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Many efforts have been made in the last few decades to selectively transport antitumor agents to their potential target sites with the aim to improve efficacy and selectivity. Indeed, this aspect could greatly improve the beneficial effects of a specific anticancer agent especially in the case of orphan tumors like the triple negative breast cancer. A possible strategy relies on utilizing a protective leaving group like alizarin as the Pt(II) ligand to reduce the deactivation processes of the pharmacophore enacted by Pt resistant cancer cells. In this study a new series of neutral mixed-ligand Pt(II) complexes bearing alizarin and a variety of diamine ligands were synthesized and spectroscopically characterized by FT-IR, NMR and UV-Vis analyses. Three Pt(II) compounds, i.e. , 2b, 6b and 7b, emerging as different both in terms of structural properties and cytotoxic effects (not effective, 10.49 ± 1.21 μM and 24.5 ± 1.5 μM, respectively), were chosen for a deeper investigation of the ability of alizarin to work as a selective carrier. The study comprises the in vitro cytotoxicity evaluation against triple negative breast cancer cell lines and ESI-MS interaction studies relative to the reaction of the selected Pt(II) complexes with model proteins and DNA fragments, mimicking potential biological targets. The results allow us to suggest the use of complex 6b as a prospective anticancer agent worthy of further investigations.

One of the main problems in chemotherapy using platinum drugs as anticancer agents is the resistance phenomenon. Synthesizing and evaluating valid alternative compounds is challenging. This review focuses on the last two years of progress in the studies of platinum (II)- and platinum (IV)-based anticancer complexes. In particular, the research studies reported herein focus on the capability of some platinum-based anticancer agents to bypass resistance to chemotherapy, which is typical of well-known drugs such as cisplatin. Regarding platinum (II) complexes, this review deals with complexes in trans conformation; complexes containing bioactive ligands, as well as those that are differently charged, all experience a different reaction mechanism compared with cisplatin. Regarding platinum (IV) compounds, the focus was on complexes with biologically active ancillary ligands that exert a synergistic effect with platinum (II)-active complexes upon reduction, or those for which controllable activation can be realized thanks to intracellular stimuli.

Visuospatial attention is strongly lateralized, with the right hemisphere commonly exhibiting stronger activation and connectivity patterns than the left hemisphere during attentive processes. However, whether such asymmetry influences inter-hemispheric information transfer and behavioral performance is not known. Here we used a region of interest (ROI) and network-based approach to determine steady-state fMRI functional connectivity (FC) in the whole cerebral cortex during a leftward/rightward covert visuospatial attention task. We found that the global FC topology between either ROIs or networks was independent on the attended side. The side of attention significantly modulated FC strength between brain networks, with leftward attention primarily involving the connections of the right visual network with dorsal and ventral attention networks in both the left and right hemisphere. High hemispheric functional segregation significantly correlated with faster target detection response times (i.e., better performance). Our findings suggest that the dominance of the right hemisphere in visuospatial attention is associated with an hemispheric functional segregation that is beneficial for behavioral performance., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Processing of incoming sensory stimulation triggers an increase of cerebral perfusion and blood oxygenation (neurovascular response) as well as an alteration of the metabolic neurochemical profile (neurometabolic response). Here, we show in human primary visual cortex (V1) that perceived and unperceived isoluminant chromatic flickering stimuli designed to have similar neurovascular responses as measured by blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) have markedly different neurometabolic responses as measured by proton functional magnetic resonance spectroscopy (1H-fMRS). In particular, a significant regional buildup of lactate, an index of aerobic glycolysis, and glutamate, an index of malate-aspartate shuttle, occurred in V1 only when the flickering was perceived, without any relation with other behavioral or physiological variables. Whereas the BOLD-fMRI signal in V1, a proxy for input to V1, was insensitive to flickering perception by design, the BOLD-fMRI signal in secondary visual areas was larger during perceived than unperceived flickering, indicating increased output from V1. These results demonstrate that the upregulation of energy metabolism induced by visual stimulation depends on the type of information processing taking place in V1, and that 1H-fMRS provides unique information about local input/output balance that is not measured by BOLD-fMRI., Competing Interests: MD, SM, MM, DM, GH, FG No competing interests declared, (© 2022, DiNuzzo et al.)

