Analyzing data in complicated 3D domains: Smoothing, semiparametric regression, and functional principal component analysis

In this work, we introduce a family of methods for the analysis of data observed at locations scattered in three-dimensional (3D) domains, with possibly complicated shapes. The proposed family of methods includes smoothing, regression, and functional principal component analysis for functional signals defined over (possibly nonconvex) 3D domains, appropriately complying with the nontrivial shape of the domain. This constitutes an important advance with respect to the literature, because the available methods to analyze data observed in 3D domains rely on Euclidean distances, which are inappropriate when the shape of the domain influences the phenomenon under study. The common building block of the proposed methods is a nonparametric regression model with differential regularization. We derive the asymptotic properties of the methods and show, through simulation studies, that they are superior to the available alternatives for the analysis of data in 3D domains, even when considering domains with simple shapes. We finally illustrate an application to a neurosciences study, with neuroimaging signals from functional magnetic resonance imaging, measuring neural activity in the gray matter, a nonconvex volume with a highly complicated structure

Simultaneous EEG-fMRI in Patients with Unverricht-Lundborg Disease: Event-Related Desynchronization/Synchronization and Hemodynamic Response Analysis

We performed simultaneous acquisition of EEG-fMRI in seven patients with Unverricht-Lundborg disease (ULD) and in six healthy controls using self-paced finger extension as a motor task. The event-related desynchronization/synchronization (ERD/ERS) analysis showed a greater and more diffuse alpha desynchronization in central regions and a strongly reduced post-movement beta-ERS in patients compared with controls, suggesting a significant dysfunction of the mechanisms regulating active movement and movement end. The event-related hemodynamic response obtained from fMRI showed delayed BOLD peak latency in the contralateral primary motor area suggesting a less efficient activity of the neuronal populations driving fine movements, which are specifically impaired in ULD

Early cortico-muscular coherence and cortical network changes in Parkinson’s patients treated with MRgFUS

IntroductionTo investigate cortical network changes using Magnetoencephalography (MEG) signals in Parkinson’s disease (PD) patients undergoing Magnetic Resonance-guided Focused Ultrasound (MRgFUS) thalamotomy.MethodsWe evaluated the MEG signals in 16 PD patients with drug-refractory tremor before and after 12-month from MRgFUS unilateral lesion of the ventralis intermediate nucleus (Vim) of the thalamus contralateral to the most affected body side. We recorded patients 24 h before (T0) and 24 h after MRgFUS (T1). We analyzed signal epochs recorded at rest and during the isometric extension of the hand contralateral to thalamotomy. We evaluated cortico-muscular coherence (CMC), the out-strength index from non-primary motor areas to the pre-central area and connectivity indexes, using generalized partial directed coherence. Statistical analysis was performed using RMANOVA and post hoct-tests.ResultsMost changes found at T1 compared to T0 occurred in the beta band and included: (1) a re-adjustment of CMC distribution; (2) a reduced out-strength from non-primary motor areas toward the precentral area; (3) strongly reduced clustering coefficient values. These differences mainly occurred during motor activation and with few statistically significant changes at rest. Correlation analysis showed significant relationships between changes of out-strength and clustering coefficient in non-primary motor areas and the changes in clinical scores.DiscussionOne day after MRgFUS thalamotomy, PD patients showed a topographically reordered CMC and decreased cortico-cortical flow, together with a reduced local connection between different nodes. These findings suggest that the reordered cortico-muscular and cortical-networks in the beta band may represent an early physiological readjustment related to MRgFUS Vim lesion

Arterially Perfused Neurosphere-Derived Cells Distribute Outside the Ischemic Core in a Model of Transient Focal Ischemia and Reperfusion In Vitro

