The present findings highlighting activation in the hippocampus to nodal-dependent derived conditional relations (Transitive and Equivalence relations) and activation in the parahippocampus to cross-class Foils is generally consistent with results obtained using serial TI paradigms [3
]. Accordingly, the present findings offer additional support for human hippocampal involvement in maintaining relational structure and flexible memory expression [7
In the serial TI paradigm subjects learn a sequence of overlapping premise pairs (i.e., A > B > C > D > E) and inference (B > D) rests on knowledge of stimulus order. Commonly there is one, sometimes two, tests of inference. While prior investigations have shown hippocampal activation during inference, it remains unclear whether such findings are restricted to conditions involving serial learning. One argument offered against the serial TI paradigm as a test of inference is based on the grounds that it is an associative task with stimuli not falling along a linear dimension and inferences may be a function of a value transfer between and among the S+ and S- stimuli [23
]. The results obtained in the present investigation using the SE paradigm appear to make some headway in clarifying hippocampal involvement in maintaining relational structure and inference. First, it was reassuring to observe hippocampal activation during Transitive relations (A:C) which parallels results reported during TI tests (B > D). But in addition, we also observed hippocampal activation during Equivalence relations (C:A). This finding demonstrates that hippocampal involvement is not dependent upon serial order within TI tasks and also that involvement is independent of the linear A, B, C training we employed. It is informative that Symmetry relations (B:A, C:B) did not elicit hippocampal activation. This finding may clarify that hippocampal activation reported during TI tests does not occur more generally to presentations of novel relations, but rather, activation is restricted to relations with intervening nodal stimuli. Lastly, prior investigations employing the serial TI paradigm have shown hippocampal activation during acquisition [6
], with one study highlighting deactivation after learning was completed [4
]. In contrast, we ensured there was accurate relational responding after training and prior to imaging. Therefore, our findings highlighting hippocampal activation during neuroimaging suggests the region may play a role in maintenance. Whether this is restricted to our use of stimulus classes remains unclear. Nevertheless, given the hypothesis that the hippocampus maintains relational structure, it seems expected that the hippocampus would show involvement after initial acquisition.
The application of SE paradigms holds the promise of opening up many new avenues of research on the role of the hippocampal complex in maintaining relational structure, especially across different sensory modalities. In the Introduction, we provided an example of a clinically based SE intervention used to establish derived relations among visual, auditory and tactile stimuli. There are no barriers we see that would limit the inclusion of taste, texture or odor into a class. This cross-modal feature of the SE paradigm stands in marked contrast with contemporary applications of serial TI paradigms where either necessity or convention dictates the use of stimuli from the same sensory modality. It is also plausible to suggest that while maintaining relational structure the hippocampal complex may play a central role in assigning functional properties to stimuli that are conditionally related. If the hippocampal complex mediates relations among stimuli, then changes in the functional properties of one stimulus would be expected to propagate to other related stimuli via the relational network. Numerous behavioral studies employing extensions of the basic SE paradigm have successfully shown how the function of one stimulus in a class, e.g. A1, may be transferred to other stimuli in the class, such as B1 and C1 [24
]. This process is known as "transfer of function" and illustrates how stimuli may acquire functional properties through the relational network without direct experience. Here is seems important to note that transfer of function occurs to stimuli that are physically dissimilar, consequently, transfer is not simply a matter of stimulus generalization
, which depends upon stimuli sharing physical properties. Relatedly, numerous behavioral studies have also successfully shown how changing the function of one stimulus in a class can change the functional properties of other stimuli in the class [25
]. This process is referred to as "transformation of function" (for a review on transfer and transformation see [26
]). In sum, the results of the present investigation, and probable role of the hippocampal complex in transfer/transformation of stimulus function, underscore the broad functionality of SE based preparations. New applications of the SE methodology promises to extend neuroscience research on medial temporal lobe functioning and higher cognitive functioning, as well as provide new insights into the effectiveness of SE based clinical treatments.