Where and when to look: Sequential effects at the millisecond level.

Learning and imitating a complex motor action requires to visually follow complex movements, but conscious perception seems too slow for such tasks. Recent findings suggest that visual perception has a higher temporal resolution at an unconscious than at a conscious level. Here we investigate whether high-temporal resolution in visual perception relies on prediction mechanisms and attention shifts based on recently experienced sequences of visual information. To that aim we explore sequential effects during four different simultaneity/asynchrony discrimination tasks. Two stimuli are displayed on each trial with varying stimulus onset asynchronies (SOA). Subjects decide whether the stimuli are simultaneous or asynchronous and give manual responses. The main finding is an advantage for different-order over same-order trials, when subjects decided that stimuli had been simultaneous on Trial t - 1 , and when Trial t is with an SOA slightly larger than Trial t - 1, or equivalent. The advantage for different-order trials disappears when the stimuli change eccentricity but not direction between trials (Experiment 2), and persists with stimuli displayed in the centre and unlikely to elicit a sense of direction (Experiment 4). It is still observed when asynchronies on Trial t - 1 are small and undetected (Experiment 3). The findings can be explained by an attention shift that is precisely planned in time and space and that incidentally allows subjects to detect an isolated stimulus on the screen, thus helping them to detect an asynchrony.

Altered Proteins in the Hippocampus of Patients with Mesial Temporal Lobe Epilepsy.

Mesial temporal lobe epilepsy (MTLE) is usually associated with drug-resistant seizures and cognitive deficits. Efforts have been made to improve the understanding of the pathophysiology of MTLE for new therapies. In this study, we used proteomics to determine the differential expression of proteins in the hippocampus of patients with MTLE compared to control samples. By using the two-dimensional electrophoresis method (2-DE), the proteins were separated into spots and analyzed by LC-MS/MS. Spots that had different densitometric values for patients and controls were selected for the study. The following proteins were found to be up-regulated in patients: isoform 1 of serum albumin (ALB), proton ATPase catalytic subunit A (ATP6V1A), heat shock protein 70 (HSP70), dihydropyrimidinase-related protein 2 (DPYSL2), isoform 1 of myelin basic protein (MBP), and dihydrolipoamide S-acethyltransferase (DLAT). The protein isoform 3 of the spectrin alpha chain (SPTAN1) was down-regulated while glutathione S-transferase P (GSTP1) and protein DJ-1 (PARK7) were found only in the hippocampus of patients with MTLE. Interactome analysis of the nine proteins of interest revealed interactions with 20 other proteins, most of them involved with metabolic processes (37%), presenting catalytic activity (37%) and working as hydrolyses (25%), among others. Our results provide evidence supporting a direct link between synaptic plasticity, metabolic disturbance, oxidative stress with mitochondrial damage, the disruption of the blood⁻brain barrier and changes in CNS structural proteins with cell death and epileptogenesis in MTLE. Besides this, the presence of markers of cell survival indicated a compensatory mechanism. The over-expression of GSTP1 in MTLE could be related to drug-resistance.

Neurochemical Changes and c-Fos Mapping in the Brain after Carisbamate Treatment of Rats Subjected to Lithium-Pilocarpine-Induced Status Epilepticus.

The administration of lithium-pilocarpine (LiPilo) in adult rats is a validated model reproducing the main clinical and neuropathological features of temporal lobe epilepsy (TLE). Previous studies have shown that carisbamate (CRS) has the property of modifying epileptogenesis in this model. When treated with CRS, about 50% of rats undergoing LiPilo status epilepticus (SE) develop non-convulsive seizures (NCS) instead of convulsive ones (commonly observed in TLE). The goal of this work was to determine some of the early changes that occur after CRS administration, as they could be involved in the insult- and epileptogenesis-modifying effects of CRS. Thus, we performed high-performance liquid chromatography (HPLC) to quantify levels of amino acids and monoamines, and c-Fos immunohistochemical labeling to map cerebral activation during seizures. Comparing rats treated one hour after SE onset with saline (CT), CRS, or diazepam (DZP), HPLC showed that 4 h after SE onset, dopamine (DA), norepinephrine (NE), and GABA levels were normal, whereas serotonin levels were increased. Using c-Fos labeling, we demonstrated increased activity in thalamic mediodorsal (MD) and laterodorsal (LD) nuclei in rats treated with CRS. In summary, at early times, CRS seems to modulate excitability by acting on some monoamine levels and increasing activity of MD and LD thalamic nuclei, suggesting a possible involvement of these nuclei in insult- and/or epileptogenesis-modifying effects of CRS.

Hippocampal Proteome of Rats Subjected to the Li-Pilocarpine Epilepsy Model and the Effect of Carisbamate Treatment.

