BOLD Activation During the Application of MOXO-CPT in School Patients With and Without Attention Deficit Hyperactivity Disorder.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects 3% of children in the world. OBJECTIVE: In this work, we seek to compare the different brain activations of pediatric patients with and without ADHD. METHODS: A functional resonance examination with BOLD contrast was applied using the MOXO-CPT test (Continuous Performance test with single and double visual-auditory distractors). RESULTS: Differences in BOLD activation were observed indicating that control children regularly presented negative BOLD activations that were not found in children with ADHD. Inhibitory activity in audiovisual association zones in control patients was greater than in patients with ADHD. The inhibition in the frontal and motor regions in the controls contrasted with the overactivation of the motor areas in patients with ADHD, this, together with the detection of cerebellar activation which attempted to modulate the responses of the different areas that lead to executive failure in patients with ADHD. CONCLUSIONS: In view of these results, it can be argued that the lack of inhibition of ADHD patients in their executive functions led to a disorganization of the different brain systems.

Cross-sectional evaluation of the association between greenness and cognitive performance in Mexican pre-pubertal boys.

BACKGROUND: Evidence shows that greenspace exposure benefits children's health and cognitive development. However, evidence assessing this association in young children in low- and middle-income economies is scarce. OBJECTIVE: To assess the association between exposure to greenness and cognitive performance in pre-pubertal boys living in Mexico City. METHODS: Cross-sectional study using data from 144 boys aged 6-11 years living in Mexico City in 2017 and enrolled in the "MetCog" study. Cognitive performance was evaluated through selected Wechsler Scale for Intelligence in Children Fourth Edition (WISC-IV) and Neuropsychological Assessment of Children (Evaluación Neuropsicológica Infantil, ENI) tests. Exposure to greenness was assessed through Normalised Difference Vegetation Index (NDVI) at 300, 500, 1500, 2000, and 3000 m buffer zones from children's residences. Multiple linear regression analysis was undertaken to assess associations between cognitive performance and greenness (aß) with 95% confidence intervals (CI) and adjusted for potential confounding variables. Significance was set at q < 0.05 after False Discovery Rate (FDR) correction. RESULTS: A positive association was found between the NDVI Interquartile Range (IQR) at 2000 m and the WISC-IV block design test score (aß 2000 = 1.18, 95% CI = 0.31, 2.06; q < 0.05), which assesses perceptual reasoning. Positive associations were found with NDVI IQR at 1500 m and WISC-IV block design (aß1500 = 1.00, 95% CI = 0.14, 1.86) and matrix reasoning (aß1500 = 0.83, 95% CI = 0.06, 1.61) scores, but neither survived FDR correction. No significant associations were found between NDVI IQR at any buffer size with other WISC-IV and ENI task scores. CONCLUSIONS: Greater exposure to greenness was associated with higher perceptual reasoning skills in 144 pre-pubertal boys living in Mexico City. Thus, urban planning should consider increasing vegetation in megacities, especially in neighbourhoods with high percentages of young children.

Hemodynamic Assessment in Bicuspid Aortic Valve Disease and Aortic Dilation: New Insights From Voxel-By-Voxel Analysis of Reverse Flow, Stasis, and Energetics.

Objectives: Clinical management decisions surrounding ascending aorta (AAo) dilation in bicuspid aortic valve (BAV) disease benefit from personalized predictive tools. 4D-flow MRI may provide patient-specific markers reflective of BAV-associated aortopathy. This study aims to explore novel 4D-flow MRI parametric voxel-by-voxel forward flow, reverse flow, kinetic energy and stasis in BAV disease. We hypothesize that novel parametric voxel-by-voxel markers will be associated with aortic dilation and referral for surgery and can enhance our understanding of BAV hemodynamics beyond standard metrics. Methods: A total of 96 subjects (73 BAV patients, 23 healthy controls) underwent MRI scan. Healthy controls had no known cardiovascular disease. Patients were clinically referred for AAo dilation assessment. Indexed diameters were obtained by dividing the aortic diameter by the patient's body surface area. Patients were followed for the occurrence of aortic surgery. 4D-flow analysis was performed by a single observer in five regions: left ventricular outflow tract (LVOT), AAo, arch, proximal descending aorta (PDAo), and distal descending aorta (DDAo). In each region peak velocity, kinetic energy (KE), forward flow (FF), reverse flow (RF), and stasis were measured on a voxel-by-voxel basis. T-tests (or non-parametric equivalent) compared flow parameters between cohorts. Univariate and multivariate analyses explored associations between diameter and parametric voxel-by-voxel parameters. Results: Compared to controls, BAV patients showed reduced stasis (p < 0.01) and increased RF and FF (p < 0.01) throughout the aorta, and KE remained similar. In the AAo, indexed diameter correlated with age (R = 0.326, p = 0.01), FF (R = -0.648, p < 0.001), RF (R = -0.441, p < 0.001), and stasis (R = -0.288, p < 0.05). In multivariate analysis, FF showed a significant inverse association with AAo indexed diameter, independent of age. During a median 179 ± 180 days of follow-up, 23 patients (32%) required aortic surgery. Compared to patients not requiring surgery, they showed increased KE and peak velocity in the proximal aorta (p < 0.01), accompanied by increased RF and reduced stasis throughout the entire aorta (p < 0.01). Conclusion: Novel voxel-by-voxel reverse flow and stasis were altered in BAV patients and are associated with aortic dilation and surgical treatment.

