Results of nonhuman animal research can provide new information that human experimentation does not permit, usually for ethical considerations or because of limited control over complex environmental and genetic influences. The new knowledge can then be used to help understand human disorders. One approach to understanding inter-species brain functions, comparative neuropsychology, involves the direct evaluation of human clinical populations by employing experimental paradigms originally developed for nonhuman animals (Oscar-Berman & Bardenhagen, 1998). Over many decades of animal research, the paradigms were perfected to study the effects of well-defined brain lesions on specific behaviors, and later the tasks were modified for human use. Generally the modifications involve changing the reward from food to money, but standard administration of the tasks in humans still involves minimal instructions, thus necessitating a degree of procedural learning in human and nonhuman animals alike. Currently, comparative neuropsychological paradigms are often used with neurological patients to link specific deficits with localized areas of neuropathology (Fuster, 1997; Oscar-Berman & Bardenhagen, 1998).
The comparative neuropsychological approach employs simple tasks that can be mastered without relying upon language skills. Precisely because these simple paradigms do not require linguistic strategies for solution, they are especially useful for working with patients whose language skills are compromised or whose cognitive skills may be minimal. Comparative neuropsychology contrasts with the traditional approach of using tasks that rely upon linguistic skills and that were designed to study human cognition
(Lezak, 1995). Because important ambiguities about its heuristic value had not been addressed empirically, only recently has comparative neuropsychology become popular for implementation with brain-damaged patients (e.g., see reviews by Oscar-Berman & Bardenhagen, 1998; Squire, 1992). Within the past decade, it has had prevalent use as a framework for comparing and contrasting the performances of disparate neurobehavioral populations on similar tasks.
Although many paradigms have been employed, two popular tasks are classical delayed-reaction tests such as delayed response (DR) and delayed alternation (DA). Both tasks measure a subject's ability to bridge a time gap (see Fuster, 1997). This ability has been termed working memory, which is a transient form of memory. Working memory is multimodal in nature, and it serves to keep newly incoming information available online; it acts much like a mental clipboard for use in problem solving, planning, and the like. In the classical DR task, the experimenter places a small reward into a reinforcement well under one of two identical stimuli. The subject is able to see the experimenter put a reward there but cannot reach it. After the experimenter covers the reinforcement wells with the stimuli, he or she lowers a screen, obscuring the stimulus tray. After a delay period, usually between 0 and 60 seconds, the experimenter raises the screen to allow the subject to make a choice. The subject then pushes one of the stimuli away and, with a correct choice, takes the reward; attentional and spatial memory skills are needed to do this. Some investigators have used automated versions of the tasks in which the cues presented to the subjects are lights or sounds, and the subjects are required to respond, after a delay period, by pressing a key or a lever (Oscar-Berman & Bardenhagen, 1998).
DA shares important features with DR. Both are spatial tasks, and both have a delay between stimulus presentation and the opportunity to make a response. In DA, however, subjects must learn to alternate responding from left to right. On each trial, the side not previously chosen is rewarded, and a brief delay (usually 5 seconds) is interposed between trials. Instead of having to notice and remember the location of a reward placed there by the experimenter (in DR), in DA, subjects must remember the side last chosen and whether or not a reward had been available. Subjects must also learn to inhibit, on each trial, the previously rewarded response (i.e., they must not perseverate with consecutive responses to one side only). Rankings of the performance levels of a wide range of mammals, including children, on delayed-reaction tasks have been reported to parallel the phylogenetic scale.
Comparative neuropsychological tasks such as DR and DA are simple to administer and do not rely on intact language abilities. Both tasks also are sensitive to abnormalities after damage to frontal brain systems. Furthermore, successful performance on DR and DA tasks is known to rely upon different underlying neuroanatomical and neuropsychological mechanisms. Thus, the prefrontal cortex is host to at least two subsystems: dorsolateral and orbitofrontal (on the ventral surface). While the dorso-lateral system contains intimate connections with other neocortical sites, its connections with limbic sites are less striking than the orbitofrontal system's. The dorsolateral system, although important for successful performance on both DR and DA, is especially important for DR performance, in which visuospatial, mnemonic, and attentional functions are considered critical. By contrast, functions involved in response inhibition have been linked more to the orbitofrontal system. With an inability to inhibit unintended responses comes abnormal perseverative responding, a salient characteristic of orbitofrontal damage. The orbitofrontal system is intimately connected with basal forebrain and limbic structures; its connections with other neocortical regions are not as extensive as the dorso-lateral system's. The orbitofrontal system, like the dorso-lateral system, supports successful performance on both DA and DR, but it is especially important for DA performance.
Comparative neuropsychological research has provided a framework that is helpful for understanding memory dysfunction in neurodegenerative disorders. In some neurodegenerative diseases (e.g., Parkinson's disease and progressive supranuclear palsy), patients may have working-memory and attentional impairments resulting from prefrontal system damage. In other disorders (e.g., Kor-sakoff's syndrome and herpes encephalopathy), there are new-learning impairments suggestive of limbic system damage (Oscar-Berman & Bardenhagen, 1998).
Implicit in nonhuman research models of human brain functioning is the assumption of homologous structural-functional relationships among the species (e.g., Milner, 1998; Wasserman, 1993). Research on brain mechanisms that underlie behaviors across species contributes to the discovery of common and divergent principles of brain-behavior relationships.
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