Optimality in multiple comparison procedures

When many (m) null hypotheses are tested with a single dataset, the control of the number of false rejections is often the principal consideration. Two popular controlling rates are the probability of making at least one false discovery (FWER) and the expected fraction of false discoveries among all rejections (FDR). Scaled multiple comparison error rates form a new family that bridges the gap between these two extremes. For example, the Scaled Expected Value (SEV) limits the number of false positives relative to an arbitrary increasing function of the number of rejections, that is, E(FP/s(R)). We discuss the problem of how to choose in practice which procedure to use, with elements of an optimality theory, by considering the number of false rejections FP separately from the number of correct rejections TP. Using this framework we will show how to choose an element in the new family mentioned above.Comment: arXiv admin note: text overlap with arXiv:1112.451

Outcome Prediction of Consciousness Disorders in the Acute Stage Based on a Complementary Motor Behavioural Tool.

Attaining an accurate diagnosis in the acute phase for severely brain-damaged patients presenting Disorders of Consciousness (DOC) is crucial for prognostic validity; such a diagnosis determines further medical management, in terms of therapeutic choices and end-of-life decisions. However, DOC evaluation based on validated scales, such as the Revised Coma Recovery Scale (CRS-R), can lead to an underestimation of consciousness and to frequent misdiagnoses particularly in cases of cognitive motor dissociation due to other aetiologies. The purpose of this study is to determine the clinical signs that lead to a more accurate consciousness assessment allowing more reliable outcome prediction. From the Unit of Acute Neurorehabilitation (University Hospital, Lausanne, Switzerland) between 2011 and 2014, we enrolled 33 DOC patients with a DOC diagnosis according to the CRS-R that had been established within 28 days of brain damage. The first CRS-R assessment established the initial diagnosis of Unresponsive Wakefulness Syndrome (UWS) in 20 patients and a Minimally Consciousness State (MCS) in the remaining13 patients. We clinically evaluated the patients over time using the CRS-R scale and concurrently from the beginning with complementary clinical items of a new observational Motor Behaviour Tool (MBT). Primary endpoint was outcome at unit discharge distinguishing two main classes of patients (DOC patients having emerged from DOC and those remaining in DOC) and 6 subclasses detailing the outcome of UWS and MCS patients, respectively. Based on CRS-R and MBT scores assessed separately and jointly, statistical testing was performed in the acute phase using a non-parametric Mann-Whitney U test; longitudinal CRS-R data were modelled with a Generalized Linear Model. Fifty-five per cent of the UWS patients and 77% of the MCS patients had emerged from DOC. First, statistical prediction of the first CRS-R scores did not permit outcome differentiation between classes; longitudinal regression modelling of the CRS-R data identified distinct outcome evolution, but not earlier than 19 days. Second, the MBT yielded a significant outcome predictability in the acute phase (p<0.02, sensitivity>0.81). Third, a statistical comparison of the CRS-R subscales weighted by MBT became significantly predictive for DOC outcome (p<0.02). The association of MBT and CRS-R scoring improves significantly the evaluation of consciousness and the predictability of outcome in the acute phase. Subtle motor behaviour assessment provides accurate insight into the amount and the content of consciousness even in the case of cognitive motor dissociation

Resting-State Connectivity of the Left Frontal Cortex to the Default Mode and Dorsal Attention Network Supports Reserve in Mild Cognitive Impairment

Reserve refers to the phenomenon of relatively preserved cognition in disproportion to the extent of neuropathology, e.g., in Alzheimer’s disease. A putative functional neural substrate underlying reserve is global functional connectivity of the left lateral frontal cortex (LFC, Brodmann Area 6/44). Resting-state fMRI-assessed global LFC-connectivity is associated with protective factors (education) and better maintenance of memory in mild cognitive impairment (MCI). Since the LFC is a hub of the fronto-parietal control network that regulates the activity of other networks, the question arises whether LFC-connectivity to specific networks rather than the whole-brain may underlie reserve. We assessed resting-state fMRI in 24 MCI and 16 healthy controls (HC) and in an independent validation sample (23 MCI/32 HC). Seed-based LFC-connectivity to seven major resting-state networks (i.e., fronto-parietal, limbic, dorsal-attention, somatomotor, default-mode, ventral-attention, visual) was computed, reserve was quantified as residualized memory performance after accounting for age and hippocampal atrophy. In both samples of MCI, LFC-activity was anti-correlated with the default-mode network (DMN), but positively correlated with the dorsal-attention network (DAN). Greater education predicted stronger LFC-DMN-connectivity (anti-correlation) and LFC-DAN-connectivity. Stronger LFC-DMN and LFC-DAN-connectivity each predicted higher reserve, consistently in both MCI samples. No associations were detected for LFC-connectivity to other networks. These novel results extend our previous findings on global functional connectivity of the LFC, showing that LFC-connectivity specifically to the DAN and DMN, two core memory networks, enhances reserve in the memory domain in MCI

Structural Brain Connectivity in School-Age Preterm Infants Provides Evidence for Impaired Networks Relevant for Higher Order Cognitive Skills and Social Cognition

