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From molecular mechanisms to global brain networks, atypical fluctuations are the hallmark of neurodegeneration. Yet, traditional fMRI research on resting-state networks (RSNs) has favored static and average connectivity methods, which by overlooking the fluctuation dynamics triggered by neurodegeneration, have yielded inconsistent results. The present multicenter study introduces a data-driven machine learning pipeline based on dynamic connectivity fluctuation analysis (DCFA) on RS-fMRI data from 300 participants belonging to three groups: behavioral variant frontotemporal dementia (bvFTD) patients, Alzheimer's disease (AD) patients, and healthy controls. We considered non-linear oscillatory patterns across combined and individual resting-state networks (RSNs), namely: the salience network (SN), mostly affected in bvFTD; the default mode network (DMN), mostly affected in AD; the executive network (EN), partially compromised in both conditions; the motor network (MN); and the visual network (VN). These RSNs were entered as features for dementia classification using a recent robust machine learning approach (a Bayesian hyperparameter tuned Gradient Boosting Machines (GBM) algorithm), across four independent datasets with different MR scanners and recording parameters. The machine learning classification accuracy analysis revealed a systematic and unique tailored architecture of RSN disruption. The classification accuracy ranking showed that the most affected networks for bvFTD were the SN + EN network pair (mean accuracy = 86.43%, AUC = 0.91, sensitivity = 86.45%, specificity = 87.54%); for AD, the DMN + EN network pair (mean accuracy = 86.63%, AUC = 0.89, sensitivity = 88.37%, specificity = 84.62%); and for the bvFTD vs. AD classification, the DMN + SN network pair (mean accuracy = 82.67%, AUC = 0.86, sensitivity = 81.27%, specificity = 83.01%). Moreover, the DFCA classification systematically outperformed canonical connectivity approaches (including both static and linear dynamic connectivity). Our findings suggest that non-linear dynamical fluctuations surpass two traditional seed-based functional connectivity approaches and provide a pathophysiological characterization of global brain networks in neurodegenerative conditions (AD and bvFTD) across multicenter data.

In patients with pharmaco-resistant focal epilepsies investigated with intracranial electroencephalography (iEEG), direct electrical stimulations of a cortical region induce cortico-cortical evoked potentials (CCEP) in distant cerebral cortex, which properties can be used to infer large scale brain connectivity. In 2013, we proposed a new probabilistic functional tractography methodology to study human brain connectivity. We have now been revisiting this method in the F-TRACT project (f-tract.eu) by developing a large multicenter CCEP database of several thousand stimulation runs performed in several hundred patients, and associated processing tools to create a probabilistic atlas of human cortico-cortical connections. Here, we wish to present a snapshot of the methods and data of F-TRACT using a pool of 213 epilepsy patients, all studied by stereo-encephalography with intracerebral depth electrodes. The CCEPs were processed using an automated pipeline with the following consecutive steps: detection of each stimulation run from stimulation artifacts in raw intracranial EEG (iEEG) files, bad channels detection with a machine learning approach, model-based stimulation artifact correction, robust averaging over stimulation pulses. Effective connectivity between the stimulated and recording areas is then inferred from the properties of the first CCEP component, i.e. onset and peak latency, amplitude, duration and integral of the significant part. Finally, group statistics of CCEP features are implemented for each brain parcel explored by iEEG electrodes. The localization (coordinates, white/gray matter relative positioning) of electrode contacts were obtained from imaging data (anatomical MRI or CT scans before and after electrodes implantation). The iEEG contacts were repositioned in different brain parcellations from the segmentation of patients' anatomical MRI or from templates in the MNI coordinate system. The F-TRACT database using the first pool of 213 patients provided connectivity probability values for 95% of possible intrahemispheric and 56% of interhemispheric connections and CCEP features for 78% of intrahemisheric and 14% of interhemispheric connections. In this report, we show some examples of anatomo-functional connectivity matrices, and associated directional maps. We also indicate how CCEP features, especially latencies, are related to spatial distances, and allow estimating the velocity distribution of neuronal signals at a large scale. Finally, we describe the impact on the estimated connectivity of the stimulation charge and of the contact localization according to the white or gray matter. The most relevant maps for the scientific community are available for download on f-tract. eu (David et al., 2017) and will be regularly updated during the following months with the addition of more data in the F-TRACT database. This will provide an unprecedented knowledge on the dynamical properties of large fiber tracts in human.