In-scanner head motion represents a major confounding factor in functional connectivity studies and it raises particular concerns when motion correlates with the effect of interest. One such instance regards research focused on functional connectivity modulations induced by sustained cognitively demanding tasks. Indeed, cognitive engagement is generally associated with substantially lower in-scanner movement compared with unconstrained, or minimally constrained, conditions. Consequently, the reliability of condition-dependent changes in functional connectivity relies on effective denoising strategies. In this study, we evaluated the ability of common denoising pipelines to minimize and balance residual motion-related artifacts between resting-state and task conditions. Denoising pipelines-including realignment/tissue-based regression, PCA/ICA-based methods (aCompCor and ICA-AROMA, respectively), global signal regression, and censoring of motion-contaminated volumes-were evaluated according to a set of benchmarks designed to assess either residual artifacts or network identifiability. We found a marked heterogeneity in pipeline performance, with many approaches showing a differential efficacy between rest and task conditions. The most effective approaches included aCompCor, optimized to increase the noise prediction power of the extracted confounding signals, and global signal regression, although both strategies performed poorly in mitigating the spurious distance-dependent association between motion and connectivity. Censoring was the only approach that substantially reduced distance-dependent artifacts, yet this came at the great cost of reduced network identifiability. The implications of these findings for best practice in denoising task-based functional connectivity data, and more generally for resting-state data, are discussed., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Spontaneous oscillations of the blood oxygenation level-dependent (BOLD) signal are spatially synchronized within specific brain networks and are thought to reflect synchronized brain activity. Networks are modulated by the performance of a task, even if the exact features and degree of such modulations are still elusive. The presence of networks showing anticorrelated fluctuations lend initially to suppose that a competitive relationship between the default mode network (DMN) and task positive networks (TPNs) supports the efficiency of brain processing. However, more recent results indicate that cooperative and competitive dynamics between networks coexist during task performance. In this study, we used graph analysis to assess the functional relevance of the topological reorganization of brain networks ensuing the execution of a steady state working-memory (WM) task. Our results indicate that the performance of an auditory WM task is associated with a switching between different topological configurations of several regions of specific networks, including frontoparietal, ventral attention, and dorsal attention areas, suggesting segregation of ventral attention regions in the presence of increased overall integration. However, the correct execution of the task requires integration between components belonging to all the involved networks., (Copyright © 2020 Moraschi, Mascali, Tommasin, Gili, Hassan, Fratini, DiNuzzo, Wise, Mangia, Macaluso and Giove.)

Since the introduction of functional magnetic resonance imaging (fMRI), several computational approaches have been developed to examine the effect of the morphology and arrangement of blood vessels on the blood oxygenation-level dependent (BOLD) signal in the brain. In the present work, we implemented the original Ogawa's model using a numerical simulation based on the finite element method (FEM) instead of the analytical models. In literature, there are different works using analytical methods to analyse the transverse relaxation rate ( R 2 ∗ ), which BOLD signal is related to, modelling the vascular system with simple and canonical geometries such as an infinite cylinder model (ICM) or a set of cylinders. We applied the numerical simulation to the extravascular BOLD signal as a function of angular vessel distribution (perpendicular vs parallel to the static magnetic field) relevant for anatomical districts characterized by geometrical symmetries, such as spinal cord. Numerical simulations confirmed analytical results for the canonical ICM. Moreover, the perturbation to the magnetic field induced by blood deoxyhaemoglobin, as quantified assuming Brownian diffusion of water molecules around the vessel, revealed that vessels contribute the most to the variation of the R 2 ∗ when they are preferentially perpendicular to the external magnetic field, regardless of their size. Our results indicate that the numerical simulation method is sensitive to the effects of different vascular geometry. This work highlights the opportunity to extend R 2 ∗ simulations to realistic models of vasculature based on high-resolution anatomical images., (© 2019 John Wiley & Sons, Ltd.)

