Brain imaging analysis can identify participants under regular mental training.

Multivariate pattern recognition approaches have become a prominent tool in neuroimaging data analysis. These methods enable the classification of groups of participants (e.g. controls and patients) on the basis of subtly different patterns across the whole brain. This study demonstrates that these methods can be used, in combination with automated morphometric analysis of structural MRI, to determine with great accuracy whether a single subject has been engaged in regular mental training or not. The proposed approach allowed us to identify with 94.87% accuracy (p<0.001) if a given participant is a regular meditator (from a sample of 19 regular meditators and 20 non-meditators). Neuroimaging has been a relevant tool for diagnosing neurological and psychiatric impairments. This study may suggest a novel step forward: the emergence of a new field in brain imaging applications, in which participants could be identified based on their mental experience.

Meditation training increases brain efficiency in an attention task.

Meditation is a mental training, which involves attention and the ability to maintain focus on a particular object. In this study we have applied a specific attentional task to simply measure the performance of the participants with different levels of meditation experience, rather than evaluating meditation practice per se or task performance during meditation. Our objective was to evaluate the performance of regular meditators and non-meditators during an fMRI adapted Stroop Word-Colour Task (SWCT), which requires attention and impulse control, using a block design paradigm. We selected 20 right-handed regular meditators and 19 non-meditators matched for age, years of education and gender. Participants had to choose the colour (red, blue or green) of single words presented visually in three conditions: congruent, neutral and incongruent. Non-meditators showed greater activity than meditators in the right medial frontal, middle temporal, precentral and postcentral gyri and the lentiform nucleus during the incongruent conditions. No regions were more activated in meditators relative to non-meditators in the same comparison. Non-meditators showed an increased pattern of brain activation relative to regular meditators under the same behavioural performance level. This suggests that meditation training improves efficiency, possibly via improved sustained attention and impulse control.

Influence of chronic cocaine treatment and sleep deprivation on sexual behavior and neurogenesis of the male rat.

The present study investigated the influence of chronic cocaine treatment on genital reflexes associated with paradoxical sleep deprivation (PSD), and possible alterations in hippocampus neurogenesis of the male rat. At 21 days of age, the rats were distributed into two groups and injected with saline or cocaine (7 mg/kg, three times a week for 12 weeks). At age 90 days, they were submitted to a four-day period of PSD (PSD groups) or maintained in home-cages (control groups), challenged with saline or cocaine administration, and placed in observation cages to assess genital reflexes. Two additional groups were used to quantify neurogenesis. PSD rats treated chronically with cocaine and challenged with saline did not differ from their respective control groups. The association of PSD with cocaine potentiated penile erection (PE) when compared to PSD-saline (saline challenged) rats, and these effects were similar to those observed in long-term cocaine treated rats. The bromodeoxyuridine (BrdU) assay indicated a reduction in BrdU-positive cells in the adult hippocampus after chronic cocaine treatment. These findings show that long-term cocaine treatment from brain development through adulthood had a marked effect on sexual responses and neuronal proliferation.

IMPACT, a protein preferentially expressed in the mouse brain, binds GCN1 and inhibits GCN2 activation.

Translational control directed by the eukaryotic translation initiation factor 2 alpha-subunit (eIF2alpha) kinase GCN2 is important for coordinating gene expression programs in response to nutritional deprivation. The GCN2 stress response, conserved from yeast to mammals, is critical for resistance to nutritional deficiencies and for the control of feeding behaviors in rodents. The mouse protein IMPACT has sequence similarities to the yeast YIH1 protein, an inhibitor of GCN2. YIH1 competes with GCN2 for binding to a positive regulator, GCN1. Here, we present evidence that IMPACT is the functional counterpart of YIH1. Overexpression of IMPACT in yeast lowered both basal and amino acid starvation-induced levels of phosphorylated eIF2alpha, as described for YIH1 (31). Overexpression of IMPACT in mouse embryonic fibroblasts inhibited phosphorylation of eIF2alpha by GCN2 under leucine starvation conditions, abolishing expression of its downstream target genes, ATF4 (CREB-2) and CHOP (GADD153). IMPACT bound to the minimal yeast GCN1 segment required for interaction with yeast GCN2 and YIH1 and to native mouse GCN1. At the protein level, IMPACT was detected mainly in the brain. IMPACT was found to be abundant in the majority of hypothalamic neurons. Scattered neurons expressing this protein at higher levels were detected in other regions such as the hippocampus and piriform cortex. The abundance of IMPACT correlated inversely with phosphorylated eIF2alpha levels in different brain areas. These results suggest that IMPACT ensures constant high levels of translation and low levels of ATF4 and CHOP in specific neuronal cells under amino acid starvation conditions.