•First to examine MRI-based subcortical volumes in the perinatally deafened cat.•Reveals large-scale disuse-driven atrophy in the deafened feline subcortex.•Magnitude of reductions in lower-level auditory nuclei are influenced by hierarchy.•Visual nuclei also exhibit reductions based on modified perceptual importance.•Deafened feline subcortex remains structurally symmetrical. In response to sensory deprivation, the brain adapts to efficiently navigate a modified perceptual environment through a process referred to as compensatory crossmodal plasticity, allowing the remaining senses to repurpose deprived regions and networks. A mechanism that has been proposed to contribute to this plasticity involves adaptations within subcortical nuclei that trigger cascading effects throughout the brain. The current study uses 7T MRI to investigate the effect of perinatal deafness on the volumes of subcortical structures in felines, focusing on key sensory nuclei within the brainstem and thalamus. Using both ROI-based and morphometric approaches, the regional macrostructure of four auditory and two visual nuclei were studied, as well as the corresponding volumetric asymmetries within and across groups. In the auditory pathway, significant bilateral volumetric reductions were revealed within the lower-level structures (cochlear nucleus, superior olivary complex, and inferior colliculus), alongside a shrinkage of solely the left medial geniculate body. Within the visual pathway, a significant bilateral volumetric reduction was found in the lateral geniculate nucleus, with the superior colliculus largely unaffected. These regional alterations, along with an extensive loss of volume throughout the brainstem of deprived cats, were attributed to disuse-driven atrophy corresponding to evolved functional demands reflective of a modified perceptual environment. Furthermore, the left-right volumetric symmetries of the control subcortex were preserved following deafness. Overall, the current study reinforces the notion that subcortical structures likely contribute to compensatory crossmodal plasticity prior to cortical processing, and that these deafness-induced adaptations appear to be influenced by both the level of the affected structure within its respective sensory processing hierarchy and the specifics of its afferent profile.

ObjectiveNeuropathological studies in amyotrophic lateral sclerosis (ALS) have shown a dissemination in a regional sequence in four anatomically defined patterns. The aim of this retrospective study was to see whether longitudinal diffusion tensor imaging (DTI) data support the pathological findings.MethodsThe application of DTI analysis to fibre structures that are prone to be involved at each neuropathological pattern of ALS was performed in a monocentre sample of 67 patients with ALS and 31 controls that obtained at least one follow-up scan after a median of 6 months.ResultsAt the group level, longitudinal ALS data showed significant differences for the stage-related tract systems. At the individual level, 27% of the longitudinally scanned patients with ALS showed an increase in ALS stage, while the remaining were stable or were at the highest ALS stage. Longitudinal fractional anisotropy changes in the respective tract systems correlated significantly with the slope of the revised ALS functional rating scale.InterpretationThe DTI-based protocol was able to image the disease patterns of ALS in vivo cross-sectionally and longitudinally, in support of DTI as a technical marker to image ALS stages.