Phasic changes in eye's pupil diameter have been repeatedly observed during cognitive, emotional and behavioral activity in mammals. Although pupil diameter is known to be associated with noradrenergic firing in the pontine Locus Coeruleus (LC), thus far the causal chain coupling spontaneous pupil dynamics to specific cortical brain networks remains unknown. In the present study, we acquired steady-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) data combined with eye-tracking pupillometry from fifteen healthy subjects that were trained to maintain a constant attentional load. Regression analysis revealed widespread visual and sensorimotor BOLD-fMRI deactivations correlated with pupil diameter. Furthermore, we found BOLD-fMRI activations correlated with pupil diameter change rate within a set of brain regions known to be implicated in selective attention, salience, error-detection and decision-making. These regions included LC, thalamus, posterior cingulate cortex (PCC), dorsal anterior cingulate and paracingulate cortex (dACC/PaCC), orbitofrontal cortex (OFC), and right anterior insular cortex (rAIC). Granger-causality analysis performed on these regions yielded a complex pattern of interdependence, wherein LC and pupil dynamics were far apart in the network and separated by several cortical stages. Functional connectivity (FC) analysis revealed the ubiquitous presence of the superior frontal gyrus (SFG) in the networks identified by the brain regions correlated to the pupil diameter change rate. No significant correlations were observed between pupil dynamics, regional activation and behavioral performance. Based on the involved brain regions, we speculate that pupil dynamics reflects brain processing implicated in changes between self- and environment-directed awareness., (Copyright © 2019 DiNuzzo, Mascali, Moraschi, Bussu, Maugeri, Mangini, Fratini and Giove.)

Purpose: Cognitive decline in Down syndrome generally shows neurodegenerative aspects similar to what is observed in Alzheimer's disease. Few studies reported information on white matter integrity. The aim of this study was to evaluate white matter alterations in a cohort of young Down subjects, without dementia, by means of DTI technique, compared to a normal control group., Methods: The study group consisted of 17 right-handed subjects with DS and many control subjects. All individuals participating in this study were examined by MR exam including DTI acquisition (32 non-coplanar directions); image processing and analysis were performed using FMRIB Software Library (FSL version 4.1.9, http://www.fmrib.ox.ac.uk/fsl )) software package. Finally, the diffusion tensor was estimated voxel by voxel and the FA map derived from the tensor. A two-sample t test was performed to assess differences between DS and control subjects., Results: The FA is decreased in DS subjects, compared to control subjects, in the region of the anterior thalamic radiation, the inferior fronto-occipital fasciculum, the inferior longitudinal fasciculum, and the cortico-spinal tract, bilaterally., Conclusions: The early white matter damage visible in our DS subjects could have great impact in the therapeutic management, in particular in better adapting the timing of therapies to counteract the toxic effect of the deposition of amyloid that leads to oxidative stress.

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., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Conflict of Interest Statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background & Objective: Brain areas of functional activation during emotional stimuli and their correlations with affective temperaments evaluated using Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A) and hopelessness levels assessed with the Beck Hopelessness Scale (BHS) have been investigated., Method: Brain activity in response to emotional stimuli was examined by Nuclear Magnetic Resonance Blood Oxygen Level Dependent (NMR BOLD) signal. Seventeen subjects (mean age ± SD = 57 ± 12), diagnosed with major affective disorders and eighteen healthy controls (HC) (mean age ± SD = 50±11) participated in this study. Higher functional activation of the left amygdala and cingulated gyrus was found in subjects with affective disorders; whereas, the right amygdala was mostly activated in the HC group. Higher BHS scores were associated with reduced BOLD activation throughout the primary somatosensorial cortex and left post-central gyrus., Conclusion: Conversely, increased BOLD activation throughout the parietal superior lobule and right anterior intraperietal sulcus, occipital cortex, and left optical radiation, right insular cortex, right frontal superior gyrus was correlated with higher BHS total scores. Future studies should investigate the nature of the associations among brain activation, suicide risk, and affective temperaments in larger samples., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

