What does preferential viewing tell us about the neurobiology of recognition memory?

Abstract

The two tests most widely used in nonhuman primates to assess the neurobiology of recognition memory produce conflicting results. Preferential viewing tests (e.g., visual paired comparison) produce robust impairments following hippocampal lesions, whereas matching tests (e.g., delayed nonmatching-to-sample) often show complete sparing. Here, we review the data, the proposed explanations for this discrepancy, and then critically evaluate those explanations. The most likely explanation is that preferential viewing tests are not a process-pure assessment of recognition memory, but also test elements of novelty-seeking, habituation, and motivation. These confounds likely explain the conflicting results. Thus, we propose that memory researchers should prefer explicit matching tests and readers interested in the neural substrates of recognition memory should give explicit matching tests greater interpretive weight.

Keywords: amnesia; delayed nonmatch to sample; hippocampus; novel object recognition; rhesus macaque; visual paired comparison.

Figure 1.. Two common tests of recognition memory: Visual Paired Comparison (VPC) and Delayed Nonmatching-to-Sample (DNMS).

Although the two tests are both commonly used, the last two decades have seen VPC become the dominant paradigm. a) VPC involves minimal training, does not make reward contingent on memory accuracy, and relies on subjects’ preexisting preference to look at novel items. The schematic illustrates the idea of VPC as implemented in a nonhuman primate experiment. In this trial, the monkey sees a yellow triangle during the first free-viewing period, sometimes called familiarization. After the memory delay, the monkey is shown the familiar image and a novel image. If the subject preferentially looks at the novel green heart during the second free-viewing period, sometimes called test, researchers infer that it must remember the yellow triangle. Some variants use two test periods to counterbalance the location of the novel image. Preferential viewing is interpreted as remembering and indiscriminate viewing is interpreted as forgetting. b) DNMS involves substantial training and makes rewards contingent on memory accuracy. In the trial depicted in the schematic, the monkey interacts with a green cylinder during study. After a memory delay, it is shown the familiar object and a novel object. It has learned through trial and error that displacing novel items will reveal food. Thus, correct choice of the novel item is interpreted as remembering and indiscriminate choice is interpreted as forgetting. The logic of delayed matching-to-sample (DMS) is similar, but the monkey has been trained that food at test is under the object seen at study. These are example trials and variants exist of each test.

Figure 2.. When directly compared within the same subjects, hippocampal damage produces profound recognition impairments when measured with VPC but usually leaves recognition spared when measured with DNMS.

Performance on VPC (left column) and DNMS (right column) in (A) monkeys with selective, excitotoxic lesions [20], (B) monkeys with radiofrequency lesions [3], (C) monkeys with aspiration lesions [21], and (D) a human amnesic patient with robustly spared explicit recognition [23]. Solid black lines represent performance of control subjects and colored dashed lines refer to subjects with brain damage. Shaded regions indicate ± SEM.