Dynamic functional connectivity (dFC) has been increasingly used to characterize the brain transient temporal functional patterns and their alterations in diseased brains. Meanwhile, naturalistic neuroimaging paradigms have been an emerging approach for cognitive neuroscience with high ecological validity. However, the test–retest reliability of dFC in naturalistic paradigm neuroimaging is largely unknown. To address this issue, we examined the test–retest reliability of dFC in functional magnetic resonance imaging (fMRI) under natural viewing condition. The intraclass correlation coefficients (ICC) of four dFC statistics including standard deviation (Std), coefficient of variation (COV), amplitude of low frequency fluctuation (ALFF), and excursion (Excursion) were used to measure the test–retest reliability. The test–retest reliability of dFC in naturalistic viewing condition was then compared with that under resting state. Our experimental results showed that: (a) Global test–retest reliability of dFC was much lower than that of static functional connectivity (sFC) in both resting‐state and naturalistic viewing conditions; (b) Both global and local (including visual, limbic and default mode networks) test–retest reliability of dFC could be significantly improved in naturalistic viewing condition compared to that in resting state; (c) There existed strong negative correlation between sFC and dFC, weak negative correlation between dFC and dFC‐ICC (i.e., ICC of dFC), as well as weak positive correlation between dFC‐ICC and sFC‐ICC (i.e., ICC of sFC). The present study provides novel evidence for the promotion of naturalistic paradigm fMRI in functional brain network studies. We examined the test–retest reliability of dynamic functional connectivity (dFC) in fMRI under natural viewing condition. Our experimental results showed that both global and local test‐retest reliability of dFC can be significantly improved in naturalistic viewing condition compared to that in resting state.

Examining the brain at rest is a powerful approach used to understand the intrinsic properties of typical and disordered human brain function, yet task-free paradigms are associated with greater head motion, particularly in young and/or clinical populations such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Inscapes, a non-social and non-verbal movie paradigm, has been introduced to increase attention, thus mitigating head motion, while reducing the task-induced activations found during typical movie watching. Inscapes has not yet been validated for use in magnetoencephalography (MEG), and it has yet to be shown whether its effects are stable in clinical populations. Across typically developing (N = 32) children and adolescents and those with ASD (N = 46) and ADHD (N = 42), we demonstrate that head motion is reduced during Inscapes. Due to the task state evoked by movie paradigms, we also expectedly observed concomitant modulations in local neural activity (oscillatory power) and functional connectivity (phase and envelope coupling) in intrinsic resting-state networks and across the frequency spectra compared to a fixation cross resting-state. Increases in local activity were accompanied by decreases in low-frequency connectivity within and between resting-state networks, primarily the visual network, suggesting that task-state evoked by Inscapes moderates ongoing and spontaneous cortical inhibition that forms the idling intrinsic networks found during a fixation cross resting-state. Importantly, these effects were similar in ASD and ADHD, making Inscapes a well-suited advancement for investigations of resting brain function in young and clinical populations.

Music learning has received increasing attention in the last decades due to the variety of functions and brain plasticity effects involved during its practice. Most previous reports interpreted the differences between music experts and laymen as the result of training. However, recent investigations suggest that these differences are due to a combination of genetic predispositions with the effect of music training. Here, we tested the relationship of the dorsal auditory-motor pathway with individual behavioural differences in short-term music learning. We gathered structural neuroimaging data from 44 healthy non-musicians (28 females) before they performed a rhythm- and a melody-learning task during a single behavioural session, and manually dissected the arcuate fasciculus (AF) in both hemispheres. The macro- and microstructural organization of the AF (i.e., volume and FA) predicted the learning rate and learning speed in the musical tasks, but only in the right hemisphere. Specifically, the volume of the right anterior segment predicted the synchronization improvement during the rhythm task, the FA in the right long segment was correlated with the learning rate in the melody task, and the volume and FA of the right whole AF predicted the learning speed during the melody task. This is the first study finding a specific relation between different branches within the AF and rhythmic and melodic materials. Our results support the relevant function of the AF as the structural correlate of both auditory-motor transformations and the feedback-feedforward loop, and suggest a crucial involvement of the anterior segment in error-monitoring processes related to auditory-motor learning. These findings have implications for both the neuroscience of music field and second-language learning investigations. •Structural connectivity markers predict behavioural individual differences.•The arcuate fasciculus supports the dorsal pathway crucial in language and music.•Structural markers in this tract differ between musicians and non-musicians.•To rule-out experience, music learning and arcuate were explored in non-musicians.•We found rhythm and melody learning related to different branches of the right arcuate.