Extreme prematurity and pregnancy conditions leading to intrauterine growth restriction (IUGR) affect thousands of newborns every year and increase their risk for poor higher order cognitive and social skills at school age. However, little is known about the brain structural basis of these disabilities. To compare the structural integrity of neural circuits between prematurely born controls and children born extreme preterm (EP) or with IUGR at school age, long-ranging and short-ranging connections were noninvasively mapped across cortical hemispheres by connection matrices derived from diffusion tensor tractography. Brain connectivity was modeled along fiber bundles connecting 83 brain regions by a weighted characterization of structural connectivity (SC). EP and IUGR subjects, when compared with controls, had decreased fractional anisotropy-weighted SC (FAw-SC) of cortico-basal ganglia-thalamo-cortical loop connections while cortico-cortical association connections showed both decreased and increased FAw-SC. FAw-SC strength of these connections was associated with poorer socio-cognitive performance in both EP and IUGR childre

Traces Of Human Functional Activity: Moment-To-Moment Fluctuations In Fmri Data

Dynamic functional connectivity (dFC) measured by functional magnetic resonance imaging (fMRI) shows evidence of large-scale networks with highly dynamic (re) configurations. We propose a novel approach to extract traces of human brain function by the construction of a trajectory in a meaningful low-dimensional space. This allows studying dFC in more detail and identify possible meaningful brain states from the moment-to-moment fluctuations of the brain signals during resting state or naturalistic conditions such as passive movie watching. Specifically, we explored dynamic organization of sub-networks derived from the time-dependent graph Laplacian in combination with Riemannian manifold distance to measure dissimilarity over time of dFC and to subsequently build the trajectory of brain activity. As a proof-of-principle, we show results for an fMRI dataset containing both rest and movie epochs in 15 healthy participants. The movie condition varied (i.e., fearful, joyful, and neutral movie excerpts) and clearly influenced the subsequent resting-state period in terms of FC brain state

Structural Correlates of Personality Dimensions in Healthy Aging and MCI

The revised NEO Personality Inventory (NEOPI-R), popularly known as the five-factor model, defines five personality factors: Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness. The structural correlates of these personality factors are still a matter of debate. In this work, we examine the impact of subtle cognitive deficits on structural substrates of personality in the elderly using DTI derived white matter (WM) integrity measure, Fractional Anisotropy (FA). We employed canonical correlation analysis (CCA) to study the relationship between personality factors of the NEOPI-R and FA measures in two population groups: healthy controls and MCI. Agreeableness was the only personality factor to be associated with FA patterns in both groups. Openness was significantly related to FA data in the MCI group and the inverse was true for Conscientiousness. Furthermore, we generated saliency maps using bootstrapping strategy which revealed a larger number of positive correlations in healthy aging in contrast to the MCI status. The MCI group was found to be associated with a predominance of negative correlations indicating that higher Agreeableness and Openness scores were mostly related to lower FA values in interhemispheric and cortico-spinal tracts and a limited number of higher FA values in cortico-cortical and cortico-subcortical connection. Altogether these findings support the idea that WM microstructure may represent a valid correlate of personality dimensions and also indicate that the presence of early cognitive deficits led to substantial changes in the associations between WM integrity and personality factors

Quantitative Analysis of Myelin and Axonal Remodeling in the Uninjured Motor Network After Stroke

Objectives: Contralesional brain connectivity plasticity was previously reported after stroke. This study aims at disentangling the biological mechanisms underlying connectivity plasticity in the uninjured motor network after an ischemic lesion. In particular, we measured generalized fractional anisotropy (GFA) and magnetization transfer ratio (MTR) to assess whether post-stroke connectivity remodeling depend on axonal and/or myelin changes. Materials and Methods: Diffusion Spectrum Imaging (DSI) and Magnetization Transfer MRI at 3T were performed in 10 patients in acute phase, at one and six months after stroke, which was affecting motor cortical and/or subcortical areas. Ten age- and gender- matched healthy volunteers were scanned one month apart for longitudinal comparison. Clinical assessment was also performed in patients prior to MRI. In the contra-lesional hemisphere, average measures and tract-based quantitative analysis of GFA and MTR was performed to assess axonal integrity and myelination along motor connections as well as their variations in time. Results and Conclusions: Mean and tract-based measures of MTR and GFA showed significant changes in a number of contralesional motor connections, confirming both axonal and myelin plasticity in our cohort of patients. Moreover, density-derived features (peak height, standard deviation-SD and skewness) of GFA and MTR along the tracts showed additional correlation with clinical scores than mean values. These findings reveal the interplay between contralateral myelin and axonal remodeling after stroke

Structural Brain Connectivity in School-Age Preterm Infants Provides Evidence for Impaired Networks Relevant for Higher Order Cognitive Skills and Social Cognition.

Extreme prematurity and pregnancy conditions leading to intrauterine growth restriction (IUGR) affect thousands of newborns every year and increase their risk for poor higher order cognitive and social skills at school age. However, little is known about the brain structural basis of these disabilities. To compare the structural integrity of neural circuits between prematurely born controls and children born extreme preterm (EP) or with IUGR at school age, long-ranging and short-ranging connections were noninvasively mapped across cortical hemispheres by connection matrices derived from diffusion tensor tractography. Brain connectivity was modeled along fiber bundles connecting 83 brain regions by a weighted characterization of structural connectivity (SC). EP and IUGR subjects, when compared with controls, had decreased fractional anisotropy-weighted SC (FAw-SC) of cortico-basal ganglia-thalamo-cortical loop connections while cortico-cortical association connections showed both decreased and increased FAw-SC. FAw-SC strength of these connections was associated with poorer socio-cognitive performance in both EP and IUGR children