Monte Carlo simulation of the effect of magnetic fields on brachytherapy dose distributions in lung tissue material.

The aim of this work was to use TOPAS Monte Carlo simulations to model the effect of magnetic fields on dose distributions in brachytherapy lung treatments, under ideal and clinical conditions. Idealistic studies were modeled consisting of either a monoenergetic electron source of 432 keV, or a polyenergetic electron source using the spectrum of secondary electrons produced by 192Ir gamma-ray irradiation. The electron source was positioned in the center of a homogeneous, lung tissue phantom (ρ = 0.26 g/cm3). Conversely, the clinical study was simulated using the VariSource VS2000 192Ir source in a patient with a lung tumor. Three contoured volumes were considered: the tumor, the planning tumor volume (PTV), and the lung. In all studies, dose distributions were calculated in the presence or absence of a constant magnetic field of 3T. Also, TG-43 parameters were calculated for the VariSource and compared with published data from EGS-brachy (EGSnrc) and PENELOPE. The magnetic field affected the dose distributions in the idealistic studies. For the monoenergetic and poly-energetic studies, the radial distance of the 10% iso-dose line was reduced in the presence of the magnetic field by 64.9% and 24.6%, respectively. For the clinical study, the magnetic field caused differences of 10% on average in the patient dose distributions. Nevertheless, differences in dose-volume histograms were below 2%. Finally, for TG-43 parameters, the dose-rate constant from TOPAS differed by 0.09% ± 0.33% and 0.18% ± 0.33% with respect to EGS-brachy and PENELOPE, respectively. The geometry and anisotropy functions differed within 1.2% ± 1.1%, and within 0.0% ± 0.3%, respectively. The Lorentz forces inside a 3T magnetic resonance machine during 192Ir brachytherapy treatment of the lung are not large enough to affect the tumor dose distributions significantly, as expected. Nevertheless, large local differences were found in the lung tissue. Applications of this effect are therefore limited by the fact that meaningful differences appeared only in regions containing air, which is not abundant inside the human.

Lisdexamfetamine Alters BOLD-fMRI Activations Induced by Odor Cues in Impulsive Children.

INTRODUCTION: Lisdexamfetamine (LDX) is a drug used to treat ADHD/impulsive patients. Impulsivity is known to affect inhibitory, emotional and cognitive function. On the other hand, smell and odor processing are known to be affected by neurological disorders, as they are modulators of addictive and impulsive behaviors specifically. We hypothesize that, after LDX ingestion, inhibitory pathways of the brain would change, and complementary behavioral regulation mechanisms would appear to regulate decision-making and impulsivity. METHODS: 20 children were studied in an aleatory crossover study. Imaging of BOLD-fMRI activity, elicited by olfactory stimulation in impulsive children, was performed after either LDX or placebo ingestion. RESULTS: Findings showed that all subjects who underwent odor stimulation presented activations of similar intensities in the olfactory centers of the brain. This contrasted with inhibitory regions of the brain such as the cingulate cortex and frontal lobe regions, which demonstrated changed activity patterns and intensities. While some differences between the placebo and medicated states were found in motor areas, precuneus, cuneus, calcarine, supramarginal, cerebellum and posterior cingulate cortex, the main changes were found in frontal, temporal and parietal cortices. When comparing olfactory cues separately, pleasant food smells like chocolate seemed not to present large differences between the medicated and placebo scenarios, when compared to non-food-related smells. CONCLUSION: It was demonstrated that LDX, first, altered the inhibitory pathways of the brain, secondly it increased activity in several brain regions which were not activated by smell in drug-naïve patients, and thirdly, it facilitated a complementary behavioral regulation mechanism, run by the cerebellum, which regulated decision-making and impulsivity in motor and frontal structures.

