The Procrustes-based perturbation model (Goodall in J R Stat Soc Ser B Methodol 53(2):285–321, 19... more The Procrustes-based perturbation model (Goodall in J R Stat Soc Ser B Methodol 53(2):285–321, 1991) allows minimization of the Frobenius distance between matrices by similarity transformation. However, it suffers from non-identifiability, critical interpretation of the transformed matrices, and inapplicability in high-dimensional data. We provide an extension of the perturbation model focused on the high-dimensional data framework, called the ProMises (Procrustes von Mises–Fisher) model. The ill-posed and interpretability problems are solved by imposing a proper prior distribution for the orthogonal matrix parameter (i.e., the von Mises–Fisher distribution) which is a conjugate prior, resulting in a fast estimation process. Furthermore, we present the Efficient ProMises model for the high-dimensional framework, useful in neuroimaging, where the problem has much more than three dimensions. We found a great improvement in functional magnetic resonance imaging connectivity analysis be...
Journal of Statistical Computation and Simulation, 2020
Permutation testing in linear models, where the number of nuisance coefficients is smaller than t... more Permutation testing in linear models, where the number of nuisance coefficients is smaller than the sample size, is a well-studied topic. The common approach of such tests is to permute residuals after regressing on the nuisance covariates. Permutation-based tests are valuable in particular because they can be highly robust to violations of the standard linear model, such as non-normality and heteroscedasticity. Moreover, in some cases they can be combined with existing, powerful permutation-based multiple testing methods. Here, we propose permutation tests for models where the number of nuisance coefficients exceeds the sample size. The performance of the novel tests is investigated with simulations. In a wide range of simulation scenarios our proposed permutation methods provided appropriate type I error rate control, unlike some competing tests, while having good power.
Impulsivity has been proposed as an endophenotype for bipolar disorder (BD); moreover, impulsivit... more Impulsivity has been proposed as an endophenotype for bipolar disorder (BD); moreover, impulsivity levels have been shown to carry prognostic significance and to be quality-of-life predictors. To date, reports about the genetic determinants of impulsivity in mood disorders are limited, with no studies on BD individuals. Individuals with BD and healthy controls (HC) were recruited in the context of an observational, multisite study (GECOBIP). Subjects were genotyped for three candidate single-nucleotide polymorphisms (SNPs) (5-HTTLPR, COMT rs4680, BDNF rs6265); impulsivity was measured through the Italian version of the Barratt Impulsiveness Scale (BIS-11). A mixed-effects regression model was built, with BIS scores as dependent variables, genotypes of the three polymorphisms as fixed effects, and centers of enrollment as random effect. Compared to HC, scores for all BIS factors were higher among subjects with euthymic BD (adjusted β for Total BIS score: 5.35, p < 0.001). No signi...
The recent finding that Broca’s area, the motor center for speech, is activated during action obs... more The recent finding that Broca’s area, the motor center for speech, is activated during action observation lends support to the idea that human language may have evolved from neural substrates already involved in gesture recognition. Although fascinating, this hypothesis can be questioned because while observing actions of others we may evoke some internal, verbal description of the observed scene. Here we present fMRI evidence that the involvement of Broca’s area during action observation is genuine. Observation of meaningful hand shadows resembling moving animals induces a bilateral activation of frontal language areas. This activation survives the subtraction of activation by semantically equivalent stimuli, as well as by meaningless hand movements. Our results demonstrate that Broca’s area plays a role in interpreting actions of others. It might act as a motor-assembly system, which links and interprets motor sequences for both speech and hand gestures.
This study investigated early adolescents’ psychophysiological response to a school-related stres... more This study investigated early adolescents’ psychophysiological response to a school-related stressor (SRS) as indexed by heart rate variability and examined the unique and interactive effects of heart rate variability and temperament on academic achievement. A total of 91 seventh graders watched an SRS video-clip while their heart rate variability was registered. Temperament and grades were also assessed. Heart rate variability decreased from baseline while watching the video-clip, indicating the activation of a stress response, and returned to basal level when recovering. Regression analyses revealed that among youth with an inhibited temperament, higher heart rate variability in the poststressor phase was related to better performance, whereas socially outgoing students performed well regardless of their recovery rate. These are among the first data to report on the link between early adolescents’ parasympathetic self-regulatory activity in response to an SRS, temperamental profil...
