwise (VS1-VS2, AS-VS1, AS-VS2) and between AS and consensual VS. Sleep parameters were also compared. RESULTS: The pairwise agreements were: between AS and VS1, 78.6% (κ = 0.70); AS and VS2, 75.0% (0.65); and VS1 and VS2, 79.5% (0.72). Agreement between AS and consensual VS was 85.6% (0.80), with the following distribution: insomnia 85.5% (0.80), narcolepsy 83.8% (0.78), idiopathic hypersomnia 86.1% (0.68), and obstructive sleep disorder 87.2% (0.82). A significant low-amplitude scorer effect was observed for most sleep parameters, not always driven by the same scorer. Hypnograms obtained with AS and VS exhibited very close sleep organization, except for 80% of rapid eye movement sleep onset in the group diagnosed with narcolepsy missed by AS. CONCLUSIONS: Agreement between AS and VS in sleep disorders is comparable to that reported in healthy individuals and to interexpert agreement in patients. ASEEGA could therefore be considered as a complementary sleep stage scoring tool in clinical practice, after improvement of rapid eye movement sleep onset detection.

Transient hypoxemia induced by cortical electrical stimulation: A mapping study in 75 patients.

OBJECTIVE: To identify which cortical regions are associated with direct electrical stimulation (DES)-induced alteration of breathing significant enough to impair pulse oximetry (SpO2). METHODS: Evolution of SpO2 after 1,352 DES was analyzed in 75 patients with refractory focal epilepsy who underwent stereo-EEG recordings. For each DES, we assessed the change in SpO2 from 30 seconds prior to DES onset to 120 seconds following the end of the DES. The primary outcome was occurrence of stimulation-induced transient hypoxemia as defined by decrease of SpO2 ≥5% within 60 seconds after stimulation onset as compared to pre-DES SpO2 or SpO2 nadir <90% during at least 5 seconds. Localization of the stimulated contacts was defined according to MarsAtlas brain parcellation and Freesurfer segmentation. RESULTS: A stimulation-induced transient hypoxemia was observed after 16 DES (1.2%) in 10 patients (13%), including 6 in whom SpO2 nadir was <90%. Among these 16 DES, 7 (44%) were localized within the perisylvian cortex. After correction for individual effects and the varying number of DES contributed by each person, significant decrease of SpO2 was significantly associated with the localization of DES (p = 0.019). CONCLUSION: Though rare, a significant decrease of SpO2 could be elicited by cortical direct electrical stimulation outside the temporo-limbic structures, most commonly after stimulation of the perisylvian cortex.

Mindfulness meditation is related to sensory-affective uncoupling of pain in trained novice and expert practitioners.

BACKGROUND: Mindfulness meditation can alleviate acute and chronic pain. It has been proposed that mindfulness meditation reduces pain by uncoupling sensory and affective pain dimensions. However, studies to date have reported mixed results, possibly due to a diversity of styles of and expertise in mindfulness meditation. Furthermore, the interrelations between mindfulness meditation and pain catastrophizing during acute pain remain little known. METHODS: This cross-sectional study investigated the effect of a style of mindfulness meditation called Open Monitoring (OM) on sensory and affective pain experience by comparing novice (2-day formal training; average ~20 hr practice) to expert practitioners (>10.000 hr practice). We implemented a paradigm that was designed to amplify the cognitive-affective aspects of pain experience by the manipulation of pain anticipation and uncertainty of stimulus length (8 or 16 s thermal pain stimuli). We collected pain intensity and unpleasantness ratings and assessed trait pain catastrophizing with the Pain Catastrophizing Scale (PCS). RESULTS: Across groups, mindfulness meditation reduced unpleasantness, but not intensity ratings compared to attentional distraction. Experts reported a lower score on PCS, reduced amplification of unpleasantness by long painful stimuli, and larger sensory-affective uncoupling than novices particularly during long painful stimuli. In experts, meditation-induced uncoupling spilled over the control condition. Across groups and task conditions, a higher score on PCS predicted lower sensory-affective uncoupling during long painful stimuli and higher ratings of pain intensity during short painful stimuli. CONCLUSION: These findings suggest that mindfulness meditation specifically down-regulates pain affect as opposed to pain intensity, and that pain catastrophizing undermines sensory-affective uncoupling of pain. SIGNIFICANCE: In this study, we found that a style of mindfulness meditation referred to as OM reduced unpleasantness but not intensity ratings compared to attentional distraction in trained novice (state effect) and expert meditators (state and trait effects). We also observed that trait pain catastrophizing scores predicted this sensory-affective uncoupling. These findings advance our understanding of the cognitive mechanisms underlying mindfulness meditation and can inform treatment strategies for chronic pain.

