Behavioral and Brain Functions

Recent advances have led to an understanding that the hippocampus is involved more broadly than explicit or declarative memory alone. Tasks which involve the acquisition of complex associations involve the hippocampus whether the learning is explicit or implicit. One hippocampal-dependent implicit task is transitive inference (TI). Recently it was suggested that implicit transitive inference does not depend upon the hippocampus (Frank, M. J., O'Reilly, R. C., & Curran, T. 2006. When memory fails, intuition reigns: midazolam enhances implicit inference in humans. Psychological Science, 17, 700–707). The authors demonstrated that intravenous midazolam, which is thought to inactivate the hippocampus, may enhance TI performance. Three critical assumptions are required but not met: 1) that deactivations of other regions could not account for the effect 2) that intravenous midazolam does indeed deactivate the hippocampus and 3) that midazolam influences explicit but not implicit memory. Each of these assumptions is seriously flawed. Consequently, the suggestion that implicit TI does not depend upon the hippocampus is unfounded. Introduction The capacity to learn complex stimulus relations and express them flexibly is thought to require the hippocampus [1]. While the hippocampus has been thought to be necessary for explicit but not implicit forms of learning and memory [2], more recent studies demonstrate hippocampal involvement in implicit tasks which require complex associations [3-8]. One task which involves both the acquisition of complex relations, flexible expression and which may be learned implicitly is the transitive inference task [8-13]. At study, participants learn complex relations among stimuli (e.g., A>B, B>C, C>D, D>E) and at test, they show flexible expression when an untrained discrimination (B? D) is correctly solved (B>D). Functional imaging studies confirm the role of the hippocampus in both implicit and explicit versions of TI [8,14-16] and, amnesic patients with damage to the hippocampus and surrounding tissue cannot perform the TI task [17]. A recent study demonstrated that the administration of intravenous midazolam improved TI performance in human participants [18] which was argued as evidence that TI is performed more easily when the hippocampus does not contribute explicit strategies. The authors argue that midazolam deactivates the hippocampus because benzodiazepines act on GABA-A receptors [19], which are densely concentrated in the hippocampus [20], and because benzodiazepines – in particular midazolam – temporarily impair explicit memory formation [21]. The assertion that intravenous midazolam improves TI performance by deactivating the hippocampus depends entirely upon three premises: 1) that other areas critical to TI are not affected, so that only hippocampal deactivation Published: 24 September 2007 Behavioral and Brain Functions 2007, 3:51 doi:10.1186/1744-9081-3-51 Received: 5 June 2007 Accepted: 24 September 2007 This article is available from: http://www.behavioralandbrainfunctions. com/content/3/1/51 © 2007 Greene; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.