A simple model for glioma grading based on texture analysis applied to conventional brain MRI.

Accuracy of glioma grading is fundamental for the diagnosis, treatment planning and prognosis of patients. The purpose of this work was to develop a low-cost and easy-to-implement classification model which distinguishes low-grade gliomas (LGGs) from high-grade gliomas (HGGs), through texture analysis applied to conventional brain MRI. Different combinations of MRI contrasts (T1Gd and T2) and one segmented glioma region (necrotic and non-enhancing tumor core, NCR/NET) were studied. Texture features obtained from the gray level size zone matrix (GLSZM) were calculated. An under-sampling method was proposed to divide the data into different training subsets and subsequently extract complementary information for the creation of distinct classification models. The sensitivity, specificity and accuracy of the models were calculated, and the best model explicitly reported. The best model included only three texture features and reached a sensitivity, specificity and accuracy of 94.12%, 88.24% and 91.18%, respectively. According to the features of the model, when the NCR/NET region was studied, HGGs had a more heterogeneous texture than LGGs in the T1Gd images, and LGGs had a more heterogeneous texture than HGGs in the T2 images. These novel results partially contrast with results from the literature. The best model proved to be useful for the classification of gliomas. Complementary results showed that the heterogeneity of gliomas depended on the MRI contrast studied. The chosen model stands out as a simple, low-cost, easy-to-implement, reproducible and highly accurate glioma classifier. Importantly, it should be accessible to populations with reduced economic and scientific resources.

Efficient CT Image Reconstruction in a GPU Parallel Environment.

Computed tomography is nowadays an indispensable tool in medicine used to diagnose multiple diseases. In clinical and emergency room environments, the speed of acquisition and information processing are crucial. CUDA is a software architecture used to work with NVIDIA graphics processing units. In this paper a methodology to accelerate tomographic image reconstruction based on maximum likelihood expectation maximization iterative algorithm and combined with the use of graphics processing units programmed in CUDA framework is presented. Implementations developed here are used to reconstruct images with clinical use. Timewise, parallel versions showed improvement with respect to serial implementations. These differences reached, in some cases, 2 orders of magnitude in time while preserving image quality. The image quality and reconstruction times were not affected significantly by the addition of Poisson noise to projections. Furthermore, our implementations showed good performance when compared with reconstruction methods provided by commercial software. One of the goals of this work was to provide a fast, portable, simple, and cheap image reconstruction system, and our results support the statement that the goal was achieved.

Brain Connectivity in Ateles geoffroyi: Resting-State Functional Magnetic Resonance Imaging of Working Memory and Executive Control.

The objective of this research was to describe the organization and connectivity of the working memory (WM) and executive control (EC) networks in Ateles geoffroyi in resting-state conditions. Recent studies have shown that resting-state activity may underlie rudimentary brain functioning, showing that several brain regions can be tonically active at rest, maximizing the efficiency of information transfer while preserving a low physical connection cost. Whole-brain resting-state images were acquired from three healthy adult Ateles monkeys (2 females, 1 male; mean age 10.5 ± SD 2.5 years). Data were analyzed with independent component analysis, and results were grouped together using the GIFT software. The present study compared the EC and WM networks obtained with human data and with results found in the literature in other primate species. Nine resting-state networks were found, which were similar to resting networks found in healthy human adults in the prefrontal basal portion and frontopolar area. Additionally, components of the WM network were found to be extending into the hypothalamus and the olfactory areas. A key finding was the discovery of connections in the WM and EC networks to the hypothalamus, the motor cortex, and the entorhinal cortex, suggesting that information is integrated from larger brain areas. The correlated areas suggest that many elements of WM and EC may be conserved across primate species. Characterization of these networks in resting-state conditions in nonhuman primate brains is a fundamental prerequisite for understanding of the neural bases underlying the evolution and function of this cognitive system.