Bilateral anterior thalamic nucleus lesions and high-frequency stimulation are protective against pilocarpine-induced seizures and status epilepticus.

OBJECTIVE: The thalamus is thought to play an important role in secondary generalization of seizures. The aim of the present study was to investigate the influence of anterior thalamic nucleus lesions and high-frequency stimulation in the pilocarpine model of secondarily generalized seizures in rats. METHODS: Adult Wistar rats underwent unilateral (n = 7) or bilateral anterior nucleus thalamotomies (n = 10), or unilateral (n = 4) or bilateral (n = 9) anterior thalamic nucleus stimulation through implanted electrodes. Control animals (n = 9) received bilateral implants but no stimulation. Seven days after these procedures, animals were provided pilocarpine (320 mg/kg intraperitoneally) to induce seizures and status epilepticus (SE). Electrographic recordings from hippocampal and cortical electrodes were evaluated, and ictal behavior was assessed. RESULTS: In the control group, 67% of the animals developed SE 15.3 +/- 8.8 minutes after pilocarpine administration. Neither unilateral anterior nucleus lesions nor stimulation significantly reduced the propensity or latency for developing seizures and SE. Bilateral thalamic stimulation did not prevent SE (observed in 56% of the animals), but it significantly prolonged the latency to its development (48.4 +/- 17.7 min, P = 0.02). Strikingly, no animal with bilateral anterior nucleus thalamotomies developed seizures or SE with pilocarpine. CONCLUSION: Bilateral anterior thalamic nuclear complex stimulation and thalamotomies were protective against SE induced by pilocarpine.

Onset of estrogen replacement has a critical effect on synaptic density of CA1 hippocampus in ovariectomized adult rats.

OBJECTIVES: The aim of this study was to evaluate differences between estrogen replacement therapy initiated either 4 or 12 days after ovariectomy on the synaptic density of the hippocampal CA1 field in rats. DESIGN: Female, adult, Wistar rats were ovariectomized bilaterally under ether anesthesia and divided among the following groups: 1) estrogen (conjugated equine estrogen 50 microg in 0.5 mL of propylene glycol, daily, p.o. gavage, for 60 days), starting 4 days after ovariectomy (n = 5); 2) propylene glycol (0.5 mL daily, p.o. gavage, for 60 days), starting 4 days after ovariectomy (n = 4); 3) estrogen (conjugated equine estrogen 50 microg in 0.5 mL of propylene glycol, daily, p.o. gavage, for 45 days), starting 12 days after ovariectomy (n = 3); 4) propylene glycol (0.5 mL daily, p.o. gavage, for 45 days), starting 12 days after ovariectomy (n = 3). At the end of the treatment, the rats were processed for electron microscopy and light analysis. RESULTS: Synaptic density in all of the CA1 strata subjected to evaluation was significantly higher in animals in which estrogen replacement was initiated 4 days after ovariectomy as compared with controls. In contrast, initiation of treatment after a 12-day interval did not result in recovery of synaptic density in any of the CA1 strata and was significantly lower than that of the animals subjected to hormone replacement after a 4-day delay (P < 0.01). CONCLUSION: The delay for hormone replacement therapy might have critical implications for modulating synaptic density.

Respiratory pattern in a rat model of epilepsy.

