Neurofeedback for cognitive enhancement and intervention and brain plasticity.

In recent years, neurofeedback has been used as a cognitive training tool to improve brain functions for clinical or recreational purposes. It is based on providing participants with feedback about their brain activity and training them to control it, initiating directional changes. The overarching hypothesis behind this method is that this control results in an enhancement of the cognitive abilities associated with this brain activity, and triggers specific structural and functional changes in the brain, promoted by learning and neuronal plasticity effects. Here, we review the general methodological principles behind neurofeedback and we describe its behavioural benefits in clinical and experimental contexts. We review the non-specific effects of neurofeedback on the reinforcement learning striato-frontal networks as well as the more specific changes in the cortical networks on which the neurofeedback control is exerted. Last, we analyse the current challenges faces by neurofeedback studies, including the quantification of the temporal dynamics of neurofeedback effects, the generalisation of its behavioural outcomes to everyday life situations, the design of appropriate controls to disambiguate placebo from true neurofeedback effects and the development of more advanced cortical signal processing to achieve a finer-grained real-time modelling of cognitive functions.

Effect of simvastatin on the synthesis and secretion of lipoproteins in relation to the metabolism of cholesterol in cultured hepatocytes.

In primary culture of rat hepatocytes, simvastatin, a powerful HMGCoA reductase inhibitor, inhibited acetate incorporation into cellular and secreted cholesterol and cholesteryl-esters, without any significant effect on triacylglycerol synthesis and secretion. When applied to the culture for 24 h at 10(-7) M, a concentration shown to inhibit cholesterol synthesis by 61%, simvastatin increased apolipoprotein BH and BL synthesis and secretion and strongly decreased apolipoprotein AI synthesis and secretion whereas apolipoprotein AIV remained unaffected. The synthesis and secretion of apolipoprotein E was only slightly affected in contrast with other situations where cholesterol synthesis decreased. All of these modifications occurred at a post-transcriptional level, as the corresponding messenger RNAs of the apolipoproteins did not vary. These results suggest that either the drug itself or variations in cholesterol synthesis might be involved in apo B and apo AI synthesis and secretion.

Extent of 14C incorporation into cholesterol of infant skin fibroblasts incubated with carboxyl-labeled oleic, -linoleic or -arachidonic acid.

In order to determine the incorporation of C1-14C derived from mono- and poly-unsaturated fatty acids into cholesterol of human cells cultured in exponential phase, infant skin fibroblasts (SF) were used at the 5th passage. On Day 6, the SF were preincubated 36 h in a medium containing 5 per cent lipoprotein-deficient serum, and thereafter [1-14C] oleic, -linoleic or -arachidonic acid-without (OL1, LI1 and AR1 group SF), or with the addition of 0.25 mM cold fatty acids (OL2), LI2 and AR2 group SF). Cholesterol specific radioactivity (SRA) peaked 1 h after, and leveled off afterwards in the OL1, LI1 and AR1 groups. Cholesterol-SRA was relatively low in the other groups, but increased progressively, giving a biphasic response: C1-14C derived from from linoleic and arachidonic acids was actively incorporated into cholesterol during the first hours, as compared to C1-14C derived from oleic acid, but stabilized between 6 and 12 h for the LI2 and AR2 group SF incubation. This result appears to be due to the stimulation of pyruvate decarboxylation, observed elsewhere, and consequently to the dilution of the radioactive units in a large pool of non-labeled acetyl-CoA units derived from glucose, when these SF were incubated with 0.25 mM polyunsaturated fatty acids.

Dietary casein levels and taurine supplementation. Effects on cysteine dioxygenase and cysteine sulfinate decarboxylase activities and tuarine concentration in brain, liver and kidney of the rat.

