schizophrenia

Cannabis disrupts synchronized brain activity

November, 2011

Effects of a cannabis-like drug on rats explain why cannabis is linked to schizophrenia and how it might impair cognition, as well as supporting our understanding of how working memory works.

Research into the effects of cannabis on cognition has produced inconsistent results. Much may depend on extent of usage, timing, and perhaps (this is speculation) genetic differences. But marijuana abuse is common among sufferers of schizophrenia and recent studies have shown that the psychoactive ingredient of marijuana can induce some symptoms of schizophrenia in healthy volunteers.

Now new research helps explain why marijuana is linked to schizophrenia, and why it might have detrimental effects on attention and memory.

In this rat study, a drug that mimics the psychoactive ingredient of marijuana (by activating the cannabinoid receptors) produced significant disruption in brain networks, with brain activity becoming uncoordinated and inaccurate.

In recent years it has become increasingly clear that synchronized brainwaves play a crucial role in information processing — especially that between the hippocampus and prefrontal cortex (see, for example, my reports last month on theta waves improving retrieval and the effect of running on theta and gamma rhythms). Interactions between the hippocampus and prefrontal cortex seem to be involved in working memory functions, and may provide the mechanism for bringing together memory and decision-making during goal-directed behaviors.

Consistent with this, during decision-making on a maze task, hippocampal theta waves and prefrontal gamma waves were impaired, and the theta synchronization between the two was disrupted. These effects correlated with impaired performance on the maze task.

These findings are consistent with earlier findings that drugs that activate the cannabinoid receptors disrupt the theta rhythm in the hippocampus and impair spatial working memory. This experiment extends that result to coordinated brainwaves beyond the hippocampus.

Similar neural activity is observed in schizophrenia patients, as well as in healthy carriers of a genetic risk variant.

The findings add to the evidence that working memory processes involve coordination between the prefrontal cortex and the hippocampus through theta rhythm synchronization. The findings are consistent with the idea that items are encoded and indexed along the phase of the theta wave into episodic representations and transferred from the hippocampus to the neocortex as a theta phase code. By disrupting that code, cannabis makes it more difficult to retain and index the information relevant to the task at hand.

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Link between brain acid and cognition offers hope for an effective ‘smart’ pill

September, 2010

Experiments with mice have found that inhibiting the production of kynurenic acid in the brain has dramatic benefits for cognitive performance.

Commercial use is a long way off, but research with mice offers hope for a ‘smart drug’ that doesn’t have the sort of nasty side-effects that, for example, amphetamines have. The mice, genetically engineered to produce dramatically less (70%) kynurenic acid, had markedly better cognitive abilities. The acid, unusually, is produced not in neurons but in glia, and abnormally high levels are produced in the brains of people with disorders such as schizophrenia, Alzheimer's and Huntington's. More acid is also typically produced as we get older.

The acid is produced in our brains after we’ve eaten food containing the amino acid tryptophan, which helps us produce serotonin (turkey is a food well-known for its high tryptophan levels). But serotonin helps us feel good (low serotonin levels are linked to depression), so the trick is to block the production of kynurenic acid without reducing the levels of serotonin. The next step is therefore to find a chemical that blocks production of the acid in the glia, and can safely be used in humans. Although no human tests have yet been performed, several major pharmaceutical companies are believed to be following up on this research.

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