Differences in spatiotemporal brain network dynamics of Montessori and traditionally schooled students.

Across development, experience has a strong impact on the way we think and adapt. School experience affects academic and social-emotional outcomes, yet whether differences in pedagogical experience modulate underlying brain network development is still unknown. In this study, we compared the brain network dynamics of students with different pedagogical backgrounds. Specifically, we characterized the diversity and stability of brain activity at rest by combining both resting-state fMRI and diffusion-weighted structural imaging data of 87 4-18 years old students experiencing either the Montessori pedagogy (i.e., student-led, trial-and-error pedagogy) or the traditional pedagogy (i.e., teacher-led, test-based pedagogy). Our results revealed spatiotemporal brain dynamics differences between students as a function of schooling experience at the whole-brain level. Students from Montessori schools showed overall higher functional integration (higher system diversity) and neural stability (lower spatiotemporal diversity) compared to traditionally schooled students. Higher integration was explained mainly through the cerebellar (CBL) functional network. In contrast, higher temporal stability was observed in the ventral attention, dorsal attention, somatomotor, frontoparietal, and CBL functional networks. This study suggests a form of experience-dependent dynamic functional connectivity plasticity, in learning-related networks.

Normative volumes and relaxation times at 3T during brain development.

While research has unveiled and quantified brain markers of abnormal neurodevelopment, clinicians still work with qualitative metrics for MRI brain investigation. The purpose of the current article is to bridge the knowledge gap between case-control cohort studies and individual patient care. Here, we provide a unique dataset of seventy-three 3-to-17 years-old healthy subjects acquired with a 6-minute MRI protocol encompassing T1 and T2 relaxation quantitative sequence that can be readily implemented in the clinical setting; MP2RAGE for T1 mapping and the prototype sequence GRAPPATINI for T2 mapping. White matter and grey matter volumes were automatically quantified. We further provide normative developmental curves based on these two imaging sequences; T1, T2 and volume normative ranges with respect to age were computed, for each ROI of a pediatric brain atlas. This open-source dataset provides normative values allowing to position individual patients acquired with the same protocol on the brain maturation curve and as such provides potentially useful quantitative biomarkers facilitating precise and personalized care.

Pervasive alterations of intra-axonal volume and network organization in young children with a 16p11.2 deletion.

Reciprocal Copy Number Variants (CNVs) at the 16p11.2 locus confer high risk for autism spectrum disorder (ASD) and other neurodevelopmental disorders (NDDs). Morphometric MRI studies have revealed large and pervasive volumetric alterations in carriers of a 16p11.2 deletion. However, the specific neuroanatomical mechanisms underlying such alterations, as well as their developmental trajectory, are still poorly understood. Here we explored differences in microstructural brain connectivity between 24 children carrying a 16p11.2 deletion and 66 typically developing (TD) children between 2 and 8 years of age. We found a large pervasive increase of intra-axonal volume widespread over a high number of white matter tracts. Such microstructural alterations in 16p11.2 deletion children were already present at an early age, and led to significant changes in the global efficiency and integration of brain networks mainly associated to language, motricity and socio-emotional behavior, although the widespread pattern made it unlikely to represent direct functional correlates. Our results shed light on the neuroanatomical basis of the previously reported increase of white matter volume, and align well with analogous evidence of altered axonal diameter and synaptic function in 16p11.2 mice models. We provide evidence of a prevalent mechanistic deviation from typical maturation of brain structural connectivity associated with a specific biological risk to develop ASD. Future work is warranted to determine how this deviation contributes to the emergence of symptoms observed in young children diagnosed with ASD and other NDDs.

Me, Myself, and I: Neural Activity for Self versus Other across Development.