Activities of cysteine dioxygenase (CO) and cysteine sulfinate decarboxylase (CSD) and the concentrations of taurine (T) in brain, liver and kidney of rats fed on diets containing 18% casein (A), 60% casein (B) and 17% casein supplemented with 1% of taurine (+T), were measured. Regardless of the diet, the three measurements were the same in the brains of the animals in the three groups. In the liver and the kidney, CO activity was also the same in all three diets, but a decrease of CSD activity associated to an increase of T was observed in rats fed on diet B. The taurine-supplemented diet led to an increase in T concentration.

Pyruvate dehydrogenase activity in the liver, brain and adipose-tissue of lipid-deprived developing rats. Effect of minute amounts of polyunsaturated fatty acids.

UNLABELLED: The present experiment was carried out using the following diets: FF, fat-free, and LP in same diet with 0.7% sunflower oil - given to the progeny of females kept on the FF diet since the mating. after 10 mM Mg2+ activation of the PDH phosphatase, and rate of [1-14C[ pyruvate decarboxylation into acetyl-CoA ester units was determined in the liver, brain and adipose-tissue of the pair-fed developing rats. RESULTS: In the male progeny, pyruvate dehydrogenase (PDH) activity was higher (61%) in the LP group livers than in the FF group livers, at the end of the 13 week experiment. Such a difference was not observed in the two group brains up to the 91 days postweaning, but was even larger (94%) between adipose-tissues of the LP and FF groups. In the female progeny kept 12 weeks on the diets, PDH activity in the LP group tissues was also higher than in the FF group tissues: 63% in the liver, 43% in adipose-tissues, and less than 10% in the brain. Therefore, a minute amount of lipids high in linoleic acid appeared to increase PDH activity, and especially in the liver and adipose-tissues of animals kept on a strictly fat-free diet. This stimulation of the PDH activity seems closely related to the phospholipid rehabilitation in the tissues (decrease in the trienoic, tetraenoic acid ratio values).

Nutritional regulation of apolipoprotein genes: effect of dietary carbohydrates and fatty acids.

The effect of nutritional factors on apolipoprotein gene expression by rat liver were studied. Dietary carbohydrates or fatty acids regulate the expression of apo E gene, by altering either gene transcription or mRNA stability. Conversely, apo AI regulation occurs at a post transcriptional level. In vivo and in vitro experiments gave contradictory results concerning apo B gene expression. The more dramatic changes in plasma lipids and apolipoproteins are obtained under dietary fish oil. Hepatocytes from fish oil-fed rats retain for several days modification in fatty acid metabolism, i.e. a shift in oleic acid channeling towards oxidation at the expense of esterification and a reduced ability to synthesize and secrete triacylglycerol. These modifications are paralleled with a decrease in the synthesis and in the secretion of apo Bs. Hepatocytes from fish oil fed rats secrete degradative forms of apo B which might result from either a sluggish VLDL synthesis and secretion or a more specific effect of n-3 long chain polyunsaturated fatty acid peroxidative products. Hepatocytes from fish oil fed rats exhibit a reduced ability to synthesize cholesterol, associated with a decrease in apo AI synthesis and secretion without any modification in apo AI mRNA. In contrast, the hepatocytes exhibit a concomitent decrease in apo E synthesis and secretion and in cellular apo E mRNA levels.

Cysteine oxidase and cysteine sulfinic acid decarboxylase in developing rat liver.

The patterns of development of cysteine oxidase (CO) and cysteine sulfinic acid decarboxylase (CSD) in rat liver are not similar. It was observed that CO is not under sex control as CSD is. The results obtained agree with the idea that, in liver, as well as in brain, CSD is the limiting factor for the regulation of taurine biosynthesis.