BACKGROUND: Treatment with neural stem cells represents a potential strategy to improve functional recovery of post-ischemic cerebral injury. The potential benefit of such treatment in acute phases of human ischemic stroke depends on the therapeutic viability of a systemic vascular delivery route. In spite of the large number of reports on the beneficial effects of intracerebral stem cells injection in experimental stroke, very few studies demonstrated the effectiveness of the systemic intravenous delivery approach. METODOLOGY/PRINCIPAL FINDINGS: We utilized a novel in vitro model of transient focal ischemia to analyze the brain distribution of neurosphere-derived cells (NCs) in the early 3 hours that follow transient occlusion of the medial cerebral artery (MCA). NCs obtained from newborn C57/BL6 mice are immature cells with self-renewal properties that could differentiate into neurons, astrocytes and oligodendrocytes. MCA occlusion for 30 minutes in the in vitro isolated guinea pig brain preparation was followed by arterial perfusion with 1x10(6) NCs charged with a green fluorescent dye, either immediately or 60 minutes after reperfusion onset. Changes in extracellular pH and K(+) concentration during and after MCAO were measured through ion-sensitive electrodes. CONCLUSION/SIGNIFICANCE: It is demonstrated that NCs injected through the vascular system do not accumulate in the ischemic core and preferentially distribute in non-ischemic areas, identified by combined electrophysiological and morphological techniques. Direct measurements of extracellular brain ions during and after MCA occlusion suggest that anoxia-induced tissue changes, such as extracellular acidosis, may prevent NCs from entering the ischemic area in our in vitro model of transitory focal ischemia and reperfusion suggesting a role played by the surrounding microenviroment in driving NCs outside the ischemic core. These findings strongly suggest that the potential beneficial effect of NCs in experimental focal brain ischemia is not strictly dependent on their homing into the ischemic region, but rather through a bystander mechanism possibly mediated by the release of neuroprotective factors in the peri-infarct region

From brain topography to brain topology: relevance of graph theory to functional neuroscience

Although several brain regions show significant specialization, higher functions such as cross-modal information integration, abstract reasoning and conscious awareness are viewed as emerging from interactions across distributed functional networks. Analytical approaches capable of capturing the properties of such networks can therefore enhance our ability to make inferences from functional MRI, electroencephalography and magnetoencephalography data. Graph theory is a branch of mathematics that focuses on the formal modelling of networks and offers a wide range of theoretical tools to quantify specific features of network architecture (topology) that can provide information complementing the anatomical localization of areas responding to given stimuli or tasks (topography). Explicit modelling of the architecture of axonal connections and interactions among areas can furthermore reveal peculiar topological properties that are conserved across diverse biological networks, and highly sensitive to disease states. The field is evolving rapidly, partly fuelled by computational developments that enable the study of connectivity at fine anatomical detail and the simultaneous interactions among multiple regions. Recent publications in this area have shown that graph-based modelling can enhance our ability to draw causal inferences from functional MRI experiments, and support the early detection of disconnection and the modelling of pathology spread in neurodegenerative disease, particularly Alzheimer's disease. Furthermore, neurophysiological studies have shown that network topology has a profound link to epileptogenesis and that connectivity indices derived from graph models aid in modelling the onset and spread of seizures. Graph-based analyses may therefore significantly help understand the bases of a range of neurological conditions. This review is designed to provide an overview of graph-based analyses of brain connectivity and their relevance to disease aimed principally at general neuroscientists and clinicians

Higher order spectral analysis of scalp EEG activity reveals non-linear behavior during rhythmic visual stimulation