Although adults and children differ in self-vs.-other perception, a developmental perspective on this discriminative ability at the brain level is missing. This study examined neural activation for self-vs.-other in a sample of 39 participants spanning four different age groups, from 4-year-olds to adults. Self-related stimuli elicited higher neural activity within two brain regions related to self-referential thinking, empathy, and social cognition processes. Second, stimuli related to 'others' (i.e., unknown peer) elicited activation within nine additional brain regions. These regions are associated with multisensory processing, somatosensory skills, language, complex visual stimuli, self-awareness, empathy, theory of mind, and social recognition. Overall, activation maps were gradually increasing with age. However, patterns of activity were non-linear within the medial cingulate cortex for 'self' stimuli and within the left middle temporal gyrus for 'other' stimuli in 7-10-year-old participants. In both cases, there were no self-vs.-other differences. It suggests a critical period where the perception of self and others are similarly processed. Furthermore, 11-19-year-old participants showed no differences between others and self within the left inferior orbital gyrus, suggesting less distinction between self and others in social learning. Understanding the neural bases of self-vs.-other discrimination during development can offer valuable insights into how social contexts can influence learning processes during development, such as when to introduce peer-to-peer teaching or group learning.

Hi-Fi fMRI: High-resolution, fast-sampled and sub-second whole-brain functional MRI at 3T in humans.

Functional magnetic resonance imaging (fMRI) is a methodological cornerstone of neuroscience. Most studies measure blood-oxygen-level-dependent (BOLD) signal using echo-planar imaging (EPI), Cartesian sampling, and image reconstruction with a one-to-one correspondence between the number of acquired volumes and reconstructed images. However, EPI schemes are subject to trade-offs between spatial and temporal resolutions. We overcome these limitations by measuring BOLD with a gradient recalled echo (GRE) with 3D radial-spiral phyllotaxis trajectory at a high sampling rate (28.24ms) on standard 3T field-strength. The framework enables the reconstruction of 3D signal time courses with whole-brain coverage at simultaneously higher spatial (1mm 3 ) and temporal (up to 250ms) resolutions, as compared to optimized EPI schemes. Additionally, artifacts are corrected before image reconstruction; the desired temporal resolution is chosen after scanning and without assumptions on the shape of the hemodynamic response. By showing activation in the calcarine sulcus of 20 participants performing an ON-OFF visual paradigm, we demonstrate the reliability of our method for cognitive neuroscience research.

Creative thinking and brain network development in schoolchildren.

Fostering creative minds has always been a premise to ensure adaptation to new challenges of human civilization. While some alternative educational settings (i.e., Montessori) were shown to nurture creative skills, it is unknown how they impact underlying brain mechanisms across the school years. This study assessed creative thinking and resting-state functional connectivity via fMRI in 75 children (4-18 y.o.) enrolled either in Montessori or traditional schools. We found that pedagogy significantly influenced creative performance and underlying brain networks. Replicating past work, Montessori-schooled children showed higher scores on creative thinking tests. Using static functional connectivity analysis, we found that Montessori-schooled children showed decreased within-network functional connectivity of the salience network. Moreover, using dynamic functional connectivity, we found that traditionally-schooled children spent more time in a brain state characterized by high intra-default mode network connectivity. These findings suggest that pedagogy may influence brain networks relevant to creative thinking-particularly the default and salience networks. Further research is needed, like a longitudinal study, to verify these results given the implications for educational practitioners. A video abstract of this article can be viewed at https://www.youtube.com/watch?v=xWV_5o8wB5g . RESEARCH HIGHLIGHTS: Most executive jobs are prospected to be obsolete within several decades, so creative skills are seen as essential for the near future. School experience has been shown to play a role in creativity development, however, the underlying brain mechanisms remained under-investigated yet. Seventy-five 4-18 years-old children, from Montessori or traditional schools, performed a creativity task at the behavioral level, and a 6-min resting-state MR scan. We uniquely report preliminary evidence for the impact of pedagogy on functional brain networks.

Virtual reality-based sensorimotor adaptation shapes subsequent spontaneous and naturalistic stimulus-driven brain activity.

