1 Rush University Medical Center, Department of Neurological Sciences, Chicago, IL, USA.
Brain. 2014 Mar;137(Pt 3):849-59. doi: 10.1093/brain/awt360. Epub 2014 Jan 29.
Visual hallucinations are frequent, disabling complications of advanced Parkinson's disease, but their neuroanatomical basis is incompletely understood. Previous structural brain magnetic resonance imaging studies suggest volume loss in the mesial temporal lobe and limbic regions in subjects with Parkinson's disease with visual hallucinations, relative to those without visual hallucinations. However, these studies have not always controlled for the presence of cognitive impairment or dementia, which are common co-morbidities of hallucinations in Parkinson's disease and whose neuroanatomical substrates may involve mesial temporal lobe and limbic regions. Therefore, we used structural magnetic resonance imaging to examine grey matter atrophy patterns associated with visual hallucinations, comparing Parkinson's disease hallucinators to Parkinson's disease non-hallucinators of comparable cognitive function. We studied 50 subjects with Parkinson's disease: 25 classified as current and chronic visual hallucinators and 25 as non-hallucinators, who were matched for cognitive status (demented or non-demented) and age (± 3 years). Subjects underwent (i) clinical evaluations; and (ii) brain MRI scans analysed using whole-brain voxel-based morphometry techniques. Clinically, the Parkinson's disease hallucinators did not differ in their cognitive classification or performance in any of the five assessed cognitive domains, compared with the non-hallucinators. The Parkinson's disease groups also did not differ significantly in age, motor severity, medication use or duration of disease. On imaging analyses, the hallucinators, all of whom experienced visual hallucinations, exhibited grey matter atrophy with significant voxel-wise differences in the cuneus, lingual and fusiform gyri, middle occipital lobe, inferior parietal lobule, and also cingulate, paracentral, and precentral gyri, compared with the non-hallucinators. Grey matter atrophy in the hallucinators occurred predominantly in brain regions responsible for processing visuoperceptual information including the ventral 'what' and dorsal 'where' pathways, which are important in object and facial recognition and identification of spatial locations of objects, respectively. Furthermore, the structural brain changes seen on magnetic resonance imaging occurred independently of cognitive function and age. Our findings suggest that when hallucinators and non-hallucinators are similar in their cognitive performance, the neural networks involving visuoperceptual pathways, rather than the mesial temporal lobe regions, distinctively contribute to the pathophysiology of visual hallucinations and may explain their predominantly visual nature in Parkinson's disease. Identification of distinct structural MRI differences associated with hallucinations in Parkinson's disease may permit earlier detection of at-risk patients and ultimately, development of therapies specifically targeting hallucinations and visuoperceptive functions.
视觉幻觉是帕金森病晚期常见且使人丧失能力的并发症，但它的神经解剖学基础尚未完全了解。先前的结构脑磁共振成像研究表明，与没有视觉幻觉的帕金森病患者相比，有视觉幻觉的帕金森病患者的内侧颞叶和边缘区域存在体积损失。然而，这些研究并未始终控制认知障碍或痴呆的存在，而这些是帕金森病幻觉的常见合并症，其神经解剖学基础可能涉及内侧颞叶和边缘区域。因此，我们使用结构磁共振成像来检查与视觉幻觉相关的灰质萎缩模式，将帕金森病幻觉者与认知功能相当的帕金森病非幻觉者进行比较。我们研究了 50 名帕金森病患者：25 名被归类为当前和慢性视觉幻觉者，25 名非幻觉者，他们在认知状态（痴呆或非痴呆）和年龄（±3 岁）方面相匹配。受试者接受了（i）临床评估；（ii）使用全脑体素形态计量学技术分析脑 MRI 扫描。临床方面，与非幻觉者相比，帕金森病幻觉者在任何五个评估认知领域的认知分类或表现上均无差异。帕金森病组在年龄、运动严重程度、药物使用或疾病持续时间方面也没有显著差异。在影像学分析中，所有经历过视觉幻觉的幻觉者，与非幻觉者相比，在楔前叶、舌回和梭状回、中枕叶、下顶叶以及扣带回、旁中央回和中央前回的脑区存在灰质萎缩，具有显著的体素差异。幻觉者的灰质萎缩主要发生在负责处理视知觉信息的大脑区域，包括腹侧“什么”和背侧“哪里”通路，它们分别对物体和面部识别以及物体空间位置的识别很重要。此外，磁共振成像上观察到的结构脑变化与认知功能和年龄无关。我们的发现表明，当幻觉者和非幻觉者在认知表现上相似时，涉及视知觉通路的神经网络而非内侧颞叶区域，独特地促成了视觉幻觉的病理生理学，并可能解释了帕金森病中视觉幻觉的主要视觉性质。识别与帕金森病幻觉相关的独特结构 MRI 差异可能允许更早地检测到高危患者，并最终开发专门针对幻觉和视知觉功能的治疗方法。
