Bootstrapped Permutation Test for Multiresponse Inference on Brain Behavior Associations

Ng, Bernard; Poline, Jean Baptiste; Thirion, Bertrand; Greicius, Michael D.

doi:10.1007/978-3-319-19992-4_9

Cited by 2 publications

(2 citation statements)

References 22 publications

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“…However, given limited number of subjects the learned classifier weights would have high variance. To identify the more stable discriminative features, we recently proposed a procedure that incorporates bootstrapping into permutation testing ( Ng et al, 2015 , Ng et al, 2016 ). Details of this procedure are presented in the Supplementary materials.…”

Section: Methodsmentioning

confidence: 99%

“…To address these important clinical questions, we employed a novel covariance projection approach ( Ng et al, 2016 ) to resting state fMRI data, in combination with a bootstrapped permutation test ( Ng et al, 2015 ), and identified specific connections that best discriminate Parkinson's disease participants ON versus OFF dopaminergic medications (Parkinson's medication-state), and Parkinson's disease versus age-matched healthy control (HC) participants (Parkinson's disease-state). To then identify connections specifically related to tremor or to bradykinesia/rigidity, we correlated symptom severity with the significant connections driving the above classifications in an independent cohort of Parkinson's disease participants.…”

Section: Introductionmentioning

confidence: 99%

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Distinct alterations in Parkinson's medication-state and disease-state connectivity

Varoquaux

Poline

et al. 2017

NeuroImage: Clinical

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Altered brain connectivity has been described in people with Parkinson's disease and in response to dopaminergic medications. However, it is unclear whether dopaminergic medications primarily ‘normalize’ disease related connectivity changes or if they induce unique alterations in brain connectivity. Further, it is unclear how these disease- and medication-associated changes in brain connectivity relate differently to specific motor manifestations of disease, such as bradykinesia/rigidity and tremor. In this study, we applied a novel covariance projection approach in combination with a bootstrapped permutation test to resting state functional MRI data from 57 Parkinson's disease and 20 healthy control participants to determine the Parkinson's medication-state and disease-state connectivity changes associated with different motor manifestations of disease. First, we identified brain connections that best classified Parkinson's disease ON versus OFF dopamine and Parkinson's disease versus healthy controls, achieving 96.9 ± 5.9% and 72.7 ± 12.4% classification accuracy, respectively. Second, we investigated the connections that significantly contribute to the classifications. We found that the connections greater in Parkinson's disease OFF compared to ON dopamine are primarily between motor (cerebellum and putamen) and posterior cortical regions, such as the posterior cingulate cortex. By contrast, connections that are greater in ON compared to OFF dopamine are between the right and left medial prefrontal cortex. We also identified the connections that are greater in healthy control compared to Parkinson's disease and found the most significant connections are associated with primary motor regions, such as the striatum and the supplementary motor area. Notably, these are different connections than those identified in Parkinson's disease OFF compared to ON. Third, we determined which of the Parkinson's medication-state and disease-state connections are associated with the severity of different motor symptoms. We found two connections correlate with both bradykinesia/rigidity severity and tremor severity, whereas four connections correlate with only bradykinesia/rigidity severity, and five connections correlate with only tremor severity. Connections that correlate with only tremor severity are anchored by the cerebellum and the supplemental motor area, but only those connections that include the supplemental motor area predict dopaminergic improvement in tremor. Our results suggest that dopaminergic medications do not simply ‘normalize’ abnormal brain connectivity associated with Parkinson's disease, but rather dopamine drives distinct connectivity changes, only some of which are associated with improved motor symptoms. In addition, the dissociation between of connections related to severity of bradykinesia/rigidity versus tremor highlights the distinct abnormalities in brain circuitry underlying these specific motor symptoms.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Distinct alterations in Parkinson's medication-state and disease-state connectivity

Varoquaux

Poline

et al. 2017

NeuroImage: Clinical

Self Cite

View full text Add to dashboard Cite

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The IMAGEN study: a decade of imaging genetics in adolescents

et al. 2020

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Imaging genetics offers the possibility of detecting associations between genotype and brain structure as well as function, with effect sizes potentially exceeding correlations between genotype and behavior. However, study results are often limited due to small sample sizes and methodological differences, thus reducing the reliability of findings. The IMAGEN cohort with 2000 young adolescents assessed from the age of 14 onwards tries to eliminate some of these limitations by offering a longitudinal approach and sufficient sample size for analyzing gene-environment interactions on brain structure and function. Here, we give a systematic review of IMAGEN publications since the start of the consortium. We then focus on the specific phenotype ‘drug use’ to illustrate the potential of the IMAGEN approach. We describe findings with respect to frontocortical, limbic and striatal brain volume, functional activation elicited by reward anticipation, behavioral inhibition, and affective faces, and their respective associations with drug intake. In addition to describing its strengths, we also discuss limitations of the IMAGEN study. Because of the longitudinal design and related attrition, analyses are underpowered for (epi-) genome-wide approaches due to the limited sample size. Estimating the generalizability of results requires replications in independent samples. However, such densely phenotyped longitudinal studies are still rare and alternative internal cross-validation methods (e.g., leave-one out, split-half) are also warranted. In conclusion, the IMAGEN cohort is a unique, very well characterized longitudinal sample, which helped to elucidate neurobiological mechanisms involved in complex behavior and offers the possibility to further disentangle genotype × phenotype interactions.

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Bootstrapped Permutation Test for Multiresponse Inference on Brain Behavior Associations

Cited by 2 publications

References 22 publications

Distinct alterations in Parkinson's medication-state and disease-state connectivity

Distinct alterations in Parkinson's medication-state and disease-state connectivity

The IMAGEN study: a decade of imaging genetics in adolescents

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