Our everyday life summons numerous novel sensorimotor experiences, to which our brain needs to adapt in order to function properly. However, tracking plasticity of naturalistic behavior and associated brain modulations is challenging. Here, we tackled this question implementing a prism adaptation-like training in virtual reality (VRPA) in combination with functional neuroimaging. Three groups of healthy participants (N = 45) underwent VRPA (with a shift either to the left/right side, or with no shift), and performed functional magnetic resonance imaging (fMRI) sessions before and after training. To capture modulations in free-flowing, task-free brain activity, the fMRI sessions included resting-state and free-viewing of naturalistic videos. We found significant decreases in spontaneous functional connectivity between attentional and default mode (DMN)/fronto-parietal networks, only for the adaptation groups, more pronouncedly in the hemisphere contralateral to the induced shift. In addition, VRPA was found to bias visual responses to naturalistic videos: Following rightward adaptation, we found upregulation of visual response in an area in the parieto-occipital sulcus (POS) only in the right hemisphere. Notably, the extent of POS upregulation correlated with the size of the VRPA-induced after-effect measured in behavioral tests. This study demonstrates that a brief VRPA exposure can change large-scale cortical connectivity and correspondingly bias visual responses to naturalistic sensory inputs.

Vision- and touch-dependent brain correlates of body-related mental processing.

In humans, the nature of sensory input influences body-related mental processing. For instance, behavioral differences (e.g., response time) can be found between mental spatial transformations (e.g., mental rotation) of viewed and touched body parts. It can thus be hypothesized that distinct brain activation patterns are associated with such sensory-dependent body-related mental processing. However, direct evidence that the neural correlates of body-related mental processing can be modulated by the nature of the sensory stimuli is still missing. We thus analyzed event-related functional magnetic resonance imaging (fMRI) data from thirty-one healthy participants performing mental rotation of visually- (images) and haptically-presented (plastic) hands. We also dissociated the neural activity related to rotation or task-related performance using models that either regressed out or included the variance associated with response time. Haptically-mediated mental rotation recruited mostly the sensorimotor brain network. Visually-mediated mental rotation led to parieto-occipital activations. In addition, faster mental rotation was associated with sensorimotor activity, while slower mental rotation was associated with parieto-occipital activations. The fMRI results indicated that changing the type of sensory inputs modulates the neural correlates of body-related mental processing. These findings suggest that distinct sensorimotor brain dynamics can be exploited to execute similar tasks depending on the available sensory input. The present study can contribute to a better evaluation of body-related mental processing in experimental and clinical settings.

Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis.

Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restores walking in people with spinal cord injury (SCI). However, EES is delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis as part of an ongoing clinical trial ( www.clinicaltrials.gov identifier NCT02936453). Within a single day, activity-specific stimulation programs enabled these three individuals to stand, walk, cycle, swim and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI.

In vitro evaluation of cerebrospinal fluid velocity measurement in type I Chiari malformation: repeatability, reproducibility, and agreement using 2D phase contrast and 4D flow MRI.

BACKGROUND: Phase contrast magnetic resonance imaging, PC MRI, is a valuable tool allowing for non-invasive quantification of CSF dynamics, but has lacked adoption in clinical practice for Chiari malformation diagnostics. To improve these diagnostic practices, a better understanding of PC MRI based measurement agreement, repeatability, and reproducibility of CSF dynamics is needed. METHODS: An anatomically realistic in vitro subject specific model of a Chiari malformation patient was scanned three times at five different scanning centers using 2D PC MRI and 4D Flow techniques to quantify intra-scanner repeatability, inter-scanner reproducibility, and agreement between imaging modalities. Peak systolic CSF velocities were measured at nine axial planes using 2D PC MRI, which were then compared to 4D Flow peak systolic velocity measurements extracted at those exact axial positions along the model. RESULTS: Comparison of measurement results showed good overall agreement of CSF velocity detection between 2D PC MRI and 4D Flow (p = 0.86), fair intra-scanner repeatability (confidence intervals ± 1.5 cm/s), and poor inter-scanner reproducibility. On average, 4D Flow measurements had a larger variability than 2D PC MRI measurements (standard deviations 1.83 and 1.04 cm/s, respectively). CONCLUSION: Agreement, repeatability, and reproducibility of 2D PC MRI and 4D Flow detection of peak CSF velocities was quantified using a patient-specific in vitro model of Chiari malformation. In combination, the greatest factor leading to measurement inconsistency was determined to be a lack of reproducibility between different MRI centers. Overall, these findings may help lead to better understanding for application of 2D PC MRI and 4D Flow techniques as diagnostic tools for CSF dynamics quantification in Chiari malformation and related diseases.

An fMRI study of error monitoring in Montessori and traditionally-schooled children.

