Journal publications

  1. Pavlína Hlavatá, Pavla Linhartová, Rastislav Šumec, Pavel Filip, Miroslav Světlák, Marek Baláž, Tomáš Kašpárek and Martin Bareš.
    Behavioral and Neuroanatomical Account of Impulsivity in Parkinson's Disease.. Frontiers in neurology 10:1338, 2019.
    Abstract Impulse control disorder (ICD) is a major non-motor complication of Parkinson's disease (PD) with often devastating consequences for patients' quality of life. In this study, we aimed to characterize the phenotype of impulsivity in PD and its neuroanatomical correlates. Thirty-seven PD patients (15 patients with ICD, 22 patients without ICD) and 36 healthy controls underwent a neuropsychological battery. The test battery consisted of anxiety and depression scales, self-report measures of impulsivity (Barratt scale and UPPS-P), behavioral measures of impulsive action (Go/No-Go task, Stop signal task) and impulsive choice (Delay discounting, Iowa gambling task), and measures of cognitive abilities (working memory, attention, executive function). Patients and controls underwent structural MRI scanning. Patients with ICD had significantly higher levels of self-reported impulsivity (Barratt scale and Lack of perseverance from UPPS-P) in comparison with healthy controls and non-impulsive PD patients, but they performed similarly in behavioral tasks, except for the Iowa gambling task. In this task, patients with ICD made significantly less risky decisions than patients without ICD and healthy controls. Patients without ICD did not differ from healthy controls in self-reported impulsivity or behavioral measurements. Both patient groups were more anxious and depressive than healthy controls. MRI scanning revealed structural differences in cortical areas related to impulse control in both patient groups. Patients without ICD had lower volumes and cortical thickness of bilateral inferior frontal gyrus. Patients with ICD had higher volumes of right caudal anterior cingulate and rostral middle frontal cortex. Despite the presence of ICD as confirmed by both clinical follow-up and self-reported impulsivity scales and supported by structural differences in various neural nodes related to inhibitory control and reward processing, patients with ICD performed no worse than healthy controls in various behavioral tasks previously hypothesized as robust impulsivity measures. These results call for caution against impetuous interpretation of behavioral tests, since various factors may and will influence the ultimate outcomes, be it the lack of sensitivity in specific, limited ICD subtypes, excessive caution of ICD patients during testing due to previous negative experience rendering simplistic tasks insufficient, or other, as of now unknown aspects, calling for further research.

  2. Juan Miguel Valverde, Artem Shatillo, Riccardo De Feo, Olli Gröhn, Alejandra Sierra and Jussi Tohka.
    Automatic Rodent Brain MRI Lesion Segmentation with Fully Convolutional Networks. In International Workshop on Machine Learning in Medical Imaging. 2019, 195–202.
    Abstract Manual segmentation of rodent brain lesions from magnetic resonance images (MRIs) is an arduous, time-consuming and subjective task that is highly important in pre-clinical research. Several automatic methods have been developed for dierent human brain MRI segmentation, but little research has targeted automatic rodent lesion segmentation. The existing tools for performing automatic lesion segmentation in rodents are constrained by strict assumptions about the data. Deep learning has been successfully used for medical image segmentation. However, there has not been any deep learning approach specically designed for tackling rodent brain lesion segmentation. In this work, we propose a novel Fully Convolutional Network (FCN), RatLesNet, for the aforementioned task. Our dataset consists of 131 T2-weighted rat brain scans from 4 dierent studies in which ischemic stroke was induced by transient middle cerebral artery occlusion.We compare our method with two other 3D FCNs originally developed for anatomical segmentation (VoxResNet and 3D-U-Net) with 5-fold cross-validation on a single study and a generalization test, where the training was done on a single study and testing on three remaining studies. The labels generated by our method were quantitatively and qualitatively better than the predictions of the compared methods. The average Dice coecient achieved in the 5-fold crossvalidation experiment with the proposed approach was 0.88, between 3.7% and 38% higher than the compared architectures. The presented architecture also outperformed the other FCNs at generalizing on dierent studies, achieving the average Dice coecient of 0.79.

