Department of Psychology, University of Wisconsin-Madison, 1202 W. Johnson Street, Madison, WI 53706, USA.
Brain. 2010 Sep;133(9):2714-26. doi: 10.1093/brain/awq209. Epub 2010 Aug 19.
Patients with early-stage Alzheimer's disease exhibit perceptual deficits in odour identification, often before the appearance of overt memory loss. This impairment coincides with the initial accumulation of pathological lesions in limbic olfactory brain regions. Although these data imply that odour stimuli may be effectively used as biological probes of limbic dysfunction, the precise neural mechanisms underlying the olfactory deficits in early Alzheimer's disease remain poorly understood. In the current study, we combined functional magnetic resonance imaging with an olfactory cross-adaptation paradigm to test the hypothesis that perceptual codes of odour quality in posterior piriform cortex are degraded in patients with Alzheimer's disease. In elderly control subjects, sequential presentation of qualitatively similar (versus qualitatively different) odourant pairs elicited cross-adapting responses in posterior piriform cortex, in accord with the pattern observed in healthy young adults. However, this profile was significantly blunted in patients with Alzheimer's disease, reflecting a functional disruption of odour quality coding in this olfactory brain area. These results highlight the potential of olfactory functional magnetic resonance imaging as a non-invasive bioassay of limbic functional integrity, and suggest that such an index could possibly aid in the early diagnosis of Alzheimer's disease. Furthermore, as a putative lesion model of odour quality processing in the human brain, our study suggests a causal role of posterior piriform cortex in differentiating olfactory objects.
早期阿尔茨海默病患者在嗅觉识别方面存在感知缺陷，这种缺陷通常出现在明显记忆丧失之前。这种损害与边缘嗅觉脑区中病理损伤的最初积累相吻合。尽管这些数据表明气味刺激可能有效地用作边缘功能障碍的生物探针，但早期阿尔茨海默病患者嗅觉缺陷的确切神经机制仍知之甚少。在目前的研究中，我们结合功能磁共振成像和嗅觉交叉适应范式，检验了这样一个假设，即后梨状皮层中气味质量的感知代码在阿尔茨海默病患者中退化。在老年对照组中，顺序呈现质量相似（而非质量不同）的气味对会在后梨状皮层中引起交叉适应反应，与健康年轻成年人观察到的模式一致。然而，在阿尔茨海默病患者中，这种模式明显减弱，反映出该嗅觉脑区中气味质量编码的功能中断。这些结果突出了嗅觉功能磁共振成像作为非侵入性生物检测边缘功能完整性的潜力，并表明这种指数可能有助于阿尔茨海默病的早期诊断。此外，作为人类大脑中气味质量处理的假定病变模型，我们的研究表明后梨状皮层在后区分嗅觉物体方面起着因果作用。
