Analytic Strategies and Cognitive Task Design to Study Neuropsychiatric Disorder

Longenecker等人（2010年）研究了精神分裂症患者和健康对照者的工作清单回忆机制。我们的小组使用加州语言学习测验（CVLT），一个广泛使用的神经心理学词汇表学习任务，检查回忆策略。CVLT列表由16个词组成，包括4个语义类别-香料，工具，水果和衣服-每个类别包含4个词。该清单是口头提出的，然后由受试者自由回忆。 以前有报道说，受试者谁记得最多的话采用语义技术，而不是穷人回忆科目谁一般使用串行技术。 在这项研究中，我们开发了新的措施，独立于回忆的表现，比较不同试验的策略，并确定是否诊断预测回忆策略。 最近的一项研究表明，精神分裂症患者在言语和视觉学习任务中表现不佳，但他们未受影响的兄弟姐妹仅在言语学习方面表现不佳，这表明言语处理可能代表认知表型。使用CVLT检查言语记忆障碍的性质表明，策略预测患者的表现。由于精神分裂症患者有广泛的缺陷，评估的情景言语记忆任务，我们使用的主题与言语障碍，以检查机制的策略，在自由列表回忆。CVLT的表现是使用第一次和第五次试验中回忆的单词，两次试验之间的改善以及所有五次试验的整体回忆来衡量的。记忆策略采用语义和串行聚类得分进行了分析。语义聚类被定义为一个接一个地回忆类别相似的词，而序列聚类被定义为根据呈现顺序顺序的词的顺序回忆。新的措施召回和转移概率计算和分析排列测试。我们的受试者是根据CVLT在五项试验中的表现选择的。从评估的450名受试者数据中，测试样本包括健康对照组（n=100）和精神分裂症患者（n =100）中50名最高和50名最低表现者。 结果：我们预测绩效水平将成为战略诊断的一个指标。同样，在先前报道的文献中，我们预计CVLT评分可以预测性能水平，而不考虑组。一般来说，回忆起最多单词的人使用语义聚类技术，而那些回忆不好的人使用序列技术。这在健康对照CVLT第五次试验中显示，其中使用语义聚类技术回忆起的单词数量最多。患者的回忆模式和策略与对照组相似，表现水平相似，无论诊断如何。 低绩效者更有可能回忆起列表中的前两个和最后四个单词，而高绩效者在所有五次试验中都增加了基于语义的过渡的参与，而低绩效者则没有。 检查我们的CVLT数据显示，高性能，患者和对照组，采用串行和语义策略。 这些策略似乎随着尝试学习而改变。因为这些信息没有被捕获的CVLT标准评分方法，我们开发了一种不同的方法来分析回忆，考虑到同时回忆策略，在学习过程中的性能变化。这种方法提供了一个框架，重新审视两个潜在的认知机制，言语回忆不佳，但也由功能性大脑网络和遗传功能多态性决定的神经生物学。 使用这个工具，我们可以了解疾病和基因对言语回忆过程的调节的个体差异。此外，我们开发了一种新的方法来计算策略，通过数据驱动的方法计算所有学习试验中回忆顺序之间的相似性，在自由回忆的单词列表。 这种方法通过计算每个可能的词对的概率而不是每次试验的概率或所有五次试验的平均值来提供更具体的信息。我们的方法评估个别单词的影响，以及预定类别和词序的相互作用。 这种方法的另一个好处是，它可以修改，以调整其他措施，如语义激活通过回忆不相邻的话或效果回忆顺序。 结论：我们开发的新方法使用标准CVLT分析公式识别并解决了问题。召回和转移概率的措施表明，在自由召回的列表中，召回的单词数量是预测的策略，语义策略导致了更高数量的单词召回。 我们还发现，高绩效的患者依赖于语义策略，这表明语义混乱可能不是精神分裂症患者的特征。总之，认知策略必须考虑独立的整体性能归因于退化的学习过程之前，表现不佳。 我们的研究结果表明，偏离公认的，广泛使用的评分技术的重要性，特别是在临床人群中的精神分裂症患者的情节记忆缺陷是一个特征。 此外，这种新的方法可以应用于其他单词列表范例和临床人群，并具有探索特定的词与词的关系以及它们如何影响口头回忆策略的敏感性。

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.