  3. Martin Bareš, Richard Apps, Laura Avanzino, Assaf Breska, Egidio D'Angelo, Pavel Filip, Marcus Gerwig, Richard B Ivry, Charlotte L Lawrenson, Elan D Louis, Nicholas A Lusk, Mario Manto, Warren H Meck, Hiroshi Mitoma and Elijah A Petter.
    Consensus paper: Decoding the Contributions of the Cerebellum as a Time Machine. From Neurons to Clinical Applications.. Cerebellum (London, England) 18:266–286, 2019.
    Abstract Time perception is an essential element of conscious and subconscious experience, coordinating our perception and interaction with the surrounding environment. In recent years, major technological advances in the field of neuroscience have helped foster new insights into the processing of temporal information, including extending our knowledge of the role of the cerebellum as one of the key nodes in the brain for this function. This consensus paper provides a state-of-the-art picture from the experts in the field of the cerebellar research on a variety of crucial issues related to temporal processing, drawing on recent anatomical, neurophysiological, behavioral, and clinical research.The cerebellar granular layer appears especially well-suited for timing operations required to confer millisecond precision for cerebellar computations. This may be most evident in the manner the cerebellum controls the duration of the timing of agonist-antagonist EMG bursts associated with fast goal-directed voluntary movements. In concert with adaptive processes, interactions within the cerebellar cortex are sufficient to support sub-second timing. However, supra-second timing seems to require cortical and basal ganglia networks, perhaps operating in concert with cerebellum. Additionally, sensory information such as an unexpected stimulus can be forwarded to the cerebellum via the climbing fiber system, providing a temporally constrained mechanism to adjust ongoing behavior and modify future processing. Patients with cerebellar disorders exhibit impairments on a range of tasks that require precise timing, and recent evidence suggest that timing problems observed in other neurological conditions such as Parkinson's disease, essential tremor, and dystonia may reflect disrupted interactions between the basal ganglia and cerebellum.The complex concepts emerging from this consensus paper should provide a foundation for further discussion, helping identify basic research questions required to understand how the brain represents and utilizes time, as well as delineating ways in which this knowledge can help improve the lives of those with neurological conditions that disrupt this most elemental sense. The panel of experts agrees that timing control in the brain is a complex concept in whom cerebellar circuitry is deeply involved. The concept of a timing machine has now expanded to clinical disorders.

  4. Silvia Tommasin, Daniele Mascali, Marta Moraschi, Tommaso Gili, Ibrahim Eid Hassan, Michela Fratini, Mauro DiNuzzo, Richard G Wise, Silvia Mangia, Emiliano Macaluso and Federico Giove.
    Scale-invariant rearrangement of resting state networks in the human brain under sustained stimulation.. NeuroImage 179:570–581, October 2018.
    Abstract Brain activity at rest is characterized by widely distributed and spatially specific patterns of synchronized low-frequency blood-oxygenation level-dependent (BOLD) fluctuations, which correspond to physiologically relevant brain networks. This network behaviour is known to persist also during task execution, yet the details underlying task-associated modulations of within- and between-network connectivity are largely unknown. In this study we exploited a multi-parametric and multi-scale approach to investigate how low-frequency fluctuations adapt to a sustained n-back working memory task. We found that the transition from the resting state to the task state involves a behaviourally relevant and scale-invariant modulation of synchronization patterns within both task-positive and default mode networks. Specifically, decreases of connectivity within networks are accompanied by increases of connectivity between networks. In spite of large and widespread changes of connectivity strength, the overall topology of brain networks is remarkably preserved. We show that these findings are strongly influenced by connectivity at rest, suggesting that the absolute change of connectivity (i.e., disregarding the baseline) may not be the most suitable metric to study dynamic modulations of functional connectivity. Our results indicate that a task can evoke scale-invariant, distributed changes of BOLD fluctuations, further confirming that low frequency BOLD oscillations show a specialized response and are tightly bound to task-evoked activation.

