The ability of bilateral medial temporal lobe amnesic patients (MT; n = 8) and normal participants (NC; n = 8) to acquire a conditional discrimination in trace and delay eyeblink conditioning paradigms was investigated. Experiment 1 assessed trace conditional discrimination learning by using a light conditional stimulus (S+/S−) and tone conditioned stimulus (CS) separated by a 1-s trace. NCs responded differentially on S+ trials (mean percent conditioned responses = 66) versus S− trials (30), whereas MTs were impaired in their acquisition of the conditional discrimination (S+ = 51, S− = 43). In Experiment 2, the temporal separation was eliminated. NCs acquired the conditional discrimination (S+ = 70, S− = 29). MTs were unable to respond differentially (S+ = 42, S− = 37). The findings indicate that the hippocampal system is essential in acquiring a conditional discrimination, even in a delay paradigm.The hippocampus and related structures play a crucial role in learning. One type of learning in which the hippocampus has been implicated is the acquisition of a conditional discrimination, a form of complex associative learning involving two conditions of differential reinforcement (Daum, Channon, & Canavan, 1989;Daum Channon, Polkey, & Gray, 1991).Investigations of associative learning in memory-disordered individuals using the eyeblink classical conditioning paradigm have ranged from relatively simple learning tasks, such as simple discrimination learning, to more complex and demanding paradigms, including trace discrimination learning and conditional discrimination learning. Daum, Channon, and Gray (1992) investigated simple two-tone discrimination learning in 16 patients who had undergone right or left unilateral temporal lobe resections as compared with a control group. Temporal lobectomy patients, regardless of laterality, were able to learn a simple two-tone discrimination and then extinguish the response to the same extent as the normal control participants.Correspondence concerning this article should be addressed to Catherine Brawn Fortier, MDRC (151-A), Building 9, VA Boston Healthcare System, 150 South Huntington Avenue, Boston, Massachusetts 02130. E-mail: cbrawn@bu.edu. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript Daum, Breitenstein, Ackermann, and Schugens (1997) later investigated discrimination reversal learning in amnesic patients. Nine amnesic patients (including both hippocampal and diencephalic damage) and 9 matched control participants were tested in both a simple discrimination and a discrimination reversal task. Similar to the control participants, amnesic patients produced a significantly greater number of conditioned responses (CRs) on reinforced trials (conditioned stimulus [CS]+) than on nonrein-forced trials (CS−) during discrimination learning, replicating Daum et al.'s (1992) earlier study. During reversal learning, however, the amnesic patients produced a similar number of CRs during both trial types, whereas the control participants were able to ...

Chronic misuse of alcohol affects an integrated neural circuit supporting the formation of associative memories acquired during eyeblink classical conditioning (R. McGlinchey-Berroth et al., 1995). The authors of this study investigated single-cue trace conditioning in amnesic and nonamnesic abstinent alcoholic individuals who either were or were not trained in a single-cue delay conditioning task. Overall, untrained alcoholic participants were severely impaired in acquisition, and alcoholic participants previously trained in single-cue delay conditioning performed similarly to untrained control participants. Individual performance in acquisition varied significantly within task but was relatively stable between the trace and delay tasks; there were nonamnesic and amnesic alcoholic participants who acquired responses at a normal rate in both delay and trace conditioning. The similarity of performances in delay and trace conditioning suggests a common source of impairment across both tasks.

A number of studies investigating trace eyeblink conditioning have found impaired, but not eliminated, acquisition of conditioned responses (CRs) in both animals and humans with hippocampal removal or damage. The underlying mechanism of this residual learning is unclear. The present study investigated whether the impaired level of learning is the product of residual hippocampal function or whether it is mediated by another memory system that has been shown to function normally in delay eyeblink conditioning. Performance of bilateral medial temporal lobe amnesic patients who had a prior history of participating in eyeblink conditioning studies was compared to a control group with a similar training history and to an untrained control group in a series of single cue trace conditioning tasks with 500 ms, 250 ms, and 0 ms trace intervals. Overall, patients acquired CRs to a level similar to the untrained controls, but were significantly impaired compared to the trained controls. The pattern of acquisition suggests that amnesic patients may be relying on the expression of previously acquired, likely cerebellar based, procedural memory representations in trace conditioning. Keywords associative learning; Pavlovian conditioning; bitemporal amnesiaIt is generally well accepted that normal acquisition of trace eyeblink conditioning requires not only an essential contribution from the cerebellum (R. F. Thompson, 1986Thompson, , 1988 but also from forebrain areas including the hippocampus. In the animal model, for example, Solomon and colleagues (Solomon, Vander Schaaf, Norbe, Weisz, & Thompson, 1986) reported that hippocampal lesions disrupt acquisition of conditioned responses (CRs) during trace conditioning. This finding that was later confirmed by Moyer, Deyo and Disterhoft (1990) who demonstrated that acquisition was eliminated using a 500 ms trace interval (but not a 300 ms trace interval) with rabbits who had relatively complete hippocampectomies. Similarly, our In our original study, we speculated two possible sources of the impaired learning observed in amnesic patients: residual hippocampal function leading to some preserved declarative memory or intact cerebellar function that, when given enough practice, can acquire some level of trace conditioning via procedural learning (McGlinchey-Berroth, Carrillo, Gabrieli, Brawn, & Disterhoft, 1997). The current study is an attempt to distinguish between these two possibilities.Five severely amnesic patients with bilateral hippocampal system damage were tested across three trace intervals: 500 ms, 250 ms, and 0 ms. Given the repeated measures design, an important factor to consider was the possibility of carry-over effects from one interval to the next. This consideration was heightened by the fact that the five patients had participated in other eyeblink conditioning studies as well; three were tested in four prior studies, one in two studies, and one in one prior study. Thus, two control groups were needed, one to control for prior history of eyeblink conditioni...

No abstract