To evaluate the efficacy of fluoxetine alone and fluoxetine+lidocaine ointment in the same patien... more To evaluate the efficacy of fluoxetine alone and fluoxetine+lidocaine ointment in the same patient group with premature ejaculation (PE). 78 patients with PE were given 20 mg fluoxetine by an 'as-needed treatment' 4 h before planned sexual activity for a period of 3 months. They were then told to add local lidocaine ointment to fluoxetine 30 min before sexual activity for an additional 3 months for most of their sexual attempts. They were asked to note their PE grades and intravaginal ejaculatory latency time (IELT) scores by stopwatch technique before and after each treatment modality; the results were compared statistically afterwards. Of 46 patients who completed the study, the mean pretreatment, fluoxetine alone and fluoxetine+lidocaine ointment treatment PE grades and IELT scores were found to be 6.52+/-1.42 and 2.58+/-0.49, 3.21+/-1.86 and 1.28+/-0.71, 2.17+/-1.56 and 1.04+/-0.72, respectively, showing a decrease in PE grades and IELT scores in combined therapy. On an ...
A new approach for multiplicity control (Optimal Subset) is presented. It is based on the selecti... more A new approach for multiplicity control (Optimal Subset) is presented. It is based on the selection of the best subset of partial (univariate) hypotheses which, when combined, produce the minimal p-value. The second step consists in multiplicity adjustment. In this work we show how to perform this new procedure in the permutation framework, choosing adequate combining functions and permutation strategies. The optimal subset approach can be very useful in exploratory studies because it performs a weak control for multiplicity which can be a valid alternative to the classic False Discovery Rate (FDR). A comparative simulation study and application to neuroimaging real data shows it is particularly useful in exploratory studies and when there is a high number of hypotheses. We also show how stepwise regression may be a special case of Optimal Subset procedures and how to adjust the p-value of the selected model taking into account the multiplicity arising from the various possible mode...
Sum-based global tests are highly popular in multiple hypothesis testing. In this paper we propos... more Sum-based global tests are highly popular in multiple hypothesis testing. In this paper we propose a general closed testing procedure for sum tests, which provides confidence lower bounds for the proportion of true discoveries (TDP), simultaneously over all subsets of hypotheses. Our method allows for an exploratory approach, as simultaneity ensures control of the TDP even when the subset of interest is selected post hoc. It adapts to the unknown joint distribution of the data through permutation testing. Any sum test may be employed, depending on the desired power properties. We present an iterative shortcut for the closed testing procedure, based on the branch and bound algorithm, which converges to the full closed testing results, often after few iterations. Even if it is stopped early, it controls the TDP. The feasibility of the method for high dimensional data is illustrated on brain imaging data. We compare the properties of different choices for the sum test through simulatio...
The Procrustes-based perturbation model (Goodall in J R Stat Soc Ser B Methodol 53(2):285–321, 19... more The Procrustes-based perturbation model (Goodall in J R Stat Soc Ser B Methodol 53(2):285–321, 1991) allows minimization of the Frobenius distance between matrices by similarity transformation. However, it suffers from non-identifiability, critical interpretation of the transformed matrices, and inapplicability in high-dimensional data. We provide an extension of the perturbation model focused on the high-dimensional data framework, called the ProMises (Procrustes von Mises–Fisher) model. The ill-posed and interpretability problems are solved by imposing a proper prior distribution for the orthogonal matrix parameter (i.e., the von Mises–Fisher distribution) which is a conjugate prior, resulting in a fast estimation process. Furthermore, we present the Efficient ProMises model for the high-dimensional framework, useful in neuroimaging, where the problem has much more than three dimensions. We found a great improvement in functional magnetic resonance imaging connectivity analysis be...
Journal of Statistical Computation and Simulation, 2020
Permutation testing in linear models, where the number of nuisance coefficients is smaller than t... more Permutation testing in linear models, where the number of nuisance coefficients is smaller than the sample size, is a well-studied topic. The common approach of such tests is to permute residuals after regressing on the nuisance covariates. Permutation-based tests are valuable in particular because they can be highly robust to violations of the standard linear model, such as non-normality and heteroscedasticity. Moreover, in some cases they can be combined with existing, powerful permutation-based multiple testing methods. Here, we propose permutation tests for models where the number of nuisance coefficients exceeds the sample size. The performance of the novel tests is investigated with simulations. In a wide range of simulation scenarios our proposed permutation methods provided appropriate type I error rate control, unlike some competing tests, while having good power.
Impulsivity has been proposed as an endophenotype for bipolar disorder (BD); moreover, impulsivit... more Impulsivity has been proposed as an endophenotype for bipolar disorder (BD); moreover, impulsivity levels have been shown to carry prognostic significance and to be quality-of-life predictors. To date, reports about the genetic determinants of impulsivity in mood disorders are limited, with no studies on BD individuals. Individuals with BD and healthy controls (HC) were recruited in the context of an observational, multisite study (GECOBIP). Subjects were genotyped for three candidate single-nucleotide polymorphisms (SNPs) (5-HTTLPR, COMT rs4680, BDNF rs6265); impulsivity was measured through the Italian version of the Barratt Impulsiveness Scale (BIS-11). A mixed-effects regression model was built, with BIS scores as dependent variables, genotypes of the three polymorphisms as fixed effects, and centers of enrollment as random effect. Compared to HC, scores for all BIS factors were higher among subjects with euthymic BD (adjusted β for Total BIS score: 5.35, p < 0.001). No signi...