The development of error monitoring is central to learning and academic achievement. However, few studies exist on the neural correlates of children's error monitoring, and no studies have examined its susceptibility to educational influences. Pedagogical methods differ on how they teach children to learn from errors. Here, 32 students (aged 8-12 years) from high-quality Swiss traditional or Montessori schools performed a math task with feedback during fMRI. Although the groups' accuracies were similar, Montessori students skipped fewer trials, responded faster and showed more neural activity in right parietal and frontal regions involved in math processing. While traditionally-schooled students showed greater functional connectivity between the ACC, involved in error monitoring, and hippocampus following correct trials, Montessori students showed greater functional connectivity between the ACC and frontal regions following incorrect trials. The findings suggest that pedagogical experience influences the development of error monitoring and its neural correlates, with implications for neurodevelopment and education.

A brief exposure to rightward prismatic adaptation changes resting-state network characteristics of the ventral attentional system.

A brief session of rightward prismatic adaptation (R-PA) has been shown to alleviate neglect symptoms in patients with right hemispheric damage, very likely by switching hemispheric dominance of the ventral attentional network (VAN) from the right to the left and by changing task-related activity within the dorsal attentional network (DAN). We have investigated this very rapid change in functional organisation with a network approach by comparing resting-state connectivity before and after a brief exposure i) to R-PA (14 normal subjects; experimental condition) or ii) to plain glasses (12 normal subjects; control condition). A whole brain analysis (comprising 129 regions of interest) highlighted R-PA-induced changes within a bilateral, fronto-temporal network, which consisted of 13 nodes and 11 edges; all edges involved one of 4 frontal nodes, which were part of VAN. The analysis of network characteristics within VAN and DAN revealed a R-PA-induced decrease in connectivity strength between nodes and a decrease in local efficiency within VAN but not within DAN. These results indicate that the resting-state connectivity configuration of VAN is modulated by R-PA, possibly by decreasing its modularity.

Remodelling the attentional system after left hemispheric stroke: Effect of leftward prismatic adaptation.

Left hemispheric stroke is known to be associated with right neglect and/or not lateralized attentional deficits. The former appears to respond favourably to leftward prismatic adaptation (L-PA), as reported in a case of a large left stroke. In normal subjects, brief exposure to L-PA was shown to enhance the representation of the right visual field within the right inferior parietal lobule, emphasizing thus right hemispheric dominance within the ventral attentional system. We have investigated whether L-PA does the same in left hemispheric stroke by comparing neural responses to left, central and right stimuli before and after a brief exposure to L-PA. Neural responses to visual stimuli were significantly modulated within a large part of the occipito-temporal cortex and in smaller clusters in the angular gyrus, the anterior temporal lobe and the insula, corresponding to decrease in activity. Within the occipito-temporal region the decrease concerned predominantly neural activity elicited by left stimuli, downregulating thus the representation of the contralateral visual field, which is characteristic of the higher-order visual areas in this region.

In-vivo probabilistic atlas of human thalamic nuclei based on diffusion- weighted magnetic resonance imaging.

The thalamic nuclei are involved in many neurodegenerative diseases and therefore, their identification is of key importance in numerous clinical treatments. Automated segmentation of thalamic subparts is currently achieved by exploring diffusion-weighted magnetic resonance imaging (DW-MRI), but in absence of such data, atlas-based segmentation can be used as an alternative. Currently, there is a limited number of available digital atlases of the thalamus. Moreover, all atlases are created using a few subjects only, thus are prone to errors due to the inter-subject variability of the thalamic morphology. In this work, we present a probabilistic atlas of anatomical subparts of the thalamus built upon a relatively large dataset where the individual thalamic parcellation was done by employing a recently proposed automatic diffusion-based clustering method. Our analyses, comparing the segmentation performance between the atlas-based and the clustering method, demonstrate the ability of the provided atlas to substitute the automated diffusion-based subdivision in the individual space when the DW-MRI is not available.

Cognitive Working Memory Training (CWMT) in adolescents suffering from Attention-Deficit/Hyperactivity Disorder (ADHD): A controlled trial taking into account concomitant medication effects.