Human spinal white matter tract anatomy has been mapped using post mortem histological information with the help of molecular tracing studies in animal models. This study used 7 Tesla diffusion MR tractography on a human cadaver that was harvested 24 hours post mortem to evaluate cuneate fasciculus anatomy in cervical spinal cord. Based on this method, for the first time much more nuanced tractographic anatomy was used to investigate possible new routes for cuneate fasciculus in the posterior and lateral funiculus. Additionally, current molecular tracing studies were reviewed, and confirmatory data was presented along with our radiological results. Both studies confirm that upon entry to the spinal cord, upper cervical level tracts (C1-2-3) travel inside lateral funiculus and lower level tracts travel medially inside the posterior funiculus after entry at posterolateral sulcus which is different than traditional knowledge of having cuneate fasciculus tracts concentrated in the lateral part of posterior funiculus. •Our data suggests a modified mapping of cuneate fascicle interposing with previously known Gracile fascicle and corresponds it with current molecular tracing data.•We describe a modified and updated tracking method called Root Back Tracking Method (RBTM) which consists of 3D contruction of seeding areas on spinal roots and enhancing the number of tracts significantly.•Our data suggests possible modifications in the approach to Spinal Cord Stimulation surgeries.•This is the first fresh human cadaver spinal tractography with 7T MRI in the literature.

The management of optic neuropathy is fundamental to neuro-ophthalmic practice. Following the invention of the ophthalmoscope, clinicians, for a century or more, relied upon fundus examination in the evaluation of optic neuropathy. However, the advent of optical coherence tomography, based on the principle of backscattering of light and interferometry, has revolutionized the analysis of optic nerve and retinal disorders. Optical coherence tomography has proven of particular value in the measurement, at the micron level, of the peripapillary retinal nerve fibre layer and the ganglion cell layer. These measurements have proven critical in the differential diagnosis and monitoring of optic neuropathy. Specifically, thinning of the peripapillary nerve fibre layer provides evidence of axonal loss affecting any sector of the optic nerve. Thinning of the macular ganglion cell layer, on the other hand, shows a more precise correlation with visual deficits due to retrograde degeneration following optic nerve damage, although limited to central retina. In daily practise, optical coherence tomography is of great value in assessing the diagnosis, prognosis and response to treatment in optic neuropathy. Particular advances have been made, for example, in the assessment of optic neuritis, papilloedema and chiasmal compression which have translated to everyday practice. As with any other imaging technology the clinician must have a clear understanding of acquisition artefacts. A further issue is the relatively limited normative database in sub-populations such as the young and individuals with a refractive error > + 5 or < −5 dioptres.

Introduction The purpose of this study was to assess the impact of brain injury on white matter development and long-term outcomes in very preterm (VPT) neonates. Methods Eighty-five VPT neonates (born <32/40 weeks gestational age (GA)) scanned within 2 weeks of birth were divided into three groups based on the presence of perinatal cerebral injury: (i) no injury, (ii) mild/moderate injury and (iii) severe injury. Diffusion tensor imaging (DTI) was acquired for each neonate and fractional anisotropy (FA), and diffusivity measures were calculated in the posterior limb of the internal capsule (PLIC) and optic radiation (OR). At 2 and 4 years of age, 41 and 44 children were assessed for motor and visual-motor abilities. Analyses determined the relation between GA and DTI measures, injury groups and DTI measures as well as developmental assessments. Results GA was related to all DTI measures within the PLIC bilaterally, FA in the OR bilaterally and AD in the left OR. The severely injured group had significantly different DTI measures in the left PLIC compared to the other two groups, independent of lateralization of lesions. Group differences in the left OR were also found, due to higher incidence of the white matter injury in the left hemisphere. No differences were found between groups and outcome measures at 2 and 4 years, with the exception of destructive periventricular venous haemorrhagic infarction (PVHI). Conclusions DTI measures of the PLIC and OR were affected by injury in VPT neonates. These findings seen shortly after birth did not always translate into long-term motor and visual-motor impairments suggesting compensatory mechanisms.