18 April 2006. Using magnetic resonance imaging, scientists have peered into the brain to determine what areas are active during tasks that challenge relational memory, which underlies our ability to make associations between different facts or objects. The imaging studies indicate that, under certain conditions, processing in the parietal cortex and a small region of the hippocampus is poorer in schizophrenia patients. Because relational memory is thought to be important for reasoning, deficient activation in these specialized regions may explain why some patients suffer from delusional thinking and compromised cognition.
Deficits in relational memory were very recently documented in schizophrenia patients. Debra Titone of McGill University in Montreal, Canada, and colleagues found that patients have difficulty in a particular aspect of relational memory called transitive inference, which requires subjects to make judgments by extrapolating previously learned information (see Titone et al., 2004). The classic example of transitive inference is the ability to predict that given A is greater than B and B is greater than C, then A is also greater than C. Now, Dost Ongur and colleagues at McLean Hospital in Belmont, Massachusetts, expand that work by examining what areas of the brain are activated during tests of transitive inference. Their findings are reported in the April Archives of General Psychiatry.
Ongur and colleagues tested 20 patients with schizophrenia and 17 normal controls. All subjects were trained with pairs of patterned cards and told that one of the cards was always the “winner,” in other words card A is greater than card B, card B is greater than card C, etc. The patients were shown four overlapping pairs: AB, BC, CD, and DE. Once the volunteers had remembered which card in each pair trumped the other, they were then shown all the pairs again while magnetic resonance images (MRI) were taken. In addition to this basic test, the subjects were also shown new pairings, such as AD, and asked to infer, based on their prior training, which card of the new pair was the likeliest winner.
The researchers found that both control subjects and schizophrenia patients did equally well in the basic test. Schizophrenia patients also did equally well when they had to make an inference, but only provided one member of the new pair was previously seen in the context of always winning or always losing, for example, AD or BE. However, when presented with an ambiguous pair, schizophrenia patients were significantly poorer at deducing which card should win. In the A>B, B>C, C>D and D>E paradigm, an ambiguous pair would be BD, because both B and D have been seen in the context of winning and losing. “If you have seen A only in the context where it always wins then you do not need to know anything ‘flexibly,’ you do not need to figure out how the cards fit into a sequence. Then it’s a lot easier to do this test because all you have to remember is A always wins,” suggested Ongur. It is the flexibility that seems to be problematic for patients with schizophrenia.
The MRI images showed that when presented with the ambiguous BD pair, control subjects showed significantly greater activation of the right parietal cortex and the left anterior hippocampus than did the schizophrenia patients. Functional MRI analysis, which measured blood flow, confirmed these regional differences. Control subjects had significantly greater blood flow in these areas when they were challenged with the BD “hard inference” task.
While the hippocampus is well-known for being involved in processing and consolidating memory, the parietal cortex is not. However, that the parietal cortex may be required for relational memory and might be deficient in schizophrenia was unexpected though not surprising, commented Ongur. Though this is not a high-profile area in schizophrenia research, it has been discussed in the context of cognitive deficits and has previously been associated with transitive inference in normal controls. It is also required for spatial and numerical processing.
How deficits in relational memory and associated brain areas relate to psychoses is not presently clear, but this kind of memory underlies a lot of reasoning. “Knowing facts about the world and then putting two separate facts together to arrive at a conclusion depends to a large extent on relational memory. And while patients with schizophrenia often have the facts about the world, they can actually arrive at delusional interpretations,” said Ongur.
Relational memory may also be a key component of episodic memory, which is also compromised in schizophrenia patients. Episodic memory, or the ability to recount events or happenings, is most likely structured in relational ways, suggested Ongur. In other words, remembering an event requires putting together an ordered series of happenings; that order depends on relating different segments in the correct sequence.—Tom Fagan.
Ongur D, Cullen TJ, Wolf DH, Rohan M, Barreira P, Zalesak M, Heckers S. The neural basis of relational memory deficits in Schizophrenia. Archives of General Psychiatry, 2006;63:356-365. Abstract