Although, cognitive working memory training (CWMT) has been reported to enhance working memory functioning in youths with attention-deficit/ hyperactivity disorder (ADHD), few studies take into account the concomitant effects of medication. Sixty adolescents aged from 11 to 15 years were randomly assigned to CWMT treatment, whereas medication was either continued or not introduced (no randomization performed). Results revealed beneficial effects of CWMT on the different components of working memory (WM), namely the phonological loop, the visuospatial sketchpad and the central executive. In particular, CWMT allowed participants to obtain a level of performance similar to the typically-developing adolescents for the phonological loop (i.e., forward digit span) as well as for the visuospatial sketchpad (i.e., board span). For the central executive (i.e., backward digit span) the concomitant effects of CWMT and medication allows participants to obtain the performance level of the typically-developing adolescents. Although, no transfers were observed with respect to other cognitive functions, in medicated patients with ADHD, CWMT reduced hyperactivity / impulsivity symptoms at 2-month follow-up. The present study gives evidence of the efficacy of CWMT to enhance WM performance, as well as, to reduce symptoms. The overall results highlight the usefulness of multimodal interventions.

Supramodal effect of rightward prismatic adaptation on spatial representations within the ventral attentional system.

Rightward prismatic adaptation (R-PA) was shown to alleviate not only visuo-spatial but also auditory symptoms in neglect. The neural mechanisms underlying the effect of R-PA have been previously investigated in visual tasks, demonstrating a shift of hemispheric dominance for visuo-spatial attention from the right to the left hemisphere both in normal subjects and in patients. We have investigated whether the same neural mechanisms underlie the supramodal effect of R-PA on auditory attention. Normal subjects underwent a brief session of R-PA, which was preceded and followed by an fMRI evaluation during which subjects detected targets within the left, central and right space in the auditory or visual modality. R-PA-related changes in activation patterns were found bilaterally in the inferior parietal lobule. In either modality, the representation of the left, central and right space increased in the left IPL, whereas the representation of the right space decreased in the right IPL. Thus, a brief exposure to R-PA modulated the representation of the auditory and visual space within the ventral attentional system. This shift in hemispheric dominance for auditory spatial attention offers a parsimonious explanation for the previously reported effects of R-PA on auditory symptoms in neglect.

A Brief Exposure to Leftward Prismatic Adaptation Enhances the Representation of the Ipsilateral, Right Visual Field in the Right Inferior Parietal Lobule.

A brief exposure to rightward prismatic adaptation (PA) was shown to shift visual field representation within the inferior parietal lobule (IPL) from the right to the left hemisphere. This change in hemispheric dominance could be interpreted as (1) a general effect of discrepancy in visuomotor alignment caused by PA or (2) a direction-specific effect of rightward PA. To test these hypotheses, we compared the effects of rightward and leftward PA on visual representation in normal human subjects. Three groups of normal subjects underwent an fMRI evaluation using a simple visual detection task before and after brief PA exposure using leftward- or rightward-deviating prisms or no prisms (L-PA, R-PA, neutral groups). A two-way ANOVA group × session revealed a significant interaction suggesting that PA-induced modulation is direction specific. Post hoc analysis showed that L-PA enhanced the representation of the right visual field within the right IPL. Thus, a brief exposure to L-PA enhanced right hemispheric dominance within the ventral attentional system, which is the opposite effect of the previously described shift in hemispheric dominance following R-PA. The direction-specific effects suggest that the underlying neural mechanisms involve the fine-tuning of specific visuomotor networks. The enhancement of right hemispheric dominance following L-PA offers a parsimonious explanation for neglect-like symptoms described previously in normal subjects.

Reshaping the brain after stroke: The effect of prismatic adaptation in patients with right brain damage.

