Data_Sheet_1_Functional topologies of spatial cognition predict cognitive and motor progression in Parkinson’s.pdf

BackgroundSpatial cognition deteriorates in Parkinson’s disease (PD), but the neural substrates are not understood, despite the risk for future dementia. It is also unclear whether deteriorating spatial cognition relates to changes in other cognitive domains or contributes to motor dysfunction.
ObjectiveThis study aimed to identify functional connectivity abnormalities in cognitively normal PD (PDCN) in regions that support spatial cognition to determine their relationship to interfacing cognitive functions and motor disability, and to determine if they predict cognitive and motor progression 2 years later in a PDCN subsample.
MethodsSixty-three PDCN and 43 controls underwent functional MRI while judging whether pictures, rotated at various angles, depicted the left or right hand. The task activates systems that respond to increases in rotation angle, a proxy for visuospatial difficulty. Angle-modulated functional connectivity was analyzed for frontal cortex, posterior cortex, and basal ganglia regions.
ResultsTwo aberrant connectivity patterns were found in PDCN, which were condensed into principal components that characterized the strength and topology of angle-modulated connectivity. One topology related to a marked failure to amplify frontal, posterior, and basal ganglia connectivity with other brain areas as visuospatial demands increased, unlike the control group (control features). Another topology related to functional reorganization whereby regional connectivity was strengthened with brain areas not recruited by the control group (PDCN features). Functional topologies correlated with diverse cognitive domains at baseline, underscoring their influences on spatial cognition. In PDCN, expression of topologies that were control features predicted greater cognitive progression longitudinally, suggesting inefficient communications within circuitry normally recruited to handle spatial demands. Conversely, stronger expression of topologies that were PDCN features predicted less longitudinal cognitive decline, suggesting functional reorganization was compensatory. Parieto-occipital topologies (control features) had different prognostic implications for longitudinal changes in motor disability. Expression of one topology predicted less motor decline, whereas expression of another predicted increased postural instability and gait disturbance (PIGD) feature severity. Concurrently, greater longitudinal decline in spatial cognition predicted greater motor and PIGD feature progression, suggesting deterioration in shared substrates.
ConclusionThese novel discoveries elucidate functional mechanisms of visuospatial cognition in PDCN, which foreshadow future cognitive and motor disability.

【背景】帕金森病（Parkinson’s disease, PD）患者的空间认知能力会出现衰退，但目前尚不明确其神经机制，尽管该群体存在未来罹患痴呆的风险。同时，空间认知衰退是否与其他认知域的变化相关，或是会导致运动功能障碍，这一点也尚未明确。
【研究目的】本研究旨在识别认知正常的帕金森病（cognitively normal PD, PDCN）患者中支持空间认知的脑区的功能连接异常，以明确这些异常与其他认知功能及运动功能障碍的关联；同时在PDCN亚组中，探究这些异常能否预测2年后的认知与运动功能进展情况。
【研究方法】本研究纳入63名PDCN患者与43名健康对照受试者，所有受试者在进行判断任务时接受功能磁共振成像（functional MRI, fMRI）扫描：任务内容为判断不同旋转角度的手部图片呈现的是左手还是右手。该任务可激活随旋转角度增加而响应增强的脑网络，以此作为视空间任务难度的替代指标。本研究针对额叶皮层、后叶皮层以及基底神经节区域，分析了受旋转角度调控的功能连接模式。
【研究结果】本研究在PDCN患者中发现了两种异常的功能连接模式，并将其整合为表征受角度调控的功能连接的强度与拓扑结构的主成分。第一种拓扑模式表现为：随着视空间任务需求增加，PDCN患者无法像健康对照组那样增强额叶、后叶皮层与基底神经节同其他脑区的连接强度（该模式被称为对照特征）。第二种拓扑模式则与功能重组相关：PDCN患者的脑区与健康对照组未激活的脑区之间的连接强度得到增强（该模式被称为PDCN特征）。在基线时，这些功能拓扑模式与多种认知域相关，进一步证实了其对空间认知的影响。在PDCN患者中，对照特征的表达强度越高，预示着纵向随访中认知功能进展程度越严重，这提示正常用于处理视空间需求的脑环路内存在低效的信息传递。反之，PDCN特征的表达强度越高，则预示着纵向随访中的认知衰退程度越轻，提示这种功能重组具有代偿作用。顶枕叶拓扑模式（对照特征）对运动功能障碍的纵向变化具有不同的预后意义：其中一种拓扑模式的高表达预示着运动衰退程度更轻，而另一种拓扑模式的高表达则预示着姿势不稳与步态障碍（postural instability and gait disturbance, PIGD）特征的严重程度更高。同时，空间认知的纵向衰退程度越显著，预示着运动功能与PIGD特征的进展程度越高，这提示二者存在共同的受损底物。
【结论】本研究的全新发现阐明了PDCN患者视空间认知的功能机制，该机制可预示患者未来出现认知与运动功能障碍的风险。