  5. Julia P Slopsema, Edgar Peña, Remi Patriat, Lauri J Lehto, Olli Gröhn, Silvia Mangia, Noam Harel, Shalom Michaeli and Matthew D Johnson.
    Clinical deep brain stimulation strategies for orientation-selective pathway activation.. Journal of neural engineering 15:056029, October 2018.
    Abstract This study investigated stimulation strategies to increase the selectivity of activating axonal pathways within the brain based on their orientations relative to clinical deep brain stimulation (DBS) lead implants. Previous work has shown how varying electrode shape and controlling the primary electric field direction through preclinical electrode arrays can produce orientation-selective axonal stimulation. Here, we significantly extend those results using computational models to evaluate the degree to which clinical DBS leads can direct stimulus-induced electric fields and generate orientation-selective activation of fiber pathways in the brain. Orientation-selective pulse paradigms were evaluated in conceptual models and in patient-specific models of subthalamic nucleus (STN)-DBS for treating Parkinson's disease. Single-contact monopolar or two-contact bipolar stimulation through clinical DBS leads with cylindrical electrodes primarily activated axons orientated parallel to the lead. Conversely, multi-contact monopolar stimulation with a cathode-leading pulse waveform selectively activated axons perpendicular to the DBS lead. Clinical DBS leads with segmented rows of electrodes and a single current source provided additional angular resolution for activating axons oriented 0°, ±22.5°, ±45°, ±67.5°, or 90° relative to the lead shaft. Employing multiple independent current sources to deliver unequal amounts of current through these leads further increased the angular resolution of activation relative to the lead shaft. The patient-specific models indicated that multi-contact cathode configurations, which are rarely used in clinical practice, could increase activation of the hyperdirect pathway collaterals projecting into STN (a putative therapeutic target), while minimizing direct activation of the corticospinal tract of internal capsule, which can elicit sensorimotor side-effects when stimulated. When combined with patient-specific tissue anisotropy and patient-specific anatomical morphologies of neural pathways responsible for therapy and side effects, orientation-selective DBS approaches show potential to significantly improve clinical outcomes of DBS therapy for a range of existing and investigational clinical indications.

  6. Pavel Filip, Pavla Linhartová, Pavlína Hlavatá, Rastislav Šumec, Marek Baláž, Martin Bareš and Tomáš Kašpárek.
    Disruption of Multiple Distinctive Neural Networks Associated With Impulse Control Disorder in Parkinson's Disease.. Frontiers in human neuroscience 12:462, 2018.
    Abstract The phenomenon of impulsivity in Parkinson's disease appears as an arduous side effect of dopaminergic therapy with potentially detrimental consequences for the life of the patients. Although conceptualized as a result of non-physiologic chronic dopaminergic stimulation, recent advances speculate on combined disruption of other networks as well. In the search for neuroanatomical correlates of this multifaceted disturbance, this study employs two distinct, well-defined tasks of close association to motor inhibition and decision-making impulsivity, Go/No Go and Delay discounting. The fMRI and functional connectivity analysis in 21 Parkinson's disease patients, including 8 patients suffering from severe impulse control disorder, and 28 healthy controls, revealed in impulsive Parkinson's disease patients not only decreased fMRI activation in the dorsolateral prefrontal cortex and bilateral striatum, but also vast functional connectivity changes of both caudate nuclei as decreased connectivity to the superior parietal cortex and increased connectivity to the insular area, clearly beyond the commonly stated areas, which indicates that orbitofronto-striatal and mesolimbic functional disruptions are not the sole mechanisms underlying impulse control disorder in Parkinson's disease. Ergo, our results present a refinement and synthesis of gradually developing ideas about the nature of impulsive control disorder in Parkinson's disease-an umbrella term encompassing various behavioral deviations related to distinct neuronal networks and presumably neurotransmitter systems, which greatly exceed the previously envisioned dopaminergic pathways as the only culprit.