PURPOSE: Apnea is known to occur during seizures, but systematic studies of ictal respiratory changes in adults are few. Data regarding respiratory pattern defects during interictal periods also are scarce. Here we sought to generate information with regard to the interictal period in animals with pilocarpine-induced epilepsy. METHODS: Twelve rats (six chronically epileptic animals and six controls) were anesthetized, given tracheotomies, and subjected to hyperventilation or hypoventilation conditions. Breathing movements caused changes in thoracic volume and forced air to flow tidally through a pneumotachograph. This flow was measured by using a differential pressure transducer, passed through a polygraph, and from this to a computer with custom software that derived ventilation (VE), tidal volume (VT), inspiratory time (TI), expiratory time (TE), breathing frequency (f), and mean inspiratory flow (VT/TI) on a breath-by-breath basis. RESULTS: The hyperventilation maneuver caused a decrease in spontaneous ventilation in pilocarpine-treated and control rats. Although VE had a similar decrease in both groups, in the epileptic group, the decrease in VE was due to a significant (p < 0.05) increase in TE peak in relation to that of the control animals. The hypoventilation maneuver led to an increase in the arterial Paco2, followed by an increase in VE. In the epileptic group, the increase in VE was mediated by a significant (p < 0.05) decrease in TE peak compared with the control group. Systemic application of KCN, to evaluate the effects of peripheral chemoreception activation on ventilation, led to a similar increase in VE for both groups. CONCLUSIONS: The data indicate that pilocarpine-treated animals have an altered ability to react to (or compensate for) blood gas changes with changes in ventilation and suggest that it is centrally determined. We speculate on the possible relation of the current findings on treating different epilepsy-associated conditions.

Characterization of reactive astrocytes in the chronic phase of the pilocarpine model of epilepsy.

PURPOSE: Astrogliosis is a prominent finding in human temporal lobe epilepsy. Work in animal models of temporal lobe epilepsy, however, have mostly concentrated on the acute phases of the studied models or have failed to demonstrate reactive gliosis during the chronic phases of such models. METHODS: Here we used the pilocarpine model of chronic seizures and Cajal's gold sublimate technique for the staining reactive astrocytes to study this issue. RESULTS: For half of the animals (nine of 17) subject to pilocarpine-induced status epilepticus (SE), when assessed 60 days later, variable levels of reactive astrocytes were seen in many thalamic, hippocampal, amygdalar, and neocortical areas. For the remaining half of the animals, however (eight of 17), despite a similar SE induction, as well as for controls, we could not detect stained reactive astrocytes. CONCLUSIONS: We hypothesize that these results might underlie possible differences in the frequency of recurrent spontaneous seizures.

Electrophysiologic abnormalities of the hippocampus in the pilocarpine/cycloheximide model of chronic spontaneous seizures.

PURPOSE: Mossy fiber sprouting (MFS) and synaptic reorganization in the dentate gyrus (DG) is considered one of the physiopathologic mechanisms in temporal lobe epilepsy. Supragranular MFS can be blocked by cycloheximide (CHX) without interfering with the genesis of spontaneous recurrent seizures. The aim of this study was to investigate electrophysiologic properties of the hippocampus in the CHX/pilocarpine (CHX/PILO) model as compared with the conventional PILO model. METHODS: In vitro electrophysiology was performed 2 months after status epilepticus (SE) induction using extracellular recordings in hippocampal slices from PILO (n = 8) and CHX/PILO animals (n = 10). Field potential responses were evoked in the CA1 and DG regions during perfusion with normal artificial cerebrospinal fluid (aCSF) and aCSF containing 3.5, 5, or 8 mM K+ without or with bicuculline added. Neo-Timm staining was used for the assessment of supragranular MFS. RESULTS: Evoked potentials in PILO- and CHX/PILO-treated rats displayed small-amplitude polyspiking activity (epileptiform responses) in CA1 and an apparently normal isolated population spike in DG. More important, PILO and CHX/PILO animals did not differ regarding electrophysiologic abnormalities, even under high K+ or high K+/bicuculline. Analysis of the neo-Timm staining revealed strong supragranular MFS in PILO-injected rats and significantly less staining in CHX/PILO rats. Thus, occurrence of abnormal stimulus responses and high K+- or high K+/bicuculline-induced epileptiform activities did not depend on the degree of MFS. CONCLUSIONS: We therefore suggest that other mechanisms such as anomalous intrinsic bursting and disinhibition rather than MFS might account for the increased hippocampal hyperexcitability in this model.

Inhibitory role of the zona incerta in the pilocarpine model of epilepsy.