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., Competing Interests: Conflict of Interest Statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background and Purpose: The aim of this study was to investigate the characteristic pattern of age-related cortical thinning in patients with Down Syndrome (DS), as assessed by MRI and automatic cortical thickness measurements., Methods: Ninety-one non-demented subjects with DS (range 11-53 years) were examined using a 1.5 T scanner. MRI-based quantification of cortical thickness was performed using FreeSurfer software package., The Pearson product-moment correlation coefficient between age and mean cortical thickness was evaluated for all subjects participating in the study., Results: A significant negative correlation between cortical thickness and age was found bilaterally in the frontal, temporal, parietal and cingulate gyrus. Specific investigation of cerebral lobes showed a more evident involvement of the frontal one, compared to others. Moreover, the age related reduction of cortical thickness appeared to be more significant and rapid in patients between 20 and 30 years of age., Conclusions: Our findings showed that Down Syndrome subjects are affected by a diffuse cortical thinning. The involvement of cortical structures can be observed at an earlier age than previous studies have reported., (Copyright © 2015 by the American Society of Neuroimaging.)

Low frequency fluctuations (LFFs) of the BOLD signal are a major discovery in the study of the resting brain with functional magnetic resonance imaging (fMRI). Two fMRI-based measures, functional connectivity (FC), a measure of signal synchronicity, and the amplitude of LFFs (ALFF), a measure of signal periodicity, have been proved to be sensitive to changes induced by several neurological diseases, including degenerative dementia. In spite of the increasing use of these measures, whether and how they are related to each other remains to be elucidated. In this work we used voxel-wise FC and ALFF computed in different frequency bands (slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.073 Hz; and full-band: 0.01-0.073 Hz), in order to assess their relationship in healthy elderly as well as the relevant changes induced by Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI). We found that in healthy elderly subjects FC and ALFF are positively correlated in anterior and posterior cingulate cortex (full-band, slow-4 and slow-5), temporal cortex (full-band and slow-5), and in a set of subcortical regions (full-band and slow-4). These correlation patterns between FC and ALFF were absent in either AD or MCI patients. Notably, the loss of correlation between FC and ALFF in the AD group was primarily due to changes in FC rather than in ALFF. Our results indicate that degenerative dementia is characterized by a loss of global connection rather than by a decrease of fluctuation amplitude.

Objective: To assess what kind of information MR examination in flexed and extended positions provides in Down syndrome subjects with suspected cranio-cervical instability., Methods: Between 2005 and 2008, 35 subjects with DS were recruited in the study. Ethics committee approval was granted and a signed informed consent was obtained from the parents. All the subjects were affected by hypotonic status and ligament laxity established by clinical evaluation, but were asymptomatic about focal neurological symptoms due to medullar damage caused by cranio-cervical instability. Each patient underwent lateral supine radiographs and MR imaging in the neutral, active flexed and extended positions. For evaluating the atlanto-axial and atlanto-occipital joint stability, multiple measurements were calculated., Results: A significant reduction of anterior subarachnoid space in flexed position was evident in DS subjects compared to healthy controls in neutral and flexed positions. Both, space available for cord and ligamentous thickness showed significant differences between DS subjects and healthy controls. In DS subjects with occipito-cervical instability, the anterior subarachnoidal space reduction was significantly reduced in flexed position., Conclusions: In DS subjects with asymptomatic cranio-cervical instability, anterior subarachnoidal evaluation and ligamentous status could add new information about the risk of spinal cord damage.

