Small P values may not yield robust findings: an example using REST-meta-PD

Jia, Xi Ze; Zhao, Na; Dong, Hao; Sun, Jia; Bartoň, Marek; Burciu, Roxana G.; Carrière, Nicolas; Cerasa, Antonio; Chen, Bo Yu; Chen, Jun; Coombes, Stephen; Defebvre, Luc; Delmaire, Christine; Dujardin, Kathy; Esposito, Fabrizio; Fan, Guoguang; Nardo, Federica Di; Feng, Yi; Fling, Brett W.; Garg, Saurabh; Gilat, Moran; Gorges, Martin; Ho, Shu Leong; Horak, Fay B.; Hu, Xiao; Huang, Biao; Huang, Pei Yu; Jia, Ze Juan; Jones, Christina B.; Kassubek, Jan; Krajcovicova, Lenka; Kurani, Ajay S.; Li, Jing; Li, Qing; Liu, Ai Ping; Liu, Bo; Liu, Hu; Liu, Wei Guo; Lopes, Renaud; Lou, Yu Ting; Luo, Wei; Madhyastha, Tara M.; Mao, Ni Ni; McAlonan, Gráinne; McKeown, Martin J.; Pang, Shirley Y.Y.; Quattrone, Andrea; Rektorová, Irena; Sarica, Alessia; Shang, Huifang; Shine, James M.; Shukla, Priyank; Slavíček, T.; Song, Xiao; Tedeschi, Gioacchino; Tessitore, Alessandro; Vaillancourt, David E.; Wang, Jian; Wang, Jue; Wang, Z. Jane; Wei, Lü; Wu, Xia; Xu, Xiao; Yan, Lei; Yang, Jing; Yang, Wan Qun; Yao, Nai Lin; Zhang, De Long; Zhang, Jiu Quan; Zhang, Min Ming; Zhang, Yan Ling; Zhou, Cai Hong; Yan, Chao‐Gan; Zuo, Xi; Hallett, Mark; Wu, Tao; Zang, Yu

doi:10.1016/j.scib.2021.06.007

Cited by 23 publications

(23 citation statements)

References 16 publications

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“…While the reduction of FC was located in the anterior putamen. The location showing decreased nigral-putamen FC overlapped well with the location of decreased putamen resting state activity as shown in a multicenter meta-analysis study (Jia et al, 2021). In addition, by using dopamine cell implantation surgery, Ma and colleagues (Ma et al, 2010) have shown that the baseline 18 F-DOPA uptake in the dorsal anterior putamen, which locates close to the cluster of our FC finding, can predict UPDRS improvement.…”

Section: Discussionsupporting

confidence: 78%

Modulation effect of substantia nigra iron deposition and functional connectivity on putamen glucose metabolism in Parkinson's disease

Zang

Song

et al. 2022

Human Brain Mapping

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Neurodegeneration of the substantia nigra affects putamen activity in Parkinson's disease (PD), yet in vivo evidence of how the substantia nigra modulates putamen glucose metabolism in humans is missing. We aimed to investigate how substantia nigra modulates the putamen glucose metabolism using a cross‐sectional design. Resting‐state fMRI, susceptibility‐weighted imaging, and [18F]‐fluorodeoxyglucose‐PET (FDG‐PET) data were acquired. Forty‐two PD patients and 25 healthy controls (HCs) were recruited for simultaneous PET/MRI scanning. The main measurements of the current study were R2* images representing iron deposition (28 PD and 25 HCs), standardized uptake value ratio (SUVr) images representing FDG‐uptake (33 PD and 25 HCs), and resting state functional connectivity maps from resting state fMRI (34 PD and 25 HCs). An interaction term based on the general linear model was used to investigate the joint modulation effect of nigral iron deposition and nigral‐putamen functional connectivity on putamen FDG‐uptake. Compared with HCs, we found increased iron deposition in the substantia nigra (p = .007), increased FDG‐uptake in the putamen (left: PFWE < 0.001; right: PFWE < 0.001), and decreased functional connectivity between the substantia nigra and the anterior putamen (left PFWE < 0.001, right: PFWE = 0.007). We then identified significant interaction effect of nigral iron deposition and nigral‐putamen connectivity on FDG‐uptake in the putamen (p = .004). The current study demonstrated joint modulation effect of the substantia nigra iron deposition and nigral‐putamen functional connectivity on putamen glucose metabolic distribution, thereby revealing in vivo pathological mechanism of nigrostriatal neurodegeneration of PD.

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Section: Discussionsupporting

confidence: 78%

Modulation effect of substantia nigra iron deposition and functional connectivity on putamen glucose metabolism in Parkinson's disease

Zang

Song

et al. 2022

Human Brain Mapping

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“…However, recent studies have shown that even if the results are corrected by multiple comparisons, the results of a small sample size are inconsistent. Small P-values may not yield robust findings (Jia et al, 2021). Therefore, we are still working on enrolling participants, and we will further validate the results when the sample size is expanded in the future.…”

Section: Limitationsmentioning

confidence: 94%

Functional Integrity of Executive Control Network Contributed to Retained Executive Abilities in Mild Cognitive Impairment

Wan

Liu

Cheng

et al. 2021

Front. Aging Neurosci.