  7. E Stefanutti, A Sierra, P Miocchi, L Massimi, F Brun, L Maugeri, I Bukreeva, A Nurmi, Begani G Provinciali, G Tromba and others.
    Assessment of the effects of different sample perfusion procedures on phase-contrast tomographic images of mouse spinal cord. Journal of Instrumentation 13(03):C03027, 2018.
    Abstract Synchrotron X-ray Phase Contrast micro-Tomography (SXrPCT) is a powerful tool in the investigation of biological tissues, including the central nervous system (CNS), and it allows to simultaneously detect the vascular and neuronal network avoiding contrast agents or destructive sample preparations. However, specific sample preparation procedures aimed to optimize the achievable contrast- and signal-to-noise ratio (CNR and SNR, respectively) are required. report and discuss the effects of perfusion with two different fixative agents (ethanol and paraformaldehyde) and with a widely used contrast medium (MICROFIL) on mouse spinal cord. As a main result, we found that ethanol enhances contrast at the grey/white matter interface and increases the contrast in correspondence of vascular features and fibres, thus providing an adequate spatial resolution to visualise the vascular network at the microscale. On the other hand, ethanol is known to induce tissue dehydration, likely reducing cell dimensions below the spatial resolution limit imposed by the experimental technique. Nonetheless, neurons remain well visible using paraformaldehyde or MICROFIL compound, as these latter media do not affect tissues with dehydration effects. Paraformaldehyde appears as the best compromise: it is not a contrast agent, like MICROFIL, but it is less invasive than ethanol and permits to visualise well both cells and blood vessels. However, a quantitative estimation of the relative grey matter volume of each sample has led us to conclude that no significant alterations in the grey matter extension compared to the white matter occur as a consequence of the perfusion procedures tested in this study.

  8. Timo Liimatainen, Hanne Laakso, Djaudat Idiyatullin, Silvia Mangia and Shalom Michaeli.
    Capturing exchange using periodic radiofrequency irradiation.. Journal of magnetic resonance (San Diego, Calif. : 1997) 296:79–84, 2018.
    Abstract The dynamics of spin system coupled by chemical exchange between two sites with different chemical shifts during periodic radiofrequency (RF) irradiation was here investigated. When the instantaneous π-flip of effective frequency during the course of frequency sweep was applied, a significant increase of exchange-induced relaxation rate constants was observed for small tip angle of magnetization in the laboratory frame of reference. This increase of the rate constants corresponds to the side bands generated by the periodic irradiation during the RF pulses. The exchange - induced relaxation rate constants depend on the exchange conditions, the RF power and the irradiation period. The described phenomenon promises applications for studying protein dynamics and for generating exchange specific relaxation contrasts in MRI.

  9. Lauri J Lehto, Pavel Filip, Hanne Laakso, Alejandra Sierra, Julia P Slopsema, Matthew D Johnson, Lynn E Eberly, Walter C Low, Olli Gröhn, Heikki Tanila, Silvia Mangia and Shalom Michaeli.
    Tuning Neuromodulation Effects by Orientation Selective Deep Brain Stimulation in the Rat Medial Frontal Cortex.. Frontiers in neuroscience 12:899, 2018.
    Abstract Previous studies that focused on treating major depressive disorder with conventional deep brain stimulation (DBS) paradigms produced inconsistent results. In this proof-of-concept preclinical study in rats ( = 8), we used novel paradigms of orientation selective DBS for stimulating the complex circuitry crossing the infralimbic cortex, an area considered analogous to human subgenual cingulate cortex. Using functional MRI at 9.4 T, we monitored whole brain responses to varying the electrical field orientation of DBS within the infralimbic cortex. Substantial alterations of functional MRI responses in the amygdala, a major node connected to the infralimbic cortex implicated in the pathophysiology of depression, were observed. As expected, the activation cluster near the electrode was insensitive to the changes of the stimulation orientation. Hence, our findings substantiate the ability of orientation selective stimulation (OSS) to recruit neuronal pathways of distinct orientations relative to the position of the electrode, even in complex circuits such as those involved in major depressive disorder. We conclude that OSS is a promising approach for stimulating brain areas that inherently require individualisation of the treatment approach.