Exploring scoring methods for research studies: Accuracy and variability of visual and automated sleep scoring.

Sleep studies face new challenges in terms of data, objectives and metrics. This requires reappraising the adequacy of existing analysis methods, including scoring methods. Visual and automatic sleep scoring of healthy individuals were compared in terms of reliability (i.e., accuracy and stability) to find a scoring method capable of giving access to the actual data variability without adding exogenous variability. A first dataset (DS1, four recordings) scored by six experts plus an autoscoring algorithm was used to characterize inter-scoring variability. A second dataset (DS2, 88 recordings) scored a few weeks later was used to explore intra-expert variability. Percentage agreements and Conger's kappa were derived from epoch-by-epoch comparisons on pairwise and consensus scorings. On DS1 the number of epochs of agreement decreased when the number of experts increased, ranging from 86% (pairwise) to 69% (all experts). Adding autoscoring to visual scorings changed the kappa value from 0.81 to 0.79. Agreement between expert consensus and autoscoring was 93%. On DS2 the hypothesis of intra-expert variability was supported by a systematic decrease in kappa scores between autoscoring used as reference and each single expert between datasets (.75-.70). Although visual scoring induces inter- and intra-expert variability, autoscoring methods can cope with intra-scorer variability, making them a sensible option to reduce exogenous variability and give access to the endogenous variability in the data.

Brain Volume Predicts Behavioral and Psychological Symptoms in Alzheimer's Disease.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are frequent and troublesome for patients and caregivers. Considering possible preventive approaches, a better understanding of underlying neural correlates of BPSD is crucial. OBJECTIVE: The aim is to assess whether brain regional volume predicts behavioral changes in mild AD. METHODS: This work took part from the PACO study, a multicenter and prospective study that included 252 patients with mild AD from 2009 to 2014. Fifty-three patients were retained. Forty healthy matched control subjects from the ADNI cohort were included as controls. Voxel-based morphometry analysis was conducted to assess regional brain volume using baseline MRI scans as a predictor of future behavioral changes over a period of 18 months. Behavior was assessed at baseline and longitudinally at 6-month intervals using the shortened form of the Neuropsychiatric Inventory (NPI). RESULTS: The volume of 23 brain structures in frontal, temporal, parietal, occipital, subcortical regions and cerebellum predicted the evolution of NPI scores. Frontal volume was the most powerful predictor with frontal gyri, anterior cingulate cortex, and orbital gyri being particularly involved. CONCLUSION: To our knowledge, this is the first study assessing regional brain volumes as predictors of behavioral changes considered at earlier stages of AD. Up to 23 brain structures were associated with an increased risk of developing BPSD. Frontal lobe volume was the strongest predictor of future evolution of NPI. The involvement of multiple structures in the prediction of behavior suggests a role of the main large-scale networks involved in cognition.

Regularized siamese neural network for unsupervised outlier detection on brain multiparametric magnetic resonance imaging: Application to epilepsy lesion screening.

In this study, we propose a novel anomaly detection model targeting subtle brain lesions in multiparametric MRI. To compensate for the lack of annotated data adequately sampling the heterogeneity of such pathologies, we cast this problem as an outlier detection problem and introduce a novel configuration of unsupervised deep siamese networks to learn normal brain representations using a series of non-pathological brain scans. The proposed siamese network, composed of stacked convolutional autoencoders as subnetworks is designed to map patches extracted from healthy control scans only and centered at the same spatial localization to 'close' representations with respect to the chosen metric in a latent space. It is based on a novel loss function combining a similarity term and a regularization term compensating for the lack of dissimilar pairs. These latent representations are then fed into oc-SVM models at voxel-level to produce anomaly score maps. We evaluate the performance of our brain anomaly detection model to detect subtle epilepsy lesions in multiparametric (T1-weighted, FLAIR) MRI exams considered as normal (MRI-negative). Our detection model trained on 75 healthy subjects and validated on 21 epilepsy patients (with 18 MRI-negatives) achieves a maximum sensitivity of 61% on the MRI-negative lesions, identified among the 5 most suspicious detections on average. It is shown to outperform detection models based on the same architecture but with stacked convolutional or Wasserstein autoencoders as unsupervised feature extraction mechanisms.

BLAST paradigm: A new test to assess brief attentional fluctuations in children with epilepsy, ADHD, and normally developing children.

