Domain-Specific Inhibitory Control Training to Improve Children's Learning of Counterintuitive Concepts in Mathematics and Science.

Evidence from cognitive neuroscience suggests that learning counterintuitive concepts in mathematics and science requires inhibitory control (IC). This prevents interference from misleading perceptual cues and naïve theories children have built from their experiences of the world. Here, we (1) investigate associations between IC, counterintuitive reasoning, and academic achievement and (2) evaluate a classroom-based computerised intervention, called Stop & Think, designed to embed IC training within the learning domain (i.e. mathematics and science content from the school curricula). Cross-sectional analyses of data from 627 children in Years 3 and 5 (7- to 10-year-olds) demonstrated that IC, measured on a Stroop-like task, was associated with counterintuitive reasoning and mathematics and science achievement. A subsample (n = 456) participated either in Stop & Think as a whole-class activity (teacher-led, STT) or using individual computers (pupil-led, STP), or had teaching as usual (TAU). For Year 3 children (but not Year 5), Stop & Think led to better counterintuitive reasoning (i.e. near transfer) in STT (p < .001, ηp 2 = .067) and STP (p < .01, ηp 2 = .041) compared to TAU. Achievement data was not available for Year 3 STP or Year 5 STT. For Year 3, STT led to better science achievement (i.e. far transfer) compared to TAU (p < .05, ηp 2 = .077). There was no transfer to the Stroop-like measure of IC. Overall, these findings support the idea that IC may contribute to counterintuitive reasoning and mathematics and science achievement. Further, we provide preliminary evidence of a domain-specific IC intervention with transferable benefits to academic achievement for Year 3 children.

Acamprosate, MK-801, and ifenprodil inhibit neurotoxicity and calcium entry induced by ethanol withdrawal in organotypic slice cultures from neonatal rat hippocampus.

BACKGROUND: The antirelapse drug acamprosate has previously been reported to inhibit activating effects of polyamines on -methyl-D-aspartic acid receptor (NMDAR) function. Because increased synthesis of polyamines has been suggested as a mechanism for potentiation of NMDAR function during ethanol withdrawal, we evaluated the effects of acamprosate, MK-801, and ifenprodil in a cell culture model of ethanol withdrawal-induced neurotoxicity. METHODS: Organotypic hippocampal cultures from 8-day-old neonatal rats were maintained in vitro for 23 days before experimental use. The ethanol withdrawal model consisted of exposing cultures to ethanol (70-100 mM) for 4 days before being "withdrawn" into Calcium-Locke's buffer for 1 hr and then into minimal medium for 23 hr. Uptake of (45)CaCl(2) and propidium iodide by damaged cells was assessed 1 hr and 24 hr after the start of ethanol withdrawal, respectively. Additional studies examined effects of exposure to NMDA (50 microM) or spermidine (100 microM) on withdrawal-induced hippocampal damage. Last, these studies examined the ability of the sodium salt of acamprosate (Na-acamprosate, 200 microM), ifenprodil (50 microM), or MK-801 (30 microM) to inhibit neurotoxicity and (45)Ca(2+) entry produced by these insults. RESULTS: Ethanol withdrawal was associated with significantly greater toxicity and (45)Ca(2+) entry, relative to controls. Exposure to spermidine and NMDA during ethanol withdrawal further increased neurotoxicity and (45)Ca(2+) entry. Acamprosate, ifenprodil, and MK-801 almost completely prevented ethanol withdrawal-induced toxicity and (45)Ca(2+) entry. Acamprosate also reduced spermidine-induced neurotoxicity during ethanol withdrawal but was ineffective against NMDA-induced toxicity or (45)Ca(2+) entry at this time. CONCLUSIONS: The results support the contention that acamprosate, like ifenprodil, interacts with polyamines and that these compounds may be effective in reducing consequences of ethanol withdrawal. NMDAR activation is also strongly implicated in ethanol withdrawal neurotoxicity, but whether acamprosate causes any of these effects in this preparation directly via the NMDAR remains uncertain.

Acamprosate has no effect on NMDA-induced toxicity but reduces toxicity induced by spermidine or by changing the medium in organotypic hippocampal slice cultures from rat.

BACKGROUND: It has been suggested that the antirelapse drug acamprosate can inhibit or potentiate glutamate/NMDA receptor-mediated responses via a polyamine site. Additionally, subchronic exposure to acamprosate increases expression of some NMDA receptor subunits. These effects on NMDA receptors imply that the drug may have neurotoxic or neuroprotective actions under different conditions, and these studies were undertaken to evaluate this possibility in hippocampal neuronal cultures. METHODS: Organotypic hippocampal cultures from 8-day-old neonatal rats were maintained in medium for 28 days. The effects of acamprosate (100 microM) alone or on neurotoxic challenges induced by either 50 microM NMDA or 100 microM spermidine were studied. Neurotoxicity was assessed by uptake of propidium iodide 24 hr after challenge. Calcium entry was measured by uptake of 45Ca2+ into the culture during the challenge. RESULTS: Acamprosate produced no neurotoxicity in these cultures after acute or subchronic exposure. In contrast, the presence of acamprosate significantly reduced "basal" propidium iodide uptake caused by the medium change procedure; similar effects were obtained with dizocilpine (MK-801; 30 microM) and, to a lesser extent, with ifenprodil (50 microM). Acamprosate did not significantly potentiate or inhibit NMDA-induced neurotoxicity, but the presence of acamprosate significantly reduced spermidine-induced neurotoxicity. CONCLUSION: No evidence was obtained that the putative agonist or coagonist effects of acamprosate on the NMDA receptor are able to cause neurotoxicity. Similarly, no evidence for inhibitory effects of acamprosate on NMDA-induced toxicity was observed under any of these conditions. However, acamprosate significantly inhibited the toxicity associated with changing medium and the toxicity induced by spermidine in these hippocampal cultures. The mechanism is unknown but is compatible with previously reported inhibition of polyamine-mediated effects.