Different Food Odors Control Brain Connectivity in Impulsive Children.

BACKGROUND: Impulsivity is a complex multi-dimensional combination of behaviors which include: ineffective impulse control, premature decision-making and inability to delay gratification. OBJECTIVE: The aim of this work was to explore how food odor perception and its emotional value is affected in impulsive children. METHODS: Here we compared two cohorts of impulsive and control children with ages between 10 and 16 years. Both groups underwent a functional magnetic resonance imaging experiment, in which foodrelated odor-cues were presented to all of them. RESULTS: Differences in regions of blood oxygen level dependent activation, as well as connectivity, were calculated. Activations were significant for all odors in the impulsive group in the temporal lobe, cerebellum, supplementary motor area, frontal cortex, medial cingulate cortex, insula, precuneus, precentral, para-hippocampal and calcarine cortices. CONCLUSION: Connectivity results showed that the expected emotional reward, based on odor perceived and processed in temporal lobes, was the main cue driving responses of impulsive children. This was followed by self-consciousness, the sensation of interaction with the surroundings and feelings of comfort and happiness, modulated by the precuneus together with somatosensory cortex and cingulum. Furthermore, reduced connectivity to frontal areas as well as to other sensory integration areas (piriform cortex), combined to show different sensory processing strategies for olfactory emotional cues in impulsive children. Finally, we hypothesize that the cerebellum plays a pivotal role in modulating decision-making for impulsive children.

Frontotemporal Lobe Degeneration as Origin of Scans Without Evidence of Dopaminergic Deficit.

The term scans without evidence of dopaminergic deficit (SWEDD) can be associated with any patient diagnosed at first with Parkinson's disease but with a negative dopamine transporter-single photon emission computed tomography (DaTSPECT), which does not confirm the presynaptic dopaminergic deficiency. Therefore, an alternative diagnosis should be sought to support parkinsonism as a clinical diagnosis. Parkinsonism is a well-known manifestation of frontotemporal lobar degeneration (FTLD), particularly frequent in those with positive DaTSPECT. Here, we reinforce previous observations that parkinsonism can be present in FTLD patients with negative DaTSPECT and therefore, FTLD may account for a percentage of patients with SWEDD. We gather the clinical observations supporting this hypothesis and describe a case report illustrating this idea. Studies suggest the result of DaTSPECT in FTLD may depend on the neuropathology and clinical subtype. However, most studies do not provide a clinical description of the clinical subtype or pathological features making the association between subtypes of FTLD and DaTSPECT results impossible at the moment. Further studies correlating clinical, neuropsychological, neuroimaging, genetic, and pathology findings are needed to better understand parkinsonism in FTLD.

A New Analysis of Resting State Connectivity and Graph Theory Reveals Distinctive Short-Term Modulations due to Whisker Stimulation in Rats.

Resting state (RS) connectivity has been increasingly studied in healthy and diseased brains in humans and animals. This paper presents a new method to analyze RS data from fMRI that combines multiple seed correlation analysis with graph-theory (MSRA). We characterize and evaluate this new method in relation to two other graph-theoretical methods and ICA. The graph-theoretical methods calculate cross-correlations of regional average time-courses, one using seed regions of the same size (SRCC) and the other using whole brain structure regions (RCCA). We evaluated the reproducibility, power, and capacity of these methods to characterize short-term RS modulation to unilateral physiological whisker stimulation in rats. Graph-theoretical networks found with the MSRA approach were highly reproducible, and their communities showed large overlaps with ICA components. Additionally, MSRA was the only one of all tested methods that had the power to detect significant RS modulations induced by whisker stimulation that are controlled by family-wise error rate (FWE). Compared to the reduced resting state network connectivity during task performance, these modulations implied decreased connectivity strength in the bilateral sensorimotor and entorhinal cortex. Additionally, the contralateral ventromedial thalamus (part of the barrel field related lemniscal pathway) and the hypothalamus showed reduced connectivity. Enhanced connectivity was observed in the amygdala, especially the contralateral basolateral amygdala (involved in emotional learning processes). In conclusion, MSRA is a powerful analytical approach that can reliably detect tiny modulations of RS connectivity. It shows a great promise as a method for studying RS dynamics in healthy and pathological conditions.

Depletion of Hypocretin/Orexin Neurons Increases Cell Proliferation in the Adult Subventricular Zone.

