Conditional associative learning (CAL) tasks involve both planning and learning and therefore rely on executive function (Gotham et al., 1988; Marié et al., 1999). During a conditional associative learning task participants are required to learn the arbitrary associations between several stimuli and responses, by trial-and-error (Petrides, 1985a). Stimuli can be either visual or verbal in nature. According to Levine, Stuss and Milberg (1997) it is important to differentiate conditional associative learning from standard paired-associate paradigms and classical conditional or discrimination learning paradigms. During paired associate learning the correct stimulus pairings are presented together enhancing the strength of the associations. Also, participants are required to only make one response. During conditional or discrimination learning tasks only one stimulus-response pair is reinforced. Responding to other stimuli is reduced through non-reward. On the other hand, in CAL all stimulus-response pairs are reinforced, and participants have to learn a conditional rule, where they have to select a different response for each stimulus (Petrides, 1986).
CAL performance has been found to be sensitive to frontal lobe function. Animal studies of nonhuman primates reported that lesions to the posterior dorsolateral prefrontal cortex (DLPFC) produced CAL performance deficits (Halsband & Passingham, 1982; Halsband & Passingham, 1985; Petrides, 1982; Petrides, 1985b). Also, lesions to the right and left frontal lobes led to CAL impairments in humans (Petrides, 1985a; Petrides, 1990). Studies using functional imaging reported increased cerebral blood flow in the DLPFC, in particular in Brodmann area 8 and the anterior cingulate (Petrides, Alivisatos, Evans & Meyer, 1993) and the cingulate cortex and dorsal premotor area (Mitz et al.,
167 1993). From these findings, it can be suggested that CAL performance relates to frontal lobe function and in particular to the DLPFC and premotor cortex. Furthermore, Toni, Krams, Turner and Passingham (1998) used PET to measure cerebral blood flow while participants performed a visuomotor conditional associative learning task. They reported that learning was related with activity within a network that was distributed throughout the ventral extrastriate and prefrontal cortex and was further associated with the basal ganglia and the parahippocampal gyrus. Later, the same group conducted an fMRI study and used a visuomotor control task in addition to the learning task (Toni, Ramnani, Josephs, Ashburner & Passingham, 2001). The results indicated learning- specific activity within a temporo-prefrontal circuit. Interestingly, they found that supportive activity from the hippocampus, parahippocampus and basal ganglia were dependent on the learning stages/phases. Therefore, during early learning stages there was increased hippocampal and parahippocampal activity, whereas during late learning stages there was increased basal ganglia activity. These findings indicate that hippocampal, parahippocampal regions and the basal ganglia are involved in conditional associative learning.
Research on CAL performance of PD patients is inconsistent. Canavan and colleagues (1989) investigated the effects of early PD on participants’ performance on a variety of learning tasks. They used one visual-motor and another visual-visual CAL task. During the former patients had to learn the associations of six different colours with six different movements using a handle. During the visual-visual task patients had learn the associations between the same six colours and six different shapes. The results indicated no differences in performance for either of the CAL tasks between the PD patients and age-matched healthy controls. However, the authors reported a minority of older patients who did have impaired task performance. On the other hand, research investigating visuospatial CAL in patients with Alzheimer-type dementia and PD reported that PD patients were impaired when performing the task (Sahakian et al., 1988). This study used a task that became increasingly more difficult by increasing the number of stimulus- response pairs (1 to 8 pairs). Also, they included de novo PD patients as well as medicated patients who were in the later stage of the illness. The results indicated that PD patients in both groups required more trials to reach the criterion and had fewer correct trials for
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the 6 and 8 pairs conditions compared to control participants. Lange, Wells, Rossor, Jenner and Marsden (1991) used the same task as Sahakian et al. (1988) did and supported their findings. On the other hand, Gotham and colleagues (1988) tested PD patients on and off medication and reported that patients were impaired on the conditional associative learning task only when they were on medication. Based on these findings they developed the ‘dopamine overdose’ hypothesis, which states that dopaminergic medication results in overstimulation of the ventral striatum which is not dopamine depleted to the same extent as the dorsal striatum in early stages of PD, thus leading to impaired functioning of the limbic and orbitofrontal circuits resulting in cognitive deficits. Another study also used a spatial CAL task and compared the performance of PD patients to that of healthy control participants (Zgaljardic et al., 2007). Their findings indicated that patients produced more errors and required more trials to reach criterion on the task. Therefore, most research suggested that PD patients are impaired on CAL tasks apart from one (Canavan et al., 1989). Nevertheless, even the latter study mentioned that older PD patients did show impaired performance when compared to younger patients or healthy controls. When considering the average age of the patients in the other studies, it may be noted that the patients’ age has an effect on the performance of such tasks. One investigation used a visual CAL task with two different learning instructions (Vriezen & Moscovitch, 1990). Their task included six pairs of numbers (1 to 6) and drawings. In addition to the typical trial-and-error learning instruction that was also implemented by other research studies they also used a feedback learning instruction. For the feedback learning instruction participants were initially told which number was associated with which drawing. The remaining test procedure was the same as for the trial-and-error learning instruction with the difference that when patients selected a wrong drawing, they were told the correct selection i.e. were provided immediate corrective feedback. They used this condition in order to assess whether deficits seen in PD are due to an inability to select the correct response from a number of potential responses or due to impaired trial-and-error learning. Their results suggested that compared to healthy control participants PD patients were only impaired on the trial-and-error learning
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version of the task, from which they further concluded that trial-and-error learning depends on the integrity of the fronto-striatal network.
4.1.2 Conditional Associative Learning and subthalamic nucleus deep brain