Recent experiments have suggested that the zona incerta might be regarded as a highly sensitive structure for seizure induction. This sensitivity has been linked to this structure's abundant expression of cholinergic receptors. Here we have decided to investigate the participation of the GABAergic system of the zona incerta, one of its major neurotransmitters with widespread projections to the neocortex, in the pilocarpine (Pilo) model of epilepsy. Stereotaxic administration of a GABA(A) agonist (muscimol), antagonist (bicuculline) or saline (controls) bilaterally into the zona incerta of adult male Wistar rats was performed 30 min prior to the systemic injection of pilocarpine. Animals were electroencephalographically and behaviorally monitored for seizure activity. Administration of muscimol had a pro-convulsant effect characterised by a higher percentage of animals developing SE with a shorter latency. Conversely, administration of bicuculline had a dose dependent anticonvulsant effect, with no animals displaying SE. Our results contribute to the further characterisation of the regulatory role of the zona incerta in seizure-related phenomena, suggesting that its modulation might be a relevant target for anticonvulsant strategies.

Spontaneous recurrent seizures and neuropathology in the chronic phase of the pilocarpine and picrotoxin model epilepsy.

In a recent publication, we have shown a potent interaction between the cholinergic and GABAergic systems in regard to seizure generation and developed the pilocarpine(pilo)/picrotoxin(PTX) model, in which combined injections of these agents have induced status epilepticus (SE) in rats. Here we report on the chronic features of this new animal model of epilepsy. Adult male Wistar rats were systemically injected with solutions containing 150/0.5 mg kg-1, 75/1.5 mg kg-1 and 50/2.0 mg kg-1 (pilo dose/PTX dose). Six epileptic and six control animals were observed for 120-131 days for the occurrence of spontaneous recurrent seizures (SRS). Electroencephalographic, neuropathologic and behavioral analyses were subsequently performed. Following SE, the animals went through a latent period and, subsequently, towards a state of 'chronic' epilepsy, characterized by the emergence of SRS. Animals that received 150/0.5 mg kg-1 presented a relatively short latent period, partial events as their most common initial seizure manifestations and a considerable subsequent progression towards generalization. The group injected with 75/1.5 mg kg-1 presented an extensive period during which the majority of the animals exclusively developed partial seizures (50 days). Animals injected with 50/2.0 mg kg-1 presented an average latent period of over 100 days. Only few animals within this group developed SRS. Our EEG, neuropathological and ictal behavioral findings, in conjunction with the fact that SE was required for the posterior development of SRS, suggest that our model parallels a human TLE condition. Even though diverse TLE models have been described, the pilo/PTX model has as a major feature the intriguing occurrence of disparities among these three groups in the chronic period, although no differences could be observed during SE induction. Future experiments conducted in this sense, might lead to important results in regard to the elucidation of mechanisms of epileptogenesis.

Convulxin does not induce convulsions when injected into the rat dorsal hippocampus

La convulxina, una neurotoxina extraída del veneno de Crotalus durissus terrificus, ejerce un efecto convulsivante cuando se inyecta por vía endovenosa en ratones y gatos. En la búsqueda de nuevos compuestos más efectivos selectivos, diversos estudios se han desarrollado en el campo de las neurotoxinas. En consecuencia, el objetivo de este trabajo fue analizar los efectos comportamentales, electroencefalograficos y neuropatológicos desencadenados por la inyección intrahipocampal de convulxina. En otra secuencia experimental, fue utilizada una mexcla de convulxina y plasma rico en plaquetas, como tentativa de testar la hipótesis de la acción indirecta de la convulxina. Los resultados han demostrado que tanto la convulxina como la mexcla de convulxina y plasma rico en plaquetas fueron incapaces de desencadenar convulsione o de causar lesiones celulares específicas (AU)

Convulxin does not induce convulsions when injected into the rat dorsal hippocampus

La convulxina, una neurotoxina extraída del veneno de Crotalus durissus terrificus, ejerce un efecto convulsivante cuando se inyecta por vía endovenosa en ratones y gatos. En la búsqueda de nuevos compuestos más efectivos selectivos, diversos estudios se han desarrollado en el campo de las neurotoxinas. En consecuencia, el objetivo de este trabajo fue analizar los efectos comportamentales, electroencefalograficos y neuropatológicos desencadenados por la inyección intrahipocampal de convulxina. En otra secuencia experimental, fue utilizada una mexcla de convulxina y plasma rico en plaquetas, como tentativa de testar la hipótesis de la acción indirecta de la convulxina. Los resultados han demostrado que tanto la convulxina como la mexcla de convulxina y plasma rico en plaquetas fueron incapaces de desencadenar convulsione o de causar lesiones celulares específicas