BACKGROUND & OBJECTIVE: Adult neurogenesis, a specific form of brain plasticity in mammals that occurs in the subventricular zone, is subject to complex regulation. Hypocretin/orexin neurons are implicated in the regulation of sleep and arousal states, among other functions. Here we report for the first time the presence of orexinergic projections within the adult rat subventricular zone. Post-mortem retrograde tracing combined with immunofluorescence indicated orexinergic projections toward the subventricular zone. To establish the relationship between the depletion of orexin neurons and the number of proliferating cells in the subventricular zone, we labeled mitotic cells. Histological analysis revealed proliferating cells to be in close contact with orexinergic fibers. Neurotoxinlesioning of orexin neurons in the lateral hypothalamus significantly activated precursor cell proliferation in the subventricular zone. Furthermore, cell proliferation in both normal and lesioned animals failed to reveal newly born orexin neurons in the lateral hypothalamus. CONCLUSION: Based on these findings, we suggest that the adult subventricular zone is affected by orexinergic signaling, the functional implication of which must be further elucidated.

Strategies for tonal and atonal musical interpretation in blind and normally sighted children: an fMRI study.

INTRODUCTION: Early childhood is known to be a period when cortical plasticity phenomena are at a maximum. Music is a stimulus known to modulate these mechanisms. On the other hand, neurological impairments like blindness are also known to affect cortical plasticity. Here, we address how tonal and atonal musical stimuli are processed in control and blind young children. We aimed to understand the differences between the two groups when processing this physiological information. RESULTS: Atonal stimuli produced larger activations in cerebellum, fusiform, and temporal lobe structures than tonal. In contrast, tonal stimuli induced larger frontal lobe representations than atonal. Control participants presented large activations in cerebellum, fusiform, and temporal lobe. A correlation/connectivity study showed that the blind group incorporated larger amounts of perceptual information (somatosensory and motor) into tonal processing through the function of the anterior prefrontal cortex (APC). They also used the visual cortex in conjunction with the Wernicke's area to process this information. In contrast, controls processed sound with perceptual stimuli from auditory cortex structures (including Wernicke's area). In this case, information was processed through the dorsal posterior cingulate cortex and not the APC. The orbitofrontal cortex also played a key role for atonal interpretation in this group. DISCUSSION: Wernicke's area, known to be involved in speech, was heavily involved for both groups and all stimuli. The two groups presented clear differences in strategies for music processing, with very different recruitment of brain regions.

Structural Neuroimaging of the Medial Temporal Lobe in Alzheimer's Disease Clinical Trials.

Atrophy in the medial temporal lobe (MTA) is being used as a criterion to support a diagnosis of Alzheimer's disease (AD). There are several structural neuroimaging approaches for quantifying MTA, including semiquantitative visual rating scales, volumetry (3D), planimetry (2D), and linear measures (1D). Current applications of structural neuroimaging in Alzheimer's disease clinical trials (ADCTs) incorporate it as a tool for improving the selection of subjects for enrollment or for stratification, for tracking disease progression, or providing evidence of target engagement for new therapeutic agents. It may also be used as a surrogate marker, providing evidence of disease-modifying effects. However, despite the widespread use of volumetric magnetic resonance imaging (MRI) in ADCTs, there are some important challenges and limitations, such as difficulties in the interpretation of results, limitations in translating results into clinical practice, and reproducibility issues, among others. Solutions to these issues may arise from other methodologies that are able to link the results of volumetric MRI from trials with conventional MRIs performed in routine clinical practice (linear or planimetric methods). Also of potential benefit are automated volumetry, using indices for comparing the relative rate of atrophy of different regions instead of absolute rates of atrophy, and combining structural neuroimaging with other biomarkers. In this review, authors present the existing structural neuroimaging approaches for MTA quantification. They then discuss solutions to the limitations of the different techniques as well as the current challenges of the field. Finally, they discuss how the current advances in AD neuroimaging can help AD diagnosis.

Magnetic Resonance Techniques Applied to the Diagnosis and Treatment of Parkinson's Disease.