BACKGROUND: Pure attentional deficits are still underdiagnosed in children with epilepsy. While attention-deficit hyperactivity disorder (ADHD) is historically the most studied cause of attentional disorders, an important number of children with epilepsy and attentional complaints do not fully meet the DSM-V (Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition) criteria for ADHD and may be excluded from specific care. Clinical tools currently available are insufficient to detect more subtle but clinically relevant attentional fluctuations. OBJECTIVE/METHODS: The recently developed Bron-Lyon Attention Stability Test (BLAST) was used to evaluate brief attentional fluctuations with a high temporal precision. Drawing on two new attentional indices, we evaluated spontaneous fluctuations of response accuracy and timing, underlying attentional stability. The main objective was to assess attentional stability in children with i) epilepsy with comorbid ADHD, ii) epilepsy without comorbid ADHD, iii) ADHD not medicated and without epilepsy, and iv) normal development. Further objectives were to assess the main determinants of attentional stability in those groups, including the effect of factors related to the epileptic condition. RESULTS: In 122 children with epilepsy (67 with comorbid ADHD), 52 children with ADHD, and 53 healthy controls, we demonstrated lower attentional stability in both the groups with epilepsy and ADHD compared with healthy children. In children with epilepsy, BLAST scores were negatively associated with earlier seizure onset and AED (antiepileptic drug) polytherapy, while the seizure frequency, epilepsy duration, or type did not influence BLAST scores. CONCLUSIONS: This study demonstrates that attentional stability is impaired in children with epilepsy and/or ADHD. Bron-Lyon Attention Stability Test seems to be a sensitive test to detect attentional stability deficit in children with epilepsy and with attentional complaints who did not meet all criteria of ADHD. We propose that BLAST could be a useful clinical neuropsychological tool to assess attentional disorders in children.

Saccadic Adaptation Boosts Ongoing Gamma Activity in a Subsequent Visuoattentional Task.

Attention and saccadic adaptation (SA) are critical components of visual perception, the former enhancing sensory processing of selected objects, the latter maintaining the eye movements accuracy toward them. Recent studies propelled the hypothesis of a tight functional coupling between these mechanisms, possibly due to shared neural substrates. Here, we used magnetoencephalography to investigate for the first time the neurophysiological bases of this coupling and of SA per se. We compared visual discrimination performance of 12 healthy subjects before and after SA. Eye movements and magnetic signals were recorded continuously. Analyses focused on gamma band activity (GBA) during the pretarget period of the discrimination and the saccadic tasks. We found that GBA increases after SA. This increase was found in the right hemisphere for both postadaptation saccadic and discrimination tasks. For the latter, GBA also increased in the left hemisphere. We conclude that oculomotor plasticity involves GBA modulation within an extended neural network which persists after SA, suggesting a possible role of gamma oscillations in the coupling between SA and attention.

Study protocol on Alzheimer's disease and related disorders: focus on clinical and imaging predictive markers in co-existing lesions.

BACKGROUND: One of the crucial challenges for the future of therapeutic approaches to Alzheimer's disease (AD) is to target the main pathological processes responsible for disability and dependency. However, a progressive cognitive impairment occurring after the age of 70, the main population affected by dementia, is often related to mixed lesions of neurodegenerative and vascular origins. Whereas young patients are mostly affected by pure lesions, ageing favours the occurrence of co-lesions of AD, cerebrovascular disease (CVD) and Lewy body dementia (LBD). Most of clinical studies report on functional and clinical disabilities in patients with presumed pure pathologies. But, the weight of co-morbid processes involved in the transition from an independent functional status to disability in the elderly with co-lesions still remains to be elucidated. Neuropathological examination often performed at late stages cannot answer this question at mild or moderate stages of cognitive disorders. Brain MRI, Single Photon Emission Computed Tomography (SPECT) with DaTscan®, amyloid Positron Emission Tomography (PET) and CerebroSpinal Fluid (CSF) AD biomarkers routinely help in performing the diagnosis of underlying lesions. The combination of these measures seems to be of incremental value for the diagnosis of mixed profiles of AD, CVD and LBD. The aim is to determine the clinical, neuropsychological, neuroradiological and biological features the most predictive of cognitive, behavioral and functional impairment at 2 years in patients with co-existing lesions. METHODS: A multicentre and prospective cohort study with clinical, neuro-imaging and biological markers assessment will recruit 214 patients over 70 years old with a cognitive disorder of AD, cerebrovascular and Lewy body type or with coexisting lesions of two or three of these pathologies and fulfilling the diagnostic criteria for dementia at a mild to moderate stage. Patients will be followed every 6 months (clinical, neuropsychological and imaging examination and collection of cognitive, behavioural and functional impairment) for 24 months. DISCUSSION: This study aims at identifying the best combination of markers (clinical, neuropsychological, MRI, SPECT-DaTscan®, PET and CSF) to predict disability progression in elderly patients presenting coexisting patterns. TRIAL REGISTRATION: NCT02052947 .