In adult rats, the administration of lithium-pilocarpine (LiPilo) reproduces most clinical and neuropathological features of human temporal lobe epilepsy (TLE). Carisbamate (CRS) possesses the property of modifying epileptogenesis in this model. Indeed, about 50% of rats subjected to LiPilo status epilepticus (SE) develop non-convulsive seizures (NCS) instead of motor seizures when treated with CRS. However, the mechanisms underlying these effects remain unknown. The aim of this study was to perform a proteomic analysis in the hippocampus of rats receiving LiPilo and developing motor seizures or NCS following CRS treatment. Fifteen adult male Sprague-Dawley rats were used. SE was induced by LiPilo injection. CRS treatment was initiated at 1 h and 9 h after SE onset and maintained for 7 days, twice daily. Four groups were studied after video-EEG control of the occurrence of motor seizures: a control group receiving saline (CT n = 3) and three groups that underwent SE: rats treated with diazepam (DZP n = 4), rats treated with CRS displaying NCS (CRS-NCS n = 4) or motor seizures (CRS-TLE n = 4). Proteomic analysis was conducted by 2D-SDS-PAGE. Twenty-four proteins were found altered. In the CRS-NCS group, proteins related to glycolysis and ATP synthesis were down-regulated while proteins associated with pyruvate catabolism were up-regulated. Moreover, among the other proteins differentially expressed, we found proteins related to inflammatory processes, protein folding, tissue regeneration, response to oxidative stress, gene expression, biogenesis of synaptic vesicles, signal transduction, axonal transport, microtubule formation, cell survival, and neuronal plasticity. Our results suggest a global reduction of glycolysis and cellular energy production that might affect brain excitability. In addition, CRS seems to modulate proteins related to many other pathways that could significantly participate in the epileptogenesis-modifying effect observed.

Sustained attention ability in schizophrenia: Investigation of conflict monitoring mechanisms.

OBJECTIVE: The main goal of the current study was to assess, with a time-on-task approach, sustained attention ability in schizophrenia, and to investigate conflict monitoring underlying this ability. METHODS: Behavioral and event-related potentials data (N2 and P3a amplitudes) were recorded in a long-lasting sustained attention Go/NoGo task (sustained attention to response task, SART), over a period of 30min, in 29 patients with schizophrenia and 29 pair-matched healthy subjects. RESULTS: Our results revealed spared sustained attention ability in patients throughout the task. Impairment of conflict detection (N2) in patients was particularly significant at the end of the task. Furthermore, both schizophrenia and healthy subjects exhibited a decline in conflict detection from the beginning to the middle of the task. Whereas controls' conflict detection recovered in the last part of the task, patients' did not, suggesting a deficit in recovery processes reflecting a lack of additional resources sustained attention Go/NoGo task. Conflict resolution (P3a) was preserved throughout the task in both groups. CONCLUSIONS: Conflict monitoring processes are increasingly impaired in schizophrenia during a long-lasting sustained attention Go/NoGo task. SIGNIFICANCE: This impairment at the end of the task may rely on deficit in recovery processes, rather than a deficit in conflict detection per se in schizophrenia.

Age-related differences in the use of automatic and controlled processes in a situation of sustained attention.

Previous studies examining sustained attention ability in older adults have yielded inconsistent results: age-related decline in studies using traditionally formatted tasks (TFT), in which subjects have to respond to rare targets, and preservation in studies using Go/No-Go tasks, in which subjects have to withhold response to rare targets. The purpose of this study was to examine whether these discrepancies could be explained by a differential use of automatic and controlled processes according to age. To that end, we used two versions of the same task differing in response mode (TFT, Go/No-Go), and the event-related potential (ERP) technique. The within-task comparison first revealed that older adults exhibited a vigilance decrement in the TFT SART, while their performance actually improved in the Go/No-Go SART. Secondly, in both tasks, ERP results notably evidenced increased P2s and non-target P3s in older adults, components related to the allocation of attentional resources. Altogether, our results suggest that in both tasks older adults adopted a controlled processing mode, which resulted in opposite effects on performance according to the nature of the task.

Anxiety and locomotion in Genetic Absence Epilepsy Rats from Strasbourg (GAERS): inclusion of Wistar rats as a second control.

OBJECTIVE: The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is a genetic model, derived from Wistar rats by selective breeding. In all previous studies, GAERS were compared to their paired selected strain not expressing spike-and-wave discharges (SWDs), namely nonepileptic controls (NECs). Because the occurrence/absence of SWDs is of polygenic origin, some other traits could have been selected along with occurrence/absence of SWDs. Therefore, we explored the importance of using a second control group consisting in Wistar rats, the strain of origin of GAERS, in addition to NECs, on locomotion and anxiety in GAERS. METHODS: A test battery encompassing home-cage, open-field, beam-walking and elevated plus-maze evaluations was used. In addition, stereologic analyses were performed to assess the volume of thalamus, amygdala, and hippocampus. The occurrence/absence of SWDs was determined in all three strains by electroencephalography (EEG) recording. RESULTS: When compared to NECs and Wistars, GAERS displayed lower exploratory activity and fastened habituation to novelty. In the plus-maze, scores of GAERS and Wistars were similar, but NECs appeared significantly less anxious (possibly in association with increased amygdala volume); evidence for weaker anxiety in NECs was also found in the open-field evaluation. The volumetric study revealed increased thalamic volume in GAERS compared to both control groups. SWDs were present in all GAERS and in 80% of Wistars. SIGNIFICANCE: Compared to the original Wistar strain as an additional control group, the selective breeding that generated the GAERS has no incidence on anxiety-related behavior, conversely to the selection of SWD suppression in NECs, in which anxiety is attenuated. These findings point to the importance of using a second control group composed of Wistar rats in studies characterizing the behavioral profile of GAERS. Thereby, possible confusions between occurrence/absence of SWDs and other features that come along with selection and/or differential brain development induced by the genetic mutations are reduced.