Parkinson's disease (PD) affects at least 10 million people worldwide. It is a neurodegenerative disease, which is currently diagnosed by neurological examination. No neuroimaging investigation or blood biomarker is available to aid diagnosis and prognosis. Most effort toward diagnosis using magnetic resonance (MR) has been focused on the use of structural/anatomical neuroimaging and diffusion tensor imaging (DTI). However, deep brain stimulation, a current strategy for treating PD, is guided by MR imaging (MRI). For clinical prognosis, diagnosis, and follow-up investigations, blood oxygen level-dependent MRI, DTI, spectroscopy, and transcranial magnetic stimulation have been used. These techniques represent the state of the art in the last 5 years. Here, we focus on MR techniques for the diagnosis and treatment of Parkinson's disease.

Tractography of the spider monkey (Ateles geoffroyi) corpus callosum using diffusion tensor magnetic resonance imaging.

The objective of this research was to describe the organization, connectivity and microstructure of the corpus callosum of the spider monkey (Ateles geoffroyi). Non-invasive magnetic resonance imaging and diffusion-tensor imaging were obtained from three subjects using a 3T Philips scanner. We hypothesized that the arrangement of fibers in spider monkeys would be similar to that observed in other non-human primates. A repeated measure (n = 3) of fractional anisotropy values was obtained of each subject and for each callosal subdivision. Measurements of the diffusion properties of corpus callosum fibers exhibited a similar pattern to those reported in the literature for humans and chimpanzees. No statistical difference was reached when comparing this parameter between the different CC regions (p = 0.066). The highest fractional anisotropy values corresponded to regions projecting from the corpus callosum to the posterior cortical association areas, premotor and supplementary motor cortices. The lowest fractional anisotropy corresponded to projections to motor and sensory cortical areas. Analyses indicated that approximately 57% of the fibers projects to the frontal cortex and 43% to the post-central cortex. While this study had a small sample size, the results provided important information concerning the organization of the corpus callosum in spider monkeys.

Rapid Bidirectional Reorganization of Cortical Microcircuits.

Mature neocortex adapts to altered sensory input by changing neural activity in cortical circuits. The underlying cellular mechanisms remain unclear. We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to show reorganization in somatosensory cortex elicited by altered whisker sensory input. We found that there was rapid expansion followed by retraction of whisker cortical maps. The cellular basis for the reorganization in primary somatosensory cortex was investigated with paired electrophysiological recordings in the periphery of the expanded whisker representation. During map expansion, the chance of finding a monosynaptic connection between pairs of pyramidal neurons increased 3-fold. Despite the rapid increase in local excitatory connectivity, the average strength and synaptic dynamics did not change, which suggests that new excitatory connections rapidly acquire the properties of established excitatory connections. During map retraction, entire excitatory connections between pyramidal neurons were lost. In contrast, connectivity between pyramidal neurons and fast spiking interneurons was unchanged. Hence, the changes in local excitatory connectivity did not occur in all circuits involving pyramidal neurons. Our data show that pyramidal neurons are recruited to and eliminated from local excitatory networks over days. These findings suggest that the local excitatory connectome is dynamic in mature neocortex.

Lateralization of responses to vibrissal stimulation: connectivity and information integration in the rat sensory-motor cortex assessed with fMRI.

Rats move their whiskers or vibrissae to gain sensory information about the world surrounding them. A single whisker can work as an independent detector but normal whisking involves the use of several vibrissae in a bilateral fashion. Here we used blood oxygen level dependent (BOLD) contrast to acquire functional magnetic resonance images (fMRI) of the rat brain activity during uni- and bilateral whisker stimulations with different timing schemes under Isoflurane anesthesia. Experiments were performed to assess the integration of bilateral information produced by normal whisking behavior. First, we showed that it was possible to obtain BOLD whisker activations using Isoflurane harmless for the animals and thus allowing for future repetitive/longitudinal studies. Second, we obtained different BOLD activation patterns depending on the number of stimulated whiskers and timing of the stimulation scheme. Third, we found lateralization of BOLD activations in the somatosensory-motor cortex. It manifested itself in considerably larger activations in the right hemisphere during equal bilateral whisker stimulation. Fourth, we found Granger Causality Analysis (GCA) to be a useful tool in information integration analysis, as it reproduced the stimulus specific Cross-correlation Analysis results. Both analyses showed that the amount of whiskers stimulated and the timing of stimulation lead to specific dynamic connectivity patterns. Finally, by adding directionality information GCA revealed meaningful lateralization of information processing in the rat whisker system consistent with the observed BOLD activation patterns.