Introduction: The aim of this study was to determine differences in the characteristic pattern of age-related cortical thinning in men and women with Down's syndrome (DS) by means of MRI and automatic cortical thickness measurements and a cross-sectional design, in a large cohort of young subjects., Methods: Eighty-four subjects with DS, 30 females (11-35 years, mean age ± SD = 22.8 ± 5.9) and 54 males (11-35 years, mean age ± SD = 21.5 ± 6.5), were examined using a 1.5-T scanner. MRI-based quantification of cortical thickness was performed using FreeSurfer software package. For all subjects participating in the study, the Pearson product-moment correlation coefficient between age and mean cortical thickness values has been evaluated., Results: A significant negative correlation between cortical thickness and age was found in female DS subjects, predominantly in frontal and parietal lobes, bilaterally. In male DS subjects, a significant negative correlation between cortical thickness and age was found in the right fronto-temporal lobes and cingulate regions. Whole brain mean cortical thickness values were significantly negative correlated with age only in female DS subjects., Conclusions: Females with Down's syndrome showed a strong correlation between cortical thickness and age, already in early age. We suggest that the cognitive impairment due to hormonal deficit in the postmenopausal period could be emphasized by the early structural decline of gray matter in female DS subjects.

Functional magnetic resonance imaging (fMRI) techniques are widely exploited for the study of brain activation. In recent years, similar approaches have been attempted for the study of spinal cord function; however, obtaining good functional images of spinal cord still represents a technical and scientific challenge. Some of the main limiting factors can be classified under the broad category of "physiological noise," and are related to 1) the cerebrospinal fluid (CSF) flux in the subarachnoid space surrounding the spinal cord; 2) the cord motion itself; and 3) the small area of the cord, which makes it critical to have a high image resolution. In addition, the different magnetic susceptibility properties of tissues surrounding the spinal cord reduce the local homogeneity of the static magnetic field, causing image distortion, reduction of the effective resolution, and signal loss, all effects that are modulated by motion. For these reasons, a number of methods have been developed for the purpose of denoising spinal cord fMRI time series. In this work, after a short introduction on the relevant features of the spinal cord anatomy, we review the main sources of physiological noise in spinal cord fMRI and discuss the main approaches useful for its mitigation., (© 2013 Wiley Periodicals, Inc.)

Purpose: To compare intraoperative dynamic contrast-enhanced (dCE) sequences with conventional CE (cCE) in the evaluation of the surgical bed after transsphenoidal removal of pituitary macroadenomas., Materials and Methods: Twenty-one patients with macroadenoma were selected. They all underwent intraoperative magnetic resonance imaging (iMRI) (1.5T) acquisitions during transsphenoidal resection of the tumor. For each patient, dCE and cCE images were acquired in the operating room after tumor removal. The mean values of surgical cavities volumes were measured and statistically compared through Student's t-test analysis. Informed consent to iMRI was obtained from the patients as a part of the surgical procedure. Institutional Review Board (IRB) approval was obtained., Results: No patient showed recurrence within at least 1 year of follow-up. Two patients showed residual tumor in the iMRI. Intraoperative analysis of the remaining 19 demonstrated that the mean value of the surgical cavities was significantly bigger in dCE than in cCE images (2955 mm(3) vs. 1963 mm(3) , respectively, P = 0.022)., Conclusion: This study demonstrated underestimation of surgical cavity by conventional iMRI, simulating residual tumor and potentially leading to unnecessary surgical revision., (© 2013 Wiley Periodicals, Inc.)

Several brain regions exhibit a sustained negative BOLD response (NBR) during specific tasks, as assessed with functional magnetic resonance imaging. The origin of the NBR and the relationships between the vascular/metabolic dynamics and the underlying neural activity are highly debated. Converging evidence indicates that NBR, in human and non-human primates, can be interpreted in terms of decrease in neuronal activity under its basal level, rather than a purely vascular phenomenon. However, the scarcity of direct experimental evidence suggests caution and encourages the ongoing utilization of multimodal approaches in the investigation of this effect.