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Background: Mild cognitive impairment (MCI) is considered to be a transitional state between normal aging and Alzheimer's dementia (AD). Recent studies have indicated that executive function (EF) declines during MCI. However, only a limited number of studies have investigated the neural basis of EF deficits in MCI. Herein, we investigate the changes of regional brain spontaneous activity and functional connectivity (FC) of the executive control network (ECN) between high EF and low EF groups.Methods: According to EF composite score (ADNI-EF) from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we divided MCI into two groups, including the MCI-highEF group and MCI-lowEF group. Resting-state functional MRI was utilized to investigate the fractional amplitude of low-frequency fluctuation (fALFF) and ECN functional connectivity across 23 healthy controls (HC), 11 MCI-highEF, and 14 MCI-lowEF participants. Moreover, a partial correlation analysis was carried out to examine the relationship between altered fALFF or connectivity of the ECN and the ADNI-EF.Results: Compared to HC, the MCI-highEF participants demonstrated increased fALFF in the left superior temporal gyrus (STG), as well as decreased fALFF in the right precentral gyrus, right postcentral gyrus, and left middle frontal gyrus (MFG). The MCI-lowEF participants demonstrated increased fALFF in the cerebellar vermis and decreased fALFF in the left MFG. Additionally, compared to HC, the MCI-highEF participants indicated no significant difference in connectivity of the ECN. Furthermore, the MCI-lowEF participants showed increased ECN FC in the left cuneus and left MFG, as well as decreased ECN functional connectivity in the right parahippocampal gyrus (PHG). Notably, the altered fALFF in the left MFG was positively correlated to ADNI-EF, while the altered fALFF in cerebellar vermis is negatively correlated with ADNI-EF across the two MCI groups and the HC group. Altered ECN functional connectivity in the right PHG is negatively correlated to ADNI-EF, while altered ECN functional connectivity in the left cuneus is negatively correlated to ADNI-EF across the three groups.Conclusions: Our current study demonstrates the presence of different patterns of regional brain spontaneous activity and ECN FC in the MCI-highEF group and MCI-lowEF group. Furthermore, the ECN FC of the MCI-highEF group was not disrupted, which may contribute to retained EF in MCI.

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“…However, it needs to be noted that these partial correlation results were obtained in a low threshold (uncorrected p < 0.05) and no results remained after correction (FDR corrected p < 0.05). We mainly attributed this to the small effect size, which likely led to non-significant results at a strict threshold ( Jia et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Intrinsic Brain Activity Alterations in Patients With Mild Cognitive Impairment-to-Normal Reversion: A Resting-State Functional Magnetic Resonance Imaging Study From Voxel to Whole-Brain Level

Wang

et al. 2022

Front. Aging Neurosci.

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Mild cognitive impairment (MCI) reversion refers to patients with MCI who revert from MCI to a normal cognitive state. Exploring the underlying neuromechanism of MCI reverters may contribute to providing new insights into the pathogenesis of Alzheimer’s disease and developing therapeutic interventions. Information on patients with MCI and healthy controls (HCs) was collected from the Alzheimer’s Disease Neuroimaging Initiative database. We redefined MCI reverters as patients with MCI whose logical memory scores changed from MCI to normal levels using the logical memory criteria. We explored intrinsic brain activity alterations in MCI reverters from voxel, regional, and whole-brain levels by comparing resting-state functional magnetic resonance imaging metrics of the amplitude of low-frequency of fluctuation (ALFF), the fractional amplitude of low-frequency fluctuation (fALFF), percent amplitude of fluctuation (PerAF), regional homogeneity (ReHo), and degree centrality (DC) between MCI reverters and HCs. Finally, partial correlation analyses were conducted between cognitive scale scores and resting-state functional magnetic resonance imaging metrics of brain regions, revealing significant group differences. Thirty-two patients with MCI from the Alzheimer’s Disease Neuroimaging Initiative database were identified as reverters. Thirty-seven age-, sex-, and education-matched healthy individuals were also enrolled. At the voxel level, compared with the HCs, MCI reverters had increased ALFF, fALFF, and PerAF in the frontal gyrus (including the bilateral orbital inferior frontal gyrus and left middle frontal gyrus), increased PerAF in the left fusiform gyrus, and decreased ALFF and fALFF in the right inferior cerebellum. Regarding regional and whole-brain levels, MCI reverters showed increased ReHo in the left fusiform gyrus and right median cingulate and paracingulate gyri; increased DC in the left inferior temporal gyrus and left medial superior frontal; decreased DC in the right inferior cerebellum and bilateral insular gyrus relative to HCs. Furthermore, significant correlations were found between cognitive performance and neuroimaging changes. These findings suggest that MCI reverters show significant intrinsic brain activity changes compared with HCs, potentially related to the cognitive reversion of patients with MCI. These results enhance our understanding of the underlying neuromechanism of MCI reverters and may contribute to further exploration of Alzheimer’s disease.

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Small P values may not yield robust findings: an example using REST-meta-PD

Cited by 23 publications

References 16 publications

Modulation effect of substantia nigra iron deposition and functional connectivity on putamen glucose metabolism in Parkinson's disease

Modulation effect of substantia nigra iron deposition and functional connectivity on putamen glucose metabolism in Parkinson's disease

Functional Integrity of Executive Control Network Contributed to Retained Executive Abilities in Mild Cognitive Impairment

Intrinsic Brain Activity Alterations in Patients With Mild Cognitive Impairment-to-Normal Reversion: A Resting-State Functional Magnetic Resonance Imaging Study From Voxel to Whole-Brain Level

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