[Fetal and neo-natal development of brown adipose tissue in guinea pigs and rats. Feto-maternal or milk transfer of essential fatty acids : lipogenesis and morphology (author's transl)]. / Développement foetal et néo-natal du tissu adipeux brun du cobaye et du rat. Transfert foeto-placentaire ou lacté des acides gras essentiels : lipogenèse et morphologie

Brown adipose tissue (BAT) lipogenesis (fatty acid, glycerol and CO2 synthesis) and its morphology determined by optical microscopy, were studied in guinea pigs and rats during intra-uterine life and during the suckling period. Following the receptor induction and after the commencement of the hormone sensitive adenylate-cyclase/lipase system (i.e. on the 60th day in guinea pigs, on the 20th day in rats), the fetal BAT releases fatty acids (NEFA) and is capable of allowing the non-shivering thermogenesis. When the maternal diet and, consequently, the fetal or neonatal BAT are supplied with considerable linoleic acid, NEFA contain a large proportion of essential fatty acids. In vitro, the greater the linoleic acid concentration in these NEFA, the less inhibited is the lipogenesis from (2-14C) pyruvate. Thus, in periods just preceding or succeeding birth, fatty acid and glycerol synthesis are higher when the feto-maternal and/or the milk supply are enriched in linoleic acid than when they contain a large proportion of endogenous fatty acids. Morphological studies indicate that the adipose cell evolution could be nonidentical in BAT more or less enriched in essential fatty acids. Linoleic enriched BAT (of animals born to females kept on a sunflower oil diet) seemed to be in a healthy physiological state at birth, perhaps due to rapid lipid renewal and synthesis in their membranes. The control BAT (of animals born to females kept on a lard diet) appeared loaded with fats and in a worse conservation state at the same age.

Effect of dietary cholic acid and cholesterol on liver and kidney cystathionase and cysteine sulfinate decarboxylase activities and taurine concentrations in the rat.

Hepatic cystathionase and cysteine sulfinate decarboxylase activities are drastically affected by cholic acid added to the diet without cholesterol. When cholic acid and cholesterol are given together, only cysteine sulfinate decarboxylase activity is changed. Neither kidney enzyme activity nor taurine concentrations in the liver and kidney are noticeably modified, whatever the diet.

Regional and subcellular distribution of taurine-synthesizing enzymes in the rat central nervous system.

The distribution of cysteine oxidase (CO) and cysteine sulfinate decarboxylase (CSD) was examined in 12 regions of the rat central nervous system (CNS). The distribution of CO activity, expressed as µmol of cysteine sulfinate formed per h per g, was the following: hypothalamus, superior and inferior colliculi, 94-99 µmol/h/g; olfactory bulbs, cerebral cortex, striatum, and hippocampus, 44-51 µmol/h/g; cerebellum, 71 µmol/h/g; pons-medula and spinal cord, 94 and 60 µmol/h/g, respectively. The distribution of CSD activity expressed as µmol of cysteine sulfinate decarboxylated per h per g was the following: hypothalamus and colliculi, 14-21 µmol/h/g; olfactory bulbs, cerebral cortex, striatum, hippocampus, and cerebellum, 8-13 µmol/h/g; pons-medulla, 7.3; and spinal cord, 3.6 µmol/h/g. No CSD activity was detected in sciatic nerve. The subcellular distribution of CO and CSD activities was studied in hypothalamus, colliculi, and cerebral cortex. CO activity was localized in synaptosomes, mitochondria, and microsomes. CSD was primarily confined to the crude mitochondrial fraction and after subfraction, recovered mainly in the synaptosomal fraction.

Selective channelling of arachidonic and linoleic acids into glycerolipids of rat hepatocytes in primary culture.