Prismatic adaptation has been repeatedly reported to alleviate neglect symptoms; in normal subjects, it was shown to enhance the representation of the left visual space within the left inferior parietal cortex. Our study aimed to determine in humans whether similar compensatory mechanisms underlie the beneficial effect of prismatic adaptation in neglect. Fifteen patients with right hemispheric lesions and 11 age-matched controls underwent a prismatic adaptation session which was preceded and followed by fMRI using a visual detection task. In patients, the prismatic adaptation session improved the accuracy of target detection in the left and central space and enhanced the representation of this visual space within the left hemisphere in parts of the temporal convexity, inferior parietal lobule and prefrontal cortex. Across patients, the increase in neuronal activation within the temporal regions correlated with performance improvements in this visual space. In control subjects, prismatic adaptation enhanced the representation of the left visual space within the left inferior parietal lobule and decreased it within the left temporal cortex. Thus, a brief exposure to prismatic adaptation enhances, both in patients and in control subjects, the competence of the left hemisphere for the left space, but the regions extended beyond the inferior parietal lobule to the temporal convexity in patients. These results suggest that the left hemisphere provides compensatory mechanisms in neglect by assuming the representation of the whole space within the ventral attentional system. The rapidity of the change suggests that the underlying mechanism relies on uncovering pre-existing synaptic connections.

Robust thalamic nuclei segmentation method based on local diffusion magnetic resonance properties.

The thalamus is an essential relay station in the cortical-subcortical connections. It is characterized by a complex anatomical architecture composed of numerous small nuclei, which mediate the involvement of the thalamus in a wide range of neurological functions. We present a novel framework for segmenting the thalamic nuclei, which explores the orientation distribution functions (ODFs) from diffusion magnetic resonance images at 3 T. The differentiation of the complex intra-thalamic microstructure is improved by using the spherical harmonic (SH) representation of the ODFs, which provides full angular characterization of the diffusion process in each voxel. The clustering was performed using the k-means algorithm initialized in a data-driven manner. The method was tested on 35 healthy volunteers and our results show a robust, reproducible and accurate segmentation of the thalamus in seven nuclei groups. Six of them closely matched the anatomy and were labeled as anterior, ventral anterior, medio-dorsal, ventral latero-ventral, ventral latero-dorsal and pulvinar, while the seventh cluster included the centro-lateral and the latero-posterior nuclei. Results were evaluated both qualitatively, by comparing the segmented nuclei to the histological atlas of Morel, and quantitatively, by measuring the clusters' extent and the clusters' spatial distribution across subjects and hemispheres. We also showed the robustness of our approach across different sequences and scanners, as well as intra-subject reproducibility of the segmented clusters using additional two scan-rescan datasets. We also observed an overlap between the path of the main long-connection tracts passing through the thalamus and the spatial distribution of the nuclei identified with our clustering algorithm. Our approach, based on SH representations of the ODFs, outperforms the one based on angular differences between the principle diffusion directions, which is considered so far as state-of-the-art method. Our findings show an anatomically reliable segmentation of the main groups of thalamic nuclei that could be of potential use in many clinical applications.

Cannabis and its effects on driving skills.

Traffic policies show growing concerns about driving under the influence of cannabis, since cannabinoids are one of the most frequently encountered psychoactive substances in the blood of drivers who are drug-impaired and/or involved in accidents, and in the context of a legalization of medical marijuana and of recreational use. The neurobiological mechanisms underlying the effects of cannabis on safe driving remain poorly understood. In order to better understand its acute and long-term effects on psychomotor functions involved in the short term ability and long-term fitness to drive, experimental research has been conducted based on laboratory, simulator or on-road studies, as well as on structural and functional brain imaging. Results presented in this review show a cannabis-induced impairment of actual driving performance by increasing lane weaving and mean distance headway to the preceding vehicle. Acute and long-term dose-dependent impairments of specific cognitive functions and psychomotor abilities were also noted, extending beyond a few weeks after the cessation of use. Some discrepancies found between these studies could be explained by factors such as history of cannabis use, routes of administration, dose ranges, or study designs (e.g. treatment blinding). Moreover, use of both alcohol and cannabis has been shown to lead to greater odds of making an error than use of either alcohol or cannabis alone. Although the correlation between blood or oral fluid concentrations and psychoactive effects of THC needs a better understanding, blood sampling has been shown to be the most effective way to evaluate the level of impairment of drivers under the influence of cannabis. The blood tests have also shown to be useful to highlight a chronic use of cannabis that suggests an addiction and therefore a long-term unfitness to drive. Besides blood, hair and repeated urine analyses are useful to confirm abstinence.