  10. Ivan Rektor, Alena Svátková, Lubomir Vojtíšek, Iva Zikmundová, Jirí Vaníček, András Király and Nikoletta Szabó.
    White matter alterations in Parkinson's disease with normal cognition precede grey matter atrophy.. PloS one 13:e0187939, 2018.
    Abstract While progressive MRI brain changes characterize advanced Parkinson's disease (PD), little has been discovered about structural alterations in the earliest phase of the disease, i.e. in patients with motor symptoms and with normal cognition. Our study aimed to detect grey matter (GM) and white matter (WM) changes in PD patients without cognitive impairment. Twenty PD patients and twenty-one healthy controls (HC) were tested for attention, executive function, working memory, and visuospatial and language domains. High-resolution T1-weighted and 60 directional diffusion-weighted 3T MRI images were acquired. The cortical, deep GM and WM volumes and density, as well as the diffusion properties of WM, were calculated. Analyses were repeated on data flipped to the side of the disease origin. PD patients did not show any significant differences from HC in cognitive functioning or in brain volumes. Decreased GM intensity was found in the left superior parietal lobe in the right (p<0.02) and left (p<0.01) flipped data. The analysis of original, un-flipped data demonstrated elevated axial diffusivity (p<0.01) in the superior and anterior corona radiata, internal capsule, and external capsule in the left hemisphere of PD relative to HC, while higher mean and radial diffusivity were discovered in the right (p<0.02 and p<0.03, respectively) and left (p<0.02 and p<0.02, respectively) in the fronto-temporal WM utilizing flipped data. PD patients without cognitive impairment and GM atrophy demonstrated widespread alterations of WM microstructure. Thus, WM impairment in PD might be a sensitive sign preceding the neuronal loss in associated GM regions.

  11. Lauri J Lehto, Djaudat Idiyatullin, Jinjin Zhang, Lynn Utecht, Gregor Adriany, Michael Garwood, Olli Gröhn, Shalom Michaeli and Silvia Mangia.
    MB-SWIFT functional MRI during deep brain stimulation in rats.. NeuroImage 159:443–448, 2017.
    Abstract Recently introduced 3D radial MRI pulse sequence entitled Multi-Band SWeep Imaging with Fourier Transformation (MB-SWIFT) having virtually zero acquisition delay was used to obtain functional MRI (fMRI) contrast in rat's brain at 9.4 T during deep brain stimulation (DBS). The results demonstrate that MB-SWIFT allows functional images free of susceptibility artifacts, and provides an excellent fMRI activation contrast in the brain. Flip angle dependence of the MB-SWIFT fMRI signal and elimination of the fMRI contrast while using saturation bands, indicate a blood flow origin of the observed fMRI contrast. MB-SWIFT fMRI modality permits activation studies in the close proximity to an implanted lead, which is not possible to achieve with conventionally used gradient echo and spin echo - echo planar imaging fMRI techniques. We conclude that MB-SWIFT fMRI is a powerful imaging modality for investigations of functional responses during DBS.

  12. Silvia Mangia, Alena Svatkova, Daniele Mascali, Mikko J Nissi, Philip C Burton, Petr Bednarik, Edward J Auerbach, Federico Giove, Lynn E Eberly, Michael J Howell, Igor Nestrasil, Paul J Tuite and Shalom Michaeli.
    Multi-modal Brain MRI in Subjects with PD and iRBD.. Frontiers in neuroscience 11:709, 2017.
    Abstract Idiopathic rapid eye movement sleep behavior disorder (iRBD) is a condition that often evolves into Parkinson's disease (PD). Therefore, by monitoring iRBD it is possible to track the neurodegeneration of individuals who may progress to PD. Here we aimed at piloting the characterization of brain tissue properties in mid-brain subcortical regions of 10 healthy subjects, 8 iRBD, and 9 early-diagnosed PD. We used a battery of magnetic resonance imaging (MRI) contrasts at 3 T, including adiabatic and non-adiabatic rotating frame techniques developed by our group, along with diffusion tensor imaging (DTI) and resting-state fMRI. Adiabatic T and T , and non-adiabatic RAFF4 (Relaxation Along a Fictitious Field in the rotating frame of rank 4) were found to have lower coefficient of variations and higher sensitivity to detect group differences as compared to DTI parameters such as fractional anisotropy and mean diffusivity. Significantly longer T were observed in the amygdala of PD subjects vs. controls, along with a trend of lower functional connectivity as measured by regional homogeneity, thereby supporting the notion that amygdalar dysfunction occurs in PD. Significant abnormalities in reward networks occurred in iRBD subjects, who manifested lower network strength of the accumbens. In agreement with previous studies, significantly longer T occurred in the substantia nigra compacta of PD vs. controls, indicative of neuronal degeneration, while regional homogeneity was lower in the substantia nigra reticulata. Finally, other trend-level findings were observed, i.e., lower RAFF4 and T in the midbrain of iRBD subjects vs. controls, possibly indicating changes in non-motor features as opposed to motor function in the iRBD group. We conclude that rotating frame relaxation methods along with functional connectivity measures are valuable to characterize iRBD and PD subjects, and with proper validation in larger cohorts may provide pathological signatures of iRBD and PD.