Rat hepatocytes in primary culture were incubated with a mixture of linoleic and arachidonic acid at various total fatty acid/serum albumin molar ratios. Mixed fatty acids were taken up at the same rate and distributed with the same pattern as fatty acids added separately. The rates of total uptake, incorporation into hepatocyte and secreted triacylglycerols and beta-oxidation were linearly related to the fatty acid/albumin ratios, whereas the rate of incorporation into phospholipids was saturable. Neither the uptake rate nor the distribution of both fatty acids considered together varied with the arachidonic acid/linoleic acid molar ratio. Changes in this ratio and in the uptake rate led to significant variations in the respective fate of the fatty acids. The preferential channelling of arachidonic acid versus linoleic acid into beta-oxidation and phosphatidylinositol was greatest at a low uptake rate and then decreased as the uptake rose. Conversely, the preferential channelling of arachidonic acid versus linoleic acid into phosphatidylcholine, but not phosphatidylethanolamine, increased with the uptake rate. Moreover, both arachidonic acid and linoleic acid were preferentially incorporated into the 1-palmitoyl molecular species of phosphatidylcholine and phosphatidylethanolamine at a low uptake rate, and of phosphatidylcholine at a high uptake rate. This could be related to the synthesis of biliary phosphatidylcholine, of which 1-palmitoyl-2-linoleoyl and 1-palmitoyl-2-arachidonoyl are the main molecular species. Linoleic and arachidonic acid were selectively distributed into distinct metabolic pools of triacylglycerol, the intrahepatocyte pool which preferentially incorporated linoleic acid at a low uptake rate and the secreted pool in which the relative enrichment of arachidonic acid increased with the uptake rate. This strengthens the central role of hepatic secretion in the supply of arachidonic acid to peripheral tissues.

The modulation of apolipoprotein E gene expression by 3,3'-5-triiodothyronine in HepG2 cells occurs at transcriptional and post-transcriptional levels.

The regulation of the synthesis and secretion of apolipoprotein E (apoE) is incompletely understood. This study examines the mechanisms responsible for regulating apoE gene expression in HepG2 cells by thyroid hormone (3,3'-5-triiodothyronine). The secretion rate of apoE was by thyroid hormone increased (1.5-1.8-fold) in pulse/chase experiments. Thyroid hormone doubled apoE mRNA concentration as determined by Northern-blot analysis. Inhibition of protein synthesis by cycloheximide increased the thyroid-hormone-induced stimulation of apoE mRNA. This suggests that the synthesis of new protein is not required for thyroid hormone to stimulate apoE mRNA. Actinomycin D was used to inhibit new transcription; there was a more rapid degradation of mature apoE mRNA in thyroid hormone-treated HepG2 cells than in control cells, suggesting that thyroid hormone acts post-transcriptionally to regulate apoE gene expression. Cycloheximide blocked the action of thyroid hormone, suggesting that thyroid hormone regulates the turnover of apoE mRNA via the synthesis of de novo protein. Nuclear run-on transcription assays demonstrated that thyroid hormone stimulated apoE gene transcription threefold in 24 h. These findings indicate that the expression of the apoE gene is controlled at both transcriptional and post-transcriptional loci by the thyroid hormone.

Permissive role of n-6 polyunsaturated fatty acids on carbohydrate oxidation in human infant skin fibroblasts: one possible mechanism of their intervention on coronary heart disease and diabetes.

UNLABELLED: Many publications indicate the beneficial effect of n-6 polyunsaturated fatty acids (n-6 PUFAs) in the control of coronary heart disease and diabetes, although the mechanism is not clear. Some of our previous results suggest that, in contrast to other lipids, n-6 PUFAs could have a permissive effect on carbohydrate oxidation. To check this hypothesis, we determined pyruvate dehydrogenase (PDH, decarboxylase: EC 1.2.4.1) activity in infant skin fibroblasts (ISF) incubated 6 hours in the presence of 0.25 mM linoleic (LI) or arachidonic (AR) acid, compared to oleic acid (OL) and control ISF incubated without addition of fatty acids. The four groups of cells were preincubated 36 hours either in the presence of fetal bovine serum (FBS), or in the presence of lipoprotein-deprived serum (LPDS). RESULTS: (1) When the ISF were maintained in the medium containing FBS, the two PUFAs had little inhibitory effect on PDH activity, in contrast with the effect of OL. (2) When the ISF were kept in the lipoprotein-deficient medium, PDH activity was low in controls and in the OL cells, but the addition of LI or AR increased the activity. This suggests the role of n-6 PUFAs in enhancing carbohydrate oxidation, under certain conditions.