Analytic Strategies and Cognitive Task Design to Study Neuropsychiatric Disorder

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Longenecker, et al 2010 investigated mechanisms underlying work list recall in patients with schizophrenia and healthy controls. Our group used the California Verbal Learning Test (CVLT), a widely used neuropsychological word list learning task, to examine recall strategies. The CVLT list consist of 16 words comprised of 4 semantic categories -spices, tools, fruits and clothes- each containing 4 words. The list were presented orally then freely recalled by the subject. It has been previously reported that subjects who recall the most words employ semantic techniques, as opposed to poor recall subjects who generally use serial techniques. In this study, we developed novel measures, independent of recall performance to compare strategies across trials and identify whether diagnosis predicts recall strategy. A recent study showed that patients with schizophrenia performed poorly on verbal and visual learning tasks, but their unaffected sibling showed poor performance only on measures of verbal learning, which suggest that verbal processing may represent a cognitive phenotype. Examining the nature of verbal memory impairment using the CVLT showed that strategy predicted performance of patients. Since patients with schizophrenia have a wide range of deficits, as assessed by episodic verbal memory tasks, we used subjects with verbal impairments to examine mechanisms of strategies used during free list recall. CVLT performance was measured using the words recalled from the first and fifth trials, the improvement between the two trials, and overall recall across all five trials. Mnemonic strategies employed were assayed using semantic and serial clustering scores. Semantic clustering was defined as recall of categorically similar words, one after another, and serial clustering was defined as sequential recall of words according to order of presentation. Novel measures of recall and transition probability were calculated and analyzed by permutation tests. Our subjects were selected based upon CVLT performance over five trials. From the 450 subject data evaluated, the test sample included 50 highest and 50 lowest performers among healthy controls (n=100) and patients with schizophrenia (n=100). Results: We predicted that performance level would be an indicator of strategy as diagnosis. Likewise, in previously reported literature, we expected CVLT scores would predict performance level regardless of group. Generally, people who recall the most words used the semantic clustering technique, and those who had poor recall employed the serial technique. This was shown in the healthy control CVLT fifth trial where the most number of words were recalled, used the semantic clustering technique. Recall patterns and strategies of patients resembled those from the control group with similar performance levels, regardless of diagnosis. Low performers were more likely to recall the first two and last four words from the list, while high performers increased involvement of semantic-based transition across all five trials, while low performers did not. Examination of our CVLT data showed that high performers, both patients and controls, employed both serial and semantic strategies. The strategies seemed to change with trial learning. Because this information was not captured on the CVLT standard scoring method, we developed a different approach to analyze recall which takes into account simultaneous recall strategies that relate the changes in performance during learning. This approach provides a framework with which to re-examine both the underlying cognitive mechanisms of poor verbal recall, but also the neurobiology as determined by both functional brain networks and genetic functional polymorphisms. Using this tool we may gain understanding of individual differences in modulation of the verbal recall process by both illness and genes. In addition, we developed a novel method to calculate strategy in free recall of word lists via a data-driven approach of computing similarities between recall orders across all learning trials. This approach offers more specific information by calculating probabilities for every possible pair of words rather than for each trial or an average value across all five trials. Our method evaluates the effects of individual words as well as the interaction of predetermined categories and word order. Another benefit of this approach is that it can be modified to adjust for additional measures such as semantic activation through recall of nonadjacent words or effects to recall order. Conclusion: The novel approach we developed identified and addresses issues using the standard CVLT analytic formulas. Recall and transition probability measures showed that in free recall of a list the number of words recalled is predictive of the strategy employed whereby semantic strategy resulted in a higher number of words recalled. We also showed that high performing patients depend on semantic strategies, which suggest that semantic disorganization may not be characteristic of patients with schizophrenia. In summary, cognitive strategy must be considered independently of overall performance before attributing poor performance to degraded learning processes. Our findings have shown the importance of departing from the accepted, widely used scoring techniques, particularly in clinical populations of patients with schizophrenia for whom episodic memory deficits are a characteristic feature. In addition, this novel approach can be applied to other word list paradigms and clinical populations and has the sensitivity to explore specific word-to-word relationships and how they impact verbal recall strategy.