  13. Lauri J Lehto, Julia P Slopsema, Matthew D Johnson, Artem Shatillo, Benjamin A Teplitzky, Lynn Utecht, Gregor Adriany, Silvia Mangia, Alejandra Sierra, Walter C Low, Olli Gröhn and Shalom Michaeli.
    Orientation selective deep brain stimulation.. Journal of neural engineering 14:016016, 2017.
    Abstract Target selectivity of deep brain stimulation (DBS) therapy is critical, as the precise locus and pattern of the stimulation dictates the degree to which desired treatment responses are achieved and adverse side effects are avoided. There is a clear clinical need to improve DBS technology beyond currently available stimulation steering and shaping approaches. We introduce orientation selective neural stimulation as a concept to increase the specificity of target selection in DBS. This concept, which involves orienting the electric field along an axonal pathway, was tested in the corpus callosum of the rat brain by freely controlling the direction of the electric field on a plane using a three-electrode bundle, and monitoring the response of the neurons using functional magnetic resonance imaging (fMRI). Computational models were developed to further analyze axonal excitability for varied electric field orientation. Our results demonstrated that the strongest fMRI response was observed when the electric field was oriented parallel to the axons, while almost no response was detected with the perpendicular orientation of the electric field relative to the primary fiber tract. These results were confirmed by computational models of the experimental paradigm quantifying the activation of radially distributed axons while varying the primary direction of the electric field. The described strategies identify a new course for selective neuromodulation paradigms in DBS based on axonal fiber orientation.

  14. Lauri J Lehto, Aloma A Albors, Alejandra Sierra, Laura Tolppanen, Lynn E Eberly, Silvia Mangia, Antti Nurmi, Shalom Michaeli and Olli Gröhn.
    Lysophosphatidyl Choline Induced Demyelination in Rat Probed by Relaxation along a Fictitious Field in High Rank Rotating Frame.. Frontiers in neuroscience 11:433, 2017.
    Abstract In this work a new MRI modality entitled Relaxation Along a Fictitious Field in the rotating frame of rank 4 (RAFF4) was evaluated in its ability to detect lower myelin content in lysophosphatidyl choline (LPC)-induced demyelinating lesions. The lesions were induced in two areas of the rat brain with either uniform or complex fiber orientations, i.e., in the corpus callosum (cc) and dorsal tegmental tract (dtg), respectively. RAFF4 showed excellent ability to detect demyelinated lesions and good correlation with myelin content in both brain areas. In comparison, diffusion tensor imaging metrices, fractional anisotropy, mean diffusivity and axonal and radial diffusivity, and magnetization transfer (MT) metrices, longitudinal relaxation during off-resonance irradiation and MT ratio, either failed to detect demyelination in dtg or showed lower correlation with myelin density quantified from gold chloride stained histological sections. Good specifity of RAFF4 to myelin was confirmed by its low correlation with cell density assesed from Nissl stained sections as well as its lack of sensitivity to pH changes in the physiological range as tested in heat denaturated bovine serum albumin phantoms. The excellent ability of RAFF4 to detect myelin content and its insensitivity to fiber orientation distribution, gliosis and pH, together with low specific absorption rate, demonstrates the promise of rotating frame of rank (RAFFn) as a valuable MRI technique for non-invasive imaging of demyelinating lesions.