Parkinson's disease is a neurological disorder associated with the disfunction of dopaminergic pathways of the basal ganglia, mainly resulting in a progressive alteration in the execution of voluntary movements. We present a functional magnetic resonance imaging (fMRI) study on cortical activations during simple motor task performance, in six early-stage hemiparkinsonian patients and seven healthy volunteers. We acquired data in three sessions, during which subjects performed the task with right or left hand, or bimanually. We observed consistent bilateral activations in cingulate cortex and dorsolateral prefrontal cortex of Parkinsonian subjects during the execution of the task with the affected hand. In addition, patients showed both larger and stronger activations in motor cortex of the affected hemisphere with respect to the healthy hemisphere. Compared with the control group, patients showed a hyperactivation of the dorsolateral prefrontal cortex of the affected hemisphere. We concluded that a presymptomatic reorganization of the motor system is likely to occur in Parkinson's disease at earlier stages than previously hypothesized. Moreover, our results support fMRI as a sensitive technique for revealing the initial involvement of motor cortex areas at the debut of this degenerative disorder., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: To compare the effects of anisotropic and Gaussian smoothing on the outcomes of diffusion tensor imaging (DTI) voxel-based (VB) analyses in the clinic, in terms of signal-to-noise ratio (SNR) enhancement and directional information and boundary structures preservation., Materials and Methods: DTI data of 30 Alzheimer's disease (AD) patients and 30 matched control subjects were obtained at 3T. Fractional anisotropy (FA) maps with variable degrees and quality (Gaussian and anisotropic) of smoothing were created and compared with an unsmoothed dataset. The two smoothing approaches were evaluated in terms of SNR improvements, capability to separate differential effects between patients and controls by a standard VB analysis, and level of artifacts introduced by the preprocessing., Results: Gaussian smoothing regionally biased the FA values and introduced a high variability of results in clinical analysis, greatly dependent on the kernel size. On the contrary, anisotropic smoothing proved itself capable of enhancing the SNR of images and maintaining boundary structures, with only moderate dependence of results on smoothing parameters., Conclusion: Our study suggests that anisotropic smoothing is more suitable in DTI studies; however, regardless of technique, a moderate level of smoothing seems to be preferable considering the artifacts introduced by this manipulation.

In this study, we assess white matter microstructural deficit correlates of apathy level in 20 patients with amnestic mild cognitive impairment by means of diffusion tensor imaging. Mean diffusivity correlated positively with apathy level in the right temporal portion of the uncinate, middle longitudinal and inferior longitudinal fasciculi and in the parathalamic white matter, the fornix and the posterior cingulum of the right hemisphere. Fractional anisotropy results confirmed evidence of disconnection associated with apathy in all white matter areas except the middle longitudinal fasciculus. These results support the view that alterations in the neural mechanisms underlying apathy level occur in the early phase of degenerative dementias.

Parkinson's disease is a neurological disorder associated with disfunction of dopaminergic pathways of the basal ganglia. In this study, we report the effects of decreasing plasma concentrations of the dopamine-agonist apomorphine on the size and extents of activity clusters observed with functional magnetic resonance imaging during a simple motor task. Eight patients at advanced disease stage and six healthy volunteers were studied during four consecutive sessions. We observed consistent activations in the primary sensorimotor area of the contralateral side and in the supplementary motor area of both patients and controls during the first session. During subsequent sessions, while the drug concentration gradually decreased in patients, they showed a fragmentation of the activity areas, with an overall decrease of involved volume and a decline of activity in the supplementary motor area. The appearing of activity in the ipsilateral motor area matched a partial recovery of supplementary motor area activation. During the last session, when patients showed severe dyskinesia, a widespread region of positive and negative correlations between signal and task was observed. We conclude that the lack of subcortical circuitry is partially reversible by apomorphine and that when the drug effects are reduced, there is a possible mechanism recruitment of alternate subcortical pathways.