The recent finding that Broca’s area, the motor center for speech, is activated during action obs... more The recent finding that Broca’s area, the motor center for speech, is activated during action observation lends support to the idea that human language may have evolved from neural substrates already involved in gesture recognition. Although fascinating, this hypothesis can be questioned because while observing actions of others we may evoke some internal, verbal description of the observed scene. Here we present fMRI evidence that the involvement of Broca’s area during action observation is genuine. Observation of meaningful hand shadows resembling moving animals induces a bilateral activation of frontal language areas. This activation survives the subtraction of activation by semantically equivalent stimuli, as well as by meaningless hand movements. Our results demonstrate that Broca’s area plays a role in interpreting actions of others. It might act as a motor-assembly system, which links and interprets motor sequences for both speech and hand gestures.
This study investigated early adolescents’ psychophysiological response to a school-related stres... more This study investigated early adolescents’ psychophysiological response to a school-related stressor (SRS) as indexed by heart rate variability and examined the unique and interactive effects of heart rate variability and temperament on academic achievement. A total of 91 seventh graders watched an SRS video-clip while their heart rate variability was registered. Temperament and grades were also assessed. Heart rate variability decreased from baseline while watching the video-clip, indicating the activation of a stress response, and returned to basal level when recovering. Regression analyses revealed that among youth with an inhibited temperament, higher heart rate variability in the poststressor phase was related to better performance, whereas socially outgoing students performed well regardless of their recovery rate. These are among the first data to report on the link between early adolescents’ parasympathetic self-regulatory activity in response to an SRS, temperamental profil...
To evaluate the efficacy of fluoxetine alone and fluoxetine+lidocaine ointment in the same patien... more To evaluate the efficacy of fluoxetine alone and fluoxetine+lidocaine ointment in the same patient group with premature ejaculation (PE). 78 patients with PE were given 20 mg fluoxetine by an 'as-needed treatment' 4 h before planned sexual activity for a period of 3 months. They were then told to add local lidocaine ointment to fluoxetine 30 min before sexual activity for an additional 3 months for most of their sexual attempts. They were asked to note their PE grades and intravaginal ejaculatory latency time (IELT) scores by stopwatch technique before and after each treatment modality; the results were compared statistically afterwards. Of 46 patients who completed the study, the mean pretreatment, fluoxetine alone and fluoxetine+lidocaine ointment treatment PE grades and IELT scores were found to be 6.52+/-1.42 and 2.58+/-0.49, 3.21+/-1.86 and 1.28+/-0.71, 2.17+/-1.56 and 1.04+/-0.72, respectively, showing a decrease in PE grades and IELT scores in combined therapy. On an ...
A new approach for multiplicity control (Optimal Subset) is presented. It is based on the selecti... more A new approach for multiplicity control (Optimal Subset) is presented. It is based on the selection of the best subset of partial (univariate) hypotheses which, when combined, produce the minimal p-value. The second step consists in multiplicity adjustment. In this work we show how to perform this new procedure in the permutation framework, choosing adequate combining functions and permutation strategies. The optimal subset approach can be very useful in exploratory studies because it performs a weak control for multiplicity which can be a valid alternative to the classic False Discovery Rate (FDR). A comparative simulation study and application to neuroimaging real data shows it is particularly useful in exploratory studies and when there is a high number of hypotheses. We also show how stepwise regression may be a special case of Optimal Subset procedures and how to adjust the p-value of the selected model taking into account the multiplicity arising from the various possible mode...
Sum-based global tests are highly popular in multiple hypothesis testing. In this paper we propos... more Sum-based global tests are highly popular in multiple hypothesis testing. In this paper we propose a general closed testing procedure for sum tests, which provides confidence lower bounds for the proportion of true discoveries (TDP), simultaneously over all subsets of hypotheses. Our method allows for an exploratory approach, as simultaneity ensures control of the TDP even when the subset of interest is selected post hoc. It adapts to the unknown joint distribution of the data through permutation testing. Any sum test may be employed, depending on the desired power properties. We present an iterative shortcut for the closed testing procedure, based on the branch and bound algorithm, which converges to the full closed testing results, often after few iterations. Even if it is stopped early, it controls the TDP. The feasibility of the method for high dimensional data is illustrated on brain imaging data. We compare the properties of different choices for the sum test through simulatio...
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