Objective. Flickering visual stimulation is known to evoke rhythmic oscillations in the electroencephalographic (EEG) activity, called steady-state visually evoked potentials (SSVEP). The presence of harmonic components in the EEG signals during SSVEP suggests the non-linearity of the visual-system response to rhythmic stimulation, but the nature of this behavior has not been deeply understood. The aim of this study is the quantitative evaluation and characterization of this non-linear phenomenon and its interference with the physiological alpha rhythm by means of spectral and higher order spectral analysis. Approach. EEG signals were acquired in a group of 12 healthy subjects during a pattern-reversal stimulation protocol at three different driving frequencies (7.5 Hz, 15 Hz and 24 Hz). Spectral power values were estimated, after Laplacian spatial filtering, to quantitatively evaluate the changes in the power of the individual alpha and stimulation frequencies related harmonic components. Bicoherence measure were employed to assess the presence of quadratic phase coupling (QPC) at each channel location. Main results. Our analysis confirmed a strong non-linear response to the rhythmic stimulus principally over the parieto-occipital channel locations and a simultaneous significant alpha power suppression during 7.5 Hz and 15 Hz stimulation. A prominent sub-harmonic component characterized the resonance behavior of the 24 Hz stimulation. Significance. The findings presented suggest that bicoherence is a useful tool for the identification of QPC interactions between stimulus-related frequency components within the same signal and the characterization of the non-linearity of SSVEP-induced harmonics generation. In addition, the applied methodology demonstrates the presence of coupled EEG rhythms (harmonics of the main oscillation) both in resting condition and during stimulation, with different characteristics in the distinct brain areas

Anatomically compliant modes of variations: New tools for brain connectivity.

Anatomical complexity and data dimensionality present major issues when analysing brain connectivity data. The functional and anatomical aspects of the connections taking place in the brain are in fact equally relevant and strongly intertwined. However, due to theoretical challenges and computational issues, their relationship is often overlooked in neuroscience and clinical research. In this work, we propose to tackle this problem through Smooth Functional Principal Component Analysis, which enables to perform dimensional reduction and exploration of the variability in functional connectivity maps, complying with the formidably complicated anatomy of the grey matter volume. In particular, we analyse a population that includes controls and subjects affected by schizophrenia, starting from fMRI data acquired at rest and during a task-switching paradigm. For both sessions, we first identify the common modes of variation in the entire population. We hence explore whether the subjects' expressions along these common modes of variation differ between controls and pathological subjects. In each session, we find principal components that are significantly differently expressed in the healthy vs pathological subjects (with p-values < 0.001), highlighting clearly interpretable differences in the connectivity in the two subpopulations. For instance, the second and third principal components for the rest session capture the imbalance between the Default Mode and Executive Networks characterizing schizophrenia patients

Na+-activated K+ current contributes to postexcitatory hyperpolarization in neocortical intrinsically bursting neurons

The ionic mechanisms underlying the termination of action-potential (AP) bursts and postburst afterhyperpolarization (AHP) in intrinsically bursting (IB) neocortical neurons were investigated by performing intracellular recordings in thin slices of rat sensorimotor cortex. The blockade of Ca(2+)-activated K(+) currents enhanced postburst depolarizing afterpotentials, but had inconsistent and minor effects on the amplitude and duration of AHPs. On the contrary, experimental conditions resulting in reduction of voltage-dependent Na(+) entry into the cells caused a significant decrease of AHP amplitude. Slice perfusion with a modified artificial cerebrospinal fluid in which LiCl (40 mM) partially replaced NaCl had negligible effects on the properties of individual APs, whereas it consistently increased burst length and led to an approximately 30% reduction in the amplitude of AHPs following individual bursts or short trains of stimulus-induced APs. Experiments performed by partially replacing Na(+) ions with choline revealed a comparable reduction in AHP amplitude associated with an inhibition of bursting activity. Moreover, in voltage-clamp experiments carried out in both in situ and acutely isolated neurons, partial substitution of extracellular NaCl with LiCl significantly and reversibly reduced the amplitude of K(+) currents evoked by depolarizing stimuli above-threshold for Na(+)-current activation. The above effect of Na(+)-to-Li(+) substitution was not seen when voltage-gated Na(+) currents were blocked with TTX, indicating the presence of a specific K(+)-current component activated by voltage-dependent Na(+) (but not Li(+)) influx. The above findings suggest that a Na(+)-activated K(+) current recruited by the Na(+) entry secondary to burst discharge significantly contributes to AHP generation and the maintenance of rhythmic burst recurrence during sustained depolarizations in neocortical IB neurons