Synopsis

Keywords: Parkinson's Disease, fMRI (resting state)

It’s unclear whether abnormal neural information stored and different temporal feature at different stages in Parkinson’s disease (PD). Here, we estimated the intrinsic timescales using the magnitude of the autocorrelation of intrinsic neural signals by resting state functional magnetic resonance imaging data in 74 PD patients, including 44 patients in the early stage and 30 patients in the late stage. Our findings suggest that PD patients exhibit abnormal intrinsic timescales in visual, sensorimotor, and cognitive systems, and at different stages, distinct patterns of intrinsic timescales in cerebral cortex, which might provide new insights for the neural substrate of PD.

Background or Purpose

Specialization and hierarchy are organizing principles for primate cortex, and cortical areas are also specialized in the temporal domain. The neural timescale in a local brain area reflects the function of that area in many trials of a task^1,2 or even in the absence of direct stimulus processing^3,4. Moreover, the intrinsic neural timescales at resting state could predict the neural activity of the brain region in a task^5-7, and the sensory and prefrontal areas exhibit shorter and longer timescales at resting state, respectively³. Parkinson’s disease (PD) is a progressive neurological disorder characterized by motor (tremor, rigidity, and slowness of movements and abnormal sensorimotor integration)^8,9 and nonmotor (visual dysfunction and cognitive impairment)^10-13 symptoms. Resting state fMRI studies also showed abnormal neural activity or functional connection in motor^14-17 and nonmotor^18-21 areas. However, whether abnormal neural information stored in sensorimotor, visual, and cognitive-related areas was also unclear. Because PD is a progressive neurodegenerative disease^22,23, we also explored the differences of intrinsic timescales among patients with PD in the early stage (PD-ES) and the late stage (PD-LS) and healthy controls (HC).

Methods

The present study estimated the intrinsic timescales by using the magnitude of the autocorrelation of intrinsic neural signals in 74 PD patients. PD patients were assessed the severity of motor symptoms and cognitive impairments by using the unified Parkinson's disease rating scale (UPDRS), a revised severity classification Hoehn and Yahr (HY) scale, Montreal cognitive assessment (MoCA), and mini-mental state examination (MMSE). Based on HY scale, 74 patients with PD were split into 44 patients with PD-ES (the scores of the HY scale were ≤2) and 30 patients with PD-LS (the scores of the HY scale were >2). To investigate the correlations among abnormal intrinsic timescale, symptom severity, age, and structural images, we calculated the Spearman rank correlation coefficients for clinical measures, age, and grey matter volume (GMV) with significant results between groups.

Results

We identified that the PD group had shorter intrinsic timescales in the bilateral lingual gyri, bilateral postcentral gyri, and right middle cingulum gyrus, and longer timescale in the right middle frontal gyrus compared with the HC group (Figure 1). The intrinsic timescale of the bilateral lingual gyri in the PD group negatively correlated with the scores of the HY scale (Figure 2). Moreover, the intrinsic timescales in bilateral lingual gyri, the right postcentral gyrus, and the right middle cingulum gyrus negatively correlated the age of the PD group, respectively (Figure 3, upper). And we found that the age in the PD group negatively correlated with the scores of MoCA and MMSE (Figure 3, lower). We also found positively significant correlation between the intrinsic timescale and the GMV in the right postcentral gyrus (Figure 4). The one-sample ANOVA revealed significant between-group differences in intrinsic timescales of bilateral lingual gyri, the left precuneus, and the right middle cingulum gyrus (Figure 5, upper). Post hoc comparisons using Bonferroni’s test showed that the PD-LS group had shorter timescale in the left precuneus than that in the PD-ES group and shorter timescales in bilateral calcarine and lingual gyri than that in the HC group (Figure 5, lower). Increasingly, longer timescales in the left superior frontal gyrus, the left inferior frontal gyrus, the right middle frontal gyrus were also found in the PD-ES group than the HC group (Figure 5, lower).

Discussion

In this study, we explored the intrinsic timescales, which relates to the functional hierarchy of the brain, in PD patients. Our findings showed abnormal temporal property of local neural activity in the visual, sensorimotor, and cognitive systems in PD, and the previous studies also found it through other neuroimaging methods^24-29. Increasingly, the PD-ES group had longer timescales in the anterior cortical regions, whereas the PD-LS group had shorter timescales in the posterior cortical regions, which might associate with cognitive impairment. The cognitive impairment of the PD-LS group was more severity than that of the PD-ES group. Distinct patterns of local cerebral glucose metabolism were also found in PD with and without mild cognitive impairment (PDNC and PDMCI): the PDNC patients had limited areas of hypometabolism in the frontal and occipital cortices, and the PDMCI patients had extensive areas of hypometabolism in the posterior cortical regions, including the temporo-parieto-occipital junction, medial parietal, and inferior temporal cortices³⁰. Hirano et al.³¹ suggested that the frontal cortex was associated with impulse control disorders and that posterior brain areas were related to cognitive decline in PD. It is reasonable that significant correlations between cognitive impairments and the age were found in PD, because PD is one of the most common age-related neurodegenerative disorders³². Furthermore, our findings suggest that the GMV and intrinsic timescales might be independent and complementary measures for PD.

Conclution

Our findings suggest that PD patients exhibit abnormal intrinsic timescales in visual, sensorimotor, and cognitive systems, which provide new insights for the neural substrate of PD. Distinct patterns of intrinsic timescales between the PD-ES and PD-LS groups also indicate that intrinsic timescale may be a new neuroimaging biomarker across disease stage in PD, which have the potential to improve clinical care and management.

Acknowledgements

This research study was supported by the National Natural Science Foundation of China (81601467, 81871327), Key Scientific Research Projects of Henan Provincial Colleges and Universities (23A320004), Medical Science and Technology Co-construction Project of Henan Province (LHGJ20220404), and Industrial Technology Foundation Public Service Platform Project of China (CEIEC-2020-ZM02-0103/03).

References

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