  15. Silvia Tommasin, Daniele Mascali, Tommaso Gili, Ibrahim Eid Assan, Marta Moraschi, Michela Fratini, Richard G Wise, Emiliano Macaluso, Silvia Mangia and Federico Giove.
    Task-Related Modulations of BOLD Low-Frequency Fluctuations within the Default Mode Network.. Frontiers in Physics 5, 2017.
    Abstract Spontaneous low-frequency Blood-Oxygenation Level-Dependent (BOLD) signals acquired during resting state are characterized by spatial patterns of synchronous fluctuations, ultimately leading to the identification of robust brain networks. The resting-state brain networks, including the Default Mode Network (DMN), are demonstrated to persist during sustained task execution, but the exact features of task-related changes of network properties are still not well characterized. In this work we sought to examine in a group of 20 healthy volunteers (age 33 ± 6 years, 8 F/12 M) the relationship between changes of spectral and spatiotemporal features of one prominent resting-state network, namely the DMN, during the continuous execution of a working memory n-back task. We found that task execution impacted on both functional connectivity and amplitude of BOLD fluctuations within large parts of the DMN, but these changes correlated between each other only in a small area of the posterior cingulate. We conclude that combined analysis of multiple parameters related to connectivity, and their changes during the transition from resting state to continuous task execution, can contribute to a better understanding of how brain networks rearrange themselves in response to a task.

  16. Daniele Mascali, Mauro DiNuzzo, Laura Serra, Silvia Mangia, Bruno Maraviglia, Marco Bozzali and Federico Giove.
    Disruption of Semantic Network in Mild Alzheimer's Disease Revealed by Resting-State fMRI.. Neuroscience 371:38–48, 2017.
    Abstract Subtle semantic deficits can be observed in Alzheimer's disease (AD) patients even in the early stages of the illness. In this work, we tested the hypothesis that the semantic control network is deregulated in mild AD patients. We assessed the integrity of the semantic control system using resting-state functional magnetic resonance imaging in a cohort of patients with mild AD (n = 38; mean mini-mental state examination = 20.5) and in a group of age-matched healthy controls (n = 19). Voxel-wise analysis spatially constrained in the left fronto-temporal semantic control network identified two regions with altered functional connectivity (FC) in AD patients, specifically in the pars opercularis (POp, BA44) and in the posterior middle temporal gyrus (pMTG, BA21). Using whole-brain seed-based analysis, we demonstrated that these two regions have altered FC even beyond the semantic control network. In particular, the pMTG displayed a wide-distributed pattern of lower connectivity to several brain regions involved in language-semantic processing, along with a possibly compensatory higher connectivity to the Wernicke's area. We conclude that in mild AD brain regions belonging to the semantic control network are abnormally connected not only within the network, but also to other areas known to be critical for language processing.

  17. Mauro DiNuzzo, Daniele Mascali, Marta Moraschi, Giorgia Bussu, Bruno Maraviglia, Silvia Mangia and Federico Giove.
    Temporal Information Entropy of the Blood-Oxygenation Level-Dependent Signals Increases in the Activated Human Primary Visual Cortex.. Frontiers in physics 5, 2017.
    Abstract Time-domain analysis of blood-oxygenation level-dependent (BOLD) signals allows the identification of clusters of voxels responding to photic stimulation in primary visual cortex (V1). However, the characterization of information encoding into temporal properties of the BOLD signals of an activated cluster is poorly investigated. Here, we used Shannon entropy to determine spatial and temporal information encoding in the BOLD signal within the most strongly activated area of the human visual cortex during a hemifield photic stimulation. We determined the distribution profile of BOLD signals during epochs at rest and under stimulation within small (19-121 voxels) clusters designed to include only voxels driven by the stimulus as highly and uniformly as possible. We found consistent and significant increases (2-4% on average) in temporal information entropy during activation in contralateral but not ipsilateral V1, which was mirrored by an expected loss of spatial information entropy. These opposite changes coexisted with increases in both spatial and temporal mutual information (i.e., dependence) in contralateral V1. Thus, we showed that the first cortical stage of visual processing is characterized by a specific spatiotemporal rearrangement of intracluster BOLD responses. Our results indicate that while in the space domain BOLD maps may be incapable of capturing the functional specialization of small neuronal populations due to relatively low spatial resolution, some information encoding may still be revealed in the temporal domain by an increase of temporal information entropy.